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Yang CH, Lin YJ, Gao SY, Chen WC, Chaou CH. Impact of the Coronavirus Disease 2019 Pandemic on the Management and Outcomes of ST-Segment Elevation Myocardial Infarction Patients: A Retrospective Cohort Study. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:422. [PMID: 40142233 PMCID: PMC11944074 DOI: 10.3390/medicina61030422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Revised: 02/14/2025] [Accepted: 02/25/2025] [Indexed: 03/28/2025]
Abstract
Background and Objectives: The coronavirus disease 2019 pandemic presented unprecedented challenges in balancing infection control measures with the timely management of ST-segment elevation myocardial infarction (STEMI), a time-sensitive condition. This study investigates the pandemic's effects on STEMI management times and outcomes at a high-volume medical center in Taiwan. Materials and Methods: A retrospective analysis of 1309 STEMI patients was conducted at Chang Gung Memorial Hospital between 2017 and 2022. Patients were divided into pre-pandemic and pandemic groups. Measurement outcomes include in-hospital mortality rate, management times (e.g., door-to-balloon time), the rates of intra-aortic balloon pump (IABP) and/or veno-arterial extracorporeal membrane oxygenation (VA-ECMO) usage, mechanical ventilation, inotropic support, and the length of intensive care unit (ICU) and hospital stay. Kaplan-Meier survival analysis and statistical comparisons were performed to assess temporal trends and prognostic outcomes. Results: No significant difference in in-hospital mortality was observed between pre-pandemic (5.85%) and pandemic (7.03%) groups (p = 0.45). The pandemic group experienced longer management times, including door-to-cath arrival (p = 0.0335) and door-to-balloon time (p = 0.014), although all times remained below the 90 min threshold. Quality improvements during the first outbreak allowed the institution to handle higher case volumes during subsequent waves without further delays. Ninety-day survival analysis showed no significant disparity between groups (p = 0.3655). Conclusions: Pandemic-related delays in STEMI management were effectively mitigated through workflow optimization, preventing significant increases in mortality rates. This study highlights the adaptability of healthcare systems in responding to crises while maintaining quality care for time-sensitive emergencies. Future multicenter studies could provide broader insights into global STEMI management strategies under pandemic conditions.
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Affiliation(s)
- Cheng-Han Yang
- Department of Emergency Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan; (C.-H.Y.); (Y.-J.L.); (S.-Y.G.); (W.-C.C.)
| | - Yu-Jen Lin
- Department of Emergency Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan; (C.-H.Y.); (Y.-J.L.); (S.-Y.G.); (W.-C.C.)
| | - Shi-Ying Gao
- Department of Emergency Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan; (C.-H.Y.); (Y.-J.L.); (S.-Y.G.); (W.-C.C.)
| | - Wei-Chen Chen
- Department of Emergency Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan; (C.-H.Y.); (Y.-J.L.); (S.-Y.G.); (W.-C.C.)
| | - Chung-Hsien Chaou
- Department of Emergency Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan; (C.-H.Y.); (Y.-J.L.); (S.-Y.G.); (W.-C.C.)
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
- Chang Gung Medical Education Research Center, Taoyuan 333, Taiwan
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Martinez-Navarro H, Zhou X, Rodriguez B. Mechanisms and Implications of Electrical Heterogeneity in Cardiac Function in Ischemic Heart Disease. Annu Rev Physiol 2025; 87:25-51. [PMID: 39541224 DOI: 10.1146/annurev-physiol-042022-020541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
A healthy heart shows intrinsic electrical heterogeneities that play a significant role in cardiac activation and repolarization. However, cardiac diseases may perturb the baseline electrical properties of the healthy cardiac tissue, leading to increased arrhythmic risk and compromised cardiac functions. Moreover, biological variability among patients produces a wide range of clinical symptoms, which complicates the treatment and diagnosis of cardiac diseases. Ischemic heart disease is usually caused by a partial or complete blockage of a coronary artery. The onset of the disease begins with myocardial ischemia, which can develop into myocardial infarction if it persists for an extended period. The progressive regional tissue remodeling leads to increased electrical heterogeneities, with adverse consequences on arrhythmic risk, cardiac mechanics, and mortality. This review aims to summarize the key role of electrical heterogeneities in the heart on cardiac function and diseases. Ischemic heart disease has been chosen as an example to show how adverse electrical remodeling at different stages may lead to variable manifestations in patients. For this, we have reviewed the dynamic electrophysiological and structural remodeling from the onset of acute myocardial ischemia and reperfusion to acute and chronic stages post-myocardial infarction. The arrhythmic mechanisms, patient phenotypes, risk stratification at different stages, and patient management strategies are also discussed. Finally, we provide a brief review on how computational approaches incorporate human electrophysiological heterogeneity to facilitate basic and translational research.
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Affiliation(s)
- Hector Martinez-Navarro
- Department of Computer Science, British Heart Foundation Centre of Research Excellence, University of Oxford, Oxford, United Kingdom; , ,
| | - Xin Zhou
- Department of Computer Science, British Heart Foundation Centre of Research Excellence, University of Oxford, Oxford, United Kingdom; , ,
| | - Blanca Rodriguez
- Department of Computer Science, British Heart Foundation Centre of Research Excellence, University of Oxford, Oxford, United Kingdom; , ,
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Bernhard B, Heydari B, Abdullah S, Francis SA, Lumish H, Wang W, Jerosch-Herold M, Harris WS, Kwong RY. Effect of six month's treatment with omega-3 acid ethyl esters on long-term outcomes after acute myocardial infarction: The OMEGA-REMODEL randomized clinical trial. Int J Cardiol 2024; 399:131698. [PMID: 38184150 DOI: 10.1016/j.ijcard.2023.131698] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 12/15/2023] [Accepted: 12/29/2023] [Indexed: 01/08/2024]
Abstract
BACKGROUND Omega-3 polyunsaturated fatty acids (O3-FA) have been shown to reduce inflammation and adverse cardiac remodeling after acute myocardial infarction (AMI). However, the impact of O3-FA on long-term clinical outcomes remains uncertain. AIMS To investigate the impact of O3-FA on adverse cardiac events in long-term follow up post AMI in a pilot-study. METHODS Consecutive patients with AMI were randomized 1:1 to receive 6 months of O3-FA (4 g/daily) or placebo in the prospective, multicenter OMEGA-REMODEL trial. Primary endpoint was a composite of major adverse cardiovascular events (MACE) encompassing all-cause death, heart failure hospitalizations, recurrent acute coronary syndrome, and late coronary artery bypass graft (CABG). RESULTS A total of 358 patients (62.8% male; 48.1 ± 16.1 years) were followed for a median of 6.6 (IQR: 5.0-9.1) years. Among those receiving O3-FA (n = 180), MACE occurred in 65 (36.1%) compared to 62 (34.8%) of 178 assigned to placebo. By intention-to-treat analysis, O3-FA treatment assignment did not reduce MACE (HR = 1.014; 95%CI = 0.716-1.436; p = 0.938), or its individual components. However, patients with a positive response to O3-FA treatment (n = 43), defined as an increase in the red blood cell omega-3 index (O3I) ≥5% after 6 months of treatment, had lower annualized MACE rates compared to those without (2.9% (95%CI = 1.2-5.1) vs 7.1% (95%CI = 5.7-8.9); p = 0.001). This treatment benefit persisted after adjustment for baseline characteristics (HRadjusted = 0.460; 95%CI = 0.218-0.970; p = 0.041). CONCLUSION In long-term follow-up of the OMEGA-REMODEL randomized trial, O3-FA did not reduce MACE after AMI by intention to treat principle, however, patients who achieved a ≥ 5% increase of O3I subsequent to treatment had favorable outcomes.
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Affiliation(s)
- Benedikt Bernhard
- Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - Bobak Heydari
- Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Stephenson Cardiac Imaging Center, University of Calgary, Calgary, Alberta, Canada
| | - Shuaib Abdullah
- Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; VA North Texas Medical Center and University of Texas-Southwestern Medical School, Dallas, TX, USA
| | - Sanjeev A Francis
- Department of Cardiovascular Medicine, Maine Medical Center, Portland, USA
| | - Heidi Lumish
- Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
| | - Wei Wang
- Division of Sleep Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - Michael Jerosch-Herold
- Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - William S Harris
- Fatty Acid Research Institute, Sioux Falls, SD 57106, USA; Sanford School of Medicine, University of South Dakota, Sioux Falls, SD 57105, USA
| | - Raymond Y Kwong
- Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
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Haybar H, Hadi H, Purrahman D, Mahmoudian-Sani MR, Saki N. Emerging roles of HOTAIR lncRNA in the pathogenesis and prognosis of cardiovascular diseases. Biomark Med 2024; 18:203-219. [PMID: 38411079 DOI: 10.2217/bmm-2023-0368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/28/2024] Open
Abstract
Highlights HOTAIR, a long noncoding RNA, plays a role in the regulation of proteins involved in the pathogenesis of cardiovascular disease. Furthermore, it has been identified as a biomarker of this type of disease. Several factors and cells contribute to atherosclerosis, a progressive disease. However, the prognosis of HOTAIR in this disease varies depending on the path in which it plays a role. For this condition, there is no single prognosis to consider.
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Affiliation(s)
- Habib Haybar
- Atherosclerosis Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Hakimeh Hadi
- Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Daryush Purrahman
- Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mohammad Reza Mahmoudian-Sani
- Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Najmaldin Saki
- Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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Zhang S, Zhu Z, Luo M, Chen L, He C, You Z, He H, Lin M, Zhang L, Lin K, Guo Y. The optimal definition and prediction nomogram for left ventricular remodelling after acute myocardial infarction. ESC Heart Fail 2023; 10:2955-2965. [PMID: 37489064 PMCID: PMC10567660 DOI: 10.1002/ehf2.14479] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 06/20/2023] [Accepted: 07/04/2023] [Indexed: 07/26/2023] Open
Abstract
AIMS Left ventricular (LV) remodelling after acute myocardial infarction (AMI) is associated with heart failure and increased mortality. There was no consensus on the definition of LV remodelling, and the prognostic value of LV remodelling with different definitions has not been compared. We aimed to find the optimal definition and develop a prediction nomogram as well as online calculator that can identify patients at risk of LV remodelling. METHODS AND RESULTS This prospective, observational study included 829 AMI patients undergoing percutaneous coronary intervention from January 2015 to January 2020. Echocardiography was performed within the 48 h of admission and at 6 months after infarction to evaluate LV remodelling, defined as a 20% increase in LV end-diastolic volume (LVEDV), a 15% increase in LV end-systolic volume (LVESV), or LV ejection fraction (LVEF) < 50% at 6 months. The impact of LV remodelling on long-term outcomes was analysed. Lasso regression was performed to screen potential predictors, and multivariable logistic regression analysis was conducted to establish the prediction nomogram. The area under the curve, calibration curve and decision curve analyses were used to determine the discrimination, calibration and clinical usefulness of the remodelling nomogram. The incidences of LV remodelling defined by LVEDV, LVESV and LVEF were 24.85% (n = 206), 28.71% (n = 238) and 14.60% (n = 121), respectively. Multivariable Cox regression models demonstrated that different definitions of LV remodelling were independently associated with the composite endpoint. However, only remodelling defined by LVEF was significantly connected with long-term mortality (hazard ratio = 2.78, 95% confidence interval 1.41-5.48, P = 0.003). Seven variables were selected to construct the remodelling nomogram, including diastolic blood pressure, heart rate, AMI type, stent length, N-terminal pro brain natriuretic peptide, troponin I, and glucose. The prediction model had an area under the receiver operating characteristics curve of 0.766. The calibration curve and decision curve analysis indicated consistency and better net benefit in the prediction model. CONCLUSIONS LV remodelling defined by LVEDV, LVESV and LVEF were independent predictors for long-term mortality or heart failure hospitalization in AMI patients after percutaneous coronary intervention. However, only remodelling defined by LVEF was suitable for predicting all-cause death. In addition, the nomogram can provide an accurate and effective tool for the prediction of postinfarct remodelling.
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Affiliation(s)
- Sicheng Zhang
- Department of CardiologyShengli Clinical Medical College of Fujian Medical University, Fujian Provincial HospitalFuzhouChina
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
- Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Provincial Center for Geriatrics, Fujian Provincial Clinical Research Center for Severe Acute Cardiovascular DiseasesFuzhouChina
- Fujian Heart Failure Center AllianceFuzhouChina
| | - Zheng Zhu
- Department of Endocrine and Metabolic Diseases, School of MedicineShanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong UniversityShanghaiChina
| | - Manqing Luo
- Department of CardiologyShengli Clinical Medical College of Fujian Medical University, Fujian Provincial HospitalFuzhouChina
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
- Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Provincial Center for Geriatrics, Fujian Provincial Clinical Research Center for Severe Acute Cardiovascular DiseasesFuzhouChina
- Fujian Heart Failure Center AllianceFuzhouChina
| | - Lichuan Chen
- Department of CardiologyShengli Clinical Medical College of Fujian Medical University, Fujian Provincial HospitalFuzhouChina
- Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Provincial Center for Geriatrics, Fujian Provincial Clinical Research Center for Severe Acute Cardiovascular DiseasesFuzhouChina
- Fujian Heart Failure Center AllianceFuzhouChina
| | - Chen He
- Department of CardiologyShengli Clinical Medical College of Fujian Medical University, Fujian Provincial HospitalFuzhouChina
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
- Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Provincial Center for Geriatrics, Fujian Provincial Clinical Research Center for Severe Acute Cardiovascular DiseasesFuzhouChina
- Fujian Heart Failure Center AllianceFuzhouChina
| | - Zhebin You
- Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Provincial Center for Geriatrics, Fujian Provincial Clinical Research Center for Severe Acute Cardiovascular DiseasesFuzhouChina
- Fujian Heart Failure Center AllianceFuzhouChina
- Department of Geriatric MedicineShengli Clinical Medical College of Fujian Medical University, Fujian Provincial HospitalFuzhouChina
| | - Haoming He
- Department of CardiologyShengli Clinical Medical College of Fujian Medical University, Fujian Provincial HospitalFuzhouChina
- Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Provincial Center for Geriatrics, Fujian Provincial Clinical Research Center for Severe Acute Cardiovascular DiseasesFuzhouChina
- Fujian Heart Failure Center AllianceFuzhouChina
| | - Maoqing Lin
- Department of CardiologyShengli Clinical Medical College of Fujian Medical University, Fujian Provincial HospitalFuzhouChina
- Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Provincial Center for Geriatrics, Fujian Provincial Clinical Research Center for Severe Acute Cardiovascular DiseasesFuzhouChina
- Fujian Heart Failure Center AllianceFuzhouChina
| | - Liwei Zhang
- Department of CardiologyShengli Clinical Medical College of Fujian Medical University, Fujian Provincial HospitalFuzhouChina
- Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Provincial Center for Geriatrics, Fujian Provincial Clinical Research Center for Severe Acute Cardiovascular DiseasesFuzhouChina
- Fujian Heart Failure Center AllianceFuzhouChina
| | - Kaiyang Lin
- Department of CardiologyShengli Clinical Medical College of Fujian Medical University, Fujian Provincial HospitalFuzhouChina
- Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Provincial Center for Geriatrics, Fujian Provincial Clinical Research Center for Severe Acute Cardiovascular DiseasesFuzhouChina
- Fujian Heart Failure Center AllianceFuzhouChina
| | - Yansong Guo
- Department of CardiologyShengli Clinical Medical College of Fujian Medical University, Fujian Provincial HospitalFuzhouChina
- Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Provincial Center for Geriatrics, Fujian Provincial Clinical Research Center for Severe Acute Cardiovascular DiseasesFuzhouChina
- Fujian Heart Failure Center AllianceFuzhouChina
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Sopova K, Tual-Chalot S, Mueller-Hennessen M, Vlachogiannis NI, Georgiopoulos G, Biener M, Sachse M, Turchinovich A, Polycarpou-Schwarz M, Spray L, Maneta E, Bennaceur K, Mohammad A, Richardson GD, Gatsiou A, Langer HF, Frey N, Stamatelopoulos K, Heineke J, Duerschmied D, Giannitsis E, Spyridopoulos I, Stellos K. Effector T cell chemokine IP-10 predicts cardiac recovery and clinical outcomes post-myocardial infarction. Front Immunol 2023; 14:1177467. [PMID: 37426649 PMCID: PMC10326041 DOI: 10.3389/fimmu.2023.1177467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 05/23/2023] [Indexed: 07/11/2023] Open
Abstract
Background and aims Preclinical data suggest that activation of the adaptive immune system is critical for myocardial repair processes in acute myocardial infarction. The aim of the present study was to determine the clinical value of baseline effector T cell chemokine IP-10 blood levels in the acute phase of ST-segment elevation myocardial infarction (STEMI) for the prediction of the left ventricular function changes and cardiovascular outcomes after STEMI. Methods Serum IP-10 levels were retrospectively quantified in two independent cohorts of STEMI patients undergoing primary percutaneous coronary intervention. Results We report a biphasic response of the effector T cell trafficking chemokine IP-10 characterized by an initial increase of its serum levels in the acute phase of STEMI followed by a rapid reduction at 90min post reperfusion. Patients at the highest IP-10 tertile presented also with more CD4 effector memory T cells (CD4 TEM cells), but not other T cell subtypes, in blood. In the Newcastle cohort (n=47), patients in the highest IP-10 tertile or CD4 TEM cells at admission exhibited an improved cardiac systolic function 12 weeks after STEMI compared to patients in the lowest IP-10 tertile. In the Heidelberg cohort (n=331), STEMI patients were followed for a median of 540 days for major adverse cardiovascular events (MACE). Patients presenting with higher serum IP-10 levels at admission had a lower risk for MACE after adjustment for traditional risk factors, CRP and high-sensitivity troponin-T levels (highest vs. rest quarters: HR [95% CI]=0.420 [0.218-0.808]). Conclusion Increased serum levels of IP-10 in the acute phase of STEMI predict a better recovery in cardiac systolic function and less adverse events in patients after STEMI.
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Affiliation(s)
- Kateryna Sopova
- Translational and Clinical Research Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Department of Cardiology, Royal Victoria Infirmary (RVI) and Freeman Hospitals, Newcastle Upon Tyne Hospitals National Health Service (NHS) Foundation Trust, Newcastle Upon Tyne, United Kingdom
- German Centre for Cardiovascular Research (DZHK), partner site Heidelberg/Mannheim, Mannheim, Germany
- Department of Cardiovascular Research, European Center for Angioscience (ECAS), Heidelberg University, Heidelberg/Mannheim, Germany
| | - Simon Tual-Chalot
- Biosciences Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom
| | - Matthias Mueller-Hennessen
- German Centre for Cardiovascular Research (DZHK), partner site Heidelberg/Mannheim, Mannheim, Germany
- Department of Internal Medicine III, Cardiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Nikolaos I. Vlachogiannis
- Biosciences Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom
| | - Georgios Georgiopoulos
- Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
| | - Moritz Biener
- German Centre for Cardiovascular Research (DZHK), partner site Heidelberg/Mannheim, Mannheim, Germany
- Department of Internal Medicine III, Cardiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Marco Sachse
- Department of Cardiovascular Research, European Center for Angioscience (ECAS), Heidelberg University, Heidelberg/Mannheim, Germany
| | - Andrey Turchinovich
- Department of Cardiovascular Research, European Center for Angioscience (ECAS), Heidelberg University, Heidelberg/Mannheim, Germany
| | - Maria Polycarpou-Schwarz
- Department of Cardiovascular Research, European Center for Angioscience (ECAS), Heidelberg University, Heidelberg/Mannheim, Germany
| | - Luke Spray
- Department of Cardiology, Royal Victoria Infirmary (RVI) and Freeman Hospitals, Newcastle Upon Tyne Hospitals National Health Service (NHS) Foundation Trust, Newcastle Upon Tyne, United Kingdom
- Biosciences Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom
| | - Eleni Maneta
- Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
| | - Karim Bennaceur
- Biosciences Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom
| | - Ashfaq Mohammad
- Department of Cardiology, Royal Victoria Infirmary (RVI) and Freeman Hospitals, Newcastle Upon Tyne Hospitals National Health Service (NHS) Foundation Trust, Newcastle Upon Tyne, United Kingdom
- Biosciences Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom
| | - Gavin David Richardson
- Biosciences Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom
| | - Aikaterini Gatsiou
- Biosciences Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom
| | - Harald F. Langer
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- German Centre for Cardiovascular Research (DZHK), partner site Heidelberg/Mannheim, Mannheim, Germany
| | - Norbert Frey
- German Centre for Cardiovascular Research (DZHK), partner site Heidelberg/Mannheim, Mannheim, Germany
- Department of Internal Medicine III, Cardiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Kimon Stamatelopoulos
- Biosciences Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom
- Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
| | - Joerg Heineke
- German Centre for Cardiovascular Research (DZHK), partner site Heidelberg/Mannheim, Mannheim, Germany
- Department of Cardiovascular Physiology, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Daniel Duerschmied
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- German Centre for Cardiovascular Research (DZHK), partner site Heidelberg/Mannheim, Mannheim, Germany
| | - Evangelos Giannitsis
- Department of Internal Medicine III, Cardiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Ioakim Spyridopoulos
- Translational and Clinical Research Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom
- Department of Cardiology, Royal Victoria Infirmary (RVI) and Freeman Hospitals, Newcastle Upon Tyne Hospitals National Health Service (NHS) Foundation Trust, Newcastle Upon Tyne, United Kingdom
| | - Konstantinos Stellos
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- German Centre for Cardiovascular Research (DZHK), partner site Heidelberg/Mannheim, Mannheim, Germany
- Department of Cardiovascular Research, European Center for Angioscience (ECAS), Heidelberg University, Heidelberg/Mannheim, Germany
- Biosciences Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom
- Department of Internal Medicine III, Cardiology, University Hospital Heidelberg, Heidelberg, Germany
- Department of Cardiovascular Physiology, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
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Casolo G, Gulizia MM, Aschieri D, Chinaglia A, Corda M, Nassiacos D, Caico SI, Chimenti C, Giaccardi M, Gotti E, Maffé S, Magnano R, Solarino G, Gabrielli D, Oliva F, Colivicchi F. ANMCO position paper: guide to the appropriate use of the wearable cardioverter defibrillator in clinical practice for patients at high transient risk of sudden cardiac death. Eur Heart J Suppl 2023; 25:D294-D311. [PMID: 37213799 PMCID: PMC10194821 DOI: 10.1093/eurheartjsupp/suad101] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/23/2023]
Abstract
Extended risk stratification and optimal management of patients with a permanently increased risk of sudden cardiac death (SCD) are becoming increasingly important. There are several clinical conditions where the risk of arrhythmic death is present albeit only transient. As an example, patients with depressed left ventricular function have a high risk of SCD that may be only transient if there will be a significant recovery of function. It is important to protect the patients while receiving and titrating to the optimal dose the recommended drugs that may lead to an improved left ventricular function. In several other conditions, a transient risk of SCD can be observed even if the left ventricular function is not compromised. Examples are patients with acute myocarditis, during the diagnostic work-up of some arrhythmic conditions or after extraction of infected catheters while eradicating the associated infection. In all these conditions, it is important to offer a protection to these patients. The wearable cardioverter defibrillator (WCD) is of particular importance as a temporary non-invasive technology for both arrhythmia monitoring and therapy in patients with increased risk of SCD. Previous studies have shown the WCD to be an effective and safe therapy for the prevention of SCD caused by ventricular tachycardia/fibrillation. The aim of this ANMCO position paper is to provide a recommendation for clinical utilization of the WCD in Italy, based upon current data and international guidelines. In this document, we will review the WCD functionality, indications, clinical evidence, and guideline recommendations. Finally, a recommendation for the utilization of the WCD in routine clinical practice will be presented, in order to provide physicians with a practical guidance for SCD risk stratification in patients who may benefit from this device.
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Affiliation(s)
- Giancarlo Casolo
- U.O.C. Cardiology, Versilia Hospital, Lido di Camaiore, Lucca 55043
| | - Michele Massimo Gulizia
- U.O.C. Cardiology, Garibaldi-Nesima Hospital, Azienda di Rilievo Nazionale e Alta Specializzazione ‘Garibaldi’, Catania
| | | | | | - Marco Corda
- S.C. Cardiology-UTIC, ARNAS ‘G. Brotzu’, Cagliari
| | - Daniele Nassiacos
- U.O.C Cardiology-UTIC, P.O. Saronno, ASST Valle Olona, Saronno, Varese
| | | | - Cristina Chimenti
- Department of Clinical Internal, Anaesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Azienda Ospedaliera Universitaria Policlinico Umberto I, Rome
| | - Marzia Giaccardi
- U.O. Cardiology, Santa Maria Annunziata Hospital, Bagno a Ripoli, Florence
| | - Enrico Gotti
- Department of Nephrological, Cardiac and Vascular Diseases, University of Modena and Reggio Emilia, Baggiovara Civil Hospital, Modena
| | - Stefano Maffé
- U.O. Cardiology, SS Trinità Hospital, ASL NO, Borgomanero, Novara
| | | | | | - Domenico Gabrielli
- U.O.C. Cardiology, Department of Cardio-Thoraco-Vascular, Azienda Ospedaliera San Camillo Forlanini, Rome
- Fondazione per il Tuo cuore—Heart Care Foundation, Florence
| | - Fabrizio Oliva
- Cardiology 1-Emodinamics, Cardiothoracovascular Department ‘A. De Gasperis’, ASST Grande Ospedale Metropolitano Niguarda, Milan
| | - Furio Colivicchi
- U.O.C. Clinical and Rehabilitation Cardiology, Presidio Ospedaliero San Filippo Neri—ASL Roma 1, Rome
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8
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Guddeti RR, Yildiz M, Nayak KR, Alraies MC, Davidson L, Henry TD, Garcia S. Impact of COVID-19 on Acute Myocardial Infarction Care. Heart Fail Clin 2023; 19:221-229. [PMID: 36863814 PMCID: PMC9973541 DOI: 10.1016/j.hfc.2022.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/03/2023]
Abstract
The global health crisis caused by the COVID-19 pandemic has evolved rapidly to overburden health care organizations around the world and has resulted in significant morbidity and mortality. Many countries have reported a substantial and rapid reduction in hospital admissions for acute coronary syndromes and percutaneous coronary intervention. The reasons for such abrupt changes in health care delivery are multifactorial and include lockdowns, reduction in outpatient services, reluctance to seek medical attention for fear of contracting the virus, and restrictive visitation policies adopted during the pandemic. This review discusses the impact of COVID-19 on important aspects of acute MI care.
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Affiliation(s)
| | - Mehmet Yildiz
- The Christ Hospital Health Network, 2139 Auburn Avenue Suite 424, Cincinnati, OH 45219, USA
| | | | | | - Laura Davidson
- Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
| | - Timothy D Henry
- The Christ Hospital Health Network, 2139 Auburn Avenue Suite 424, Cincinnati, OH 45219, USA
| | - Santiago Garcia
- The Christ Hospital Health Network, 2139 Auburn Avenue Suite 424, Cincinnati, OH 45219, USA.
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9
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Fujii S, Kobayashi S, Chang Y, Nawata J, Yoshitomi R, Tanaka S, Kohno M, Nakamura Y, Ishiguchi H, Suetomi T, Uchinoumi H, Oda T, Okuda S, Okamura T, Yamamoto T, Yano M. RyR2-targeting therapy prevents left ventricular remodeling and ventricular tachycardia in post-infarction heart failure. J Mol Cell Cardiol 2023; 178:36-50. [PMID: 36963751 DOI: 10.1016/j.yjmcc.2023.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 03/15/2023] [Accepted: 03/21/2023] [Indexed: 03/26/2023]
Abstract
BACKGROUND Dantrolene binds to the Leu601-Cys620 region of the N-terminal domain of cardiac ryanodine receptor (RyR2), which corresponds to the Leu590-Cys609 region of the skeletal ryanodine receptor, and suppresses diastolic Ca2+ leakage through RyR2. OBJECTIVE We investigated whether the chronic administration of dantrolene prevented left ventricular (LV) remodeling and ventricular tachycardia (VT) after myocardial infarction (MI) by the same mechanism with the mutation V3599K of RyR2, which indicated that the inhibition of diastolic Ca2+ leakage occurred by enhancing the binding affinity of calmodulin (CaM) to RyR2. METHODS AND RESULTS A left anterior descending coronary artery ligation MI model was developed in mice. Wild-type (WT) were divided into four groups: sham-operated mice (WT-Sham), sham-operated mice treated with dantrolene (WT-Sham-DAN), MI mice (WT-MI), and MI mice treated with dantrolene (WT-MI-DAN). Homozygous V3599K RyR2 knock-in (KI) mice were divided into two groups: sham-operated mice (KI-Sham) and MI mice (KI-MI). The mice were followed for 12 weeks. Survival was significantly higher in the WT-MI-DAN (73%) and KI-MI groups (70%) than the WT-MI group (40%). Echocardiography, pathological tissue, and epinephrine-induced VT studies showed that LV remodeling and VT were prevented in the WT-MI-DAN and KI-MI groups compared to the WT-MI group. An increase in diastolic Ca2+ spark frequency and a decrease in the binding affinity of CaM to the RyR2 were observed at 12 weeks after MI in the WT-MI group, although significant improvements in these values were observed in the WT-MI-DAN and KI-MI groups. CONCLUSIONS Pharmacological or genetic stabilization of RyR2 tetrameric structure improves survival after MI by suppressing LV remodeling and proarrhythmia.
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Affiliation(s)
- Shohei Fujii
- Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan
| | - Shigeki Kobayashi
- Department of Therapeutic Science for Heart Failure in the Elderly, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan.
| | - Yaowei Chang
- Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan
| | - Junya Nawata
- Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan
| | - Ryosuke Yoshitomi
- Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan
| | - Shinji Tanaka
- Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan
| | - Michiaki Kohno
- Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan
| | - Yoshihide Nakamura
- Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan
| | - Hironori Ishiguchi
- Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan
| | - Takeshi Suetomi
- Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan
| | - Hitoshi Uchinoumi
- Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan
| | - Tetsuro Oda
- Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan
| | - Shinichi Okuda
- Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan
| | - Takayuki Okamura
- Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan
| | - Takeshi Yamamoto
- Department of Laboratory Medicine, Faculty of Health Sciences, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan
| | - Masafumi Yano
- Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan
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10
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Pathophysiology of LV Remodeling Following STEMI: A Longitudinal Diffusion Tensor CMR Study. JACC Cardiovasc Imaging 2023; 16:159-171. [PMID: 36412993 PMCID: PMC9902278 DOI: 10.1016/j.jcmg.2022.04.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 02/28/2022] [Accepted: 04/07/2022] [Indexed: 11/20/2022]
Abstract
BACKGROUND Adverse LV remodeling post-ST-segment elevation myocardial infarction (STEMI) is associated with a poor prognosis, but the underlying mechanisms are not fully understood. Diffusion tensor (DT)-cardiac magnetic resonance (CMR) allows in vivo characterization of myocardial architecture and provides unique mechanistic insight into pathophysiologic changes following myocardial infarction. OBJECTIVES This study evaluated the potential associations between DT-CMR performed soon after STEMI and long-term adverse left ventricular (LV) remodeling following STEMI. METHODS A total of 100 patients with STEMI underwent CMR at 5 days and 12 months post-reperfusion. The protocol included DT-CMR for assessing fractional anisotropy (FA), secondary eigenvector angle (E2A) and helix angle (HA), cine imaging for assessing LV volumes, and late gadolinium enhancement for calculating infarct and microvascular obstruction size. Adverse remodeling was defined as a 20% increase in LV end-diastolic volume at 12 months. RESULTS A total of 32 patients experienced adverse remodeling at 12 months. Compared with patients without adverse remodeling, they had lower FA (0.23 ± 0.03 vs 0.27 ± 0.04; P < 0.001), lower E2A (37 ± 6° vs 51 ± 7°; P < 0.001), and, on HA maps, a lower proportion of myocytes with right-handed orientation (RHM) (8% ± 5% vs 17% ± 9%; P < 0.001) in their acutely infarcted myocardium. On multivariable logistic regression analysis, infarct FA (odds ratio [OR]: <0.01; P = 0.014) and E2A (OR: 0.77; P = 0.001) were independent predictors of adverse LV remodeling after adjusting for left ventricular ejection fraction (LVEF) and infarct size. There were no significant changes in infarct FA, E2A, or RHM between the 2 scans. CONCLUSIONS Extensive cardiomyocyte disorganization (evidenced by low FA), acute loss of sheetlet angularity (evidenced by low E2A), and a greater loss of organization among cardiomyocytes with RHM, corresponding to the subendocardium, can be detected within 5 days post-STEMI. These changes persist post-injury, and low FA and E2A are independently associated with long-term adverse remodeling.
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11
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Tang X, Nishimura A, Ariyoshi K, Nishiyama K, Kato Y, Vasileva EA, Mishchenko NP, Fedoreyev SA, Stonik VA, Kim HK, Han J, Kanda Y, Umezawa K, Urano Y, Akaike T, Nishida M. Echinochrome Prevents Sulfide Catabolism-Associated Chronic Heart Failure after Myocardial Infarction in Mice. Mar Drugs 2023; 21:52. [PMID: 36662225 PMCID: PMC9863521 DOI: 10.3390/md21010052] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 01/06/2023] [Accepted: 01/09/2023] [Indexed: 01/15/2023] Open
Abstract
Abnormal sulfide catabolism, especially the accumulation of hydrogen sulfide (H2S) during hypoxic or inflammatory stresses, is a major cause of redox imbalance-associated cardiac dysfunction. Polyhydroxynaphtoquinone echinochrome A (Ech-A), a natural pigment of marine origin found in the shells and needles of many species of sea urchins, is a potent antioxidant and inhibits acute myocardial ferroptosis after ischemia/reperfusion, but the chronic effect of Ech-A on heart failure is unknown. Reactive sulfur species (RSS), which include catenated sulfur atoms, have been revealed as true biomolecules with high redox reactivity required for intracellular energy metabolism and signal transduction. Here, we report that continuous intraperitoneal administration of Ech-A (2.0 mg/kg/day) prevents RSS catabolism-associated chronic heart failure after myocardial infarction (MI) in mice. Ech-A prevented left ventricular (LV) systolic dysfunction and structural remodeling after MI. Fluorescence imaging revealed that intracellular RSS level was reduced after MI, while H2S/HS- level was increased in LV myocardium, which was attenuated by Ech-A. This result indicates that Ech-A suppresses RSS catabolism to H2S/HS- in LV myocardium after MI. In addition, Ech-A reduced oxidative stress formation by MI. Ech-A suppressed RSS catabolism caused by hypoxia in neonatal rat cardiomyocytes and human iPS cell-derived cardiomyocytes. Ech-A also suppressed RSS catabolism caused by lipopolysaccharide stimulation in macrophages. Thus, Ech-A has the potential to improve chronic heart failure after MI, in part by preventing sulfide catabolism.
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Affiliation(s)
- Xiaokang Tang
- Division of Cardiocirculatory Signaling, National Institute for Physiological Sciences (NIPS), National Institutes of Natural Sciences, Okazaki 444-8787, Japan
- Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, Okazaki 444-8787, Japan
- Department of Physiological Sciences, SOKENDAI (School of Life Science, The Graduate University for Advanced Studies), Okazaki 444-8787, Japan
| | - Akiyuki Nishimura
- Division of Cardiocirculatory Signaling, National Institute for Physiological Sciences (NIPS), National Institutes of Natural Sciences, Okazaki 444-8787, Japan
- Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, Okazaki 444-8787, Japan
- Department of Physiological Sciences, SOKENDAI (School of Life Science, The Graduate University for Advanced Studies), Okazaki 444-8787, Japan
| | - Kohei Ariyoshi
- Department of Physiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Kazuhiro Nishiyama
- Department of Physiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Yuri Kato
- Department of Physiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Elena A. Vasileva
- G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Vladivostok 690022, Russia
| | - Natalia P. Mishchenko
- G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Vladivostok 690022, Russia
| | - Sergey A. Fedoreyev
- G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Vladivostok 690022, Russia
| | - Valentin A. Stonik
- G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Vladivostok 690022, Russia
| | - Hyoung-Kyu Kim
- Cardiovascular and Metabolic Disease Center (CMDC), Inje University, Busan 47392, Republic of Korea
| | - Jin Han
- Cardiovascular and Metabolic Disease Center (CMDC), Inje University, Busan 47392, Republic of Korea
| | - Yasunari Kanda
- Division of Pharmacology, National Institute of Health Sciences, Kawasaki 210-9501, Japan
| | - Keitaro Umezawa
- Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan
| | - Yasuteru Urano
- Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan
- Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan
| | - Takaaki Akaike
- Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
| | - Motohiro Nishida
- Division of Cardiocirculatory Signaling, National Institute for Physiological Sciences (NIPS), National Institutes of Natural Sciences, Okazaki 444-8787, Japan
- Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, Okazaki 444-8787, Japan
- Department of Physiological Sciences, SOKENDAI (School of Life Science, The Graduate University for Advanced Studies), Okazaki 444-8787, Japan
- Department of Physiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan
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12
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Vallorz EL, Janda J, Mansour HM, Schnellmann RG. Kidney targeting of formoterol containing polymeric nanoparticles improves recovery from ischemia reperfusion-induced acute kidney injury in mice. Kidney Int 2022; 102:1073-1089. [PMID: 35779607 DOI: 10.1016/j.kint.2022.05.032] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 04/22/2022] [Accepted: 05/20/2022] [Indexed: 12/14/2022]
Abstract
The β2 adrenergic receptor agonist, formoterol, is an inducer of mitochondrial biogenesis and restorer of mitochondrial and kidney function in acute and chronic models of kidney injury. Unfortunately, systemic administration of formoterol has the potential for adverse cardiovascular effects, increased heart rate, and decreased blood pressure. To minimize these effects, we developed biodegradable and biocompatible polymeric nanoparticles containing formoterol that target the kidney, thereby decreasing the effective dose, and lessen cardiovascular effects while restoring kidney function after injury. Male C57Bl/6 mice, treated with these nanoparticles daily, had reduced ischemia-reperfusion-induced serum creatinine and kidney cortex kidney injury molecule-1 levels by 78% and 73% respectively, compared to control mice six days after injury. With nanoparticle therapy, kidney cortical mitochondrial number and proteins reduced by ischemic injury, recovered to levels of sham-operated mice. Tubular necrosis was reduced 69% with nanoparticles treatment. Nanoparticles improved kidney recovery even when the dosing frequency was reduced from daily to two days per week. Finally, compared to treatment with formoterol-free drug alone, these nanoparticles did not increase heart rate nor decrease blood pressure. Thus, targeted kidney delivery of formoterol-containing nanoparticles is an improvement in standard formoterol therapy for ischemia-reperfusion-induced acute kidney injuries by decreasing the dose, dosing frequency, and cardiac side effects.
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Affiliation(s)
- Ernest L Vallorz
- Department of Pharmacology and Toxicology, The University of Arizona R. Ken Coit College of Pharmacy, Skaggs Pharmaceutical Sciences Center, Tucson, Arizona, USA
| | - Jaroslav Janda
- Department of Pharmacology and Toxicology, The University of Arizona R. Ken Coit College of Pharmacy, Skaggs Pharmaceutical Sciences Center, Tucson, Arizona, USA
| | - Heidi M Mansour
- Department of Pharmacology and Toxicology, The University of Arizona R. Ken Coit College of Pharmacy, Skaggs Pharmaceutical Sciences Center, Tucson, Arizona, USA; The University of Arizona College of Medicine, Tucson, Arizona, USA; The University of Arizona, BIO5 Institute, Tucson, Arizona, USA
| | - Rick G Schnellmann
- Department of Pharmacology and Toxicology, The University of Arizona R. Ken Coit College of Pharmacy, Skaggs Pharmaceutical Sciences Center, Tucson, Arizona, USA; The University of Arizona College of Medicine, Tucson, Arizona, USA; The University of Arizona, BIO5 Institute, Tucson, Arizona, USA; Southern Arizona VA Health Care System, USA.
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13
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Meng T, Wang P, Ding J, Du R, Gao J, Li A, Yu S, Liu J, Lu X, He Q. Global Research Trends on Ventricular Remodeling: A Bibliometric Analysis From 2012 to 2022. Curr Probl Cardiol 2022; 47:101332. [PMID: 35870550 DOI: 10.1016/j.cpcardiol.2022.101332] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Accepted: 07/17/2022] [Indexed: 11/03/2022]
Abstract
Ventricular remodeling is the progressive pathologic change of the original substance and morphology of the ventricle caused by various injuries and has attracted increasing attention in the past decade. This study aims to conduct a bibliometric analysis of articles on ventricular remodeling published in the Web of Science Core Collection database from 2012 to 2022 to understand the current research state in the field of ventricular remodeling and provide insights for clinicians and researchers. As a result, a total of 1710 articles on ventricular remodeling were included. Annual publications have been gradually increasing and have remained at a high level over the past 10 years. The United States of America contributed the most publications, followed by China. Circulation was the most mainstream and authoritative journal focusing on ventricular remodeling. Research hotspot analysis suggested that myocardial infarction was the primary risk factor for ventricular remodeling, and emerging risk factor studies have focused on pulmonary hypertension, aortic stenosis, and diabetes. The mechanisms in the pathogenesis of ventricular remodeling were mainly closely associated with inflammation, apoptosis, oxidative stress, and myocardial fibrosis. Intensive investigation of the interactions between different mechanisms might be a future research direction. In terms of treatment, cardiac resynchronization therapy was a hot topic of research. These findings can help researchers grasp the research status of ventricular remodeling and determine future research directions.
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Affiliation(s)
- Tiantian Meng
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Peng Wang
- Department of Traditional Chinese Medicine, Beijing Jiangong Hospital, Beijing, China
| | - Jingyi Ding
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Ruolin Du
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jing Gao
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Anqi Li
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Shanshan Yu
- Graduate School, Henan University of Chinese Medicine, Zhengzhou, Henan, China
| | - Jin Liu
- Graduate School, Henan University of Chinese Medicine, Zhengzhou, Henan, China
| | - Xinyu Lu
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Qingyong He
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
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14
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Krummen DE, Villongco CT, Ho G, Schricker AA, Field ME, Sung K, Kacena KA, Martinson MS, Hoffmayer KS, Hsu JC, Raissi F, Feld GK, McCulloch AD, Han FT. Forward-Solution Noninvasive Computational Arrhythmia Mapping: The VMAP Study. Circ Arrhythm Electrophysiol 2022; 15:e010857. [PMID: 36069189 PMCID: PMC9509662 DOI: 10.1161/circep.122.010857] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 08/16/2022] [Indexed: 11/16/2022]
Abstract
BACKGROUND The accuracy of noninvasive arrhythmia source localization using a forward-solution computational mapping system has not yet been evaluated in blinded, multicenter analysis. This study tested the hypothesis that a computational mapping system incorporating a comprehensive arrhythmia simulation library would provide accurate localization of the site-of-origin for atrial and ventricular arrhythmias and pacing using 12-lead ECG data when compared with the gold standard of invasive electrophysiology study and ablation. METHODS The VMAP study (Vectorcardiographic Mapping of Arrhythmogenic Probability) was a blinded, multicenter evaluation with final data analysis performed by an independent core laboratory. Eligible episodes included atrial and ventricular: tachycardia, fibrillation, pacing, premature atrial and ventricular complexes, and orthodromic atrioventricular reentrant tachycardia. Mapping system results were compared with the gold standard site of successful ablation or pacing during electrophysiology study and ablation. Mapping time was assessed from time-stamped logs. Prespecified performance goals were used for statistical comparisons. RESULTS A total of 255 episodes from 225 patients were enrolled from 4 centers. Regional accuracy for ventricular tachycardia and premature ventricular complexes in patients without significant structural heart disease (n=75, primary end point) was 98.7% (95% CI, 96.0%-100%; P<0.001 to reject predefined H0 <0.80). Regional accuracy for all episodes (secondary end point 1) was 96.9% (95% CI, 94.7%-99.0%; P<0.001 to reject predefined H0 <0.75). Accuracy for the exact or neighboring segment for all episodes (secondary end point 2) was 97.3% (95% CI, 95.2%-99.3%; P<0.001 to reject predefined H0 <0.70). Median spatial accuracy was 15 mm (n=255, interquartile range, 7-25 mm). The mapping process was completed in a median of 0.8 minutes (interquartile range, 0.4-1.4 minutes). CONCLUSIONS Computational ECG mapping using a forward-solution approach exceeded prespecified accuracy goals for arrhythmia and pacing localization. Spatial accuracy analysis demonstrated clinically actionable results. This rapid, noninvasive mapping technology may facilitate catheter-based and noninvasive targeted arrhythmia therapies. REGISTRATION URL: https://www. CLINICALTRIALS gov; Unique identifier: NCT04559061.
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Affiliation(s)
- David E. Krummen
- Department of Medicine, University of California San Diego, La Jolla
- Veterans Affairs San Diego Healthcare System, San Diego
| | | | - Gordon Ho
- Department of Medicine, University of California San Diego, La Jolla
- Veterans Affairs San Diego Healthcare System, San Diego
| | | | | | - Kevin Sung
- Department of Medicine, University of California San Diego, La Jolla
| | | | | | - Kurt S. Hoffmayer
- Department of Medicine, University of California San Diego, La Jolla
- Veterans Affairs San Diego Healthcare System, San Diego
| | - Jonathan C. Hsu
- Department of Medicine, University of California San Diego, La Jolla
| | - Farshad Raissi
- Department of Medicine, University of California San Diego, La Jolla
| | - Gregory K. Feld
- Department of Medicine, University of California San Diego, La Jolla
| | - Andrew D. McCulloch
- Department of Medicine, University of California San Diego, La Jolla
- Department of Bioengineering, University of California San Diego, La Jolla
| | - Frederick T. Han
- Department of Medicine, University of California San Diego, La Jolla
- Veterans Affairs San Diego Healthcare System, San Diego
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15
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Xia R, Tomsits P, Loy S, Zhang Z, Pauly V, Schüttler D, Clauss S. Cardiac Macrophages and Their Effects on Arrhythmogenesis. Front Physiol 2022; 13:900094. [PMID: 35812333 PMCID: PMC9257039 DOI: 10.3389/fphys.2022.900094] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Accepted: 05/30/2022] [Indexed: 12/24/2022] Open
Abstract
Cardiac electrophysiology is a complex system established by a plethora of inward and outward ion currents in cardiomyocytes generating and conducting electrical signals in the heart. However, not only cardiomyocytes but also other cell types can modulate the heart rhythm. Recently, cardiac macrophages were demonstrated as important players in both electrophysiology and arrhythmogenesis. Cardiac macrophages are a heterogeneous group of immune cells including resident macrophages derived from embryonic and fetal precursors and recruited macrophages derived from circulating monocytes from the bone marrow. Recent studies suggest antiarrhythmic as well as proarrhythmic effects of cardiac macrophages. The proposed mechanisms of how cardiac macrophages affect electrophysiology vary and include both direct and indirect interactions with other cardiac cells. In this review, we provide an overview of the different subsets of macrophages in the heart and their possible interactions with cardiomyocytes under both physiologic conditions and heart disease. Furthermore, we elucidate similarities and differences between human, murine and porcine cardiac macrophages, thus providing detailed information for researchers investigating cardiac macrophages in important animal species for electrophysiologic research. Finally, we discuss the pros and cons of mice and pigs to investigate the role of cardiac macrophages in arrhythmogenesis from a translational perspective.
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Affiliation(s)
- Ruibing Xia
- Department of Medicine I, University Hospital Munich, Ludwig-Maximilians-University Munich (LMU), Munich, Germany
- Institute of Surgical Research at the Walter-Brendel-Centre of Experimental Medicine, University Hospital Munich, Ludwig-Maximilians-University Munich (LMU), Munich, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance, Munich, Germany
| | - Philipp Tomsits
- Department of Medicine I, University Hospital Munich, Ludwig-Maximilians-University Munich (LMU), Munich, Germany
- Institute of Surgical Research at the Walter-Brendel-Centre of Experimental Medicine, University Hospital Munich, Ludwig-Maximilians-University Munich (LMU), Munich, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance, Munich, Germany
| | - Simone Loy
- Department of Medicine I, University Hospital Munich, Ludwig-Maximilians-University Munich (LMU), Munich, Germany
- Institute of Surgical Research at the Walter-Brendel-Centre of Experimental Medicine, University Hospital Munich, Ludwig-Maximilians-University Munich (LMU), Munich, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance, Munich, Germany
| | - Zhihao Zhang
- Department of Medicine I, University Hospital Munich, Ludwig-Maximilians-University Munich (LMU), Munich, Germany
- Institute of Surgical Research at the Walter-Brendel-Centre of Experimental Medicine, University Hospital Munich, Ludwig-Maximilians-University Munich (LMU), Munich, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance, Munich, Germany
| | - Valerie Pauly
- Department of Medicine I, University Hospital Munich, Ludwig-Maximilians-University Munich (LMU), Munich, Germany
- Institute of Surgical Research at the Walter-Brendel-Centre of Experimental Medicine, University Hospital Munich, Ludwig-Maximilians-University Munich (LMU), Munich, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance, Munich, Germany
| | - Dominik Schüttler
- Department of Medicine I, University Hospital Munich, Ludwig-Maximilians-University Munich (LMU), Munich, Germany
- Institute of Surgical Research at the Walter-Brendel-Centre of Experimental Medicine, University Hospital Munich, Ludwig-Maximilians-University Munich (LMU), Munich, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance, Munich, Germany
| | - Sebastian Clauss
- Department of Medicine I, University Hospital Munich, Ludwig-Maximilians-University Munich (LMU), Munich, Germany
- Institute of Surgical Research at the Walter-Brendel-Centre of Experimental Medicine, University Hospital Munich, Ludwig-Maximilians-University Munich (LMU), Munich, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance, Munich, Germany
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16
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Al-Mukhtar O, Vogrin S, Lampugnani ER, Noaman S, Dinh DT, Brennan AL, Reid C, Lefkovits J, Cox N, Stub D, Chan W. Temporal Changes in Pollen Concentration Predict Short-Term Clinical Outcomes in Acute Coronary Syndromes. J Am Heart Assoc 2022; 11:e023036. [PMID: 35289185 PMCID: PMC9075470 DOI: 10.1161/jaha.121.023036] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Background Atmospheric changes in pollen concentration may affect human health by triggering various allergic processes. We sought to assess if changes in pollen concentrations were associated with different acute coronary syndrome (ACS) subtype presentations and short-term clinical outcomes. Methods and Results We analyzed data in consecutive patients presenting with ACS (unstable angina, non-ST-segment-elevation myocardial infarction, and ST-segment-elevation myocardial infarction) treated with percutaneous coronary intervention between January 2014 and December 2017 and enrolled in the VCOR (Victorian Cardiac Outcomes Registry). Baseline characteristics were compared among patients exposed to different grass and total pollen concentrations. The primary outcome was occurrence of ACS subtypes and 30-day major adverse cardiac and cerebrovascular events (composite of mortality, myocardial infarction, stent thrombosis, target vessel revascularization, or stroke). Of 15 379 patients, 7122 (46.3%) presented with ST-segment-elevation myocardial infarction, 6781 (44.1%) with non-ST-segment-elevation myocardial infarction, and 1476 (9.6%) with unstable angina. The mean age was 62.5 years, with men comprising 76% of patients. No association was observed between daily or seasonal grass and total pollen concentrations with the frequency of ACS subtype presentation. However, grass and total pollen concentrations in the preceding days (2-day average for grass pollen and 7-day average for total pollen) correlated with in-hospital mortality (odds ratio [OR], 2.17 [95% CI, 1.12-4.21]; P=0.021 and OR, 2.78 [95% CI, 1.00-7.74]; P=0.05), respectively, with a trend of 2-day grass pollen for 30-day major adverse cardiac and cerebrovascular events (OR, 1.50 [95% CI, 0.97-2.32]; P=0.066). Conclusions Increased pollen concentrations were not associated with differential ACS subtype presentation but were significantly related to in-hospital mortality following percutaneous coronary intervention, underscoring a potential biologic link between pollen exposure and clinical outcomes.
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Affiliation(s)
- Omar Al-Mukhtar
- Department of Cardiology Western Health Melbourne Victoria Australia
| | - Sara Vogrin
- Department of Medicine Western HealthMelbourne Medical SchoolUniversity of Melbourne Melbourne Victoria Australia
| | - Edwin R Lampugnani
- School of Biosciences The University of Melbourne Melbourne Victoria Australia
| | - Samer Noaman
- Department of Cardiology Western Health Melbourne Victoria Australia.,Department of Cardiology Alfred Health Melbourne Victoria Australia
| | - Diem T Dinh
- School of Public Health and Preventive Medicine Monash University Melbourne Victoria Australia
| | - Angela L Brennan
- School of Public Health and Preventive Medicine Monash University Melbourne Victoria Australia
| | - Christopher Reid
- School of Public Health and Preventive Medicine Monash University Melbourne Victoria Australia.,NHMRC Centre of Research Excellence in Cardiovascular Outcomes Improvement Curtin University Perth Western Australia Australia
| | - Jeffrey Lefkovits
- School of Public Health and Preventive Medicine Monash University Melbourne Victoria Australia.,Department of Cardiology Royal Melbourne Hospital Melbourne Victoria Australia
| | - Nicholas Cox
- Department of Cardiology Western Health Melbourne Victoria Australia.,Department of Medicine Western HealthMelbourne Medical SchoolUniversity of Melbourne Melbourne Victoria Australia
| | - Dion Stub
- Department of Cardiology Western Health Melbourne Victoria Australia.,Department of Cardiology Alfred Health Melbourne Victoria Australia.,Baker Heart and Diabetes Institute Melbourne Victoria Australia
| | - William Chan
- Department of Cardiology Western Health Melbourne Victoria Australia.,Department of Medicine Western HealthMelbourne Medical SchoolUniversity of Melbourne Melbourne Victoria Australia.,Department of Cardiology Alfred Health Melbourne Victoria Australia.,Baker Heart and Diabetes Institute Melbourne Victoria Australia
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17
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Guddeti RR, Yildiz M, Nayak KR, Alraies MC, Davidson L, Henry TD, Garcia S. Impact of COVID-19 on Acute Myocardial Infarction Care. Cardiol Clin 2022; 40:345-353. [PMID: 35851458 PMCID: PMC8940572 DOI: 10.1016/j.ccl.2022.03.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
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18
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Cai Y, Kang L, Li H, Luo Y, Wen J, Gong Z, Chu Q, Qiu Y, Luo C, Chen K, Zhao X, Li R. Effects of Home-Based Baduanjin Exercise on Left Ventricular Remodeling in Patients With Acute Anterior ST-Segment Elevation Myocardial Infarction: Study Protocol for a Randomized Controlled Trial. Front Cardiovasc Med 2022; 9:778583. [PMID: 35224034 PMCID: PMC8863751 DOI: 10.3389/fcvm.2022.778583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Accepted: 01/03/2022] [Indexed: 12/02/2022] Open
Abstract
Background Left ventricular (LV) remodeling after ST-segment elevation myocardial infarction (STEMI) is a major pathological basis associated with heart failure and increased mortality. Exercise-based cardiac rehabilitation has been verified to significantly improve prognosis and quality of life. As a traditional Chinese Qigong, Baduanjin exercise has effectively alleviated adverse LV remodeling in STEMI patients. Despite this, participation in exercise rehabilitation remains low, and home-based exercise rehabilitation may be an alternative approach. Besides, anterior STEMI is reported to have higher risk of adverse LV remodeling. However, the efficiency regarding home-based Baduanjin exercise on LV remodeling in anterior STEMI patients remains uncertain currently. Methods/Design A single-blind, randomized controlled clinical trial was conducted to explore the efficacy and safety of home-based Baduanjin exercise in anterior STEMI patients compared with moderate intensity aerobic walking. A total of 114 participants were assigned randomly to the Baduanjin group or walking control group at a 1:1 ratio. Eligible participants practiced Baduanjin or walking exercise (5 times a week) for 12 weeks, and then followed up for another 12 weeks. The primary outcome is a relative change in the LV end-diastolic volume. The secondary outcomes include the plasma levels of hypersensitive C-reactive protein and interleukin 6, health-related quality of life measured by EQ-5D-5L, LV ejection fraction, patient health questionnaire-9, generalized anxiety disorder screener-7, short physical performance battery score, and clinical endpoint events. The proportion of circulating regulatory T-cells were also assessed. Adverse events were recorded throughout the trial for safety evaluation. Data were be analyzed by researchers blinded to the treatment allocation. Discussion This study provided powerful evidence for the use of home-based Baduanjin exercise in anterior STEMI patients in alleviating LV remodeling and improving clinical outcomes. Trial Registration The Research Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine has approved this study (ZYYECK[2020]045). Written informed consent of patients were required. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR2100047298). Dissemination Our results will be published in peer-reviewed journals and disseminated through academic conferences and the Internet.
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Affiliation(s)
- Yinhe Cai
- The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Liang Kang
- The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Haiyi Li
- The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yuan Luo
- The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Junmao Wen
- The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Zhaohui Gong
- Department of Cardiovascular Medicine, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Qingmin Chu
- Department of Cardiovascular Medicine, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yijun Qiu
- Department of Cardiovascular Medicine, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Chuanjin Luo
- Department of Cardiovascular Medicine, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Keyu Chen
- Department of Interventional Room, The First Hospital Affiliated of Guangzhou University of Chinese Medicine, Guangzhou, China
- Keyu Chen
| | - Xinjun Zhao
- Department of Cardiovascular Medicine, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Xinjun Zhao
| | - Rong Li
- Department of Cardiovascular Medicine, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- *Correspondence: Rong Li
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19
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Zhao G, Feng Y, Xue L, Cui M, Zhang Q, Xu F, Peng N, Jiang Z, Gao D, Zhang X. Anisotropic conductive reduced graphene oxide/silk matrices promote post-infarction myocardial function by restoring electrical integrity. Acta Biomater 2022; 139:190-203. [PMID: 33836222 DOI: 10.1016/j.actbio.2021.03.073] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 03/29/2021] [Accepted: 03/30/2021] [Indexed: 02/07/2023]
Abstract
Myocardial infarction (MI) remains the leading cause of death globally, often leading to impaired cardiac function and pathological myocardial microenvironment. Electrical conduction abnormalities of the infarcted myocardium not only induce adverse myocardial remodeling but also prevent tissue repair. Restoring the myocardial electrical integrity, particularly the anisotropic electrical signal propagation within the injured area after infarction is crucial for an effective function recovery. Herein, optimized reduced graphene oxide (rGO) functionalized electrospun silk fibroin (rGO/silk) biomaterials presenting anisotropic conductivity and enhanced suturablity were developed and investigated as cardiac patches for their potential in improving the post-MI myocardial function of rat models. The results show that the anisotropic conductive rGO/silk patches exhibit remarkable therapeutic effect on repairing the infarcted myocardium compared to the nonconductive silk and isotropic conductive rGO/silk patches as determined by the enhanced pumping function, reduced susceptibility to arrhythmias, thickened left ventricular walls and improved survival of functional cardiomyocytes. Their notable effect on promoting the angiogenesis of capillaries in the infarcted myocardium has also been demonstrated. This study highlights an effective and biomimetic reconstruction of the electrical myocardial microenvironment based on the anisotropic conductive rGO/silk biomaterials as a promising option for promoting the repair of infarcted myocardium. STATEMENT OF SIGNIFICANCE: The dysfunctional electrical microenvironment in the infarcted myocardium not only aggravates the adverse myocardial remodeling but also limits the effect of cardiac regenerative medicine. Although various conductive biomaterials have been employed to restore the electrical network in the infarcted myocardium in vivo, the anisotropic nature of the myocardial electrical microenvironment which enables directional electrical signal propagation were neglected. In this study, an anisotropic conductive rGO/silk biomaterial system is developed to improve the myocardial function post infarction by restoring the anisotropic electrical microenvironment in the infarcted myocardium. The promoted effects of anisotropic conductive grafts on repairing infarcted hearts are demonstrated with improved pumping function, cardiomyocyte survival, resistance to ventricular fibrillation, and angiogenesis of capillary network.
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Affiliation(s)
- Guoxu Zhao
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Center for Mitochondrial Biology and Medicine, School of Life Science and Technology, International Joint Laboratory for Micro/Nano Manufacturing and Measurement Technology, Xi'an Key Laboratory for Biomedical Testing and High-end Equipment, Xi'an Jiaotong University, Xi'an 710049, Shannxi, PR China; School of Material Science and Chemical Engineering, Xi'an Technological University, Xi'an 710021, Shaanxi, PR China
| | - Yanjing Feng
- Department of Cardiology, The Second Affiliated Hospital, School of Medical, Xi'an Jiaotong University, Xi'an 710004, Shaanxi, PR China
| | - Li Xue
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Center for Mitochondrial Biology and Medicine, School of Life Science and Technology, International Joint Laboratory for Micro/Nano Manufacturing and Measurement Technology, Xi'an Key Laboratory for Biomedical Testing and High-end Equipment, Xi'an Jiaotong University, Xi'an 710049, Shannxi, PR China
| | - Mengjie Cui
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Center for Mitochondrial Biology and Medicine, School of Life Science and Technology, International Joint Laboratory for Micro/Nano Manufacturing and Measurement Technology, Xi'an Key Laboratory for Biomedical Testing and High-end Equipment, Xi'an Jiaotong University, Xi'an 710049, Shannxi, PR China
| | - Qi Zhang
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Center for Mitochondrial Biology and Medicine, School of Life Science and Technology, International Joint Laboratory for Micro/Nano Manufacturing and Measurement Technology, Xi'an Key Laboratory for Biomedical Testing and High-end Equipment, Xi'an Jiaotong University, Xi'an 710049, Shannxi, PR China
| | - Feng Xu
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Bioinspired Engineering and Biomechanics Center (BEBC), School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, Shaanxi, PR China
| | - Niancai Peng
- International Joint Laboratory for Micro/Nano Manufacturing and Measurement Technology, State Key Laboratory for Manufacturing Systems Engineering, Xi'an Key Laboratory for Biomedical Testing and High-end Equipment, Xi'an Jiaotong University, Xi'an 710049, Shaanxi, PR China
| | - Zhuangde Jiang
- International Joint Laboratory for Micro/Nano Manufacturing and Measurement Technology, State Key Laboratory for Manufacturing Systems Engineering, Xi'an Key Laboratory for Biomedical Testing and High-end Equipment, Xi'an Jiaotong University, Xi'an 710049, Shaanxi, PR China
| | - Dengfeng Gao
- Department of Cardiology, The Second Affiliated Hospital, School of Medical, Xi'an Jiaotong University, Xi'an 710004, Shaanxi, PR China.
| | - Xiaohui Zhang
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Center for Mitochondrial Biology and Medicine, School of Life Science and Technology, International Joint Laboratory for Micro/Nano Manufacturing and Measurement Technology, Xi'an Key Laboratory for Biomedical Testing and High-end Equipment, Xi'an Jiaotong University, Xi'an 710049, Shannxi, PR China.
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20
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Landolina M, Boriani G, Biffi M, Cattafi G, Capucci A, Dello Russo A, Facchin D, Rordorf R, Sagone A, Del Greco M, Morani G, Nicolis D, Meloni S, Grammatico A, Gasparini M. Determinants of worse prognosis in patients with cardiac resynchronization therapy defibrillators. Are ventricular arrhythmias an adjunctive risk factor? J Cardiovasc Med (Hagerstown) 2022; 23:42-48. [PMID: 34392257 DOI: 10.2459/jcm.0000000000001236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
AIMS Cardiac resynchronization therapy (CRT) is indicated in patients with systolic heart failure (HF), severe left ventricle (LV) dysfunction and interventricular dyssynchrony.In prospective observational research, we aimed to evaluate whether CRT-induced LV reverse remodelling and occurrence of ventricular arrhythmias (VT/VF) independently contribute to prognosis in patients with CRT defibrillators (CRT-D). METHODS In 95 Italian cardiological centres, after a screening period of 6 months, patients were categorized according to VT/VF occurrence and CRT response, defined as LV end-systolic volume relative reduction >15% or LV ejection fraction absolute increase >5%. The main endpoint was death or HF hospitalizations. RESULTS Among 1308 CRT-D patients (80% male, mean age 66 years), at 6 months, follow-up 71% were identified as CRT responders and 12% experienced appropriate VT/VF detections. The main endpoint was significantly and independently associated with previous myocardial infarction, New York Heart Association Class, VT/VF occurrence and with CRT response. CRT nonresponder patients who suffered VT/VF in the screening period had a risk of death or HF hospitalizations [HR = 7.82, 95% confidence interval (CI) = 3.95-15.48] significantly (P < 0.001) higher than CRT responders without VT/VF occurrence. This risk is mitigated without VT/VF occurrence (HR = 3.47, 95% CI = 2.03-5.91, P < 0.001) or in case of CRT response (HR = 3.11, 95% CI = 1.44-6.72, P = 0.004). CONCLUSION Our data show that both CRT response and occurrence of VT/VF independently contribute to the risk of death or HF-related hospitalizations in CRT-D patients. Early VT/VF occurrence may be identified as a marker of disease severity than can be mitigated by CRT response both in terms of all-cause mortality and long-term VT/VF onset. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT00147290 and NCT00617175.
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Affiliation(s)
| | | | - Mauro Biffi
- Azienda Ospedaliero-Universitaria di Bologna, Bologna
| | | | | | | | | | | | - Antonio Sagone
- Università Statale di Milano (UNIMI), Facoltà di Medicina e Chirurgia, IRCCS Multimedica, Milan
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21
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Wen ZJ, Xin H, Wang YC, Liu HW, Gao YY, Zhang YF. Emerging roles of circRNAs in the pathological process of myocardial infarction. MOLECULAR THERAPY. NUCLEIC ACIDS 2021; 26:828-848. [PMID: 34729251 PMCID: PMC8536508 DOI: 10.1016/j.omtn.2021.10.002] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Myocardial infarction (MI) is defined as cardiomyocyte death in a clinical context consistent with ischemic insult. MI remains one of the leading causes of morbidity and mortality worldwide. Although there are a number of effective clinical methods for the diagnosis and treatment of MI, further investigation of novel biomarkers and molecular therapeutic targets is required. Circular RNAs (circRNAs), novel non-coding RNAs, have been reported to function mainly by acting as microRNA (miRNA) sponges or binding to RNA-binding proteins (RBPs). The circRNA-miRNA-mRNA (protein) regulatory pathway regulates gene expression and affects the pathological mechanisms of various diseases. Undoubtedly, a more comprehensive understanding of the relationship between MI and circRNA will lay the foundation for the development of circRNA-based diagnostic and therapeutic strategies for MI. Therefore, this review summarizes the pathophysiological process of MI and various approaches to measure circRNA levels in MI patients, tissues, and cells; highlights the significance of circRNAs in the regulation MI pathogenesis and development; and provides potential clinical insight for the diagnosis, prognosis, and treatment of MI.
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Affiliation(s)
- Zeng-Jin Wen
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Hui Xin
- Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yong-Chen Wang
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Hao-Wen Liu
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Yan-Yan Gao
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Yin-Feng Zhang
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
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22
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Rostamzadeh F, Najafipour H, Jafarinejad-Farsangi S, Ansari-Asl Z. Beneficial effects of PEGylated graphene quantum dot on arrhythmias induced by myocardial infarction. Biotechnol Appl Biochem 2021; 69:2222-2228. [PMID: 34766653 DOI: 10.1002/bab.2280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 11/06/2021] [Indexed: 11/10/2022]
Abstract
Arrhythmias are one of the leading causes of early death following myocardial infarction (MI) and heart failure. Graphene derivatives have emerged as an therapeutic target that have electrical conductivity. The study aimed to evaluate the impacts of polyethylene glycol-graphene quantum dots (GQDs-PEG) on arrhythmias created by MI in the rat. Animals were randomly assigned to five groups of sham, MI, and MI + GQDs-PEG at doses of 5, 10, and 20 mg/kg. MI was induced by the closure of the left anterior descending artery. The day after MI, animals were administered vehicle (phosphate buffered saline) or GQDs-PEG at different doses every other day for 2 weeks. On day 15, electrocardiogram (ECG), mean arterial pressure (MAP), and heart contractility indices were recorded by the PowerLab data acquisition system. GQDs-PEG 20 mg/kg increased contractility and improved the reduction of MAP in the MI group. The prolonged QT and QTc intervals, inverted T wave, and deviated ST segment were modified by GQDs-PEG 10 and 20 mg/kg in rats with MI. The amplitude of the Q wave was also decreased in a dose-dependent manner in the GQDs-PEG-treated rats. The results demonstrated that 2 weeks of treatment with GQDs-PEG normalized ECG abnormalities and improved left ventricular dysfunction in rats with MI.
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Affiliation(s)
- Farzaneh Rostamzadeh
- Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Hamid Najafipour
- Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
| | - Saeideh Jafarinejad-Farsangi
- Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
| | - Zeinab Ansari-Asl
- Department of Chemistry, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran
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23
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Aimo A, Panichella G, Barison A, Maffei S, Cameli M, Coiro S, D'Ascenzi F, Di Mario C, Liga R, Marcucci R, Morrone D, Olivotto I, Tritto I, Emdin M. Sex-related differences in ventricular remodeling after myocardial infarction. Int J Cardiol 2021; 339:62-69. [PMID: 34314766 DOI: 10.1016/j.ijcard.2021.07.036] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Revised: 07/11/2021] [Accepted: 07/15/2021] [Indexed: 11/24/2022]
Abstract
The epidemiology, clinical features and outcome of myocardial infarction (MI) display significant differences between men and women. Prominent sex differences have also been suggested in left ventricular (LV) remodeling after MI. Ventricular remodeling refers to a deterioration of LV geometry and function often leading to heart failure (HF) development and an increased risk of adverse cardiovascular events. Women have a lower propensity to the acquisition of a spherical geometry and LV dysfunction. These differences can be attributed at least partially to a lower frequency of transmural infarction and smaller areas of microvascular obstruction in women, as well as to a less prominent activation of neuroendocrine systems and apoptotic, inflammatory and profibrotic pathways in women. Estrogens might play a role in this difference, which could partially persist even after the menopause because of a persisting intramyocardial synthesis of estrogens in women. Conversely, androgens may exert a detrimental influence. Future studies should better clarify sex differences in the predictors, clinical correlates, prognostic impact and disease mechanisms of remodeling, as well as the existence of sex-specific therapeutic targets. This research effort should hopefully allow to optimize the treatment of MI during the acute and post-acute phase, possibly through different therapeutic strategies in men and women, with the goal of reducing the risk of HF development and improving patient outcome.
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Affiliation(s)
- Alberto Aimo
- Istituto di Scienze della Vita, Scuola Superiore Sant'Anna, Pisa, Italy; Fondazione Toscana Gabriele Monasterio, Pisa, Italy.
| | | | - Andrea Barison
- Istituto di Scienze della Vita, Scuola Superiore Sant'Anna, Pisa, Italy; Fondazione Toscana Gabriele Monasterio, Pisa, Italy
| | | | - Matteo Cameli
- Department of Medical Biotechnologies, Section of Cardiology, University of Siena, Italy
| | - Stefano Coiro
- Division of Cardiology, University of Perugia, Italy
| | - Flavio D'Ascenzi
- Department of Medical Biotechnologies, Section of Cardiology, University of Siena, Italy
| | - Carlo Di Mario
- Structural Interventional Cardiology, Careggi University Hospital, Florence, Italy
| | - Riccardo Liga
- Cardio-Thoracic and Vascular Department, University Hospital, Pisa, Italy
| | - Rossella Marcucci
- Experimental and Clinical Medicine, University of Florence, Atherothrombotic Center, AOU Careggi, Florence, Italy
| | - Doralisa Morrone
- Cardio-Thoracic and Vascular Department, University Hospital, Pisa, Italy
| | - Iacopo Olivotto
- Cardiomiopathy Unit, AOU Careggi, Florence, Italy. Società Italiana di Cardiologia, Sezione Regionale Tosco-Umbra
| | | | - Michele Emdin
- Istituto di Scienze della Vita, Scuola Superiore Sant'Anna, Pisa, Italy; Fondazione Toscana Gabriele Monasterio, Pisa, Italy
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24
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Schmitz T, Meisinger C, Kirchberger I, Thilo C, Amann U, Baumeister SE, Linseisen J. Impact of COVID-19 pandemic lockdown on myocardial infarction care. Eur J Epidemiol 2021; 36:619-627. [PMID: 34091769 PMCID: PMC8179954 DOI: 10.1007/s10654-021-00764-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Accepted: 05/19/2021] [Indexed: 02/06/2023]
Abstract
The aim of this study was to evaluate the impact of the COVID-19 pandemic lockdown on acute myocardial infarction (AMI) care, and to identify underlying stressors in the German model region for complete AMI registration. The analysis was based on data from the population-based KORA Myocardial Infarction Registry located in the region of Augsburg, Germany. All cases of AMI (n = 210) admitted to one of four hospitals in the city of Augsburg or the county of Augsburg from February 10th, 2020, to May 19, 2020, were included. Patients were divided into three groups, namely pre-lockdown, strict lockdown, and attenuated lockdown period. An additional survey was conducted asking the patients for stress and fears in the 4 weeks prior to their AMI. The AMI rate declined by 44% in the strict lockdown period; in the attenuated lockdown period the rate was 17% lower compared to the pre-lockdown period. The downward trend in AMI rates during lockdown was seen in STEMI and NSTEMI patients, and independent of sex and age. The door-to-device time decreased by 70–80% in the lockdown-periods. In the time prior to the infarction, patients felt stressed mainly due to fear of infection with Sars-CoV-2 and less because of the restrictions and consequences of the lockdown. A strict lockdown due to the Covid-19 pandemic had a marked impact on AMI care even in a non-hot-spot region with relatively few cases of COVID-19. Fear of infection with the virus is presumably the main reason for the drop in hospitalizations due to AMI.
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Affiliation(s)
- Timo Schmitz
- Chair of Epidemiology, University of Augsburg, University Hospital Augsburg, Augsburg, Germany.
- Independent Research Group Clinical Epidemiology, German Research Center for Environmental Health, Helmholtz Zentrum München, Munich, Germany.
| | - Christa Meisinger
- Chair of Epidemiology, University of Augsburg, University Hospital Augsburg, Augsburg, Germany
- Independent Research Group Clinical Epidemiology, German Research Center for Environmental Health, Helmholtz Zentrum München, Munich, Germany
| | - Inge Kirchberger
- Chair of Epidemiology, University of Augsburg, University Hospital Augsburg, Augsburg, Germany
- Independent Research Group Clinical Epidemiology, German Research Center for Environmental Health, Helmholtz Zentrum München, Munich, Germany
| | - Christian Thilo
- Department of Internal Medicine I - Cardiology, University Hospital of Augsburg, Augsburg, Germany
| | - Ute Amann
- Independent Research Group Clinical Epidemiology, German Research Center for Environmental Health, Helmholtz Zentrum München, Munich, Germany
| | - Sebastian E Baumeister
- Chair of Epidemiology, University of Augsburg, University Hospital Augsburg, Augsburg, Germany
- Independent Research Group Clinical Epidemiology, German Research Center for Environmental Health, Helmholtz Zentrum München, Munich, Germany
- University Hospital Münster, Münster, Germany
| | - Jakob Linseisen
- Chair of Epidemiology, University of Augsburg, University Hospital Augsburg, Augsburg, Germany
- Independent Research Group Clinical Epidemiology, German Research Center for Environmental Health, Helmholtz Zentrum München, Munich, Germany
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Zhao S, Dai Y, Ning X, Tang M, Zhao Y, Li Z, Zhang S. Vagus Nerve Stimulation in Early Stage of Acute Myocardial Infarction Prevent Ventricular Arrhythmias and Cardiac Remodeling. Front Cardiovasc Med 2021; 8:648910. [PMID: 33981734 PMCID: PMC8107219 DOI: 10.3389/fcvm.2021.648910] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Accepted: 03/30/2021] [Indexed: 11/17/2022] Open
Abstract
Aims: To evaluate whether low level left vagus nerve stimulation (LLVNS) in early stage of myocardial infarction (MI) could effectively prevent ventricular arrhythmias (VAs) and protect cardiac function, and explore the underlying mechanisms. Methods and Results: After undergoing implantable cardioverter defibrillators (ICD) and left cervical vagal stimulators implantation and MI creation, 16 dogs were randomly divided into three groups: the MI (n = 6), MI+LLVNS (n = 5), and sham operation (n = 5) groups. LLVNS was performed for 3 weeks. VAs, the left ventricular function, the density of the nerve fibers in the infarction area and gene expression profiles were analyzed. Compared with the MI group, dogs in the MI+LLVNS group had a lower VAs incidence (p < 0.05) and better left ventricular function. LLVNS significantly inhibited excessive sympathetic nerve sprouting with the evidences of decreased density of TH, GAP43 and NF positive nerves (p < 0.05). The gene expression profiling found a total of 206 genes differentially expressed between MI+LLVNS and MI dogs, mainly involved in cardiac tissue remodeling, cardiac neural remodeling, immune response and apoptosis. These genes, including 55 up-regulated genes and 151 down-regulated genes, showed more protective expressions under LLVNS. Conclusions: This study suggests that LLVNS was delivered without altering heart rate, contributing to reduced incidences of VAs and improved left ventricular function. The potential mechanisms included suppressing cardiac neuronal sprouting, inhibiting excessive sympathetic nerve sprouting and subduing pro-inflammatory responses by regulating gene expressions from a canine experimental study.
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Affiliation(s)
- Shuang Zhao
- State Key Laboratory of Cardiovascular Disease, Arrhythmia Center, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yan Dai
- State Key Laboratory of Cardiovascular Disease, Arrhythmia Center, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaohui Ning
- State Key Laboratory of Cardiovascular Disease, Arrhythmia Center, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Min Tang
- State Key Laboratory of Cardiovascular Disease, Arrhythmia Center, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yunzi Zhao
- State Key Laboratory of Cardiovascular Disease, Arrhythmia Center, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zeyi Li
- State Key Laboratory of Cardiovascular Disease, Arrhythmia Center, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shu Zhang
- State Key Laboratory of Cardiovascular Disease, Arrhythmia Center, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Rath B, Köbe J, Reinke F, Eckardt L. [Management of premature ventricular ectopy in cardiac resynchronization therapy : Treatment strategies for an optimized cardiac resynchronization]. Herzschrittmacherther Elektrophysiol 2021; 32:41-47. [PMID: 33515111 DOI: 10.1007/s00399-021-00745-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 01/10/2021] [Indexed: 11/29/2022]
Abstract
Cardiac resynchronization therapy (CRT) is an integral part in the treatment of chronic heart failure. However, a high degree of biventricular pacing is essential for the effectiveness of this therapy. In addition to atrial fibrillation, premature ventricular contractions (PVC) are a common cause of reduced biventricular stimulation in CRT. In addition to the prognostically unfavorable reduction of biventricular pacing, PVC are generally associated with reduced outcome in the presence of structural heart disease. Options to increase biventricular stimulation percentage by reprogramming the CRT devices are limited in the majority of cases. Due to the mutual relationship between cardiomyopathy and ventricular arrhythmias, adequate heart failure therapy is essential for the reduction of ventricular ectopy. In addition to beta-blocker therapy, specific antiarrhythmic medication is mostly limited to class III antiarrhythmic drugs due to the structural heart disease usually present in CRT patients. Catheter ablation is superior to pharmacological therapy especially in the field of idiopathic PVC, but promising data are also available for catheter ablation of PVC in structural heart disease and CRT nonresponders.
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Affiliation(s)
- Benjamin Rath
- Klinik für Kardiologie II: Rhythmologie, Universitätsklinikum Münster, Albert-Schweitzer Campus 1, 48149, Münster, Deutschland.
| | - Julia Köbe
- Klinik für Kardiologie II: Rhythmologie, Universitätsklinikum Münster, Albert-Schweitzer Campus 1, 48149, Münster, Deutschland
| | - Florian Reinke
- Klinik für Kardiologie II: Rhythmologie, Universitätsklinikum Münster, Albert-Schweitzer Campus 1, 48149, Münster, Deutschland
| | - Lars Eckardt
- Klinik für Kardiologie II: Rhythmologie, Universitätsklinikum Münster, Albert-Schweitzer Campus 1, 48149, Münster, Deutschland
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Rodríguez-Leor O, Cid-Álvarez B, Pérez de Prado A, Rossello X, Ojeda S, Serrador A, López-Palop R, Martín-Moreiras J, Rumoroso JR, Cequier Á, Ibáñez B, Cruz-González I, Romaguera R, Moreno R, Villa M, Ruíz-Salmerón R, Molano F, Sánchez C, Muñoz-García E, Íñigo L, Herrador J, Gómez-Menchero A, Gómez-Menchero A, Caballero J, Ojeda S, Cárdenas M, Gheorghe L, Oneto J, Morales F, Valencia F, Ruíz JR, Diarte JA, Avanzas P, Rondán J, Peral V, Pernasetti LV, Hernández J, Bosa F, Lorenzo PLM, Jiménez F, Hernández JMDLT, Jiménez-Mazuecos J, Lozano F, Moreu J, Novo E, Robles J, Moreiras JM, Fernández-Vázquez F, Amat-Santos IJ, Gómez-Hospital JA, García-Picart J, Blanco BGD, Regueiro A, Carrillo-Suárez X, Tizón H, Mohandes M, Casanova J, Agudelo-Montañez V, Muñoz JF, Franco J, Del Castillo R, Salinas P, Elizaga J, Sarnago F, Jiménez-Valero S, Rivero F, Oteo JF, Alegría-Barrero E, Sánchez-Recalde Á, Ruíz V, Pinar E, Pinar E, Planas A, Ledesma BL, Berenguer A, Fernández-Cisnal A, Aguar P, Pomar F, Jerez M, Torres F, García R, Frutos A, Nodar JMR, García K, Sáez R, Torres A, Tellería M, Sadaba M, Mínguez JRL, Merchán JCR, Portales J, Trillo R, Aldama G, Fernández S, Santás M, Pérez MPP. [Impact of COVID-19 on ST-segment elevation myocardial infarction care. The Spanish experience]. Rev Esp Cardiol 2020; 73:994-1002. [PMID: 33071427 PMCID: PMC7546233 DOI: 10.1016/j.recesp.2020.07.033] [Citation(s) in RCA: 84] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 07/28/2020] [Indexed: 12/29/2022]
Abstract
INTRODUCTION AND OBJECTIVES The COVID-19 outbreak has had an unclear impact on the treatment and outcomes of patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to assess changes in STEMI management during the COVID-19 outbreak. METHODS Using a multicenter, nationwide, retrospective, observational registry of consecutive patients who were managed in 75 specific STEMI care centers in Spain, we compared patient and procedural characteristics and in-hospital outcomes in 2 different cohorts with 30-day follow-up according to whether the patients had been treated before or after COVID-19. RESULTS Suspected STEMI patients treated in STEMI networks decreased by 27.6% and patients with confirmed STEMI fell from 1305 to 1009 (22.7%). There were no differences in reperfusion strategy (> 94% treated with primary percutaneous coronary intervention in both cohorts). Patients treated with primary percutaneous coronary intervention during the COVID-19 outbreak had a longer ischemic time (233 [150-375] vs 200 [140-332] minutes, P < .001) but showed no differences in the time from first medical contact to reperfusion. In-hospital mortality was higher during COVID-19 (7.5% vs 5.1%; unadjusted OR, 1.50; 95%CI, 1.07-2.11; P < .001); this association remained after adjustment for confounders (risk-adjusted OR, 1.88; 95%CI, 1.12-3.14; P = .017). In the 2020 cohort, there was a 6.3% incidence of confirmed SARS-CoV-2 infection during hospitalization. CONCLUSIONS The number of STEMI patients treated during the current COVID-19 outbreak fell vs the previous year and there was an increase in the median time from symptom onset to reperfusion and a significant 2-fold increase in the rate of in-hospital mortality. No changes in reperfusion strategy were detected, with primary percutaneous coronary intervention performed for the vast majority of patients. The co-existence of STEMI and SARS-CoV-2 infection was relatively infrequent.
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Affiliation(s)
- Oriol Rodríguez-Leor
- Institut del Cor, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, España
- Centro de Investigación Biomédica en Red Enfermedades Cardiovaculares (CIBERCV), Instituto de Salud Carlos III, Madrid, España
- Institut de Recerca en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, España
| | - Belén Cid-Álvarez
- Servicio de Cardiología, Hospital Clínico de Santiago de Compostela, Santiago de Compostela, A Coruña, España
| | | | - Xavier Rossello
- Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, España
- Servicio de Cardiología, Institut d'Investigació Sanitària de les Illes Balears (IdISBa), Hospital Universitari Son Espases, Palma de Mallorca, Balearic Islands, España
- Centro de Investigación Biomédica en Red Enfermedades Cardiovaculares (CIBERCV), Instituto de Salud Carlos III, Madrid, España
| | - Soledad Ojeda
- Servicio de Cardiología, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba, Córdoba, España
| | - Ana Serrador
- Servicio de Cardiología, Hospital Clínico de Valladolid, Valladolid, España
- Centro de Investigación Biomédica en Red Enfermedades Cardiovaculares (CIBERCV), Instituto de Salud Carlos III, Madrid, España
| | - Ramón López-Palop
- Servicio de Cardiología, Hospital Virgen de la Arrixaca, El Palmar, Murcia, España
| | - Javier Martín-Moreiras
- Servicio de Cardiología, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, España
- Centro de Investigación Biomédica en Red Enfermedades Cardiovaculares (CIBERCV), Instituto de Salud Carlos III, Madrid, España
| | - José Ramón Rumoroso
- Servicio de Cardiología, Hospital de Galdakao-Usansolo, Galdakao, Vizcaya, España
| | - Ángel Cequier
- Servicio de Cardiología, Hospital de Bellvitge-Instituto de Investigación Biomédica de Bellvitge (IDIBELL), Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, España
| | - Borja Ibáñez
- Centro de Investigación Biomédica en Red Enfermedades Cardiovaculares (CIBERCV), Instituto de Salud Carlos III, Madrid, España
- Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, España
- Servicio de Cardiología, Hospital Universitario IIS-Fundación Jiménez Díaz, Madrid, España
| | - Ignacio Cruz-González
- Servicio de Cardiología, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, España
- Centro de Investigación Biomédica en Red Enfermedades Cardiovaculares (CIBERCV), Instituto de Salud Carlos III, Madrid, España
| | - Rafael Romaguera
- Servicio de Cardiología, Hospital de Bellvitge-Instituto de Investigación Biomédica de Bellvitge (IDIBELL), Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, España
| | - Raúl Moreno
- Servicio de Cardiología, Hospital Universitario La Paz, Madrid, España
- Centro de Investigación Biomédica en Red Enfermedades Cardiovaculares (CIBERCV), Instituto de Salud Carlos III, Madrid, España
| | | | | | | | | | | | | | | | | | | | | | | | | | | | - Jesús Oneto
- Hospital Universitario de Jerez de la Frontera
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Juan Franco
- Hospital Universitario Fundación Jiménez Díaz
| | | | - Pablo Salinas
- Hospital Clínico San Carlos y Hospital Príncipe de Asturias
| | | | | | | | | | | | | | | | | | | | - Eduardo Pinar
- Luciano Consuegra-Sánchez, Hospital Universitario Santa Lucía de Cartagena
| | - Ana Planas
- Hospital General Universitario de Castellón
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Ramiro Trillo
- Hospital Clínico Universitario Santiago de Compostela
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Rodríguez-Leor O, Cid-Álvarez B, Pérez de Prado A, Rossello X, Ojeda S, Serrador A, López-Palop R, Martín-Moreiras J, Rumoroso JR, Cequier Á, Ibáñez B, Cruz-González I, Romaguera R, Moreno R, Villa M, Ruíz-Salmerón R, Molano F, Sánchez C, Muñoz-García E, Íñigo L, Herrador J, Gómez-Menchero A, Gómez-Menchero A, Caballero J, Ojeda S, Cárdenas M, Gheorghe L, Oneto J, Morales F, Valencia F, Ruíz JR, Diarte JA, Avanzas P, Rondán J, Peral V, Pernasetti LV, Hernández J, Bosa F, Lorenzo PLM, Jiménez F, Hernández JMDLT, Jiménez-Mazuecos J, Lozano F, Moreu J, Novo E, Robles J, Moreiras JM, Fernández-Vázquez F, Amat-Santos IJ, Gómez-Hospital JA, García-Picart J, Blanco BGD, Regueiro A, Carrillo-Suárez X, Tizón H, Mohandes M, Casanova J, Agudelo-Montañez V, Muñoz JF, Franco J, Del Castillo R, Salinas P, Elizaga J, Sarnago F, Jiménez-Valero S, Rivero F, Oteo JF, Alegría-Barrero E, Sánchez-Recalde Á, Ruíz V, Pinar E, Pinar E, Planas A, Ledesma BL, Berenguer A, Fernández-Cisnal A, Aguar P, Pomar F, Jerez M, Torres F, García R, Frutos A, Nodar JMR, García K, Sáez R, Torres A, Tellería M, Sadaba M, Mínguez JRL, Merchán JCR, Portales J, Trillo R, Aldama G, Fernández S, Santás M, Pérez MPP. Impact of COVID-19 on ST-segment elevation myocardial infarction care. The Spanish experience. REVISTA ESPANOLA DE CARDIOLOGIA (ENGLISH ED.) 2020; 73:994-1002. [PMID: 32917566 PMCID: PMC7834732 DOI: 10.1016/j.rec.2020.08.002] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 07/28/2020] [Indexed: 12/29/2022]
Abstract
INTRODUCTION AND OBJECTIVES The COVID-19 outbreak has had an unclear impact on the treatment and outcomes of patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to assess changes in STEMI management during the COVID-19 outbreak. METHODS Using a multicenter, nationwide, retrospective, observational registry of consecutive patients who were managed in 75 specific STEMI care centers in Spain, we compared patient and procedural characteristics and in-hospital outcomes in 2 different cohorts with 30-day follow-up according to whether the patients had been treated before or after COVID-19. RESULTS Suspected STEMI patients treated in STEMI networks decreased by 27.6% and patients with confirmed STEMI fell from 1305 to 1009 (22.7%). There were no differences in reperfusion strategy (> 94% treated with primary percutaneous coronary intervention in both cohorts). Patients treated with primary percutaneous coronary intervention during the COVID-19 outbreak had a longer ischemic time (233 [150-375] vs 200 [140-332] minutes, P<.001) but showed no differences in the time from first medical contact to reperfusion. In-hospital mortality was higher during COVID-19 (7.5% vs 5.1%; unadjusted OR, 1.50; 95%CI, 1.07-2.11; P <.001); this association remained after adjustment for confounders (risk-adjusted OR, 1.88; 95%CI, 1.12-3.14; P=.017). In the 2020 cohort, there was a 6.3% incidence of confirmed SARS-CoV-2 infection during hospitalization. CONCLUSIONS The number of STEMI patients treated during the current COVID-19 outbreak fell vs the previous year and there was an increase in the median time from symptom onset to reperfusion and a significant 2-fold increase in the rate of in-hospital mortality. No changes in reperfusion strategy were detected, with primary percutaneous coronary intervention performed for the vast majority of patients. The co-existence of STEMI and SARS-CoV-2 infection was relatively infrequent.
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Affiliation(s)
- Oriol Rodríguez-Leor
- Institut del Cor, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain; Centro de Investigación Biomédica en Red Enfermedades Cardiovaculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain; Institut de Recerca en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain.
| | - Belén Cid-Álvarez
- Servicio de Cardiología, Hospital Clínico de Santiago de Compostela, Santiago de Compostela, A Coruña, Spain
| | | | - Xavier Rossello
- Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Servicio de Cardiología, Institut d'Investigació Sanitària de les Illes Balears (IdISBa), Hospital Universitari Son Espases, Palma de Mallorca, Islas Baleares, Spain; Centro de Investigación Biomédica en Red Enfermedades Cardiovaculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
| | - Soledad Ojeda
- Servicio de Cardiología, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba, Córdoba, Spain
| | - Ana Serrador
- Servicio de Cardiología, Hospital Clínico de Valladolid, Valladolid, Spain; Centro de Investigación Biomédica en Red Enfermedades Cardiovaculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
| | - Ramón López-Palop
- Servicio de Cardiología, Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain
| | - Javier Martín-Moreiras
- Servicio de Cardiología, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain; Centro de Investigación Biomédica en Red Enfermedades Cardiovaculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
| | - José Ramón Rumoroso
- Servicio de Cardiología, Hospital de Galdakao-Usansolo, Galdakao, Vizcaya, Spain
| | - Ángel Cequier
- Servicio de Cardiología, Hospital de Bellvitge-Instituto de Investigación Biomédica de Bellvitge (IDIBELL), Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Borja Ibáñez
- Centro de Investigación Biomédica en Red Enfermedades Cardiovaculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Servicio de Cardiología, Hospital Universitario IIS-Fundación Jiménez Díaz, Madrid, Spain
| | - Ignacio Cruz-González
- Servicio de Cardiología, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain; Centro de Investigación Biomédica en Red Enfermedades Cardiovaculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
| | - Rafael Romaguera
- Servicio de Cardiología, Hospital de Bellvitge-Instituto de Investigación Biomédica de Bellvitge (IDIBELL), Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Raúl Moreno
- Servicio de Cardiología, Hospital Universitario La Paz, Madrid, Spain; Centro de Investigación Biomédica en Red Enfermedades Cardiovaculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
| | | | | | | | | | | | | | | | | | | | | | | | | | | | - Jesús Oneto
- Hospital Universitario de Jerez de la Frontera
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Juan Franco
- Hospital Universitario Fundación Jiménez Díaz
| | | | - Pablo Salinas
- Hospital Clínico San Carlos y Hospital Príncipe de Asturias
| | | | | | | | | | | | | | | | | | | | - Eduardo Pinar
- Luciano Consuegra-Sánchez, Hospital Universitario Santa Lucía de Cartagena
| | - Ana Planas
- Hospital General Universitario de Castellón
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Ramiro Trillo
- Hospital Clínico Universitario Santiago de Compostela
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Rodriguez-Leor O, Cid-Alvarez B. ST-Segment Elevation Myocardial Infarction Care During COVID-19: Losing Sight of the Forest for the Trees. JACC Case Rep 2020; 2:1625-1627. [PMID: 32328589 PMCID: PMC7177148 DOI: 10.1016/j.jaccas.2020.04.011] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Affiliation(s)
- Oriol Rodriguez-Leor
- Institut del Cor, Hospital Germans Trias i Pujol, Badalona, Spain
- Institut de Recerca Germans Trias i Pujol, Badalona, Spain
| | - Belen Cid-Alvarez
- Department of Cardiology, Complexo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain
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Legallois D, Macquaire C, Hodzic A, Allouche S, El Khouakhi I, Manrique A, Milliez P, Saloux E, Beygui F. Serum neprilysin levels are associated with myocardial stunning after ST-elevation myocardial infarction. BMC Cardiovasc Disord 2020; 20:316. [PMID: 32615924 PMCID: PMC7333398 DOI: 10.1186/s12872-020-01578-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Accepted: 06/10/2020] [Indexed: 12/11/2022] Open
Abstract
Background Left ventricular remodeling following ST-elevation myocardial infarction (STEMI) is associated with poor outcome, including heart failure (HF). Neprilysin inhibition leads to improved outcome in patients with altered left ventricular ejection fraction (LVEF). Methods We aimed to assess the association between serum levels of neprilysin and left ventricular (LV) volumes, function and remodeling in STEMI patients with successful myocardial reperfusion and no clinical sign of HF. Sixty-eight patients were admitted for STEMI and had both plasma neprilysin measurement at baseline and 3D transthoracic echocardiogram at baseline and after a median follow-up of 7 months. We compared 3 groups: a group with a low-level of plasma neprilysin (< 125 pg/mL, i.e. the lower limit of detection of the assay) and the two other groups were defined as being below or above the median value of the remaining samples. Results Median age was 58.5 ± 12.8 years and 56 (82.4%) were men. Median LVEF was 45.0 ± 8.5%. Baseline characteristics were comparable between groups (low-level of neprilysin group [≤125 pg/mL, n = 38], medium-level of neprilysin group [126–450 pg/mL, n = 15] and a high-level group [> 450 pg/mL, n = 15]). At baseline there was a non-significant trend towards lower end-diastolic volume (p = 0.07) but significantly lower LVEF in the high neprilysin group (46.4 ± 8.3%, 47.1 ± 8.1% and 39.1 ± 6.9%, p < 0.01). At follow-up, the magnitude of LVEF increase was significantly more important in the high neprilysin group compared to the other groups (p = 0.022 for relative change in LVEF and 6.6 ± 7.3%, 3.6 ± 9.0% and 11.3 ± 8.4%, p = 0.031 for absolute change in LVEF) resulting in similar LVEF levels at follow-up between all groups (53.0 ± 8.9%, 50.6 ± 9.7% and 50.4 ± 9.9%, p = 0.55). Conclusions Initial high neprilysin levels may identify patients with stunned myocardium early after STEMI, with a recovery of contractility leading to improved LVEF at follow-up. Future studies will have to assess the role of neprilysin in the setting of STEMI and the potential benefit of its blockade.
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Affiliation(s)
- Damien Legallois
- Department of Cardiology, EA4650 Signalisation, Electrophysiologie et imagerie des lésions d'ischémie-reperfusion myocardique (SEILIRM), FHU REMOD-VHF, Normandie Univ, UNICAEN, CHU de Caen Normandie, 14000, Caen, France.
| | - Clémence Macquaire
- Department of Cardiology, Normandie Univ, UNICAEN, CHU de Caen Normandie, 14000, Caen, France
| | - Amir Hodzic
- Department of Clinical Physiology, INSERM Comete, Normandie Univ, UNICAEN, CHU de Caen Normandie, 14000, Caen, France
| | - Stéphane Allouche
- Department of Biochemistry, EA4650 Signalisation, Electrophysiologie et imagerie des lésions d'ischémie-reperfusion myocardique (SEILIRM), FHU REMOD-VHF, Normandie Univ, UNICAEN, CHU de Caen Normandie, 14000, Caen, France
| | - Ismaïl El Khouakhi
- Department of Cardiology, Normandie Univ, UNICAEN, CHU de Caen Normandie, 14000, Caen, France
| | - Alain Manrique
- Department of Nuclear Medicine, EA4650 Signalisation, Electrophysiologie et imagerie des lésions d'ischémie-reperfusion myocardique (SEILIRM), GIP Cyceron, FHU REMOD-VHF, Normandie Univ, UNICAEN, CHU de Caen Normandie, 14000, Caen, France
| | - Paul Milliez
- Department of Cardiology, EA4650 Signalisation, Electrophysiologie et imagerie des lésions d'ischémie-reperfusion myocardique (SEILIRM), FHU REMOD-VHF, Normandie Univ, UNICAEN, CHU de Caen Normandie, 14000, Caen, France
| | - Eric Saloux
- Department of Cardiology, EA4650 Signalisation, Electrophysiologie et imagerie des lésions d'ischémie-reperfusion myocardique (SEILIRM), FHU REMOD-VHF, Normandie Univ, UNICAEN, CHU de Caen Normandie, 14000, Caen, France
| | - Farzin Beygui
- Department of Cardiology, EA4650 Signalisation, Electrophysiologie et imagerie des lésions d'ischémie-reperfusion myocardique (SEILIRM), FHU REMOD-VHF, Normandie Univ, UNICAEN, CHU de Caen Normandie, 14000, Caen, France.,ACTION academic research group, Pitié Salpêtrière University Hospital, Paris, France
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Left-Ventricular Function After 3 Months of Sacubitril-Valsartan in Acute Decompensated Heart Failure. J Cardiovasc Transl Res 2020; 14:290-298. [PMID: 32557158 DOI: 10.1007/s12265-020-10041-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Accepted: 05/26/2020] [Indexed: 10/24/2022]
Abstract
There is limited data on the effect of sacubitril-valsartan on the echocardiographic parameters in acute decompensated heart failure (ADHF). We prospectively enrolled 68 consecutive patients with ADHF who received sacubitril-valsartan (N = 34, S/V group) or angiotensin inhibition-based therapy (N = 34, ACEi/ARB group). Two-dimensional echocardiography with speckle tracking (2D-STE) was performed at baseline and after 3 months of treatment. Changes in 2D-STE parameters, including global longitudinal strain (GLS), were compared between the groups by t test and ANCOVA. Baseline characteristics were similar between the groups. Following 3 months of treatment, LVEF and GLS significantly improved in the S/V group (mean LVEF from 27 to 34.5% and GLS from - 6.6 to - 9.4%) but not in ACEi/ARB group. The improvement in LVEF and GLS was more prominent in patients with non-ischemic cardiomyopathy. In patients with ADHF 3-month treatment with sacubitril-valsartan, compared to guideline directed medical therapy without sacubitril, improves LVEF and GLS. Graphical Abstract A typical change in GLS in a patient with acute decompensated heart failure after 3 months of sacubitril-valsartan.
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The effect of nutraceuticals on multiple signaling pathways in cardiac fibrosis injury and repair. Heart Fail Rev 2020; 27:321-336. [PMID: 32495263 DOI: 10.1007/s10741-020-09980-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Cardiac fibrosis is one of the most common pathological conditions caused by different heart diseases, including myocardial infarction and diabetic cardiomyopathy. Cardiovascular disease is one of the major causes of mortality worldwide. Cardiac fibrosis is caused by different processes, including inflammatory reactions and oxidative stress. The process of fibrosis begins by changing the balance between production and destruction of extracellular matrix components and stimulating the proliferation and differentiation of cardiac fibroblasts. Many studies have focused on finding drugs with less adverse effects for the treatment of cardiovascular disease. Some studies show that nutraceuticals are effective in preventing and treating diseases, including cardiovascular disease, and that they can reduce the risk. However, big clinical studies to prove the therapeutic properties of all these substances and their adverse effects are lacking so far. Therefore, in this review, we tried to summarize the knowledge on pathways and mechanisms of several nutraceuticals which have shown their usefulness in the prevention of cardiac fibrosis.
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Tawfik W, El-Sherif A, Bendary A, Mahros M, Salem M. Impact of global longitudinal strain on left ventricular remodeling and clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI). Echocardiography 2020; 37:570-577. [PMID: 32240553 DOI: 10.1111/echo.14648] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Revised: 03/02/2020] [Accepted: 03/12/2020] [Indexed: 12/01/2022] Open
Abstract
BACKGROUND Predicting left ventricle (LV) remodeling is important for outcome prediction in patients with ST-segment elevation myocardial infarction (STEMI). Novel echocardiographic techniques may be beneficial for those patients. OBJECTIVES We hypothesized that the semiautomated calculation of baseline global longitudinal strain (GLS) can predict LV remodeling and 6-month clinical outcomes in these patients. METHODS During the period from March to December 2018, 130 patients with successful reperfusion of STEMI were prospectively included. Within 48 hours, patients underwent a baseline GLS study with follow-up study at 6 months. Patients were divided into two groups: group I: patients who showed adverse LV remodeling and group II: patients who did not. The endpoint was a composite of cardiovascular mortality, readmission due to heart failure, and urgent revascularization. RESULTS The mean baseline GLS changed from -13.1 ± 3.5% for group I and -16.8 ± 3.1% for group II, to -10.2 ± 4.7% and -12.6 ± 3.1%, respectively, at 6-month follow-up. ROC analysis demonstrated a cutoff value of baseline GLS > -12.5% predicted LV remodeling with 64.5% sensitivity and 89% specificity (AUC 0.797, 95% CI 0.690-0.904). Multivariate logistic regression analysis model using 6-month MACEs occurrence as a dependent factor showed baseline GLS value> -12.5% to be the only significant independent predictor MACEs occurrence (OR 0.704, 95% CI 0.597-0.829, P < .001). Linear regression analysis showed that for every point estimate deterioration of baseline GLS, there was a significant corresponding 2.55 mL increase in LVEDV at 6-month follow-up (CI -4.501 to -0.612, P = .01). CONCLUSION GLS measurement can predict remodeling and adverse clinical events in STEMI patients.
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Affiliation(s)
- Wael Tawfik
- Cardiology Department, Benha Faculty of Medicine, Benha University, Benha, Egypt
| | - Amr El-Sherif
- Cardiology Department, Benha Faculty of Medicine, Benha University, Benha, Egypt
| | - Ahmed Bendary
- Cardiology Department, Benha Faculty of Medicine, Benha University, Benha, Egypt
| | - Mohammed Mahros
- Cardiology Department, Benha Faculty of Medicine, Benha University, Benha, Egypt
| | - Mohamed Salem
- Cardiology Department, Benha Faculty of Medicine, Benha University, Benha, Egypt
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Cheng Y, Luo D, Zhao Y, Rong J. N-Propargyl caffeate amide (PACA) prevents cardiac fibrosis in experimental myocardial infarction by promoting pro-resolving macrophage polarization. Aging (Albany NY) 2020; 12:5384-5398. [PMID: 32203054 PMCID: PMC7138579 DOI: 10.18632/aging.102959] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Accepted: 01/24/2020] [Indexed: 12/28/2022]
Abstract
Macrophages control the initiation and resolution of cardiac fibrosis in post-infarction cardiac remodeling. The aim of the present study was to investigate whether N-propargyl caffeate amide (PACA) could suppress myocardial fibrosis via regulating macrophage polarization. By using rat model of isoproterenol-induced myocardial fibrosis, we discovered that PACA could reduce cardiac fibrosis in a dose-dependent manner. To elucidate the anti-fibrotic mechanisms, we examined whether PACA affected pro-inflammatory M1 and pro-resolving macrophage biomarkers in macrophage polarization. As result, PACA reduced the expression of pro-inflammatory M1 biomarkers (e.g., iNOS, TNF-α, CXCL10, IL-6, CCL2 and CD80) while increased the expression of pro-resolving M2a biomarkers (e.g., IL-10, arginase-1, FZZ1, YM-1 and CD163) in LPS-stimulated RAW264.7 macrophages. PACA also suppressed the elevation of M1 biomarker ED1 in the early phase but up-regulated the expression of pro-resolving biomarker ED2 in the later phase. Moreover, PACA reduced the expression of pro-fibrotic TGF-β1 and PDGF-α while maintained or even increased the production of pro-apoptotic MMP-13, MMP-9 and TRAIL. Importantly, mechanistic studies revealed that PACA might promote the switch of macrophage polarization towards a pro-resolving macrophage phenotype via activating PPAR-γ pathway. Taken together, this study suggested that PACA might be a drug candidate for preventing cardiac fibrosis in myocardial infarction.
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Affiliation(s)
- Yuanyuan Cheng
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Dan Luo
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Yingke Zhao
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Jianhui Rong
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.,The University of Hong Kong Shenzhen Institute of Research and Innovation (HKU-SIRI), Shenzhen, China
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van der Bijl P, Abou R, Goedemans L, Gersh BJ, Holmes DR, Ajmone Marsan N, Delgado V, Bax JJ. Left ventricular remodelling after ST-segment elevation myocardial infarction: sex differences and prognosis. ESC Heart Fail 2020; 7:474-481. [PMID: 32059084 PMCID: PMC7160476 DOI: 10.1002/ehf2.12618] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Revised: 12/13/2019] [Accepted: 01/03/2020] [Indexed: 12/13/2022] Open
Abstract
Aims Left ventricular (LV) remodelling after ST‐segment elevation myocardial infarction (STEMI) worsens outcome. The effect of sex on LV post‐infarct remodelling is unknown. We therefore investigated the sex distribution and long‐term prognosis of LV post‐infarct remodelling after STEMI in the contemporary era of primary percutaneous coronary intervention (PCI) and optimal pharmacotherapy. Methods and results Data were obtained from an ongoing primary PCI STEMI registry. LV remodelling was defined as ≥20% increase in LV end‐diastolic volume at either 3, 6, or 12 months post‐infarct, and LV remodelling impact on outcome was evaluated with a log‐rank test. A total population of 1995 STEMI patients were analysed (mean age 60 ± 12 years): 1527 (77%) men and 468 (23%) women. The mean age of male patients was 60±11 versus 63±13 years for women (P < 0.001). A total of 953 (48%) patients experienced LV remodelling in the first 12 months of follow‐up, and it was equally frequent amongst men (n = 729, 48%) and women (n = 224, 48%). After a median follow‐up of 94 (interquartile range 69–119) months, 225 patients died: 171 (11%) men and 54 (12%) women. No survival difference was seen between remodellers and non‐remodellers in the male (P = 0.113) and female (P = 0.920) groups. Conclusion LV post‐infarct remodelling incidence, as well as long‐term survival of LV remodellers and non‐remodellers, was similar in men and women who were treated with primary PCI and optimal pharmacotherapy post‐STEMI.
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Affiliation(s)
- Pieter van der Bijl
- Department of Cardiology, Heart Lung Centre, Leiden University Medical Centre, Leiden, The Netherlands.,Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA
| | - Rachid Abou
- Department of Cardiology, Heart Lung Centre, Leiden University Medical Centre, Leiden, The Netherlands
| | - Laurien Goedemans
- Department of Cardiology, Heart Lung Centre, Leiden University Medical Centre, Leiden, The Netherlands
| | - Bernard J Gersh
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA
| | - David R Holmes
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA
| | - Nina Ajmone Marsan
- Department of Cardiology, Heart Lung Centre, Leiden University Medical Centre, Leiden, The Netherlands
| | - Victoria Delgado
- Department of Cardiology, Heart Lung Centre, Leiden University Medical Centre, Leiden, The Netherlands
| | - Jeroen J Bax
- Department of Cardiology, Heart Lung Centre, Leiden University Medical Centre, Leiden, The Netherlands
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36
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Chu AA, Wu TT, Zhang L, Zhang Z. The prognostic value of left atrial and left ventricular strain in patients after ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. Cardiol J 2020; 28:678-689. [PMID: 32037499 DOI: 10.5603/cj.a2020.0010] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Revised: 12/27/2019] [Accepted: 01/20/2020] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Global longitudinal strain (GLS) based on two-dimensional speckle-tracking echocardiography (2D-STE) might better reflect left ventricular (LV) contractile performance than conventional parameters. Recently, left atrial (LA) strain has been used as a more accurate alternative to assessing LA performance. The aim in this study was to assess the clinical prognostic value of left ventricular GLS (LV GLS) and peak atrial longitudinal strain (PALS) in patients after ST-segment elevation myocardial infarction (STEMI). METHODS The study enrolled 199 patients who underwent primary percutaneous coronary intervention (pPCI) for first STEMI. Conventional and 2D-STE were performed within 48 h after pPCI. LV GLS and PALS were related to LV remodeling at 6-month follow-up and to adverse events. RESULTS Diabetes mellitus, GLS and PALS independently predicted LV remodeling. With multivariable Cox proportional hazards, diabetes mellitus, GLS and PALS were predictive of adverse clinical outcomes. However, PALS did not add significant incremental value beyond LV GLS in the prediction of LV remodeling (increase in area under the receiver-operator characteristic curve [AUC]: 0.05, p = 0.24) and clinical events (even a decrease in AUC: 0.03, p = 0.69). CONCLUSIONS Both GLS and PALS provide independent prognostic value for adverse LV remodeling and clinical outcomes after STEMI. However, the ability of the combination of PALS and GLS to predict LV remodeling and clinical outcomes may not be superior to that of a single indicator.
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Affiliation(s)
- Ai-Ai Chu
- Heart Center, The First Hospital of Lanzhou University, Lanzhou University, Lanzhou, China.,Department of Cardiology, Gansu Provincial Hospital, Lanzhou, China
| | - Ting-Ting Wu
- Heart Center, The First Hospital of Lanzhou University, Lanzhou University, Lanzhou, China
| | - Lu Zhang
- Heart Center, The First Hospital of Lanzhou University, Lanzhou University, Lanzhou, China
| | - Zheng Zhang
- Heart Center, The First Hospital of Lanzhou University, Lanzhou University, Lanzhou, China.
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Left Ventricular Post-Infarct Remodeling: Implications for Systolic Function Improvement and Outcomes in the Modern Era. JACC-HEART FAILURE 2019; 8:131-140. [PMID: 31838030 DOI: 10.1016/j.jchf.2019.08.014] [Citation(s) in RCA: 86] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Revised: 08/28/2019] [Accepted: 08/29/2019] [Indexed: 11/24/2022]
Abstract
OBJECTIVES This study sought to investigate the impact of post-infarct left ventricular (LV) remodeling on outcomes in the contemporary era. BACKGROUND LV remodeling after ST-segment elevation myocardial infarction (STEMI) is associated with heart failure and increased mortality. Pivotal studies have mostly been performed in the era of thrombolysis, whereas the long-term prognostic impact of LV remodeling has not been reinvestigated in the current era of primary percutaneous coronary intervention (PCI) and optimal pharmacotherapy. METHODS Data were obtained from an ongoing registry of patients with STEMI (all treated with primary PCI). Baseline, 3-month, 6-month, and 12-month echocardiograms were analyzed. LV remodeling was defined as a ≥20% increase in LV end-diastolic volume at 3, 6, or 12 months post-infarct. The impact of LV remodeling on outcomes was analyzed. RESULTS A total of 1,995 patients with STEMI were studied (mean age 60 ± 12 years, 77% men), 953 (48%) of whom demonstrated remodeling in the first 12 months of follow-up. After a median follow-up of 94 (interquartile range: 69 to 119) months, 225 (11%) patients had died. There was no difference in survival between remodelers and nonremodelers (p = 0.144). However, LV remodelers were more likely to be admitted to hospital for heart failure than were nonremodelers (p < 0.001). CONCLUSIONS In the contemporary era, in which STEMI is treated with primary PCI and optimal pharmacotherapy, almost one-half of patients demonstrate LV post-infarct remodeling. However, there is no difference in long-term survival between LV remodelers and nonremodelers, and LV remodelers experience a higher rate of heart failure hospitalization, which indicates the need to intensify preventative strategies in these patients.
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38
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Benito-González T, Estévez-Loureiro R, Garrote-Coloma C, Arellano-Serrano C, Tundidor-Sanz E, Fernández-Lozano I, Toquero J, Pérez de Prado A, Goicolea J, Fernández-Vázquez F. Effect of Successful Edge-to-Edge Mitral Valve Repair on Ventricular Arrhythmic Burden in Patients With Functional Mitral Regurgitation and Implantable Cardiac Devices. Am J Cardiol 2019; 124:1113-1119. [PMID: 31376913 DOI: 10.1016/j.amjcard.2019.06.027] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2019] [Revised: 06/13/2019] [Accepted: 06/18/2019] [Indexed: 12/29/2022]
Abstract
Significant mitral regurgitation (MR) may be present in up to half of patients with heart failure (HF) and it is associated with adverse cardiac remodeling and myocardial stretch. These are potential triggers for ventricular arrhythmias (VA) in patients with HF, and therefore MR may enhance electrical ventricular vulnerability. Our aim was to evaluate VA burden before and after percutaneous mitral valve repair (PMVR) in patients with implantable cardiac devices. We conducted a prospective registry of all consecutive patients (n = 34, age 69.0 ± 12.2 years, 77% male) with significant functional mitral regurgitation (FMR) who underwent MitraClip implantation in 2 centers between June 2014 and July 2018. VA burden was defined as the total number of events during device follow-up before and after PMVR. Among patients presenting VA during follow-up before or after PMVR, device success at hospital discharge was related to a significant reduction in the incidence of Nonsustained ventricular tachycardia (VT, p = 0.002) and any sustained VT or rapid VT/ventricular fibrillation (p = 0.034). Regarding implantable cardiac defibrillator (ICD) therapies, successful PMVR was related to a reduction in incidence of either antitachycardia pacing or appropriate shocks (p = 0.045) and in the occurrence of any defibrillation shocks (p = 0.045). Overall, effective repair lead to a significant reduction in the VA burden, with a significant decrease in the occurrence of any VA (p = 0.004) and any ICD therapies (p = 0.045). In conclusion, device success after PMVR was related to a reduction in overall arrhythmic burden and ICD therapies in our cohort.
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Affiliation(s)
| | - Rodrigo Estévez-Loureiro
- Department of Cardiology, University Hospital of León, León, Spain; Department of Cardiology, University Hospital of Puerta de Hierro, Majadahonda, Madrid, Spain.
| | | | - Carlos Arellano-Serrano
- Department of Cardiology, University Hospital of Puerta de Hierro, Majadahonda, Madrid, Spain
| | | | | | - Jorque Toquero
- Department of Cardiology, University Hospital of Puerta de Hierro, Majadahonda, Madrid, Spain
| | | | - Javier Goicolea
- Department of Cardiology, University Hospital of Puerta de Hierro, Majadahonda, Madrid, Spain
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Liu QH, Qiao X, Zhang LJ, Wang J, Zhang L, Zhai XW, Ren XZ, Li Y, Cao XN, Feng QL, Cao JM, Wu BW. I K1 Channel Agonist Zacopride Alleviates Cardiac Hypertrophy and Failure via Alterations in Calcium Dyshomeostasis and Electrical Remodeling in Rats. Front Pharmacol 2019; 10:929. [PMID: 31507422 PMCID: PMC6718093 DOI: 10.3389/fphar.2019.00929] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Accepted: 07/22/2019] [Indexed: 01/08/2023] Open
Abstract
Intracellular Ca2+ overload, prolongation of the action potential duration (APD), and downregulation of inward rectifier potassium (IK1) channel are hallmarks of electrical remodeling in cardiac hypertrophy and heart failure (HF). We hypothesized that enhancement of IK1 currents is a compensation for IK1 deficit and a novel modulation for cardiac Ca2+ homeostasis and pathological remodeling. In adult Sprague-Dawley (SD) rats in vivo, cardiac hypertrophy was induced by isoproterenol (Iso) injection (i.p., 3 mg/kg/d) for 3, 10, and 30 days. Neonatal rat ventricular myocytes (NRVMs) were isolated from 1 to 3 days SD rat pups and treated with 1 μmol/L Iso for 24 h in vitro. The effects of zacopride, a selective IK1/Kir2.1 channel agonist, on cardiac remodeling/hypertrophy were observed in the settings of 15 μg/kg in vivo and 1 μmol/L in vitro. After exposing to Iso for 3 days and 10 days, rat hearts showed distinct concentric hypertrophy and fibrosis and enhanced pumping function (P < 0.01 or P < 0.05), then progressed to dilatation and dysfunction post 30 days. Compared with the age-matched control, cardiomyocytes exhibited higher cytosolic Ca2+ (P < 0.01 or P < 0.05) and lower SR Ca2+ content (P < 0.01 or P < 0.05) all through 3, 10, and 30 days of Iso infusion. The expressions of Kir2.1 and SERCA2 were downregulated, while p-CaMKII, p-RyR2, and cleaved caspase-3 were upregulated. Iso-induced electrophysiological abnormalities were also manifested with resting potential (RP) depolarization (P < 0.01), APD prolongation (P < 0.01) in adult cardiomyocytes, and calcium overload in cultured NRVMs (P < 0.01). Zacopride treatment effectively retarded myocardial hypertrophy and fibrosis, preserved the expression of Kir2.1 and some key players in Ca2+ homeostasis, normalized the RP (P < 0.05), and abbreviated APD (P < 0.01), thus lowered cytosolic [Ca2 +]i (P < 0.01 or P < 0.05). IK1channel blocker BaCl2 or chloroquine largely reversed the cardioprotection of zacopride. We conclude that cardiac electrical remodeling is concurrent with structural remodeling. By enhancing cardiac IK1, zacopride prevents Iso-induced electrical remodeling around intracellular Ca2+ overload, thereby attenuates cardiac structural disorder and dysfunction. Early electrical interventions may provide protection on cardiac remodeling.
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Affiliation(s)
- Qing-Hua Liu
- Department of Pathophysiology, Shanxi Medical University, Taiyuan, China
| | - Xi Qiao
- Department of Pathophysiology, Shanxi Medical University, Taiyuan, China
| | - Li-Jun Zhang
- Department of Pathophysiology, Shanxi Medical University, Taiyuan, China
| | - Jin Wang
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan, China
| | - Li Zhang
- Clinical Laboratory, Children's Hospital of Shanxi, Taiyuan, China
| | - Xu-Wen Zhai
- Clinical Skills Teaching Simulation Hospital, Shanxi Medical University, Taiyuan, China
| | - Xiao-Ze Ren
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan, China
| | - Yu Li
- Department of Internal Medicine, The Hospital of Beijing Sports University, Beijing, China
| | - Xiao-Na Cao
- Department of Internal Medicine, The Hospital of Beijing Sports University, Beijing, China
| | - Qi-Long Feng
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan, China
| | - Ji-Min Cao
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan, China
| | - Bo-Wei Wu
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan, China
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Joseph G, Zaremba T, Johansen MB, Ekeloef S, Heiberg E, Engblom H, Jensen SE, Sogaard P. Echocardiographic global longitudinal strain is associated with infarct size assessed by cardiac magnetic resonance in acute myocardial infarction. Echo Res Pract 2019; 6:81-89. [PMID: 31516720 PMCID: PMC6733366 DOI: 10.1530/erp-19-0026] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 08/07/2019] [Indexed: 01/29/2023] Open
Abstract
The aim of this study was to investigate if there was an association between infarct size (IS) measured by cardiac magnetic resonance (CMR) and echocardiographic global longitudinal strain (GLS) in the early stage of acute myocardial infarction in patients with preserved left ventricular ejection fraction (LVEF). Patients with ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention were assessed with CMR and transthoracic echocardiogram within 1 week of hospital admission. Two-dimensional speckle tracking was performed using a semi-automatic algorithm (EchoPac, GE Healthcare). Longitudinal strain curves were generated in a 17-segment model covering the entire left ventricular myocardium. GLS was calculated automatically. LVEF was measured by auto-LVEF in EchoPac. IS was measured by late gadolinium enhancement CMR in short-axis views covering the left ventricle. The study population consisted of 49 patients (age 60.4 ± 9.7 years; 92% male). The study population had preserved echocardiographic LVEF with a mean of 45.8 ± 8.7%. For each percent increase of IS, we found an impairment in GLS by 1.59% (95% CI 0.57–2.61), P = 0.02, after adjustment for sex, age and LVEF. No significant association between IS and echocardiographic LVEF was found: −0.25 (95% CI: −0.61 to 0.11), P = 0.51. At the segmental level, the strongest association between IS and longitudinal strain was found in the apical part of the LV: impairment of 1.69% (95% CI: 1.14–2.23), P < 0.001, for each percent increase in IS. In conclusion, GLS was significantly associated with IS in the early stage of acute myocardial infarction in patients with preserved LVEF, and this association was strongest in the apical part of the LV. No association between IS and LVEF was found.
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Affiliation(s)
- Gowsini Joseph
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.,Department of Cardiology, North Denmark Regional Hospital, Hjorring, Denmark.,Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark
| | - Tomas Zaremba
- Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark
| | | | - Sarah Ekeloef
- Department of Cardiology, Nephrology and Endocrinology, North Zealand Hospital, Hillerod, Denmark
| | - Einar Heiberg
- Department of Clinical Physiology, Lund University and Skaane University Hospital, Lund, Sweden
| | - Henrik Engblom
- Department of Clinical Physiology, Lund University and Skaane University Hospital, Lund, Sweden
| | - Svend Eggert Jensen
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.,Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark
| | - Peter Sogaard
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.,Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark
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41
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Benito-González T, Estévez-Loureiro R, Villablanca PA, Armeni P, Iglesias-Gárriz I, Minguito C, Garrote C, de Prado AP, Tundidor-Sanz E, Gualis J, Fernández-Vázquez F. Percutaneous Mitral Valve Repair Vs. Stand-Alone Medical Therapy in Patients with Functional Mitral Regurgitation and Heart Failure. CARDIOVASCULAR REVASCULARIZATION MEDICINE 2019; 21:52-60. [PMID: 31326258 DOI: 10.1016/j.carrev.2019.06.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Revised: 06/12/2019] [Accepted: 06/20/2019] [Indexed: 10/26/2022]
Abstract
BACKGROUND Functional mitral regurgitation (FMR) is a common finding among patients with heart failure (HF) and it is related to adverse events. Outcomes in patients undergoing transcatheter mitral valve repair (TMVR) are still a matter of debate. We performed a meta-analysis to assess mid- and long-term outcomes of patients with FMR treated with MitraClip® compared to medical management. METHODS We conducted an electronic database search of all published data PubMed Central, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and Google Scholar databases. The primary end-point was all-cause mortality. The secondary end-points were hospitalizations for HF, need for heart transplantation or left ventricular assist device, unplanned mitral valve surgery, myocardial infarction and stroke. RESULTS Five studies (n = 1513 patients) were included in the analysis. The summary estimate including all the available studies showed a statistically significant reduction in all-cause mortality favoring MitraClip® (HR 0.56, CI 95% [0.38-0.84]) and HF hospitalizations (HR 0.65; CI 95% [0.46-0.92]). A significant reduction in the indication for advanced HF therapies (OR 0.48; CI 95% [0.25-0.90]) or the need for unplanned mitral valve surgery (OR 0.20; CI 95% [0.07-0.57]) was also found in the group of patients that underwent TMVR. No differences in the incidence of myocardial infarction or stroke were found between both groups of treatment. No publication bias was detected. CONCLUSION TMVR with MitraClip® system was related to a significant reduction in all-cause mortality, hospitalizations for HF and the need for HF transplant, left ventricular assist device or unplanned surgery beyond 1-year follow up.
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Affiliation(s)
| | | | - Pedro A Villablanca
- Department of Cardiology, Center for Structural Heart Disease, Henry Ford Hospital, Detroit, United States of America
| | | | | | - Carlos Minguito
- Department of Cardiology, University Hospital of León, León, Spain
| | - Carmen Garrote
- Department of Cardiology, University Hospital of León, León, Spain
| | | | | | - Javier Gualis
- Department of Cardiac Surgery, University Hospital of León, León, Spain
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Human iPS cell-derived engineered heart tissue does not affect ventricular arrhythmias in a guinea pig cryo-injury model. Sci Rep 2019; 9:9831. [PMID: 31285568 PMCID: PMC6614415 DOI: 10.1038/s41598-019-46409-z] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Accepted: 06/25/2019] [Indexed: 01/14/2023] Open
Abstract
Human iPSC-derived engineered heart tissue (hEHT) has been used to remuscularize injured hearts in a guinea pig infarction model. While beneficial effects on cardiac remodeling have been demonstrated, the arrhythmogenic potential of hEHTs is a major concern. We investigated whether hiPSC-derived hEHTs increase the incidence of ventricular arrhythmias. HEHTs were created from human iPSC-derived cardiomyocytes and endothelial cells. Left-ventricular cryo-injury was induced in guinea pigs (n = 37) and telemetry sensors for continuous ECG monitoring were implanted. 7 days following the cryo-injury, hEHTs or cell-free constructs were transplanted into the surviving animals (n = 15 and n = 9). ECGs were recorded over the following 28 days. 10 hEHT animals and 8 control animals survived the observation period and were included in the final analysis. After implantation of hEHTs or cell-free constructs, ventricular arrhythmias (premature ventricular contractions, couplets, triplets and non-sustained ventricular tachycardia) were observed in animals of both groups. The fraction of animals with the respective arrhythmias as well as the rate of arrhythmic events did not differ between groups. Following hEHT implantation, no clinically relevant sustained ventricular tachycardia or ventricular fibrillation was detected. Our telemetric data provides first evidence for the electrical safety of human iPSC-derived EHTs in this experimental model, thereby supporting further development of this approach.
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Dietary flaxseed protects against ventricular arrhythmias and left ventricular dilation after a myocardial infarction. J Nutr Biochem 2019; 71:63-71. [PMID: 31284167 DOI: 10.1016/j.jnutbio.2019.06.004] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Revised: 06/06/2019] [Accepted: 06/06/2019] [Indexed: 02/02/2023]
Abstract
Dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been associated with a lower incidence of cardiovascular events and sudden cardiac death. Flaxseed is a rich plant source of n-3 PUFAs and can retard the progression and accelerate the regression of atherosclerotic plaques. The aim of the study was to examine the preventive and therapeutic effects of dietary flaxseed on arrhythmias and heart dysfunction that develops after a myocardial infarction (MI). The left anterior descending coronary artery was ligated in rats to induce the MI. Rats were randomized into five groups: sham MI with normal chow, MI with normal chow, MI with 10% milled flaxseed supplementation (flax), MI with 4.4% supplemented flax oil enriched in alpha-linolenic acid (ALA) and MI with flax lignan secoisolariciresinol diglucoside (SDG) supplementation (0.44%). Animals were fed with their respective diets for 2 weeks before and for 8 weeks after the surgery. Echocardiography and continuous electrocardiographic recordings were obtained after ligation to confirm the induction of the MI, to check for arrhythmias and to assess cardiac function. Histological examination was also performed to evaluate cardiac fibrosis. Dietary supplementation with flaxseed, ALA or SDG before and after the induction of the MI significantly reduced the incidence of arrhythmias and resulted in significantly smaller infarct size, less left ventricle dilation, and decreased myocardial fibrosis and tumor necrosis factor-α levels compared to the control MI group. Together, this study supports a beneficial effect of dietary flaxseed in patients for the prevention and treatment of arrhythmias and ventricular remodeling post-MI.
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Paiman EHM, Androulakis AFA, Shahzad R, Tao Q, Zeppenfeld K, Lamb HJ, van der Geest RJ. Association of cardiovascular magnetic resonance-derived circumferential strain parameters with the risk of ventricular arrhythmia and all-cause mortality in patients with prior myocardial infarction and primary prevention implantable cardioverter defibrillator. J Cardiovasc Magn Reson 2019; 21:28. [PMID: 31096987 PMCID: PMC6521513 DOI: 10.1186/s12968-019-0536-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Accepted: 03/27/2019] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Impaired left ventricular (LV) contraction and relaxation may further promote adverse remodeling and may increase the risk of ventricular arrhythmia (VA) in ischemic cardiomyopathy. We aimed to examine the association of cardiovascular magnetic resonance (CMR)-derived circumferential strain parameters for LV regional systolic function, LV diastolic function and mechanical dispersion with the risk of VA in patients with prior myocardial infarction and primary prevention implantable cardioverter defibrillator (ICD). METHODS Patients with an ischemic cardiomyopathy who underwent CMR prior to primary prevention ICD implantation, were retrospectively identified. LV segmental circumferential strain curves were extracted from short-axis cine CMR. For LV regional strain analysis, the extent of moderately and severely impaired strain (percentage of LV segments with strain between - 10% and - 5% and > - 5%, respectively) were calculated. LV diastolic function was quantified by the early and late diastolic strain rate. Mechanical dispersion was defined as the standard deviation in delay time between each strain curve and the patient-specific reference curve. Cox proportional hazard ratios (HR) (95%CI) were calculated to assess the association between LV strain parameters and appropriate ICD therapy. RESULTS A total of 121 patients (63 ± 11 years, 84% men, LV ejection fraction (LVEF) 27 ± 9%) were included. During a median (interquartile range) follow-up of 47 (27;69) months, 30 (25%) patients received appropriate ICD therapy. The late diastolic strain rate (HR 1.1 (1.0;1.2) per - 0.25 1/s, P = 0.043) and the extent of moderately impaired strain (HR 1.5 (1.0;2.2) per + 10%, P = 0.048) but not the extent of severely impaired strain (HR 0.9 (0.6;1.4) per + 10%, P = 0.685) were associated with appropriate ICD therapy, independent of LVEF, late gadolinium enhancement (LGE) scar border size and acute revascularization. Mechanical dispersion was not related to appropriate ICD therapy (HR 1.1 (0.8;1.6) per + 25 ms, P = 0.464). CONCLUSIONS In an ischemic cardiomyopathy population referred for primary prevention ICD implantation, the extent of moderately impaired strain and late diastolic strain rate were associated with the risk of appropriate ICD therapy, independent of LVEF, scar border size and acute revascularization. These findings suggest that disturbed LV contraction and relaxation may contribute to an increased risk of VA after myocardial infarction.
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MESH Headings
- Aged
- Arrhythmias, Cardiac/diagnosis
- Arrhythmias, Cardiac/mortality
- Arrhythmias, Cardiac/physiopathology
- Arrhythmias, Cardiac/prevention & control
- Defibrillators, Implantable
- Electric Countershock/adverse effects
- Electric Countershock/instrumentation
- Electric Countershock/mortality
- Female
- Humans
- Magnetic Resonance Imaging
- Male
- Middle Aged
- Myocardial Infarction/diagnostic imaging
- Myocardial Infarction/mortality
- Myocardial Infarction/physiopathology
- Predictive Value of Tests
- Primary Prevention/instrumentation
- Retrospective Studies
- Risk Assessment
- Risk Factors
- Time Factors
- Treatment Outcome
- Ventricular Dysfunction, Left/diagnostic imaging
- Ventricular Dysfunction, Left/mortality
- Ventricular Dysfunction, Left/physiopathology
- Ventricular Dysfunction, Left/therapy
- Ventricular Function, Left
- Ventricular Remodeling
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Affiliation(s)
- Elisabeth H. M. Paiman
- Department of Radiology, Leiden University Medical Center, P.O. Box 9600, postal zone C2-S, 2300 RC Leiden, The Netherlands
| | - Alexander F. A. Androulakis
- Department of Cardiology, Leiden University Medical Center, P.O. Box 9600, postal zone C2-S, 2300 RC Leiden, The Netherlands
| | - Rahil Shahzad
- LKEB, Division of Image Processing, Department of Radiology, Leiden University Medical Center, P.O. Box 9600, postal zone C2-S, 2300 RC Leiden, The Netherlands
| | - Qian Tao
- LKEB, Division of Image Processing, Department of Radiology, Leiden University Medical Center, P.O. Box 9600, postal zone C2-S, 2300 RC Leiden, The Netherlands
| | - Katja Zeppenfeld
- Department of Cardiology, Leiden University Medical Center, P.O. Box 9600, postal zone C2-S, 2300 RC Leiden, The Netherlands
| | - Hildo J. Lamb
- Department of Radiology, Leiden University Medical Center, P.O. Box 9600, postal zone C2-S, 2300 RC Leiden, The Netherlands
| | - Rob J. van der Geest
- LKEB, Division of Image Processing, Department of Radiology, Leiden University Medical Center, P.O. Box 9600, postal zone C2-S, 2300 RC Leiden, The Netherlands
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Wang L, Yuan D, Zheng J, Wu X, Wang J, Liu X, He Y, Zhang C, Liu C, Wang T, Zhou Z. Chikusetsu saponin IVa attenuates isoprenaline-induced myocardial fibrosis in mice through activation autophagy mediated by AMPK/mTOR/ULK1 signaling. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2019; 58:152764. [PMID: 31005723 DOI: 10.1016/j.phymed.2018.11.024] [Citation(s) in RCA: 77] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Revised: 11/17/2018] [Accepted: 11/17/2018] [Indexed: 06/09/2023]
Abstract
BACKGROUND Myocardial fibrosis is a common pathological manifestation of many cardiovascular diseases at the end stage. Autophagy has been demonstrated to play a protective role in the cardiac fibrosis. Our previous studies have demonstrated that the Saponins from Panax japonicus effectively ameliorated the degree of fibrosis in rat acute myocardial ischemia injury model though the mechanisms are not clear. HYPOTHESIS We hypothesized that Chikusetsusaponin IVa (CS), a major component of Saponins from Panaxjaponicus, may improve isoprenaline induced myocardial fibrosis via AMPK/mTOR/ULK1 mediated autophagy METHODS: Continuous subcutaneous injection of isoproterenol for 21 days was used to induce myocardial fibrosis in mice and high and low doses (15 mg/kg and 5 mg/kg) of CS was administered by oral gavage to observe the efficacy. Animals were sacrificed 12 h after the last administration and samples were collected. H&E staining, Masson staining and wheat germ agglutinin (WGA) staining were used to evaluate histopathological changes, collagen deposition and myocardial cell hypertrophy. Autophagy-related markers (LC3β, Beclin1 and p62) and AMPK/mTOR/ULK1 pathway-related markers were evaluated by western blot. RESULTS CS effectively attenuated isoprenaline-induced myocardial fibrosis in vivo, reduced the heart index, inhibited inflammatory infiltration, decreased collagen deposition and myocardial cell size. CS treatment rescued the expression of autophagy-related markers. CS activated autophagy through the activation of AMPK, which in turn inhibited the phosphorylation of mTOR and ULK1(Ser757), rather than directly phosphorylate ULK1(Ser555) by AMPK. CONCLUSION Our data demonstrated that CS attenuated isoprenaline-induced myocardial fibrosis by activating autophagy through AMPK/mTOR/ULK1 pathway. Our findings suggested that CS is a potential candidate drug against cardiac fibrosis and have identified potential drug targets for the treatment of heart diseases.
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Affiliation(s)
- Luopei Wang
- Medical College of China Three Gorges University, Yichang 443002, PR China
| | - Ding Yuan
- RENHE Hospital of China Three Gorges University, Yichang 443000, PR China
| | - Jie Zheng
- Medical College of China Three Gorges University, Yichang 443002, PR China
| | - Xuecui Wu
- Medical College of China Three Gorges University, Yichang 443002, PR China
| | - Juntao Wang
- Medical College of China Three Gorges University, Yichang 443002, PR China
| | - Xiu Liu
- Medical College of China Three Gorges University, Yichang 443002, PR China
| | - Yumin He
- Medical College of China Three Gorges University, Yichang 443002, PR China
| | - Changcheng Zhang
- Medical College of China Three Gorges University, Yichang 443002, PR China
| | - Chaoqi Liu
- Medical College of China Three Gorges University, Yichang 443002, PR China
| | - Ting Wang
- Medical College of China Three Gorges University, Yichang 443002, PR China; Yichang Key Laboratory of ischemic cardiovascular and cerebrovascular disease translational medicine (Three Gorges University), Yichang 443000, PR China.
| | - Zhiyong Zhou
- Medical College of China Three Gorges University, Yichang 443002, PR China; Yichang Key Laboratory of ischemic cardiovascular and cerebrovascular disease translational medicine (Three Gorges University), Yichang 443000, PR China.
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Zeglinski MR, Moghadam AR, Ande SR, Sheikholeslami K, Mokarram P, Sepehri Z, Rokni H, Mohtaram NK, Poorebrahim M, Masoom A, Toback M, Sareen N, Saravanan S, Jassal DS, Hashemi M, Marzban H, Schaafsma D, Singal P, Wigle JT, Czubryt MP, Akbari M, Dixon IM, Ghavami S, Gordon JW, Dhingra S. Myocardial Cell Signaling During the Transition to Heart Failure. Compr Physiol 2018; 9:75-125. [DOI: 10.1002/cphy.c170053] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Cathepsin K-deficiency impairs mouse cardiac function after myocardial infarction. J Mol Cell Cardiol 2018; 127:44-56. [PMID: 30465799 DOI: 10.1016/j.yjmcc.2018.11.010] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Revised: 11/08/2018] [Accepted: 11/16/2018] [Indexed: 11/22/2022]
Abstract
BACKGROUND Extracellular matrix metabolism and cardiac cell death participate centrally in myocardial infarction (MI). This study tested the roles of collagenolytic cathepsin K (CatK) in post-MI left ventricular remodeling. METHODS AND RESULTS Patients with acute MI had higher plasma CatK levels (20.49 ± 7.07 pmol/L, n = 26) than those in subjects with stable angina pectoris (8.34 ± 1.66 pmol/L, n = 28, P = .01) or those without coronary heart disease (6.63 ± 0.84 pmol/L, n = 93, P = .01). CatK protein expression increases in mouse hearts at 7 and 28 days post-MI. Immunofluorescent staining localized CatK expression in cardiomyocytes, endothelial cells, fibroblasts, macrophages, and CD4+ T cells in infarcted mouse hearts at 7 days post-MI. To probe the direct participation of CatK in MI, we produced experimental MI in CatK-deficient mice (Ctsk-/-) and their wild-type (Ctsk+/+) littermates. CatK-deficiency yielded worsened cardiac function at 7 and 28 days post-MI, compared to Ctsk+/+ littermates (fractional shortening percentage: 5.01 ± 0.68 vs. 8.62 ± 1.04, P < .01, 7 days post-MI; 4.32 ± 0.52 vs. 7.60 ± 0.82, P < .01, 28 days post-MI). At 7 days post-MI, hearts from Ctsk-/- mice contained less CatK-specific type-I collagen fragments (10.37 ± 1.91 vs. 4.60 ± 0.49 ng/mg tissue extract, P = .003) and more fibrosis (1.67 ± 0.93 vs. 0.69 ± 0.20 type-III collagen positive area percentage, P = .01; 14.25 ± 4.12 vs. 6.59 ± 0.79 α-smooth muscle actin-positive area percentage, P = .016; and 0.82 ± 0.06 vs. 0.31 ± 0.08 CD90-positive area percentage, P = .008) than those of Ctsk+/+ mice. Immunostaining demonstrated that CatK-deficiency yielded elevated cardiac cell death but reduced cardiac cell proliferation. In vitro studies supported a role of CatK in cardiomyocyte survival. CONCLUSION Plasma CatK levels are increased in MI patients. Heart CatK expression is also elevated post-MI, but CatK-deficiency impairs post-MI cardiac function in mice by increasing myocardial fibrosis and cardiomyocyte death.
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Ter Horst EN, Krijnen PAJ, Hakimzadeh N, Robbers LFHJ, Hirsch A, Nijveldt R, Lommerse I, Fontijn RD, Meinster E, Delewi R, van Royen N, Zijlstra F, van Rossum AC, van der Schoot CE, van der Pouw Kraan TCTM, Horrevoets AJ, van der Laan AM, Niessen HWM, Piek JJ. Elevated monocyte-specific type I interferon signalling correlates positively with cardiac healing in myocardial infarct patients but interferon alpha application deteriorates myocardial healing in rats. Basic Res Cardiol 2018; 114:1. [PMID: 30443679 PMCID: PMC6244641 DOI: 10.1007/s00395-018-0709-7] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2018] [Accepted: 11/05/2018] [Indexed: 02/07/2023]
Abstract
Monocytes are involved in adverse left ventricular (LV) remodelling following myocardial infarction (MI). To provide therapeutic opportunities we aimed to identify gene transcripts in monocytes that relate to post-MI healing and evaluated intervention with the observed gene activity in a rat MI model. In 51 MI patients treated by primary percutaneous coronary intervention (PCI), the change in LV end-diastolic volume index (EDVi) from baseline to 4-month follow-up was assessed using cardiovascular magnetic resonance imaging (CMR). Circulating monocytes were collected at day 5 (Arterioscler Thromb Vasc Biol 35:1066-1070, 2015; Cell Stem Cell 16:477-487, 2015; Curr Med Chem 13:1877-1893, 2006) after primary PCI for transcriptome analysis. Transcriptional profiling and pathway analysis revealed that patients with a decreased LV EDVi showed an induction of type I interferon (IFN) signalling (type I IFN pathway: P value < 0.001; false discovery rate < 0.001). We subsequently administered 15,000 Units of IFN-α subcutaneously in a rat MI model for three consecutive days following MI. Cardiac function was measured using echocardiography and infarct size/cardiac inflammation using (immuno)-histochemical analysis. We found that IFN-α application deteriorated ventricular dilatation and increased infarct size at day 28 post-MI. Moreover, IFN-α changed the peripheral monocyte subset distribution towards the pro-inflammatory monocyte subset whereas in the myocardium, the presence of the alternative macrophage subset was increased at day 3 post-MI. Our findings suggest that induction of type I IFN signalling in human monocytes coincides with adverse LV remodelling. In rats, however, IFN-α administration deteriorated post-MI healing. These findings underscore important but also contradictory roles for the type I IFN response during cardiac healing following MI.
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Affiliation(s)
- Ellis N Ter Horst
- Department of Cardiology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
- Netherlands Heart Institute, Moreelsepark 1, Utrecht, The Netherlands.
- Department of Pathology, Amsterdam UMC, VU University Amsterdam, de Boelelaan 1117, 1081HV, Amsterdam, The Netherlands.
- Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
| | - Paul A J Krijnen
- Department of Pathology, Amsterdam UMC, VU University Amsterdam, de Boelelaan 1117, 1081HV, Amsterdam, The Netherlands
- Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands
| | - Nazanin Hakimzadeh
- Department of Cardiology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
- Department of Biomedical Engineering and Physics, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
| | - Lourens F H J Robbers
- Department of Cardiology, Amsterdam UMC, VU University Amsterdam, de Boelelaan 1117, Amsterdam, The Netherlands
| | - Alexander Hirsch
- Department of Cardiology and Radiology, Erasmus Medical Centre, Dr. Molewaterplein 40, Rotterdam, The Netherlands
| | - Robin Nijveldt
- Department of Cardiology, Amsterdam UMC, VU University Amsterdam, de Boelelaan 1117, Amsterdam, The Netherlands
| | - Ingrid Lommerse
- Department of Experimental Immunohematology, Sanquin Research, Amsterdam UMC, location AMC, Plesmanlaan 125, Amsterdam, The Netherlands
| | - Ruud D Fontijn
- Department of Molecular Cell Biology and Immunology, Amsterdam UMC, VU University Amsterdam, de Boelelaan 1117, Amsterdam, The Netherlands
| | - Elisa Meinster
- Department of Pathology, Amsterdam UMC, VU University Amsterdam, de Boelelaan 1117, 1081HV, Amsterdam, The Netherlands
- Department of Molecular Cell Biology and Immunology, Amsterdam UMC, VU University Amsterdam, de Boelelaan 1117, Amsterdam, The Netherlands
| | - Ronak Delewi
- Department of Cardiology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
| | - Niels van Royen
- Department of Cardiology, Radboud University Medical Centre, Geert Grooteplein Zuid 10, Nijmegen, The Netherlands
| | - Felix Zijlstra
- Department of Cardiology, Erasmus Medical Centre, Dr. Molewaterplein 40, Rotterdam, The Netherlands
| | - Albert C van Rossum
- Department of Cardiology, Amsterdam UMC, VU University Amsterdam, de Boelelaan 1117, Amsterdam, The Netherlands
| | - C Ellen van der Schoot
- Department of Experimental Immunohematology, Sanquin Research, Amsterdam UMC, location AMC, Plesmanlaan 125, Amsterdam, The Netherlands
| | - Tineke C T M van der Pouw Kraan
- Department of Molecular Cell Biology and Immunology, Amsterdam UMC, VU University Amsterdam, de Boelelaan 1117, Amsterdam, The Netherlands
| | - Anton J Horrevoets
- Department of Molecular Cell Biology and Immunology, Amsterdam UMC, VU University Amsterdam, de Boelelaan 1117, Amsterdam, The Netherlands
| | - Anja M van der Laan
- Department of Cardiology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
| | - Hans W M Niessen
- Department of Pathology, Amsterdam UMC, VU University Amsterdam, de Boelelaan 1117, 1081HV, Amsterdam, The Netherlands
- Department of Cardiac Surgery, Amsterdam UMC, VU University Amsterdam, de Boelelaan 1117, Amsterdam, The Netherlands
- Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands
| | - Jan J Piek
- Department of Cardiology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
- Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands
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Athanasuleas CL, Stanley AWH, Buckberg GD. Mitral regurgitation: anatomy is destiny. Eur J Cardiothorac Surg 2018; 54:627-634. [PMID: 29718159 DOI: 10.1093/ejcts/ezy174] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Accepted: 03/18/2018] [Indexed: 11/13/2022] Open
Abstract
Mitral regurgitation (MR) occurs when any of the valve and ventricular mitral apparatus components are disturbed. As MR progresses, left ventricular remodelling occurs, ultimately causing heart failure when the enlarging left ventricle (LV) loses its conical shape and becomes globular. Heart failure and lethal ventricular arrhythmias may develop if the left ventricular end-systolic volume index exceeds 55 ml/m2. These adverse changes persist despite satisfactory correction of the annular component of MR. Our goal was to describe this process and summarize evolving interventions that reduce the volume of the left ventricle and rebuild its elliptical shape. This 'valve/ventricle' approach addresses the spherical ventricular culprit and offsets the limits of treating MR by correcting only its annular component.
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Affiliation(s)
- Constantine L Athanasuleas
- Section of Cardiothoracic Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA
| | | | - Gerald D Buckberg
- Department of Cardiothoracic Surgery, University of California Los Angeles, Los Angeles, CA, USA
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Burger H, Schmitt J, Knaut M, Eitz T, Starck CT, Hakmi S, Siebel A, Böning A. Einsatz des tragbaren Kardioverter-Defibrillators nach kardiochirurgischen Eingriffen. ZEITSCHRIFT FUR HERZ THORAX UND GEFASSCHIRURGIE 2018. [DOI: 10.1007/s00398-018-0246-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
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