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Zhao Z, Wang Y, Jiang C, Yang Z, Zhang J, Lai Y, Wang J, Li S, Peng X, Li M, Li E, Guo H, Li J, Kong X, He L, Zuo S, Guo X, Li S, Liu N, Tang R, Sang C, Long D, Du X, He L, Dong J, Ma C. Impact of sodium-glucose cotransporter 2 inhibitor on recurrence and cardiovascular outcomes after catheter ablation for atrial fibrillation in patients with heart failure. Heart Rhythm 2025; 22:935-943. [PMID: 39168296 DOI: 10.1016/j.hrthm.2024.08.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 07/30/2024] [Accepted: 08/12/2024] [Indexed: 08/23/2024]
Abstract
BACKGROUND The impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on atrial fibrillation (AF) recurrence outcomes and adverse cardiovascular outcomes in heart failure (HF) patients after AF ablation is unknown. OBJECTIVE We investigated whether SGLT2i reduces the risk of AF recurrence and adverse cardiovascular outcomes in HF patients after AF ablation. METHODS HF patients with AF undergoing catheter ablation between January 2017 and December 2022 from the China-AF Registry were included. Patients were stratified into 2 groups on the basis of the use of SGLT2i at discharge and were 1:1 matched by propensity score, with SGLT2i using (n = 368) and non-SGLT2i using (n = 368) in each group. The primary outcome was AF recurrence after a 3-month blanking period. RESULTS During a total of 1315 person-years of follow-up, AF recurred in 83 patients (22.6%) in the SGLT2i group and 132 patients (35.8%) in the non-SGLT2i group. SGLT2i was associated with a lower risk of AF recurrence (adjusted hazard ratio, 0.56; 95% CI, 0.43-0.74; P < .001). The composite risk of cardiovascular death, thrombotic events, or cardiovascular hospitalization was significantly lower in the SGLT2i group compared with those without SGLT2i (adjusted hazard ratio, 0.58; 95% CI, 0.41-0.80; P = .001). Although there was a trend toward benefit, the differences in all-cause mortality, cardiovascular death, or thrombotic events were insignificant between the 2 groups. CONCLUSION The use of SGLT2i was associated with a lower risk of AF recurrence and the composite outcome of cardiovascular death, thrombotic events, or cardiovascular hospitalization after catheter ablation for AF in patients with HF.
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Affiliation(s)
- Zixu Zhao
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University and National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Yiping Wang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University and National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Chao Jiang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University and National Clinical Research Center for Cardiovascular Diseases, Beijing, China.
| | - Zejun Yang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University and National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Jingrui Zhang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University and National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Yiwei Lai
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University and National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Jue Wang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University and National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Sitong Li
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University and National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Xiaodong Peng
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University and National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Mingxiao Li
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University and National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Enze Li
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University and National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Hang Guo
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University and National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Jiahe Li
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University and National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Xiangyi Kong
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University and National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Liu He
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University and National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Song Zuo
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University and National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Xueyuan Guo
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University and National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Songnan Li
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University and National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Nian Liu
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University and National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Ribo Tang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University and National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Caihua Sang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University and National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Deyong Long
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University and National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Xin Du
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University and National Clinical Research Center for Cardiovascular Diseases, Beijing, China; Heart Health Research Center, Beijing, China
| | - Liping He
- Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia, China.
| | - Jianzeng Dong
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University and National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Changsheng Ma
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University and National Clinical Research Center for Cardiovascular Diseases, Beijing, China.
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Matsumoto S, Henderson AD, Jhund PS, Bauersachs J, Chioncel O, Claggett BL, Comin-Colet J, Desai AS, Filippatos G, Lam CSP, Pitt B, Scheerer MF, Lay-Flurrie J, Amarante F, Brinker M, Schou M, Senni M, Shah SJ, Voors AA, Zannad F, Zieroth S, Vaduganathan M, Solomon SD, McMurray JJV. Finerenone and Atrial Fibrillation in Heart Failure: A Secondary Analysis of the FINEARTS-HF Randomized Clinical Trial. JAMA Cardiol 2025:2832032. [PMID: 40156827 PMCID: PMC11955084 DOI: 10.1001/jamacardio.2025.0848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2025] [Accepted: 03/05/2025] [Indexed: 04/01/2025]
Abstract
Importance Heart failure (HF) with mildly reduced or preserved ejection fraction and atrial fibrillation (AF) are closely intertwined. Objective To examine the efficacy and safety of the nonsteroidal mineralocorticoid receptor antagonist finerenone in patients with HF with mildly reduced or preserved ejection fraction according to the absence or presence of AF and the type of AF (paroxysmal vs persistent or permanent). Design, Setting, and Participants Prespecified analyses were conducted in the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF) randomized clinical trial. The trial was conducted across 653 sites in 37 countries. Participants were adults aged 40 years and older with symptomatic HF and left ventricular ejection fraction of 40% or greater, randomized between September 2020 and January 2023. Data analysis was conducted from September 1 to October 1, 2024. Intervention Finerenone (titrated to 20 mg or 40 mg) or placebo. Main Outcomes and Measures The primary outcome was the composite of total HF events and cardiovascular death. New-onset AF or atrial flutter (AFL) was a prespecified exploratory outcome. Results Among 5984 patients (mean [SD] age, 72.0 [9.6] years; 2724 [45.5%] female) with known AF status at baseline, 1384 (23.1%) had paroxysmal AF and 1886 (31.5%) had persistent or permanent AF. Patients with both types of AF were older and had worse HF status compared with those without AF (2714 patients [45.4%]). Both types of AF were associated with a higher unadjusted risk of the primary outcome compared with no AF (event rate per 100 person-years of follow-up, 20.3 [95% CI, 17.9-23.1] with paroxysmal AF, 19.8 [95% CI, 17.8-22.0] with persistent or permanent AF, and 11.9 [95% CI, 10.7-13.3] with no AF; rate ratio [RR], 1.62 [95% CI, 1.37-1.92] with paroxysmal AF and 1.66 [95% CI, 1.43-1.93] with persistent or permanent AF vs no AF); however, the associations were attenuated after adjustment for known prognostic variables. The benefit of finerenone on the primary outcome (overall RR, 0.84 [95% CI, 0.74-0.95]) was not modified by baseline AF status (RR, 0.80 [95% CI, 0.65-0.98] with no AF, 0.83 [95% CI, 0.65-1.06] with paroxysmal AF, and 0.85 [95% CI, 0.69-1.05] with persistent or permanent AF; P for interaction = .94). New-onset AF or AFL occurred in 6.5% of patients and was associated with a higher subsequent adjusted risk of the primary outcome (rate ratio, 3.65 [95% CI, 2.57-5.18]; P < .001). The subdistribution hazard ratio for new-onset AF or AFL among those receiving finerenone vs placebo was 0.77 (95% CI, 0.57-1.04; P = .09). Conclusions and Relevance The efficacy of finerenone was consistent regardless of AF status. New-onset AF was associated with a substantially higher risk of subsequent outcomes. Trial Registration ClinicalTrials.gov Identifier: NCT04435626.
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Affiliation(s)
- Shingo Matsumoto
- British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom
- Division of Cardiovascular Medicine, Department of Internal Medicine, Toho University Faculty of Medicine, Tokyo, Japan
| | - Alasdair D. Henderson
- British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom
| | - Pardeep S. Jhund
- British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom
| | - Johann Bauersachs
- Department of Cardiology and Angiology, Hannover Medical School, Hanover, Germany
| | - Ovidiu Chioncel
- Emergency Institute for Cardiovascular Diseases “Prof. Dr. C.C. Iliescu,” University of Medicine Carol Davila, Bucharest, Romania
| | - Brian L. Claggett
- Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
| | - Josep Comin-Colet
- Department of Cardiology, Bellvitge University Hospital, and Bellvitge Biomedical Research Institute, Centro de Investigación Biomédica En Red Enfermedades Cardiovasculares, University of Barcelona, L’Hospitalet de Llobregat, Barcelona, Spain
| | - Akshay S. Desai
- Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
| | - Gerasimos Filippatos
- Department of Cardiology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Carolyn S. P. Lam
- National Heart Centre Singapore and Duke-National University of Singapore, Singapore, Singapore
| | - Bertram Pitt
- Department of Medicine, University of Michigan School of Medicine, Ann Arbor
| | | | - James Lay-Flurrie
- Research & Development, Pharmaceuticals, Bayer plc, Reading, United Kingdom
| | - Flaviana Amarante
- Cardiology and Nephrology Clinical Development, Bayer SA, São Paulo, Brazil
| | - Meike Brinker
- Research & Development, Pharmaceuticals, Bayer AG, Wuppertal, Germany
| | - Morten Schou
- Department of Cardiology, Herlev-Gentofte University Hospital, Hellerup, Denmark
| | - Michele Senni
- Cardiovascular Department, University of Milano-Bicocca, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Sanjiv J. Shah
- Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Adriaan A. Voors
- Department of Cardiology, University of Groningen, Groningen, the Netherlands
| | - Faiez Zannad
- Université de Lorraine, Inserm Clinical Investigation Center at Institut Lorrain du Coeur et des Vaisseaux, University Hospital of Nancy, Nancy, France
| | - Shelley Zieroth
- Section of Cardiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Muthiah Vaduganathan
- Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
| | - Scott D. Solomon
- Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
| | - John J. V. McMurray
- British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom
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Feng Q, Wu M, Mai Z. Emerging horizons: clinical applications and multifaceted benefits of SGLT-2 inhibitors beyond diabetes. Front Cardiovasc Med 2025; 12:1482918. [PMID: 40182430 PMCID: PMC11965600 DOI: 10.3389/fcvm.2025.1482918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2025] [Accepted: 03/10/2025] [Indexed: 04/05/2025] Open
Abstract
SGLT-2 inhibitors, initially developed for type 2 diabetes, demonstrate profound cardiorenal and metabolic benefits. This review synthesizes evidence from clinical trials and mechanistic studies to elucidate their roles in cardiovascular diseases, chronic kidney disease, and non-alcoholic fatty liver disease. Key findings include a notable reduction in cardiovascular death/heart failure hospitalization, a marked decrease in heart failure hospitalization risk, and significant improvements in renal and hepatic outcomes. Emerging mechanisms, such as autophagy induction, ketone utilization, and anti-inflammatory effects, underpin these benefits. Ongoing trials explore their potential in non-diabetic populations, positioning SGLT-2 inhibitors as transformative agents in multisystem disease management.
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Affiliation(s)
- Qing Feng
- Department of Cardiology, Kaiping Central Hospital, Kaiping, China
| | - Miaoqiong Wu
- Department of Endocrinology, Kaiping Central Hospital, Kaiping, China
| | - Zizhao Mai
- School of Stomatology, Stomatological Hospital, Southern Medical University, Guangzhou, Guangdong, China
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4
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Austreim M, Nouhravesh N, Malik ME, Abassi N, Zahir D, Garred CH, Andersen CF, Hansen ML, Olesen JB, Fosbøl E, Østergaard L, Køber L, Schou M. Temporal trends in mortality, heart failure hospitalization, and stroke in heart failure patients with and without atrial fibrillation: a nationwide study from 1997 to 2018 on 152 059 patients. EUROPEAN HEART JOURNAL. QUALITY OF CARE & CLINICAL OUTCOMES 2025; 11:130-139. [PMID: 39038992 DOI: 10.1093/ehjqcco/qcae061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 07/04/2024] [Accepted: 07/18/2024] [Indexed: 07/24/2024]
Abstract
AIMS We aimed to investigate temporal trends in all-cause mortality, heart failure (HF) hospitalization, and stroke from 1997 to 2018 in patients diagnosed with both HF and atrial fibrillation (AF). METHODS AND RESULTS From Danish nationwide registers, we identified 152 059 patients with new-onset HF between 1997 and 2018. Patients were grouped according to year of new-onset HF and AF-status: Prevalent AF (n = 34 734), New-onset AF (n = 12 691), and No AF (n = 104 634). Median age decreased from 76 to 73 years between 1997 and 2018. The proportion of patients with prevalent or new-onset AF increased from 24.7% (n = 9256) to 35.8% (n = 14 970). Five-year risk of all-cause mortality went from 69.1% [confidence interval (CI): 67.9-70.2%] to 51.3% (CI: 49.9-52.7%), 62.3% (CI: 60.5-64.4%) to 43.0% (CI: 40.5-45.5%), and 61.9% (CI: 61.3-62.4%) to 36.7% (CI: 35.9-37.6%) for the Prevalent AF, New-onset AF, and No AF-group, respectively. Minimal changes were observed in the risk of HF-hospitalization. Five-year stroke risk decreased from 8.5% (CI: 7.8-9.1%) to 5.0% (CI: 4.4-5.5%) for the prevalent AF group, 8.2% (CI: 7.2-9.2%) to 4.6% (CI: 3.7-5.5%) for new-onset AF, and 6.3% (CI: 6.1-6.6%) to 4.9% (CI: 4.6-5.3%) for the No AF group. Simultaneously, anticoagulant therapy increased for patients with prevalent (from 42.7 to 93.1%) and new-onset AF (from 41.9 to 92.5%). CONCLUSION From 1997 to 2018, we observed an increase in patients with HF and co-existing AF. Mortality decreased for all patients, regardless of AF-status. Anticoagulation therapy increased, and stroke risk for patients with AF was reduced to a similar level as patients without AF in 2013-2018.
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Affiliation(s)
- Marte Austreim
- Department of Cardiology, Herlev and Gentofte University Hospital, 2900 Copenhagen, Denmark
| | - Nina Nouhravesh
- Department of Cardiology, Herlev and Gentofte University Hospital, 2900 Copenhagen, Denmark
| | - Mariam E Malik
- Department of Cardiology, Herlev and Gentofte University Hospital, 2900 Copenhagen, Denmark
| | - Noor Abassi
- Department of Cardiology, Herlev and Gentofte University Hospital, 2900 Copenhagen, Denmark
| | - Deewa Zahir
- Department of Cardiology, Herlev and Gentofte University Hospital, 2900 Copenhagen, Denmark
| | | | - Camilla F Andersen
- Department of Cardiology, Herlev and Gentofte University Hospital, 2900 Copenhagen, Denmark
| | - Morten Lock Hansen
- Department of Cardiology, Herlev and Gentofte University Hospital, 2900 Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark
| | - Jonas Bjerring Olesen
- Department of Cardiology, Herlev and Gentofte University Hospital, 2900 Copenhagen, Denmark
| | - Emil Fosbøl
- Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark
| | - Lauge Østergaard
- Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark
| | - Lars Køber
- Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark
| | - Morten Schou
- Department of Cardiology, Herlev and Gentofte University Hospital, 2900 Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark
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5
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Zhang M, Sun L, Wu X, Qin Y, Lin M, Ding X, Zhu W, Jiang Z, Jin S, Leng C, Wang J, Lv X, Cai Q. Effects of 3-month dapagliflozin on left atrial function in treatment-naïve patients with type 2 diabetes mellitus: Assessment using 4-dimensional echocardiography. Hellenic J Cardiol 2025; 82:43-53. [PMID: 38092177 DOI: 10.1016/j.hjc.2023.12.002] [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] [Received: 08/13/2023] [Revised: 11/21/2023] [Accepted: 12/09/2023] [Indexed: 12/25/2023] Open
Abstract
BACKGROUND The sodium-glucose transporter-2 (SGLT-2) inhibitor dapagliflozin can improve left ventricular (LV) performance in patients with type 2 diabetes mellitus (T2DM). However, the effects on left atrial (LA) function in treatment-naïve T2DM patients remain unclear. The aim of our study was 1) to investigate the effects of 3-month treatment with dapagliflozin on LA function in treatment-naïve patients with T2DM using 4-dimensional automated LA quantification (4D Auto LAQ) and 2) to explore linked covariation patterns of changes in clinical and LA echocardiographic variables. METHODS 4D Auto LAQ was used to evaluate LA volumes, longitudinal and circumferential strains in treatment-naïve T2DM patients at baseline, at follow-up, and in healthy control (HC). Sparse canonical correlation analysis (sCCA) was performed to capture the linked covariation patterns between changes in clinical and LA echocardiographic variables within the treatment-naïve T2DM patient group. RESULTS This study finally included 61 treatment-naïve patients with T2DM without cardiovascular disease and 39 healthy controls (HC). Treatment-naïve T2DM patients showed reduced LA reservoir and conduit function at baseline compared to HC, independent of age, sex, BMI, and blood pressure (LASr: 21.11 ± 5.39 vs. 27.08 ± 5.31 %, padjusted = 0.017; LAScd: -11.51 ± 4.48 vs. -16.74 ± 4.51 %, padjusted = 0.013). After 3-month treatment with dapagliflozin, T2DM patients had significant improvements in LA reservoir and conduit function independent of BMI and blood pressure changes (LASr: 21.11 ± 5.39 vs. 23.84 ± 5.74 %, padjusted < 0.001; LAScd: -11.51 ± 4.48 vs. -12.75 ± 4.70 %, padjusted < 0.001). The clinical and LA echocardiographic parameters showed significant covariation (r = 0.562, p = 0.039). In the clinical dataset, changes in heart rate, insulin, and BMI were most associated with the LA echocardiographic variate. In the LA echocardiographic dataset, changes in LAScd, LASr, and LASr_c were most associated with the clinical variate. CONCLUSION Compared with HC, treatment-naïve patients with T2DM had lower LA function, and these patients benefited from dapagliflozin administration, particularly in LA function.
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Affiliation(s)
- Miao Zhang
- Department of Ultrasound Medicine, Beijing Chao Yang Hospital, Capital Medical University, Beijing 100020, China
| | - Lanlan Sun
- Department of Ultrasound Medicine, Beijing Chao Yang Hospital, Capital Medical University, Beijing 100020, China
| | - Xiaopeng Wu
- Department of Ultrasound Medicine, Beijing Chao Yang Hospital, Capital Medical University, Beijing 100020, China
| | - Yunyun Qin
- Department of Ultrasound Medicine, Beijing Chao Yang Hospital, Capital Medical University, Beijing 100020, China
| | - Mingming Lin
- Department of Ultrasound Medicine, Beijing Chao Yang Hospital, Capital Medical University, Beijing 100020, China
| | - Xueyan Ding
- Department of Ultrasound Medicine, Beijing Chao Yang Hospital, Capital Medical University, Beijing 100020, China
| | - Weiwei Zhu
- Department of Ultrasound Medicine, Beijing Chao Yang Hospital, Capital Medical University, Beijing 100020, China
| | - Zhe Jiang
- Department of Ultrasound Medicine, Beijing Chao Yang Hospital, Capital Medical University, Beijing 100020, China
| | - Shan Jin
- Department of Ultrasound Medicine, Beijing Chao Yang Hospital, Capital Medical University, Beijing 100020, China
| | - Chenlei Leng
- Department of Ultrasound Medicine, Beijing Chao Yang Hospital, Capital Medical University, Beijing 100020, China
| | | | - Xiuzhang Lv
- Department of Ultrasound Medicine, Beijing Chao Yang Hospital, Capital Medical University, Beijing 100020, China.
| | - Qizhe Cai
- Department of Ultrasound Medicine, Beijing Chao Yang Hospital, Capital Medical University, Beijing 100020, China.
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6
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Kondo T, Jhund PS, Anand IS, Claggett BL, Desai AS, Docherty KF, Lam CSP, Lefkowitz MP, Maggioni AP, Martinez FA, Redfield MM, Rouleau JL, Van Veldhuisen DJ, Zannad F, Zile MR, Packer M, Solomon SD, McMurray JJV. Effects of Sacubitril/Valsartan According to Natriuretic Peptide Levels in Patients Enrolled in PARADIGM-HF and PARAGON-HF. JACC. HEART FAILURE 2025:S2213-1779(25)00088-5. [PMID: 40088233 DOI: 10.1016/j.jchf.2024.12.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 11/19/2024] [Accepted: 12/13/2024] [Indexed: 03/17/2025]
Abstract
BACKGROUND Recent trials of new heart failure (HF) treatments suggest the effect of therapy may vary by N-terminal pro-B type natriuretic peptide (NT-proBNP) level. OBJECTIVES The authors examined the efficacy of sacubitril/valsartan according to NT-proBNP levels in patients with reduced, mildly reduced, and preserved left ventricular ejection fraction (LVEF) enrolled in PARADIGM-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin-Converting-Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial) and PARAGON-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin-Receptor Blockers Global Outcomes in HF with Preserved Ejection Fraction). METHODS Individual patient data from PARADIGM-HF and PARAGON-HF were pooled and participants were divided into categories defined by quintiles of NT-proBNP level. The primary outcome examined was the composite of HF hospitalization or cardiovascular death. RESULTS Among the 13,195 patients enrolled in both trials, 13,142 (99.6%) had a baseline NT-proBNP level measured. The rate of the primary outcome (per 100 person-years) increased with NT-proBNP levels: quintile 1, 5.9 (95% CI: 5.3-6.5); quintile 2, 7.5 (95% CI: 6.9-8.2); quintile 3, 9.0 (95% CI: 8.2-9.7); quintile 4, 12.0 (95% CI: 11.1-12.9); and quintile 5, 20.8 (95% CI: 19.6-22.2). The relative risk reduction in the primary outcome with sacubitril/valsartan was consistent across NT-proBNP levels: the HR in quintile 1 was 0.79 (95% CI: 0.65-0.96); quintile 2, 0.87 (95% CI: 0.72-1.04); quintile 3, 0.79 (95% CI: 0.66-0.93); quintile 4, 0.85 (95% CI: 0.73-0.99); and quintile 5, 0.86 (95% CI: 0.76-0.97; P for interaction = 0.86). The absolute risk reduction was greatest in NT-proBNP quintile 5; the number needed to treat for the primary outcome over the median follow-up of 31 months was 16 in quintile 5 vs 37 in quintile 1. CONCLUSIONS The relative risk reductions with sacubitril/valsartan were consistent irrespective of NT-proBNP level in HF patients across the range of LVEF. Consequently, the absolute risk reductions were greatest in patients with higher NT-proBNP levels. (PARADIGM-HF; NCT01035255; and PARAGON-HF; NCT01920711).
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Affiliation(s)
- Toru Kondo
- British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom; Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Pardeep S Jhund
- British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom
| | - Inder S Anand
- VA Medical Center and University of Minnesota, Minneapolis, Minnesota
| | - Brian L Claggett
- Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Akshay S Desai
- Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Kieran F Docherty
- British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom
| | - Carolyn S P Lam
- National Heart Centre Singapore and Duke-National University of Singapore, Singapore
| | | | | | | | - Margaret M Redfield
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Jean L Rouleau
- Institut de Cardiologie de Montréal, Université de Montréal, Montréal, Quebec, Canada
| | - Dirk J Van Veldhuisen
- Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Faiez Zannad
- Investigation Network Initiative-Cardiovascular and Renal Clinical Trialists, University Hospital, University of Lorraine, Nancy, France
| | - Michael R Zile
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Milton Packer
- Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, Texas, USA
| | - Scott D Solomon
- Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - John J V McMurray
- British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
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7
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Kittipibul V, Lam CSP. Heart failure with preserved ejection fraction and atrial fibrillation: epidemiology, pathophysiology, and diagnosis interplay. Heart Fail Rev 2025:10.1007/s10741-025-10488-0. [PMID: 39849281 DOI: 10.1007/s10741-025-10488-0] [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] [Accepted: 01/13/2025] [Indexed: 01/25/2025]
Abstract
Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) are increasingly prevalent cardiovascular conditions, particularly among the elderly population. These two conditions share common risk factors and often coexist, leading to a complex interplay that alters the clinical course of each other. The pathophysiology of HFpEF is multifaceted and intricately linked, with atrial disease serving as a common pathophysiological pathway. Diagnosis of HFpEF in the setting of AF, and vice versa, can be challenging; thus, effective screening and diagnostic strategies are needed. Understanding the complex relationship between HFpEF and AF is crucial for optimal patient management by timely disease recognition and identification of therapeutic interventions or treatment strategies.
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Affiliation(s)
- Veraprapas Kittipibul
- Duke Clinical Research Institute, Durham, NC, USA
- Division of Cardiology, Duke University School of Medicine, Durham, NC, USA
| | - Carolyn S P Lam
- National Heart Centre Singapore and Duke-National University of Singapore, Singapore, Singapore.
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Bidaoui G, Assaf A, Marrouche N. Atrial Fibrillation in Heart Failure: Novel Insights, Challenges, and Treatment Opportunities. Curr Heart Fail Rep 2024; 22:3. [PMID: 39572434 PMCID: PMC11582326 DOI: 10.1007/s11897-024-00691-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/04/2024] [Indexed: 11/24/2024]
Abstract
PURPOSE OF REVIEW Atrial fibrillation and heart failure frequently co-exist. This review discusses the comorbidity of atrial fibrillation and heart failure, the bi-directional link between them, and the recent advances in the management of these co-existing diseases. RECENT FINDINGS Catheter ablation received a class 1 A recommendation for patients with AF and HF, after overwhelming evidence in heart failure with reduced ejection fraction and end-stage heart failure, while clinical trials are still lacking in patients with preserved ejection. Guideline-medical therapy of heart failure decreases the incidence of atrial fibrillation and the progression of atrial myopathy. Based on the current evidence, management of patients with both HF and AF should be include early optimization of comorbidity control, guideline-medical therapy for heart failure, and rhythm control preferentially through catheter ablation in properly selected patients.
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Affiliation(s)
- Ghassan Bidaoui
- Tulane Research Innovation for Arrhythmia Discovery (TRIAD), New Orleans, LA, USA
| | - Ala' Assaf
- Tulane Research Innovation for Arrhythmia Discovery (TRIAD), New Orleans, LA, USA
| | - Nassir Marrouche
- Tulane Research Innovation for Arrhythmia Discovery (TRIAD), New Orleans, LA, USA.
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Verma S, Butler J, Borlaug BA, Davies MJ, Kitzman DW, Petrie MC, Shah SJ, Jensen TJ, Rasmussen S, Rönnbäck C, Merkely B, O'Keefe E, Kosiborod MN. Atrial Fibrillation and Semaglutide Effects in Obesity-Related Heart Failure With Preserved Ejection Fraction: STEP-HFpEF Program. J Am Coll Cardiol 2024; 84:1603-1614. [PMID: 39217565 PMCID: PMC11486552 DOI: 10.1016/j.jacc.2024.08.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 08/13/2024] [Accepted: 08/14/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND Obesity is a key factor in the development and progression of both heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF). In the STEP-HFpEF Program (comprising the STEP-HFpEF [Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity] and STEP-HFpEF DM [Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes] trials), once-weekly semaglutide 2.4 mg improved HF-related symptoms, physical limitations, and exercise function and reduced body weight in patients with obesity-related HFpEF. Whether the effects of semaglutide in this patient group differ in participants with and without AF (and across various AF types) has not been fully examined. OBJECTIVES The goals of this study were: 1) to evaluate baseline characteristics and clinical features of patients with obesity-related HFpEF with and without a history of AF; and 2) to determine if the efficacy of semaglutide across all key trial outcomes are influenced by baseline history of AF (and AF types) in the STEP-HFpEF Program. METHODS This was a secondary analysis of pooled data from the STEP-HFpEF and STEP-HFpEF DM trials. Patients with heart failure, left ventricular ejection fraction ≥45%, body mass index ≥30 kg/m2, and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) <90 points were randomized 1:1 to receive once-weekly semaglutide 2.4 mg or matching placebo for 52 weeks. Dual primary endpoints (change in KCCQ-CSS and percent change in body weight), confirmatory secondary endpoints (change in 6-minute walk distance; hierarchical composite endpoint comprising all-cause death, HF events, thresholds of change in KCCQ-CSS, and 6-minute walk distance; and C-reactive protein [CRP]), and exploratory endpoint (change in N-terminal pro-B-type natriuretic peptide [NT-proBNP]) were examined according to investigator-reported history of AF (yes/no). Responder analyses examined the proportions of patients who experienced a ≥5-, ≥10, ≥15, and ≥20-point improvement in KCCQ-CSS per history of AF. RESULTS Of the 1,145 participants, 518 (45%) had a history of AF (40% paroxysmal, 24% persistent AF, and 35% permanent AF) and 627 (55%) did not. Participants with (vs without) AF were older, more often male, had higher NT-proBNP levels, included a higher proportion of those with NYHA functional class III symptoms, and used more antithrombotic therapies, beta-blockers, and diuretics. Semaglutide led to larger improvements in KCCQ-CSS (11.5 points [95% CI: 8.3-14.8] vs 4.3 points [95% CI: 1.3-7.2]; P interaction = 0.001) and the hierarchal composite endpoint (win ratio of 2.25 [95% CI: 1.79-2.83] vs 1.30 [95% CI: 1.06-1.59]; P interaction < 0.001) in participants with AF vs without AF, respectively. The proportions of patients receiving semaglutide vs those receiving placebo experiencing ≥5-, ≥10-, ≥15-, and ≥20-point improvement in KCCQ-CSS were also higher in those with (vs without) AF (all P interaction values <0.05). Semaglutide consistently reduced CRP, NT-proBNP, and body weight regardless of AF status (all P interaction values not significant). There were fewer serious adverse events and serious cardiac disorders in participants treated with semaglutide vs placebo irrespective of AF history. CONCLUSIONS In the STEP-HFpEF Program, AF was observed in nearly one-half of patients with obesity-related HFpEF and was associated with several features of more advanced HF. Treatment with semaglutide led to significant improvements in HF-related symptoms, physical limitations, and exercise function, as well as reductions in weight, CRP, and NT-proBNP in people with and without AF and across AF types. The magnitude of semaglutide-mediated improvements in HF-related symptoms and physical limitations was more pronounced in those with AF vs without AF at baseline. (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity [STEP-HFpEF; NCT04788511]; Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes [STEP-HFpEF DM; NCT04916470]).
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Affiliation(s)
- Subodh Verma
- Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, Ontario, Canada
| | - Javed Butler
- Baylor Scott and White Research Institute, Dallas, Texas, USA
| | - Barry A Borlaug
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Melanie J Davies
- Diabetes Research Centre, University of Leicester, Leicester, United Kingdom; NIHR Leicester Biomedical Research Centre, Leicester, United Kingdom
| | - Dalane W Kitzman
- Department of Internal Medicine, Sections on Cardiovascular Medicine and Geriatrics and Gerontology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
| | - Mark C Petrie
- School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom
| | - Sanjiv J Shah
- Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | | | | | | | - Bela Merkely
- Heart and Vascular Centre, Semmelweis University, Budapest, Hungary
| | - Evan O'Keefe
- Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA
| | - Mikhail N Kosiborod
- Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA.
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Parwani AS, Kääb S, Friede T, Tilz RR, Bauersachs J, Frey N, Hindricks G, Lewalter T, Rienstra M, Rillig A, Scherr D, Steven D, Kirchhof P, Pieske B. Catheter-based ablation to improve outcomes in patients with atrial fibrillation and heart failure with preserved ejection fraction: Rationale and design of the CABA-HFPEF-DZHK27 trial. Eur J Heart Fail 2024; 26:2203-2212. [PMID: 39023141 DOI: 10.1002/ejhf.3373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 06/05/2024] [Accepted: 06/23/2024] [Indexed: 07/20/2024] Open
Abstract
AIMS Atrial fibrillation (AF) is common in heart failure (HF) and negatively impacts outcomes. The role of ablation-based rhythm control in patients with AF and HF with preserved (HFpEF) or mildly reduced ejection fraction (HFmrEF) is not known. The CABA-HFPEF-DZHK27 (CAtheter-Based Ablation of atrial fibrillation compared to conventional treatment in patients with Heart Failure with Preserved Ejection Fraction) trial will determine whether early catheter ablation for AF can prevent adverse cardiovascular outcomes in patients with HFpEF or HFmrEF. METHODS CABA-HFPEF-DZHK27 (NCT05508256) is an investigator-initiated, prospective, randomized, open, interventional multicentre strategy trial with blinded outcome assessment. Approximately 1548 patients with paroxysmal or persistent AF diagnosed within 24 months prior to enrolment and HFpEF or HFmrEF will be randomized to early catheter ablation within 4 weeks after randomization or to usual care. All patients receive anticoagulation, rate control, and HF management according to current guideline recommendations. Usual care can include rhythm control in symptomatic patients. Patients will be followed until the end of the trial for the primary outcome, a composite of cardiovascular death, stroke, and total unplanned hospitalizations for HF or acute coronary syndrome. The safety outcome comprises complications of catheter ablation and death. The trial is powered for a rate ratio of 0.75 (two-sided alpha = 0.05, 1-beta = 0.8). CONCLUSION CABA-HFPEF-DZHK27 will define the role of systematic and early catheter ablation in patients with AF and HFpEF or HFmrEF.
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Affiliation(s)
- Abdul S Parwani
- Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Berlin, Germany
- German Centre for Cardiovascular Research (DZHK) Partner Site Berlin, Berlin, Germany
| | - Stefan Kääb
- Department of Cardiology, Ludwig-Maximilians-University Hospital Munich, Munich, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
| | - Tim Friede
- Department of Medical Statistics University Medical Center Göttingen, Göttingen, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Göttingen, Göttingen, Germany
| | - Roland Richard Tilz
- Clinic for Rhythmology, University Hospital Lübeck, Lübeck, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Lübeck, Lübeck, Germany
| | - Johann Bauersachs
- Department of Cardiology und Angiology, Hannover Medical School, Hannover, Germany
| | - Norbert Frey
- Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, Mannheim, Germany
| | - Gerhard Hindricks
- Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Berlin, Germany
- German Centre for Cardiovascular Research (DZHK) Partner Site Berlin, Berlin, Germany
| | | | - Michiel Rienstra
- Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Andreas Rillig
- Department of Cardiology, Heart and Vascular Center, University Medical Center Hamburg Eppendorf, Hamburg, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Hamburg, Hamburg, Germany
| | - Daniel Scherr
- Department of Cardiology, Medical University of Graz, Graz, Austria
| | - Daniel Steven
- Department of Cardiology, Heart Center University Hospital Cologne, Cologne, Germany
| | - Paulus Kirchhof
- Department of Cardiology, Heart and Vascular Center, University Medical Center Hamburg Eppendorf, Hamburg, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Hamburg, Hamburg, Germany
| | - Burkert Pieske
- Department of Cardiology, University Medical Center Rostock, Rostock, Germany
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11
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Krittanawong C, Britt WM, Rizwan A, Siddiqui R, Khawaja M, Khan R, Joolharzadeh P, Newman N, Rivera MR, Tang WHW. Clinical Update in Heart Failure with Preserved Ejection Fraction. Curr Heart Fail Rep 2024; 21:461-484. [PMID: 39225910 DOI: 10.1007/s11897-024-00679-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/02/2024] [Indexed: 09/04/2024]
Abstract
PURPOSE OF REVIEW To review the most recent clinical trials and data regarding epidemiology, pathophysiology, diagnosis, and treatment of heart failure with preserved ejection fraction with an emphasis on the recent trends in cardiometabolic interventions. RECENT FINDINGS Heart failure with preserved ejection fraction makes up approximately half of overall heart failure and is associated with significant morbidity, mortality, and overall burden on the healthcare system. It is a complex, heterogenous syndrome and clinical trials, to this point, have not revealed quite as many effective treatment options when compared to heart failure with reduced ejection fraction. Nevertheless, there is an expanding amount of data insight into the pathogenesis of this disease and the potential for newer therapies and management strategies. Heart failure with preserved ejection fraction pathology has been found to be linked to abnormal energetics, myocyte hypertrophy, cell signaling, inflammation, ischemia, and fibrosis. These mechanisms also intricately overlap with the significant comorbidities often associated with heart failure with preserved ejection fraction including, but not limited to, atrial fibrillation, chronic kidney disease, hypertension, obesity and coronary artery disease. Treatment of this disease, therefore, should focus on the management and strict regulation of these comorbidities by pharmacologic and nonpharmacologic means. In this review, a clinical update is provided reviewing the most recent clinical trials and data regarding epidemiology, pathophysiology, diagnosis, and treatment of heart failure with preserved ejection fraction with an emphasis on the recent trend in cardiometabolic interventions.
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Affiliation(s)
| | - William Michael Britt
- Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA
| | - Affan Rizwan
- Baylor College of Medicine, Houston, TX, 77030, USA
| | - Rehma Siddiqui
- Department of Internal Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA
| | - Muzamil Khawaja
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA, 30322, USA
| | - Rabisa Khan
- Department of Internal Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA
| | - Pouya Joolharzadeh
- John T Milliken Department of Medicine, Division of Cardiovascular Disease, Barnes-Jewish Hospital, St Louis, United States
| | - Noah Newman
- Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA
| | - Mario Rodriguez Rivera
- Advanced Heart Failure and Transplant, Barnes-Jewish Hospital Washington University in St Louis School of Medicine, St.Louis, MO, USA
| | - W H Wilson Tang
- Kaufman Center for Heart Failure Treatment and Recovery, Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland, OH, 44195, USA
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Karakasis P, Fragakis N, Patoulias D, Theofilis P, Sagris M, Koufakis T, Vlachakis PK, Rangraze IR, El Tanani M, Tsioufis K, Rizzo M. The Emerging Role of Glucagon-like Peptide-1 Receptor Agonists in the Management of Obesity-Related Heart Failure with Preserved Ejection Fraction: Benefits beyond What Scales Can Measure? Biomedicines 2024; 12:2112. [PMID: 39335625 PMCID: PMC11429383 DOI: 10.3390/biomedicines12092112] [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: 08/14/2024] [Revised: 09/09/2024] [Accepted: 09/12/2024] [Indexed: 09/30/2024] Open
Abstract
Obesity is a significant predisposing factor for heart failure with preserved ejection fraction (HFpEF). Although a substantial proportion of individuals with HFpEF also have obesity, those with obesity are under-represented in clinical trials for heart failure. In turn, current guidelines provided limited recommendations for the medical management of this patient population. Both obesity and diabetes induce a pro-inflammatory state that can contribute to endothelial dysfunction and coronary microvascular impairment, finally resulting in HFpEF. Additionally, obesity leads to increased epicardial and chest wall adiposity, which enhances ventricular interdependence. This condition is further aggravated by plasma and blood volume expansion and excessive vasoconstriction, ultimately worsening HFpEF. Despite the well-documented benefits of GLP-1 receptor agonists in subjects with diabetes, obesity, or both, their role in obesity-related HFpEF remains unclear. In light of the recently published literature, this review aims to investigate the potential mechanisms and synthesize the available clinical evidence regarding the role of GLP-1 receptor agonists in patients with obesity-related HFpEF.
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Affiliation(s)
- Paschalis Karakasis
- Second Department of Cardiology, Hippokration General Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece;
| | - Nikolaos Fragakis
- Second Department of Cardiology, Hippokration General Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece;
| | - Dimitrios Patoulias
- Second Propedeutic Department of Internal Medicine, Faculty of Medicine, School of Health Sciences Aristotle, University of Thessaloniki, 54642 Thessaloniki, Greece; (D.P.); (T.K.)
| | - Panagiotis Theofilis
- First Cardiology Department, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece; (P.T.); (M.S.); (P.K.V.); (K.T.)
| | - Marios Sagris
- First Cardiology Department, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece; (P.T.); (M.S.); (P.K.V.); (K.T.)
| | - Theocharis Koufakis
- Second Propedeutic Department of Internal Medicine, Faculty of Medicine, School of Health Sciences Aristotle, University of Thessaloniki, 54642 Thessaloniki, Greece; (D.P.); (T.K.)
| | - Panayotis K. Vlachakis
- First Cardiology Department, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece; (P.T.); (M.S.); (P.K.V.); (K.T.)
| | - Imran Rashid Rangraze
- Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah P.O. Box 11172, United Arab Emirates; (I.R.R.); (M.E.T.); (M.R.)
| | - Mohamed El Tanani
- Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah P.O. Box 11172, United Arab Emirates; (I.R.R.); (M.E.T.); (M.R.)
| | - Konstantinos Tsioufis
- First Cardiology Department, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece; (P.T.); (M.S.); (P.K.V.); (K.T.)
| | - Manfredi Rizzo
- Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah P.O. Box 11172, United Arab Emirates; (I.R.R.); (M.E.T.); (M.R.)
- School of Medicine, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (Promise), University of Palermo, 90100 Palermo, Italy
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von Haehling S, Assmus B, Bekfani T, Dworatzek E, Edelmann F, Hashemi D, Hellenkamp K, Kempf T, Raake P, Schütt KA, Wachter R, Schulze PC, Hasenfuss G, Böhm M, Bauersachs J. Heart failure with preserved ejection fraction: diagnosis, risk assessment, and treatment. Clin Res Cardiol 2024; 113:1287-1305. [PMID: 38602566 PMCID: PMC11371894 DOI: 10.1007/s00392-024-02396-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 02/02/2024] [Indexed: 04/12/2024]
Abstract
The aetiology of heart failure with preserved ejection fraction (HFpEF) is heterogenous and overlaps with that of several comorbidities like atrial fibrillation, diabetes mellitus, chronic kidney disease, valvular heart disease, iron deficiency, or sarcopenia. The diagnosis of HFpEF involves evaluating cardiac dysfunction through imaging techniques and assessing increased left ventricular filling pressure, which can be measured directly or estimated through various proxies including natriuretic peptides. To better narrow down the differential diagnosis of HFpEF, European and American heart failure guidelines advocate the use of different algorithms including comorbidities that require diagnosis and rigorous treatment during the evaluation process. Therapeutic recommendations differ between guidelines. Whilst sodium glucose transporter 2 inhibitors have a solid evidence base, the recommendations differ with regard to the use of inhibitors of the renin-angiotensin-aldosterone axis. Unless indicated for specific comorbidities, the use of beta-blockers should be discouraged in HFpEF. The aim of this article is to provide an overview of the current state of the art in HFpEF diagnosis, clinical evaluation, and treatment.
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Affiliation(s)
- Stephan von Haehling
- Department of Cardiology and Pneumology, University of Göttingen Medical Center, Robert-Koch-Strasse 40, 37075, Göttingen, Germany.
- German Center for Cardiovascular Research (DZHK), Partner Site Göttingen, Göttingen, Germany.
| | - Birgit Assmus
- Department of Cardiology and Angiology, Universitätsklinikum Gießen und Marburg, Giessen, Germany
| | - Tarek Bekfani
- Department of Cardiology and Angiology, Universitätsklinikum Magdeburg, Magdeburg, Germany
| | - Elke Dworatzek
- Institute of Gender in Medicine, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Frank Edelmann
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany
- Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité - Medical Heart Center of Charité and German Heart Institute Berlin, Campus Virchow-Klinikum, Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
| | - Djawid Hashemi
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany
- Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité - Medical Heart Center of Charité and German Heart Institute Berlin, Campus Virchow-Klinikum, Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, BIH Charité Digital Clinician Scientist Program, Berlin, Germany
| | - Kristian Hellenkamp
- Department of Cardiology and Pneumology, University of Göttingen Medical Center, Robert-Koch-Strasse 40, 37075, Göttingen, Germany
| | - Tibor Kempf
- Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany
| | - Philipp Raake
- I. Medical Department, Cardiology, Pneumology, Endocrinology and Intensive Care Medicine, University Hospital Augsburg, University of Augsburg, Augsburg, Germany
| | - Katharina A Schütt
- Department of Internal Medicine I, University Hospital RWTH Aachen, Aachen, Germany
| | - Rolf Wachter
- Department of Cardiology and Pneumology, University of Göttingen Medical Center, Robert-Koch-Strasse 40, 37075, Göttingen, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Göttingen, Göttingen, Germany
- Klinik und Poliklinik für Kardiologie, Universitätsklinikum Leipzig, Leipzig, Germany
| | - Paul Christian Schulze
- Department of Internal Medicine I, Division of Cardiology, University Hospital Jena, FSU, Jena, Germany
| | - Gerd Hasenfuss
- Department of Cardiology and Pneumology, University of Göttingen Medical Center, Robert-Koch-Strasse 40, 37075, Göttingen, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Göttingen, Göttingen, Germany
| | - Michael Böhm
- Kardiologie, Angiologie und Internistische Intensivmedizin, Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Saarland University, Homburg, Germany
| | - Johann Bauersachs
- Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany
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Tao SB, Lu X, Ye ZW, Tong NW. Update on evidence-based clinical application of sodium-glucose cotransporter inhibitors: Insight to uncommon cardiovascular disease scenarios in diabetes. World J Diabetes 2024; 15:1461-1476. [PMID: 39099824 PMCID: PMC11292321 DOI: 10.4239/wjd.v15.i7.1461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Revised: 04/28/2024] [Accepted: 05/29/2024] [Indexed: 07/08/2024] Open
Abstract
In this paper, we concentrate on updating the clinical research on sodium-glucose cotransporter inhibitors (SGLTis) for patients with type 2 diabetes who have heart failure with a preserved injection fraction, acute heart failure, atrial fibrillation, primary prevention of atherosclerotic cardiovascular disease/cardiovascular disease, and acute myocardial infarction. We searched the data of randomized controlled trials and meta-analyses of SGLTis in patients with diabetes from PubMed between January 1, 2020 and April 6, 2024 for our review. According to our review, certain SGLTis (empagliflozin, dapagliflozin, canagliflozin, and tofogliflozin), but not sodium-glucose cotransporter 1 inhibitor (SGLT1i), exhibit relatively superior clinical safety and effectiveness for treating the abovementioned diseases. Proper utilization of SGLTis in these patients can foster clinical improvement and offer an alternative medication option. However, clinical trials involving SGLTis for certain diseases have relatively small sample sizes, brief intervention durations, and conclusions based on weak evidence, necessitating additional data. These findings are significant and valuable for providing a more comprehensive reference and new possibilities for the clinical utilization and scientific exploration of SGLTis.
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Affiliation(s)
- Shi-Bing Tao
- Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
- Research Centre for Diabetes and Metabolism, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
- Department of Endocrinology and Metabolism, Ziyang Central Hospital, Ziyang 641300, Sichuan Province, China
| | - Xi Lu
- Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
- Research Centre for Diabetes and Metabolism, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Zi-Wei Ye
- Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Nan-Wei Tong
- Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
- Research Centre for Diabetes and Metabolism, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
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Mauriello A, Ascrizzi A, Roma AS, Molinari R, Caturano A, Imbalzano E, D’Andrea A, Russo V. Effects of Heart Failure Therapies on Atrial Fibrillation: Biological and Clinical Perspectives. Antioxidants (Basel) 2024; 13:806. [PMID: 39061875 PMCID: PMC11273474 DOI: 10.3390/antiox13070806] [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: 05/28/2024] [Revised: 06/21/2024] [Accepted: 07/02/2024] [Indexed: 07/28/2024] Open
Abstract
Heart failure (HF) and atrial fibrillation (AF) are prevalent cardiovascular diseases that contribute significantly to morbidity, mortality, hospitalisation, and healthcare costs. It is not uncommon for these conditions to coexist and have mutually reinforcing effects. A critical factor in the aetiology of these conditions is oxidative stress, driven by reactive oxygen species (ROS), which contributes to atrial remodelling and fibrosis. The recent introduction of new drugs for the treatment of heart failure has also had an impact on the management of atrial fibrillation due to their influence on oxidative stress. The objective of this review is to analyse the effects of these therapies, including their role in mitigating ROS, on the prevention and treatment of AF in HF patients.
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Affiliation(s)
- Alfredo Mauriello
- Cardiology Unit, Department of Medical and Translational Sciences, University of Campania “Luigi Vanvitelli”, Monaldi Hospital, 80131 Naples, Italy; (A.M.); (A.A.); (A.S.R.); (R.M.)
- Cardiology and Intensive Care Unit, Department of Cardiology, Umberto I Hospital, 84014 Nocera Inferiore, Italy;
| | - Antonia Ascrizzi
- Cardiology Unit, Department of Medical and Translational Sciences, University of Campania “Luigi Vanvitelli”, Monaldi Hospital, 80131 Naples, Italy; (A.M.); (A.A.); (A.S.R.); (R.M.)
| | - Anna Selvaggia Roma
- Cardiology Unit, Department of Medical and Translational Sciences, University of Campania “Luigi Vanvitelli”, Monaldi Hospital, 80131 Naples, Italy; (A.M.); (A.A.); (A.S.R.); (R.M.)
| | - Riccardo Molinari
- Cardiology Unit, Department of Medical and Translational Sciences, University of Campania “Luigi Vanvitelli”, Monaldi Hospital, 80131 Naples, Italy; (A.M.); (A.A.); (A.S.R.); (R.M.)
| | - Alfredo Caturano
- Department of Clinical and Experimental Medicine, University of Messina, 98100 Messina, Italy;
| | - Egidio Imbalzano
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy;
| | - Antonello D’Andrea
- Cardiology and Intensive Care Unit, Department of Cardiology, Umberto I Hospital, 84014 Nocera Inferiore, Italy;
| | - Vincenzo Russo
- Cardiology Unit, Department of Medical and Translational Sciences, University of Campania “Luigi Vanvitelli”, Monaldi Hospital, 80131 Naples, Italy; (A.M.); (A.A.); (A.S.R.); (R.M.)
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16
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Hamatani Y, Enzan N, Iguchi M, Yoshizawa T, Kawaji T, Ide T, Tohyama T, Matsushima S, Abe M, Tsutsui H, Akao M. Atrial fibrillation type and long-term clinical outcomes in hospitalized patients with heart failure: insight from JROADHF. EUROPEAN HEART JOURNAL. QUALITY OF CARE & CLINICAL OUTCOMES 2024; 10:193-202. [PMID: 38236704 DOI: 10.1093/ehjqcco/qcae005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Revised: 12/20/2023] [Accepted: 01/16/2024] [Indexed: 05/24/2024]
Abstract
AIMS Atrial fibrillation (AF) type (paroxysmal, persistent, or permanent) is important in determining therapeutic management; however, clinical outcomes by AF type are largely unknown for hospitalized patients with heart failure (HF). METHODS AND RESULTS The Japanese Registry Of Acute Decompensated Heart Failure is a retrospective, multicenter, and nationwide registry of patients hospitalized for acute HF in Japan. Follow-up data were collected up to 5 years after hospitalization. Patients were divided based on diagnosis and AF type into 3 groups [without AF, paroxysmal AF, and sustained AF (defined as a composite of persistent and permanent AF)], and compared the backgrounds and outcomes between the groups. Of 12 895 hospitalized HF patients [mean age: 78 ± 13 years, female: 6077 (47%), and mean left ventricular ejection fraction: 47 ± 17%], 1725 had paroxysmal AF, and 3672 had sustained AF. Compared with patients without AF, sustained AF had a higher risk of the primary composite endpoint of cardiovascular (CV) death or HF hospitalization [hazard ratio (HR): 1.09, 95% confidence interval (CI): 1.01-1.17; P = 0.03], mainly driven by HF hospitalization [HR: 1.16, 95% CI: 1.06-1.26; P < 0.001], whereas the corresponding risk for the primary endpoint in patients with paroxysmal AF was not elevated (HR: 1.03, 95% CI: 0.94-1.13; P = 0.53) after adjustment by multivariable Cox regression analysis. These results were consistent among the subgroups of patients with reduced or preserved ejection fraction (interaction P = 0.74). CONCLUSION Among hospitalized patients with HF, sustained AF, but not paroxysmal AF, was significantly associated with a higher risk for CV death or HF hospitalization, indicating the importance of accounting for AF type in HF patients.
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Affiliation(s)
- Yasuhiro Hamatani
- Department of Cardiology, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan
| | - Nobuyuki Enzan
- Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Moritake Iguchi
- Department of Cardiology, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan
| | - Takashi Yoshizawa
- Department of Cardiology, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan
| | - Tetsuma Kawaji
- Department of Cardiology, Mitsubishi Kyoto Hospital, Kyoto 615-8087, Japan
| | - Tomomi Ide
- Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Takeshi Tohyama
- Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Shouji Matsushima
- Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
| | - Mitsuru Abe
- Department of Cardiology, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan
| | - Hiroyuki Tsutsui
- School of Medicine and Graduate School, International University of Health and Welfare, Fukuoka 814-0001, Japan
| | - Masaharu Akao
- Department of Cardiology, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan
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17
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Zhang HD, Ding L, Mi LJ, Zhang AK, Zhang K, Jiang ZH, Yu FY, Yan XX, Shen YJ, Tang M. Sodium-glucose co-transporter-2 inhibitors for the prevention of atrial fibrillation: a systemic review and meta-analysis. Eur J Prev Cardiol 2024; 31:770-779. [PMID: 37966828 DOI: 10.1093/eurjpc/zwad356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 10/22/2023] [Accepted: 11/09/2023] [Indexed: 11/16/2023]
Abstract
AIMS Sodium-glucose co-transporter-2 (SGLT2) inhibitors are reported to have cardiac benefits. The effects of SGLT2 inhibitors on the prevention of atrial fibrillation (AF) remain inconclusive. We aimed to investigate whether SGLT2 inhibitors can prevent AF occurrence in patients with cardiometabolic diseases. METHODS AND RESULTS We searched MEDLINE, EMBASE, and the Cochrane CENTRAL database up to 1 July 2023. Randomized, placebo-controlled trials of SGLT2 inhibitors in patients with diabetes, heart failure, chronic kidney diseases (CKDs), or cardiometabolic risk factors were included. The primary outcome was AF occurrence. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated in the overall population and selected subgroups. Forty-six trials comprising 101 100 patients were included. Overall, no significant risk reduction of AF occurrence was observed with SGLT2 inhibitors, although there was a favourable trend (RR 0.90, 95% CI 0.80-1.01). In trials with follow-up durations of over 1 year, a similar result was achieved (RR 0.90, 95% CI 0.80-1.01). The results were consistent across different SGLT2 inhibitors, with RRs (95% CIs) of 0.82 (0.60-1.12) for canagliflozin, 0.87 (0.73-1.03) for dapagliflozin, 0.97 (0.78-1.22) for empagliflozin, 0.99 (0.66-1.50) for sotagliflozin, and 0.87 (0.58-1.29) for ertugliflozin. Analyses in different doses of SGLT2 inhibitors yielded similar results. The associations between SGLT2 inhibitors and AF occurrence were also absent in patients with diabetes, heart failure, and CKDs. CONCLUSION For patients with cardiometabolic diseases or risk factors, SGLT2 inhibitors did not decrease the risk of AF occurrence, regardless of follow-up duration, type or dose of the drug, or the patient population.
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Affiliation(s)
- Hong-Da Zhang
- State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Fuwai Hospital, 167 Beilishi Road, Xicheng District, Beijing 100037, China
| | - Lei Ding
- State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Fuwai Hospital, 167 Beilishi Road, Xicheng District, Beijing 100037, China
| | - Li-Jie Mi
- State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Fuwai Hospital, 167 Beilishi Road, Xicheng District, Beijing 100037, China
| | - Ai-Kai Zhang
- State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Fuwai Hospital, 167 Beilishi Road, Xicheng District, Beijing 100037, China
| | - Kuo Zhang
- State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Fuwai Hospital, 167 Beilishi Road, Xicheng District, Beijing 100037, China
| | - Zi-Han Jiang
- State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Fuwai Hospital, 167 Beilishi Road, Xicheng District, Beijing 100037, China
| | - Feng-Yuan Yu
- State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Fuwai Hospital, 167 Beilishi Road, Xicheng District, Beijing 100037, China
| | - Xin-Xin Yan
- State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Fuwai Hospital, 167 Beilishi Road, Xicheng District, Beijing 100037, China
| | - Yu-Jing Shen
- State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Fuwai Hospital, 167 Beilishi Road, Xicheng District, Beijing 100037, China
| | - Min Tang
- State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Fuwai Hospital, 167 Beilishi Road, Xicheng District, Beijing 100037, China
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18
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Linz D, Andrade JG, Arbelo E, Boriani G, Breithardt G, Camm AJ, Caso V, Nielsen JC, De Melis M, De Potter T, Dichtl W, Diederichsen SZ, Dobrev D, Doll N, Duncker D, Dworatzek E, Eckardt L, Eisert C, Fabritz L, Farkowski M, Filgueiras-Rama D, Goette A, Guasch E, Hack G, Hatem S, Haeusler KG, Healey JS, Heidbuechel H, Hijazi Z, Hofmeister LH, Hove-Madsen L, Huebner T, Kääb S, Kotecha D, Malaczynska-Rajpold K, Merino JL, Metzner A, Mont L, Ng GA, Oeff M, Parwani AS, Puererfellner H, Ravens U, Rienstra M, Sanders P, Scherr D, Schnabel R, Schotten U, Sohns C, Steinbeck G, Steven D, Toennis T, Tzeis S, van Gelder IC, van Leerdam RH, Vernooy K, Wadhwa M, Wakili R, Willems S, Witt H, Zeemering S, Kirchhof P. Longer and better lives for patients with atrial fibrillation: the 9th AFNET/EHRA consensus conference. Europace 2024; 26:euae070. [PMID: 38591838 PMCID: PMC11003300 DOI: 10.1093/europace/euae070] [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] [Received: 12/22/2023] [Accepted: 02/16/2024] [Indexed: 04/10/2024] Open
Abstract
AIMS Recent trial data demonstrate beneficial effects of active rhythm management in patients with atrial fibrillation (AF) and support the concept that a low arrhythmia burden is associated with a low risk of AF-related complications. The aim of this document is to summarize the key outcomes of the 9th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). METHODS AND RESULTS Eighty-three international experts met in Münster for 2 days in September 2023. Key findings are as follows: (i) Active rhythm management should be part of the default initial treatment for all suitable patients with AF. (ii) Patients with device-detected AF have a low burden of AF and a low risk of stroke. Anticoagulation prevents some strokes and also increases major but non-lethal bleeding. (iii) More research is needed to improve stroke risk prediction in patients with AF, especially in those with a low AF burden. Biomolecules, genetics, and imaging can support this. (iv) The presence of AF should trigger systematic workup and comprehensive treatment of concomitant cardiovascular conditions. (v) Machine learning algorithms have been used to improve detection or likely development of AF. Cooperation between clinicians and data scientists is needed to leverage the potential of data science applications for patients with AF. CONCLUSIONS Patients with AF and a low arrhythmia burden have a lower risk of stroke and other cardiovascular events than those with a high arrhythmia burden. Combining active rhythm control, anticoagulation, rate control, and therapy of concomitant cardiovascular conditions can improve the lives of patients with AF.
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Affiliation(s)
- Dominik Linz
- Department of Cardiology, Maastricht University Medical Center, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands
- Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jason G Andrade
- Division of Cardiology, Vancouver General Hospital, Vancouver, Canada
- Montreal Heart Institute, Montreal, Canada
| | - Elena Arbelo
- Institut Clínic Cardiovascular, Hospital Clinic, Universitat de Barcelona, Barcelona, Catalonia, Spain
- Institut d’Investigació August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
- European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart—ERN GUARD-Heart
| | - Giuseppe Boriani
- Cardiology Division, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Polyclinic of Modena, Modena, Italy
| | - Guenter Breithardt
- Department of Cardiovascular Medicine, University Hospital, Münster, Germany
- Atrial Fibrillation NETwork (AFNET), Muenster, Germany
| | - A John Camm
- Cardiology Clinical Academic Group, Molecular and Clinical Sciences Institute, St. George's University of London, London, UK
| | - Valeria Caso
- Stroke Unit, Santa Maria della Misericordia Hospital, University of Perugia, Perugia, Italy
| | - Jens Cosedis Nielsen
- Department of Cardiology, Aarhus University Hospital and Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | | | | | - Wolfgang Dichtl
- Department of Internal Medicine III, Cardiology and Angiology, Medical University Innsbruck, Innsbruck, Austria
| | | | - Dobromir Dobrev
- Institute of Pharmacology, Faculty of Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Nicolas Doll
- Department of Cardiac Surgery, Schüchtermann-Klinik, Bad Rothenfelde, Germany
| | - David Duncker
- Hannover Heart Rhythm Center, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany
| | | | - Lars Eckardt
- Atrial Fibrillation NETwork (AFNET), Muenster, Germany
- Department of Cardiology II—Electrophysiology, University Hospital Münster, Münster, Germany
| | | | - Larissa Fabritz
- Atrial Fibrillation NETwork (AFNET), Muenster, Germany
- University Center of Cardiovascular Science, UHZ, UKE, Hamburg, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site: Hamburg/Kiel/Lübeck, Hamburg, Germany
- Institute of Cardiovascular Sciences, University of Birmingham, Edgbaston, Birmingham, UK
| | - Michal Farkowski
- Department of Cardiology, Ministry of Interior and Administration, National Medical Institute, Warsaw, Poland
| | - David Filgueiras-Rama
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Novel Arrhythmogenic Mechanisms Program, Madrid, Spain
- Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Cardiovascular Institute, C/ Profesor Martín Lagos, Madrid, Spain
| | - Andreas Goette
- Atrial Fibrillation NETwork (AFNET), Muenster, Germany
- Department of Cardiology and Intensive Care Medicine, St Vincenz-Hospital Paderborn, Paderborn, Germany
| | - Eduard Guasch
- Institut d’Investigació August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
- Clinic Barcelona, University of Barcelona, Barcelona, Spain
| | - Guido Hack
- Bristol-Myers Squibb GmbH & Co. KGaA, Munich, Germany
| | | | - Karl Georg Haeusler
- Atrial Fibrillation NETwork (AFNET), Muenster, Germany
- Department of Neurology, Universitätsklinikum Würzburg (UKW), Würzburg, Germany
| | - Jeff S Healey
- Division of Cardiology, McMaster University, Hamilton, Ontario, Canada
- Population Health Research Institute, Hamilton, Ontario, Canada
| | - Hein Heidbuechel
- Antwerp University Hospital, Cardiovascular Sciences, University of Antwerp, Antwerp, Belgium
| | - Ziad Hijazi
- Antwerp University Hospital, Cardiovascular Sciences, University of Antwerp, Antwerp, Belgium
- Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden
- Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
| | | | - Leif Hove-Madsen
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
- Biomedical Research Institute Barcelona (IIBB-CSIC), Barcelona, Spain
- IR Sant Pau, Hospital de Sant Pau, Barcelona, Spain
| | | | - Stefan Kääb
- European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart—ERN GUARD-Heart
- Department of Medicine I, University Hospital, LMU Munich, Munich, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance, Munich, Germany
| | - Dipak Kotecha
- Institute of Cardiovascular Sciences, University of Birmingham, Edgbaston, Birmingham, UK
- NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Trust, Birmingham, UK
| | - Katarzyna Malaczynska-Rajpold
- Lister Hospital, East and North Hertfordshire NHS Trust, Stevenage, UK
- Royal Brompton Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, UK
| | - José Luis Merino
- La Paz University Hospital, IdiPaz, Autonomous University of Madrid, Madrid, Spain
| | - Andreas Metzner
- Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Martinistr. 52, Hamburg, Germany
| | - Lluís Mont
- Institut Clínic Cardiovascular, Hospital Clinic, Universitat de Barcelona, Barcelona, Catalonia, Spain
- Institut d’Investigació August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
| | - Ghulam Andre Ng
- Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
- NIHR Leicester Biomedical Research Centre, Leicester, UK
| | - Michael Oeff
- Atrial Fibrillation NETwork (AFNET), Muenster, Germany
- Cardiology Department, Medizinische Hochschule Brandenburg, Brandenburg/Havel, Germany
| | - Abdul Shokor Parwani
- Department of Cardiology, Deutsches Herzzentrum der Charité (CVK), Berlin, Germany
| | | | - Ursula Ravens
- Atrial Fibrillation NETwork (AFNET), Muenster, Germany
- Institute of Experimental Cardiovascular Medicine, University Clinic Freiburg, Freiburg, Germany
| | - Michiel Rienstra
- University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Prashanthan Sanders
- Centre for Heart Rhythm Disorders, University of Adelaide and Royal Adelaide Hospital, Adelaide, Australia
| | - Daniel Scherr
- Division of Cardiology, Medical University of Graz, Graz, Austria
| | - Renate Schnabel
- Atrial Fibrillation NETwork (AFNET), Muenster, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site: Hamburg/Kiel/Lübeck, Hamburg, Germany
- Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Martinistr. 52, Hamburg, Germany
| | - Ulrich Schotten
- Atrial Fibrillation NETwork (AFNET), Muenster, Germany
- Departments of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
| | - Christian Sohns
- Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Klinik für Elektrophysiologie—Rhythmologie, Bad Oeynhausen, Germany
| | - Gerhard Steinbeck
- Atrial Fibrillation NETwork (AFNET), Muenster, Germany
- Center for Cardiology at Clinic Starnberg, Starnberg, Germany
| | - Daniel Steven
- Atrial Fibrillation NETwork (AFNET), Muenster, Germany
- Heart Center, Department of Electrophysiology, University Hospital Cologne, Cologne, Germany
| | - Tobias Toennis
- German Centre for Cardiovascular Research (DZHK), Partner Site: Hamburg/Kiel/Lübeck, Hamburg, Germany
- Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Martinistr. 52, Hamburg, Germany
| | | | - Isabelle C van Gelder
- University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | | | - Kevin Vernooy
- Department of Cardiology, Maastricht University Medical Center, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands
| | - Manish Wadhwa
- Medical Office, Philips Ambulatory Monitoring and Diagnostics, San Diego, CA, USA
| | - Reza Wakili
- Atrial Fibrillation NETwork (AFNET), Muenster, Germany
- Department of Medicine and Cardiology, Goethe University, Frankfurt, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Germany
| | - Stephan Willems
- Atrial Fibrillation NETwork (AFNET), Muenster, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site: Hamburg/Kiel/Lübeck, Hamburg, Germany
- Asklepios Hospital St. Georg, Department of Cardiology and Internal Care Medicine, Faculty of Medicine, Semmelweis University Campus, Hamburg, Germany
| | | | - Stef Zeemering
- Departments of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
| | - Paulus Kirchhof
- Atrial Fibrillation NETwork (AFNET), Muenster, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site: Hamburg/Kiel/Lübeck, Hamburg, Germany
- Institute of Cardiovascular Sciences, University of Birmingham, Edgbaston, Birmingham, UK
- Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Martinistr. 52, Hamburg, Germany
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19
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Razaghizad A, Huynh T, Sharma A. The controversy between atrial fibrillation subtypes and worsening heart failure. EUROPEAN HEART JOURNAL. QUALITY OF CARE & CLINICAL OUTCOMES 2024:qcae018. [PMID: 38449340 DOI: 10.1093/ehjqcco/qcae018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/08/2024]
Affiliation(s)
- Amir Razaghizad
- Centre for Outcomes Research and Evaluation Research Institute of the McGill University Health Centre Montreal, QC, Canada
- Division of Cardiology, McGill University Health Centre McGill University Montreal Quebec Canada
| | - Thao Huynh
- Division of Cardiology, McGill University Health Centre McGill University Montreal Quebec Canada
| | - Abhinav Sharma
- Centre for Outcomes Research and Evaluation Research Institute of the McGill University Health Centre Montreal, QC, Canada
- Division of Cardiology, McGill University Health Centre McGill University Montreal Quebec Canada
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20
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Newman JD, O'Meara E, Böhm M, Savarese G, Kelly PR, Vardeny O, Allen LA, Lancellotti P, Gottlieb SS, Samad Z, Morris AA, Desai NR, Rosano GMC, Teerlink JR, Giraldo CS, Lindenfeld J. Implications of Atrial Fibrillation for Guideline-Directed Therapy in Patients With Heart Failure: JACC State-of-the-Art Review. J Am Coll Cardiol 2024; 83:932-950. [PMID: 38418008 DOI: 10.1016/j.jacc.2023.12.033] [Citation(s) in RCA: 21] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Revised: 11/29/2023] [Accepted: 12/18/2023] [Indexed: 03/01/2024]
Abstract
Atrial fibrillation (AF) and heart failure (HF) are common cardiovascular conditions that frequently coexist. Among patients with HF, more than one-half also have AF. Both are associated with significant morbidity and mortality. Moreover, the prevalence of each is increasing globally, and this trend is expected to continue owing to an aging population and increased life expectancy. Diagnosis of AF in a patient with HF is associated with greater symptom burden, more frequent hospitalizations, and a worse prognosis. Guideline-directed medical therapy (GDMT) for HF can affect the incidence of AF. Once present, AF can influence the efficacy of some components of GDMT for HF. In this review, we discuss the effect of GDMT for HF across the spectrum of ejection fraction on prevention of AF as well as the benefit of GDMT in patients with vs without AF.
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Affiliation(s)
| | - Eileen O'Meara
- Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada
| | - Michael Böhm
- University of the Saarland, Homberg/Saar, Germany
| | - Gianluigi Savarese
- Division of Cardiology, Department of Medicine, Karolinska Institute, Stockholm, Sweden; Heart and Vascular and Neuro Theme, Karolinska University Hospital, Stockholm, Sweden
| | | | - Orly Vardeny
- University of Minnesota Medical School, Minneapolis, Minnesota, USA
| | - Larry A Allen
- Division of Cardiology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA
| | | | - Stephen S Gottlieb
- Division of Cardiovascular Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA; Baltimore Veterans Administration Medical Center, Baltimore, Maryland, USA
| | | | | | - Nihar R Desai
- Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut, USA
| | - Giuseppe M C Rosano
- Center for Clinical and Basic Research, IRCCS San Raffaele Pisana, Rome, Italy
| | | | | | - JoAnn Lindenfeld
- Vanderbilt Heart and Vascular Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
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21
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Zheng S, Lai Y, Jiang C, He L, Zhao Z, Li W, Tang R, Sang C, Long D, Du X, Ma C, Dong J. Effect of SGLT2 inhibitors on cardiovascular events in patients with atrial fibrillation: A systematic review and meta-analysis of randomized controlled trials. Pacing Clin Electrophysiol 2024; 47:58-65. [PMID: 38010824 DOI: 10.1111/pace.14880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 09/14/2023] [Accepted: 11/08/2023] [Indexed: 11/29/2023]
Abstract
BACKGROUND Sodium-glucose cotransporter 2 inhibitors (SGLT2i) is reported to reduce incident atrial fibrillation (AF) in patients with or without diabetes; however, its cardiovascular (CV) benefit for AF patients remains unclear. SS AIMS To investigate the effect of SGLT2i on the incidence of CV events in patients with AF. METHODS Six randomized controlled trials (RCTs) assessing the effects of SGLT2i on CV outcomes in patients with or without AF were included (PROSPERO: CRD 42023431535). The primary endpoint was the composite outcome of heart failure (HF) hospitalization and CV death. Additionally, we assessed the effects of treatment in prespecified subgroups on HF hospitalization, CV death, and all-cause mortality. RESULTS Among 38,529 participants from all trials, 5018 patients with AF were treated with SGLT2i. The follow-up period of these trials ranged from 2.3 to 3.3 years. SGLT2i treatment was significantly associated with the risk reduction of primary endpoint in patients with AF (risk ratio [RR] 0.81, 95% confidence interval [CI] 0.74-0.88; p < 0.001), consistent with the finding in the general population (p for interaction = 0.76). SGLT2i was also associated with a consistent reduction in the risk of HF hospitalization in patients with AF (RR 0.76, 95% CI 0.69-0.84; p < 0.001) or not (RR 0.72, 95% CI 0.64-0.80; p < 0.0001), with no statistical difference between them (p for interaction = 0.41). Meta-regression further revealed no significant association between the prevalence of HF with reduced ejection fraction or diabetes and the effect size of SGLT2i. CONCLUSIONS The treatment effects of SGLT2i were associated with a lower incidence of CV events, especially HF hospitalization, in patients with AF.
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Affiliation(s)
- Shiyue Zheng
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Yiwei Lai
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Chao Jiang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Liu He
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, National Clinical Research Center for Cardiovascular Diseases, Beijing, China
| | - Zixu Zhao
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Wenjie Li
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Ribo Tang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Caihua Sang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Deyong Long
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Xin Du
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Changsheng Ma
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Jianzeng Dong
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
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Escobar C, Pascual-Figal D, Manzano L, Nuñez J, Camafort M. Current Role of SLGT2 Inhibitors in the Management of the Whole Spectrum of Heart Failure: Focus on Dapagliflozin. J Clin Med 2023; 12:6798. [PMID: 37959263 PMCID: PMC10649290 DOI: 10.3390/jcm12216798] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 10/21/2023] [Accepted: 10/25/2023] [Indexed: 11/15/2023] Open
Abstract
Heart failure (HF) is associated with a high morbidity and mortality burden. In light of more recent evidence, SGLT2 inhibitors are currently recommended as first-line therapy in managing patients with HF, regardless of ejection fraction, to reduce HF burden. The DAPA-HF and DELIVER trials, and particularly, the pooled analysis of both studies, have shown that dapagliflozin significantly reduces the risk of cardiovascular death, all-cause death, total HF hospitalizations, and MACE in the whole spectrum of HF, with sustained benefits over time. Recent data have shown that the full implementation of dapagliflozin in clinical practice would translate into a robust reduction in hospitalizations for HF and death in real-life populations. Many pathophysiological mechanisms have been involved in these benefits, particularly the positive effects of dapagliflozin on reversing cardiac (atrial and ventricular) remodeling, reducing cardiac fibrosis and inflammation, and improving endothelial dysfunction. In this manuscript, we reviewed from a practical point of view the role of dapagliflozin in the management of the whole spectrum of patients with HF.
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Affiliation(s)
- Carlos Escobar
- Cardiology Department, University Hospital La Paz, 28046 Madrid, Spain
| | - Domingo Pascual-Figal
- Cardiology Department, Hospital Clinico Universitario Virgen de la Arrixaca, 30120 Murcia, Spain;
- Spanish National Cardiovascular Research Centre (CNIC), 28029 Madrid, Spain
- Department of Medicine, Universidad de Murcia, 30100 Murcia, Spain
| | - Luis Manzano
- Internal Medicine Department, University Hospital Ramon y Cajal, Alcala de Henares University, 28034 Madrid, Spain;
| | - Julio Nuñez
- Cardiology Department, University Hospital Clínico of Valencia, Instituto de Investigación Sanitaria (INCLIVA), 46010 Valencia, Spain;
- CIBER Cardiovascular, 28029 Madrid, Spain
| | - Miguel Camafort
- Internal Medicine Department, Hospital Clinic, University of Barcelona, 08036 Barcelona, Spain;
- CIBER OBN, ISCIII (Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III), 28222 Madrid, Spain
- Working Group of Cardiovascular Risk, Nutrition, and Aging, IDIBAPS (Instituto de Investigaciones Biomédicas August Pi i Sunyer), 08036 Barcelona, Spain
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Lv J, Guo L, Wang R, Chen J. Efficacy and Safety of Sodium-Glucose Cotransporter-2 Inhibitors in Nondiabetic Patients with Chronic Kidney Disease: A Review of Recent Evidence. KIDNEY DISEASES (BASEL, SWITZERLAND) 2023; 9:326-341. [PMID: 37901712 PMCID: PMC10601939 DOI: 10.1159/000530395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 03/20/2023] [Indexed: 10/31/2023]
Abstract
Background Sodium-glucose cotransporter-2 inhibitors (SGLT2i) were initially developed as glucose-lowering agents in patients with type-2 diabetes. However, available data from clinical trials and meta-analyses suggest that SGLT2i have pleiotropic benefits in reducing mortality and delaying the progression of chronic kidney disease (CKD) in both diabetic and nondiabetic patients. Thus, we herein review the current evidence regarding the efficacy and safety of SGLT2i in patients with nondiabetic CKD and appraise the recently reported clinical trials that might facilitate the management of CKD in routine clinical practice. Summary The benefits of SGLT2i on nondiabetic CKD are multifactorial and are mediated by a combination of mechanisms. The landmark DAPA-CKD trial revealed that dapagliflozin administered with renin-angiotensin system blockade drugs reduced the risk of a sustained decline (at least 50%) in the estimated glomerular filtration rate, end-stage kidney disease, or death from cardiorenal causes. The recent EMPA-KIDNEY trial showed that empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes. These benefits were consistent in patients with and without diabetes. Moreover, a meta-analysis of DAPA-HF and EMPEROR-Reduced trials confirmed reductions in the combined risk of cardiovascular death or worsening heart failure including composite renal endpoint. Key Messages Considering the robust data available from DAPA-CKD, EMPA-KIDNEY, and other trials such as EMPEROR-Preserved, DIAMOND that included nondiabetic patients, it may be necessary to update current guidelines to include SGLT2i as a first-line therapy for CKD and reevaluate current CKD therapeutic approaches.
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Affiliation(s)
- Junhao Lv
- Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, China
- National Key Clinical Department of Kidney Diseases, Institute of Nephrology, Zhejiang University, Hangzhou, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
| | - Luying Guo
- Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, China
- National Key Clinical Department of Kidney Diseases, Institute of Nephrology, Zhejiang University, Hangzhou, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
| | - Rending Wang
- Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, China
- National Key Clinical Department of Kidney Diseases, Institute of Nephrology, Zhejiang University, Hangzhou, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
| | - Jianghua Chen
- Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, China
- National Key Clinical Department of Kidney Diseases, Institute of Nephrology, Zhejiang University, Hangzhou, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
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Patel RB, Reddy VY, Komtebedde J, Wegerich SW, Sekaric J, Swarup V, Walton A, Laurent G, Chetcuti S, Rademann M, Bergmann M, McKenzie S, Bugger H, Bruno RR, Herrmann HC, Nair A, Gupta DK, Lim S, Kapadia S, Gordon R, Vanderheyden M, Noel T, Bailey S, Gertz ZM, Trochu JN, Cutlip DE, Leon MB, Solomon SD, van Veldhuisen DJ, Auricchio A, Shah SJ. Atrial Fibrillation Burden and Atrial Shunt Therapy in Heart Failure With Preserved Ejection Fraction. JACC. HEART FAILURE 2023; 11:1351-1362. [PMID: 37480877 DOI: 10.1016/j.jchf.2023.05.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Revised: 05/12/2023] [Accepted: 05/17/2023] [Indexed: 07/24/2023]
Abstract
BACKGROUND Atrial fibrillation (AF) is a common comorbidity in patients with heart failure with preserved ejection fraction (HFpEF) and in heart failure with mildly reduced ejection fraction (HFmrEF). OBJECTIVES This study sought to describe AF burden and its clinical impact among individuals with HFpEF and HFmrEF who participated in a randomized clinical trial of atrial shunt therapy (REDUCE LAP-HF II [A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure]) and to evaluate the effect of atrial shunt therapy on AF burden. METHODS Study investigators characterized AF burden among patients in the REDUCE LAP-HF II trial by using ambulatory cardiac patch monitoring at baseline (median patch wear time, 6 days) and over a 12-month follow-up (median patch wear time, 125 days). The investigators determined the association of baseline AF burden with long-term clinical events and examined the effect of atrial shunt therapy on AF burden over time. RESULTS Among 367 patients with cardiac monitoring data at baseline and follow-up, 194 (53%) had a history of AF or atrial flutter (AFL), and median baseline AF burden was 0.012% (IQR: 0%-1.3%). After multivariable adjustment, baseline AF burden ≥0.012% was significantly associated with heart failure (HF) events (HR: 2.00; 95% CI: 1.17-3.44; P = 0.01) both with and without a history of AF or AFL (P for interaction = 0.68). Adjustment for left atrial reservoir strain attenuated the baseline AF burden-HF event association (HR: 1.71; 95% CI: 0.93-3.14; P = 0.08). Of the 367 patients, 141 (38%) had patch-detected AF during follow-up without a history of AF or AFL. Atrial shunt therapy did not change AF incidence or burden during follow-up. CONCLUSIONS In HFpEF and HFmrEF, nearly 40% of patients have subclinical AF by 1 year. Baseline AF burden, even at low levels, is associated with HF events. Atrial shunt therapy does not affect AF incidence or burden. (A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure [REDUCE LAP-HF II]; NCT03088033).
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Affiliation(s)
- Ravi B Patel
- Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA; Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Illinois, USA
| | - Vivek Y Reddy
- Helmsley Electrophysiology Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | | | | | | | | | | | - Gabriel Laurent
- Department of Cardiology, Dijon University Hospital, Dijon, France
| | - Stanley Chetcuti
- Division of Cardiology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA
| | - Matthias Rademann
- Department of Cardiology, University of Giessen, Bad Nauheim, Germany
| | - Martin Bergmann
- Department of Interventional Cardiology, Cardiologicum, Hamburg, Germany
| | - Scott McKenzie
- School of Medicine, University of Queensland, The Prince Charles Hospital, Brisbane, Australia
| | - Heiko Bugger
- Division of Cardiology, Medical University of Graz, Graz, Austria
| | - Raphael Romano Bruno
- Division of Cardiology, Pulmonology, and Vascular Medicine, Faculty of Medicine, University Hospital Dusseldorf, Heinrich-Heine-University Dusseldorf, Dusseldorf, Germany
| | - Howard C Herrmann
- Division of Cardiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Ajith Nair
- Division of Cardiology, Baylor College of Medicine, Houston, Texas, USA
| | - Deepak K Gupta
- Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Scott Lim
- Division of Cardiology, University of Virginia School of Medicine, Charlottesville, Virginia, USA
| | - Samir Kapadia
- Division of Cardiology, Cleveland Clinic, Cleveland, Ohio, USA
| | - Robert Gordon
- Division of Cardiology, NorthShore University Health System, Evanston, Illinois, USA
| | | | - Thomas Noel
- Southern Medical Group, P.A., Tallahassee, Florida, USA
| | - Steven Bailey
- Division of Cardiology, Louisiana State University School of Medicine, Baton Rouge, Louisiana, USA
| | - Zachary M Gertz
- Division of Cardiology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Jean-Noël Trochu
- Nantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France
| | - Donald E Cutlip
- Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Martin B Leon
- Columbia University Irving Medical Center, New York-Presbyterian Hospital, New York, New York, USA
| | - Scott D Solomon
- Division of Cardiology, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Dirk J van Veldhuisen
- Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Angelo Auricchio
- Division of Cardiology, Ticino Cardiocentro Institute, Lugano, Switzerland
| | - Sanjiv J Shah
- Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
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25
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Suzuki S, Kitai T, Skoularigis J, Spiliopoulos K, Xanthopoulos A. Catheter Ablation for Atrial Fibrillation in Patients with Heart Failure: Current Evidence and Future Opportunities. J Pers Med 2023; 13:1394. [PMID: 37763161 PMCID: PMC10532515 DOI: 10.3390/jpm13091394] [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: 08/18/2023] [Revised: 09/14/2023] [Accepted: 09/15/2023] [Indexed: 09/29/2023] Open
Abstract
Atrial fibrillation (AF) and heart failure (HF) are highly prevalent cardiac disorders worldwide, and both are associated with poor prognosis. The incidence of AF and HF has been increasing substantially in recent years, mainly due to the progressive aging of the population. These disorders often coexist, and may have a causal relationship, with one contributing to the development or progression of the other. AF is a significant risk factor for adverse outcomes in HF patients, including mortality, hospitalization, and stroke. Although the optimal treatment for AF with HF remains unclear, catheter ablation (CA) has emerged as a promising treatment option. This review provides a comprehensive overview of the current scientific evidence regarding the efficacy of CA for managing AF in HF patients. In addition, the potential benefits and risks associated with CA are also discussed. We will also explore the factors that may influence treatment outcomes and highlight the remaining gaps in knowledge in this field.
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Affiliation(s)
- Sho Suzuki
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka 564-8565, Japan
- Department of Cardiovascular Medicine, Shinshu University School of Medicine, Nagano 390-8621, Japan
| | - Takeshi Kitai
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka 564-8565, Japan
| | - John Skoularigis
- Department of Cardiology, University Hospital of Larissa, 41110 Larissa, Greece
| | - Kyriakos Spiliopoulos
- Department of Cardiothoracic Surgery, University of Thessaly, Biopolis, 41110 Larissa, Greece
| | - Andrew Xanthopoulos
- Department of Cardiology, University Hospital of Larissa, 41110 Larissa, Greece
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26
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Díez-Villanueva P, Jimenez-Mendez C, Pérez Á, Esteban-Fernández A, Datino T, Martínez-Sellés M, Ayesta A. Do Elderly Patients with Heart Failure and Reduced Ejection Fraction Benefit from Pharmacological Strategies for Prevention of Arrhythmic Events? Cardiology 2023; 148:195-206. [PMID: 37040727 DOI: 10.1159/000530424] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Accepted: 03/20/2023] [Indexed: 04/13/2023]
Abstract
BACKGROUND Heart failure is associated with aging. It is one of the leading causes of morbidity and mortality in Western countries and constitutes the main cause of hospitalization among elderly patients. The pharmacological therapy of patients with heart failure with reduced ejection fraction (HFrEF) has greatly improved during the last years. However, elderly patients less frequently receive recommended medical treatment. SUMMARY The quadruple therapy (sacubitril/valsartan, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors) is nowadays the cornerstone of medical treatment since it associates lower risk of heart failure hospitalizations and mortality (also of arrhythmic origin). Cardiac arrhythmias, including sudden cardiac death, are common in patients with HFrEF, entailing worse prognosis. Previous studies addressing the role of blocking the renin-angiotensin-aldosterone system and beta-adrenergic receptors in HFrEF have suggested different beneficial effects on arrhythmia mechanisms. Therefore, the lower mortality associated with the use of the four pillars of HFrEF therapy depends, in part, on lower sudden (mostly arrhythmic) cardiac death. KEY MESSAGES In this review, we highlight and assess the role of the four pharmacological groups that constitute the central axis of the medical treatment of patients with HFrEF in clinical prognosis and prevention of arrhythmic events, with special focus on the elderly patient, since evidence supports that most benefits provided are irrespective of age, but elderly patients receive less often guideline-recommended medical treatment.
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Affiliation(s)
| | | | - Ángel Pérez
- Cardiology Department, Hospital Universitario de Burgos, Burgos, Spain
- Facultad de Ciencias de la Salud, Universidad Isabel I, Burgos, Spain
| | | | - Tomás Datino
- Cardiology Department, Hospital Universitario Quirón and Complejo Hospitalario Ruber Juan Bravo, Madrid, Spain
- Universidad Europea de Madrid, Madrid, Spain
| | - Manuel Martínez-Sellés
- Cardiology Department, Hospital Universitario Gregorio Marañón, Madrid, Spain
- Universidad Complutense and Universidad Europea, Madrid, Spain
| | - Ana Ayesta
- Cardiology Department, Hospital Universitario Central de Asturias, Oviedo, Spain
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27
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Girerd N, Zannad F. SGLT2 inhibition in heart failure with reduced or preserved ejection fraction: Finding the right patients to treat. J Intern Med 2023; 293:550-558. [PMID: 36871279 DOI: 10.1111/joim.13620] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/06/2023]
Abstract
Sodium-glucose transport inhibitors (SGLT2i) are effective in heart failure (HF) with ejection fraction (EF) <40% (referred to as HF with reduced EF - HFrEF) and left ventricular EF (LVEF) >40%. Current evidence suggests that SGLT2i should be initiated across a large spectrum of EFs and renal function in patients with HF and with and without diabetes. We reviewed the benefits of SGLT2i in the entire spectrum of HF and provided some clues that may guide physicians in their strategy of initiating and maintaining SGLT2i (with or without SGLT1i effect) therapy. Taken together, the evidence thus far arises from an array of trials performed in different settings (acute/chronic), risk categories, and phenotypes of HF (HFrEF/HFpEF), and in addition to the most common HF therapies, supports the homogenous effect of SGLT2i across a large spectrum of patients with HF. SGLT2i appear to be effective and well-tolerated drugs in the majority of clinical HF scenarios, regardless of LVEF, estimated glomerular filtration rate, diabetic status or the level of the acuteness of the clinical setting. Therefore, most patients with HF should be treated with SGLT2i. However, in the face of the therapeutic inertia that has been observed in HF over the past decades, the actual implementation of SGLT2i in routine practice remains the most significant challenge.
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Affiliation(s)
- Nicolas Girerd
- Université de Lorraine, INSERM, Centre d'Investigations Cliniques-Plurithématique 14-33, CHRU Nancy, Vandoeuvre les Nancy, France
| | - Faiez Zannad
- Université de Lorraine, INSERM, Centre d'Investigations Cliniques-Plurithématique 14-33, CHRU Nancy, Vandoeuvre les Nancy, France
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28
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Patel RB, Greene SJ, Xu H, Alhanti B, Peterson P, Yancy CW, Piccini J, Fonarow GC, Vaduganathan M. Intersection of atrial fibrillation and heart failure with mildly reduced and preserved ejection fraction in >400 000 participants in the Get With The Guidelines-Heart Failure Registry. Eur J Heart Fail 2023; 25:63-73. [PMID: 36343200 PMCID: PMC10157723 DOI: 10.1002/ejhf.2729] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 10/29/2022] [Accepted: 10/29/2022] [Indexed: 11/09/2022] Open
Abstract
AIMS Although atrial fibrillation (AF) frequently coexists with heart failure with preserved ejection fraction (HFpEF), few data are available evaluating AF-specific care patterns and post-discharge outcomes in patients hospitalized for HFpEF. We evaluated AF-specific medical therapies and post-discharge outcomes among patients hospitalized for heart failure with mildly reduced ejection fraction (HFmrEF) or HFpEF by AF history. METHODS AND RESULTS Trends in AF prevalence were evaluated among patients hospitalized for HFmrEF or HFpEF in the Get With The Guidelines-Heart Failure Registry from 2014 to 2020. Among those with linked Centers for Medicare & Medicaid Services post-discharge data, we assessed associations of AF with 12-month outcomes and determined trends in post-discharge prescriptions. Among 429 464 patients (median age 76 years [interquartile range 65-85], 57% women), 216 486 (50%) had a history of AF. Over time, the proportion of patients with AF increased slightly. Among the 79 895 patients with post-discharge data, AF was independently associated with higher risk of mortality and all-cause readmissions at 12 months, with stronger associations in HFpEF than in HFmrEF (mortality hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.09-1.16 vs. HR 1.03, 95% CI 0.97-1.10; pinteraction = 0.009). Anti-arrhythmic drug use after heart failure hospitalization was low (18%) and increased modestly over time. Amiodarone accounted for 71% of total anti-arrhythmic drug prescriptions. Overall use of anticoagulants after heart failure hospitalization has significantly increased from 52% in 2014 to 61% in 2019, but remained modest. CONCLUSION Prevalence of AF is rising among patients hospitalized with HFpEF. Those with comorbid AF face elevated post-discharge risks of death and rehospitalization. Current use of pharmacological rhythm control is low.
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Affiliation(s)
- Ravi B Patel
- Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Stephen J Greene
- Duke Clinical Research Institute, Durham, NC, USA
- Division of Cardiology, Duke University School of Medicine, Durham, NC, USA
| | - Haolin Xu
- Duke Clinical Research Institute, Durham, NC, USA
| | | | - Pamela Peterson
- Department of Medicine, Denver Health Medical Center, Denver, CO, USA
| | - Clyde W Yancy
- Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Jonathan Piccini
- Duke Clinical Research Institute, Durham, NC, USA
- Division of Cardiology, Duke University School of Medicine, Durham, NC, USA
| | - Gregg C Fonarow
- Department of Medicine, Anschutz Medical Center, Aurora, CO, USA
- Ahmanson-University of California, Los Angeles Cardiomyopathy Center, University of California-Los Angeles, Los Angeles, CA, USA
| | - Muthiah Vaduganathan
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
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