|
1
|
Dalsania AK, Park CM, Nagraj S, Lorenzatti D, Filtz A, Weissler-Snir A, Garcia MJ, Slipczuk L, Schenone AL. A Practical Approach to Multimodality Imaging in Hypertrophic Cardiomyopathy. J Clin Med 2025; 14:2606. [PMID: 40283436 PMCID: PMC12027606 DOI: 10.3390/jcm14082606] [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: 03/10/2025] [Revised: 03/30/2025] [Accepted: 04/04/2025] [Indexed: 04/29/2025] Open
Abstract
Hypertrophic cardiomyopathy remains underdiagnosed despite a growing number of effective treatment interventions that can improve care. Multimodality imaging has become integral to diagnosing and managing hypertrophic cardiomyopathy, providing a comprehensive assessment of the disease. In particular, it enhances the diagnostic accuracy and deepens the understanding of the mechanisms underlying patient symptoms, enabling targeted therapeutic approaches. Additionally, multimodality imaging allows for better risk stratification, assessment of therapy response, and guidance of interventions to deliver personalized medicine. The practical tools outlined in this review can help providers integrate multimodality imaging strategies to provide better care and improve the patient experience.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | | | - Aldo L. Schenone
- Montefiore Einstein Center for Heart & Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA; (A.K.D.); (C.M.P.); (S.N.); (D.L.); (A.F.); (A.W.-S.); (M.J.G.); (L.S.)
| |
Collapse
|
|
2
|
Touma R, Pareddy AR, Abidov A. Value of Advanced Cardiac CTA in Clinical Assessment of Hypertrophic Cardiomyopathy: A Literature Review and Practical Implications. Echocardiography 2025; 42:e70111. [PMID: 39964029 DOI: 10.1111/echo.70111] [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: 12/30/2024] [Revised: 02/04/2025] [Accepted: 02/07/2025] [Indexed: 05/10/2025] Open
Abstract
Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac anomaly with a potentially unfavorable clinical outcome. The essential role of multimodality imaging in HCM is well recognized by major professional cardiac imaging societies and has been incorporated into the HCM clinical practice guidelines. Appropriate utilization of cardiac imaging tools is cardinal for accurate diagnosis and appropriate management for HCM patients to mitigate their lifelong risk of adverse events. Echocardiography is the imaging modality of choice for clinical diagnosis of HCM. Cardiac magnetic resonance (CMR) and coronary computed tomography angiogram (CCTA) offer complementary practical information for an inclusive evaluation in such patients. CCTA provides a thorough analysis of the cardiac anatomy and function that is paramount in HCM clinical decision-making. This review summarizes the utility of CCTA in the clinical assessment of patients with HCM. It outlines the multi-role of CCTA in HCM, including the quantification of cardiac parameters, myocardial tissue characterization, left ventricular (LV) functional analysis, the definition of cardiac and coronary arteries (CA) anatomy, and the provision of a roadmap for septal reduction therapies (SRT), mitral valve (MV) intervention, and atrial fibrillation (AF) ablation.
Collapse
Affiliation(s)
- Rabih Touma
- Department of Medicine/Division of Cardiology, Wayne State University School of Medicine, Detroit, Michigan, USA
- Department of Medicine/Division of Cardiology, John D. Dingell VA, Medical Center, Detroit, Michigan, USA
| | - Anisha R Pareddy
- Department of Medicine/Division of Cardiology, Wayne State University School of Medicine, Detroit, Michigan, USA
- Department of Medicine/Division of Cardiology, John D. Dingell VA, Medical Center, Detroit, Michigan, USA
| | - Aiden Abidov
- Department of Medicine/Division of Cardiology, Wayne State University School of Medicine, Detroit, Michigan, USA
- Department of Medicine/Division of Cardiology, John D. Dingell VA, Medical Center, Detroit, Michigan, USA
| |
Collapse
|
|
3
|
Izumi Y, Takanashi S, Kitamura M, Takamisawa I, Saito M, Otaki Y, Iwakura T, Takayama M. Morphological anomalies in obstructive hypertrophic cardiomyopathy: Insights from four-dimensional computed tomography and surgical correlation. J Cardiol 2025; 85:28-37. [PMID: 39002717 DOI: 10.1016/j.jjcc.2024.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 06/21/2024] [Accepted: 07/03/2024] [Indexed: 07/15/2024]
Abstract
Hypertrophic cardiomyopathy (HCM) is a genetic disorder in which left ventricular outflow tract obstruction critically affects symptoms and prognosis. Traditionally, left ventricular outflow tract obstruction was primarily attributed to septal hypertrophy with systolic anterior motion of the mitral valve. However, recent evidence highlights significant contributions from the mitral valve and papillary muscle anomalies, as well as an apical-basal muscle bundle observed in HCM patients. Accurate morphological assessment is essential when considering septal reduction therapy. While transesophageal echocardiography and cardiac magnetic resonance are recommended for assessing the anomalous structures, four-dimensional computed tomography offers superior spatial resolution and multiplanar reconstruction capabilities. These features enable the evaluation of details of the morphological anomalies, such as the apical-basal muscle band, papillary muscle anomalies, subaortic stenosis, and right ventricular outflow tract obstruction. Based on the detailed assessment of these morphological features, four-dimensional computed tomography has been utilized for planning of surgical correction in a comprehensive HCM center. This approach facilitates the intervention strategies and may improve outcomes in septal reduction therapy for obstructive HCM.
Collapse
Affiliation(s)
- Yuki Izumi
- Hypertrophic Cardiomyopathy Center, Sakakibara Heart Institute, Tokyo, Japan; Department of Cardiology, Sakakibara Heart Institute, Tokyo, Japan.
| | - Shuichiro Takanashi
- Hypertrophic Cardiomyopathy Center, Sakakibara Heart Institute, Tokyo, Japan; Department of Cardiovascular Surgery, Sakakibara Heart Institute, Tokyo, Japan
| | - Mitsunobu Kitamura
- Hypertrophic Cardiomyopathy Center, Sakakibara Heart Institute, Tokyo, Japan; Department of Cardiology, Sakakibara Heart Institute, Tokyo, Japan
| | - Itaru Takamisawa
- Hypertrophic Cardiomyopathy Center, Sakakibara Heart Institute, Tokyo, Japan; Department of Cardiology, Sakakibara Heart Institute, Tokyo, Japan
| | - Mika Saito
- Department of Pediatric Cardiology, Sakakibara Heart Institute, Tokyo, Japan
| | - Yuka Otaki
- Hypertrophic Cardiomyopathy Center, Sakakibara Heart Institute, Tokyo, Japan; Department of Radiology, Sakakibara Heart Institute, Tokyo, Japan
| | - Tomohiro Iwakura
- Hypertrophic Cardiomyopathy Center, Sakakibara Heart Institute, Tokyo, Japan; Department of Cardiovascular Surgery, Sakakibara Heart Institute, Tokyo, Japan
| | - Morimasa Takayama
- Hypertrophic Cardiomyopathy Center, Sakakibara Heart Institute, Tokyo, Japan; Department of Cardiology, Sakakibara Heart Institute, Tokyo, Japan
| |
Collapse
|
|
4
|
Banthiya S, Check L, Atkins J. Hypertrophic Cardiomyopathy as a Form of Heart Failure with Preserved Ejection Fraction: Diagnosis, Drugs, and Procedures. US CARDIOLOGY REVIEW 2024; 18:e17. [PMID: 39508003 PMCID: PMC11539043 DOI: 10.15420/usc.2023.21] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Accepted: 03/13/2024] [Indexed: 11/08/2024] Open
Abstract
Hypertrophic cardiomyopathy (HCM) is a complex and heterogeneous cardiac disorder characterized by cardiac hypertrophy disproportionate to loading stimuli (e.g. hypertension or aortic stenosis). Diagnosing HCM requires a thorough examination of clinical symptoms, with echocardiography as the key initial imaging tool. Multimodality imaging further supports diagnosis, helps assess left ventricular outflow obstruction, and aids in risk stratification for sudden cardiac death. The cornerstone of HCM management remains pharmacological therapy with β-blockers and calcium channel blockers serving as first-line agents to alleviate symptoms and reduce left ventricular outflow tract obstruction. More recently, cardiac myosin inhibitors have revolutionized the treatment paradigm for obstructive HCM. Procedural interventions such as septal reduction therapy are reserved for refractory cases. Genetic testing and risk stratification for sudden cardiac death play a critical role in treatment decisions, guiding further testing in first-degree relatives and ICD implantation in high-risk individuals. Exercise recommendations have evolved based on recent data, challenging traditional restrictions and emphasizing individualized plans.
Collapse
Affiliation(s)
- Sukriti Banthiya
- Department of Internal Medicine, Ascension Providence Hospital/Michigan State University College of Human MedicineSouthfield, MI
| | - Larissa Check
- Department of Cardiology, Medical University of South CarolinaCharleston, SC
| | - Jessica Atkins
- Department of Cardiology, Medical University of South CarolinaCharleston, SC
| |
Collapse
|
|
5
|
Mazur M, Braksator W, Popjes E. Hypertrophic Cardiomyopathy: From Medical Treatment to Advanced Heart Failure Therapies. Curr Cardiol Rep 2024; 26:985-994. [PMID: 38990491 DOI: 10.1007/s11886-024-02095-6] [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: 07/02/2024] [Indexed: 07/12/2024]
Abstract
PURPOSE OF REVIEW There has been much debate surrounding novel medical therapies and heart transplantation listing challenges in patients with hypertrophic cardiomyopathy (HCM). RECENT FINDINGS Recent clinical trials led to FDA approval of mavacamten (a cardiac myosin inhibitor), offering symptom relief and potentially delaying/avoiding invasive septal reduction therapies for some patients with HCM and left ventricular outflow obstruction (LVOTO). For those with refractory symptoms and end-stage heart failure, heart transplantation remains the gold standard. However, the concern for the organ allocation system failing to prioritize those individuals persists. HCM is a heterogeneous genetic condition with variable penetration and clinical presentation. Even though a large portion of patients remain asymptomatic, an important minority develops debilitating symptoms refractory to medical therapy. Post-HT short- and long-term outcomes are favorable. However, HT waitlist mortality remains high. For highly selected patients with HCM, a left ventricular assist device is a viable option.
Collapse
Affiliation(s)
- Matylda Mazur
- Heart and Vascular Institute, Kaufman Center for Heart Failure, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
| | - Wojciech Braksator
- Department of Cardiology and Noninvasive Cardiovascular Imaging, Faculty of Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Eric Popjes
- Heart and Vascular Institute, Pennsylvania State Health Milton S. Hershey Medical Center, Hershey, PA, USA
| |
Collapse
|
|
6
|
Yuan V, Vukadinovic M, Kwan AC, Rader F, Li D, Ouyang D. Clinical and genetic associations of asymmetric apical and septal left ventricular hypertrophy. EUROPEAN HEART JOURNAL. DIGITAL HEALTH 2024; 5:591-600. [PMID: 39318696 PMCID: PMC11417484 DOI: 10.1093/ehjdh/ztae060] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 05/17/2024] [Accepted: 07/16/2024] [Indexed: 09/26/2024]
Abstract
Aims Increased left ventricular mass has been associated with adverse cardiovascular outcomes including incident cardiomyopathy and atrial fibrillation. Such associations have been studied in relation to total left ventricular hypertrophy, while the regional distribution of myocardial hypertrophy is extremely variable. The clinically significant and genetic associations of such variability require further study. Methods and results Here, we use deep learning-derived phenotypes of disproportionate patterns of hypertrophy, namely, apical and septal hypertrophy, to study genome-wide and clinical associations in addition to and independent from total left ventricular mass within 35 268 UK Biobank participants. Using polygenic risk score and Cox regression, we quantified the relationship between incident cardiovascular outcomes and genetically determined phenotypes in the UK Biobank. Adjusting for total left ventricular mass, apical hypertrophy is associated with elevated risk for cardiomyopathy and atrial fibrillation. Cardiomyopathy risk was increased for subjects with increased apical or septal mass, even in the absence of global hypertrophy. We identified 17 genome-wide associations for left ventricular mass, 3 unique associations with increased apical mass, and 3 additional unique associations with increased septal mass. An elevated polygenic risk score for apical mass corresponded with an increased risk of cardiomyopathy and implantable cardioverter-defibrillator implantation. Conclusion Apical and septal mass may be driven by genes distinct from total left ventricular mass, suggesting unique genetic profiles for patterns of hypertrophy. Focal hypertrophy confers independent and additive risk to incident cardiovascular disease. Our findings emphasize the significance of characterizing distinct subtypes of left ventricular hypertrophy. Further studies are needed in multi-ethnic cohorts.
Collapse
Affiliation(s)
- Victoria Yuan
- School of Medicine, University of California, Los Angeles, CA, USA
| | - Milos Vukadinovic
- Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, 127 S San Vicente Blvd, Los Angeles, CA 90034, USA
- Samueli Bioengineering, University of California, Los Angeles, CA, USA
| | - Alan C Kwan
- Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, 127 S San Vicente Blvd, Los Angeles, CA 90034, USA
| | - Florian Rader
- Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, 127 S San Vicente Blvd, Los Angeles, CA 90034, USA
| | - Debiao Li
- Cedars-Sinai Medical Center, Biomedical Imaging Research Institute, Los Angeles, CA, USA
| | - David Ouyang
- Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, 127 S San Vicente Blvd, Los Angeles, CA 90034, USA
- Division of Artificial Intelligence in Medicine, Department of Medicine, Cedars-Sinai Medical Center, 127 S San Vicente Blvd, Los Angeles, CA 90034, USA
| |
Collapse
|
|
7
|
Ommen SR, Ho CY, Asif IM, Balaji S, Burke MA, Day SM, Dearani JA, Epps KC, Evanovich L, Ferrari VA, Joglar JA, Khan SS, Kim JJ, Kittleson MM, Krittanawong C, Martinez MW, Mital S, Naidu SS, Saberi S, Semsarian C, Times S, Waldman CB. 2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2024; 83:2324-2405. [PMID: 38727647 DOI: 10.1016/j.jacc.2024.02.014] [Citation(s) in RCA: 90] [Impact Index Per Article: 90.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/20/2024]
Abstract
AIM The "2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy" provides recommendations to guide clinicians in the management of patients with hypertrophic cardiomyopathy. METHODS A comprehensive literature search was conducted from September 14, 2022, to November 22, 2022, encompassing studies, reviews, and other evidence on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through May 23, 2023, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. STRUCTURE Hypertrophic cardiomyopathy remains a common genetic heart disease reported in populations globally. Recommendations from the "2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy" have been updated with new evidence to guide clinicians.
Collapse
|
|
8
|
Ommen SR, Ho CY, Asif IM, Balaji S, Burke MA, Day SM, Dearani JA, Epps KC, Evanovich L, Ferrari VA, Joglar JA, Khan SS, Kim JJ, Kittleson MM, Krittanawong C, Martinez MW, Mital S, Naidu SS, Saberi S, Semsarian C, Times S, Waldman CB. 2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation 2024; 149:e1239-e1311. [PMID: 38718139 DOI: 10.1161/cir.0000000000001250] [Citation(s) in RCA: 159] [Impact Index Per Article: 159.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/05/2024]
Abstract
AIM The "2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy" provides recommendations to guide clinicians in the management of patients with hypertrophic cardiomyopathy. METHODS A comprehensive literature search was conducted from September 14, 2022, to November 22, 2022, encompassing studies, reviews, and other evidence on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through May 23, 2023, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. STRUCTURE Hypertrophic cardiomyopathy remains a common genetic heart disease reported in populations globally. Recommendations from the "2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy" have been updated with new evidence to guide clinicians.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | | | | | - Victor A Ferrari
- AHA/ACC Joint Committee on Clinical Practice Guidelines liaison
- SCMR representative
| | | | - Sadiya S Khan
- ACC/AHA Joint Committee on Performance Measures representative
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
9
|
Malik AA, Saraswati U, Miranda WR, Covington M, Scott CG, Lee AT, Arruda‐Olson A, Geske JB, Klarich KW, Anand V. Invasive Cardiac Hemodynamics in Apical Hypertrophic Cardiomyopathy. J Am Heart Assoc 2024; 13:e032520. [PMID: 38686858 PMCID: PMC11179883 DOI: 10.1161/jaha.123.032520] [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: 09/11/2023] [Accepted: 03/11/2024] [Indexed: 05/02/2024]
Abstract
BACKGROUND Symptomatic limitations in apical hypertrophic cardiomyopathy may occur because of diastolic dysfunction with resultant elevated left ventricular filling pressures, cardiac output limitation to exercise, pulmonary hypertension (PH), valvular abnormalities, and/or arrhythmias. In this study, the authors aimed to describe invasive cardiac hemodynamics in a cohort of patients with apical hypertrophic cardiomyopathy. METHODS AND RESULTS Patients presenting to a comprehensive hypertrophic cardiomyopathy center with apical hypertrophic cardiomyopathy were identified (n=542) and those who underwent invasive hemodynamic catheterization (n=47) were included in the study. Of these, 10 were excluded due to postmyectomy status or incomplete hemodynamic data. The mean age was 56±18 years, 16 (43%) were women, and ejection fraction was preserved (≥50%) in 32 (91%) patients. The most common indication for catheterization was dyspnea (48%) followed by suspected PH (13%), and preheart transplant evaluation (10%). Elevated left ventricular filling pressures at rest or exercise were present in 32 (86%) patients. PH was present in 30 (81%) patients, with 6 (20%) also having right-sided heart failure. Cardiac index was available in 25 (86%) patients with elevated resting filling pressures. Of these, 19 (76%) had reduced cardiac index and all 6 with right-sided heart failure had reduced cardiac index. Resting hemodynamics were normal in 8 of 37 (22%) patients, with 5 during exercise; 3 of 5 (60%) patients had exercise-induced elevation in left ventricular filling pressures. CONCLUSIONS In patients with apical hypertrophic cardiomyopathy undergoing invasive hemodynamic cardiac catheterization, 86% had elevated left ventricular filling pressures at rest or with exercise, 81% had PH, and 20% of those with PH had concomitant right-sided heart failure.
Collapse
Affiliation(s)
- Awais A. Malik
- Mayo Clinic, Department of Cardiovascular MedicineJacksonvilleFLUSA
| | - Ushasi Saraswati
- Mayo Clinic, Department of Cardiovascular MedicineRochesterMNUSA
| | | | - Megan Covington
- Mayo Clinic, Department of Cardiovascular MedicineRochesterMNUSA
| | | | - Alex T. Lee
- Mayo Clinic, Department of Quantitative Health SciencesRochesterMNUSA
| | | | - Jeffrey B. Geske
- Mayo Clinic, Department of Cardiovascular MedicineRochesterMNUSA
| | - Kyle W. Klarich
- Mayo Clinic, Department of Cardiovascular MedicineRochesterMNUSA
| | - Vidhu Anand
- Mayo Clinic, Department of Cardiovascular MedicineRochesterMNUSA
| |
Collapse
|
|
10
|
Nikoo MH, Zarrabi M, Moaref A, Razeghian-Jahromi I. Global Longitudinal Strain May Be the One that Appropriately Identifies Candidates of ICD Implantation. Cardiol Res Pract 2024; 2024:2214072. [PMID: 38264236 PMCID: PMC10805553 DOI: 10.1155/2024/2214072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 09/20/2023] [Accepted: 01/06/2024] [Indexed: 01/25/2024] Open
Abstract
Hypertrophic cardiomyopathy (HCM) significantly contributes to an elevated risk of sudden cardiac death. Primary prevention is implemented by using an implantable cardioverter defibrillator (ICD). However, all of the HCM patients do not really need ICD therapy. Providing a superior index for ICD indication compared with the current indices like ejection fraction is essential to differentiate high-risk patients efficiently. The present study assessed the potential of global longitudinal strain (GLS) for the differentiation of HCM patients based on their need for ICD shocks. Patients with HCM were considered in four defined centers between March and June 2021. Those with previous ICD implantation or current candidates for ICD therapy were included in the study. Participants were subjected to speckle-tracking echocardiography, and GLS as well as some other echocardiographic parameters were recorded. Afterwards, data from implanted ICDs were extracted. Patients who received ICD shocks (appropriate) due to ventricular tachycardia (VT)/ventricular fibrillation (VF) were categorized in group A. The remaining patients were constituted group B who received inappropriate shocks, i.e., other than VT/VF. Overall, 34 patients were found eligible to participate with a mean age of 62 ± 16.1 years including 64.7% of males. Among a variety of echocardiographic parameters, GLS was the sole one that was significantly higher in group A compared with that in group B. Our findings revealed that only GLS could predict fatal arrhythmias. To substantiate, the odds of VT were raised by 43% with a single increase in GLS unit. GLS showed the highest accuracy for ICD indication among HCM patients and, therefore, could be a solid and early criterion to predict the incidence of life-threatening arrhythmias. In this regard, identifying appropriate HCM patients with respect to their need for ICD therapy is feasible.
Collapse
Affiliation(s)
- Mohammad Hossein Nikoo
- Cardiovascular Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- Department of Cardiovascular Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
- Non-Communicable Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Zarrabi
- Cardiovascular Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Alireza Moaref
- Cardiovascular Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- Department of Cardiovascular Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | | |
Collapse
|
|
11
|
Curran L, de Marvao A, Inglese P, McGurk KA, Schiratti PR, Clement A, Zheng SL, Li S, Pua CJ, Shah M, Jafari M, Theotokis P, Buchan RJ, Jurgens SJ, Raphael CE, Baksi AJ, Pantazis A, Halliday BP, Pennell DJ, Bai W, Chin CW, Tadros R, Bezzina CR, Watkins H, Cook SA, Prasad SK, Ware JS, O’Regan DP. Genotype-Phenotype Taxonomy of Hypertrophic Cardiomyopathy. CIRCULATION. GENOMIC AND PRECISION MEDICINE 2023; 16:e004200. [PMID: 38014537 PMCID: PMC10729901 DOI: 10.1161/circgen.123.004200] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 10/25/2023] [Indexed: 11/29/2023]
Abstract
BACKGROUND Hypertrophic cardiomyopathy (HCM) is an important cause of sudden cardiac death associated with heterogeneous phenotypes, but there is no systematic framework for classifying morphology or assessing associated risks. Here, we quantitatively survey genotype-phenotype associations in HCM to derive a data-driven taxonomy of disease expression. METHODS We enrolled 436 patients with HCM (median age, 60 years; 28.8% women) with clinical, genetic, and imaging data. An independent cohort of 60 patients with HCM from Singapore (median age, 59 years; 11% women) and a reference population from the UK Biobank (n=16 691; mean age, 55 years; 52.5% women) were also recruited. We used machine learning to analyze the 3-dimensional structure of the left ventricle from cardiac magnetic resonance imaging and build a tree-based classification of HCM phenotypes. Genotype and mortality risk distributions were projected on the tree. RESULTS Carriers of pathogenic or likely pathogenic variants for HCM had lower left ventricular mass, but greater basal septal hypertrophy, with reduced life span (mean follow-up, 9.9 years) compared with genotype negative individuals (hazard ratio, 2.66 [95% CI, 1.42-4.96]; P<0.002). Four main phenotypic branches were identified using unsupervised learning of 3-dimensional shape: (1) nonsarcomeric hypertrophy with coexisting hypertension; (2) diffuse and basal asymmetrical hypertrophy associated with outflow tract obstruction; (3) isolated basal hypertrophy; and (4) milder nonobstructive hypertrophy enriched for familial sarcomeric HCM (odds ratio for pathogenic or likely pathogenic variants, 2.18 [95% CI, 1.93-2.28]; P=0.0001). Polygenic risk for HCM was also associated with different patterns and degrees of disease expression. The model was generalizable to an independent cohort (trustworthiness, M1: 0.86-0.88). CONCLUSIONS We report a data-driven taxonomy of HCM for identifying groups of patients with similar morphology while preserving a continuum of disease severity, genetic risk, and outcomes. This approach will be of value in understanding the causes and consequences of disease diversity.
Collapse
Affiliation(s)
- Lara Curran
- National Heart and Lung Institute (L.C., K.A.M., S.L.Z., P.T., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.)
- Royal Brompton and Harefield Hospitals, Guy’s and St. Thomas’ NHS Foundation Trust (L.C., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.)
| | - Antonio de Marvao
- Medical Research Council Laboratory of Medical Sciences, Imperial College London, United Kingdom (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.)
- Department of Women and Children’s Health (A.d.M.)
- British Heart Foundation Centre of Research Excellence, School of Cardiovascular & Metabolic Medicine and Sciences, King’s College London, United Kingdom (A.d.M.)
| | - Paolo Inglese
- Medical Research Council Laboratory of Medical Sciences, Imperial College London, United Kingdom (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.)
| | - Kathryn A. McGurk
- National Heart and Lung Institute (L.C., K.A.M., S.L.Z., P.T., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.)
- Medical Research Council Laboratory of Medical Sciences, Imperial College London, United Kingdom (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.)
| | - Pierre-Raphaël Schiratti
- Medical Research Council Laboratory of Medical Sciences, Imperial College London, United Kingdom (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.)
| | - Adam Clement
- Medical Research Council Laboratory of Medical Sciences, Imperial College London, United Kingdom (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.)
| | - Sean L. Zheng
- National Heart and Lung Institute (L.C., K.A.M., S.L.Z., P.T., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.)
- Medical Research Council Laboratory of Medical Sciences, Imperial College London, United Kingdom (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.)
| | - Surui Li
- Biomedical Image Analysis Group, Department of Computing (S.L., W.B.)
- Medical Research Council Laboratory of Medical Sciences, Imperial College London, United Kingdom (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.)
| | - Chee Jian Pua
- National Heart Research Institute Singapore, Singapore, PRC (C.J.P., C.W.L.C., S.A.C.)
| | - Mit Shah
- Medical Research Council Laboratory of Medical Sciences, Imperial College London, United Kingdom (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.)
| | - Mina Jafari
- National Heart and Lung Institute (L.C., K.A.M., S.L.Z., P.T., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.)
- Biomedical Image Analysis Group, Department of Computing (S.L., W.B.)
- Department of Brain Sciences, Imperial College London, London, United Kingdom (W.B.)
- Royal Brompton and Harefield Hospitals, Guy’s and St. Thomas’ NHS Foundation Trust (L.C., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.)
- Medical Research Council Laboratory of Medical Sciences, Imperial College London, United Kingdom (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.)
- Department of Women and Children’s Health (A.d.M.)
- British Heart Foundation Centre of Research Excellence, School of Cardiovascular & Metabolic Medicine and Sciences, King’s College London, United Kingdom (A.d.M.)
- National Heart Research Institute Singapore, Singapore, PRC (C.J.P., C.W.L.C., S.A.C.)
- Department of Cardiology, National Heart Center Singapore, Singapore, PRC (C.W.L.C.)
- Cardiovascular Sciences ACP, Duke NUS Medical School, Singapore (C.W.L.C.)
- Mayo Clinic Rochester, MN (C.E.R.)
- Department of Experimental Cardiology, Heart Center, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands (S.J.J., C.R.B.)
- Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA (S.J.J.)
- Cardiovascular Genetics Centre, Montreal Heart Institute (R.T.)
- Faculty of Medicine, Université de Montréal, QC, Canada (R.T.)
- Radcliffe Department of Medicine, University of Oxford, United Kingdom (H.W.)
| | - Pantazis Theotokis
- National Heart and Lung Institute (L.C., K.A.M., S.L.Z., P.T., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.)
- Medical Research Council Laboratory of Medical Sciences, Imperial College London, United Kingdom (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.)
| | - Rachel J. Buchan
- National Heart and Lung Institute (L.C., K.A.M., S.L.Z., P.T., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.)
- Royal Brompton and Harefield Hospitals, Guy’s and St. Thomas’ NHS Foundation Trust (L.C., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.)
- Medical Research Council Laboratory of Medical Sciences, Imperial College London, United Kingdom (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.)
| | - Sean J. Jurgens
- Department of Experimental Cardiology, Heart Center, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands (S.J.J., C.R.B.)
- Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA (S.J.J.)
| | - Claire E. Raphael
- National Heart and Lung Institute (L.C., K.A.M., S.L.Z., P.T., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.)
- Royal Brompton and Harefield Hospitals, Guy’s and St. Thomas’ NHS Foundation Trust (L.C., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.)
- Mayo Clinic Rochester, MN (C.E.R.)
| | - Arun John Baksi
- National Heart and Lung Institute (L.C., K.A.M., S.L.Z., P.T., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.)
- Royal Brompton and Harefield Hospitals, Guy’s and St. Thomas’ NHS Foundation Trust (L.C., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.)
| | - Antonis Pantazis
- National Heart and Lung Institute (L.C., K.A.M., S.L.Z., P.T., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.)
- Royal Brompton and Harefield Hospitals, Guy’s and St. Thomas’ NHS Foundation Trust (L.C., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.)
| | - Brian P. Halliday
- National Heart and Lung Institute (L.C., K.A.M., S.L.Z., P.T., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.)
- Royal Brompton and Harefield Hospitals, Guy’s and St. Thomas’ NHS Foundation Trust (L.C., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.)
| | - Dudley J. Pennell
- National Heart and Lung Institute (L.C., K.A.M., S.L.Z., P.T., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.)
- Royal Brompton and Harefield Hospitals, Guy’s and St. Thomas’ NHS Foundation Trust (L.C., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.)
| | - Wenjia Bai
- Biomedical Image Analysis Group, Department of Computing (S.L., W.B.)
- Department of Brain Sciences, Imperial College London, London, United Kingdom (W.B.)
| | - Calvin W.L. Chin
- National Heart Research Institute Singapore, Singapore, PRC (C.J.P., C.W.L.C., S.A.C.)
- Department of Cardiology, National Heart Center Singapore, Singapore, PRC (C.W.L.C.)
- Cardiovascular Sciences ACP, Duke NUS Medical School, Singapore (C.W.L.C.)
| | - Rafik Tadros
- Cardiovascular Genetics Centre, Montreal Heart Institute (R.T.)
- Faculty of Medicine, Université de Montréal, QC, Canada (R.T.)
| | - Connie R. Bezzina
- Department of Experimental Cardiology, Heart Center, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands (S.J.J., C.R.B.)
| | - Hugh Watkins
- Radcliffe Department of Medicine, University of Oxford, United Kingdom (H.W.)
| | - Stuart A. Cook
- Department of Women and Children’s Health (A.d.M.)
- National Heart Research Institute Singapore, Singapore, PRC (C.J.P., C.W.L.C., S.A.C.)
| | - Sanjay K. Prasad
- National Heart and Lung Institute (L.C., K.A.M., S.L.Z., P.T., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.)
- Royal Brompton and Harefield Hospitals, Guy’s and St. Thomas’ NHS Foundation Trust (L.C., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.)
| | - James S. Ware
- National Heart and Lung Institute (L.C., K.A.M., S.L.Z., P.T., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.)
- Royal Brompton and Harefield Hospitals, Guy’s and St. Thomas’ NHS Foundation Trust (L.C., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.)
- Medical Research Council Laboratory of Medical Sciences, Imperial College London, United Kingdom (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.)
| | - Declan P. O’Regan
- Medical Research Council Laboratory of Medical Sciences, Imperial College London, United Kingdom (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.)
| |
Collapse
|
|
12
|
Almeida ALC, Melo MDTD, Bihan DCDSL, Vieira MLC, Pena JLB, Del Castillo JM, Abensur H, Hortegal RDA, Otto MEB, Piveta RB, Dantas MR, Assef JE, Beck ALDS, Santo THCE, Silva TDO, Salemi VMC, Rocon C, Lima MSM, Barberato SH, Rodrigues AC, Rabschkowisky A, Frota DDCR, Gripp EDA, Barretto RBDM, Silva SME, Cauduro SA, Pinheiro AC, Araujo SPD, Tressino CG, Silva CES, Monaco CG, Paiva MG, Fisher CH, Alves MSL, Grau CRPDC, Santos MVCD, Guimarães ICB, Morhy SS, Leal GN, Soares AM, Cruz CBBV, Guimarães Filho FV, Assunção BMBL, Fernandes RM, Saraiva RM, Tsutsui JM, Soares FLDJ, Falcão SNDRS, Hotta VT, Armstrong ADC, Hygidio DDA, Miglioranza MH, Camarozano AC, Lopes MMU, Cerci RJ, Siqueira MEMD, Torreão JA, Rochitte CE, Felix A. Position Statement on the Use of Myocardial Strain in Cardiology Routines by the Brazilian Society of Cardiology's Department Of Cardiovascular Imaging - 2023. Arq Bras Cardiol 2023; 120:e20230646. [PMID: 38232246 PMCID: PMC10789373 DOI: 10.36660/abc.20230646] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2024] Open
Abstract
Central Illustration : Position Statement on the Use of Myocardial Strain in Cardiology Routines by the Brazilian Society of Cardiology's Department Of Cardiovascular Imaging - 2023 Proposal for including strain in the integrated diastolic function assessment algorithm, adapted from Nagueh et al.67 Am: mitral A-wave duration; Ap: reverse pulmonary A-wave duration; DD: diastolic dysfunction; LA: left atrium; LASr: LA strain reserve; LVGLS: left ventricular global longitudinal strain; TI: tricuspid insufficiency. Confirm concentric remodeling with LVGLS. In LVEF, mitral E wave deceleration time < 160 ms and pulmonary S-wave < D-wave are also parameters of increased filling pressure. This algorithm does not apply to patients with atrial fibrillation (AF), mitral annulus calcification, > mild mitral valve disease, left bundle branch block, paced rhythm, prosthetic valves, or severe primary pulmonary hypertension.
Collapse
Affiliation(s)
| | | | | | - Marcelo Luiz Campos Vieira
- Instituto do Coração da Faculdade de Medicina da Universidade de São Paulo (Incor/FMUSP), São Paulo, SP - Brasil
| | - José Luiz Barros Pena
- Faculdade Ciências Médicas de Minas Gerais, Belo Horizonte, MG - Brasil
- Hospital Felicio Rocho, Belo Horizonte, MG - Brasil
| | | | - Henry Abensur
- Beneficência Portuguesa de São Paulo, São Paulo, SP - Brasil
| | | | | | | | | | | | | | | | | | - Vera Maria Cury Salemi
- Instituto do Coração da Faculdade de Medicina da Universidade de São Paulo (Incor/FMUSP), São Paulo, SP - Brasil
| | - Camila Rocon
- Hospital do Coração (HCor), São Paulo, SP - Brasil
| | - Márcio Silva Miguel Lima
- Instituto do Coração da Faculdade de Medicina da Universidade de São Paulo (Incor/FMUSP), São Paulo, SP - Brasil
| | | | | | | | | | - Eliza de Almeida Gripp
- Hospital Pró-Cardiaco, Rio de Janeiro, RJ - Brasil
- Hospital Universitário Antônio Pedro da Universidade Federal Fluminense (UFF), Rio de Janeiro, RJ - Brasil
| | | | | | | | | | | | | | | | | | | | | | | | | | - Maria Veronica Camara Dos Santos
- Departamento de Cardiologia Pediátrica (DCC/CP) da Sociedade Brasileira de Cardiologia (SBC), São Paulo, SP - Brasil
- Sociedade Brasileira de Oncologia Pediátrica, São Paulo, SP - Brasil
| | | | | | - Gabriela Nunes Leal
- Instituto da Criança e do Adolescente do Hospital das Clinicas Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP - Brasil
| | | | | | | | | | | | | | | | | | | | - Viviane Tiemi Hotta
- Instituto do Coração da Faculdade de Medicina da Universidade de São Paulo (Incor/FMUSP), São Paulo, SP - Brasil
- Grupo Fleury, São Paulo, SP - Brasil
| | | | - Daniel de Andrade Hygidio
- Hospital Nossa Senhora da Conceição, Tubarão, SC - Brasil
- Universidade do Sul de Santa Catarina (UNISUL), Tubarão, SC - Brasil
| | - Marcelo Haertel Miglioranza
- EcoHaertel - Hospital Mae de Deus, Porto Alegre, RS - Brasil
- Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS - Brasil
| | | | | | | | | | - Jorge Andion Torreão
- Hospital Santa Izabel, Salvador, BA - Brasil
- Santa Casa da Bahia, Salvador, BA - Brasil
| | - Carlos Eduardo Rochitte
- Instituto do Coração da Faculdade de Medicina da Universidade de São Paulo (Incor/FMUSP), São Paulo, SP - Brasil
- Hospital do Coração (HCor), São Paulo, SP - Brasil
| | - Alex Felix
- Diagnósticos da América SA (DASA), São Paulo, SP - Brasil
- Instituto Nacional de Cardiologia (INC), Rio de Janeiro, RJ - Brasil
| |
Collapse
|
|
13
|
Arbelo E, Protonotarios A, Gimeno JR, Arbustini E, Barriales-Villa R, Basso C, Bezzina CR, Biagini E, Blom NA, de Boer RA, De Winter T, Elliott PM, Flather M, Garcia-Pavia P, Haugaa KH, Ingles J, Jurcut RO, Klaassen S, Limongelli G, Loeys B, Mogensen J, Olivotto I, Pantazis A, Sharma S, Van Tintelen JP, Ware JS, Kaski JP. 2023 ESC Guidelines for the management of cardiomyopathies. Eur Heart J 2023; 44:3503-3626. [PMID: 37622657 DOI: 10.1093/eurheartj/ehad194] [Citation(s) in RCA: 893] [Impact Index Per Article: 446.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/26/2023] Open
|
|
14
|
Elsouri KN, Camacho Ramos J, Stepanek K, Turan A, Kesselman MM, Demory ML. Adult Onset Hypertrophic Cardiomyopathy (HCM) Not Detected by Echocardiogram: A Case Presentation. Cureus 2023; 15:e45932. [PMID: 37885492 PMCID: PMC10599216 DOI: 10.7759/cureus.45932] [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: 10/16/2022] [Accepted: 09/25/2023] [Indexed: 10/28/2023] Open
Abstract
Hypertrophic cardiomyopathy (HCM) is a genetic myocardial disease of the sarcomere protein. The age of diagnosis of HCM tends to be between the second to third decades of life. However, the recent occurrence of HCM in the fifth and sixth decades of life has been seen in an increasing number of cases. In all cases, a transthoracic echocardiogram (TTE) is considered the gold standard of imaging. Here, we present a case of a 54-year-old Caucasian male who presented to the emergency department (ED) with dyspnea while on vacation. An electrocardiogram (ECG) taken at the time did not suggest any abnormalities. After returning home, a stress test conducted indicated left anterior descending (LAD) artery stenosis. Following treatment, symptoms improved temporarily but eventually came back. Repeat ECGs and TTEs done over the next two years indicated grade II diastolic dysfunction and mild left ventricular hypertrophy, which led to changes in the medication regime. Nevertheless, his condition progressively deteriorated over time. Repeat appearances to the ED led to the utilization of magnetic resonance imaging (MRI) to assess cardiac morphology function and velocity flow. The results were consistent with HCM. This case presents a unique obstacle for the diagnosis of adult-onset HCM. The change made to his medication regimen seemingly aggravated the patients' condition. This case highlights the need for further imaging, beyond the gold standard, in adult males with repeated complaints of dyspnea on exertion (DOE).
Collapse
Affiliation(s)
- Kawther N Elsouri
- Osteopathic Medicine, Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine, Fort Lauderdale, USA
| | - Jerry Camacho Ramos
- General Practice, Nova Southeastern University Dr. Kiran C. Patel College of Allopathic Medicine, Fort Lauderdale, USA
| | - Kevin Stepanek
- Internal Medicine, Trinity Health Oakland Hospital, Pontiac, USA
| | - Aydin Turan
- Internal Medicine, Trinity Health Oakland Hospital, Pontiac, USA
| | - Marc M Kesselman
- Rheumatology, Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine, Fort Lauderdale, USA
| | - Michelle L Demory
- Microbiology and Immunology, Nova Southeastern University Dr. Kiran C. Patel College of Allopathic Medicine, Fort Lauderdale, USA
| |
Collapse
|
|
15
|
Dai J, Wang T, Xu K, Sun Y, Li Z, Chen P, Wang H, Wu D, Chen Y, Xiao L, Liu H, Wei H, Li R, Peng L, Yu T, Wang Y, Sun Z, Wang DW. Machine learning modeling identifies hypertrophic cardiomyopathy subtypes with genetic signature. Front Med 2023; 17:768-780. [PMID: 37121957 DOI: 10.1007/s11684-023-0982-1] [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: 07/25/2022] [Accepted: 01/05/2023] [Indexed: 05/02/2023]
Abstract
Previous studies have revealed that patients with hypertrophic cardiomyopathy (HCM) exhibit differences in symptom severity and prognosis, indicating potential HCM subtypes among these patients. Here, 793 patients with HCM were recruited at an average follow-up of 32.78 ± 27.58 months to identify potential HCM subtypes by performing consensus clustering on the basis of their echocardiography features. Furthermore, we proposed a systematic method for illustrating the relationship between the phenotype and genotype of each HCM subtype by using machine learning modeling and interactome network detection techniques based on whole-exome sequencing data. Another independent cohort that consisted of 414 patients with HCM was recruited to replicate the findings. Consequently, two subtypes characterized by different clinical outcomes were identified in HCM. Patients with subtype 2 presented asymmetric septal hypertrophy associated with a stable course, while those with subtype 1 displayed left ventricular systolic dysfunction and aggressive progression. Machine learning modeling based on personal whole-exome data identified 46 genes with mutation burden that could accurately predict subtype propensities. Furthermore, the patients in another cohort predicted as subtype 1 by the 46-gene model presented increased left ventricular end-diastolic diameter and reduced left ventricular ejection fraction. By employing echocardiography and genetic screening for the 46 genes, HCM can be classified into two subtypes with distinct clinical outcomes.
Collapse
Affiliation(s)
- Jiaqi Dai
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Tao Wang
- Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, 100101, China
| | - Ke Xu
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yang Sun
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Zongzhe Li
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Peng Chen
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Hong Wang
- Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Dongyang Wu
- Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yanghui Chen
- Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Lei Xiao
- Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Hao Liu
- Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Haoran Wei
- Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Rui Li
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Liyuan Peng
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Ting Yu
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yan Wang
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Zhongsheng Sun
- Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, 100101, China.
| | - Dao Wen Wang
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
- Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan, 430030, China.
| |
Collapse
|
|
16
|
Fumagalli C, Bonanni F, Beltrami M, Ruggieri R, Zocchi C, Tassetti L, Maurizi N, Berteotti M, Zampieri M, Argirò A, Lovero F, Tomberli A, di Bari M, Marchionni N, Pieragnoli P, Ricciardi G, Checchi L, Cappelli F, Fumagalli S, Olivotto I. Incidence of stroke in patients with hypertrophic cardiomyopathy in stable sinus rhythm during long-term monitoring. Int J Cardiol 2023; 381:70-75. [PMID: 37061097 DOI: 10.1016/j.ijcard.2023.04.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 03/29/2023] [Accepted: 04/04/2023] [Indexed: 04/17/2023]
Abstract
INTRODUCTION Patients with hypertrophic cardiomyopathy (HCM) are at increased risk of stroke, but the incidence and factors associated with cardioembolic events in HCM patients without atrial fibrillation (AF) remain unresolved. We determined the incidence of stroke in patients in sinus rhythm (SR) monitored with a cardiac implantable electronic device (CIED). METHODS All consecutive patients diagnosed with HCM and referred to CIED implantation with >16 years at diagnosis and ≥ 1 year follow-up post CIED implantation were retrospectively reviewed. Severe LA dilatation was defined as ≥48 mm. Patients were stratified by rhythm as: Pre-existing AF (AF present prior to CIED); De novo AF (AF present after CIED implantation); SR: no episodes of AF. RESULTS Of 1651 patients, 185 (11.2%) implanted with a CIED were included (57% men, age: 54 ± 17 years). Baseline, pre-existing AF was present in 73 (39%) patients. Ischemic stroke was reported in 19 (10.3%, 1.78%/year) patients and was similar across the three groups (2.3%/year vs 1.1%/year vs 0.6%/year in patients in SR vs pre-existing AF vs de novo AF, respectively, p = 0.235). In SR patients, a LAD≥48 mm posed the greatest risk of stroke (Hazard Ratio: 10.03,95% Confidence-Interval 2.79-16.01). At Cox multivariable analysis, after adjustment for oral anticoagulation, LA was independently associated with stroke while rhythm was not. CONCLUSIONS in HCM patients with CIED long-term monitoring and no prior history of AF, stroke rates were similar in those with de novo AF or stable SR. Severe LA dilatation was a powerful risk factor, irrespective of AF.
Collapse
Affiliation(s)
- Carlo Fumagalli
- Cardiomyopathy Unit, Cardiothoracic and Vascular Department and Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy; Department of Advanced Medical and Surgical Sciences, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
| | - Francesca Bonanni
- Cardiomyopathy Unit, Cardiothoracic and Vascular Department and Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy
| | - Matteo Beltrami
- Cardiomyopathy Unit, Cardiothoracic and Vascular Department and Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy
| | - Roberta Ruggieri
- Cardiomyopathy Unit, Cardiothoracic and Vascular Department and Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy
| | - Chiara Zocchi
- Cardiomyopathy Unit, Cardiothoracic and Vascular Department and Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy
| | - Luigi Tassetti
- Cardiomyopathy Unit, Cardiothoracic and Vascular Department and Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy
| | - Niccolò Maurizi
- University Hospital of Lausanne, Cardiology Department, Lausanne, Switzerland
| | - Martina Berteotti
- Cardiomyopathy Unit, Cardiothoracic and Vascular Department and Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy
| | - Mattia Zampieri
- Cardiomyopathy Unit, Cardiothoracic and Vascular Department and Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy
| | - Alessia Argirò
- Cardiomyopathy Unit, Cardiothoracic and Vascular Department and Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy
| | - Fabrizio Lovero
- Cardiomyopathy Unit, Cardiothoracic and Vascular Department and Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy
| | - Alessia Tomberli
- Cardiomyopathy Unit, Cardiothoracic and Vascular Department and Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy
| | - Mauro di Bari
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Niccolò Marchionni
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Paolo Pieragnoli
- Cardiothoracovascular Department, Careggi University Hospital, Florence, Italy
| | - Giuseppe Ricciardi
- Cardiothoracovascular Department, Careggi University Hospital, Florence, Italy
| | - Luca Checchi
- Cardiothoracovascular Department, Careggi University Hospital, Florence, Italy
| | - Francesco Cappelli
- Tuscan Regional Amyloid Center, Careggi University Hospital, Florence, Italy; Division of Interventional Structural Cardiology, Cardiothoracovascular Department, Careggi University Hospital, Florence, Italy
| | - Stefano Fumagalli
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Iacopo Olivotto
- Cardiomyopathy Unit, Cardiothoracic and Vascular Department and Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| |
Collapse
|
|
17
|
Averbuch T, White JA, Fine NM. Anderson-Fabry disease cardiomyopathy: an update on epidemiology, diagnostic approach, management and monitoring strategies. Front Cardiovasc Med 2023; 10:1152568. [PMID: 37332587 PMCID: PMC10272370 DOI: 10.3389/fcvm.2023.1152568] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 05/09/2023] [Indexed: 06/20/2023] Open
Abstract
Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder caused by deficient activity of the enzyme alpha-galactosidase. While AFD is recognized as a progressive multi-system disorder, infiltrative cardiomyopathy causing a number of cardiovascular manifestations is recognized as an important complication of this disease. AFD affects both men and women, although the clinical presentation typically varies by sex, with men presenting at a younger age with more neurologic and renal phenotype and women developing a later onset variant with more cardiovascular manifestations. AFD is an important cause of increased myocardial wall thickness, and advances in imaging, in particular cardiac magnetic resonance imaging and T1 mapping techniques, have improved the ability to identify this disease non-invasively. Diagnosis is confirmed by the presence of low alpha-galactosidase activity and identification of a mutation in the GLA gene. Enzyme replacement therapy remains the mainstay of disease modifying therapy, with two formulations currently approved. In addition, newer treatments such as oral chaperone therapy are now available for select patients, with a number of other investigational therapies in development. The availability of these therapies has significantly improved outcomes for AFD patients. Improved survival and the availability of multiple agents has presented new clinical dilemmas regarding disease monitoring and surveillance using clinical, imaging and laboratory biomarkers, in addition to improved approaches to managing cardiovascular risk factors and AFD complications. This review will provide an update on clinical recognition and diagnostic approaches including differentiation from other causes of increased ventricular wall thickness, in addition to modern strategies for management and follow-up.
Collapse
Affiliation(s)
- Tauben Averbuch
- Division of Cardiology, Department of Cardiac Sciences, University of Calgary, Calgary, AB, Canada
| | - James A. White
- Division of Cardiology, Department of Cardiac Sciences, University of Calgary, Calgary, AB, Canada
- Stephenson Cardiac Imaging Center, Alberta Health Services, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Nowell M. Fine
- Division of Cardiology, Department of Cardiac Sciences, University of Calgary, Calgary, AB, Canada
| |
Collapse
|
|
18
|
Kim K, Lee SD, Lee HJ, Kim H, Kim HR, Cho YH, Jang JY, Kang MG, Koh JS, Hwang SJ, Hwang JY, Park JR. Role and Clinical Importance of Progressive Changes in Echocardiographic Parameters in Predicting Outcomes in Patients With Hypertrophic Cardiomyopathy. J Cardiovasc Imaging 2023; 31:85-95. [PMID: 37096673 PMCID: PMC10133807 DOI: 10.4250/jcvi.2022.0053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 11/29/2022] [Accepted: 12/11/2022] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND The prognostic utility of follow-up transthoracic echocardiography (FU-TTE) in patients with hypertrophic cardiomyopathy (HCM) is unclear, specifically in terms of whether changes in echocardiographic parameters in routine FU-TTE parameters are associated with cardiovascular outcomes. METHODS From 2010 to 2017, 162 patients with HCM were retrospectively enrolled in this study. Using echocardiography, HCM was diagnosed based on morphological criteria. Patients with other diseases that cause cardiac hypertrophy were excluded. TTE parameters at baseline and FU were analyzed. FU-TTE was designated as the last recorded value in patients who did not develop any cardiovascular event or the latest exam before event development. Clinical outcomes were acute heart failure, cardiac death, arrhythmia, ischemic stroke, and cardiogenic syncope. RESULTS Median interval between the baseline TTE and FU-TTE was 3.3 years. Median clinical FU duration was 4.7 years. Septal trans-mitral velocity/mitral annular tissue Doppler velocity (E/e'), tricuspid regurgitation velocity, left ventricular ejection fraction (LVEF), and left atrial volume index (LAVI) at baseline were recorded. LVEF, LAVI, and E/e' values were associated with poor outcomes. However, no delta values predicted HCM-related cardiovascular outcomes. Logistic regression models incorporating changes in TTE parameters had no significant findings. Baseline LAVI was the best predictor of a poor prognosis. In survival analysis, an already enlarged or increased size LAVI was associated with poorer clinical outcomes. CONCLUSIONS Changes in echocardiographic parameters extracted from TTE did not assist in predicting clinical outcomes. Cross-sectionally evaluated TTE parameters were superior to changes in TTE parameters between baseline and FU at predicting cardiovascular events.
Collapse
Affiliation(s)
- Kyehwan Kim
- Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital and Gyeongsang National University School of Medicine, Jinju, Korea
| | - Seung Do Lee
- Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital and Gyeongsang National University School of Medicine, Jinju, Korea
| | - Hyo Jin Lee
- Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital and Gyeongsang National University School of Medicine, Jinju, Korea
| | - Hangyul Kim
- Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital and Gyeongsang National University School of Medicine, Jinju, Korea
| | - Hye Ree Kim
- Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital and Gyeongsang National University School of Medicine, Jinju, Korea
| | - Yun Ho Cho
- Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Changwon Hospital and Gyeongsang National University School of Medicine, Changwon, Korea
| | - Jeong Yoon Jang
- Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Changwon Hospital and Gyeongsang National University School of Medicine, Changwon, Korea
| | - Min Gyu Kang
- Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital and Gyeongsang National University School of Medicine, Jinju, Korea
| | - Jin-Sin Koh
- Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital and Gyeongsang National University School of Medicine, Jinju, Korea
| | - Seok-Jae Hwang
- Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital and Gyeongsang National University School of Medicine, Jinju, Korea
| | - Jin-Yong Hwang
- Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital and Gyeongsang National University School of Medicine, Jinju, Korea
| | - Jeong Rang Park
- Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital and Gyeongsang National University School of Medicine, Jinju, Korea
| |
Collapse
|
|
19
|
Differential diagnosis of common etiologies of left ventricular hypertrophy using a hybrid CNN-LSTM model. Sci Rep 2022; 12:20998. [PMID: 36470931 PMCID: PMC9722705 DOI: 10.1038/s41598-022-25467-w] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Accepted: 11/30/2022] [Indexed: 12/12/2022] Open
Abstract
Differential diagnosis of left ventricular hypertrophy (LVH) is often obscure on echocardiography and requires numerous additional tests. We aimed to develop a deep learning algorithm to aid in the differentiation of common etiologies of LVH (i.e. hypertensive heart disease [HHD], hypertrophic cardiomyopathy [HCM], and light-chain cardiac amyloidosis [ALCA]) on echocardiographic images. Echocardiograms in 5 standard views (parasternal long-axis, parasternal short-axis, apical 4-chamber, apical 2-chamber, and apical 3-chamber) were obtained from 930 subjects: 112 with HHD, 191 with HCM, 81 with ALCA and 546 normal subjects. The study population was divided into training (n = 620), validation (n = 155), and test sets (n = 155). A convolutional neural network-long short-term memory (CNN-LSTM) algorithm was constructed to independently classify the 3 diagnoses on each view, and the final diagnosis was made by an aggregate network based on the simultaneously predicted probabilities of HCM, HCM, and ALCA. Diagnostic performance of the algorithm was evaluated by the area under the receiver operating characteristic curve (AUC), and accuracy was evaluated by the confusion matrix. The deep learning algorithm was trained and verified using the training and validation sets, respectively. In the test set, the average AUC across the five standard views was 0.962, 0.982 and 0.996 for HHD, HCM and CA, respectively. The overall diagnostic accuracy was significantly higher for the deep learning algorithm (92.3%) than for echocardiography specialists (80.0% and 80.6%). In the present study, we developed a deep learning algorithm for the differential diagnosis of 3 common LVH etiologies (HHD, HCM and ALCA) by applying a hybrid CNN-LSTM model and aggregate network to standard echocardiographic images. The high diagnostic performance of our deep learning algorithm suggests that the use of deep learning can improve the diagnostic process in patients with LVH.
Collapse
|
|
20
|
Celenk V, Celenk C. Myocardial bridging in adult with hypertrophic cardiomyopathy: Imaging findings with coronary computed tomography angiography. Radiol Case Rep 2022; 17:4627-4631. [PMID: 36204398 PMCID: PMC9530407 DOI: 10.1016/j.radcr.2022.08.095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 08/22/2022] [Accepted: 08/25/2022] [Indexed: 11/20/2022] Open
Abstract
Myocardial bridgin in an adult with hypertrophic cardiomyopathy is a rare congenital coronary artery anomaly. It is often detected incidentally, and its true incidence in the general population is not known. Myocardial bridging may cause compression of a coronary artery, and it has been suggested that myocardial ischemia may result. Symptoms of myocardial bridging in the adult with hypertrophic cardiomyopathy are syncope, palpitations, dyspnea, and chest pain. Also, arrhythmia and myocardial infarction can be seen; these can cause sudden death, especially in athletes and young people. We present a case of a 48-year-old male with hypertrophic cardiomyopathy and myocardial bridging detected by coronary computed tomography angiography who complained of chest pain.
Collapse
Affiliation(s)
- Vefa Celenk
- Department of Cardiology, Institute of Cardiology, İstanbul University- Cerrahpasha, İstanbul, Turkey
| | - Cetin Celenk
- Department of Radiology, Faculty of Medicine, Ondokuzmayıs University
| |
Collapse
|
|
21
|
Hanås S, Larsson A, Rydén J, Lilliehöök I, Häggström J, Tidholm A, Höglund K, Ljungvall I, Holst BS. Cardiac troponin I in healthy Norwegian Forest Cat, Birman and domestic shorthair cats, and in cats with hypertrophic cardiomyopathy. J Feline Med Surg 2022; 24:e370-e379. [PMID: 36073987 PMCID: PMC9511503 DOI: 10.1177/1098612x221117115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
OBJECTIVES The aims of this study were to assess the potential associations between the serum cardiac troponin I (cTnI) concentration in healthy cats and feline characteristics, systolic blood pressure, heart rate (HR), echocardiographic measurements and storage time; and to compare cTnI concentrations in healthy cats with concentrations in cats with hypertrophic cardiomyopathy (HCM), with or without left atrial enlargement (LAE) and in cats with HCM, to assess potential associations between cTnI concentration and echocardiographic variables. METHODS Cardiac TnI was analysed using an Abbott ARCHITECT ci16200 analyser in serum from prospectively included healthy Norwegian Forest Cat (NF; n = 33), Birman (n = 33) and domestic shorthair (DSH; n = 30) cats, and from 39 cats with HCM, with or without LAE. RESULTS In healthy cats, higher cTnI concentrations were found in Birman cats than in NF cats (P = 0.014) and in neutered male cats than in intact females (P = 0.032). Cardiac TnI was positively associated with HR (P <0.0001). In cats with HCM, cTnI concentration was positively associated with left ventricular wall thickness and with left atrial-to-aortic root ratio (all P ⩽0.010). Cats with HCM had higher cTnI concentrations than healthy cats, and cTnI concentrations were higher in cats with HCM and LAE than in those with HCM without LAE (all P = 0.0003). CONCLUSIONS AND RELEVANCE Breed and sex may affect serum cTnI concentrations in healthy cats. The cTnI concentration increased with increasing severity of HCM.
Collapse
Affiliation(s)
- Sofia Hanås
- Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden
- Evidensia Specialist Animal Hospital Strömsholm, Strömsholm, Sweden
| | - Anders Larsson
- Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden
| | - Jesper Rydén
- Department of Energy and Technology, Swedish University of Agricultural Sciences, Uppsala, Sweden
| | - Inger Lilliehöök
- Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden
| | - Jens Häggström
- Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden
| | - Anna Tidholm
- Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden
- Anicura Albano Animal Hospital, Stockholm, Sweden
| | - Katja Höglund
- Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden
| | - Ingrid Ljungvall
- Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden
| | - Bodil S Holst
- Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden
| |
Collapse
|
|
22
|
Mavacamten, a novel revolutionizing therapy in hypertrophic obstructive cardiomyopathy: A literature review. Rev Port Cardiol 2022; 41:693-703. [DOI: 10.1016/j.repc.2021.09.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 08/25/2021] [Accepted: 09/13/2021] [Indexed: 11/23/2022] Open
|
|
23
|
Guigui SA, Torres C, Escolar E, Mihos CG. Systolic anterior motion of the mitral valve in hypertrophic cardiomyopathy: a narrative review. J Thorac Dis 2022; 14:2309-2325. [PMID: 35813751 PMCID: PMC9264047 DOI: 10.21037/jtd-22-182] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 04/15/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND AND OBJECTIVE The prevalence of hypertrophic cardiomyopathy (HCM) is estimated to be 1 in 200 to 500 individuals, with systolic anterior motion (SAM) of the mitral valve (MV) and left ventricular outflow tract (LVOT) obstruction present in 60% to 70%. In this narrative review, we aim to elucidate the pathophysiology of SAM-septal contact and LVOT obstruction in HCM by presenting a detailed review on the anatomy of the MV apparatus in HCM, examining the various existing theories pertaining to the SAM phenomenon as supported by cardiac imaging, and providing a critical assessment of management strategies for SAM in HCM. METHODS A literature review was performed using PubMed, EMBASE, Ovid, and the Cochrane Library, of all scientific articles published through December 2021. A focus was placed on descriptive studies, reports correlating echocardiographic findings with pathologic diagnosis, and outcomes studies. KEY CONTENT AND FINDINGS The pathophysiology of SAM involves the complex interplay between HCM morphology, MV apparatus anatomic abnormalities, and labile hemodynamic derangements. Echocardiography and cardiac magnetic resonance (CMR) vector flow mapping have identified drag forces, as opposed to the "Venturi effect", as the main hydraulic forces responsible for SAM. The degree of mitral regurgitation with SAM is variable, and its severity is correlated with degree of LVOT obstruction and outcomes. First line therapy for the amelioration of SAM and LVOT obstruction is medical therapy with beta-blockers, non-dihydropyridine calcium-channel blockers, and disopyramide, in conjunction with lifestyle modifications. In refractory cases septal reduction therapy is performed, which may be combined with a 'resect-plicate-release' procedure, anterior mitral leaflet extension, surgical edge-to-edge MV repair, anterior mitral leaflet retention plasty, or secondary chordal cutting. CONCLUSIONS Recent scientific advances in the field of HCM have allowed for a maturation of our understanding of the SAM phenomenon. Cardiac imaging plays a critical role in its diagnosis, treatment, and surveillance, and in our ability to apply the appropriate therapeutic regimens. The increasing prevalence of HCM places an emphasis on continued basic and clinical research to further improve outcomes for this challenging population.
Collapse
Affiliation(s)
- Sarah A. Guigui
- Echocardiography Laboratory, Columbia University Division of Cardiology, Mount Sinai Heart Institute, Miami Beach, FL, USA
- Columbia University Division of Cardiology, Mount Sinai Heart Institute, Miami Beach, FL, USA
| | - Christian Torres
- Columbia University Division of Cardiology, Mount Sinai Heart Institute, Miami Beach, FL, USA
| | - Esteban Escolar
- Columbia University Division of Cardiology, Mount Sinai Heart Institute, Miami Beach, FL, USA
- Coronary Care Unit, Columbia University Division of Cardiology, Mount Sinai Heart Institute, Miami Beach, FL, USA
| | - Christos G. Mihos
- Echocardiography Laboratory, Columbia University Division of Cardiology, Mount Sinai Heart Institute, Miami Beach, FL, USA
- Columbia University Division of Cardiology, Mount Sinai Heart Institute, Miami Beach, FL, USA
| |
Collapse
|
|
24
|
Cha MJ, Kim C, Park CH, Hong YJ, Shin JM, Kim TH, Cha YJ, Park CH. Differential Diagnosis of Thick Myocardium according to Histologic Features Revealed by Multiparametric Cardiac Magnetic Resonance Imaging. Korean J Radiol 2022; 23:581-597. [PMID: 35555885 PMCID: PMC9174501 DOI: 10.3348/kjr.2021.0815] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 02/21/2022] [Accepted: 02/27/2022] [Indexed: 11/16/2022] Open
Abstract
Left ventricular (LV) wall thickening, or LV hypertrophy (LVH), is common and occurs in diverse conditions including hypertrophic cardiomyopathy (HCM), hypertensive heart disease, aortic valve stenosis, lysosomal storage disorders, cardiac amyloidosis, mitochondrial cardiomyopathy, sarcoidosis and athlete's heart. Cardiac magnetic resonance (CMR) imaging provides various tissue contrasts and characteristics that reflect histological changes in the myocardium, such as cellular hypertrophy, cardiomyocyte disarray, interstitial fibrosis, extracellular accumulation of insoluble proteins, intracellular accumulation of fat, and intracellular vacuolar changes. Therefore, CMR imaging may be beneficial in establishing a differential diagnosis of LVH. Although various diseases share LV wall thickening as a common feature, the histologic changes that underscore each disease are distinct. This review focuses on CMR multiparametric myocardial analysis, which may provide clues for the differentiation of thickened myocardium based on the histologic features of HCM and its phenocopies.
Collapse
Affiliation(s)
- Min Jae Cha
- Department of Radiology, Chung-Ang University Hospital, Seoul, Korea
| | - Cherry Kim
- Department of Radiology, Korea University Ansan Hospital, Ansan, Korea
| | - Chan Ho Park
- Department of Radiology, Soonchunhyang University Cheonan Hospital, Cheonan, Korea
| | - Yoo Jin Hong
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Min Shin
- Department of Radiology and Research Institute of Radiological Science, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Tae Hoon Kim
- Department of Radiology and Research Institute of Radiological Science, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Yoon Jin Cha
- Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
| | - Chul Hwan Park
- Department of Radiology and Research Institute of Radiological Science, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
| |
Collapse
|
|
25
|
Nagueh SF, Phelan D, Abraham T, Armour A, Desai MY, Dragulescu A, Gilliland Y, Lester SJ, Maldonado Y, Mohiddin S, Nieman K, Sperry BW, Woo A. Recommendations for Multimodality Cardiovascular Imaging of Patients with Hypertrophic Cardiomyopathy: An Update from the American Society of Echocardiography, in Collaboration with the American Society of Nuclear Cardiology, the Society for Cardiovascular Magnetic Resonance, and the Society of Cardiovascular Computed Tomography. J Am Soc Echocardiogr 2022; 35:533-569. [PMID: 35659037 DOI: 10.1016/j.echo.2022.03.012] [Citation(s) in RCA: 78] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Hypertrophic cardiomyopathy (HCM) is defined by the presence of left ventricular hypertrophy in the absence of other potentially causative cardiac, systemic, syndromic, or metabolic diseases. Symptoms can be related to a range of pathophysiologic mechanisms including left ventricular outflow tract obstruction with or without significant mitral regurgitation, diastolic dysfunction with heart failure with preserved and heart failure with reduced ejection fraction, autonomic dysfunction, ischemia, and arrhythmias. Appropriate understanding and utilization of multimodality imaging is fundamental to accurate diagnosis as well as longitudinal care of patients with HCM. Resting and stress imaging provide comprehensive and complementary information to help clarify mechanism(s) responsible for symptoms such that appropriate and timely treatment strategies may be implemented. Advanced imaging is relied upon to guide certain treatment options including septal reduction therapy and mitral valve repair. Using both clinical and imaging parameters, enhanced algorithms for sudden cardiac death risk stratification facilitate selection of HCM patients most likely to benefit from implantable cardioverter-defibrillators.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | | | | | - Saidi Mohiddin
- Inherited/Acquired Myocardial Diseases, Barts Health NHS Trust, St Bartholomew's Hospital, London, UK
| | - Koen Nieman
- Cardiovascular Medicine and Radiology (CV Imaging), Stanford University Medical Center, CA
| | - Brett W Sperry
- Saint Luke's Mid America Heart Institute, Kansas City, MO
| | - Anna Woo
- Toronto General Hospital, Toronto, Canada
| |
Collapse
|
|
26
|
Clinical Characteristics and Prognostic Importance of Left Ventricular Apical Aneurysms in Hypertrophic Cardiomyopathy. JACC: CARDIOVASCULAR IMAGING 2022; 15:1696-1711. [DOI: 10.1016/j.jcmg.2022.03.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 03/04/2022] [Accepted: 03/31/2022] [Indexed: 11/20/2022]
|
|
27
|
Strachinaru M, Huurman R, Bowen DJ, Schinkel AFL, Hirsch A, Michels M. Relation Between Early Diastolic Mid-Ventricular Flow and Elastic Forces Indicating Aneurysm Formation in Hypertrophic Cardiomyopathy. J Am Soc Echocardiogr 2022; 35:846-856.e2. [PMID: 35489541 DOI: 10.1016/j.echo.2022.04.010] [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: 11/15/2021] [Revised: 04/20/2022] [Accepted: 04/20/2022] [Indexed: 11/19/2022]
Abstract
BACKGROUND The early diastolic paradoxical mid-ventricular flow (EDF) is suggestive of apical aneurysm (AA) formation in hypertrophic cardiomyopathy (HCM). We aimed to determine whether EDF may be a useful screening tool in patients, following the time progression of HCM to the aneurysmal stage. METHODS 121 HCM patients with dominant hypertrophy in the mid and apical segments, based on echocardiography and/or cardiovascular magnetic resonance (CMR), were selected from our HCM database comprising 1332 patients. They were further stratified according to the presence of AA. All imaging studies in a period of 16 years (2005-2021) were considered for time progression. Mid-ventricular Doppler (PW, CW, color and color M-mode) were analyzed. RESULTS 35 patients (29% of the study group and 2.6% of all HCM patients) had AA. EDF had a sensitivity of 92% and specificity of 98.6% for the detection of AA in the study group. In 108 patients follow-up echocardiography was performed (median 5 [3-9] studies). Sixteen patients (15%), with 10 [7-12] years follow-up, displayed progressive time changes in LV apical morphology and/or mid-LV flow. Ten patients (9%) progressed to an AA, during 7 [4-11] years follow-up. Patients progressing to AA were younger (p=0.009), with more severe LV hypertrophy (p=0.01) and more often a significant mid-LV systolic gradient (≥ 30mmHg, p<0.001). A wall thickness over 20mm had 70% sensitivity and 69% specificity in detecting evolution towards AA. With significant systolic gradient, sensitivity was 80% and specificity 62%. Furthermore, patients with AA had higher incidence of ventricular tachycardia (Log-rank p=0.03). CONCLUSION EDF reliably detects AA presence and should prompt for extra imaging studies. In HCM with mid and apical dominant involvement there is a progressive trend towards aneurysm formation, especially in patients with wall thickness over 20mm and significant mid-LV systolic gradient (≥30mmHg), which can be monitored through serial Doppler studies.
Collapse
Affiliation(s)
- Mihai Strachinaru
- Department of Cardiology, Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
| | - Roy Huurman
- Department of Cardiology, Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Daniel J Bowen
- Department of Cardiology, Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Arend F L Schinkel
- Department of Cardiology, Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Alexander Hirsch
- Department of Cardiology and Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Michelle Michels
- Department of Cardiology, Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| |
Collapse
|
|
28
|
Sun D, Schaff HV, Nishimura RA, Geske JB, Dearani JA, Ommen SR. Transapical Ventricular Remodeling for Hypertrophic Cardiomyopathy With Systolic Cavity Obliteration. Ann Thorac Surg 2022; 114:1284-1289. [PMID: 35339438 DOI: 10.1016/j.athoracsur.2022.02.073] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 01/21/2022] [Accepted: 02/22/2022] [Indexed: 11/16/2022]
Abstract
BACKGROUND Some patients with hypertrophic cardiomyopathy (HCM) present with reduced left ventricular (LV) stroke volume and elongated systolic cavity obliteration due to symmetric LV hypertrophy. In this report, we detail our experience with transapical septal myectomy to enlarge the LV volume and to relieve cavity obliteration in this unique subgroup of patients with HCM. METHODS We analyzed 38 patients with HCM who had extended symmetric LV hypertrophy and underwent transapical septal myectomy to enlarge the LV cavity from February 2001 to May 2021. RESULTS At the time of evaluation for operation, 84.2% (n = 32) of the patients were in New York Heart Association class III/IV. The peak oxygen consumption was 51.5% (44.0%-58.0%) of the normal predicted values on the preoperative exercise stress test (n = 16). Preoperative left atrial sizes in this cohort were enlarged (left atrial volume index, 39.0 [33.5-51.5] mL/m2), despite only 4 patients with moderate or greater mitral valve regurgitation. All patients underwent transapical septal myectomy to enlarge the LV cavity size. There was no postoperative (within 30 days) death. During a median (interquartile range) follow-up of 3.4 (0.7-6.9) years, the estimated survival rates were 100%, 92%, and 87% at 1, 3, and 5 years, respectively. Follow-up surveys suggested that 16 of the 17 contacted patients experienced improvement in their heart function after the procedure. CONCLUSIONS Transapical myectomy to enlarge LV cavity volume can be performed safely with good early survival and functional results. This procedure is an important alternative to cardiac transplantation for HCM patients with systolic cavity obliteration and progressive heart failure.
Collapse
Affiliation(s)
- Daokun Sun
- Department of Cardiovascular Surgery, Mayo Clinic, Rochester, Minnesota
| | - Hartzell V Schaff
- Department of Cardiovascular Surgery, Mayo Clinic, Rochester, Minnesota.
| | - Rick A Nishimura
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota
| | - Jeffrey B Geske
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota
| | - Joseph A Dearani
- Department of Cardiovascular Surgery, Mayo Clinic, Rochester, Minnesota
| | - Steve R Ommen
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota
| |
Collapse
|
|
29
|
Suay-Corredera C, Alegre-Cebollada J. The mechanics of the heart: zooming in on hypertrophic cardiomyopathy and cMyBP-C. FEBS Lett 2022; 596:703-746. [PMID: 35224729 DOI: 10.1002/1873-3468.14301] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 01/10/2022] [Accepted: 01/14/2022] [Indexed: 11/10/2022]
Abstract
Hypertrophic cardiomyopathy (HCM), a disease characterized by cardiac muscle hypertrophy and hypercontractility, is the most frequently inherited disorder of the heart. HCM is mainly caused by variants in genes encoding proteins of the sarcomere, the basic contractile unit of cardiomyocytes. The most frequently mutated among them is MYBPC3, which encodes cardiac myosin-binding protein C (cMyBP-C), a key regulator of sarcomere contraction. In this review, we summarize clinical and genetic aspects of HCM and provide updated information on the function of the healthy and HCM sarcomere, as well as on emerging therapeutic options targeting sarcomere mechanical activity. Building on what is known about cMyBP-C activity, we examine different pathogenicity drivers by which MYBPC3 variants can cause disease, focussing on protein haploinsufficiency as a common pathomechanism also in nontruncating variants. Finally, we discuss recent evidence correlating altered cMyBP-C mechanical properties with HCM development.
Collapse
|
|
30
|
Echocardiographic Deformation Imaging for Early Detection of Genetic Cardiomyopathies: JACC Review Topic of the Week. J Am Coll Cardiol 2022; 79:594-608. [PMID: 35144751 DOI: 10.1016/j.jacc.2021.11.045] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 11/12/2021] [Accepted: 11/22/2021] [Indexed: 12/14/2022]
Abstract
Clinical screening of the relatives of patients with genetic cardiomyopathies is challenging, as they often lack detectable cardiac abnormalities at presentation. Life-threatening adverse events can already occur in these early stages of disease, so sensitive tools to reveal the earliest signs of disease are needed. The utility of echocardiographic deformation imaging for early detection has been explored for this population in multiple studies but has not been broadly implemented in clinical practice. The authors discuss contemporary evidence on the utility of deformation imaging in relatives of patients with genetic cardiomyopathies. The available body of data shows that deformation imaging reveals early disease-specific abnormalities in dilated cardiomyopathy, hypertrophic cardiomyopathy, and arrhythmogenic cardiomyopathy. Deformation imaging seems promising to enhance the screening and follow-up protocols in relatives, and the authors propose measures to accelerate its implementation in clinical care.
Collapse
|
|
31
|
Del Rio-Pertuz G, Sethi P, Swaminath D, Argueta-Sosa E. Hypertrophic Cardiomyopathy in the Elderly: A Case Identified With Genetic Screening. J Investig Med High Impact Case Rep 2022; 10:23247096221109204. [PMID: 35778879 PMCID: PMC9251991 DOI: 10.1177/23247096221109204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Hypertrophic cardiomyopathy (HCM) is a hereditary disease with an autosomal dominant pattern of inheritance, that is caused by a mutation in one of several sarcomere genes that encodes components of the contractile system of the heart. Hypertrophic cardiomyopathy has been described as a disease that is more heavily diagnosed in the second decade of life, that may present with abnormal syncopal episodes or sudden cardiac death. However, with a better understanding of the genetic changes that occur in HCM and with improved imaging techniques, there has now been an increased recognition of a late-onset disease that can occur in the elderly population. We report a case of a 73-year-old woman who was found to have HCM after various clinical events took place.
Collapse
Affiliation(s)
- Gaspar Del Rio-Pertuz
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
| | - Pooja Sethi
- Division of Cardiology, Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
| | - Deephak Swaminath
- Division of Cardiology, Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
| | - Erwin Argueta-Sosa
- Division of Cardiology, Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
| |
Collapse
|
|
32
|
Vriz O, AlSergani H, Elshaer AN, Shaik A, Mushtaq AH, Lioncino M, Alamro B, Monda E, Caiazza M, Mauro C, Bossone E, Al-Hassnan ZN, Albert-Brotons D, Limongelli G. A complex unit for a complex disease: the HCM-Family Unit. Monaldi Arch Chest Dis 2021; 92. [PMID: 34964577 DOI: 10.4081/monaldi.2021.2147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Accepted: 11/30/2021] [Indexed: 11/23/2022] Open
Abstract
Hypertrophic cardiomyopathy (HCM) is a group of heterogeneous disorders that are most commonly passed on in a heritable manner. It is a relatively rare disease around the globe, but due to increased rates of consanguinity within the Kingdom of Saudi Arabia, we speculate a high incidence of undiagnosed cases. The aim of this paper is to elucidate a systematic approach in dealing with HCM patients and since HCM has variable presentation, we have summarized differentials for diagnosis and how different subtypes and genes can have an impact on the clinical picture, management and prognosis. Moreover, we propose a referral multi-disciplinary team HCM-Family Unit in Saudi Arabia and an integrated role in a network between King Faisal Hospital and Inherited and Rare Cardiovascular Disease Unit-Monaldi Hospital, Italy (among the 24 excellence centers of the European Reference Network (ERN) GUARD-Heart). Graphical Abstract.
Collapse
Affiliation(s)
- Olga Vriz
- Department of Cardiology, King Faisal Specialist Hospital and Research Center, Riyadh.
| | - Hani AlSergani
- Department of Cardiology, King Faisal Specialist Hospital and Research Center, Riyadh.
| | | | | | | | - Michele Lioncino
- Inherited and Rare Cardiovascular Disease Unit, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", AORN dei Colli, Monaldi Hospital, Naples.
| | - Bandar Alamro
- Department of Cardiology, King Faisal Specialist Hospital and Research Center, Riyadh.
| | - Emanuele Monda
- Inherited and Rare Cardiovascular Disease Unit, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", AORN dei Colli, Monaldi Hospital, Naples.
| | - Martina Caiazza
- Inherited and Rare Cardiovascular Disease Unit, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", AORN dei Colli, Monaldi Hospital, Naples.
| | - Ciro Mauro
- Department of Cardiology, Cardarelli Hospital, Naples.
| | | | - Zuhair N Al-Hassnan
- Cardiovascular Genetics Program and Department of Medical Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh.
| | - Dimpna Albert-Brotons
- Department of Cardiology, King Faisal Specialist Hospital and Research Center, Riyadh.
| | - Giuseppe Limongelli
- Inherited and Rare Cardiovascular Disease Unit, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", AORN dei Colli, Monaldi Hospital, Naples.
| |
Collapse
|
|
33
|
Bazrafshan S, Sibilia R, Girgla S, Viswanathan SK, Puckelwartz MJ, Sangha KS, Singh RR, Kakroo M, Jandarov R, Harris DM, Rubinstein J, Becker RC, McNally EM, Sadayappan S. South Asian-Specific MYBPC3 Δ25bp Deletion Carriers Display Hypercontraction and Impaired Diastolic Function Under Exercise Stress. Front Cardiovasc Med 2021; 8:766339. [PMID: 35004883 PMCID: PMC8733148 DOI: 10.3389/fcvm.2021.766339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2021] [Accepted: 11/22/2021] [Indexed: 11/13/2022] Open
Abstract
Background: A 25-base pair (25bp) intronic deletion in the MYBPC3 gene enriched in South Asians (SAs) is a risk allele for late-onset left ventricular (LV) dysfunction, hypertrophy, and heart failure (HF) with several forms of cardiomyopathy. However, the effect of this variant on exercise parameters has not been evaluated. Methods: As a pilot study, 10 asymptomatic SA carriers of the MYBPC3 Δ25bp variant (52.9 ± 2.14 years) and 10 age- and gender-matched non-carriers (NCs) (50.1 ± 2.7 years) were evaluated at baseline and under exercise stress conditions using bicycle exercise echocardiography and continuous cardiac monitoring. Results: Baseline echocardiography parameters were not different between the two groups. However, in response to exercise stress, the carriers of Δ25bp had significantly higher LV ejection fraction (%) (CI: 4.57 ± 1.93; p < 0.0001), LV outflow tract peak velocity (m/s) (CI: 0.19 ± 0.07; p < 0.0001), and higher aortic valve (AV) peak velocity (m/s) (CI: 0.103 ± 0.08; p = 0.01) in comparison to NCs, and E/A ratio, a marker of diastolic compliance, was significantly lower in Δ25bp carriers (CI: 0.107 ± 0.102; p = 0.038). Interestingly, LV end-diastolic diameter (LVIDdia) was augmented in NCs in response to stress, while it did not increase in Δ25bp carriers (CI: 0.239 ± 0.125; p = 0.0002). Further, stress-induced right ventricular systolic excursion velocity s' (m/s), as a marker of right ventricle function, increased similarly in both groups, but tricuspid annular plane systolic excursion increased more in carriers (slope: 0.008; p = 0.0001), suggesting right ventricle functional differences between the two groups. Conclusions: These data support that MYBPC3 Δ25bp is associated with LV hypercontraction under stress conditions with evidence of diastolic impairment.
Collapse
Affiliation(s)
- Sholeh Bazrafshan
- Division of Cardiovascular Health and Disease, Department of Internal Medicine, Heart, Lung and Vascular Institute, College of Medicine, University of Cincinnati, Cincinnati, OH, United States
| | - Robert Sibilia
- Division of Cardiovascular Health and Disease, Department of Internal Medicine, Heart, Lung and Vascular Institute, College of Medicine, University of Cincinnati, Cincinnati, OH, United States
| | - Saavia Girgla
- Division of Cardiovascular Health and Disease, Department of Internal Medicine, Heart, Lung and Vascular Institute, College of Medicine, University of Cincinnati, Cincinnati, OH, United States
| | - Shiv Kumar Viswanathan
- Division of Cardiovascular Health and Disease, Department of Internal Medicine, Heart, Lung and Vascular Institute, College of Medicine, University of Cincinnati, Cincinnati, OH, United States
| | - Megan J. Puckelwartz
- Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Kiranpal S. Sangha
- Division of Cardiovascular Health and Disease, Department of Internal Medicine, Heart, Lung and Vascular Institute, College of Medicine, University of Cincinnati, Cincinnati, OH, United States
| | - Rohit R. Singh
- Division of Cardiovascular Health and Disease, Department of Internal Medicine, Heart, Lung and Vascular Institute, College of Medicine, University of Cincinnati, Cincinnati, OH, United States
| | - Mashhood Kakroo
- Division of Cardiovascular Health and Disease, Department of Internal Medicine, Heart, Lung and Vascular Institute, College of Medicine, University of Cincinnati, Cincinnati, OH, United States
| | - Roman Jandarov
- Division of Cardiovascular Health and Disease, Department of Internal Medicine, Heart, Lung and Vascular Institute, College of Medicine, University of Cincinnati, Cincinnati, OH, United States
| | - David M. Harris
- Division of Cardiovascular Health and Disease, Department of Internal Medicine, Heart, Lung and Vascular Institute, College of Medicine, University of Cincinnati, Cincinnati, OH, United States
| | - Jack Rubinstein
- Division of Cardiovascular Health and Disease, Department of Internal Medicine, Heart, Lung and Vascular Institute, College of Medicine, University of Cincinnati, Cincinnati, OH, United States
| | - Richard C. Becker
- Division of Cardiovascular Health and Disease, Department of Internal Medicine, Heart, Lung and Vascular Institute, College of Medicine, University of Cincinnati, Cincinnati, OH, United States
| | - Elizabeth M. McNally
- Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Sakthivel Sadayappan
- Division of Cardiovascular Health and Disease, Department of Internal Medicine, Heart, Lung and Vascular Institute, College of Medicine, University of Cincinnati, Cincinnati, OH, United States
| |
Collapse
|
|
34
|
Trongtorsak A, Polpichai N, Thangjui S, Kewcharoen J, Yodsuwan R, Devkota A, Friedman HJ, Estrada AQ. Gender-Related Differences in Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis. Pulse (Basel) 2021; 9:38-46. [PMID: 34722354 DOI: 10.1159/000517618] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Accepted: 05/29/2021] [Indexed: 12/21/2022] Open
Abstract
Background Gender-related differences in phenotypic expression and outcomes have been established in many cardiac conditions; however, the impact of gender in hypertrophic cardiomyopathy (HCM) remains unclear. We conducted a systematic review and meta-analysis to assess the differences in clinical outcomes between female and male HCM patients. Methods We searched MEDLINE and EMBASE from inception to October 2020. Included were cohort studies that compared outcomes of interest including all-cause mortality, HCM-related mortality, and worsening heart failure (HF) or HF hospitalization between male and female. Data from each study were combined using the random effects model to calculate pooled odds ratio (OR) with 95% confidence interval (CI). Results Eleven retrospective cohort studies with a total of 9,427 patients (3,719 females) were included. Female gender was significantly associated with an increased risk of all-cause mortality (pooled OR = 1.63, 95% CI: 1.26-2.10, p ≤ 0.001), HCM-related mortality (pooled OR = 1.47, 95% CI: 1.08-2.01, p = 0.015), and worsening HF or HF hospitalization (pooled OR = 2.05, 95% CI: 1.76-2.39, p ≤ 0.001). Conclusions Female gender was associated with a worse prognosis in HCM. These findings suggest the need for improved care in women including early identification of disease and more possible aggressive management. Moreover, gender-based strategy may benefit in HCM patients.
Collapse
Affiliation(s)
- Angkawipa Trongtorsak
- Internal Medicine Residency Program, AMITA Health Saint Francis Hospital, Chicago, Illinois, USA
| | - Natchaya Polpichai
- Faculty of Medicine Songklanagarin Hospital, Prince of Songkla University, Songkhla, Thailand
| | - Sittinun Thangjui
- Internal Medicine Residency Program, Bassett Healthcare Network, New York, New York, USA
| | - Jakrin Kewcharoen
- Internal Medicine Residency Program, University of Hawaii, Honolulu, Hawaii, USA
| | - Ratdanai Yodsuwan
- Internal Medicine Residency Program, Bassett Healthcare Network, New York, New York, USA
| | - Amrit Devkota
- Internal Medicine Residency Program, AMITA Health Saint Francis Hospital, Chicago, Illinois, USA
| | - Harvey J Friedman
- Department of Pulmonary Medicine and Critical Care, AMITA Health Saint Francis Hospital, Chicago, Illinois, USA
| | - Alfonso Q Estrada
- Department of Cardiovascular Medicine, AMITA Health Saint Francis Hospital, Chicago, Illinois, USA
| |
Collapse
|
|
35
|
Ion Channel Impairment and Myofilament Ca 2+ Sensitization: Two Parallel Mechanisms Underlying Arrhythmogenesis in Hypertrophic Cardiomyopathy. Cells 2021; 10:cells10102789. [PMID: 34685769 PMCID: PMC8534456 DOI: 10.3390/cells10102789] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Revised: 10/07/2021] [Accepted: 10/13/2021] [Indexed: 11/17/2022] Open
Abstract
Life-threatening ventricular arrhythmias are the main clinical burden in patients with hypertrophic cardiomyopathy (HCM), and frequently occur in young patients with mild structural disease. While massive hypertrophy, fibrosis and microvascular ischemia are the main mechanisms underlying sustained reentry-based ventricular arrhythmias in advanced HCM, cardiomyocyte-based functional arrhythmogenic mechanisms are likely prevalent at earlier stages of the disease. In this review, we will describe studies conducted in human surgical samples from HCM patients, transgenic animal models and human cultured cell lines derived from induced pluripotent stem cells. Current pieces of evidence concur to attribute the increased risk of ventricular arrhythmias in early HCM to different cellular mechanisms. The increase of late sodium current and L-type calcium current is an early observation in HCM, which follows post-translation channel modifications and increases the occurrence of early and delayed afterdepolarizations. Increased myofilament Ca2+ sensitivity, commonly observed in HCM, may promote afterdepolarizations and reentry arrhythmias with direct mechanisms. Decrease of K+-currents due to transcriptional regulation occurs in the advanced disease and contributes to reducing the repolarization-reserve and increasing the early afterdepolarizations (EADs). The presented evidence supports the idea that patients with early-stage HCM should be considered and managed as subjects with an acquired channelopathy rather than with a structural cardiac disease.
Collapse
|
|
36
|
Left Ventricular Apical Aneurysms in Hypertrophic Cardiomyopathy: Equivalent Detection by Magnetic Resonance Imaging and Contrast Echocardiography. J Am Soc Echocardiogr 2021; 34:1262-1272. [PMID: 34375676 DOI: 10.1016/j.echo.2021.07.015] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 07/13/2021] [Accepted: 07/30/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Left ventricular (LV) apical aneurysm is a unique morphological entity and novel adverse risk marker existing within the broad phenotypic spectrum of hypertrophic cardiomyopathy (HCM). Its true prevalence in the HCM population is likely underestimated because of inherent limitations of conventional noncontrast echocardiography. The authors hypothesized that contrast echocardiography is a reliable imaging technique compared with cardiovascular magnetic resonance (CMR) for the detection of apical aneurysms. The aim of this study was to assess the effectiveness of contrast echocardiography in the detection of LV apical aneurysms in patients with HCM in comparison with the gold standard, CMR. METHODS One hundred twelve patients with HCM identified from an institutional clinical database, who underwent echocardiographic and CMR examinations within 12 months and had LV apical aneurysms identified on either or both imaging modalities, were retrospectively analyzed. Discordant cases were reviewed by an expert panel, and a consensus was reached regarding the presence or absence of an apical aneurysm. The reason for any discrepancy was recorded. RESULTS The mean age of the patients was 59 ± 13 years, and 73% were men. Sixty-four (57%) underwent contrast echocardiography. The median interval between echocardiography and CMR was 118 days (interquartile range, 61-237 days). Thirty-nine patients (35%) had discordance between echocardiographic and CMR findings, of whom 20 had aneurysms reported on echocardiography but not CMR and 19 vice versa. Upon reanalysis by the expert panel, aneurysms were initially missed on CMR in 16 patients (80%), largely because of interpretation error secondary to small aneurysms, with a mean aneurysm size of 0.82 ± 0.38 cm in these cases. Before secondary review by the expert panel, contrast echocardiography had sensitivity of 97% compared with 85% for CMR (P = .0198) and 64% for noncontrast echocardiography (P = .0001). After secondary review, contrast echocardiography had sensitivity of 98% compared with 67% for noncontrast echocardiography (P = .0001) and 97% for CMR (P = 1.00). CONCLUSIONS Contrast echocardiography has high sensitivity for detecting LV apical aneurysms and should be used routinely in the evaluation and risk stratification of patients with HCM.
Collapse
|
|
37
|
Ommen SR, Mital S, Burke MA, Day SM, Deswal A, Elliott P, Evanovich LL, Hung J, Joglar JA, Kantor P, Kimmelstiel C, Kittleson M, Link MS, Maron MS, Martinez MW, Miyake CY, Schaff HV, Semsarian C, Sorajja P, O'Gara PT, Beckman JA, Levine GN, Al-Khatib SM, Armbruster A, Birtcher KK, Ciggaroa J, Dixon DL, de las Fuentes L, Deswal A, Fleisher LA, Gentile F, Goldberger ZD, Gorenek B, Haynes N, Hernandez AF, Hlatky MA, Joglar JA, Jones WS, Marine JE, Mark D, Palaniappan L, Piano MR, Tamis-Holland J, Wijeysundera DN, Woo YJ. 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Thorac Cardiovasc Surg 2021; 162:e23-e106. [PMID: 33926766 DOI: 10.1016/j.jtcvs.2021.04.001] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
|
|
38
|
Keane S, Fabre A, Keane D. Characterization of atrial histology in a patient with hypertrophic cardiomyopathy: Possible evidence of a primary atrial myopathy. HeartRhythm Case Rep 2021; 7:413-417. [PMID: 34194992 PMCID: PMC8226312 DOI: 10.1016/j.hrcr.2021.03.017] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Affiliation(s)
- Stephen Keane
- Department of Cardiology, St. Vincent’s University Hospital, Dublin, Ireland
| | - Aurelie Fabre
- Department of Pathology, St. Vincent’s University Hospital, Dublin, Ireland
| | - David Keane
- Department of Cardiology, St. Vincent’s University Hospital, Dublin, Ireland
| |
Collapse
|
|
39
|
Komatsu J, Imai RI, Nakaoka Y, Nishida K, Seki SI, Kubo T, Yamasaki N, Kitaoka H, Kubokawa SI, Kawai K, Hamashige N, Doi YL. Importance of Paroxysmal Atrial Fibrillation and Sex Differences in the Prevention of Embolic Stroke in Hypertrophic Cardiomyopathy. Circ Rep 2021; 3:273-278. [PMID: 34007941 PMCID: PMC8099667 DOI: 10.1253/circrep.cr-20-0101] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Background:
Although atrial fibrillation (AF) is a well-known risk factor for embolic stroke in hypertrophic cardiomyopathy (HCM), there is a paucity of information derived from HCM patients who have experienced embolic stroke. Methods and Results:
From 141 consecutive HCM patients who had been hospitalized between 2000 and 2018, the clinical characteristics and management of 86 patients with AF were analyzed retrospectively. The incidence of embolic stroke was 36% (n=31 patients). The median (interquartile range) age of embolic stroke was younger in male than female HCM patients (71 [64–80] vs. 83 [77–87] years, respectively; P=0.009). The prevalence of paroxysmal AF (74%) was significantly higher than that of chronic AF (26%) in 31 patients with embolic stroke (P=0.007). The CHADS2
score in patients with embolic stroke was not particularly useful in predicting the occurrence of embolic stroke. Conclusions:
One-third of HCM patients with AF developed embolic stroke, and male HCM patients were younger at the time of the embolic stroke than female HCM patients. The prevalence of paroxysmal AF was significantly higher than that of chronic AF in patients with AF and embolic stroke. Early introduction of anticoagulation therapy is recommended at the first documentation of paroxysmal AF.
Collapse
Affiliation(s)
- Junya Komatsu
- Department of Cardiology, Chikamori Hospital Kochi Japan
| | | | - Yoko Nakaoka
- Department of Cardiology, Chikamori Hospital Kochi Japan
| | - Koji Nishida
- Department of Cardiology, Chikamori Hospital Kochi Japan
| | - Shu-Ichi Seki
- Department of Cardiology, Chikamori Hospital Kochi Japan
| | - Toru Kubo
- Department of Cardiology and Aging Science, Kochi Medial School Kochi Japan
| | - Naohito Yamasaki
- Department of Cardiology and Aging Science, Kochi Medial School Kochi Japan
| | - Hiroaki Kitaoka
- Department of Cardiology and Aging Science, Kochi Medial School Kochi Japan
| | | | - Kazuya Kawai
- Department of Cardiology, Chikamori Hospital Kochi Japan
| | | | - Yoshinori L Doi
- Department of Cardiology, Chikamori Hospital Kochi Japan.,Cardiomyopathy Institute, Chikamori Hospital Kochi Japan
| |
Collapse
|
|
40
|
Joseph N, Craft M, Mill L, Erickson CC, Danford DA, Kutty S, Li L. Assessment of mitral valve function in children and young adults with hypertrophic cardiomyopathy using three-dimensional echocardiography. Int J Cardiol 2021; 332:182-188. [PMID: 33753187 DOI: 10.1016/j.ijcard.2021.03.040] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Revised: 03/09/2021] [Accepted: 03/15/2021] [Indexed: 11/16/2022]
Abstract
OBJECTIVE The objective of this study was to assess papillary muscle (PM) and mitral valve (MV) structure and function in children and young adults with mild and moderate hypertrophic cardiomyopathy (HCM) using real-time three-dimensional echocardiography (3DE) and to correlate them with HCM related adverse outcomes. METHODS Transthoracic research 3DE was performed in HCM patients and controls matched for age and gender. Anterolateral and posteromedial PM mass, apical displacement of anterolateral PM, and left ventricular (LV) mass were measured and indexed to body surface area. The MV annulus and leaflet structure and function were analyzed. Individual PMs were manually planimetered by tracing the endocardial borders on each mid systole frame, taking care to distinguish PMs as distinct from the LV wall. Apical PM displacement was expressed as ratio of the distance between the apex and the base of the anterolateral PM to the entire length of the LV lateral wall (APL index). All 3DE measurements were correlated to adverse outcomes. RESULTS Forty subjects were studied, including 20 HCM patients (age 18.1 ± 9.6 years, 16 male and 4 female), and 20 controls (18.2 ± 9.6 years, 16 male and 4 female). The indexed LV mass in HCM was 74.8 ± 25.8 g/m2 compared to 50.8 ± 12.4 g/m2 in controls (p = 0.001). The anterolateral, posteromedial and combined PM mass were 3.1 ± 2.2 g/m2, 1.7 ± 1.2 g/m2 and 4.9 ± 2.7 g/m2 in HCM, in contrast to respective measurements of 1.1 ± 0.6 g/m2, 1.2 ± 0.6 g/m2 and 2.3 ± 0.8 g/m2 in controls (p < 0.001, p = 0.062, and p < 0.001, respectively). The mitral valve annular parameters (annulus circumference, height and area) in HCM were not significantly different from controls. The APL index in HCM was less than in controls (0.44 ± 0.07 vs. 0.55 ± 0.04, p < 0.001). The LV lateral wall length and LV mass correlated with adverse HCM outcomes, while the APL index and PM total mass were not associated with adverse events. CONCLUSION It is feasible to evaluate PM muscles and MV annulus geometry in children and young adults with HCM using 3DE. The morphologic and functional changes of anterolateral PM may occur in the absence of MV annulus changes. Prospective validation will be required to determine if LV lateral wall length and LV mass may be used as predictors of adverse events.
Collapse
Affiliation(s)
- Navya Joseph
- University of Nebraska Medical Center, Omaha, NE, United States
| | - Mary Craft
- University of Nebraska Medical Center, Omaha, NE, United States; Children's Hospital and Medical Center, Omaha, NE, United States
| | - LuAnn Mill
- University of Nebraska Medical Center, Omaha, NE, United States
| | - Christopher C Erickson
- University of Nebraska Medical Center, Omaha, NE, United States; Children's Hospital and Medical Center, Omaha, NE, United States
| | - David A Danford
- University of Nebraska Medical Center, Omaha, NE, United States; Children's Hospital and Medical Center, Omaha, NE, United States
| | - Shelby Kutty
- Johns Hopkins Hospital and School of Medicine, Baltimore, MD, United States.
| | - Ling Li
- University of Nebraska Medical Center, Omaha, NE, United States; Children's Hospital and Medical Center, Omaha, NE, United States
| |
Collapse
|
|
41
|
Sultan FAT, Saadia S. Patterns of Left Ventricular Hypertrophy and Late Gadolinium Enhancement on Cardiac MRI in Patients with Hypertrophic Cardiomyopathy and their Prognostic Significance - An Experience from a South Asian Country. J Clin Imaging Sci 2021; 11:14. [PMID: 33767906 PMCID: PMC7981941 DOI: 10.25259/jcis_235_2020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Accepted: 02/17/2021] [Indexed: 11/04/2022] Open
Abstract
Objectives Cardiac magnetic resonance (CMR) imaging is very pertinent in the diagnosis and risk stratification of patients with hypertrophic cardiomyopathy (HCM). We aimed to assess the patterns of left ventricular (LV) hypertrophy, late gadolinium enhancement (LGE), and their prognostic significance in HCM patients in Pakistani population, as no such data are available from Pakistan. Material and Methods This was a retrospective, single center study. All patients who had confirmed diagnosis of HCM on CMR at Aga Khan University Hospital during the period of 2011-2019 were identified and included in the study. Results A total of 74 patients were included with the mean age of 45.6 ± 15 years and the majority 71.6 % (n = 53) being male. Maximal LV wall thickness was 21.1 ± 5 mm, asymmetrical septal hypertrophy being the most common pattern (62.2%, n = 46). LGE was present in 75.7% (n = 56) with most common site being septum plus LV free wall (24.3%, n =18). Mean ejection fraction% was found to be lower in patients with LGE (P < 0.001). Major adverse cardiac events (MACE) were observed in 40.5% (n = 30). Presence of LGE and right ventricular involvement was found to have a statistically significant association with MACE (P value 0.018 and 0.046, respectively). In multivariable analysis, only LGE was significantly associated with MACE (odd ratio: 4.65; 95% CI: 1.21-17.88). Conclusion Asymmetrical septal hypertrophy was the most common pattern of hypertrophy. LGE was present in three fourth of the study population and it was significantly associated with MACE.
Collapse
Affiliation(s)
| | - Sheema Saadia
- Department of Medicine, Aga Khan University Hospital, Karachi, Sindh, Pakistan
| |
Collapse
|
|
42
|
Efthimiadis G, Zegkos T, Parcharidou D, Ntelios D, Panagiotidis T, Gossios T, Karvounis H. A simple algorithm for a clinical step-by-step approach in the management of hypertrophic cardiomyopathy. Future Cardiol 2021; 17:1395-1405. [PMID: 33615852 DOI: 10.2217/fca-2020-0230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease with an autosomal dominant pattern and a reported prevalence of about 0.2%. In this review, we present a simple algorithm for the management of first diagnosed HCM patients. Initially, the clinical examination, medical and detailed family history and the ECG are essential. The etiological diagnosis of left ventricular hypertrophy is important in order to differentiate HCM due to sarcomeric genes mutation from other phenocopies, such as cardiac amyloidosis. The next step consists of the cardiovascular imaging and ambulatory electrocardiography. Cardiopulmonary exercise testing may also be considered if available. All of the above provide evidence for the critical step of the risk stratification of patients for sudden cardiac death. The therapeutic strategy, with respect to obstructive and nonobstructive disease, arrhythmias and end-stage HCM is also described.
Collapse
Affiliation(s)
- Georgios Efthimiadis
- 1st Cardiology department, Laboratory of Cardiomyopathies and Inherited Cardiac Diseases, AHEPA University hospital, Thessaloniki 54636, Greece
| | - Thomas Zegkos
- 1 Cardiology department, Laboratory of Cardiomyopathies and Inherited Cardiac Diseases, AHEPA University hospital, Thessaloniki 54636, Greece
| | - Despoina Parcharidou
- 1 Cardiology department, Laboratory of Cardiomyopathies and Inherited Cardiac Diseases, AHEPA University hospital, Thessaloniki 54636, Greece
| | - Dimitris Ntelios
- 1 Cardiology department, Laboratory of Cardiomyopathies and Inherited Cardiac Diseases, AHEPA University hospital, Thessaloniki 54636, Greece
| | - Theofilos Panagiotidis
- 1 Cardiology department, Laboratory of Cardiomyopathies and Inherited Cardiac Diseases, AHEPA University hospital, Thessaloniki 54636, Greece
| | - Thomas Gossios
- Barts Heart Centre, St Bartholomew's Hospital, W Smithfield, London, EC1A 7BE, UK
| | - Haralambos Karvounis
- 1 Cardiology department, Laboratory of Cardiomyopathies and Inherited Cardiac Diseases, AHEPA University hospital, Thessaloniki 54636, Greece
| |
Collapse
|
|
43
|
Castagno D, Di Donna P, Olivotto I, Frontera A, Calò L, Scaglione M, Arretini A, Anselmino M, Giustetto C, De Ferrari GM, Cecchi F, Haissaguerre M, Gaita F. Transcatheter ablation for atrial fibrillation in patients with hypertrophic cardiomyopathy: Long-term results and clinical outcomes. J Cardiovasc Electrophysiol 2021; 32:657-666. [PMID: 33428271 DOI: 10.1111/jce.14880] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 12/01/2020] [Accepted: 12/05/2020] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Radiofrequency transcatheter ablation (RFCA) for atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM) has been proven feasible. However, the long-term results of RFCA and its impact on clinical course of HCM are unknown. The aim of this study was to analyse clinical outcomes and long-term efficacy of RFCA in a multicentre cohort of patients with HCM and concomitant AF. METHODS Patients with HCM and AF consecutively undergoing RFCA were included. Ablation failure was defined as recurrence of AF, atrial tachycardia, or flutter lasting more than 3 min and occurring after the blanking period. RESULTS Overall, 116 patients with symptomatic AF refractory to antiarrhythmic drugs were included. Over a median follow-up of 6.0 years (interquartile range: 3.0-8.9 years) recurrence rate after a single RFCA was 32.3 per 100 patient/years with 26% of patients free from AF relapses at 6-year follow-up. Among patients experiencing AF recurrence, 51 (66%) underwent at least one redo-procedure. The overall recurrence rate considering redo-procedures was 12.6 per 100 patients/years with 53% of patients free from AF relapses at 6 years. At last follow-up, with an average of 1.6 procedures, 67 (61%) patients were in sinus rhythm (SR). Patients remaining in SR showed better functional status compared with those experiencing arrhythmic recurrences (NYHA Class 1.6 ± 0.1 vs. 2.0 ± 0.1, p = .009). CONCLUSIONS RFCA of AF in HCM patients is an effective and safe strategy favoring long-term SR maintenance, reduction of atrial arrhythmic events, and improved functional status. However, most patients need repeat procedures and continuation of antiarrhythmic drugs.
Collapse
Affiliation(s)
- Davide Castagno
- Division of Cardiology, Department of Medical Sciences, "Città della Salute della Scienza" Hospital, University of Turin, Turin, Italy
| | - Paolo Di Donna
- Division of Cardiology, Department of Internal Medicine, Cardinal Massaia Hospital, Asti, Italy
| | - Iacopo Olivotto
- Cardiomyopathy Unit, Cardiothoracovascular Department, Careggi University Hospital, Florence, Italy
| | - Antonio Frontera
- Department of Cardiac Pacing and Electrophysiology, IHU Liryc, Electrophysiology and Heart Modeling Institute, Bordeaux University, Bordeaux, France.,University Hospital (CHU), Pessac-Bordeaux, France
| | - Leonardo Calò
- Division of Cardiology, Policlinico Casilino, ASL Rome B, Rome, Italy
| | - Marco Scaglione
- Division of Cardiology, Department of Internal Medicine, Cardinal Massaia Hospital, Asti, Italy
| | - Anna Arretini
- Cardiomyopathy Unit, Cardiothoracovascular Department, Careggi University Hospital, Florence, Italy
| | - Matteo Anselmino
- Division of Cardiology, Department of Medical Sciences, "Città della Salute della Scienza" Hospital, University of Turin, Turin, Italy
| | - Carla Giustetto
- Division of Cardiology, Department of Medical Sciences, "Città della Salute della Scienza" Hospital, University of Turin, Turin, Italy
| | - Gaetano Maria De Ferrari
- Division of Cardiology, Department of Medical Sciences, "Città della Salute della Scienza" Hospital, University of Turin, Turin, Italy
| | - Franco Cecchi
- Cardiomyopathy Unit, Cardiothoracovascular Department, Careggi University Hospital, Florence, Italy
| | - Michel Haissaguerre
- Department of Cardiac Pacing and Electrophysiology, IHU Liryc, Electrophysiology and Heart Modeling Institute, Bordeaux University, Bordeaux, France.,University Hospital (CHU), Pessac-Bordeaux, France
| | - Fiorenzo Gaita
- Division of Cardiology, Department of Medical Sciences, "Città della Salute della Scienza" Hospital, University of Turin, Turin, Italy
| |
Collapse
|
|
44
|
Tandon R, Dutt S, Bansal N, Singh G, Singh B, Goyal A, Chabbra S, Aslam N, Mohan B, Wander G. Echocardiography Study of Hypertrophic Cardiomyopathy Phenotypes: An Indian Perspective. JOURNAL OF THE INDIAN ACADEMY OF ECHOCARDIOGRAPHY & CARDIOVASCULAR IMAGING 2021. [DOI: 10.4103/jiae.jiae_71_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
|
|
45
|
Ommen SR, Mital S, Burke MA, Day SM, Deswal A, Elliott P, Evanovich LL, Hung J, Joglar JA, Kantor P, Kimmelstiel C, Kittleson M, Link MS, Maron MS, Martinez MW, Miyake CY, Schaff HV, Semsarian C, Sorajja P. 2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2020; 76:3022-3055. [PMID: 33229115 DOI: 10.1016/j.jacc.2020.08.044] [Citation(s) in RCA: 184] [Impact Index Per Article: 36.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
AIM This executive summary of the hypertrophic cardiomyopathy clinical practice guideline provides recommendations and algorithms for clinicians to diagnose and manage hypertrophic cardiomyopathy in adult and pediatric patients as well as supporting documentation to encourage their use. METHODS A comprehensive literature search was conducted from January 1, 2010, to April 30, 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. STRUCTURE Many recommendations from the earlier hypertrophic cardiomyopathy guidelines have been updated with new evidence or a better understanding of earlier evidence. This summary operationalizes the recommendations from the full guideline and presents a combination of diagnostic work-up, genetic and family screening, risk stratification approaches, lifestyle modifications, surgical and catheter interventions, and medications that constitute components of guideline directed medical therapy. For both guideline-directed medical therapy and other recommended drug treatment regimens, the reader is advised to follow dosing, contraindications and drug-drug interactions based on product insert materials.
Collapse
|
|
46
|
Ommen SR, Mital S, Burke MA, Day SM, Deswal A, Elliott P, Evanovich LL, Hung J, Joglar JA, Kantor P, Kimmelstiel C, Kittleson M, Link MS, Maron MS, Martinez MW, Miyake CY, Schaff HV, Semsarian C, Sorajja P. 2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2020; 142:e533-e557. [PMID: 33215938 DOI: 10.1161/cir.0000000000000938] [Citation(s) in RCA: 142] [Impact Index Per Article: 28.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Aim This executive summary of the hypertrophic cardiomyopathy clinical practice guideline provides recommendations and algorithms for clinicians to diagnose and manage hypertrophic cardiomyopathy in adult and pediatric patients as well as supporting documentation to encourage their use. Methods A comprehensive literature search was conducted from January 1, 2010, to April 30, 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Structure Many recommendations from the earlier hypertrophic cardiomyopathy guidelines have been updated with new evidence or a better understanding of earlier evidence. This summary operationalizes the recommendations from the full guideline and presents a combination of diagnostic work-up, genetic and family screening, risk stratification approaches, lifestyle modifications, surgical and catheter interventions, and medications that constitute components of guideline directed medical therapy. For both guideline-directed medical therapy and other recommended drug treatment regimens, the reader is advised to follow dosing, contraindications and drug-drug interactions based on product insert materials.
Collapse
Affiliation(s)
| | | | | | | | - Anita Deswal
- ACC/AHA Joint Committee on Clinical Practice Guidelines Liaison
- HFSA Representative
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
47
|
Ommen SR, Mital S, Burke MA, Day SM, Deswal A, Elliott P, Evanovich LL, Hung J, Joglar JA, Kantor P, Kimmelstiel C, Kittleson M, Link MS, Maron MS, Martinez MW, Miyake CY, Schaff HV, Semsarian C, Sorajja P. 2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2020; 76:e159-e240. [PMID: 33229116 DOI: 10.1016/j.jacc.2020.08.045] [Citation(s) in RCA: 437] [Impact Index Per Article: 87.4] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
|
|
48
|
Ommen SR, Mital S, Burke MA, Day SM, Deswal A, Elliott P, Evanovich LL, Hung J, Joglar JA, Kantor P, Kimmelstiel C, Kittleson M, Link MS, Maron MS, Martinez MW, Miyake CY, Schaff HV, Semsarian C, Sorajja P. 2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy. Circulation 2020; 142:e558-e631. [DOI: 10.1161/cir.0000000000000937] [Citation(s) in RCA: 216] [Impact Index Per Article: 43.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
| | | | | | | | | | - Anita Deswal
- ACC/AHA Joint Committee on Clinical Practice Guidelines Liaison
- HFSA Representative
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
49
|
Moreno Garijo J, Amador Y, Fan CS, Silverton N, Ralph-Edwards A, Woo A, Mashari A, Meineri M. Association Between Three-Dimensional Left Ventricular Outflow Tract Area and Gradients After Myectomy in Hypertrophic Obstructive Cardiomyopathy. J Cardiothorac Vasc Anesth 2020; 35:1654-1662. [PMID: 33431273 DOI: 10.1053/j.jvca.2020.12.014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 12/04/2020] [Accepted: 12/07/2020] [Indexed: 11/11/2022]
Abstract
OBJECTIVE Determine whether the intraoperative three-dimensional left ventricular outflow tract cross-sectional area may be inversely correlated with pressure gradients as a determinant of surgical success after septal myectomy in hypertrophic cardiomyopathy patients. DESIGN Perioperative data were obtained by retrospective review. SETTING Toronto General Hospital, University of Toronto, Toronto, Canada, a tertiary hospital. PARTICIPANTS The study comprised 67 patients with hypertrophic obstructive cardiomyopathy. INTERVENTIONS Transthoracic and intraoperative transesophageal echocardiographic assessment of pressure gradients. Transesophageal measurement of the three-dimensional left ventricular outflow tract cross-sectional area. MEASUREMENTS AND MAIN RESULTS The smallest left ventricular outflow tract area increased on average 1.883 cm2 (98.3%) after septal myectomy. There was a significant correlation between the increase in the area and the transesophageal pressure gradients (r = -0.32; p = 0.01) after myectomy, but none with postoperative transthoracic gradients at rest (r = -0.10; p = 0.42). Postoperative transesophageal and transthoracic gradients were significantly correlated (r = 0.26; p = 0.04). The best risk factors to predict high residual gradients were preoperative transesophageal gradient >97 mmHg, postoperative transesophageal area <3.16 cm2, and moderate or more residual transesophageal mitral regurgitation (specificity 89%, 81%, and 78%, respectively). CONCLUSIONS Three-dimensional left ventricular outflow tract area measurements with transesophageal echocardiography after myectomy correlated fairly well with postoperative transesophageal pressure gradients. Patients with residual transthoracic elevated gradients after surgery at follow-up had a smaller transesophageal area and higher transesophageal pressure gradients immediately after the procedure. However, transesophageal pressure gradients after myectomy correlated poorly with follow-up transthoracic gradients at rest.
Collapse
Affiliation(s)
- J Moreno Garijo
- Department of Anesthesia and Pain Management, Toronto General Hospital, Toronto, ON, Canada.
| | - Y Amador
- Department of Anesthesia and Pain Management, Toronto General Hospital, Toronto, ON, Canada
| | - C S Fan
- Department of Biostatistics, Toronto General Hospital, Toronto, ON, Canada
| | - N Silverton
- Department of Anesthesiology, University of Utah Health, Salt Lake City, UT
| | - A Ralph-Edwards
- Department of Cardiac Surgery, Toronto General Hospital, Toronto, ON, Canada
| | - A Woo
- Department of Cardiology, Toronto General Hospital, Toronto, ON, Canada
| | - A Mashari
- Department of Anesthesia and Pain Management, Toronto General Hospital, Toronto, ON, Canada
| | - M Meineri
- Department of Anesthesia and Pain Management, Toronto General Hospital, Toronto, ON, Canada
| |
Collapse
|
|
50
|
Post-Mortem Cardiac Magnetic Resonance for the Diagnosis of Hypertrophic Cardiomyopathy. Diagnostics (Basel) 2020; 10:diagnostics10110981. [PMID: 33233445 PMCID: PMC7700290 DOI: 10.3390/diagnostics10110981] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 11/19/2020] [Accepted: 11/20/2020] [Indexed: 12/04/2022] Open
Abstract
Background: Post-mortem cardiac magnetic resonance (PMCMR) is an emerging tool supporting forensic medicine for the identification of the causes of cardiac death, such as hypertrophic cardiomyopathy (HCM). We proposed a new method of PMCMR to diagnose HCM despite myocardial rigor mortis. Methods: We performed CMR in 49 HCM patients, 30 non-HCM hypertrophy, and 32 healthy controls. In cine images, rigor mortis was simulated by the analysis of the cardiac phase corresponding to 25% of diastole. Left ventricular mass, mean, and standard deviation (SD) of WT, maximal WT, minimal WT, and their difference were compared for the identification of HCM. These parameters were validated at PMCMR, evaluating eight hearts with HCM, 10 with coronary artery disease, and 10 with non-cardiac death. Results: The SD of WT with a cut-off of > 2.4 had the highest accuracy to identify HCM (AUC 0.95, 95% CI = 0.89–0.98). This was particularly evident in the female population of HCM (AUC=0.998), with 100% specificity (95% CI = 85–100%) and 96% sensitivity (95% CI = 79–99%). Using this parameter, at PMCMR, all of the eight patients with HCM were correctly identified with no false positives. Conclusions: PMCMR allows identification of HCM as the cause of sudden death using the SD of WT > 2.4 as the diagnostic parameter.
Collapse
|