Mohiddin, Saidi

Importance Current risk prediction guidelines for hypertrophic cardiomyopathy predict only sudden cardiac death and are imperfect, leading to avoidable deaths and unnecessary implantable cardioverter defibrillators. Objective To combine prospectively collected clinical history, imaging, genetic, and biomarker data to improve risk prediction of adverse events in hypertrophic cardiomyopathy. Design, Setting, and Participants A total of 2750 patients with hypertrophic cardiomyopathy were prospectively enrolled in the registry-based study from 44 sites in North America and Europe with expertise in hypertrophic cardiomyopathy and cardiac magnetic resonance (CMR) imaging. Participants were enrolled from April 1, 2014, to April 7, 2017. Exposures Patients underwent a health history questionnaire, blood sampling for biomarkers and genotyping, and contrast-enhanced CMR. Patients were followed up yearly by telephone and through records review regarding event documentation. Main Outcomes and Measures The predefined composite adjudicated primary end point was time to first event for hypertrophic cardiomyopathy–related deaths; nonfatal sustained ventricular arrhythmias (VAs) requiring cardioversion or defibrillation; and left ventricular (LV) assist device implant or heart transplant. A secondary end point was a composite of sudden cardiac death and nonfatal VA events. The elastic-net method identified the most important predictors. Cox proportional hazards regression assessed associations with time to the first end point. Results Of the 2750 prospectively enrolled patients, 2698 (98%) had analyzable data after 9 were excluded because they had hypertrophic cardiomyopathy phenocopies and 43 withdrew. Of these remaining patients, 1919 (71%) were male, mean age was 50 years (SD, 11 years), and 423 (16%) were from underrepresented racial and minority groups. The mean follow-up was 6.9 years (SD, 2.1 years). The primary event model in 104 patients included LV scar as a percentage of LV mass by late gadolinium enhancement (LGE%; hazard ratio [HR], 1.86; 95% CI, 1.58-2.20; P < .001), LV mass index (HR, 1.09; 95% CI, 1.01-1.17; P = .03), LV end-systolic volume index (HR, 1.28; 95% CI, 1.12-1.46; P < .001 ), all per 10-unit increase, history of heart failure at study entry (HR, 2.89; 95% CI, 1.75-4.77; P < .001), and log N-terminal pro–B-type natriuretic peptide (NT-proBNP; HR, 1.41; 95% CI, 1.17-1.70; P < .001) level per log unit, (C index for all, 0.77). An LGE percentage of the LV mass of 9% or higher substantially increased the primary composite event rate ( P = .001). The secondary sudden cardiac death and VA risk factor model (in 69 patients) included LGE%, LV mass index, LV ejection fraction, and log(NT-proBNP) (C index, 0.76). Conclusions and Relevance These results provide prospective evidence for incorporating cardiac magnetic resonance and NT-proBNP in the evaluation of patients with hypertrophic cardiomyopathy. Trial Registration ClinicalTrials.gov Identifier: NCT01915615

Abstract Dilated cardiomyopathy (DCM) is a clinical diagnosis characterized by the presence of left ventricular dilatation and systolic dysfunction unexplained by abnormal loading conditions or coronary artery disease. However, a broad range of phenotypic manifestations, encompassing isolated scar, DCM with preserved ejection fraction, and overt DCM, should be regarded as a diagnostic classification representing a broad spectrum of underlying aetiologies, including both inherited and acquired heart muscle disorders. A multimodal non-invasive imaging approach is essential for accurate morpho-functional assessment of cardiac chambers and is key to establish the cardiac phenotype and to rule out an underlying ischaemic aetiology. Furthermore, advanced imaging techniques enable deep cardiovascular phenotyping and non-invasive tissue characterization. The aim of this review is to propose a systematic approach to the diagnosis of DCM, emphasizing the importance of genetics and clinical findings for a precise and practical clinical approach. Also, we strive to qualify the role of cardiac imaging in the diagnosis of DCM, particularly on the relevance of novel techniques and clinical utility of actionable parameters to improve current diagnostic schemes and risk stratification algorithms. We further elaborate on the role of cardiac imaging to deliver optimal guidance to aetiology-based therapeutic approaches, verification of treatment response and disease progression monitoring.

Abstract Aims In light of recent advances in imaging techniques, molecular understanding and therapeutic options in hypertrophic cardiomyopathy (HCM), we performed a systematic review of current guidelines for the diagnosis and management of HCM in order to identify consensus and discrepant areas in the clinical practice guidelines. Methods and results We systematically reviewed the English language guidelines and recommendations for the management of HCM in adults. MEDLINE and EMBASE databases were searched for guidelines published in the last 10 years. Following a systematic search, three guidelines on the diagnosis and management of HCM were identified, all of which were robustly developed (AGREE rigour of development score ≥50%). These guidelines were authored by the major European (European Society of Cardiology; 2023), American (American Heart Association /American College of Cardiology/American Medical Society for Sports Medicine /Heart Rhythm Society/Pediatric and Congenital Electrophysiology Society/Society for Cardiovascular Magnetic Resonance; 2024), and Japanese [Japanese Circulation Society (JCS)/Japanese Heart Failure Society (JHFS); 2018] cardiovascular societies. There was broad consensus on echocardiographic recommendations, the medical and invasive management of HCM, the application of genetic testing and family screening, and exercise and reproductive recommendations in HCM. There were areas of variability in the definition and diagnostic criteria for HCM, cardiovascular magnetic resonance imaging recommendations, and assessment of sudden cardiac death (SCD) risk and prevention strategies. Due to the JCS/JHFS guidelines being older, there are no recommendations on the use of cardiac myosin ATPase inhibitors. Conclusion Contemporary guidelines for HCM achieve consensus across a broad range of criteria and recommendations concerning diagnosis and management. However, variations in the approach towards risk assessment for SCD exist between the guidelines. There are also more subtle differences concerning diagnostic criteria and the utility of late gadolinium enhancement for risk stratification, which will likely evolve as the evidence-base broadens.

Abstract The management of acute myocarditis (AM) is addressed in multiple clinical guidelines. We systematically reviewed current guidelines developed by national and international medical organizations on the management of AM to aid clinical practice. Publications in MEDLINE, EMBASE and Cochrane were identified between 1 January 2013 and 12 April 2024. Additionally, the websites of relevant organizations and the Guidelines International Network, Guideline Central, and NHS knowledge and library hub were reviewed. Two reviewers independently screened titles and abstracts, two reviewers assessed the rigour of guideline development, and one reviewer extracted the recommendations. Two of the three guidelines identified showed good rigour of development. Those rigorously developed agreed on the definition of AM, sampling serum troponin as part of the workflow for AM, testing for B-type natriuretic peptides in heart failure, key diagnostic imaging in the form of cardiovascular magnetic resonance, coronary angiography to exclude significant coronary disease, indications for endomyocardial biopsy (EMB), and indications for immunosuppression and advanced treatment options. Discrepancies exist in sampling creatine kinase-myocardial bound as a marker of myocardial injury, indications for EMB, and indications for immunosuppression and treatment of uncomplicated AM. Evidence is lacking for the use of 18F-Fluorodeoxyglucose Positron Emission Tomography for myocardial imaging, exercise restriction, follow-up measures, and genetic testing, and there are few high-quality randomized trials to support treatment recommendations. Recommendations for management of AM in the guidelines have largely been developed from expert opinion rather than trial data.

Abstract Background The risk of adverse cardiovascular events in patients with acute myocarditis (AM) and desmosomal gene variants (DGV) remains unknown. Purpose To ascertain the risk of death, ventricular arrhythmias, recurrent myocarditis, and heart failure (main endpoint) in patients with AM and pathogenic or likely pathogenetic DGV. Methods In a retrospective international study from 23 hospitals, 97 patients were included: 36 with AM and DGV (DGV(+)), 25 with AM and negative gene testing (DGV(−)), and 36 AM patients without genetics (w/o genetics). All patients had troponin elevation plus findings consistent with AM on histology or at cardiac magnetic resonance imaging (CMRI). In 86 patients CMRI changes in function and structure were re-assessed at follow-up. Results In the DGV(+) AM group (88.9% DSP variants), median age was 24 years, 91.7% presented with chest pain, and median left ventricular (LV) ejection fraction was 56% on CMRI (p=NS vs. the other 2 groups). Kaplan-Meier curves demonstrated a higher risk of the main endpoint in DGV(+) AM compared to DGV(−) and w/o genetics patients (62.3% vs. 17.5% vs. 5.3% at 5 years respectively; p<0.0001), driven by myocarditis recurrence and ventricular arrhythmias (Figure 1A, B). At follow-up CMRI, a higher number of late-gadolinium enhanced segments was found in DGV(+) AM. Conclusions Patients with AM and evidence of DGV have a higher incidence of adverse cardiovascular events compared with AM patients without DGV. Further prospective studies are needed to ascertain if genetic testing might improve risk stratification of patients with AM who are considered at low risk. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Italian Ministry of Health

Background: Identification of people with hypertrophic cardiomyopathy (HCM) who are at risk of sudden cardiac death (SCD) and require a prophylactic implantable cardioverter defibrillator is challenging. In 2014, the European Society of Cardiology proposed a new risk stratification method based on a risk prediction model (HCM Risk-SCD) that estimates the 5-year risk of SCD. The aim was to externally validate the 2014 European Society of Cardiology recommendations in a geographically diverse cohort of patients recruited from the United States, Europe, the Middle East, and Asia. Methods: This was an observational, retrospective, longitudinal cohort study. Results: The cohort consisted of 3703 patients. Seventy three (2%) patients reached the SCD end point within 5 years of follow-up (5-year incidence, 2.4% [95% confidence interval {CI}, 1.9–3.0]). The validation study revealed a calibration slope of 1.02 (95% CI, 0.93–1.12), C-index of 0.70 (95% CI, 0.68–0.72), and D-statistic of 1.17 (95% CI, 1.05–1.29). In a complete case analysis (n= 2147; 44 SCD end points at 5 years), patients with a predicted 5-year risk of <4% (n=1524; 71%) had an observed 5-year SCD incidence of 1.4% (95% CI, 0.8–2.2); patients with a predicted risk of ≥6% (n=297; 14%) had an observed SCD incidence of 8.9% (95% CI, 5.96–13.1) at 5 years. For every 13 (297/23) implantable cardioverter defibrillator implantations in patients with an estimated 5-year SCD risk ≥6%, 1 patient can potentially be saved from SCD. Conclusions: This study confirms that the HCM Risk-SCD model provides accurate prognostic information that can be used to target implantable cardioverter defibrillator therapy in patients at the highest risk of SCD.