Revisiting Diagnosis and Treatment of Hypertrophic Cardiomyopathy: Current Practice and Novel Perspectives

Q: What is the clinical evidence from this study?

Study design: Review. Population: Sarcomeric hypertrophic cardiomyopathy (HCM). Intervention: Cardiac myosin inhibitors (mavacamten and aficamten) and conventional HCM therapies vs. Placebo or standard empirical medical/invasive therapy. Primary outcome: Reduction in left ventricular outflow tract obstruction (LVOTO) and improvement in symptoms and functional capacity.

Q: What does this research mean for the field?

Selective cardiac myosin modulators such as mavacamten and aficamten reduce left ventricular outflow tract obstruction and improve symptoms in patients with obstructive hypertrophic cardiomyopathy. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Davide Mansour; Lorenzo V. Molinari; Kristian Galanti; Cesare Mantini; Mohammed Y Khanji; C. Anwar A. Chahal; Marco Zimarino; Giulia Renda; Luigi Sciarra; Francesco Pelliccia; Sabina Gallina; Fabrizio Ricci

doi:10.3390/jcm12175710

September 1, 2023Journal of Clinical MedicineOpen Access

Revisiting Diagnosis and Treatment of Hypertrophic Cardiomyopathy: Current Practice and Novel Perspectives

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Why the study?

Despite advances in understanding the pathophysiology of sarcomeric hypertrophic cardiomyopathy, treatment options remain limited.

Key Points

To review current clinical management and examine emerging diagnostic tools and targeted therapeutic strategies for sarcomeric hypertrophic cardiomyopathy, focusing on cardiac myosin modulators.
Synthesized current clinical guideline recommendations, multimodal imaging protocols, and pharmacological trial evidence for sarcomeric hypertrophic cardiomyopathy.
Evaluated diagnostic workflows spanning multi-generational pedigree analysis, transthoracic echocardiography, global longitudinal strain, and cardiovascular magnetic resonance imaging.
Selective cardiac myosin modulators, specifically mavacamten and aficamten, reduce left ventricular outflow tract obstruction and improve clinical symptoms in patients with obstructive hypertrophic cardiomyopathy.
Cardiovascular magnetic resonance imaging with late gadolinium enhancement identifies replacement myocardial fibrosis, serving as an established tool for assessing sudden cardiac death and heart failure risk.
Novel molecular approaches, including CRISPR/Cas9 gene editing, allele-specific siRNA silencing, and artificial intelligence-driven monitoring, offer emerging pathways for precision disease modification.

Structured PICO

P

Population

Patients with sarcomeric hypertrophic cardiomyopathy (HCM), covering diagnostic evaluation, sudden cardiac death risk stratification, conventional therapies, and novel cardiac myosin inhibitors.

I

Intervention

Conventional pharmacological therapies (beta-blockers, non-dihydropyridine calcium channel blockers, disopyramide, cibenzoline, ranolazine, eleclazine, ARBs, ARNIs), invasive septal reduction therapies (surgical septal myectomy, alcohol septal ablation), lifestyle modifications, and novel selective cardiac myosin inhibitors (mavacamten, aficamten)

O

Outcome

Symptom relief, reduction of left ventricular outflow tract obstruction (LVOTO), improvement in functional capacity (peak VO2, NYHA class), and prevention of sudden cardiac death (SCD) and disease progression

Limitations

Narrative review format without pooled quantitative meta-analysis
Current HCM guidelines are largely based on small observational studies, case series, or expert consensus rather than large randomized trials
Conventional non-selective pharmacological therapies do not prevent disease progression and provide complete relief of obstruction in only a small subgroup of patients
Limited global access to specialized high-volume centers required for safe invasive septal reduction therapies
Narrative review format with no primary pooled statistical analysis
Most current clinical practice guidelines rely on small observational studies, case series, or expert consensus
Conventional empirical therapies fail to halt disease progression or reverse established hypertrophy and fibrosis
Access to high-volume specialized centers for invasive septal reduction therapy is limited globally

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Implication

This comprehensive narrative review synthesizes current guideline-directed diagnosis and management of hypertrophic cardiomyopathy while highlighting how emerging cardiac myosin inhibitors like mavacamten shift treatment from empirical symptom control toward targeted molecular therapy.

Abstract

Sarcomeric hypertrophic cardiomyopathy (HCM) is a prevalent genetic disorder characterised by left ventricular hypertrophy, myocardial disarray, and an increased risk of heart failure and sudden cardiac death. Despite advances in understanding its pathophysiology, treatment options for HCM remain limited. This narrative review aims to provide a comprehensive overview of current clinical practice and explore emerging therapeutic strategies for sarcomeric HCM, with a focus on cardiac myosin inhibitors. We first discuss the conventional management of HCM, including lifestyle modifications, pharmacological therapies, and invasive interventions, emphasizing their limitations and challenges. Next, we highlight recent advances in molecular genetics and their potential applications in refining HCM diagnosis, risk stratification, and treatment. We delve into emerging therapies, such as gene editing, RNA-based therapies, targeted small molecules, and cardiac myosin modulators like mavacamten and aficamten, which hold promise in modulating the underlying molecular mechanisms of HCM. Mavacamten and aficamten, selective modulators of cardiac myosin, have demonstrated encouraging results in clinical trials by reducing left ventricular outflow tract obstruction and improving symptoms in patients with obstructive HCM. We discuss their mechanisms of action, clinical trial outcomes, and potential implications for the future of HCM management. Furthermore, we examine the role of precision medicine in HCM management, exploring how individualised treatment strategies, including exercise prescription as part of the management plan, may optimise patient outcomes. Finally, we underscore the importance of multidisciplinary care and patient-centred approaches to address the complex needs of HCM patients. This review also aims to encourage further research and collaboration in the field of HCM, promoting the development of novel and more effective therapeutic strategies, such as cardiac myosin modulators, to hopefully improve the quality of life and outcome of patients with sarcomeric HCM.

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Cite This Study

Mansour et al. (2023) conducted a review in Sarcomeric hypertrophic cardiomyopathy (HCM). Cardiac myosin inhibitors (mavacamten and aficamten) and conventional HCM therapies vs. Placebo or standard empirical medical/invasive therapy was evaluated on Reduction in left ventricular outflow tract obstruction (LVOTO) and improvement in symptoms and functional capacity.

synapsesocial.com/papers/6a8047b89b5ec1a8804708dd https://doi.org/10.3390/jcm12175710

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Revisiting Diagnosis and Treatment of Hypertrophic Cardiomyopathy: Current Practice and Novel Perspectives

Figures

Key Points

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Revisiting Diagnosis and Treatment of Hypertrophic Cardiomyopathy: Current Practice and Novel Perspectives

Figures

Key Points

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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