Efficacy and Safety of Pharmacologic Therapies in Nonobstructive Hypertrophic Cardiomyopathy: A Systematic Review
- 1University of Illinois College of Medicine
- 2Midwestern University Chicago College of Osteopathic Medicine
- 3Mayo Clinic
Abstract
BACKGROUND: Nonobstructive hypertrophic cardiomyopathy (HCM) affects approximately one-third of all patients with HCM and carries substantial morbidity, yet no approved disease-modifying therapies exist. We conducted a systematic review of prospective interventional studies evaluating pharmacologic therapies in adults with nonobstructive HCM. METHODS: A systematic search of PubMed, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov was performed through September 2025. Eligible studies included randomized and nonrandomized prospective interventional trials. A narrative synthesis was performed by pharmacologic class and outcome domain. RESULTS: Twenty-nine clinical trials evaluating 9 pharmacologic classes were identified: cardiac myosin inhibitors, cardiac sarcomere modulators, metabolic modulators, angiotensin II receptor blockers, angiotensin receptor-neprilysin inhibitors, mineralocorticoid receptor antagonists, SGLT2 (sodium-glucose cotransporter 2) inhibitors, beta blockers, and calcium channel blockers. Cardiac myosin inhibitors demonstrated reductions in left ventricular hypertrophy, improvements in diastolic function, and marked reductions in cardiac biomarkers, although improvements in exercise capacity and symptoms were variable. SGLT2 inhibition showed concordant improvements in diastolic function, atrial remodeling, biomarkers, and functional status in patients with symptomatic nonobstructive HCM and comorbid type 2 diabetes. Angiotensin receptor blockade showed signals of structural remodeling with valsartan and candesartan without consistent functional benefit. Mineralocorticoid receptor antagonism and angiotensin receptor-neprilysin inhibition demonstrated largely neutral effects. Among metabolic modulators, ninerafaxstat improved ventilatory efficiency and quality of life in patients with greater baseline symptom burden. CONCLUSIONS: Pharmacologic responsiveness in nonobstructive HCM is variable and appears to be mechanism- and disease stage-dependent. Ongoing trials evaluating cardiac myosin inhibitors, SGLT inhibitors, and novel therapeutic agents including ninerafaxstat and EDG-7500 will be critical in further defining the therapeutic landscape.
Related
- The Evolving Landscape of Hypertrophic Cardiomyopathy: Clinical Assessment, Precision Therapies, and Emerging Strategies
- Cardiac Myosin Inhibitors in Adults with Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy: A Systematic Review and Meta-analysis of Randomized Controlled Trials
- A late bloom at the apex: development of apical hypertrophic cardiomyopathy phenotype in advanced age
- Research trends and hotspot analysis of sudden cardiac death in hypertrophic cardiomyopathy : A bibliometric analysis
- Managing a mavacamten non-responder in obstructive hypertrophic cardiomyopathy: A case report
BibTeX
@article{patel2026efficacy,
title = {{Efficacy and Safety of Pharmacologic Therapies in Nonobstructive Hypertrophic Cardiomyopathy: A Systematic Review}},
author = {Shivam Patel and Akash Gandhi and Arman Pabani and Richa Shah and Pal Shah and Matthew W. Martinez and Aakash Bavishi},
journal = {Journal of the American Heart Association},
year = {2026},
month = oct,
doi = {10.1161/jaha.126.051256},
url = {https://www.ahajournals.org/doi/10.1161/JAHA.126.051256},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Efficacy and Safety of Pharmacologic Therapies in Nonobstructive Hypertrophic Cardiomyopathy: A Systematic Review
AU - Shivam Patel
AU - Akash Gandhi
AU - Arman Pabani
AU - Richa Shah
AU - Pal Shah
AU - Matthew W. Martinez
AU - Aakash Bavishi
PY - 2026
DA - 2026/10/23
JO - Journal of the American Heart Association
DO - 10.1161/jaha.126.051256
UR - https://www.ahajournals.org/doi/10.1161/JAHA.126.051256
AB - BACKGROUND: Nonobstructive hypertrophic cardiomyopathy (HCM) affects approximately one-third of all patients with HCM and carries substantial morbidity, yet no approved disease-modifying therapies exist. We conducted a systematic review of prospective interventional studies evaluating pharmacologic therapies in adults with nonobstructive HCM. METHODS: A systematic search of PubMed, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov was performed through September 2025. Eligible studies included randomized and nonrandomized prospective interventional trials. A narrative synthesis was performed by pharmacologic class and outcome domain. RESULTS: Twenty-nine clinical trials evaluating 9 pharmacologic classes were identified: cardiac myosin inhibitors, cardiac sarcomere modulators, metabolic modulators, angiotensin II receptor blockers, angiotensin receptor-neprilysin inhibitors, mineralocorticoid receptor antagonists, SGLT2 (sodium-glucose cotransporter 2) inhibitors, beta blockers, and calcium channel blockers. Cardiac myosin inhibitors demonstrated reductions in left ventricular hypertrophy, improvements in diastolic function, and marked reductions in cardiac biomarkers, although improvements in exercise capacity and symptoms were variable. SGLT2 inhibition showed concordant improvements in diastolic function, atrial remodeling, biomarkers, and functional status in patients with symptomatic nonobstructive HCM and comorbid type 2 diabetes. Angiotensin receptor blockade showed signals of structural remodeling with valsartan and candesartan without consistent functional benefit. Mineralocorticoid receptor antagonism and angiotensin receptor-neprilysin inhibition demonstrated largely neutral effects. Among metabolic modulators, ninerafaxstat improved ventilatory efficiency and quality of life in patients with greater baseline symptom burden. CONCLUSIONS: Pharmacologic responsiveness in nonobstructive HCM is variable and appears to be mechanism- and disease stage-dependent. Ongoing trials evaluating cardiac myosin inhibitors, SGLT inhibitors, and novel therapeutic agents including ninerafaxstat and EDG-7500 will be critical in further defining the therapeutic landscape.
SN - 2047-9980
ER -