Hypertrophic cardiomyopathy, the most common genetic cardiomyopathy, affects an estimated 1 in 200 to 1 in 500 people worldwide, yet its diagnosis and treatment have been transformed in recent years by advances in cardiovascular imaging, genetic testing and a new class of drugs. A comprehensive review published in the journal Cardiovascular Ultrasound brings together the current state of knowledge on how the condition is identified, risk-stratified and managed, from first-line echocardiography through to emerging surgical and catheter-based techniques. The review, authored by a multidisciplinary team led by Eluisa La Franca and Francesco Fulvio Faletra, emphasizes that hypertrophic cardiomyopathy shows marked clinical and prognostic heterogeneity, ranging from asymptomatic individuals to patients with heart failure, arrhythmias and sudden cardiac death.
The condition is defined slightly differently by the major cardiology societies. The European Society of Cardiology takes a broad view, describing an unexplained increase in left ventricular wall thickness or mass that encompasses a range of phenocopies presenting with a thick heart phenotype. The American Heart Association offers a narrower definition, considering it a primary genetic myocardial disease characterized by left ventricular hypertrophy not explained by other cardiac, systemic or metabolic conditions. Under both frameworks, the diagnosis rests on a wall thickness of at least 15 millimetres in any myocardial segment when no other cause or abnormal loading condition explains the hypertrophy. In first-degree relatives of affected patients, a thickness greater than 13 millimetres is diagnostic, while in children the threshold is a wall thickness more than two standard deviations from the predicted value.
Genetics underpins much of the modern understanding of the disease. Pathogenic or likely pathogenic variants in sarcomeric genes are found in approximately 30 to 60 percent of patients, depending on the population studied and the extent of testing performed. Inheritance is mostly autosomal dominant, with high genetic and allelic diversity, incomplete age-related penetrance and variable expressivity, meaning the same variant running through a family can produce different phenotypes. More than 1,400 pathogenic variants have been identified across numerous genes. The primary genetic test remains multigene panel analysis using next-generation sequencing, and in selected familial cohorts undergoing comprehensive testing that includes single-nucleotide variants, small insertions and deletions and copy-number variants, a causal variant can be identified in up to roughly 85 percent of cases, approaching 90 percent when all variant classes are searched. In about 40 percent of patients, however, no sarcomeric gene variant is found, and a negative result should prompt consideration of phenocopies such as cardiac amyloidosis, Fabry disease, glycogen storage disorders, mitochondrial diseases and RASopathies.
Family evaluation is a central pillar of care. When hypertrophic cardiomyopathy is newly diagnosed, detailed family history, genetic counselling and clinical screening with electrocardiography, echocardiography and cardiac magnetic resonance where appropriate are recommended for first-degree relatives. If a pathogenic variant is found in the proband, cascade testing can be extended to at-risk relatives, whereas variants of uncertain significance do not justify cascade testing and should prompt clinical surveillance alone. Mutation carriers without phenotypic expression are reviewed every one to three years if under 60 and every three to five years thereafter, and relatives who are both genotype- and phenotype-negative can be discharged from active surveillance. Because variants may be reclassified over time, periodic re-evaluation of genetic findings is advisable.
Electrocardiography remains a cornerstone of diagnosis because it is widely accessible and highly cost-effective. Typical findings include narrow Q-waves in the inferior and lateral leads reflecting septal hypertrophy, deep S-waves in V1 to V3 or tall R-waves in V4 to V6 with T-wave inversion, and signs of left atrial enlargement. Giant symmetric negative T-waves in V3 to V5 are typical of the apical form, and a pseudo-STEMI pattern should not be misread as an acute coronary syndrome. The electrocardiogram is abnormal in 94 to 96 percent of affected adults and in more than 97 percent of paediatric cases, and electrocardiographic abnormalities often precede the detection of hypertrophy on imaging. Artificial intelligence is now entering this space: convolutional neural network models have achieved area under the curve values of 0.96 to 0.98 for identifying the condition from standard 12-lead electrocardiograms, with false positive rates as low as 13.5 percent, and real-world implementation has identified previously undiagnosed cases across diverse populations.
Transthoracic echocardiography remains the first-line imaging method for screening, diagnosis, prognostic stratification and long-term monitoring. It allows comprehensive visualization of ventricular hypertrophy, systolic function, mitral valve anatomy, systolic anterior motion and left ventricular outflow tract obstruction. Wall thickness should be measured in end-diastole across all segments, preferably in parasternal short-axis views, and contrast-enhanced imaging is recommended when the extent of hypertrophy is uncertain, particularly at the apex. Compared with cardiac magnetic resonance, echocardiography may over- or underestimate wall thickness depending on location, with overestimation occurring in more than 50 percent of cases. Combining two-dimensional imaging with three-dimensional techniques improves diagnostic accuracy, and deep learning models trained across multiple institutions using a federated approach have demonstrated excellent discrimination of the condition from other causes of left ventricular hypertrophy, outperforming cardiologists in sensitivity at a comparable specificity. Global longitudinal strain has emerged as a key marker of subclinical dysfunction, with values less negative than minus 10 percent associated with worse outcomes.
Cardiac magnetic resonance is recommended by the 2023 European guidelines as a key tool in the initial assessment, providing precise measurement of wall thickness and mass and uniquely enabling tissue characterization through late gadolinium enhancement, which identifies myocardial fibrosis and is present in approximately 65 percent of patients, typically as a mid-wall patchy pattern. Increased native T1 times help differentiate the condition from hypertensive heart disease, Fabry disease and cardiac amyloidosis, while extracellular volume quantification offers additional prognostic value. Cardiac computed tomography complements the evaluation in patients who cannot undergo magnetic resonance and is the preferred tool for characterizing myocardial bridging, with photon-counting CT now showing excellent agreement with magnetic resonance for fibrosis quantification.
On the therapeutic front, beta-blockers remain the most commonly used drugs, with non-dihydropyridine calcium channel blockers as alternatives and disopyramide used for its negative inotropic effect. The most significant recent advance is the development of cardiac myosin inhibitors. In the randomized phase 3 EXPLORER-HCM trial, mavacamten achieved its primary endpoint, improving functional capacity and reducing symptoms and outflow tract obstruction, the latter evident after four weeks. In the VALOR-HCM trial, 16 weeks of mavacamten treatment produced a 60 percent reduction in patients eligible for septal reduction therapy, with sustained freedom from such therapy observed at 128 weeks. Aficamten, a second-generation inhibitor with a shorter half-life and more predictable pharmacokinetic relationship, proved superior to metoprolol in reducing gradients and improving symptoms in the MAPLE-HCM trial, although follow-up in aficamten studies remains shorter than in mavacamten trials. These drugs require regular echocardiographic follow-up, with treatment interruption if the ejection fraction falls below 50 percent.
When medications fail or are not tolerated, surgical myectomy or alcohol septal ablation remains the mainstay, with myectomy carrying a postoperative 30-day mortality below 1 percent in experienced high-volume centres and a 10-year all-cause mortality of 8 percent. Alcohol septal ablation, less invasive but with higher pacemaker risk and residual gradient, is reserved for older or high-risk patients. Emerging alternatives include percutaneous intramyocardial septal radiofrequency ablation, which has demonstrated sustained gradient reductions and functional improvement at medium-term follow-up but remains investigational, and endocardial radiofrequency ablation, supported by more limited evidence. Transcatheter edge-to-edge repair has also shown promise, with a registry of 35 high-surgical-risk patients reporting technical success in 94 percent and a gradient reduction from 62 to 16 millimetres of mercury. For the 5 to 7 percent of patients who progress to advanced heart failure, heart transplantation is the preferred treatment with one-year survival exceeding 90 percent, and early integration of palliative care is recommended for those ineligible for such therapies.
The review’s authors are candid about the limitations of the evidence base, noting that it is dominated by non-randomized and referral-centre cohorts, that diagnostic and biomarker measurement standards remain incompletely validated for routine prognostic use, and that key populations including children and non-White ancestries are underrepresented. They highlight outstanding questions around disease modification, which remains unproven, the management of genotype-positive individuals without phenotypic expression, and imprecise risk stratification for sudden cardiac death. Much of current care, they conclude, is still built on observational evidence and expert opinion, reflecting the paucity of adequately powered randomized trials and the slow, variable natural history of the condition, even as advanced imaging and targeted therapies have transformed day-to-day management.
Subject of Research: Diagnosis and therapeutic management of hypertrophic cardiomyopathy
Article Title: Hypertrophic cardiomyopathy: state of the art on diagnosis and current therapeutic approach
Article References: La Franca, E., Parisi, F., Lucchino, A., Sade, L. E., Wong, T., Loddo, I., Alioto, L., Gentile, G., Pilato, M., Cipriani, M., & Faletra, F. F. (2026). Hypertrophic cardiomyopathy: state of the art on diagnosis and current therapeutic approach. Cardiovascular Ultrasound, 24(1), Article 21. https://doi.org/10.1186/s12947-026-00382-6
Image Credits: AI Generated
DOI: 10.1186/s12947-026-00382-6
Keywords: hypertrophic cardiomyopathy, echocardiography, cardiac magnetic resonance, genetic testing, cardiac myosin inhibitors, mavacamten, aficamten, septal reduction, sudden cardiac death, left ventricular outflow tract obstruction, heart failure, electrocardiography
News Source: Juliet Wilcox. (October 28, 2026). Imaging, genetics and myosin inhibitors reshape hypertrophic cardiomyopathy care. Scienmag.
