Hypertrophic cardiomyopathy (HCM) is one of the leading causes of sudden cardiac death (SCD), particularly in young and middle-aged individuals. Current arrhythmic risk stratification mainly relies on clinical and imaging-based models, including the ESC HCM Risk-SCD score and guideline-recommended risk markers. However, these approaches show only moderate predictive accuracy at the individual level, highlighting the need for novel biomarkers able to improve risk prediction.

Cardiac magnetic resonance (CMR) plays a central role in phenotypic characterization and prognostic assessment of HCM, particularly through the evaluation of late gadolinium enhancement (LGE), a marker of myocardial fibrosis. Recent studies suggest that radiomic analysis of LGE images can identify quantitative features of myocardial scar heterogeneity that provide additional prognostic information beyond conventional fibrosis burden assessment. Radiomics applied to pre-contrast cine CMR sequences may also capture quantitative features related to myocardial shape, texture, and contractile dynamics, potentially associated with myocardial disarray, mechanical alterations, and electromechanical instability.

Integration of CMR radiomics with genetic data may allow a more comprehensive characterization of the arrhythmic substrate in HCM. In obstructive hypertrophic cardiomyopathy (oHCM), left ventricular outflow tract obstruction is a major determinant of symptoms and prognosis. Mavacamten, a selective cardiac myosin inhibitor, has been shown to significantly reduce LVOT gradient and improve symptoms and cardiac remodeling. However, it remains unknown whether CMR radiomics can detect phenotypic changes associated with mavacamten treatment and whether these changes may contribute to dynamic reassessment of arrhythmic risk.

This is a prospective, multicenter, non-profit observational study enrolling adult patients diagnosed with hypertrophic cardiomyopathy (HCM) who undergo cardiac magnetic resonance (CMR) imaging as part of routine clinical practice.

The study aims to evaluate the role of CMR radiomics in predicting arrhythmic risk in patients with HCM and to investigate phenotypic evolution in patients with obstructive hypertrophic cardiomyopathy (oHCM) treated with Mavacamten. Specifically, the study will assess whether radiomic features extracted from CMR imaging can improve the identification of patients at risk of malignant ventricular arrhythmic events and whether radiomic analysis can detect phenotypic modifications associated with mavacamten treatment that may contribute to longitudinal reassessment of arrhythmic risk.

Eligible participants will include adult patients with a diagnosis of hypertrophic cardiomyopathy, including both obstructive and non-obstructive forms, who undergo clinically indicated CMR examinations. In addition, the study will include a subgroup of patients with obstructive HCM initiating treatment with mavacamten, for whom both baseline CMR assessment and longitudinal follow-up CMR evaluation will be available.

Approximately 2,000 patients are expected to be enrolled in the study. Clinical data, standard CMR parameters, and radiomic features extracted from imaging sequences will be collected and analyzed in order to develop predictive models for arrhythmic risk stratification and to evaluate potential imaging biomarkers associated with disease progression and treatment-related phenotypic changes.

Inclusion Criteria:

• Age ≥ 18 years at the time of enrollment
• Diagnosis of hypertrophic cardiomyopathy (HCM) according to current ESC guideline criteria, defined as left ventricular wall thickness unexplained solely by loading conditions
• Availability of a clinically indicated cardiac magnetic resonance (CMR) examination performed according to standard protocols and of sufficient diagnostic quality for radiomic analysis
• Written informed consent for participation in the study and for data processing, when required by applicable regulations and local center procedures

For the subgroup of patients with obstructive HCM treated with mavacamten only:

• Initiation of mavacamten therapy according to clinical indication
• Availability of baseline CMR and follow-up CMR performed at a later time point

Exclusion Criteria:

• Age < 18 years
• Absence of a diagnosis of hypertrophic cardiomyopathy according to current ESC guideline criteria
• Presence of phenocopies of hypertrophic cardiomyopathy or other structural cardiac diseases that may interfere with phenotypic characterization of HCM, including but not limited to cardiac amyloidosis, Fabry disease, infiltrative or storage cardiomyopathies, and other forms of secondary left ventricular hypertrophy not consistent with HCM
• Inadequate quality of cardiac magnetic resonance (CMR) images for radiomic analysis, including motion artifacts, low spatial resolution, incomplete acquisitions, or lack of technical adequacy of required sequences
• Absence of required CMR sequences for the planned analyses (in particular cine and/or late gadolinium enhancement [LGE] sequences)
• Inability to achieve reliable myocardial segmentation in relevant sequences due to technical or anatomical reasons
• Prior septal reduction therapy (surgical myectomy or alcohol septal ablation), when such intervention substantially alters myocardial morphology and prevents meaningful comparison with native phenotype radiomic analysis

Adult patients with a diagnosis of hypertrophic cardiomyopathy (HCM), including both obstructive and non-obstructive forms, undergoing clinically indicated cardiac magnetic resonance (CMR) imaging as part of routine clinical practice will be included in the study.

The study will also include a subgroup of patients with obstructive hypertrophic cardiomyopathy (oHCM) initiating treatment with mavacamten, for whom both baseline CMR assessment and follow-up CMR evaluation will be available.