Radiomics Analysis of CMR Imaging for Arrhythmic Risk Prediction in Hypertrophic Cardiomyopathy, With Longitudinal Risk Reassessment After Mavacamten Therapy in Obstructive Patients

NCT07695272 | Active Not Recruiting

• 1 other identifier: L2-618
• Study Type: observational
• Target: 2,000
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hypertrophic Cardiomyopathy (HCM); Cardiac Myosin Inhibitors

Outcome Measures

Primary Outcomes (1)

• Composite of malignant ventricular arrhythmic events

  * Sustained ventricular tachycardia * Ventricular fibrillation * Appropriate implantable cardioverter-defibrillator (ICD) therapy * Sudden cardiac death Events will be adjudicated based on clinical records, device interrogation data, and death certificates where available.

  60 months

Secondary Outcomes (4)

• Longitudinal changes in radiomic features in mavacamten-treated patients

  60 months

• Predictive performance of radiomic models

  60 months

• Incremental prognostic value over ESC and AHA/ACC models

  60 months

• Association between genotype and arrhythmic risk

  60 months

Study Arms (1)

Prospective Cohort

Adult patients diagnosed with 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 enrolled 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 longitudinal follow-up CMR evaluation will be available

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Azienda Sanitaria Universitaria Giuliano Isontina (ASU GI): collaborator
• Azienda Ospedaliera di Padova: collaborator
• IRCCS Azienda Ospedaliero-Universitaria di Bologna: collaborator
• Centro Cardiologico Monzino: lead
• Azienda Ospedaliero-Universitaria Careggi: collaborator
• Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy: collaborator

Study Sites (1)

Centro Cardiologico Monzino; IRCCS

Milan, Milan, 20133, Italy

Location

MeSH Terms

Conditions

Cardiomyopathy, Hypertrophic

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases

Study Officials

• Gianluca Pontone, MD

  Centro Cardiologico Monzino

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2026
• First Posted: July 10, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): June 1, 2031
• Last Updated: July 10, 2026

Record last verified: 2026-06

Locations

IT (1)