Myocardial Energetic Restoration in the Treatment of Obstructive Hypertrophic Cardiomyopathy (MERIT HCM)

Hypertrophic Cardiomyopathy (HCM) is the most common inherited heart condition, where the heart muscles can thicken to the point of obstructing blood flow out of the heart. This condition is associated with a chronic state of energy loss in the heart muscle.

Till more recently, a new class of medication (cardiac myosin inhibitors) have been introduced to directly target the heart muscle proteins (sarcomeres) to reduce the strength of contraction and relieve obstruction of blood flow out of the heart. While clinical trials have shown this class of medication significantly improves physical capacity and patient symptoms, it is still unclear, based on small scale published studies, where this improvement is achieved by restoring the fundamental energy balance within the heart.

Our research study aims to answer this question and prove mechanistic insights of the use of this class of medication in the HCM population with blood flow obstruction (otherwise known as obstructive HCM) by using a specialised non-invasive MRI technique which accurately measures the heart energy score (specifically known as the PCr/ATP ratio) in each participant. Our objective is to determine how a patient with obstructive HCM have their energy scores affected, and improve over time with this medication therapy. If positive, this finding could establish the use of PCr/ATP ratio as a crucial, objective biomarker for monitoring therapeutic response and informing personalised dosing strategies for patient in the future.

Study Overview

• Status: Not yet recruiting
• Conditions: Hypertrophic Cardiomyopathy (HCM)

• Study Type: Observational
• Enrollment (Estimated): 20

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The cohort consists of adults diagnosed with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) who are clinically eligible for and planning to initiate treatment with mavacamten.

Description

Inclusion Criteria:

• at least 18 years of age and
• Have a confirmed diagnosis of oHCM that is not solely explained by abnormal loading conditions such as significant hypertension or valvular disease
• Qualify for mavacamten therapy by exhibiting a peak Left Ventricular Outflow Tract (LVOT) gradient of ≥ 50mmHg at rest or with provocation, New York Heart Association (NYHA) functional class II or III symptoms, and a baseline Left Ventricular Ejection Fraction (LVEF) of ≥ 55%

Exclusion Criteria:

• HCM phenocopies such as cardiac amyloidosis or Fabry's disease
• Undergone a septal reduction therapy (myectomy or ablation) within the preceding 6 months
• Any contraindications to mavacamten (e.g., baseline LVEF < 55%, pregnancy/breastfeeding)
• Inability to safely undergo a cardiac MRI, such as having non-compatible metal implants or severe claustrophobia

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in PCr/ATP ratio	The main goal is to determine if mavacamten therapy (cardiac myosin inhibitor) significantly improves the heart-muscle energy levels of patients with obstructive hypertrophic cardiomyopathy, as measured by the "energy score" (PCr/ATP) on a specialised MRI scan.	24 weeks

Collaborators and Investigators

• Sponsor: University of Manchester

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: December 29, 2025
• First Submitted That Met QC Criteria: December 29, 2025
• First Posted (Estimated): January 12, 2026

Study Record Updates

• Last Update Posted (Estimated): January 12, 2026
• Last Update Submitted That Met QC Criteria: December 29, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: hypertrophic cardiomyopathy
• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Cardiomyopathies; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Cardiomyopathy, Hypertrophic
• Other Study ID Numbers: 367806

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No