Hypertrophic Cardiomyopathy (HCM)
Conditions
Brief summary
This study is a prospective interventional cohort study aimed at evaluating the therapeutic efficacy and clinical utility of Mavacamten-a targeted myosin inhibitor specifically developed for obstructive hypertrophic cardiomyopathy (HCM)-in patients with HCM characterized by mid-to-apical left ventricular obstruction.
Interventions
DRUGmavacamten
Add Mavacamten to guideline-directed standard medical therapy for patients with hypertrophic cardiomyopathy (HCM) and mid-to-apical left ventricular obstruction.
Administer an appropriate dose of beta-blockers according to the patient's tolerance.
DRUGdiltiazem
Administer an appropriate dose of diltiazem according to the patient's tolerance.
Sponsors
Second Affiliated Hospital, Zhejiang University, School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients diagnosed with HCM according to the 2023 Chinese Guidelines for the Diagnosis and Treatment of Adult Hypertrophic Cardiomyopathy, meeting one of the following: 1. Left ventricular wall thickness ≥15 mm at end-diastole in any segment as assessed by echocardiography or cardiac magnetic resonance imaging (CMR); 2. Left ventricular wall thickness ≥13 mm in individuals with a confirmed pathogenic gene mutation or in genetically affected family members; 3. Exclusion of other cardiovascular, systemic, or metabolic disorders that may cause ventricular hypertrophy. * Symptomatic non-outflow tract obstructive HCM patients (meeting criterion a and at least one of b or c): <!-- --> 1. Presence of clinical symptoms such as dyspnea, chest pain, dizziness, palpitations, or syncope, with New York Heart Association (NYHA) functional class II-III; 2. Maximal pressure gradient (PGmax) \>30 mmHg in the mid-ventricle under resting or Valsalva maneuver as assessed by echocardiography; 3. PGmax \>30 mmHg in the apical region under resting or Valsalva maneuver on echocardiography. ③Ability to provide written informed consent (ICF) and any required privacy authorization prior to study enrollment.
Exclusion criteria
\- * Obstructive hypertrophic cardiomyopathy (HCM), defined as a maximal left ventricular outflow tract pressure gradient (LVOT-PGmax) ≥30 mmHg at rest and during the Valsalva maneuver on echocardiography; * Maximal right ventricular outflow tract pressure gradient (RVOT-PGmax) ≥16 mmHg at rest; ③ Left ventricular ejection fraction (LVEF) \<50% on echocardiography; * Uncontrolled primary hypertension; * Moderate or severe aortic valve stenosis and/or primary mitral valve disease with severe mitral regurgitation; ⑥ Known infiltrative or storage disorders mimicking the HCM phenotype (e.g., Fabry disease, cardiac amyloidosis); ⑦ Presence of severe infections, hepatic dysfunction, renal impairment, or other serious conditions significantly affecting life expectancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage change in pressure gradient during the Valsalva maneuver | Week 36 | The percentage reduction in the pressure gradient at the site of left ventricular obstruction during the Valsalva maneuver at week 36, compared to baseline, as measured by echocardiography. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anterior papillary muscle to the interventricular septum distance | Week 36 | Percentage Increase in the distance from the anterior papillary muscle to the interventricular septum |
| Left atrial global longitudinal strain | Week 36 | Left Atrial Global Longitudinal Strain (LA GLS) is an echocardiographic parameter derived from speckle-tracking imaging that measures the longitudinal deformation of the left atrial myocardium throughout the cardiac cycle. |
| Left ventricular global longitudinal strain | Week 36 | Left Ventricular Global Longitudinal Strain (LVGLS) is a sensitive echocardiographic parameter derived from speckle-tracking imaging that quantifies the myocardial deformation in the longitudinal direction. It reflects the shortening of myocardial fibers along the long axis of the left ventricle during systole. |
| Percentage change in resting pressure gradient | Week 36 | The percentage reduction in the pressure gradient at the site of left ventricular obstruction at rest measured by echocardiography at week 36 compared to baseline. |
| Absolute change in pressure gradient during the Valsalva maneuver | Week 36 | The absolute decrease in number of the pressure gradient at the site of left ventricular obstruction during the Valsalva maneuver measured by echocardiography at week 36 compared to baseline. |
| The proportion of patients with a pressure gradient <30 mmHg during the Valsalva maneuver | Week 36 | The proportion of patients with a pressure gradient \<30 mmHg at the site of obstruction during the Valsalva maneuver at week 36. |
| BNP | Week 36 | Number decrease in BNP levels from baseline to week 36. |
| Troponin T | Week 36 | Number decrease in Troponin T levels from baseline to week 36. |
| New-onset atrial fibrillation | From baseline to week 36 | Rate of new-onset atrial fibrillation in each group during the study period |
| LVEF<50% | From baseline to week 36 | The proportion of patients in each group with LVEF \<50% accompanied by signs and symptoms of heart failure worsening and/or an increase in BNP of ≥30% compared to the previous measurement during the study period. |
| LVEF<40% | From baseline to week 36 | Rate of LVEF \<40% in each group during the study period. |
Countries
China
Outcome results
None listed