The Effect of TASH in Patients With HOCM

Study Overview
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Brief Summary
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To examine patients with hypertrophic obstructive cardiomyopathy (HOCM) before and after septal alcohol ablation, to investigate the effect of the treatment in regards to changes in myocardial function, perfusion, invasive hemodynamics and exercise tolerance.

Detailed Description
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Patients with HOCM who develop symptoms of heart failure are treated initially with non-vasodilating ß-blockers or verapamil to decrease myocardial contractility and heart rate. A substantial part of patients remain symptomatic despite medical treatment. In these patients interventional or surgical treatments (septal reduction therapies (SRT)) to reduce left ventricular outflow tract obstruction (LVOTO) is considered in the presence of moderate to-severe symptoms (New York Heart Association - functional class (NYHA) III-IV) and/or recurrent exertional syncope and an LVOTO gradient ≥50 mm Hg. In some centers, invasive therapy is also considered in patients with mild symptoms (NYHA Class II) who have a resting or maximum provoked gradient of ≥50 mm Hg (with exercise or Valsalva's maneuver) and moderate-to-severe mitral valve regurgitation. Advanced treatment options are alcohol septal ablation (ASA) or surgical myectomy often combined with mitral valve reconstructive surgery. These treatments have similar outcomes in terms of gradient reduction, symptom improvement and exercise capacity No previous trials have examined the effect of ASA in HOCM with respect to changes in central hemodynamics and myocardial performance during exercise. 24 HOCM patients will be examined prior to ASA, and approximately six-nine months after ASA. The examination set-up consists of simultaneous 1) transthoracic echocardiography (TTE), 2) right heart catheterization (RHC) and 3) cardiopulmonary exercise test (CPX).

Official Title
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The Effect of Alcohol Septal Ablation Therapy on Left Ventricular Function and Invasive Hemodynamics at Rest and During Exercise in Patients With Hypertrophic Obstructive Cardiomyopathy

Conditions
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Hypertrophic Obstructive Cardiomyopathy

Intervention / Treatment
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* Procedure: alcohol septal ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Left ventricular wall thickness ≥ 15 mm in one or more myocardial segments that is not explained by loading conditions LVOT gradients ≥ 30 mmHg at rest and/or ≥ 50 mmHg at Valsalva's maneuver or exercise NYHA ≥ III Exclusion Criteria: < 18 years Fertile women who do not use anti-contraceptives Pregnancy Patients are allowed to have a pacemaker (eg. an implantable cardioverter defibrillator (ICD)) but cannot be pace-dependent Amiodarone treatment Persistent or permanent atrial fibrillation/flutter Previous SRT Alcohol or drug abuse Significant co-morbidity (judged by the investigator) Patients who cannot give valid consent (e.g. mental illness or dementia) or who do not understand Danish.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: prospective controlled study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Hypertrophic obstructive cardiomyopathy<br>injection of 1-4 mL of 96% ethanol into a septal perforator of the left anterior coronary artery to produce a myocardial infarction | Procedure: alcohol septal ablation<br>* injection of 1-4 mL of 96% ethanol into a septal perforator of the left anterior coronary artery to produce a myocardial infarction<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary capillary wedge pressure (PCWP) during exercise | Change in PCWP at 75 watt (or maximum exercise, if this is < 75 W) | Changes will be evaluated after an expected average of 6-9 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary capillary wedge pressure (PCWP) at rest | Changes in PCWP at rest | Changes will be evaluated after an expected average of 6-9 months after treatment | 
| Peak oxygen uptake (VO2-max) | Changes in maximal oxygen consumption (L/min) measured during cardiopulmonary exercise test | Changes will be evaluated after an expected average of 6-9 months after treatment | 
| Work capacity | work capacity measured in watt during a cardiopulmonary exercise test | Changes will be evaluated after an expected average of 6-9 months after treatment | 
| LVOT gradient during maximum exercise | Changes of the LVOT gradient during maximum exercise, measured in mmHg during 2D echocardiography | Changes will be evaluated after an expected average of 6-9 months after treatment | 
| Coronary flow reserve | Changes in the ratio of maximum coronary blood flow (induced by infusion of adenosin) to resting coronary blood flow, estimated by 2D doppler echocardiography | Changes will be evaluated after an expected average of 6-9 months after treatment | 
| Changes in biomarkers | Changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) ng/l and troponin T ng/l | Changes will be evaluated after an expected average of 6-9 months after treatment | 
| Change in GLS (%) at peak exercise | Change in global longitudinal strain (GLS) in % at peak exercise | Changes will be evaluated after an expected average of 6-9 months after treatment | 
| Changes of symptoms and quality of life estimated by KCCQ | Changes of symptoms and quality of life with Kansas City Cardiomyopathy Questionnaire (KCCQ) assessed by clinical evaluation | Changes will be evaluated after an expected average of 6-9 months after treatment |