Myocardial Fibrosis | Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy
Myocardial Fibrosis research study
What is the primary objective of this study?
Hypertrophic Cardiomyopathy (HCM) is the most common genetic cardiomyopathy and remains the leading cause of sudden cardiac death in young people and an important cause of heart failure symptoms and death at any age. In HCM, pathological remodeling of the left ventricle involving myocardial fibrosis is likely a major contributor to cardiac dysfunction and also a nidus for the generation of ventricular arrhythmias. Serum markers of collagen turnover have been shown to reliably reflect the magnitude of myocardial fibrosis in a variety of cardiovascular diseases. In addition, aldosterone antagonist drugs have been shown to decrease fibrous tissue formation in the myocardium in certain pathologic cardiovascular states in which aldosterone production is increased. In HCM, aldosterone production is up-regulated and has been implicated in the formation of myocardial fibrosis. Therefore, the specific aims of this proposal are to: 1. assess serum markers of collagen turnover at baseline and correlate these findings with a variety of clinical and morphologic disease parameters 2. examine the effects of a 12-month treatment with the aldosterone antagonist spironolactone on magnitude of fibrosis as measured by serum markers of collagen turnover as well as changes in clinical and morphologic disease parameters. The results of this proposal will offer important insights into the clinical significance of myocardial fibrosis in this primary genetic cardiomyopathy. The demonstration that spironolactone decreases fibrosis and improves clinical course would provide the rational for a larger multicenter clinical trial evaluating this novel therapy for improving clinical outcome in patients with HCM.
Who is eligible to participate?
Inclusion Criteria: 1. Hypertrophic cardiomyopathy 2. Able to swallow pills 3. No prior septal reduction therapy 4. Negative serum or hCG pregnancy test Exclusion Criteria: 1. Unable or unwilling to perform treadmill cardiopulmonary exercise test 2. Prior surgical myectomy or alcohol septal ablation 3. Known or suspected infiltrative or glycogen storage disease 4. Significant coronary artery disease, defined as atherosclerotic coronary artery narrowing >70% of the luminal diameter by coronary angiography 5. Severe obstructive pulmonary disease, defined as forced expiratory volume in 1 second (FEV1) <50% of predicted. 6. Prior intolerance or adverse reaction to aldosterone receptor antagonist. 7. History of hyper or hypoaldosteronism 8. Baseline serum potassium >5.0 mmol/L. 9. Calculated creatinine clearance <30 ml/min using Cockcroft-Gault formula. 10. Pregnant or breast feeding 11. Poorly controlled systemic hypertension, defined as systolic blood pressure ≥150 mmHg or diastolic pressure ≥100 mmHg, during 2 clinic visits. 12. Known conditions associated with elevated serum concentrations of PIIINP (e.g., chronic liver disease, diabetes mellitus, tumors, pulmonary fibrosis, bone and rheumatoid diseases, extensive wounds) or PINP (e.g., alcoholic liver disease, metabolic bone disease, thyroid disorders), including recent trauma (≤2 weeks) or surgery (≤6 months) 13. Taking drugs known to directly influence collagen metabolism including, amiodorone, ACE or angiotensin II inhibitors, aldosterone antagonists, statins, glucocorticoids and estrogens 14. Patients with ICDs/pacemakers will be recruited in the study, but will be excluded from the CMR component.
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:spironolactonespironolactone 50mg daily
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
Start Date: November 2007
Completed Date: November 2012
Phase: Phase 4
Primary Outcome: changes in serum markers of collagen turnover
Secondary Outcome: measures of diastolic function by echocardiography
Study sponsors, principal investigator, and references
Lead Sponsor: Tufts Medical Center