Multicenter Trial Aims to Alter Course of Hypertrophic Cardiomyopathy

Cardiomyopathy experts in the Cardiovascular Genetics Center at Brigham and Women’s Hospital are leading an international trial investigating benefits of therapy given in early hypertrophic cardiomyopathy (HCM). The multicenter trial aims to alter the course of hypertrophic cardiomyopathy and offers a targeted approach to sarcomere mutation carriers.

“Current therapy for HCM only palliates symptoms,” said Carolyn Y. Ho, MD, Medical Director of the Cardiovascular Genetics Center. “We are continuing our efforts to find ways to change the course of HCM by providing therapy early in the disease process with the ultimate goal of preventing HCM from developing at all.”


The Valsartan for Attenuating Disease Evolution in Early Sarcomeric HCM (VANISH) trial is a multicenter, Phase II, randomized clinical trial to assess the safety and efficacy of valsartan, an angiotensin receptor blocker, in attenuating disease evolution in early HCM. Sarcomere mutation carriers with asymptomatic or mildly symptomatic overt disease (NYHA class I-II) and mutation carriers without left ventricular hypertrophy (LVH) are being studied over a two-year period. Trial participants are between 8 and 45 years of age and are currently being enrolled at over 14 sites in the United States and Canada. Expansion to South America and Europe is planned in the near future.

A composite z-score statistical analysis approach will be used to detect treatment response reflecting different domains of myocardial injury, hemodynamic stress, collagen metabolism, functional capacity, myocardial fibrosis, cardiac morphology, and cardiac function. The study also will measure the impact of valsartan treatment on disease pathology, clinical outcomes and assessment of symptom burden, and incidence of adverse drug reactions, frequency of subject drop-out, and responses to validated quality-of-life metrics.

For more information or to refer a patient for consideration for the VANISH trial, please contact Principal Investigator Carolyn Y. Ho, MD, at (617) 732-7317 or

Pilot Study Success

The VANISH trial builds on the results of the team’s recent pilot trial that randomly assigned 38 sarcomere mutation carriers without LVH to therapy with diltiazem or placebo (JACC Heart Fail. 2015 Feb;3(2):180-8.). Treatment duration of the pilot study ranged from 12 to 42 months. Study procedures included electrocardiography, echocardiography, cardiac magnetic resonance imaging, and serum biomarker measurement.

Diltiazem was well tolerated and was not associated with serious adverse events. Some promising results of this pilot study included:

  • Left ventricular end diastolic diameter improved towards normal in the diltiazem group but decreased further in controls;
  • Mean LV thickness-to-dimension ratio was stable in the diltiazem group, but increased in controls;
  • Among MYBPC3 mutation carriers, LV wall thickness and mass, diastolic filling, and cardiac troponin I levels improved in those taking diltiazem compared with controls.

“Genetic testing to identify sarcomere mutation carriers offers us the opportunity to modify the progression and emergence of disease at a time when disease-modifying therapy may be most effective. Such strategies have the potential to transform clinical practice in HCM,” said Dr. Ho. “The goal of our Center is to use our research discoveries to improve clinical care for our patients and families with HCM and other inherited heart disease using targeted approaches.”

About the Cardiovascular Genetics Center

The Cardiovascular Genetics Program at Brigham and Women’s Hospital is composed of a multidisciplinary team of internationally recognized physicians and investigators who collaborate to apply the latest discoveries in research on inherited cardiac disease to deliver personalized care for patients. The team provides genetic testing, counseling, and specialized care for families with inherited heart disease, including:

  • Hypertrophic cardiomyopathy;
  • Dilated cardiomyopathy;
  • Arrhythmogenic Right Ventricular Cardiomyopathy;
  • Long QT Syndrome and other inherited arrhythmias, including Brugada Syndrome, catecholaminergic polymorphic ventricular tachycardia; Familial atrial fibrillation;
  • Familial sudden cardiac death;
  • Inherited aortic aneurysms;
  • Marfan syndrome and other connective tissue disorders;
  • Premature coronary artery disease/myocardial infarction.

Christine Seidman, MD,
Director, Cardiovascular Genetics Center, Brigham and Women's Hospital

Carolyn Y. Ho, MD,
Medical Director, Cardiovascular Genetics Center, Brigham and Women's Hospital

Neal K. Lakdawala, MD,
Cardiovascular Genetics Center, Brigham and Women's Hospital

Calum A. MacRae, MD, PhD,
Chief, Division of Cardiovascular Medicine; Cardiovascular Genetics Center, Brigham and Women's Hospital

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