REGRESSION OF HYPERTROPHY (AND FIBROSIS?) IN HYPERTROPHIC CARDIOMYOPATHY


Michael A. Fifer, M.D., Massachusetts General Hospital, Boston, MA, USA

Left ventricular (LV) hypertrophy and fibrosis are important determinants of morbidity and mortality in hypertrophic cardiomyopathy (HCM). Regression of hypertrophy remote from the interventricular septum is observed after septal reduction therapy with myectomy or alcohol ablation. A number of drug classes have been put forward as potential modifiers of the natural history of HCM. Animal and human studies have suggested that angiotensin II receptor blockers (ARBs) attenuate progression of hypertrophy and fibrosis in HCM. In a mouse model of HCM, the ARB losartan reversed cardiac interstitial fibrosis. In double-blind fashion, we randomly assigned patients (3 women; age 51±13 years) with HCM to receive placebo (n=9) or losartan 50 mg twice a day (n=11) for 1 year. Patients with LV outflow tract gradient > 30 mmHg at rest or with Valsalva maneuver were excluded. CMR was performed at baseline and at 1 year to measure LV mass and extent of fibrosis as assessed by late gadolinium enhancement (LGE). There was a trend towards a significant difference in the percent change in LV mass (median [interquartile range], +5 [-4, +21] % on placebo vs. -5 [-11, -0.9] % on losartan; p=0.06). There was a significant difference in the percent change in extent of LGE (mean ± standard deviation, +31±26 % on placebo vs. -23±45 % on losartan; p=0.03).Our study demonstrated attenuation of progression of myocardial fibrosis by losartan in patients with nonobstructive HCM. A similarly designed study by another group showed no demonstrable effect of spironolactone. Verification of our results in a larger trial is required to confirm a place for ARBs in the management of HCM. We are currently participating in a multicenter trial of the ARB valsartan in genotype positive patients with overt or latent HCM.