Effects of Losartan on Left Ventricular Hypertrophy and Fibrosis in Patients With Nonobstructive Hypertrophic Cardiomyopathy

Abstract

Structured Abstract Objectives To evaluate the effects of losartan on left ventricular (LV) hypertrophy and fibrosis in patients with nonobstructive hypertrophic cardiomyopathy (HCM). Background Despite evidence that myocardial hypertrophy and fibrosis are mediated by angiotensin II and are important determinants of morbidity and mortality in HCM, no prior study has evaluated the effects of angiotensin receptor blockers (ARBs) on LV hypertrophy and fibrosis with cardiac magnetic resonance imaging (CMR). Methods In double-blind fashion, 20 patients (3 women; age 51±13 years) with HCM were randomly assigned to receive placebo (n=9) or losartan 50 mg twice a day (n=11) for 1 year. CMR was performed at baseline and 1 year to measure LV mass and extent of fibrosis as assessed by late gadolinium enhancement (LGE). Results 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, with the placebo group having larger increase (+31 ± 26 % on placebo vs. −23 ± 45 % on losartan; p=0.03). Conclusions This pilot study suggests attenuation of progression of myocardial hypertrophy and fibrosis by losartan in patients with nonobstructive HCM. Confirmation of these results in a larger trial is required to confirm a place for ARBs in the management of HCM.

Cardiac Fibrosis

“…158–160 Clinically, losartan is thought to attenuate the progression of myocardial hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy. 161 These data present a compelling argument that AngII is a potent fibrotic mediator, and that the protective effects of AngII antagonists may partly be due to their ability to reduce cardiac fibrosis. Further studies will be needed to mechanistically establish the effects of AngII inhibition specifically in CFs, which may lead to refinement of ACE/AngII/receptor inhibitors and allow for more direct targeting of the pathway’s pathologic activation of this cell population.…”

Functional effects of losartan in hypertrophic cardiomyopathy—a randomised clinical trial

“…Penicka et al 13 found that a decrease in LVM was accompanied by an increase in tissue velocities and an increase in exercise time in patients (n=12) treated with candesartan compared with patients treated with placebo (n=11). On the other hand, Shimada et al 18 did not identify significant differences in functional measures between the treatment arms despite a decrease in LGE and a trend towards a decrease in LVM in patients treated with losartan (n=20). In this much larger study, we found no effect of losartan on any of the assessed structural or functional variables.…”

Getting to the Heart of the Matter

“…46 Importantly, in a small study, losartan was shown to diminish progression of myocardial hypertrophy and fibrosis in patients with nonobstructive hypertrophic cardiomyopathy. 47 These data collectively suggest that the protective effects of losartan may be due, in part, to its ability to suppress cardiac fibrosis.…”