Cardiomyopathy
Effect of Losartan on Left Ventricular Diastolic Function in Patients With Nonobstructive Hypertrophic Cardiomyopathy

https://doi.org/10.1016/j.amjcard.2005.07.065Get rights and content

In hypertrophic cardiomyopathy (HC), diastolic dysfunction of the left ventricle is a prominent feature caused by myocardial hypertrophy and fibrosis. Angiotensin II has trophic and profibrotic effects on the heart, and the blockade of angiotensin II receptors reverses hypertrophy and fibrosis in human cardiac diseases and in animal HC. This study investigated the short-term (6 months) effects of losartan 100 mg/day in 20 patients with nonobstructive HC, with an emphasis on left ventricular (LV) diastolic dysfunction, compared with 10 patients with HC who were not treated. At the final evaluation, significant changes were observed in the losartan group: a left atrial diameter decrease (p <0.0001), a tissue Doppler early (Ea) mitral annulus diastolic velocity increase (p = 0.003) and an E/Ea ratio decrease (p = 0.0002), and a significant decrease in plasma levels of the aminoterminal fragment of pro–brain natriuretic peptide (NT–pro-BNP) from a median of 860 to 606 pg/ml (p = 0.001). A significant correlation was found between percentage changes in NT–pro-BNP and the E/Ea ratio from baseline to 6 months (r = 0.61, p = 0.002). In the 2 groups, echocardiographic LV wall and cavity measures did not change. In conclusion, in selected patients with nonobstructive HC, losartan during a 6-month period improved LV diastolic function.

Section snippets

Selection of participants

The study subjects were consecutively recruited from the HC ambulatory center of the Heart Institute of the University of Sao Paulo Medical School, a university tertiary referral center. The elected patients fulfilled the entry criteria, which were as follows: established clinical diagnosis of HC supported by echocardiographic left ventricular (LV) wall thickness ≥15 mm, age 18 to 50 years, sinus rhythm, normal blood pressure (upper limit 140/90 mm Hg), a normal LV ejection fraction, and the

Results

Table 1 lists baseline characteristics of the study population. There were no significant differences in categorical and numerical variables between treated and nontreated groups on entry into the study. A large proportion of patients were symptomatic, which can be ascribed to the selected pattern of this HC population. Overall, the largest obtained LV outflow peak gradient at rest was 24 mm Hg. Using 30 mm as the cut-off value for massive hypertrophy, the mean interventricular septum thickness

Discussion

In this study, symptomatic improvement, left atrial diameter reduction, Doppler changes, and plasma NT–pro-BNP reduction were concordant findings, suggesting that angiotensin II antagonism with losartan was able to induce the amelioration of LV diastolic dysfunction in our patients with HC. The reported symptomatic reduction needs to be interpreted with caution, because a placebo effect cannot be ruled out. Left atrial enlargement has been associated with chronic diastolic dysfunction,12 and

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