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CLINICAL RESEARCH: HEART FAILURE

Impact of Blockade of Histamine H₂ Receptors on Chronic Heart Failure Revealed by Retrospective and Prospective Randomized Studies

Cardiovascular Division, National Cardiovascular Center, Suita, Japan

Manuscript received April 11, 2006; revised manuscript received May 18, 2006, accepted May 23, 2006.

^_* Reprint requests and correspondence: Dr. Masafumi Kitakaze, Cardiovascular Division, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita City, Osaka Pref. 565-8565, Japan (Email: kitakaze{at}zf6.so-net.ne.jp).

OBJECTIVES: The goal of this work was to determine whether the blockade of histamine H₂ receptors is beneficial for the pathophysiology of chronic heart failure (CHF).

BACKGROUND: Because CHF is one of the major life-threatening diseases, we need to find a novel effective therapy. Intriguingly, our previous study, which predicts the involvement of histamine in CHF, suggests that we should test this hypothesis in patients with CHF.

METHODS: We selected 159 patients who received famotidine among symptomatic CHF patients for the retrospective study. We blindly selected age- and gender-matched CHF patients receiving drugs for gastritis other than histamine H₂ receptor blockers as a control group. For the prospective study, 50 symptomatic CHF patients were randomly divided into 2 groups. One group received famotidine of 30 mg/day for 6 months, and the other group received teprenone.

RESULTS: In the retrospective study, famotidine of 20 to 40 mg decreased both left ventricular end-diastolic and end-systolic lengths (LVDd and LVDs, respectively) and the plasma B-type natriuretic peptide (BNP) levels (182 ± 21 vs. 259 ± 25 pg/ml, p < 0.05) with unaltered fractional shortening (FS). In a randomized, open-label study, compared with teprenone, famotidine of 30 mg prospectively decreased both New York Heart Association functional class (p < 0.05) and plasma BNP levels (183 ± 26 pg/ml vs. 285 ± 41 pg/ml, p < 0.05); this corresponded to decreasing both LVDd (57 ± 2 mm vs. 64 ± 2 mm, p < 0.05) and LVDs (47 ± 2 mm vs. 55 ± 2 mm, p < 0.05) with unaltered FS (15 ± 1% vs. 17 ± 1%). The frequency of readmission because of worsening of CHF was lower in the famotidine group (4% and 24%, p < 0.05). On the other hand, teprenone had no effects on CHF.

CONCLUSIONS: Famotidine improved both cardiac symptoms and ventricular remodeling associated with CHF. Histamine H₂ receptor blockers may have therapeutic benefits for CHF.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   AMP = adenosine monophosphate   BNP = brain natriuretic peptide   CHF = chronic heart failure   FS = fractional shortening   GERD = gastroesophageal reflux disease   LVDd = left ventricular end-diastolic volume   LVDs = left ventricular end-systolic volume   NYHA = New York Heart Association

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