Different from heart failure with reduced ejection fraction (HFREF), for which large studies have demonstrated the effectiveness of drug treatment to improve morbidity and mortality, no treatment study has shown definitive results in patients with heart failure with normal ejection fraction (HFNEF). HFNEF is more prevalent in women and the elderly and it is associated with multiple comorbidities. Although the optimum treatment has yet to be defined, the control of arterial hypertension and decreased fluid overload are important measures to control the syndrome. In Brazil, the recommendations for the treatment of HF are based on the Review of the II Directives of the Brazilian Society of Cardiology for the diagnosis and treatment of Heart Failure-2002. However, none of the recommendations is specific for patients with HFNEF, as they are based on general measures proposed by specialists. This review aims at demonstrating the scientific evidence from recent clinical trials in HFNEF and future perspectives in terms of new medications.

Background-In pulmonary arterial hypertension (PH), sympathetic adrenergic activity is highly elevated. Sympathetic overactivity is a compensatory mechanism at first, but might be detrimental for cardiac function in the long run. We therefore investigated whether chronic low-dose treatment with bisoprolol (a cardioselective ␤-blocker) has beneficial effects on cardiac function in experimental PH. Methods and Results-PH was induced in rats by a single injection of monocrotaline (60 mg/kg). Pressure telemetry in PH rats revealed that 10 mg/kg bisoprolol was the lowest dose that blunted heart rate response during daily activity. Ten days after monocrotaline injection, echocardiography was performed and PH rats were randomized for bisoprolol treatment (oral gavage) or vehicle (nϭ7/group). At end of study (body mass loss Ͼ5%), echocardiography was repeated, with additional pressure-volume measurements and histomolecular analyses. Compared with control, right ventricular (RV) systolic pressure and arterial elastance (measure of vascular resistance) more than tripled in PH. Bisoprolol delayed time to right heart failure (PϽ0.05). RV afterload was unaffected, however, bisoprolol treatment increased RV contractility and filling (both PϽ0.01), and partially restored right ventriculo-arterial coupling and cardiac output (both PϽ0.05). Bisoprolol restored RV ␤-adrenergic receptor signaling. Histology revealed significantly less RV fibrosis and myocardial inflammation in bisoprolol treated PH rats. Conclusions-In experimental PH, treatment with bisoprolol delays progression toward right heart failure, and partially preserves RV systolic and diastolic function. These promising results suggest a therapeutic role for ␤-blockers in PH that warrants further clinical investigation. (Circ Heart Fail. 2012;5:97-105.)Key Words: pulmonary hypertension Ⅲ right ventricular dysfunction Ⅲ ␤-adrenergic receptor blocker Ⅲ pressure-volume relationship Ⅲ Wistar rats P ulmonary arterial hypertension (PH) is a fatal disease, characterized by progressive vascular remodeling and increased right ventricular (RV) afterload, which eventually leads to manifest right heart failure (RHF) and premature death. Current available medical treatments aim to reduce RV afterload, thereby secondarily improving RV function. 1 No treatment is currently available that improves RV function directly, partially because it was not considered a therapeutic target in PH. 2 Clinical Perspective on p 105Recently, several reports have shown that sympathetic activity is increased in patients with PH. [3][4][5][6][7] Similar to left heart failure (LHF), "ventricle-specific" down regulation of ␤ 1 -adrenergic receptors was observed in RV samples of PH patients. 8 In addition, we recently demonstrated that exercise training was detrimental in experimental and progressive PH. 9 The deleterious effects could be related to bouts of exercise-induced sympathetic stimulation.Although increased adrenergic activity is a compensatory mechanism to maintain cardiac function by increasi...