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Apelin is an endogenous peptide that increases cardiac inotropism through its APJ receptor. Certain findings indicate that the apelinergic system may have a pathophysiological role in cardiovascular disease and there is evidence showing the role of the apelinergic system in blood pressure regulation in vitro and in animal models. The role of the apelin-APJ system in cardiovascular physiology and its interaction with other neuroendocrine pathways has not been fully elucidated. However, the small number of reported studies indicates that apelin signaling may be involved in the regulation of blood pressure, cardiac contractile function, fluid balance, angiogenesis and inhibition of apoptosis. We evaluated the possible relationship between the G212A and A445C APJ polymorphisms and coronary artery disease (CAD) in Italian patients and in healthy controls by RFLP-PCR. We analyzed the allelic and genotypic frequencies of APJ polymorphisms in 664 patients (378 with hypertension) and 143 controls. There were no differences between allelic and genotypic frequencies in patients in respect to the controls for both polymorphisms analyzed. In the CAD population, there was an increased frequency of the G212 allele in patients with hypertension in respect to patients without hypertension. No differences were present in the two subgroups for the A445C polymorphism. Although the functional role of the G212A polymorphism has not yet been identified, it is possible to hypothesize that the presence of the A allele may cause a gain in function of the apelin/APJ system associated with a lower risk of hypertension.

Cardiac resynchronization therapy (CRT) is a novel and effective therapy for patients with heart failure. The aim of CRT is to improve the heart's pumping efficiency by the resynchronization of the chambers. Electrical dyssynchrony shows itself as bundle branch block with prolongation of QRS >120 ms. Mechanical dyssynchrony (atrioventricular, interventricular and intraventricular) is evidenced by echocardiographic parameters. A cardioverter-defibrillator function can be included with the pulse generator in patients with high risk of sudden death. The estimate of perioperative death associated with CRT was 0.3% with a low rate of complications, similar to that seen in standard pacemaker placement. In 10% of patients there was an implant failure due to the difficulty in accessing the coronary sinus. Approximately one third of patients are non-responder with no significant improvement after implantation. The beneficial effect of CRT on soft endpoints and mortality (symptoms, NYHA class, 6-min walking test, quality of life score, ejection fraction) was demonstrated in the earliest randomized clinical trials. Current guidelines for CRT are based on inclusion and exclusion criteria in the large randomized trials that have been performed and patients with chronic atrial fibrillation are included. Unresolved issues are the identification of non-responders and the efficacy of CRT in patients with mechanical dyssynchrony without electrical dyssynchrony and in NYHA functional class I/II patients with ejection fraction < or = 35%.