Abstract: Cardiac pacing from the right ventricular apex is the most common site of cardiac pacing. During the last decade, several studies demonstrated the harmful effects of the iatrogenic left bundle branch block, which is observed in cardiac pacing from the right ventricular apex. These observations led to an interest in alternative right ventricular pacing sites aiming to achieve a more "physiological" pattern of ventricular activation. Alternate site pacing may involve His bun- dle, other right ventricular sites (outflow or septal sites), or left ventricular sites in either unifocal or bifocal or biventricular modes. Pacing from the right ventricular outflow tract has been studied extensively. Several studies showed that right ventricular outflow tract pacing has better hemodynamic effects and less harmful influence. Bifocal right ventricular (apical and outflow tract) pacing has been proposed for patients with heart failure where the coronary sinus approach to effect biventricular pacing turns out to be unsuccessful because of various reasons. Some studies examined left ventricular pacing alone as an alternative mode of pacing, and the results were quite encouraging but not conclusive. Finally, in heart failure patients not responding to biventricular pacing, the triple site pacing mode has been recently proposed. In triple site pacing, the leads are inserted in the right ventricular apex and outflow tract in conjunction with lateral left ventricular pacing. Improvement of exercise capacity and increased ejection fraction were observed with this triventricular pacing. Although more data from specifically designed randomized studies are needed, there are many alternative pacing sites, especially for patients at high risk of heart failure, which seems to be less harmful and better tolerated by the patients.

Abstract: The purpose of our study was assessment of the relative contribution of the systems involved in blood gas exchange to the limited exercise capacity in patients with beta-thalassemia major (TM) using integrative cardiopulmonary exercise testing (CPET) with estimation of oxygen kinetics. The study consisted of 15 consecutive TM patients and 15 matched controls who performed spirometric evaluation, measurement of maximum inspiratory pressure (Pimax) and an incremental symptom-limited CPET on a cycle ergometer. Exercise capacity was markedly reduced in TM patients as assessed by peak oxygen uptake (pVO(2), mL/kg/min: 22.1+/-6.6 vs 33.8+/-8.3; P<0.001) and anaerobic threshold (mL/kg/min: 13.0+/-3.0 vs 18.7+/-4.6; P<0.001) compared with controls. No ventilatory limitation to exercise was noted in TM patients (VE/VCO(2) slope: 23.4+/-3.2 vs 27.8+/-2.6; P<0.001 and breathing reserve, %: 42.9+/-17.0 vs 29.5+/-12.0; P<0.005) and no difference in oxygen cost of work (peak VO(2)/WR, mL/min W: 12.2+/-1.7 vs 12.2+/-1.5; P=NS). Delayed recovery oxygen kinetics after exercise was observed in TM patients (VO(2)/t slope, mL/kg/min(2): 0.67+/-0.27 vs 0.93+/-0.23; P<0.05) that was significantly correlated with Pimax at rest (r: 0.81; P<0.001). The latter was also significantly correlated to pVO(2) (r: 0.84; P<0.001) and inversely correlated to ferritin levels (r: -0.6; P<0.02). Exercise capacity is markedly reduced in TM patients and this reduction is highly associated with the limited functional status of peripheral muscles.

Abstract: BACKGROUND: This study was designed to investigate the association of the 894G>T polymorphism in the eNOS gene with risk of acute myocardial infarction (AMI), extent of coronary artery disease (CAD) on coronary angiography, and in-hospital mortality after AMI. METHODS: We studied 1602 consecutive patients who were enrolled in the GEMIG study. The control group was comprised by 727 individuals, who were randomly selected from the general adult population. RESULTS: The prevalence of the Asp298 variant of eNOS was not found to be significantly and independently associated with risk of AMI (RR = 1.08, 95%CI = 0.77-1.51, P = 0.663), extent of CAD on angiography (OR = 1.18, 95%CI = 0.63-2.23, P = 0.605) and in-hospital mortality (RR = 1.08, 95%CI = 0.29-4.04, P = 0.908). CONCLUSION: In contrast to previous reports, homozygosity for the Asp298 variant of the 894G>T polymorphism in the eNOS gene was not found to be associated with risk of AMI, extent of CAD and in-hospital mortality after AMI.

Abstract: BACKGROUND: Prolonged oxygen uptake kinetics (O2 kinetics), following the onset of a constant workload of exercise has been associated with a poor prognosis in patients with chronic heart failure. This study aimed to determine both continuous and interval training effects on the different O2-kinetics phases in these patients. DESIGN: Twenty-one patients (60+/-8 years) with stable chronic heart failure participated in a 36-session exercise rehabilitation program (three times weekly). Patients were randomly assigned to interval training (n=11; 100% of peak work rate for 30 s, alternating with 30 s-rest) and to continuous training (n=10; 50% of peak work rate). METHODS: Before and after the completion of the program, all patients performed both incremental symptom-limited and constant workload submaximal cardiopulmonary exercise tests. Phase I O2-kinetics was evaluated by time (t), from the start of exercise until the onset of decreased respiratory exchange ratio and phase II by the time constant (tau) of the response from the end of phase I until steady state. RESULTS: After training, there was a significant increase in peak oxygen uptake and peak work rate in both continuous (15.3+/-4.4 vs. 16.6+/-4.5 ml/kg per min; P=0.03 and 81.8+/-40.1 vs. 94.7+/-46.1 W; P=0.03) and interval training groups (14.2+/-3.1 vs. 15.4+/-4.2 ml/kg per min; P=0.03 and 82.5+/-24.1 vs. 93.7+/-30.1 W; P=0.04). Patients who underwent interval training had a significant decrease in t (39.7+/-3.7 to 36.1+/-6.9 s; P=0.05), but not tau (59.6+/-9.4 to 58.9+/-8.5 s; P=ns), whereas those assigned to continuous training had a significant decrease in both t (40.6+/-6.1 to 36.4+/-5.4 s; P=0.01) and tau (63.3+/-23.6 to 42.5+/-16.7 s; P=0.03). CONCLUSIONS: Exercise training improves O2 kinetics in chronic heart failure patients. Both continuous and interval training improve phase I O2-kinetics, but continuous training results in superior improvement of the phase II O2-kinetics, an indirect index of muscle oxidative capacity.

Abstract: The role of heart rate reduction in the management of myocardial ischemia and chronic stable angina is pivotal. However, broad use and appropriate dosing of commonly used rate-slowing drugs is limited by their poor tolerability. Ivabradine is a selective inhibitor of the If currents of the sinoatrial node cells. If currents activity determines the slope of the depolarization curve towards the threshold level controlling heart rate in patients with sinus rhythm. Ivabradine, a compound of the benzocyclobutane (S 16257), exhibits a unique specificity for the If current and has a more favorable profile of adverse reactions compared to other If inhibitors. Accordingly, ivabradine has been used in the treatment of stable angina, where it presented anti-anginal and anti-ischemic effects equivalent to the effects of atenolol and amlodipine. Clinical studies proved the efficacy of ivabradine in patients with stable angina, while clinical data are awaited to verify its probable value in the treatment of atrial tachyarrhythmias and tachycardia due to ventricular dysfunction. Thus, the clinical value of ivabradine, which has completed clinical development for stable angina, is expected to exceed its role in the treatment of myocardial ischemia. In this context, ivabradine, promising efficacious and safe pharmacological management of heart rate, is a huge step in cardiovascular therapeutics.