Background: recent short-term observations have shown an improvement in cardiac function and heart failure symptoms from atrio-biventricular pacing. This study was designed to assess the safety and feasibility of an atrio-biventricular transvenous pacing system, and examine the long-term effects of cardiac resynchronization in patients with advanced heart failure and ventricular conduction abnormalities. Methods and results: between August, 1997 and November, 1998, 103 patients received a cardiac resynchronization system (CRS) consisting of a pulse generator interfaced with an atrio-biventricular lead system, including a lead designed for left ventricular (LV) pacing via cardiac veins. Baseline evaluation included 12-lead electrocardiogram, estimation of New York Heart Association (NYHA) functional class, assessment of quality of life (QOL), and distance covered during a 6-min walk (6-MW). Detailed echocardiographic data were also collected in a subset of 46 patients. Measurements were repeated in all surviving patients at 1, 3, 6 and 12 months after implantation of the CRS. A single, self-limiting procedure-related complication occurred. Over a follow-up of 12 months, 21 patients died. The 12-month actuarial survival was 78% (CI 70-87%). Nine surviving patients were withdrawn from the study during long-term follow-up for miscellaneous reasons. At each point of follow-up, a significant shortening of QRS duration was measured. In addition, significant improvements were observed in mean NYHA functional class, 6-MW and QOL score. In the 46 patients with complete echocardiographic data, LV ejection fraction increased from 21.7"6.4% at baseline to 26.1"9.0% at last follow-up (Ps0.006), LV end diastolic dimension decreased from 72.7"9.2 to 71.6"9.1 mm (Ps0.233), interventricular mechanical delay decreased from 27.5"32.1 to 20.3"25.5 ms (Ps 0.243), mitral regurgitation apical four-chamber area decreased from 7. 66"5.5 to 6.69"5.9 cm (Ps0.197), and left ventricular 2 filling time increased from 363"127 to 408"111 ms (Ps0.002). Conclusions: long-term cardiac resynchronization can be safely and reliably achieved by transvenous atrial synchronized right and left ventricular pacing. These changes were accompanied by clinically relevant improvements in functional status and QOL, as well as a measurable increase in LV performance. The outcome of randomised controlled trials is awaited. ᮊ

Background-The mechanisms underlying the variation in collateral formation between patients, even with similar patterns of coronary artery disease, remain unclear. This study investigates whether circulating humoral or cellular factors can provide an insight into this variation. Methods and Results-Thirty patients with isolated left anterior descending coronary artery disease underwent percutaneous coronary intervention with collateral flow index (CFI) determined using a pressure wire. Patients with inadequate (CFI Ͻ0.25) compared with those with adequate (CFI Ն0.25) collateral support had, or tended to have, lower concentrations of coronary sinus growth factors and plasma exerting a weaker effect on endothelial cell migration and angiogenesis in vitro. However, there was an inverse correlation between serum mitogenicity and CFI (rϭϪ0.61, PϽ0.01). No significant differences were detected between the 2 groups in plasma levels of total vascular endothelial growth factor, vascular endothelial growth factor 165 , or placental growth factor. There was a strong positive correlation between numbers of CD34/CD133-positive circulating hemopoietic precursor cells and CFI (rϭ0.75, PϽ0.001). In patients with inadequate, compared with those with adequate, CFI, the numbers of differentiated endothelial progenitor cells (EPCs) appearing in the circulation and in culture were significantly reduced by 75% (PϽ0.05) and 70% (PϽ0.05), respectively. Conclusions-In this study, inadequate coronary collateral development is associated with reduced numbers of circulating EPCs and impaired chemotactic and proangiogenic but not mitogenic activity. These findings are consistent with current efforts to enhance collateral formation by augmentation of circulating EPCs.