BLOCK-HF: CRT gains new ground

The detrimental effects of chronic right ventricular (RV) pacing were first demonstrated 10 years ago when the DAVID trial clearly demonstrated the hazards of unnecessary RV pacing including worsening left ventricular (LV) function, increased heart failure hospitalization and increased mortality. This finding was confirmed in other studies, prompting the development of various device algorithms to ensure that periods of RV pacing are kept at an absolute minimum, with the ultimate aim of preserving LV function. More recently, the 2012 AHA/ACC/HRS and the 2013 ESC/EHRA practice guidelines recommended de novo cardiac resynchronization therapy (CRT) in patients who had indications for permanent pacing with underlying severe LV dysfunction. It is unknown whether receiving a biventricular (BiV) pacing device at the time of the initial implant – rather than a standard pacemaker – would help preserve LV function in patients with milder degrees of LV systolic dysfunction and a conventional indication for anti-bradycardia pacing. The Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK-HF) trial was designed to answer this question. The prospective, multicenter, double-blind study randomized 691 patients with LV ejection fraction (LVEF) of #50%, New York Heart Association (NYHA) functional class I-III heart failure symptoms, and atrioventricular (AV) block to undergo either standard RV pacing or BiV pacing. To preserve doubleblinding and equalize risk, a full set of CRT leads was implanted in both groups, with the LV lead being active only in patients randomized to the BiV group. Patients with a “guideline indication” for CRT were excluded from the study. The study’s protocol was revised in 2005 (two years after launching the trial) to allow for using implantable cardioverter-defibrillators (ICDs) when indicated. The mean LVEF for the cohort was 40 ^ 8% (43% in the pacemaker group and 33% in the ICD group) and the mean QRS duration was 124 ^ 31 ms. The primary end-point was a composite of all-cause mortality, urgent heart failure care requiring intravenous diuretics or increase in LV end-systolic volume index (LVESVI).15% from baseline. Secondary endpoints included all-cause mortality, death or hospitalization for heart failure and death or urgent care for heart failure. The study was funded by Medtronic and the results were recently published in the New England Journal of Medicine. After a mean follow-up period of 37 months, at least one of the components of the primary endpoint occurred in 186 of 349 patients (53.3%) in the BiV-pacing group versus 220 of 342 patients (64.3%) in the RV-pacing group. Owing to missing LVESVI values, data for 83 patients in the BiV pacing group and 71 in the RV-pacing group were censored before a primary endpoint event occurred and were not included in the final analysis of the primary outcome. There were 97 cross-overs (84 to BiV-pacing and 13 to the RV-pacing), with 44 crossovers occurring before meeting the primary endpoint. After accounting for censoring and using an intention-to-treat analysis, 160 patients (45.8%) in the BiV-pacing group and 190 patients (55.6%) in the RV-pacing group had events that were included in the primary end-point [HR 1⁄4 0.74 (0.60–0.90), posterior probability of HR 1⁄4 0.9978 (achieving the predetermined threshold for statistical significance of more the 0.9775 for combined hazard ratio of less than 1)]. This represents a statistically significant 27% relative risk reduction with BiV pacing. Importantly, the favorable effect of BiV-pacing was observed whether an ICD was implanted or not and