Editor’s Note: The following guest post is published with the permission of its author, Edward J. Schloss, MD, (Twitter ID @EJSMD) the medical director of cardiac electrophysiology at Christ Hospital in Cincinnati, OH. Dr. Schloss was an investigator in the BLOCK HF trial.
In what has been described as a “game changer” for the field of cardiac pacing, the BLOCK HF trial was reported at today’s AHA Scientific Sessions showing benefit of biventricular pacing over conventional RV pacing in patients with AV block and LV dysfunction.
Since the development of pacemakers over 50 years ago, doctors have treated patients with AV block with right ventricular pacing. Until about 10 years ago, this was felt to be harmless and potentially beneficial. Pacing algorithms were designed to force right ventricular pacing and create what was termed a “physiologic AV delay” in the hopes that controlling the timing of atrial and ventricular contraction would improve hemodynamics.
The DAVID trial, reported in 2003, turned the conventional wisdom upside-down, and first clearly showed the hazards of unnecessary RV pacing. DAVID was designed with the hypothesis that dual chamber pacing in patients receiving ICDs without bradycardia indications would result in improved hemodynamics and therefore improved outcomes as compared to conventional backup ventricular pacing. To the surprise of the investigators, the opposite proved true. The group receiving dual chamber pacing had about a 40% increase in mortality and heart failure hospitalization as compared to the minimal pacing group over one year. As this data was confirmed with additional trials, doctors moved to minimize right ventricular pacing in their patients and new minimal pacing algorithms were developed by industry.
Paralleling the movement to minimize right ventricular pacing, the technique of cardiac resynchronization therapy (CRT) for treatment of heart failure took off. Here the benefit of pacing right and left ventricles together was established for patients with heart failure and evidence of dyssnchronous ventricular contraction.
The BLOCK HF trial was planned to test the hypothesis that biventricular pacing would be superior to right ventricular pacing in patients with left ventricular dysfunction and heart block requiring pacing. Enrollment began in December 2003.
BLOCK HF enrolled patients indicated for ventricular pacing due to AV block who had at least mild LV dysfunction (LVEF <50% on optimal HF medical therapy) and NYHA functional class I-III. All patients then received biventricular devices (pacer or ICD depending on clinical indication) and then were randomized in blinded fashion to conventional dual chamber (RA-RV) pacing vs. biventricular (RA-RV&LV) pacing. Primary endpoint was the time to first event: total mortality, heart failure exacerbation requiring acute care or >= 15% increase in echocardiographic left ventricular end-systolic volume.
Enrollment and follow up continued with serial echoes and clinical assessments for over seven years with mean follow up just over three years. The sample size was determined by a pre-specified adaptive statistical analysis that took into account the results of repeated interim analyses. The study would complete for success, hazard or futility. A total of 691 patients completed randomization and were included in the final analysis (with 102 exited or lost to follow up). The study population was predominantly male with average age in 70s, and NYHA class II predominated. LVEF was average 43% in the pacemaker group and 33% in the ICD group.
In the final analysis, biventricular pacing led to a 26% reduction in the combined endpoint of death, heart failure exacerbation or LV enlargement. Excluding the echo endpoint, the clinical parameters remained favorable, with a 27% reduction in death or heart failure exacerbation. The heart failure curves diverge early and remain parallel and the mortality curves diverge at about four years and continue to separate.
In last night’s investigator meeting, Dr. Anne Curtis, the study PI, called BLOCK HF a “game changer” that could lead to a new indication for biventricular pacing in patients with heart block and LV dysfunction. She acknowledged the limitations of the trial including a high crossover rate (predominantly RV to BiV) and some missing echo data. The very long follow up, however, could be interpreted as an advantage for the trial.
As an investigator in the trial, I was very eager to see this data and encouraged by the results. The trial was slow to enroll with very long follow up and we were just happy to see it reach fruition. Over the years, I’ve seen numerous patients develop heart failure after initiation of conventional pacing and it’s good to know that we may be able to prevent this if a new indication arises from the BLOCK HF data.
As in all trials, we will need to be cautious in the application of the data. BLOCK HF should not spell the end for right ventricular pacing. For those patients with normal LV function or those who get minimal ventricular pacing (such as sick sinus patients), conventional RV pacing is still appropriate and avoids the additional cost complexity and hazard of adding an LV lead.