BLOCK-HF

Published

Curtis A.B., et al. "Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block". The New England Journal of Medicine. 2013. 368(17):1585-1593.
PubMed • Full text • PDF

Clinical Question

In patients with high grade atrioventricular block and left ventricular systolic dysfunction (NYHA class I-III, LVEF ≤ 50%) does biventricular pacing reduce death, urgent heart failure care and adverse left ventricular remodeling compared to right ventricular pacing?

Bottom Line

In patients with high grade AV block and mild-to-moderate heart failure, biventricular pacing is associated with a 10% absolute reduction in death, urgent heart failure care and adverse LV remodeling compared with right ventricular pacing, with the difference driven primarily by reduced heart failure hospitalizations and reduced LV remodeling.

Major Points

In patients with high-grade sinoatrial (SA) or atrioventricular (AV) node dysfunction, cardiac pacing is the primary treatment modality. Multiple RCTs in recent years including the MOST, DAVID, and Yu et al., 2009 trials have demonstrated the deleterious effects of right ventricular (RV) pacing on cardiac function in patients with heart failure and AV block. Conventional right ventricular apical pacing has been shown to result in worsening left ventricular (LV) function in a subset of patients due to non-physiological myocardial activation leading to ventricular dyssynchrony. It is thought that ventricular dyssynchrony results in maladaptive electrical, metabolic, and mechanical remodeling of the LV leading to impaired contractility . As an alternative, synchronously pacing both ventricles with cardiac resynchronization therapy (CRT) has been shown to mitigate ventricular dyssynchrony and improve clinical outcomes. CRT devices, however, are more technically challenging to place and are associated with higher costs and complication rates.

CRT has a class I indication in patients with LVEF ≤ 35% with coexistent LBBB with QRS ≥ 150ms and NYHA II-IV symptoms according to the 2012 ACC/AHA/HRS consensus guidelines., based on demonstrated benefit in patients with established heart failure with evidence of electrical dyssynchrony. (see MADIT-CRT). However, the role of CRT (compared to conventional RV pacing) as a prophylactic measure to reduce risk of CHF progression in patients with pre-existing heart failure with high anticipated pacing burden was unknown.

Published in 2013, the Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK-HF) trial compared biventricular pacing vs. RV pacing in patients requiring a pacemaker/ICD for high-grade AV block and LVEF ≤ 50% with NYHA class I-III symptoms of heart failure while excluding patients with indications for CRT that were based on current practice guidelines (i.e., LVEF <35%, LBBB, or QRS > 150msec). CRT resulted in a 10% absolute reduction in death, urgent heart failure care and adverse LV remodeling. This difference was driven primarily by reductions in heart failure hospitalization and reduced remodeling although there were numerically fewer deaths in the CRT group as well. LV lead complications were rare (< 5%).

Importantly, these findings suggest that CRT may be the pacing method of choice in patients with pre-existing heart failure who are likely to require a high degree of pacing support (median ventricular pacing > 97% in both groups). This adds to the growing body of evidence demonstrating that conventional RV pacing may be harmful in established CHF and that CRT may mitigate this harm. Given that the latest CRT guidelines were released while BLOCK-HF was ongoing, it is also possible that some patients would be expected to benefit from CRT on the basis of traditional indications as well. Importantly, the primary outcome was largely driven by patients achieving a >15% increase in left ventricular end-systolic volume index (LVESI) [a surrogate marker for LV remodeling] which may not always be clinically significant, although there remained a significant difference in the composite outcome of death or heart failure hospitalization (the primary outcome with LV remodeling removed).

In summary, on the strength of BLOCK-HF it appears that most patients with pre-existing systolic dysfunction with distal conduction system disease with high anticipated need for RV pacing benefit from upfront CRT rather than a traditional RV pacemaker. Given the relatively low but nevertheless important increase in complication rates with CRT, future studies investigating the relative cost/benefit of upfront CRT vs. RV pacing in various subpopulations of CHF are needed to better delineate who is most likely to derive benefit from this approach.

Guidelines

As of June 2017, no guidelines have been published that reflect the results of this trial.

Design

• Prospective, multicenter, double-blind, randomized, controlled trial
• N = 691
  • 349 to biventricular pacing
  • 342 to right ventricular pacing
• Setting: 58 centers in the United States, 2 centers in Canada
• Enrollment: 2003-2011
• Mean follow-up: 37 months
• Analysis: Intention-to-treat
• Primary outcome: Composite of death, urgent care visit for heart failure and >15% increase in left ventricular end-systolic volume index (surrogate marker for LV remodeling)
• Secondary outcomes: Death or urgent care visit, death or hospitalization for heart failure, death, hospitalization for heart failure

Population

Inclusion Criteria

• Patients with class I or IIa indication for a pacemaker due to high grade AV block AND with NYHA class I-III heart failure with LVEF ≤50%
  • High grade AV block defined as documented third-degree AV block OR demonstration of second-degree AV block OR PR interval >300msec when paced at 100bpm

Exclusion Criteria

• Previous receipt of a cardiac implantable electrical device
• Unstable angina
• Acute myocardial infarction
• Percutaneous or surgical coronary intervention within 30 days before enrollment
• Valvular disease with an indication for valve repair or replacement
• Indication for a CRT device

Baseline Characteristics

“From ‘All Patients’ in the RV pacing group”

• Demographics: Male sex (72.8%), Age 73
• Cardiac History:
  • LVEF 39.6%
  • LVEF fraction >35% (70.2%)
  • CAD: 64.0%
  • MI: 36.3%
  • HTN: 83.9%
  • Atrial fibrillation: 54.1%
  • Diabetes: 36.3%
• Heart Failure history:
  • NYHA Class I: 18.4%
  • NYHA Class II: 53.8%
  • NYHA Class III: 27.8%
  • Ischemic cardiomyopathy: 43.9%
  • Nonischemic cardiomyopathy: 26.3%
  • Unknown cardiomyopathy: 2.6%
  • Other cardiomyopathy: 2.3%
• Electrophysiologic properties:
  • Heart rate 68.8 bpm
  • QRS duration 123.0 msec
  • AV block:
    • 1st degree: 19.3%
    • 2nd degree: 31.6%
    • 3rd degree: 48.8%
  • Bundle-branch block:
    • Left: 29.8%
    • Right: 21.6%

Interventions

• Patients meeting inclusion criteria randomized to receive biventricular pacing or right ventricular pacing
• Patients followed for a mean of 37 months
• Initially patients enrolled in the study received pacemakers only but with evidence of survival benefit of an ICD in HF patients, protocol was revised to include ICD placement in patients who met criteria

Outcomes

“Comparisons are Biventricular pacing vs. Right Ventricular pacing expressed as hazard ratios”

Primary Outcomes

Composite of death, urgent care visit for heart failure and LV remodeling

Pacemaker group: 0.73 (95% CI 0.58-0.91)

ICD group: 0.75 (95% CI 0.57-1.02)

All patients: 0.74 (0.60-0.90)

Secondary Outcomes

Death or urgent care visit

Pacemaker group: 0.73 (95% CI 0.56-0.94)

ICD group: 0.73 (95% CI 0.53-1.02)

All patients: 0.73 (95% CI0.57-0.92)

Death or hospitalization for heart failure

Pacemaker group: 0.77 (95% CI 0.58-1.00)

ICD group: 0.80 (95% CI 0.58-1.13)

All patients: 0.78 (95% CI0.61-0.99)

Death

Pacemaker group: 0.83 (95% CI 0.59-1.17)

ICD group: 0.84 (95% CI 0.55-1.28)

All patients: 0.83 (95% CI0.61-1.14)

Hospitalization for heart failure

Pacemaker group: 0.68 (95% CI 0.49-0.94)

ICD group: 0.73 (95% CI 0.50-1.11)

All patients: 0.70 (95% CI0.52-0.93)

Adverse Events

• 113 of 809 (14%) patients in whom implantation was attempted had serious adverse events
  • 10.3% had events related to the procedure or CRT system
  • 3% of patients with lead dislodgment, 1.1% of patients with new onset atrial fibrillation
• Among the 7758 patients with implanted devices, 4.9% had the following serious adverse events related to the CRT system within 6 months after implantation: lead dislodgement, device lead damage, pacing failure (“failure to capture”), implantation- site infection, and inappropriate device stimulation of tissue
  • No significant difference between the two pacing groups

Criticisms

• High crossover rate
  • However crossover largely occurred after the primary end point and trended toward patients moving from the right ventricular to biventricular pacing group suggesting an even higher benefit in the biventricular group
• A large subset of patients were censored from the analysis due to missing echocardiographic data
  • Notably, death or urgent care visit for HF still significantly lower in CRT group after removal of LV remodeling outcome
• Since all patients in this study underwent LV lead placement, it is unclear whether the benefits of biventricular pacing are mitigated by increased complications from LV lead placement.

Funding

• Study supported by Medtronic plc
• Study authors with numerous ties to industry