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BLOCK-HF: a game changer or a step too far?
  1. Klaus K Witte
  1. Correspondence to Division of Cardiovascular and Diabetes Research, Multidisciplinary Cardiovascular Research Centre (MCRC), Leeds Institute of Genetics, Health and Therapeutics, LIGHT building, University of Leeds, Clarendon Way, Leeds LS2 9JT, UK; k.k.witte{at}leeds.ac.uk

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Heart failure or asymptomatic left ventricular (LV) systolic dysfunction (LVSD) is seen in up to 40% of patients with permanent pacemakers,1 related to the percentage of right ventricular (RV) pacing and the medical background of the patient. It is likely that RV pacing has a detrimental effect on LV function, although many patients receiving RV pacemakers already have or will subsequently develop other risk factors for LV dysfunction.1 Whether patients at risk of heart failure benefit from receiving a cardiac resynchronisation therapy (CRT) device at the time of the initial implant rather than a standard pacemaker is unknown. The recent publication of the Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK-HF) study in the New England Journal of Medicine sets out to answer this question.2

BLOCK-HF started recruitment in 2003. Enrolment criteria included first-degree block with a PR interval of >300 ms (when paced at 100 bts/min), second-degree block or third-degree block, in the presence of LVSD with an ejection fraction (EF)≤50%. All patients were implanted with CRT devices (either pacemakers or defibrillators), and subsequently randomised in a 1:1 allocation to have the LV coronary sinus lead active or not in a double-blind fashion. Out of 918 patients assessed, 809 were listed for an implant, of whom 757 (94%) were successfully implanted (484 CRT-pacemakers and 207 CRT-defibrillators) with 691 randomised (349 to biventricular pacing and 342 to RV pacing). The final analysis with a mean follow-up of 37 months excluded 83 CRT and 71 RV patients due to missing echo data. There were 97 crossovers (84 to CRT and 13 to RV).

Enrolled patients were mostly men (75%) aged 73 years, of whom 20% had first-degree atrioventricular (AV) block, 11% had second-degree type I and 21% had second-degree type II block. Only 48% of patients had complete heart block. Mean EF was 40%, and mean QRS duration was 125 ms. High rates of paced beats (>95%) were seen in both groups and for each indication.

The primary endpoint of the study was a composite of death from any cause, urgent heart failure care requiring intravenous diuretic therapy or increase in LV end systolic volume index of >15% from baseline. This occurred in 186 (53%) of the CRT group and in 220 (64%) of the RV pacing group; a 26% lower relative risk in those randomised to CRT (HR 0.74 (0.60–0.90)). Secondary endpoints including death from any cause or hospitalisation for heart failure and all-cause mortality were also analysed. There was a lower rate of death and urgent heart failure care (HR 0.73 (0.57–0.92)) in the CRT group.

These headline data have led to speculation that all patients with AV block should now be considered for CRT rather than standard pacemakers. Is it therefore now necessary to provide a cardiologist capable of CRT in every district general hospital currently undertaking standard RV pacemaker implantation?

In order to answer this question, we need to examine the trial more closely in terms of patient cohort, outcomes and complication rates. First, many patients had class II (55%) or III (27%) heart failure, the mean QRS duration in the trial was 125 ms, and around 30% had an LVEF under 35%. It seems possible therefore that many patients were indicated for CRT based upon current guidelines.3 Second, it is well recognised that implanting a pacemaker programmed to deliver high rates of RV pacing, even if avoidable, in individuals with and without LVSD, increases the rates of adverse outcomes.4 ,5 These two features alone might contribute to an outcome in favour of CRT.

However, the key problem with assessing the utility of CRT over RV pacing in this study is the lack of a true control arm. Implanting CRT hardware in all restricts analyses to comparisons with retrospective, observational, and therefore, incomparable RV pacing data. This is no small issue. CRT procedures have higher complication rates, 14% in BLOCK-HF (10% due to the LV lead) than standard RV pacing, consistently related to volume such that complication rates might be even higher outside of a trial setting. Furthermore, CRT system implantation takes longer than standard pacemaker implantation and battery longevity is shorter, such that the opportunity cost of CRT cannot be assumed to be neutral. Cost-benefit and cost-utility analyses require data from a ‘standard care’ group and an ‘intervention’ group in order to measure the balance of the higher utility and lower cost associated with fewer heart failure hospitalisations with the lower utility and higher cost associated with longer procedures and more frequent complications and battery replacements from a CRT strategy.

So what information does BLOCK-HF offer UK physicians, providers and commissioners?

CRT, an established treatment for people with heart failure, LVSD and QRS prolongation should already be offered to patients with these features who require a pacemaker for bradycardia. It is too early, however, to suggest that all patients with AV block should receive CRT. We still have too many unanswered questions. It is unclear, for example, which patients will develop LV dysfunction or heart failure in response to RV pacing; most will not.6 We need well-conducted longitudinal studies of RV pacing to help us stratify patients at the time of the initial implant into high-risk and low-risk groups for the development of LV dysfunction or heart failure. It is not even clear which patients will go on to require high rates of pacing. In our survey of almost 500 patients attending for pacemaker generator replacement, more than 20% of patients implanted for a diagnosis of complete heart block had less than 80% ventricular pacing at the time of generator replacement,1 and even in patients with significant AV delay, there are algorithms proven to greatly reduce RV pacing.7 ,8 We also need to know more about the natural history of LV dysfunction in the pacemaker population. There are, for example, no data of the efficacy of medical therapy in this subgroup of heart failure patients making the additional benefit of a CRT device impossible to quantify. As a result of these unknowns, it is possible, given the high rate of device-related complications from BLOCK-HF, that patients at low risk of developing heart failure suffer harm from a CRT device, but without a control arm, a utility analysis to refute this possibility cannot be undertaken.

In summary, most patients with AV block, even those with modest LVSD, are adequately treated with an RV pacemaker. Some will develop heart failure subsequently, and in these, an upgrade procedure to CRT is safe and effective,9–11 but at present, we know too little about who will develop heart failure and in whom CRT at baseline would prevent it, to implant such a device in everyone. Until we know more, it is too early to change the pacing strategy for most patients with heart block.

References

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Footnotes

  • Competing interests None.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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