RV Pacing May Worsen Even Preserved-EF Heart Failure: Pooled Analysis

Patrice Wendling

April 11, 2019

A pooled patient-level analysis supports emerging evidence that conventional right ventricular pacing may be deleterious in heart failure with preserved ejection fraction (HFpEF).

Among more than 8000 patients, the unadjusted rate of cardiovascular (CV) death or HF hospitalization was nearly twice as high with previous pacemaker implantation as without (13.6 vs 7.6 per 100 person-years of follow-up).

The excess risk persisted for the primary composite outcome (hazard ratio [HR], 1.17; 95% CI, 1.02 - 1.33) and HF hospitalization (HR, 1.37; 95% CI, 1.12 - 1.60) but not for CV death after full adjustment (HR, 0.85; 95% CI, 0.70 - 1.04).

"This finding along with earlier reports that bundle branch block is also associated with worse outcomes in HFpEF suggests the possibility that RV pacing-induced LV dyssynchony may be detrimental in HFpEF patients," Li Shen, MBChB, PhD, University of Glasgow, United Kingdom, and colleagues report April 10 in the Journal of the American College of Cardiology: Heart Failure.

Although numerous trials have shown the detrimental effects of RV pacing on left ventricular (LV) function and clinical outcomes in HF with reduced EF (HFrEF), the potential consequences of RV pacing are poorly understood in patients with HFpEF, he noted.

Following the BLOCK HF trial, however, guidelines recommended cardiac resynchronization therapy (CRT) over RV pacing in patients with HFrEF and atrioventricular (AV) block, and suggested clinicians consider upgrading to CRT in HFrEF patients with a conventional pacemaker and high frequency of RV pacing.

"Clearly, the key question for clinical practice, raised by the current findings, is whether the use of CRT rather than RV pacing may be as preferable in HFpEF patients in need of a pacemaker as it is in those with HFrEF," Shen and colleagues say.

The investigators pooled data from patients enrolled in the CHARM-Preserved, I-PRESERVE, and TOPCAT studies and because of variability in the design of the trials, restricted the analysis to 8466 patients with an LVEF of at least 45%. Of these, 682 patients (8%) had a pacemaker.

Patients with a pacemaker had a lower body mass index and blood pressure than those without a pacemaker but were significantly older, had more atrial fibrillation/flutter, more advanced renal dysfunction, and used more diuretics. Median LVEF was 57.5% and 58.2%, respectively.

Despite more underlying conduction disease in the pacemaker group than in those without a pacemaker, the increased CV death risk was due to higher rates of pump failure death (1.8 vs 0.8 per 100 person-years) rather than sudden death (1.6 vs 1.4 per 100 person-years).

Although no longer significant in the fully adjusted model (HR, 1.00; 95% CI, 0.70 - 1.42), the excess risk for pump-failure death remains plausible given the likely detrimental effects of RV pacing on LV function, such as decreased ventricular relaxation, longer Tau, slower filling, increased ventricular filling pressure, and mitral regurgitation, the authors note.

The team acknowledged there were substantial differences between the two groups and that data were not available for the indication and mode of pacing.

Still, supplementary analyses showed the worst outcomes occurred in patients with a paced rhythm on their baseline ECG, compared with those with a nonpaced rhythm or no pacemaker. Rates of HF hospitalization or CV death per 100 person-years were 14.6, 11.5, and 7.6, respectively, in unadjusted analyses and were significantly higher in those with a paced rhythm vs no pacemaker after full adjustment (HR, 1.23; 95% CI, 1.05 -1.43).

Although these analyses were underpowered, they provide some support for a biologically causative relationship between RV pacing and worse outcomes, the authors suggest. In addition, preliminary results of the BIOPACE study in patients with AV block showed a nonsignificant trend favoring biventricular pacing over RV pacing, regardless of LVEF status. Of note, there was no interaction between LVEF and pacemaker implantation for any of the outcomes of interest in the pooled analysis.

Results of the two trials "raise the possibility that CRT may be preferable to RV pacing in patients with HFpEF. Clearly, however, the hypothesis needs to be tested in a prospective randomized clinical trial," the authors conclude.

In an accompanying editorial, David M. Kaye MBBS, PhD, and Hitesh C. Patel, MBBS, PhD, from the Alfred Hospital and Baker Heart and Diabetes Institute, Melbourne, Australia, write: " Notwithstanding the potential limitations of the work by Shen et al., this study adds a further electrical dimension to be considered when reviewing the pathophysiological elements that have combined to cause an individual HFpEF patient's clinical presentation and subsequent disease course."

Commenting further, they note that, "in this context, the study prompts one to question whether the presence of a pacemaker is simply a metric of disease origin or severity, or whether the application of pacing promotes the progression of HFpEF, and therefore, whether alternate pacing modalities should be considered."

Shen, McMurray, Kaye, and Patel report no relevant conflicts of interest.

JACC Heart Fail. Published online April 10, 2019. Abstract, Editorial

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