Long-Term Implications of Cumulative Right Ventricular Pacing Among Patients With an Implantable Cardioverter-Defibrillator

Study Questions:

Does the burden of right ventricular (RV) pacing impact long-term survival in patients with implantable cardioverter-defibrillators (ICDs) placed for primary prevention?

Methods:

This was a substudy of the Multicenter Automatic Defibrillator Trial-II (MADIT-II), which studied the impact of ICD therapy versus standard medical therapy in patients with ischemic cardiomyopathy and a left ventricular ejection fraction ≤30%. In the ICD arm, patients received either a single-chamber (56%) or dual-chamber device (44%), with programming set at VVI 40-50 or DDD 60-70, respectively. The cumulative percent of RV pacing was calculated as the number of RV paced beats over total number of beats during device implant. Patients were dichotomized into low RV pacing (≤50% pacing), high RV pacing (>50% pacing), and no ICD groups. Cox proportional hazards were used to evaluate the contribution of ICD therapy and RV pacing on all-cause mortality.

Results:

There were 490 patients in the medical arm and 567 in the ICD arm, of whom 369 (65%) and 198 (35%) had low and high RV pacing burdens, respectively. Patients in the high RV pacing group were more likely to be older, with a wider QRS and higher blood urea nitrogen. Compared with medical therapy, ICD implantation reduced 3-year mortality by 64% overall (p < 0.001), with similar mortality reductions in the low RV pacing (65% reduction) and high RV pacing (62% reduction) groups. While the survival benefit persisted in those (n = 201) with low RV pacing burdens (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.46-0.80) compared with medical therapy on longer-term follow-up (4-8 years), the benefit waned abolished in those patients (n = 75) with high RV pacing burdens (HR, 0.89; 95% CI, 0.66-1.20) compared with medical therapy. Further subgroup analysis and interaction testing demonstrated that patients without a left bundle branch block (LBBB) electrocardiogram morphology and concomitant high RV pacing had the worst long-term outcomes.

Conclusions:

High burden RV pacing is associated with reduced survival benefit from ICD implant, especially in those without an LBBB.

Perspective:

This analysis provides thought-provoking information on the impact of RV pacing on mortality, and even more importantly, the reduced benefit of ICD therapy in those with high burden RV pacing. The results need to be interpreted with some prejudice, however, since it is a substudy and patient groups were not randomized by RV pacing category. Chronic RV pacing burden was highly dichotomized (>75% of patients had RV pacing burdens of <10% or >90%). The association between chronic RV pacing and heart failure progression has been demonstrated in other studies, and it is not entirely surprising that ICD therapy does not improve long-term survival in those more likely to develop progressive heart failure. To tease this out, the mode of death (heart failure vs. arrhythmic), time-dependent burden of RV pacing, the burden of rehospitalization for HF, and other heart failure markers (B-type natriuretic peptide or ejection fraction decrement) at follow-up would be needed. The survival benefit of ICD therapy in the short-term remains clinically important.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Prevention, Implantable Devices, SCD/Ventricular Arrhythmias, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Follow-Up Studies, Cardiomyopathies, Heart Failure, Stroke Volume, Electrocardiography, Heart Ventricles, Defibrillators, Implantable, Primary Prevention, Natriuretic Peptide, Brain


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