Chronic right ventricular pacing, adverse remodelling, and CRT: an ounce of prevention?

In medicine, it is encouraging when research yields results consistent with our understanding of the operative mechanisms, especially when there is a direct potential impact on clinical practice. Chan et al. have provided us with such a result and a clear message. The 2-year follow-up in the Pacing to Avoid Cardiac Enlargement (PACE) trial confirms that chronic right ventricular (RV) pacing in patients with bradycardia and preserved left ventricular (LV) function leads to sustained and progressive deterioration of LV ejection fraction (EF) and increases in LV volumes. This adverse remodelling process was prevented by pacing with cardiac resynchronization therapy (CRT). Adverse LV remodelling is a complex maladaptive process involving structural, haemodynamic, histopathological, and genetic changes. The process may be multifactorial and is frequently encountered in patients after loss of myocardium (myocardial infarction), volume overload (valvular insufficiency), or pressure overload (hypertension). It involves both LV hypertrophy and dilatation, and is initially an adaptive response that serves to maintain stroke volume. If persistent and progressive, the process becomes maladaptive and leads to further deterioration of LV function, LV dilatation, and eventually the typical symptoms of heart failure (HF). It is evident that substantial prolongation of the QRS interval, especially with a left bundle branch pattern, results in a delayed and dyssynchonous LV contraction. This dyssynchrony may be a major contributor that can both initiate and aggravate the process of adverse remodelling. In patients with symptomatic HF, systolic dysfunction, and QRS prolongation, CRT has been shown to be highly efficacious in reducing morbidity and prolonging survival. There is concordance between the reductions in LV volumes, the best indices of LV remodelling, and improvement in clinical outcomes. Acute and chronic RV pacing results in substantial widening of the QRS complex and induces both interand intraventricular dyssynchrony. Improvements in measures of dyssynchrony following CRT in patients with HF and previous RV pacing have been demonstrated. The recently published, focused ESC Guideline Update on devices in heart failure provides a class I recommendation with level of evidence A for CRT, both for patients with systolic dysfunction, New York Heart Association (NYHA) III/IV symptoms, and a QRS .120 ms and for patients with NYHA II symptoms and a QRS .150 ms. The current recommendations for patients with a conventional indication for pacing, systolic dysfunction, and symptomatic HF are class 1 with a QRS .120 ms and class II for patients with QRS ,120 ms. The PACE trial was designed to compare apical RV pacing with CRT in patients with bradycardia and a preserved EF. A total of 177 patients with a conventional indication for a pacemaker and preserved LV function (EF .45%), were, following successful implantation of a CRT device, randomized and programmed to either RV pacing or CRT pacing. The trial evaluated LV function and measurements of remodelling over 12 months at a blinded core laboratory using three-dimensional echocardiography. The results published in the New England Journal of Medicine last year demonstrated significant and substantial reductions in LVEF and increases in end-systolic LV volumes in the RV pacing group during the 1-year follow-up. Evidence of deterioration in LV function was not observed in the group with CRT pacing. The results of the 2-year follow-up of the PACE trial of Chan et al. are impressive, consistent with the original report, and demonstrate that the deleterious effects of chronic RV pacing on LV function and volumes are sustained and progressive. The co-primary endpoints were LVEF and LV end-systolic volume (ESV). A total of 163 patients (92%), still on their original randomization, were available for follow-up. The reported total