ABC | Volume 111, Nº5, November 2018

Original Article Baseline Prolonged PR Interval and Outcome of Cardiac Resynchronization Therapy: A Systematic Review and Meta-analysis Pattara Rattanawong, 1 Narut Prasitlumkum, 1 Tanawan Riangwiwat, 1 Napatt Kanjanahattakij, 2 Wasawat Vutthikraivit, 3 Pakawat Chongsathidkiet, 4 Ross J Simpson 5 University of Hawaii Internal Medicine Residency Program, 1 Honolulu, Hawai – USA Department of Internal Medicine, Einstein Medical Center, 2 Philadelphia – USA Department of Internal Medicine, Texas Tech University, 3 Texas – USA Duke University Medical Center, 4 North Carolina – USA The University of North Carolina, 5 Chapel Hill, North Carolina – USA Mailing Address: Pattara Rattanawong • 1133 waimanu st #2007. 96814, Honolulu, Hawai – USA E-mail: pattara.rattanawong@gmail.com , pattarar@hawaii.edu Manuscript received November 23, 2017, revised manuscript March 19, 2018, accepted May 09, 2018 DOI: 10.5935/abc.20180198 Abstract Background: Recent studies suggest that baseline prolonged PR interval is associated with worse outcome in cardiac resynchronization therapy (CRT). However, a systematic review and meta-analysis of the literature have not been made. Objective: To assess the association between baseline prolonged PR interval and adverse outcomes of CRT by a systematic review of the literature and a meta-analysis. Methods: We comprehensively searched the databases of MEDLINE and EMBASE from inception toMarch 2017. The included studies were published prospective or retrospective cohort studies that compared all-cause mortality, HF hospitalization, and composite outcome of CRT with baseline prolonged PR (> 200 msec) versus normal PR interval. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate the risk ratios and 95% confidence intervals. Results: Six studies from January 1991 to May 2017 were included in this meta-analysis. All-cause mortality rate is available in four studies involving 17,432 normal PR and 4,278 prolonged PR. Heart failure hospitalization is available in two studies involving 16,152 normal PR and 3,031 prolonged PR. Composite outcome is available in four studies involving 17,001 normal PR and 3,866 prolonged PR. Prolonged PR interval was associated with increased risk of all‑cause mortality (pooled risk ratio = 1.34, 95 % confidence interval: 1.08-1.67, p < 0.01, I 2  = 57.0%), heart failure hospitalization (pooled risk ratio = 1.30, 95 % confidence interval: 1.16-1.45, p < 0.01, I 2  = 6.6%) and composite outcome (pooled risk ratio = 1.21, 95% confidence interval: 1.13-1.30, p < 0.01, I 2  = 0%). Conclusions: Our systematic review and meta-analysis support the hypothesis that baseline prolonged PR interval is a predictor of all-cause mortality, heart failure hospitalization, and composite outcome in CRT patients. (Arq Bras Cardiol. 2018; 111(5):710-719) Keywords: Heart Failure/complications; Heart Conduction System/physiopathology; Ventricular Dysfunction/ complications; Cardiac Resynchronization/methods; Review; Meta-Analysis. Introduction It has been widely accepted that surface electrocardiogram findings are associated with prognosis in congestive heart failure (HF) patients who have required cardiac resynchronization therapy (CRT), particularly the QRS complex. QRS duration and morphology is a well-established predictor of outcome among patients receiving CRT as well as selection criteria for CRT implantation according to the current guidelines of the American College of Cardiology/American Heart Association/ Heart Rhythm Society. 1 More recently, baseline PR interval has been invoked as an additional factor that may affect CRT outcomes. 2 A prolonged PR interval is a marker of a ventricular substrate that is less amenable to resynchronization. It also reflects a combination of intrinsic intra-atrial and atrioventricular conduction which impacts diastolic filling time. 2,3 There are no clear evidence and explanation why PR prolongation might contribute to the outcome of CRT patients. Nonetheless, there is controversial evidence in literature regarding the association between baseline PR prolongation and outcomes of HF patients who require CRT implantation. Some studies implied that PR prolongation was associated with higher morbidity and mortality amongst these patients, 2,4-7 while others suggested it is associated with favorable outcomes. 8-10 However, a systematic literature review and meta-analysis of the association between PR interval and CRT outcome have not been made. We have first conducted a systematic literature review and meta-analysis to comprehensively analyze whether baseline 710