ABC | Volume 111, Nº5, November 2018

Original Article Rattanawong et al PR interval and chronic resynchronization therapy Arq Bras Cardiol. 2018; 111(5):710-719 Table 3 – Intra-study risks of bias of included studies Study Clear definition of study population? Clear definition of outcomes and assessment? Independent assessment of outcomes? (e.g. by third party) Sufficient Follow-up duration? Selective loss during Follow-up? Limitations identified? Freidman Yes Yes Yes Yes No Yes Januszkiewicz Yes Yes No Yes No Yes Kronborg Yes Yes Yes Yes No Yes Kutyifa Yes Yes Yes Yes No No Olshansky No Yes Yes No No Yes Ying-Hsiang Yes Yes No Yes No Yes AV valve regurgitation and improve diastolic function. 19 On the other hand, with the presence of intra-atrial conduction disturbance, CRT implantation could have deleterious impact on these patients as it shortens the appropriate PR interval and causes paradoxical effect, leading to worsening heart failure. 20 Alternatively, PR prolongation may simply be a rough marker of “sicker” heart failure patients. 17,21,22 In current heart failure guidelines, the duration of QRS, the type of bundle branch block and the presence of atrial fibrillation have been utilized as criteria for pacemaker device implantation. 23 Also, CRT has a range of effects which has promoted interest in refining selection criteria for this important therapy. In our analysis, we imply hat the PR interval is a promising prognostic marker in patients with heart failure requiring CRT. Thus, PR interval may also be a valuable adjunctive selection criteria. As our study has substantial heterogeneity in all cause mortality, we performed sensitivity analysis and found that after exclusion of Freidman et al., 2 the heterogeneity decreased from 57.0% to 0%. We concluded that the most likely explanation could be from the definition criteria of the recruited studies. Friedman is the only study that defined prolonged PR as more than 230 msec whereas every other study defined prolonged PR as more than 200 msec. Therefore, a meta-regression was conducted to investigate the statistical significance of PR definition affecting the results. However, meta-regression showed non-significant changes in all-cause mortality in PR interval > 230 msec compared with PR interval > 200 msec. Our study has some limitations. Despite the fact that our funnel plot does not show biased data set, there are only six studies included in the analysis. In addition, PR prolongation is generally defined as PR interval exceeding 200 milliseconds. However, among the six included studies, there is only one study that defines prolonged PR interval as 230 ms and above. 2 Given the total number of subjects, the heterogeneity of sample is small. While there are other possible predictor variables that are not included in this study, they were already analyzed in Rickard et al. 24 Lastly, instead of using cardiac cause-specific mortality, all‑cause mortality was used as outcome of interest in the included studies, whichmight overestimate the total outcome. Conclusion In conclusion, among patients requiring CRT, prolonged PR interval is an independent indicator for all-cause mortality, HF hospitalization, and composite outcome. Our result suggests that PR interval should be considered as one of the important predictors of CRT response when addressing risk stratification. Acknowledgement We would like to thank Elysse Tom, MD for critical reading. Author contributions Conception and design of the research and Statistical analysis: Rattanawong P; Acquisition of data: Prasitlumkum N, Riangwiwat T, Kanjanahattakij N, Chongsathidkiet P; Analysis and interpretation of the data: Rattanawong P, PrasitlumkumN, Riangwiwat T, Kanjanahattakij N, Vutthikraivit W, Chongsathidkiet P; Writing of the manuscript: PrasitlumkumN, Riangwiwat T, Vutthikraivit W; Critical revision of the manuscript for intellectual content: Simpson RJ. Potential Conflict of Interest No potential conflict of interest relevant to this article was reported. Sources of Funding There were no external funding sources for this study. Study Association This study is not associatedwith any thesis or dissertationwork. Ethics approval and consent to participate This article does not contain any studies with human participants or animals performed by any of the authors. 714