title: Prolonged PR interval, first-degree heart block and adverse cardiovascular outcomes: a systematic review and meta-analysis.
abstract: OBJECTIVE
  First-degree atrioventricular block is frequently encountered in clinical practice and is generally considered a benign process. However, there is emerging evidence that prolonged PR interval may be associated with adverse outcomes. This study aims to determine if prolonged PR interval is associated with adverse cardiovascular outcomes and mortality.
  
  
  METHODS
  We searched MEDLINE and EMBASE for studies that evaluated clinical outcomes associated with prolonged and normal PR intervals. Relevant studies were pooled using random effects meta-analysis for risk of mortality, cardiovascular mortality, heart failure, coronary heart disease, atrial fibrillation and stroke or transient ischaemic attack (TIA). Sensitivity analyses were performed considering the population type and the use of adjustments.
  
  
  RESULTS
  Our search yielded 14 studies that were undertaken between 1972 and 2011 with 400,750 participants. Among the studies that adjusted for potential confounders, the pooled results suggest an increased risk of mortality with prolonged PR interval risk ratio (RR) 1.24 95% CI 1.02 to 1.51, five studies. Prolonged PR interval was associated with significant risk of heart failure or left ventricular dysfunction (RR 1.39 95% CI 1.18 to 1.65, three studies) and atrial fibrillation (RR 1.45 95% CI 1.23 to 1.71, eight studies) but not cardiovascular mortality, coronary heart disease or myocardial infarction or stroke or TIA. Similar observations were recorded when limited to studies of first-degree heart block.
  
  
  CONCLUSIONS
  Data from observational studies suggests a possible association between prolonged PR interval and significant increases in atrial fibrillation, heart failure and mortality. Future prospective studies are needed to confirm the relationships reported, consider possible mechanisms and define the optimal monitoring strategy for such patients.
authors.affiliation: Keele Cardiovascular Research Group, Institutes of Science and Technology in Medicine and Primary Care and Health Sciences, Stoke-on-Trent, UK The Heart Centre, Royal Stoke University Hospital, Stoke-on-Trent, UK.
authors.forename: Chun Shing
authors.initials: CS
authors.lastname: Kwok
authors.affiliation: Keele Cardiovascular Research Group, Institutes of Science and Technology in Medicine and Primary Care and Health Sciences, Stoke-on-Trent, UK Cardiology Department, St Helens and Knowsley Teaching Hospital (NHS) Trust, Whiston Hospital, Prescot, UK.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Rashid
authors.affiliation: The Heart Centre, Royal Stoke University Hospital, Stoke-on-Trent, UK.
authors.forename: Rhys
authors.initials: R
authors.lastname: Beynon
authors.affiliation: The Heart Centre, Royal Stoke University Hospital, Stoke-on-Trent, UK.
authors.forename: Diane
authors.initials: D
authors.lastname: Barker
authors.affiliation: The Heart Centre, Royal Stoke University Hospital, Stoke-on-Trent, UK.
authors.forename: Ashish
authors.initials: A
authors.lastname: Patwala
authors.affiliation: The Heart Centre, Royal Stoke University Hospital, Stoke-on-Trent, UK.
authors.forename: Adrian
authors.initials: A
authors.lastname: Morley-Davies
authors.affiliation: The Heart Centre, Royal Stoke University Hospital, Stoke-on-Trent, UK.
authors.forename: Duwarakan
authors.initials: D
authors.lastname: Satchithananda
authors.affiliation: Keele Cardiovascular Research Group, Institutes of Science and Technology in Medicine and Primary Care and Health Sciences, Stoke-on-Trent, UK The Heart Centre, Royal Stoke University Hospital, Stoke-on-Trent, UK.
authors.forename: James
authors.initials: J
authors.lastname: Nolan
authors.affiliation: Epidemiology Group, The Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: Phyo K
authors.identifier: http://orcid.org/0000-0003-3852-6158
authors.initials: PK
authors.lastname: Myint
authors.affiliation: Farr Institute, University of Manchester, Manchester, UK.
authors.forename: Iain
authors.initials: I
authors.lastname: Buchan
authors.affiliation: Department of Public Health & Primary Care, Norwich Medical School, University of East Anglia, Norwich, UK.
authors.forename: Yoon K
authors.initials: YK
authors.lastname: Loke
authors.affiliation: Keele Cardiovascular Research Group, Institutes of Science and Technology in Medicine and Primary Care and Health Sciences, Stoke-on-Trent, UK The Heart Centre, Royal Stoke University Hospital, Stoke-on-Trent, UK Farr Institute, University of Manchester, Manchester, UK.
authors.forename: Mamas A
authors.initials: MA
authors.lastname: Mamas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054537:Atrioventricular Block / Q000150:complications*; D053840:Brugada Syndrome / Q000150:complications; D000075224:Cardiac Conduction System Disease; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D064887:Observational Studies as Topic; D011379:Prognosis