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Clinical Implications of Electrocardiographic Bundle Branch Block in Primary Care

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Clinical Implications of Electrocardiographic Bundle Branch Block in Primary Care Cardiac risk factors and prevention ORIGINAL RESEARCH ARTICLE Heart: first published as 10.1136/heartjnl-2018-314295 on 25 May 2019. Downloaded from Clinical implications of electrocardiographic bundle branch block in primary care Peter Vibe Rasmussen, 1,2 Morten Wagner Skov,2,3 Jonas Ghouse,2,3 Adrian Pietersen,4 Steen Møller Hansen,5 Christian Torp-Pedersen,5,6 Lars Køber,3,7 Stig Haunsø,2,3,7 Morten Salling Olesen,2,8 Jesper Hastrup Svendsen,3,7 Jacob Melgaard,6 Claus Graff,6 Anders Gaardsdal Holst,3,9 Jonas Bille Nielsen2,10,11 ► Additional material is ABSTRact In the primary care setting, patients are referred published online only. To view Objectives Electrocardiographic bundle branch block for 12-lead standard ECG recording based on a please visit the journal online broad range of indications, ranging from typical (http:// dx. doi. org/ 10. 1136/ (BBB) is common but the prognostic implications in heartjnl- 2018- 314295). primary care are unclear. We sought to investigate the symptoms of CV disease to more diffuse symptoms relationship between electrocardiographic BBB subtypes as well as monitoring of medical treatment (eg, QTc For numbered affiliations see and the risk of cardiovascular (CV) outcomes in a primary interval-prolonging drugs) or as part of a routine end of article. care population free of major CV disease. health check. Opportunistic ECG recordings Methods Retrospective cohort study of primary care will often result in identification of various BBB Correspondence to subtypes. However, to the best of our knowledge, Peter Vibe Rasmussen, patients referred for electrocardiogram (ECG) recording Department of Cardiology, between 2001 and 2011. Cox regression models were there are no clear and uniform recommendations or Herlev-Gentofte Hospital, used to estimate hazard ratios (HR) as well as absolute available risk prediction models aimed at handling Hellerup, Denmark ; peter. vibe. risks of CV outcomes based on various BBB subtypes. and informing general practice patients who present rasmussen@ gmail. com Results We included 202 268 individuals with a with a potentially asymptomatic BBB subtype. PVR and MWS contributed median follow-up period of 7.8 years (Inter-quartile To address this, we used a middle-aged and equally. range [IQR] 4.9–10.6). Left bundle branch block (LBBB) elderly primary care population free from major was associated with heart failure (HF) in both men CV disease, to (1) Estimate prevalences of BBB. Received 16 October 2018 (HR 3.96, 95% CI 3.30 to 4.76) and women (HR 2.51, (2) Describe associations between BBB subtypes Revised 7 March 2019 and CV outcomes. (3) Test if the BBB subtypes are Accepted 15 March 2019 95% CI 2.15 to 2.94) and with CV death in men (HR Published Online First 1.80, 95% CI 1.38 to 2.35). Right bundle branch block clinically useful in improving risk prediction of CV 25 May 2019 (RBBB) was associated with pacemaker implantation in events. (4) If so, to develop a model useful in risk both men (HR 3.26, 95% CI 2.74 to 3.89) and women prediction of CV events in primary care patients http://heart.bmj.com/ (HR 3.69, 95% CI 2.91 to 4.67), HF in both sexes and with different BBB subtypes. weakly associated with CV death in men. Regarding LBBB, we found an increasing hazard of HF with METHODS increasing QRS-interval duration (HR 1.25, 95% CI 1.11 Study population to 1.42 per 10 ms increase in men and HR 1.23, 95% CI The present study is a part of the Copenhagen ECG 1.08 to 1.40 per 10 ms increase in women). Absolute study, comprising all individuals referred for ECG 10-year risk predictions across age-specific and sex- on September 30, 2021 by guest. Protected copyright. recording at the Copenhagen General Practitioners’ specific subgroups revealed clinically relevant differences Laboratory (CGPL) between 2001 and 2011. CGPL between having various BBB subtypes. is a centralised core facility used by general practi- Conclusions Opportunistic findings of BBB subtypes in tioners in the area of Copenhagen for the purpose of primary care patients without major CV disease should conducting various clinical examinations including be considered warnings of future HF and pacemaker ECG recording, as described previously.6–8 implantation. Individuals were excluded if they, at the time of inclusion (date of first ECG recording), were <40 years of age, had a pacemaker or implantable cardioverter-defibrillator, had an ECG unsuitable INTRODUCTION for measurement (see section on electrocardiog- ► http:// dx. doi. org/ 10.1136/ The use of surface 12-lead electrocardio- raphy) or had a history of myocardial infarction heartjnl- 2019- 314751 gram (ECG) often results in identification of bundle (MI), atrial fibrillation (AF), ischaemic stroke, heart branch block (BBB), even in individuals free of failure (HF) or valvular heart disease. We chose known cardiopulmonary disease. BBB comprises to exclude individuals <40 years of age due to a the subtypes incomplete right bundle branch block © Author(s) (or their very low event rate and consequently low statistical (IRBBB), right bundle branch block (RBBB), left employer(s)) 2019. No power. commercial re-use. See rights bundle branch block (LBBB) and non-specific and permissions. Published intraventricular conduction defect (NIVCD). BBB by BMJ. subtypes have been associated with an adverse prog- Baseline variables and outcomes To cite: Rasmussen PV, nosis in patients with known cardiovascular (CV) Using Danish administrative healthcare registers and Skov MW, Ghouse J, et al. disease and in people recruited from the general a unique personal identification number assigned to Heart 2019;105:1160–1167. population with and without CV disease.1–5 all persons with permanent residence in Denmark, 1160 Rasmussen PV, et al. Heart 2019;105:1160–1167. doi:10.1136/heartjnl-2018-314295 Cardiac risk factors and prevention we followed individuals over time with respect to death, emigra- mortality using individuals without the BBB subtype in ques- tion, use of prescription drugs and any hospital, or outpatient tion as reference. In case of a significant association between Heart: first published as 10.1136/heartjnl-2018-314295 on 25 May 2019. Downloaded from clinic diagnoses. We identified baseline variables regarding any of the BBB subtypes and an outcome of interest, we further comorbidity and medication status as described in detail previ- tested the association between QRS duration, measured as a ously.6–8 In brief, diabetes was defined as a register diagnosis continuous variable, and the event within subjects with the of diabetes mellitus or treatment with glucose-lowering drugs. specific BBB subtype. MI, AF, HF, pacemaker implantation, valvular heart disease and Time-on-study was used as time scale in all survival ischaemic stroke were defined from hospital discharge diagnoses analyses. All Cox models were adjusted for the following and procedure codes in the Danish National Patient Registry. covariates obtained at baseline: age, hypertension, diabetes Hypertension was defined as a register diagnosis of hyperten- mellitus, a categorical variable of Charlson Comorbidity sion or simultaneous treatment with two types of antihyperten- Index (0, 1, >2 points) and left ventricular hypertrophy. As sive medication prior to or at inclusion. Finally, we constructed many CV diseases are known to present differently across the the Charlson Comorbidity Index which is a score combining two sexes, all analyses were conducted separately in men and several disease-specific comorbidities; for a list of included codes women.12 Follow-up began on the day of first ECG recording see online supplementary table 1.9 Our end points of interest and ended in case of emigration, event of interest, death or were incident HF, MI, pacemaker implantation, AF, CV death on 31 December 2013, whichever came first. Proportional and death from all causes. For a list of diagnostic codes see hazard assumptions were tested and accepted by evaluating online supplementary table 2. The use of Danish administrative log-log plots. We considered a two-sided p value <0.05 as registers ensures complete nationwide coverage. Thus, we were statistically significant. able to interpret all cases of values not observed as not present and could define all variables without missing values. Absolute risk prediction Risk predictions were performed in a competing risk setting Electrocardiography by combining a Cox model for all-cause mortality with a 13 All ECGs were digitally recorded and stored in the MUSE Cox model of the outcome in question. Absolute risks were Cardiology Information System (GE Healthcare, Wauwatosa, reported in a risk chart stratified by 10-year age groups, sex Wisconsin, USA) and were processed using version 21 of the and comorbidity (yes vs no) defined as either a Charlson Marquette 12SL algorithm.8 We excluded ECGs with rhythms Comorbidity Score >1, hypertension or diabetes mellitus. different from sinus rhythm and other findings not suitable for Differences in time-dependent area under the receiver oper- the study analyses (eg, advanced atrioventricular block, delta ating characteristics curve (AUC) were calculated to investi- waves, pace spikes, ventricular rates <30 beats per minute and gate the added discriminative value of BBB subtypes in risk 14 15 >120 beats per minute). We defined BBB subtypes according prediction of CV outcomes. Data were split into a training to the American Heart Association (AHA), American College and test set with 101 splits using randomly chosen seeds. Ulti- of Cardiology Foundation (ACCF), and Heart Rhythm Society mately, the seed with the median AUC in the models without (HRS) recommendations for standardisation and interpretation BBB was chosen. Model performance and calibration were http://heart.bmj.com/ of the ECG implementing a few minor modifications as the evaluated and accepted using Brier scores and calibration 12SL algorithm cannot directly measure a notch or slur in the plots showing the observed frequency versus the predicted 16 17 R-wave.10 risk.
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