Nielsen JB, Strandberg SE, Pietersen A, Graff C, Holst AG, for the Copenhagen ECG Study. Left Anterior Fascicular Block and the Risk of Cardiovascular Outcomes. JAMA Intern Med. 2014;174(6):1001-1003. doi:10.1001/jamainternmed.2014.578
Left anterior fascicular block (LAFB) is considered a failure or delay of conduction in the left anterior fascicle.1 Despite the fact that little is known about the long-term prognosis associated with LAFB, it has generally been thought of as a benign electrocardiographic (ECG) finding.2 This view was recently challenged in an article by Mandyam et al,3 which reported an association between LAFB and an increased risk of atrial fibrillation (AF), heart failure (HF), and all-cause and cardiovascular death in individuals free of overt cardiovascular disease. However, the findings by Mandyam et al were limited by the fact that only 39 individuals with LAFB were eligible for inclusion. Using a large contemporary primary care population, we aimed to validate the findings of Mandyam et al by replicating their analyses in our population.
The study population consisted of all patients who underwent ECG recording at the Copenhagen General Practitioners’ Laboratory at the request of their general practitioners from 2001 to 2011.4 All ECGs were recorded and analyzed digitally. We defined LAFB as a QRS axis between −45° and −90° and QRS duration of less than 120 milliseconds in the absence of ventricular hypertrophy, inferior myocardial infarction, and ventricular preexcitation on the baseline ECG in accordance with the definition established by Mandyam et al.3 Data on drug use, comorbidity, and outcomes were collected from administrative Danish registries.5 We excluded individuals younger than 25 years and individuals with a history of AF, hypertension, myocardial infarction, valvular heart disease, congenital heart disease, HF, and diabetes mellitus. A detailed description of identification of clinical covariates and outcomes can be found elsewhere.4 Study participants were observed from their first ECG recording (baseline) until the first event of interest, death, emigration, or October 8, 2011, which was the end of follow-up. A Cox proportional hazards regression model was used to assess the association between LAFB, measured at the baseline ECG, and the risk of AF, HF, and all-cause and cardiovascular death. Proportional hazard assumptions were checked and accepted. P < .05 (2-sided) was considered statistically significant. Because our study was based on data from anonymized and encrypted administrative registers, no approval from an ethics committee was required and participants did not give oral or written consent. This was in accordance with Danish law. The project was approved by the Danish Data Protection Agency.
Clinical characteristics of the 227 543 primary care patients (1.6% with LAFB) eligible for inclusion are provided in Table 1. During a median follow-up of 5.7 years (interquartile range, 3.0-8.4 years), 6718 developed AF, 4034 developed HF, and 17 531 died (3679 from a cardiovascular cause). Univariate Cox proportional hazards models revealed statistically significant associations between LAFB and the risk of AF, HF, and all-cause and cardiovascular death (Table 2). However, after we adjusted for age and sex, only the risk of all-cause mortality remained statistically significant.
In a large primary care population free of major cardiovascular disease, we found the association between LAFB and the risk of AF, HF, and cardiovascular death to be entirely confounded by age and sex. The association with all-cause mortality remained statistically significant, but the effect seems to be of only minor clinical relevance. Moreover, the fact that the point estimates of the hazard ratios for all-cause and cardiovascular death are similar indicates that LAFB is not a useful marker of future cardiovascular morbidity and mortality.
Our results are in contrast to the recent findings by Mandyam et al, indicating that LAFB is a clinically relevant marker of various cardiovascular outcomes. The conflicting results could be explained by the fact that our cohort represents an everyday clinical setting of primary care patients in whom an ECG would be considered and used as a clinical tool, whereas the cohort observed by Mandyam et al represents a more random sample of the general population.
Differences in population demographics could be another explanation for the conflicting results. In particular, the cohort observed by Mandyam et al was significantly older than ours. However, when restricting our analysis to elderly individuals (data not shown), we came to an identical conclusion, indicating that the current ECG definition of LAFB is not always a clinically important marker of cardiovascular morbidity and mortality beyond what can be explained by age and sex.
Corresponding Author: Jonas B. Nielsen, MD, Department of Cardiology, Laboratory of Molecular Cardiology, Copenhagen University Hospital, Rigshospitalet, Bldg 9312, Juliane Maries Vej 20, 2100 Copenhagen Ø, Denmark (firstname.lastname@example.org).
Published Online: April 7, 2014. doi:10.1001/jamainternmed.2014.578.
Author Contributions: Drs Nielsen and Holst had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Nielsen, Holst.
Acquisition, analysis, and interpretation of data: All authors.
Drafting of the manuscript: Nielsen, Strandberg.
Critical revision of the manuscript for important intellectual content: Pietersen, Graff, Holst.
Statistical analysis: Nielsen.
Obtained funding: Nielsen, Graff, Holst.
Administrative, technical, or material support: Pietersen, Graff.
Study supervision: Holst.
Conflict of Interest Disclosures: Dr Holst is an employee of Novo Nordisk A/S, Bagsvaerd, Denmark.
Funding/Support: This study was supported by the University of Copenhagen, the Danish National Research Foundation, The John and Birthe Meyer Foundation, and grant 11-107456 from The Danish Council for Independent Research.
Role of the Sponsors: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; the preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication.
Group Information: The Copenhagen ECG Study Group Members are Jonas B. Nielsen, MD, Claus Graff, MSc, PhD, Adrian Pietersen, MD, Anders G. Holst, MD, PhD, Bent Lind, MD, DMSci, Johannes J. Struijk, MSc, PhD, Stig Haunsø, MD, DMSci, Lars Køber, MD, DMSci, and Jesper H. Svendsen, MD, DMSci.