Author + information
- Jason J. Rose, MD†,
- L. Kristin Newby, MD, MHS†,
- Samuel Broderick, MS†,
- Karen Chiswell, PhD†,
- Frans Van de Werf, MD, PhD‡,
- Paul W. Armstrong, MD§,
- Kenneth W. Mahaffey, MD†,
- Robert A. Harrington, MD†,
- E. Magnus Ohman, MD†,
- Robert P. Giugliano, MD, SM∥,
- Shaun G. Goodman, MD¶,
- Harvey D. White, DSc#,
- Robert M. Califf, MD†,
- Christopher B. Granger, MD† and
- Renato D. Lopes, MD, PhD†,⁎ ()
- ↵⁎Duke Clinical Research Institute, Duke University Medical Center, Box 3850, 2400 Pratt Street, Room 0311, Terrace Level, Durham, North Carolina 27705
To the Editor:
Acute coronary syndrome (ACS) patients presenting with left bundle branch block (LBBB) have higher mortality rates and worse overall outcomes than patients without LBBB (1,2). We compared clinical characteristics of 29,176 patients with and without LBBB enrolled in non–ST-segment elevation (NSTE) ACS clinical trials of antithrombotic therapy and explored the relationship of LBBB with outcomes.
We used 5 trials: GUSTO IIb (Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes, NSTE cohort) (n = 8,011, 27.5%), PARAGON-A (Platelet IIb/IIIa Antagonist for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network A) (n = 2,282, 7.8%), PARAGON-B (Platelet IIb/IIIa Antagonist for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network B) (n = 5,224, 17.9%), SYNERGY (Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors) (n = 4,256, 14.6%), and EARLY ACS (Early versus Delayed, Provisional Eptifibatide in Acute Coronary Syndromes) (n = 9,403, 32.2%). LBBB status was identified on the case report form and/or by the electrocardiogram core laboratory. Inclusion of patients with LBBB in these trials was generally by investigator discretion. If LBBB was known to be new or believed to represent an ST-segment elevation MI (STEMI) equivalent, the patient was excluded. Angiographic and echocardiographic data were reported on the case report form or obtained from a core angiography laboratory.
Our primary analysis examined 1-year mortality among survivors to hospital discharge (n = 24,848). We also examined in-hospital mortality (n = 25,934) and death or MI from hospital discharge to 30 days post-discharge among patients who survived event free to hospital discharge (n = 23,044).
Of 29,176 total patients, 27,832 (95.4%) had information on LBBB at baseline; LBBB was present in 490 (1.8%). LBBB patients were older, were more often female, had more comorbidities, and had a higher Killip class. In a subgroup with in-hospital assessment, they also had a lower left ventricular ejection fraction (40% vs. 55%, p < 0.001). Among 11,083 patients who had coronary angiographic data available (125 with and 10,958 without LBBB), right coronary artery lesion severity was greater among those with LBBB than without (80% vs. 72%, p = 0.032). Lesion severity was similar for the left anterior descending (LAD), left main, and left circumflex coronary arteries. Overall, 29.3% (3,242 of 11,083) had 100% occlusion in ≥1 main coronary vessel. Among patients with LAD lesions, more patients with LBBB than without had total LAD occlusion (26.8%, 19 of 71 vs. 14.9%, 1,265 of 8,467; p = 0.0055).
Patients with LBBB had greater in-hospital mortality than those without (4.3% vs. 2.6%), but the difference was not significant after adjustment for baseline characteristics (odds ratio: 0.99, 95% confidence interval [CI]: 0.62 to 1.59). Death or MI at 30 days post-discharge was also similar between groups (1.6% vs. 1.4%; adjusted odds ratio: 0.94, 95% CI: 0.43 to 2.05). Mortality between hospital discharge and 1-year post-discharge was higher among patients with LBBB at discharge (13.6%) than without (4.3%) (Fig. 1). After adjustment, 1-year mortality was nearly 2-fold greater among LBBB patients (hazard ratio: 1.84, 95% CI: 1.4 to 2.4). Results were similar in sensitivity analyses using LBBB at baseline instead of discharge.
LBBB has been associated with higher long-term mortality among acute MI patients; yet it is less certain whether LBBB independently predicts mortality (2). LBBB has not been studied in solely NSTE ACS populations. In mixed STEMI and NSTE ACS populations, there has been no clear association between LBBB and 1-year mortality (3). We demonstrated that LBBB at discharge was independently associated with nearly 2-fold higher 1-year mortality among NSTE ACS patients, but found no significant association with in-hospital or short-term outcomes. This contrasts with STEMI, in which LBBB patients had higher short-term mortality and in-hospital complications (1).
Lower left ventricular ejection fraction in the LBBB population could help to explain worse 1-year mortality. No data were available on use of implantable cardiac defibrillator devices or resynchronization therapy, which could additionally have affected this observed association.
Nearly twice as many LBBB patients had total LAD occlusion versus those without LBBB (26.8% vs. 14.9%). We could not distinguish between those with chronic occlusion (with collateral flow) versus acute (i.e., misdiagnosed STEMI), beyond presuming previous coronary artery bypass graft (52.6% [10 of 19] with LBBB vs. 46.2% [584 of 1,265] without) represented revascularized LAD. Electrocardiograms were not available to determine Sgarbossa criteria; thus, we could not determine based on these criteria whether some LBBB patients represented patients with possible STEMI (4). Further, there is not consensus that LBBB is a marker of acute MI or coronary disease severity among patients presenting with potentially ischemic symptoms (5). However, the more frequent total LAD occlusion and more severe coronary lesions we observed illustrate the importance of coronary angiography in NSTE ACS patients with LBBB.
In this retrospective study, we could not account for unmeasured confounders, and cause–effect relationships cannot be established. LBBB was classified by individual investigators, and protocols varied by trial – potentially introducing selection bias or misclassification of some STEMI patients as having NSTE ACS. We were unable to adjust for severity of coronary disease (particularly in LAD), which could contribute to differences in mortality. There were few patients with LBBB and relatively few events, limiting power to detect differences between those with and without LBBB.
LBBB patients were older and had more comorbidities than those without LBBB. Short-term and in-hospital ischemic outcomes were similar, but LBBB patients had nearly 2-fold higher 1-year mortality after adjustment for other factors. Thus, it may be reasonable to consider LBBB in addition to other factors to identify NSTE ACS patients at higher longer-term risk.
Please note: Dr. Newby has received honoraria from and is president of the Society of Chest Pain Centers; she has also received research funding and/or consulting fees from Amgen, Amylin, AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, diaDexus, Eli Lilly, Genentech, GlaxoSmithKline, Johnson & Johnson, Merck & Co., Murdock Study, NHLBI, Novartis, Regado Biosciences, and Roche. Dr. Van de Werf is on the advisory boards and Speaker's Bureaus of Merck Sharp and Dohme, Boehringer Ingelheim, and AstraZeneca. Dr. Armstrong is a consultant for AstraZeneca and Eli Lilly; and has received research funding from Boehringer-Ingelheim, Hoffmann LaRoche, sanofi-aventis Canada, and, in conjunction with the Duke Clinical Research Institute, Merck Sharp & Dohme. Dr. Harrington has received research funding and advisory consulting fees from Bristol-Myers Squibb, Gilead Pharmaceuticals, Johnson & Johnson, Merck, Orexigen, and WebMD. Dr. Ohman has received research funding from Eli Lilly, Daiichi Sankyo, and Gilead; and is a consultant for Pozen, Jansen Pharmaceutical, and, through Duke University, Faculty Connection. Dr. Giugliano has received a research grant from Merck & Co. Dr. Goodman has received funding for the ECG Core Laboratory from sanofi-aventis for the SYNERGY trial; sanofi-aventis also provided financial support to the Canadian Heart Research Centre for the ECG Core Laboratory for the SYNERGY ECG substudy. Dr. White has received financial support from sanofi-aventis, Eli Lilly, The Medicines Company, the National Institutes of Health, Pfizer, Roche, Johnson & Johnson, Schering Plough, Merck Sharp & Dohme, AstraZeneca, GlaxoSmithKline, Daiichi Sankyo Pharma Development, and Bristol-Myers Squibb; and is on the advisory boards of Merck Sharpe & Dohme and Regado Biosciences. Dr. Califf is a consultant for Avalere Health, Bayer, Biogen, Brandeis University, Eli Lilly, FivePrime, Heart.org, the Kowa Research Institute, and Merck & Co; has been a speaker for Heart.org and the Kowa Research Institute; and has received research funding from Merck & Co. Dr. Granger has received consulting and/or speaker's fees from Boehringer-Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Hoffmann-La Roche, Medtronic Foundation, Merck & Co, Novartis, Eli Lilly, Pfizer, sanofi-aventis, Takeda, The Medicines Company, and AstraZeneca. Dr. Lopes is a consultant for and has received research funding from Bristol-Myers Squibb. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
- GUSTO I Investigators
- Stenestrand U.,
- Tabrizi F.,
- Lindbäck J.,
- Englund A.,
- Rosenqvist M.,
- Wallentin L.