Association of incident LBBB with clinical endpoints in multivariate Cox regression models*
Endpoint
No new LBBB, n (%)
Incident LBBB, n (%)
HR (95% CIs)
P
Primary composite endpoint
988 (25.8)
28 (19.7)
1.91 (1.26–2.88)
< 0.001
Stroke
502 (12.9)
6 (4.0)
0. 66 (0.36–1.20)
0.655
Myocardial infarction
360 (9.2)
5 (3.3)
1.06 (0.43–2.62)
0.893
CV mortality
364 (9.0)
21 (13.2)
3.04 (1.83–5.05)
< 0.001
Sudden cardiac death
564 (14.6)
7 (4.8)
1.26 (0.82–1.93)
0.294
Hospitalization for heart failure
264 (6.7)
12 (8.4)
3.55 (1.90–6.64)
< 0.001
All-cause mortality
705 (17.7)
34 (21.6)
2.97 (2.04–4.33)
< 0.001
Adjusted for diabetes, isolated systolic hypertension, prevalent CV disease, Framingham risk score, randomized treatment assignments and degree of ECG-LVH at baseline as fixed covariates, and incident LBBB, ECG-LVH by Cornell voltage and diastolic and systolic blood pressures obtained on LIFE study follow-up examinations as time-varying covariates. All-cause mortality was considered as a competing end-point for outcomes including non-fatal events
Declarations
Acknowledgments
The authors thank the 945 clinical investigators who participated in the LIFE study.
Author contributions
CNB, ZL and PMO contributed to the conception and design of this LIFE sub-study. CNB, ZL and PMO performed the statistical analyses. ZL wrote the first draft of the manuscript. All authors contributed to manuscript revision, read and approved the submitted version.
Conflicts of interest
Sverre E. Kjeldsen has received lecture honoraria within the past 3 years from Getz Pharma, Merck Healthcare KGaA, Sanofi-Aventis and Vector-Intas. The other authors declare that they have no conflicts of interest.
Ethical approval
Ethical committees for all participating clinical centers approved the LIFE study. The study was performed in accordance with the Declaration of Helsinki. The study was chaired by an academic steering committee, and it was overseen by an independent data and safety monitoring board.
Consent to participate
Written informed consent to participate in the study was obtained from all participants.
Consent to publication
Not applicable.
Availability of data and materials
The data that support the findings of this study are available from the corresponding author (PMO) upon dire need.
Funding
Merck & Co., Inc. supported the LIFE study with an unrestricted grant from 1993. Merck had a non-voting member of the Steering Committee, which designed the study and wrote the protocol. Merck did monitoring, and accumulated data in a Merck database until study end in 2002. Merck provided the study steering committee with free access to blinded data until 2002 and then un-blinded data after the database was cleared for queries and frozen. The steering committee including a committee statistician validated independently the main outcomes. The steering committee has always been free to analyze and interpret the data, make decisions to publish and write the papers. Merck has not had any formal role after 2002 except for sporadically providing expert statistical assistance.
Sundström J, Lind L, Andrén B, Lithell H.Left ventricular geometry and function are related to electrocardiographic characteristics and diagnoses. Clin Physiol. 1998;18:463–70. [DOI] [PubMed]
Ozdemir K, Altunkeser BB, Daniş G, Ozdemir A, Uluca Y, Tokaç M, et al. Effect of the isolated left bundle branch block on systolic and diastolic functions of left ventricle. J Am Soc Echocardiogr. 2001;14:1075–9. [DOI] [PubMed]
Grines CL, Bashore TM, Boudoulas H, Olson S, Shafer P, Wooley CF.Functional abnormalities in isolated left bundle branch block. The effect of interventricular asynchrony. Circulation. 1989;79:845–53. [DOI] [PubMed]
Hamby RI, Weissman RH, Prakash MN, Hoffman I.Left bundle branch block: a predictor of poor left ventricular function in coronary artery disease. Am Heart J.1983;106:471–7. [DOI] [PubMed]
Li ZB, Wachtell K, Okin PM, Gerdts E, Liu JE, Nieminen MS, et al. Association of left bundle branch block with left ventricular structure and function in hypertensive patients with left ventricular hypertrophy: the LIFE study. J Hum Hypertens. 2004;18:397–402. [DOI] [PubMed]
Baldasseroni S, Opasich C, Gorini M, Lucci D, Marchionni N, Marini M, et al. Left bundle-branch block is associated with increased 1-year sudden and total mortality rate in 5517 outpatients with congestive heart failure: a report from the Italian network on congestive heart failure. Am Heart J. 2002;143:398–405. [DOI] [PubMed]
Huang X, Shen W, Gong L.Clinical significance of complete left bundle branch block in dilated cardiomyopathy. Chin Med Sci J. 1995;10:158–60. [PubMed]
Li Z, Dahlöf B, Okin PM, Kjeldsen SE, Wachtell K, Ibsen H, et al. Left bundle branch block and cardiovascular morbidity and mortality in hypertensive patients with left ventricular hypertrophy: the Losartan Intervention For Endpoint Reduction in Hypertension study. J Hypertens. 2008;26:1244–9. [DOI] [PubMed]
Dahlöf B, Devereux R, de Faire U, Fyhrquist F, Hedner T, Ibsen H, et al. The Losartan Intervention For Endpoint reduction (LIFE) in Hypertension study: rationale, design, and methods. The LIFE Study Group. Am J Hypertens. 1997;10:705–13. [PubMed]
Dahlöf B, Devereux RB, Julius S, Kjeldsen SE, Beevers G, de Faire U, et al. Characteristics of 9194 patients with left ventricular hypertrophy: the LIFE Study. Losartan Intervention For Endpoint Reduction in Hypertension. Hypertension. 1998;32:989–97. [DOI] [PubMed]
Dahlöf B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet.2002;359:995–1003. [DOI] [PubMed]
Oikarinen L, Nieminen MS, Viitasalo M, Toivonen L, Jern S, Dahlöf B, et al. QRS duration and QT interval predict mortality in hypertensive patients with left ventricular hypertrophy: the Losartan Intervention for Endpoint Reduction in Hypertension Study. Hypertension. 2004;43:1029–34. [DOI] [PubMed]
Oikarinen L, Nieminen MS, Viitasalo M, Toivonen L, Wachtell K, Papademetriou V, et al. Relation of QT interval and QT dispersion to echocardiographic left ventricular hypertrophy and geometric pattern in hypertensive patients. The LIFE study. The Losartan Intervention For Endpoint Reduction. J Hypertens. 2001;19:1883–91. [DOI] [PubMed]
Kjeldsen SE, Dahlöf B, Devereux RB, Julius S, Aurup P, Edelman J et al.;LIFE (Losartan Intervention for Endpoint Reduction) Study Group. Effects of losartan on cardiovascular morbidity and mortality in patients with isolated systolic hypertension and left ventricular hypertrophy: a Losartan Intervention for Endpoint Reduction (LIFE) substudy. JAMA. 2002;288:1491–8. [DOI] [PubMed]
Fine JP, Gray RJ.A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509. [DOI]
Johnson RP, Messer AL, Shreenivas, White PD.Prognosis in bundle branch block. II. Factors influencing the survival period in left bundle branch block. Am Heart J. 1951;41:225–38. [DOI] [PubMed]
Graybiel A, Sprague HB.Bundle branch block; an analysis of 395 cases. Am J Med Sci.1933;185:395–401.
Bauer GE.Bundle branch block: some usual and some unusual features. Australas Ann Med. 1964;13:62–71. [DOI] [PubMed]
Smith S, Hayes WL.The prognosis of complete left bundle branch block. Am Heart J.1965;70:157–9. [DOI] [PubMed]
Bauer GE.Development of bundle branch block. Am J Cardiol.1964;14:346–51. [DOI]
Campbell M.The outlook with bundle-branch block. Br Heart J. 1969;31:575–9. [DOI] [PubMed] [PMC]
Mulcahy R, Hickey N, Maurer B.Aetiology of bundle-branch block. Br Heart J. 1968;30:34–7. [DOI] [PubMed] [PMC]
Rasmussen H, Moe T.Pathogenesis of left bundle branch block. Br Heart J. 1948;10:141–7. [DOI] [PubMed] [PMC]
Lamb LE, Kable KD, Averill KH.Electrocardiographic findings in 67,375 asymptomatic subjects. V. Left bundle branch block. Am J Cardiol. 1960;6:130–42. [DOI] [PubMed]
Lamb LE, Johnson RL.Left bundle branch block in flying personnel: a report of 56 cases. Aerospace Med. 1964;35:97–104. [PubMed]
Schneider JF, Thomas HE Jr, Kreger BE, McNamara PM, Kannel WB.Newly acquired left bundle-branch block: the Framingham study. Ann Intern Med.1979;90:303–10. [DOI] [PubMed]
Eriksson P, Hansson PO, Eriksson H, Dellborg M.Bundle-branch block in a general male population: the study of men born 1913. Circulation. 1998;98:2494–500. [DOI] [PubMed]
Okin PM, Devereux RB, Kjeldsen SE, Edelman JM, Dahlöf B.Incidence of heart failure in relation to QRS duration during antihypertensive therapy: the LIFE study. J Hypertens. 2009;27:2271–7. [DOI] [PubMed]
Aksnes TA, Schmieder RE, Kjeldsen SE, Ghani S, Hua TA, Julius S.Impact of new-onset diabetes mellitus on development of atrial fibrillation and heart failure in high-risk hypertension (from the VALUE Trial). Am J Cardiol. 2008;101:634–8. [DOI] [PubMed]
Dahlöf B, Burke TA, Krobot K, Carides GW, Edelman JM, Devereux RB, et al. Population impact of losartan use on stroke in the European Union (EU): projections from the Losartan Intervention For Endpoint reduction in hypertension (LIFE) Study. J Hum Hypertens. 2004;18:367–73. [DOI] [PubMed]
Matsuyama N, Tsutsumi T, Kubota N, Nakajima T, Suzuki H, Takeyama Y.Direct action of an angiotensin II receptor blocker on angiotensin II-induced left atrial conduction delay in spontaneously hypertensive rats. Hypertens Res. 2009;32:721–6. [DOI] [PubMed]
