Higher left ventricular mass-wall stress-heart rate product and outcome in aortic valve stenosis

Eva Gerdts, Sahrai Saeed, Helga Midtbø, Anne Rossebø, John Boyd Chambers, Eigir Einarsen, Edda Bahlmann, Richard Devereux, Eva Gerdts, Sahrai Saeed, Helga Midtbø, Anne Rossebø, John Boyd Chambers, Eigir Einarsen, Edda Bahlmann, Richard Devereux

Abstract

Objective: Whether increased myocardial oxygen demand could help explain the association of left ventricular (LV) hypertrophy with higher adverse event rate in patients with aortic valve stenosis (AS) is unknown.

Methods: Data from 1522 patients with asymptomatic mostly moderate AS participating in the Simvastatin-Ezetimibe in AS study followed for a median of 4.3 years was used. High LV mass-wall stress-heart rate product was identified as >upper 95% CI limit in normal subjects. The association of higher LV mass-wall stress-heart rate product with major cardiovascular (CV) events, combined CV death and hospitalised heart failure and all-cause mortality was tested in Cox regression analyses, and reported as HR and 95% CI.

Results: High LV mass-wall stress-heart rate product was found in 19% at baseline, and associated with male sex, higher body mass index, hypertension, LV hypertrophy, more severe AS and lower LV ejection fraction (all p<0.01). Adjusting for these confounders in time-varying Cox regression analysis, 1 SD higher LV mass-wall stress-heart rate product was associated with higher HR of major CV events (HR 1.16(95% CI 1.06 to 1.29)), combined CV death and hospitalised heart failure (HR 1.29(95% CI 1.09 to 1.54)) and all-cause mortality (HR 1.34(95% CI 1.13 to 1.58), all p<0.01).

Conclusion: In patients with initially mild-moderate AS, higher LV mass-wall stress-heart rate product was associated with higher mortality and heart failure hospitalisation. Our results suggest that higher myocardial oxygen demand is contributing to the higher adverse event rate reported in AS patients with LV hypertrophy.

Trial registration number: NCT000092677;Post-results.

Trial registration: ClinicalTrials.gov NCT00092677.

Keywords: aortic stenosis; echocardiography; hypertension.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Association of high LV mass–wall stress–heart rate product with HRs of major cardiovascular events (A) and all-cause mortality (B) in the study population. Kaplan-Meier plots.

References

    1. Devereux RB, Alderman MH. Role of preclinical cardiovascular disease in the evolution from risk factor exposure to development of morbid events. Circulation 1993;88:1444–55. 10.1161/01.CIR.88.4.1444
    1. Levy D, Garrison RJ, Savage DD, et al. . Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 1990;322:1561–6. 10.1056/NEJM199005313222203
    1. Devereux RB, Roman MJ, Palmieri V, et al. . Left ventricular wall stresses and wall stress–mass–heart rate products in hypertensive patients with electrocardiographic left ventricular hypertrophy. J Hypertens 2000;18:1129–38. 10.1097/00004872-200018080-00019
    1. Dweck MR, Joshi S, Murigu T, et al. . Midwall fibrosis is an independent predictor of mortality in patients with aortic stenosis. J Am Coll Cardiol 2011;58:1271–9. 10.1016/j.jacc.2011.03.064
    1. Liao Y, Cooper RS, McGee DL, et al. . The relative effects of left ventricular hypertrophy, coronary artery disease, and ventricular dysfunction on survival among black adults. JAMA 1995;273:1592–7. 10.1001/jama.1995.03520440046035
    1. Galderisi M, de Simone G, D’Errico A, et al. . Independent association of coronary flow reserve with left ventricular relaxation and filling pressure in arterial hypertension. Am J Hypertens 2008;21:1040–6. 10.1038/ajh.2008.226
    1. Irvine T, Kenny A. Aortic stenosis and angina with normal coronary arteries: the role of coronary flow abnormalities. Heart 1997;78:213–4. 10.1136/hrt.78.3.213
    1. Koyanagi S, Eastham CL, Harrison DG, et al. . Increased size of myocardial infarction in dogs with chronic hypertension and left ventricular hypertrophy. Circ Res 1982;50:55–62. 10.1161/01.RES.50.1.55
    1. Koyanagi S, Eastham C, Marcus ML. Effects of chronic hypertension and left ventricular hypertrophy on the incidence of sudden cardiac death after coronary artery occlusion in conscious dogs. Circulation 1982;65:1192–7. 10.1161/01.CIR.65.6.1192
    1. Inou T, Lamberth WC, Koyanagi S, et al. . Relative importance of hypertension after coronary occlusion in chronic hypertensive dogs with LVH. Am J Physiol 1987;253(5 Pt 2):H1148–H1158. 10.1152/ajpheart.1987.253.5.H1148
    1. Devereux RB, Bang CN, Roman MJ, et al. . Left ventricular wall stress-mass-heart rate product and cardiovascular events in treated hypertensive patients: LIFE study. Hypertension 2015;66:945–53. 10.1161/HYPERTENSIONAHA.114.05582
    1. Saeed S, Gerdts E. Managing complications of hypertension in aortic valve stenosis patients. Expert Rev Cardiovasc Ther 2018;16:897–907. 10.1080/14779072.2018.1535899
    1. Rieck ÅE, Cramariuc D, Boman K, et al. . Hypertension in aortic stenosis: implications for left ventricular structure and cardiovascular events. Hypertension 2012;60:90–7. 10.1161/HYPERTENSIONAHA.112.194878
    1. Gerdts E, Rossebø AB, Pedersen TR, et al. . Relation of left ventricular mass to prognosis in initially asymptomatic mild to moderate aortic valve stenosis. Circ Cardiovasc Imaging 2015;8:e003644 10.1161/CIRCIMAGING.115.003644
    1. Rossebø AB, Pedersen TR, Boman K, et al. . Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med 2008;359:1343–56. 10.1056/NEJMoa0804602
    1. Lang RM, Bierig M, Devereux RB, et al. . Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18:1440–63. 10.1016/j.echo.2005.10.005
    1. Baumgartner H, Falk V, Bax JJ, et al. . ESC/EACTS Guidelines for the management of valvular heart disease. The Task Force for the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2017;2017:2739–91.
    1. Gaasch WH, Zile MR, Hoshino PK, et al. . Stress-shortening relations and myocardial blood flow in compensated and failing canine hearts with pressure-overload hypertrophy. Circulation 1989;79:872–83. 10.1161/01.CIR.79.4.872
    1. de Simone G, Devereux RB, Koren MJ, et al. . Midwall left ventricular mechanics. An independent predictor of cardiovascular risk in arterial hypertension. Circulation 1996;93:259–65.
    1. Devereux RB, de Simone G, Pickering TG, et al. . Relation of left ventricular midwall function to cardiovascular risk factors and arterial structure and function. Hypertension 1998;31:929–36. 10.1161/01.HYP.31.4.929
    1. Bahlmann E, Gerdts E, Cramariuc D, et al. . Prognostic value of energy loss index in asymptomatic aortic stenosis. Circulation 2013;127:1149–56. 10.1161/CIRCULATIONAHA.112.078857
    1. Stanton T, Dunn FG. Hypertension, Left Ventricular Hypertrophy, and Myocardial Ischemia. Med Clin North Am 2017;101:29–41. 10.1016/j.mcna.2016.08.003
    1. Lønnebakken MT, Rieck AE, Gerdts E. Contrast stress echocardiography in hypertensive heart disease. Cardiovasc Ultrasound 2011;9:33 10.1186/1476-7120-9-33
    1. Galiuto L, Lotrionte M, Crea F, et al. . Impaired coronary and myocardial flow in severe aortic stenosis is associated with increased apoptosis: a transthoracic Doppler and myocardial contrast echocardiography study. Heart 2006;92:208–12. 10.1136/hrt.2005.062422
    1. Hein S, Arnon E, Kostin S, et al. . Progression from compensated hypertrophy to failure in the pressure-overloaded human heart: structural deterioration and compensatory mechanisms. Circulation 2003;107:984–91.
    1. Rieck AE, Gerdts E, Lønnebakken MT, et al. . Global left ventricular load in asymptomatic aortic stenosis: covariates and prognostic implication (the SEAS trial). Cardiovasc Ultrasound 2012;10:43 10.1186/1476-7120-10-43
    1. Antonini-Canterin F, Huang G, Cervesato E, et al. . Symptomatic aortic stenosis: does systemic hypertension play an additional role? Hypertension 2003;41:1268–72. 10.1161/01.HYP.0000070029.30058.59
    1. Pellikka PA, Sarano ME, Nishimura RA, et al. . Outcome of 622 adults with asymptomatic, hemodynamically significant aortic stenosis during prolonged follow-up. Circulation 2005;111:3290–5. 10.1161/CIRCULATIONAHA.104.495903
    1. Hansson NH, Sörensen J, Harms HJ, et al. . Myocardial oxygen consumption and efficiency in aortic valve stenosis patients with and without heart failure. J Am Heart Assoc 2017;6:pii: e004810 10.1161/JAHA.116.004810
    1. Bang CN, Greve AM, Rossebø AB, et al. . Antihypertensive treatment with β‐blockade in patients with asymptomatic aortic stenosis and association with cardiovascular events. J Am Heart Assoc 2017;6:pii: e006709 10.1161/JAHA.117.006709

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner