Prevalence of right ventricular dysfunction and prognostic significance in heart failure with preserved ejection fraction

Prathap Kanagala, Jayanth R Arnold, Anvesha Singh, Jamal N Khan, Gaurav S Gulsin, Pankaj Gupta, Iain B Squire, Leong L Ng, Gerry P McCann, Prathap Kanagala, Jayanth R Arnold, Anvesha Singh, Jamal N Khan, Gaurav S Gulsin, Pankaj Gupta, Iain B Squire, Leong L Ng, Gerry P McCann

Abstract

There is a paucity of data characterizing right ventricular performance in heart failure with preserved ejection fraction (HFpEF) using the gold standard of cardiovascular magnetic resonance imaging (CMR). We aimed to assess the proportion of right ventricular systolic dysfunction (RVD) in HFpEF and the relation to clinical outcomes. As part of a single-centre, prospective, observational study, 183 subjects (135 HFpEF, and 48 age- and sex-matched controls) underwent extensive characterization with CMR. transthoracic echocardiography, blood sampling and six-minute walk testing. Patients were followed for the composite endpoint of death or HF hospitalization. RVD (defined as right ventricular ejection fraction < 47%) controls was present in 19% of HFpEF. Patients with RVD presented more frequently with lower systolic blood pressure, atrial fibrillation, radiographic evidence of pulmonary congestion and raised cardiothoracic ratio and larger right ventricular volumes. During median follow-up of 1429 days, 47% (n = 64) of HFpEF subjects experienced the composite endpoint of death (n = 22) or HF hospitalization (n = 42). RVD was associated with an increased risk of composite events (Log-Rank p = 0.001). In multivariable Cox regression analysis, RVD was an independent predictor of adverse outcomes (adjusted Hazard Ratio [HR] 3.946, 95% CI 1.878-8.290, p = 0.0001) along with indexed extracellular volume (HR 1.742, CI 1.176-2.579, p = 0.006) and E/E' (HR 1.745, CI 1.230-2.477, p = 0.002). RVD as assessed by CMR is prevalent in nearly one-fifth of HFpEF patients and is independently associated with death and/or hospitalization with HF.The trial was registered retrospectively on ClinicalTrials.gov (Identifier: NCT03050593). The date of registration was February 06, 2017.

Keywords: Cardiovascular magnetic resonance imaging; Heart failure with preserved ejection fraction; Prevalence; Prognosis; Right ventricular dysfunction.

Conflict of interest statement

All authors declare that they have no competing interests relevant to this study. All authors also state that they have full control of all primary data and that they agree to allow the journal to review their data if requested.

Figures

Fig. 1
Fig. 1
Assessment of ventricular volumes, function and mass. End-diastolic (a) and end-systolic (b) cine frames illustrating manually drawn contours of the left ventricular endocardium (pink), left ventricular epicardium (green) and right ventricular endocardium (yellow) for volumetric and mass analysis. (white arrows) papillary muscles and trabeculations were excluded from left ventricular mass calculations
Fig. 2
Fig. 2
Study recruitment overview. Flow chart illustrating recruitment and reasons for exclusion. CMR cardiovascular magnetic resonance imaging, HFpEF heart failure with preserved ejection fraction, RV right ventricle
Fig. 3
Fig. 3
Survival analysis stratified according to the presence or absence of right ventricular dysfunction. Kaplan–Meier analysis for the composite endpoint of death and/or hospitalization with heart failure; RVD right ventricular dysfunction

References

    1. Di Salvo TG, Mathier M, Semigran MJ, et al. Preserved right ventricular ejection fraction predicts exercise capacity and survival in advanced heart failure. J Am Coll Cardiol. 1995;25(5):1143–1153. doi: 10.1016/0735-1097(94)00511-N.
    1. Gulati A, Ismail TF, Jabbour A, et al. The prevalence and prognostic significance of right ventricular systolic dysfunction in nonischemic dilated cardiomyopathy. Circulation. 2013;128(15):1623–1633. doi: 10.1161/CIRCULATIONAHA.113.002518.
    1. Owan TE, Hodge DO, Herges RM, et al. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006;355(3):251–259. doi: 10.1056/NEJMoa052256.
    1. Gorter TM, van Veldhuisen DJ, Bauersachs J, et al. Right heart dysfunction and failure in heart failure with preserved ejection fraction: mechanisms and management. Position statement on behalf of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Failure. 2017;10:20. doi: 10.1002/ejhf.1029.
    1. Zakeri R, Mohammed SF. Epidemiology of right ventricular dysfunction in heart failure with preserved ejection fraction. Curr Heart Fail Rep. 2015;12(5):295–301. doi: 10.1007/s11897-015-0267-3.
    1. Champion HC, Michelakis ED, Hassoun PM. Comprehensive invasive and noninvasive approach to the right ventricle-pulmonary circulation unit: state of the art and clinical and research implications. Circulation. 2009;120(11):992–1007. doi: 10.1161/CIRCULATIONAHA.106.674028.
    1. Grothues F, Moon JC, Bellenger NG, et al. Interstudy reproducibility of right ventricular volumes, function, and mass with cardiovascular magnetic resonance. Am Heart J. 2004;147(2):218–223. doi: 10.1016/j.ahj.2003.10.005.
    1. Aschauer S, Kammerlander AA, Zotter-Tufaro C, et al. The right heart in heart failure with preserved ejection fraction: insights from cardiac magnetic resonance imaging and invasive haemodynamics. Eur J Heart Fail. 2016;18(1):71–80. doi: 10.1002/ejhf.418.
    1. Goliasch G, Zotter-Tufaro C, Aschauer S, et al. Outcome in heart failure with preserved ejection fraction: the role of myocardial structure and right ventricular performance. PLoS ONE. 2015;10(7):e0134479. doi: 10.1371/journal.pone.0134479.
    1. Kanagala P, Arnold JR, Singh A, et al. Characterizing heart failure with preserved and reduced ejection fraction: an imaging and plasma biomarker approach. PLoS ONE. 2020;15(4):e0232280. doi: 10.1371/journal.pone.0232280.
    1. Kanagala P, Arnold JR, Cheng ASH, et al. Left atrial ejection fraction and outcomes in heart failure with preserved ejection fraction. Int J Cardiovasc Imaging. 2019 doi: 10.1007/s10554-019-01684-9.
    1. Kanagala P, Cheng ASH, Singh A, et al. Diagnostic and prognostic utility of cardiovascular magnetic resonance imaging in heart failure with preserved ejection fraction: implications for clinical trials. J Cardiovasc Magn Reson. 2018;20(1):4. doi: 10.1186/s12968-017-0424-9.
    1. Palau P, Dominguez E, Nunez E, et al. Six-minute walk test in moderate to severe heart failure with preserved ejection fraction: useful for functional capacity assessment? Int J Cardiol. 2016;203:800–802. doi: 10.1016/j.ijcard.2015.11.074.
    1. Kanagala P, Arnold JR, Singh A, et al. Intra-study and inter-technique validation of cardiovascular magnetic resonance imaging derived left atrial ejection fraction as a prognostic biomarker in heart failure with preserved ejection fraction. Int J Cardiovasc Imaging. 2020;36(5):921–928. doi: 10.1007/s10554-020-01785-w.
    1. Kanagala P, Cheng ASH, Singh A, et al. Relationship between focal and diffuse fibrosis assessed by CMR and clinical outcomes in heart failure with preserved ejection fraction. JACC Cardiovasc Imaging. 2019 doi: 10.1016/j.jcmg.2018.11.031.
    1. Hudsmith LE, Petersen SE, Francis JM, et al. Normal human left and right ventricular and left atrial dimensions using steady state free precession magnetic resonance imaging. J Cardiovasc Magn R. 2005;7(5):775–782. doi: 10.1080/10976640500295516.
    1. Schulz-Menger J, Bluemke DA, Bremerich J, et al. Standardized image interpretation and post processing in cardiovascular magnetic resonance: Society for Cardiovascular Magnetic Resonance (SCMR) board of trustees task force on standardized post processing. J Cardiovasc Magn Reson. 2013;15:35. doi: 10.1186/1532-429X-15-35.
    1. Singh A, Horsfield MA, Bekele S, et al. Myocardial T1 and extracellular volume fraction measurement in asymptomatic patients with aortic stenosis: reproducibility and comparison with age-matched controls. Eur Heart J Cardiovasc Imaging. 2015 doi: 10.1093/ehjci/jev007.
    1. Marcus FI, McKenna WJ, Sherrill D, et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the Task Force Criteria. Eur Heart J. 2010;31(7):806–814. doi: 10.1093/eurheartj/ehq025.
    1. Haddad F, Doyle R, Murphy DJ, et al. Right ventricular function in cardiovascular disease, part II: pathophysiology, clinical importance, and management of right ventricular failure. Circulation. 2008;117(13):1717–1731. doi: 10.1161/CIRCULATIONAHA.107.653584.
    1. Mohammed SF, Hussain I, AbouEzzeddine OF, et al. Right ventricular function in heart failure with preserved ejection fraction: a community-based study. Circulation. 2014;130(25):2310–2320. doi: 10.1161/CIRCULATIONAHA.113.008461.
    1. Melenovsky V, Hwang SJ, Lin G, et al. Right heart dysfunction in heart failure with preserved ejection fraction. Eur Heart J. 2014;35(48):3452–3462. doi: 10.1093/eurheartj/ehu193.
    1. Burke MA, Katz DH, Beussink L, et al. Prognostic importance of pathophysiologic markers in patients with heart failure and preserved ejection fraction. Circ Heart Fail. 2013 doi: 10.1161/CIRCHEARTFAILURE.113.000854.
    1. Shah AM, Claggett B, Sweitzer NK, et al. Cardiac structure and function and prognosis in heart failure with preserved ejection fraction: findings from the echocardiographic study of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) Trial. Circ Heart Fail. 2014;7(5):740–751. doi: 10.1161/CIRCHEARTFAILURE.114.001583.
    1. Lam CS, Donal E, Kraigher-Krainer E, et al. Epidemiology and clinical course of heart failure with preserved ejection fraction. Eur J Heart Fail. 2011;13(1):18–28. doi: 10.1093/eurjhf/hfq121.
    1. Gorter TM, van Melle JP, Rienstra M, et al. Right heart dysfunction in heart failure with preserved ejection fraction: the impact of atrial fibrillation. J Cardiac Fail. 2018;24(3):177–185. doi: 10.1016/j.cardfail.2017.11.005.
    1. Obokata M, Reddy YNV, Melenovsky V, et al. Deterioration in right ventricular structure and function over time in patients with heart failure and preserved ejection fraction. Eur Heart J. 2019;40(8):689–697. doi: 10.1093/eurheartj/ehy809.
    1. Testani JM, Khera AV, St John Sutton MG, et al. Effect of right ventricular function and venous congestion on cardiorenal interactions during the treatment of decompensated heart failure. Am J Cardiol. 2010;105(4):511–516. doi: 10.1016/j.amjcard.2009.10.020.
    1. Genereux P, Pibarot P, Redfors B, et al. Staging classification of aortic stenosis based on the extent of cardiac damage. Eur Heart J. 2017;38(45):3351–3358. doi: 10.1093/eurheartj/ehx381.
    1. Fung JW, Sanderson JE, Yip GW, et al. Impact of atrial fibrillation in heart failure with normal ejection fraction: a clinical and echocardiographic study. J Cardiac Fail. 2007;13(8):649–655. doi: 10.1016/j.cardfail.2007.04.014.
    1. Borlaug BA, Kane GC, Melenovsky V, et al. Abnormal right ventricular-pulmonary artery coupling with exercise in heart failure with preserved ejection fraction. Eur Heart J. 2016;37(43):3293–3302. doi: 10.1093/eurheartj/ehw241.
    1. Patel RB, Li E, Benefield BC, et al. Diffuse right ventricular fibrosis in heart failure with preserved ejection fraction and pulmonary hypertension. ESC Heart Fail. 2020;7(1):253–263. doi: 10.1002/ehf2.12565.
    1. Aziz EF, Kukin M, Javed F, et al. Right ventricular dysfunction is a strong predictor of developing atrial fibrillation in acutely decompensated heart failure patients, ACAP-HF data analysis. J Cardiac Fail. 2010;16(10):827–834. doi: 10.1016/j.cardfail.2010.05.004.
    1. Tongers J, Schwerdtfeger B, Klein G, et al. Incidence and clinical relevance of supraventricular tachyarrhythmias in pulmonary hypertension. Am Heart J. 2007;153(1):127–132. doi: 10.1016/j.ahj.2006.09.008.
    1. Zakeri R, Chamberlain AM, Roger VL, et al. Temporal relationship and prognostic significance of atrial fibrillation in heart failure patients with preserved ejection fraction: a community-based study. Circulation. 2013;128(10):1085–1093. doi: 10.1161/CIRCULATIONAHA.113.001475.
    1. Stewart S, Jenkins A, Buchan S, et al. The current cost of heart failure to the National Health Service in the UK. Eur J Heart Fail. 2002;4(3):361–371. doi: 10.1016/S1388-9842(01)00198-2.
    1. Paulus WJ, van Ballegoij JJ. Treatment of heart failure with normal ejection fraction: an inconvenient truth! J Am Coll Cardiol. 2010;55(6):526–537. doi: 10.1016/j.jacc.2009.06.067.
    1. Guazzi M, Vicenzi M, Arena R, et al. Pulmonary hypertension in heart failure with preserved ejection fraction: a target of phosphodiesterase-5 inhibition in a 1-year study. Circulation. 2011;124(2):164–174. doi: 10.1161/CIRCULATIONAHA.110.983866.
    1. Alfakih K, Plein S, Bloomer T, et al. Comparison of right ventricular volume measurements between axial and short axis orientation using steady-state free precession magnetic resonance imaging. J Magn Reson Imaging. 2003;18(1):25–32. doi: 10.1002/jmri.10329.
    1. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37(27):2129–2200. doi: 10.1093/eurheartj/ehw128.
    1. Shah AM, Shah SJ, Anand IS, et al. Cardiac structure and function in heart failure with preserved ejection fraction: baseline findings from the echocardiographic study of the treatment of preserved cardiac function heart failure with an aldosterone antagonist trial. Circ Heart Fail. 2013 doi: 10.1161/CIRCHEARTFAILURE.113.000887.
    1. Mehra MR, Uber PA, Park MH, et al. Obesity and suppressed B-type natriuretic peptide levels in heart failure. J Am Coll Cardiol. 2004;43(9):1590–1595. doi: 10.1016/j.jacc.2003.10.066.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe