Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Oct;8(5):4243-4254.
doi: 10.1002/ehf2.13533. Epub 2021 Aug 10.

Predictors of long-term outcome in heart failure with preserved ejection fraction: a follow-up from the KaRen study

Angiza Shahim  1 , Marion Hourqueig  2 , Erwan Donal  2 , Emmanuel Oger  3 , Ashwin Venkateshvaran  1   4 , Jean-Claude Daubert  2 , Gianluigi Savarese  1   4 , Cecilia Linde  1   4 , Lars H Lund  1   4 , Camilla Hage  1   4
Affiliations

Predictors of long-term outcome in heart failure with preserved ejection fraction: a follow-up from the KaRen study

Angiza Shahim et al. ESC Heart Fail. 2021 Oct.

Abstract

Aims: Heart failure (HF) with preserved ejection fraction (HFpEF) has poor long-term prognosis. We assessed rates and predictors of outcome 10 years after an acute episode of HF.

Methods and results: The Karolinska-Rennes (KaRen) study enrolled HFpEF patients with acute HF, ejection fraction ≥ 45%, and N-terminal pro-brain natriuretic peptide > 300 ng/L in 2007-11. Clinical data were collected at enrolment and after 4-8 weeks including detailed echocardiography. Follow-up data were collected 10 years after study initiation, starting from 6 months after enrolment until 2018 assessed by telephone. Independent predictors of primary (all-cause mortality or HF hospitalization) and secondary (all-cause mortality) outcomes were assessed by multivariable Cox regression. Of 539 patients, long-term follow-up data were available for 397 patients [52% female; median (interquartile range) age 79 (73, 84) years]. Over a follow-up of 5.44 (2.06-7.89) years, 1, 3, 5, and 10 year mortality rates were 15%, 31%, 47%, and 74%, respectively, with an incidence rate of 130/1000 patient-years. The primary outcome was met in 84% of the population, with an incidence rate of 227/1000 patient-years. The independent predictors of the primary outcome were tricuspid regurgitation peak velocity (m/s) [hazard ratio 1.87 (1.34-2.62)], diabetes mellitus [1.75 (1.11-2.74)], and cancer [1.75 (1.01-3.03)] while female sex was associated with reduced risk [0.64 (0.41-0.98)].

Conclusions: In HFpEF, 1, 3, 5, and 10 year mortality was 15%, 31%, 47%, and 74% and mortality or first HF hospitalization was 35%, 54%, 67%, and 84%, respectively. Independent predictors of mortality or HF hospitalization were tricuspid regurgitation peak velocity, diabetes mellitus, cancer, and male sex. In clinical management of HFpEF, attention should be paid to both cardiac and non-cardiac conditions.

Keywords: Diastolic heart failure; HFpEF; Mortality; Predictors; Prognosis.

PubMed Disclaimer

Conflict of interest statement

C.H. receives consulting fees from Novartis and Roche Diagnostics and speaker honoraria from Novartis and MSD; E.D. receives research facilities from General Electric Healthcare and a grant from Novartis. He has also teaching facilities provided by Bristol‐Myer‐Squibb; C.L. receives research grants from Swedish Heart‐Lung Foundation and Stockholm County Council and speaker honoraria from Medtronic, Abbot, Microport, Boston Scientific, Novartis, Vifor, Impulse Dynamics, and Bayer; G.S. reports grants and personal fees from Vifor, grants and non‐financial support from Boehringer Ingelheim, personal fees from Società Prodotti Antibiotici, grants from MSD, grants and personal fees from AstraZeneca, personal fees from Roche, personal fees from Servier, grants from Novartis, personal fees from GENESIS, personal fees from Cytokinetics, and personal fees from Medtronic, outside the submitted work; L.H.L. was funded by the Swedish Research Council, the Swedish Heart Lung Foundation, and the Stockholm County Council and receives research grants from AstraZeneca, Novartis, Boehringer Ingelheim, ViforPharma, and Boston Scientific and consulting or speaker's honoraria from AstraZeneca, Novartis, Boehringer Ingelheim, ViforPharma, Bayer, Sanofi, Fresenius, Merck, Myokardia, MedScape, Radcliffe Cardiology, and Lexicon. Other authors have no conflict of interest to declare.

Figures

Figure 1
Figure 1
Flow chart showing patient inclusion in the 10 year follow‐up analysis of the Karolinska‐Rennes (KaRen) study.
Figure 2
Figure 2
The Kaplan–Meier survival curves of the primary outcome (all‐cause mortality or first heart failure hospitalization)—Survival curves for (A) all subjects and (B) sex and (C) subjects with tricuspid regurgitation peak velocity (TR) classified as low (<2.8 m/s), medium (2.8–3.1 m/s), or high (>3.1 m/s) and (D) E/e′ ratio classified as >13 or ≤13.
Figure 3
Figure 3
The Kaplan–Meier survival curves of the secondary outcome (all‐cause mortality)—Survival curves for (A) all subjects and (B) sex and (C) subjects with tricuspid regurgitation peak velocity (TR) classified as low (<2.8 m/s), medium (2.8–3.1 m/s), or high (>3.1 m/s) and (D) E/e′ ratio classified as >13 or ≤13.
Figure 4
Figure 4
Predictors of all‐cause mortality or first heart failure hospitalization—Forest plot depicting multivariable hazard ratios for the primary outcome (time to all‐cause mortality or first heart failure hospitalization). ACE inhibitor, angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blocker; BMI, body mass index; CI, confidence interval; eGFR, estimated glomerular filtration rate; IVST, interventricular septal thickness; LV s′, systolic peak of mitral annulus velocity; LVEF, left ventricular ejection fraction; MRA, mineralocorticoid receptor antagonists; NT‐proBNP, N‐terminal pro–B‐type natriuretic peptide; NYHA, New York Heart Association; TR, tricuspid regurgitation peak velocity.
Figure 5
Figure 5
Predictors of all‐cause mortality—Forest plot depicting multivariable hazard ratios for the secondary outcome (time to all‐cause mortality). Abbreviations as in Figure 4 .
See this image and copyright information in PMC

References

    1. Savarese G, Lund LH. Global public health burden of heart failure. Card Fail Rev 2017; 3: 7. - PMC - PubMed
    1. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, Falk V, González‐Juanatey JR, Harjola V‐P, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GMC, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P, Filippatos G, McMurray JJV, Aboyans V, Achenbach S, Agewall S, Al‐Attar N, Atherton JJ, Bauersachs J, John Camm A, Carerj S, Ceconi C, Coca A, Elliott P, Erol Ç, Ezekowitz J, Fernández‐Golfín C, Fitzsimons D, Guazzi M, Guenoun M, Hasenfuss G, Hindricks G, Hoes AW, Iung B, Jaarsma T, Kirchhof P, Knuuti J, Kolh P, Konstantinides S, Lainscak M, Lancellotti P, Lip GYH, Maisano F, Mueller C, Petrie MC, Piepoli MF, Priori SG, Torbicki A, Tsutsui H, Veldhuisen VJD, Windecker S, Yancy C, Zamorano JL, Zamorano JL, Aboyans V, Achenbach S, Agewall S, Badimon L, Barón‐Esquivias G, Baumgartner H, Bax JJ, Bueno H, Carerj S, Dean V, Erol Ç, Fitzsimons D, Gaemperli O, Kirchhof P, Kolh P, Lancellotti P, Lip GYH, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Roffi M, Torbicki A, Vaz Carneiro A, Windecker S, Sisakian HS, Isayev E, Kurlianskaya A, Mullens W, Tokmakova M, Agathangelou P, Melenovsky V, Wiggers H, Hassanein M. 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: 2129–2200. - PubMed
    1. Bhatia RS, Tu JV, Lee DS, Austin PC, Fang J, Haouzi A, Gong Y, Liu PP. Outcome of heart failure with preserved ejection fraction in a population‐based study. N Engl J Med 2006; 355: 260–269. - PubMed
    1. Shah KS, Xu H, Matsouaka RA, Bhatt DL, Heidenreich PA, Hernandez AF, Devore AD, Yancy CW, Fonarow GC. Heart failure with preserved, borderline, and reduced ejection fraction: 5‐year outcomes. J Am Coll Cardiol 2017; 70: 2476–2486. - PubMed
    1. Solomon SD, McMurray JJV, Anand IS, Ge J, Lam CSP, Maggioni AP, Martinez F, Packer M, Pfeffer MA, Pieske B, Redfield MM, Rouleau JL, van Veldhuisen DJ, Zannad F, Zile MR, Desai AS, Claggett B, Jhund PS, Boytsov SA, Comin‐Colet J, Cleland J, Düngen H‐D, Goncalvesova E, Katova T, Kerr Saraiva JF, Lelonek M, Merkely B, Senni M, Shah SJ, Zhou J, Rizkala AR, Gong J, Shi VC, Lefkowitz MP. Angiotensin–neprilysin inhibition in heart failure with preserved ejection fraction. N Engl J Med 2019; 381: 1609–1620. - PubMed

Publication types