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. 2023 Jun;10(3):1835-1846.
doi: 10.1002/ehf2.14302. Epub 2023 Mar 10.

Long-term outcomes in heart failure with preserved ejection fraction: Predictors of cardiac and non-cardiac mortality

Angiza Shahim  1 , Marion Hourqueig  2 , Lars H Lund  1   3 , Gianluigi Savarese  1   3 , Emmanuel Oger  4 , Ashwin Venkateshvaran  1   3 , Lina Benson  1 , Jean-Claude Daubert  5 , Cecilia Linde  1   3 , Erwan Donal  5   6 , Camilla Hage  1   3
Affiliations

Long-term outcomes in heart failure with preserved ejection fraction: Predictors of cardiac and non-cardiac mortality

Angiza Shahim et al. ESC Heart Fail. 2023 Jun.

Abstract

Aims: Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with cardiovascular (CV) and non-CV events, but long-term risk is poorly studied. We assessed incidence and predictors of the long-term CV and non-CV events.

Methods and results: Patients presenting with acute HF, EF ≥ 45%, and N-terminal pro-brain natriuretic peptide > 300 ng/L were enrolled in the Karolinska-Rennes study in 2007-11 and were reassessed after 4-8 weeks in a stable state. Long-term follow-up was conducted in 2018. The Fine-Gray sub-distribution hazard regression was used to detect predictors of CV and non-CV deaths, investigated separately from baseline acute presentation (demographic data only) and from the 4-8 week outpatient visit (including echocardiographic data). Of 539 patients enrolled [median age 78 (interquartile range: 72-84) years; 52% female], 397 patients were available for the long-term follow-up. Over a median follow-up time from acute presentation of 5.4 (2.1-7.9) years, 269 (68%) patients died, 128 (47%) from CV and 120 (45%) from non-CV causes. Incidence rates per 1000 patient-years were 62 [95% confidence interval (CI) 52-74] for CV and 58 (95% CI 48-69) for non-CV death. Higher age and coronary artery disease (CAD) were independent predictors of CV death, and anaemia, stroke, kidney disease, and lower body mass index (BMI) and sodium concentrations of non-CV death. From the stable 4-8 week visit, anaemia, CAD, and tricuspid regurgitation (>3.1 m/s) were independent predictors of CV death, and higher age of non-CV death.

Conclusions: In patients with acute decompensated HFpEF, over 5 years of follow-up, nearly two-thirds of patients died, half from CV and the other half from non-CV causes. CAD and tricuspid regurgitation were associated with CV death. Stroke, kidney disease, lower BMI, and lower sodium were associated with non-CV death. Anaemia and higher age were associated with both outcomes. [Correction added on 24 March 2023, after first online publication: In the first sentence of the Conclusions, 'two-thirds' has been inserted before 'of patients died...' in this version.].

Keywords: Cardiovascular mortality; Diastolic heart failure; Heart failure with preserved ejection fraction; Non-cardiovascular mortality; Outcome; Prognosis.

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Conflict of interest statement

L.H.L. receives research grants from the Swedish Research Council, the Swedish Heart Lung Foundation, and the Stockholm County Council; research grants from AstraZeneca, Novartis, Boerhinger 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. G.S. reports grants and personal fees from Vifor and AstraZeneca; grants and non‐financial support from Boehringer Ingelheim; personal fees from Società Prodotti Antibiotici, Roche, Servier, GENESIS, Cytokinetics, and Medtronic; and grants from MSD and Novartis, outside the submitted work. C.L. receives research grants from the Swedish Heart Lung Foundation and the Stockholm County Council and speaker honoraria from Medtronic, Abbot, Microport, Boston Scientific, Novartis, Vifor, Impulse Dynamics, and Bayer. C.H. is supported by the Stockholm Country Council (grant 20180899) and has received consulting fees from Novartis and Roche Diagnostics, and speaker and honoraria from MSD and Novartis. E.D. receives research facilities from General Electric Healthcare, grant from Novartis, and teaching facilities from Bristol Myers Squibb. Other authors have no conflict of interest to declare.

Figures

Figure 1
Figure 1
Flow chart showing patient inclusion in the long‐term follow‐up analysis of the Karolinska‐Rennes (KaRen) study.
Figure 2
Figure 2
Cumulative incidence curves of cardiovascular, non‐cardiovascular, and unknown cause of death.
Figure 3
Figure 3
Associations between CV and non‐CV deaths and variables assessed at enrolment/baseline at hospital presentation. Independent predictors presented as adjusted SHR (and 95% CI) in 368 HFpEF patients. *NT‐proBNP tertiles defined as 1st = 305–1575 ng/L, 2nd = 1576–3723 ng/L, and 3rd = 3724–32 200 ng/L. AF, atrial fibrillation; BMI, body mass index; CAD, coronary artery disease; CI, confidence interval; CV, cardiovascular; HFpEF, heart failure with preserved ejection fraction; Non‐CV, non‐cardiovascular; NT‐proBNP, N‐terminal pro‐brain natriuretic peptide; NYHA, New York Heart Association; SBP, systolic blood pressure; SHR, sub‐distribution hazard ratio.
Figure 4
Figure 4
Associations between CV and non‐CV deaths in stable state 4–8 weeks after enrolment including echocardiographic variables. Independent predictors presented as adjusted SHR (and 95% CI) in 194 HFpEF patients. AF, atrial fibrillation; CAD, coronary artery disease; CI, confidence interval; COPD, chronic obstructive pulmonary disease; CV, cardiovascular; HFpEF, heart failure with preserved ejection fraction; Non‐CV, non‐cardiovascular; SHR, sub‐distribution hazard ratio; Vmax, maximal velocity.
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