Prognostic Importance of Impaired Systolic Function in Heart Failure With Preserved Ejection Fraction and the Impact of Spironolactone
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Background—: Impairment in left ventricular systolic function has been described in heart failure (HF) with preserved ejection fraction (HFpEF), but its prognostic relevance is not known. We determined whether left ventricular longitudinal strain (LS) is predictive of cardiovascular outcomes in HFpEF beyond clinical and conventional echocardiographic measures. Methods and Results—: LS was assessed by 2-dimensional speckle-tracking echocardiography at baseline in 447 patients with HFpEF enrolled in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. At a median follow-up of 2.6 years (interquartile range, 1.5–3.9 years), 115 patients experienced the primary composite outcome of cardiovascular death, HF hospitalization, or aborted cardiac arrest. Impaired LS, defined as an absolute LS <15.8%, was present in 52% of patients and was predictive of the composite outcome (adjusted hazard ratio, 2.14; 95% confidence interval, 1.26–3.66; P =0.005), cardiovascular death alone (adjusted hazard ratio, 3.20; 95% confidence interval, 1.44–7.12; P =0.004), and HF hospitalization alone (adjusted hazard ratio, 2.23; 95% confidence interval, 1.16–4.28; P =0.016) after adjustment for clinical and conventional echocardiographic variables. LS was the strongest echocardiographic predictor of the composite outcome. Exploratory analysis in a subset of 131 patients with follow-up LS assessed after 12 to 18 months demonstrated a trend toward improvement in LS associated with spironolactone in patients enrolled in the Americas but not in Russia or Georgia. Conclusions—: Impaired left ventricular systolic function is a powerful predictor of HF hospitalization, cardiovascular death, or aborted cardiac arrest in HFpEF independent of clinical predictors. Impaired LS represents a novel imaging biomarker to identify patients with HFpEF at particularly high risk for cardiovascular morbidity and mortality. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00094302.
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- Authors
- Shah, A. M., Claggett, B., Sweitzer, N. K., Shah, S. J., Anand, I. S., Liu, L., Pitt, B., Pfeffer, M. A., & Solomon, S. D.
- Affiliations
- Northwestern University (US)
- ORCID
- Venue
- Circulation
- Published
- 2015-08-04
- Volume
- 132
- Issue
- 5
- Pages
- 402-414
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC4526442
- OpenAlex
- W2105400632
- Cited by
- 478
- References
- 60
- Citations by year
- 2026: 14 · 2025: 33 · 2024: 36 · 2023: 45 · 2022: 63 · 2021: 52 · 2020: 59 · 2019: 47 · 2018: 37 · 2017: 41 · 2016: 39 · 2015: 9
- FWCI
- 30.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health and Human Services (HHSN268201100007C, HHSN268201100012C, HHSN268201100005C, HHSN268201100008C, HHSN268201100006C, HHSN268201100010C, HHSN268201100011C, HHSN268201100009C)
- American Heart Association (HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, 14CRP20380422, HHSN268201100012C, HHSN268201100005C, HHSN268201100009C, HHSN268201100011C, HHSN268201100010C)
- National Heart, Lung, and Blood Institute (HHSN268201 100012C, HHSN268201100007I, HHSN268201100007C, HHSN2682 01100008C, HH-SN-268201100006C, HHSN268201100011C, HHSN2682011-00005I, HHSN2682011-00009I, HHSN268201100005C, HHSN268201100005G, HHSN268201100010C, HHSN268201100011I, HHSN26820 1100009C, K08HL116792, HHSN2682011-00008I, HHSN268200425207C)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac pacing and defibrillation studies
- Keywords
- heart failure with preserved ejection fraction, left ventricular systolic function, left ventricular longitudinal strain, spironolactone, prognosis, cardiovascular mortality, heart failure hospitalization, speckle tracking echocardiography, imaging biomarkers, TOPCAT trial, mineralocorticoid receptor antagonists
- MeSH terms
- Aged, Aged, 80 and over, Mineralocorticoid Receptor Antagonists, Double-Blind Method, Electrocardiography, Female, Follow-Up Studies, Heart Arrest, Hospitalization, Humans, Male, Middle Aged, Prognosis, Spironolactone, Stroke Volume, Incidence, Survival Rate, Treatment Outcome, Ventricular Dysfunction, Left, Internationality, Heart Failure, Systolic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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