Prognostic importance of impaired systolic function in heart failure with preserved ejection fraction and the impact of spironolactone

Amil M. Shah, Brian Claggett, Nancy K Sweitzer, Sanjiv J. Shah, Inder S. Anand, Li Liu, Bertram Pitt, Marc A. Pfeffer, Scott D. Solomon

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)402-414
Number of pages13
JournalCirculation
Volume132
Issue number5
DOIs
StatePublished - Aug 4 2015

Fingerprint

Spironolactone
Heart Failure
Hospitalization
Confidence Intervals
Heart Arrest
Left Ventricular Function
Mineralocorticoid Receptor Antagonists
Russia
Echocardiography
Biomarkers
Clinical Trials
Morbidity
Mortality

Keywords

  • clinical trial
  • heart failure
  • heart ventricles
  • preserved left ventricular function
  • spironolactone
  • strain

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Prognostic importance of impaired systolic function in heart failure with preserved ejection fraction and the impact of spironolactone. / Shah, Amil M.; Claggett, Brian; Sweitzer, Nancy K; Shah, Sanjiv J.; Anand, Inder S.; Liu, Li; Pitt, Bertram; Pfeffer, Marc A.; Solomon, Scott D.

In: Circulation, Vol. 132, No. 5, 04.08.2015, p. 402-414.

Research output: Contribution to journalArticle

Shah, Amil M. ; Claggett, Brian ; Sweitzer, Nancy K ; Shah, Sanjiv J. ; Anand, Inder S. ; Liu, Li ; Pitt, Bertram ; Pfeffer, Marc A. ; Solomon, Scott D. / Prognostic importance of impaired systolic function in heart failure with preserved ejection fraction and the impact of spironolactone. In: Circulation. 2015 ; Vol. 132, No. 5. pp. 402-414.
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AU - Shah, Sanjiv J.

AU - Anand, Inder S.

AU - Liu, Li

AU - Pitt, Bertram

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AU - Solomon, Scott D.

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N2 - 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.

AB - 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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