Sudden Death in Heart Failure With Preserved Ejection Fraction: A Competing Risks Analysis From the TOPCAT Trial

Muthiah Vaduganathan, Brian L. Claggett, Neal A. Chatterjee, Inder S. Anand, Nancy K Sweitzer, James C. Fang, Eileen O'Meara, Sanjiv J. Shah, Sheila M. Hegde, Akshay S. Desai, Eldrin F. Lewis, Jean Rouleau, Bertram Pitt, Marc A. Pfeffer, Scott D. Solomon

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Objectives: This study investigated the rates and predictors of SD or aborted cardiac arrest (ACA) in HFpEF. Background: Sudden death (SD) may be an important mode of death in heart failure with preserved ejection fraction (HFpEF). Methods: We studied 1,767 patients with HFpEF (EF ≥45%) enrolled in the Americas region of the TOPCAT (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function) trial. We identified independent predictors of composite SD/ACA with stepwise backward selection using competing risks regression analysis that accounted for nonsudden causes of death. Results: During a median 3.0-year (25th to 75th percentile: 1.9 to 4.4 years) follow-up, 77 patients experienced SD/ACA, and 312 experienced non-SD/ACA. Corresponding incidence rates were 1.4 events/100 patient-years (25th to 75th percentile: 1.1 to 1.8 events/100 patient-years) and 5.8 events/100 patient-years (25th to 75th percentile: 5.1 to 6.4 events/100 patient-years). SD/ACA was numerically lower but not statistically reduced in those randomized to spironolactone: 1.2 events/100 patient-years (25th to 75th percentile: 0.9 to 1.7 events/100 patient-years) versus 1.6 events/100 patient-years (25th to 75th percentile: 1.2 to 2.2 events/100 patient-years); the subdistributional hazard ratio was 0.74 (95% confidence interval: 0.47 to 1.16; p = 0.19). After accounting for competing risks of non-SD/ACA, male sex and insulin-treated diabetes mellitus were independently predictive of composite SD/ACA (C-statistic = 0.65). Covariates, including eligibility criteria, age, ejection fraction, coronary artery disease, left bundle branch block, and baseline therapies, were not independently associated with SD/ACA. Sex and diabetes mellitus status remained independent predictors in sensitivity analyses, excluding patients with implantable cardioverter-defibrillators and when predicting SD alone. Conclusions: SD accounted for ∼20% of deaths in HFpEF. Male sex and insulin-treated diabetes mellitus identified patients at higher risk for SD/ACA with modest discrimination. These data might guide future SD preventative efforts in HFpEF. (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [TOPCAT]); NCT00094302

Original languageEnglish (US)
JournalJACC: Heart Failure
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Sudden Death
Heart Failure
Heart Arrest
Systolic Heart Failure
Mineralocorticoid Receptor Antagonists
Diabetes Mellitus
Insulin
Spironolactone
Bundle-Branch Block
Implantable Defibrillators
Coronary Artery Disease
Cause of Death
Therapeutics
Regression Analysis
Confidence Intervals

Keywords

  • heart failure with preserved ejection fraction
  • risk prediction
  • sudden death

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Sudden Death in Heart Failure With Preserved Ejection Fraction : A Competing Risks Analysis From the TOPCAT Trial. / Vaduganathan, Muthiah; Claggett, Brian L.; Chatterjee, Neal A.; Anand, Inder S.; Sweitzer, Nancy K; Fang, James C.; O'Meara, Eileen; Shah, Sanjiv J.; Hegde, Sheila M.; Desai, Akshay S.; Lewis, Eldrin F.; Rouleau, Jean; Pitt, Bertram; Pfeffer, Marc A.; Solomon, Scott D.

In: JACC: Heart Failure, 01.01.2018.

Research output: Contribution to journalArticle

Vaduganathan, M, Claggett, BL, Chatterjee, NA, Anand, IS, Sweitzer, NK, Fang, JC, O'Meara, E, Shah, SJ, Hegde, SM, Desai, AS, Lewis, EF, Rouleau, J, Pitt, B, Pfeffer, MA & Solomon, SD 2018, 'Sudden Death in Heart Failure With Preserved Ejection Fraction: A Competing Risks Analysis From the TOPCAT Trial', JACC: Heart Failure. https://doi.org/10.1016/j.jchf.2018.02.014
Vaduganathan, Muthiah ; Claggett, Brian L. ; Chatterjee, Neal A. ; Anand, Inder S. ; Sweitzer, Nancy K ; Fang, James C. ; O'Meara, Eileen ; Shah, Sanjiv J. ; Hegde, Sheila M. ; Desai, Akshay S. ; Lewis, Eldrin F. ; Rouleau, Jean ; Pitt, Bertram ; Pfeffer, Marc A. ; Solomon, Scott D. / Sudden Death in Heart Failure With Preserved Ejection Fraction : A Competing Risks Analysis From the TOPCAT Trial. In: JACC: Heart Failure. 2018.
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abstract = "Objectives: This study investigated the rates and predictors of SD or aborted cardiac arrest (ACA) in HFpEF. Background: Sudden death (SD) may be an important mode of death in heart failure with preserved ejection fraction (HFpEF). Methods: We studied 1,767 patients with HFpEF (EF ≥45{\%}) enrolled in the Americas region of the TOPCAT (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function) trial. We identified independent predictors of composite SD/ACA with stepwise backward selection using competing risks regression analysis that accounted for nonsudden causes of death. Results: During a median 3.0-year (25th to 75th percentile: 1.9 to 4.4 years) follow-up, 77 patients experienced SD/ACA, and 312 experienced non-SD/ACA. Corresponding incidence rates were 1.4 events/100 patient-years (25th to 75th percentile: 1.1 to 1.8 events/100 patient-years) and 5.8 events/100 patient-years (25th to 75th percentile: 5.1 to 6.4 events/100 patient-years). SD/ACA was numerically lower but not statistically reduced in those randomized to spironolactone: 1.2 events/100 patient-years (25th to 75th percentile: 0.9 to 1.7 events/100 patient-years) versus 1.6 events/100 patient-years (25th to 75th percentile: 1.2 to 2.2 events/100 patient-years); the subdistributional hazard ratio was 0.74 (95{\%} confidence interval: 0.47 to 1.16; p = 0.19). After accounting for competing risks of non-SD/ACA, male sex and insulin-treated diabetes mellitus were independently predictive of composite SD/ACA (C-statistic = 0.65). Covariates, including eligibility criteria, age, ejection fraction, coronary artery disease, left bundle branch block, and baseline therapies, were not independently associated with SD/ACA. Sex and diabetes mellitus status remained independent predictors in sensitivity analyses, excluding patients with implantable cardioverter-defibrillators and when predicting SD alone. Conclusions: SD accounted for ∼20{\%} of deaths in HFpEF. Male sex and insulin-treated diabetes mellitus identified patients at higher risk for SD/ACA with modest discrimination. These data might guide future SD preventative efforts in HFpEF. (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [TOPCAT]); NCT00094302",
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author = "Muthiah Vaduganathan and Claggett, {Brian L.} and Chatterjee, {Neal A.} and Anand, {Inder S.} and Sweitzer, {Nancy K} and Fang, {James C.} and Eileen O'Meara and Shah, {Sanjiv J.} and Hegde, {Sheila M.} and Desai, {Akshay S.} and Lewis, {Eldrin F.} and Jean Rouleau and Bertram Pitt and Pfeffer, {Marc A.} and Solomon, {Scott D.}",
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T1 - Sudden Death in Heart Failure With Preserved Ejection Fraction

T2 - A Competing Risks Analysis From the TOPCAT Trial

AU - Vaduganathan, Muthiah

AU - Claggett, Brian L.

AU - Chatterjee, Neal A.

AU - Anand, Inder S.

AU - Sweitzer, Nancy K

AU - Fang, James C.

AU - O'Meara, Eileen

AU - Shah, Sanjiv J.

AU - Hegde, Sheila M.

AU - Desai, Akshay S.

AU - Lewis, Eldrin F.

AU - Rouleau, Jean

AU - Pitt, Bertram

AU - Pfeffer, Marc A.

AU - Solomon, Scott D.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Objectives: This study investigated the rates and predictors of SD or aborted cardiac arrest (ACA) in HFpEF. Background: Sudden death (SD) may be an important mode of death in heart failure with preserved ejection fraction (HFpEF). Methods: We studied 1,767 patients with HFpEF (EF ≥45%) enrolled in the Americas region of the TOPCAT (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function) trial. We identified independent predictors of composite SD/ACA with stepwise backward selection using competing risks regression analysis that accounted for nonsudden causes of death. Results: During a median 3.0-year (25th to 75th percentile: 1.9 to 4.4 years) follow-up, 77 patients experienced SD/ACA, and 312 experienced non-SD/ACA. Corresponding incidence rates were 1.4 events/100 patient-years (25th to 75th percentile: 1.1 to 1.8 events/100 patient-years) and 5.8 events/100 patient-years (25th to 75th percentile: 5.1 to 6.4 events/100 patient-years). SD/ACA was numerically lower but not statistically reduced in those randomized to spironolactone: 1.2 events/100 patient-years (25th to 75th percentile: 0.9 to 1.7 events/100 patient-years) versus 1.6 events/100 patient-years (25th to 75th percentile: 1.2 to 2.2 events/100 patient-years); the subdistributional hazard ratio was 0.74 (95% confidence interval: 0.47 to 1.16; p = 0.19). After accounting for competing risks of non-SD/ACA, male sex and insulin-treated diabetes mellitus were independently predictive of composite SD/ACA (C-statistic = 0.65). Covariates, including eligibility criteria, age, ejection fraction, coronary artery disease, left bundle branch block, and baseline therapies, were not independently associated with SD/ACA. Sex and diabetes mellitus status remained independent predictors in sensitivity analyses, excluding patients with implantable cardioverter-defibrillators and when predicting SD alone. Conclusions: SD accounted for ∼20% of deaths in HFpEF. Male sex and insulin-treated diabetes mellitus identified patients at higher risk for SD/ACA with modest discrimination. These data might guide future SD preventative efforts in HFpEF. (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [TOPCAT]); NCT00094302

AB - Objectives: This study investigated the rates and predictors of SD or aborted cardiac arrest (ACA) in HFpEF. Background: Sudden death (SD) may be an important mode of death in heart failure with preserved ejection fraction (HFpEF). Methods: We studied 1,767 patients with HFpEF (EF ≥45%) enrolled in the Americas region of the TOPCAT (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function) trial. We identified independent predictors of composite SD/ACA with stepwise backward selection using competing risks regression analysis that accounted for nonsudden causes of death. Results: During a median 3.0-year (25th to 75th percentile: 1.9 to 4.4 years) follow-up, 77 patients experienced SD/ACA, and 312 experienced non-SD/ACA. Corresponding incidence rates were 1.4 events/100 patient-years (25th to 75th percentile: 1.1 to 1.8 events/100 patient-years) and 5.8 events/100 patient-years (25th to 75th percentile: 5.1 to 6.4 events/100 patient-years). SD/ACA was numerically lower but not statistically reduced in those randomized to spironolactone: 1.2 events/100 patient-years (25th to 75th percentile: 0.9 to 1.7 events/100 patient-years) versus 1.6 events/100 patient-years (25th to 75th percentile: 1.2 to 2.2 events/100 patient-years); the subdistributional hazard ratio was 0.74 (95% confidence interval: 0.47 to 1.16; p = 0.19). After accounting for competing risks of non-SD/ACA, male sex and insulin-treated diabetes mellitus were independently predictive of composite SD/ACA (C-statistic = 0.65). Covariates, including eligibility criteria, age, ejection fraction, coronary artery disease, left bundle branch block, and baseline therapies, were not independently associated with SD/ACA. Sex and diabetes mellitus status remained independent predictors in sensitivity analyses, excluding patients with implantable cardioverter-defibrillators and when predicting SD alone. Conclusions: SD accounted for ∼20% of deaths in HFpEF. Male sex and insulin-treated diabetes mellitus identified patients at higher risk for SD/ACA with modest discrimination. These data might guide future SD preventative efforts in HFpEF. (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [TOPCAT]); NCT00094302

KW - heart failure with preserved ejection fraction

KW - risk prediction

KW - sudden death

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