Developing and validating models to predict sudden death and pump failure death in patients with heart failure and preserved ejection fraction.

Abstract

BACKGROUND:

Sudden death (SD) and pump failure death (PFD) are leading modes of death in heart failure and preserved ejection fraction (HFpEF). Risk stratification for mode-specific death may aid in patient enrichment for new device trials in HFpEF.

METHODS:

Models were derived in 4116 patients in the Irbesartan in Heart Failure with Preserved Ejection Fraction trial (I-Preserve), using competing risks regression analysis. A series of models were built in a stepwise manner, and were validated in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Preserved and Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trials.

RESULTS:

The clinical model for SD included older age, men, lower LVEF, higher heart rate, history of diabetes or myocardial infarction, and HF hospitalization within previous 6 months, all of which were associated with a higher SD risk. The clinical model predicting PFD included older age, men, lower LVEF or diastolic blood pressure, higher heart rate, and history of diabetes or atrial fibrillation, all for a higher PFD risk, and dyslipidaemia for a lower risk of PFD. In each model, the observed and predicted incidences were similar in each risk subgroup, suggesting good calibration. Model discrimination was good for SD and excellent for PFD with Harrell's C of 0.71 (95% CI 0.68-0.75) and 0.78 (95% CI 0.75-0.82), respectively. Both models were robust in external validation. Adding ECG and biochemical parameters, model performance improved little in the derivation cohort but decreased in validation. Including NT-proBNP substantially increased discrimination of the SD model, and simplified the PFD model with marginal increase in discrimination.

CONCLUSIONS:

The clinical models can predict risks for SD and PFD separately with good discrimination and calibration in HFpEF and are robust in external validation. Adding NT-proBNP further improved model performance. These models may help to identify high-risk individuals for device intervention in future trials.

CLINICAL TRIAL REGISTRATION:

I-Preserve: ClinicalTrials.gov NCT00095238; TOPCAT: ClinicalTrials.gov NCT00094302; CHARM-Preserved: ClinicalTrials.gov NCT00634712.

• Authors: Li Shen, Pardeep S Jhund, Inder S Anand, Peter E Carson, Akshay S Desai, Christopher B Granger, Lars Køber, Michel Komajda, Robert S McKelvie, Marc A Pfeffer, Scott D Solomon, Karl Swedberg, Michael R Zile, John J V McMurray
• Journal: Clinical research in cardiology : official journal of the German Cardiac Society (Clin Res Cardiol) Vol. 110 Issue 8 Pg. 1234-1248 (Aug 2021) ISSN: 1861-0692 [Electronic] Germany
• PMID: 33301080 (Publication Type: Journal Article, Validation Study)
• Copyright: © 2020. The Author(s).

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Benzimidazoles
• Biomarkers
• Biphenyl Compounds
• Mineralocorticoid Receptor Antagonists
• Peptide Fragments
• Tetrazoles
• pro-brain natriuretic peptide (1-76)
• Natriuretic Peptide, Brain
• Irbesartan
• candesartan

Topics

• Aged
• Angiotensin II Type 1 Receptor Blockers (therapeutic use)
• Benzimidazoles (therapeutic use)
• Biomarkers (blood)
• Biphenyl Compounds (therapeutic use)
• Death, Sudden, Cardiac (prevention & control)
• Defibrillators, Implantable
• Electrocardiography
• Female
• Heart Failure (drug therapy, mortality, physiopathology)
• Humans
• Irbesartan (therapeutic use)
• Male
• Mineralocorticoid Receptor Antagonists (therapeutic use)
• Natriuretic Peptide, Brain (blood)
• Peptide Fragments (blood)
• Predictive Value of Tests
• Randomized Controlled Trials as Topic
• Risk Assessment (methods)
• Sex Factors
• Stroke Volume (physiology)
• Tetrazoles (therapeutic use)