Greater Pain Severity Is Associated with Worse Outcomes in Patients with Heart Failure


We examined the relationship between pain severity and outcomes in patients with heart failure with reduced ejection fraction (HFrEF) in the HF-ACTION randomized controlled trial. Trends of health-related quality of life (HRQoL) measures grouped by patients’ self-reported baseline bodily pain severity were compared using correlation tests, and the association between pain severity and clinical outcomes (including a primary composite endpoint of all-cause mortality and all-cause hospitalization) was assessed using multivariable adjusted analyses. Of the 2310 patients, 22.9% reported no pain, 45.8% very mild/mild, 24.9% moderate, and 6.4% severe/very severe. Greater pain severity was associated with worse HRQoL measures (EuroQoL-5D-3L and Kansas City Cardiomyopathy Questionnaire; both p < 0.0001). Compared to those reporting no pain, patients reporting severe/very severe pain had greater risk for the primary endpoint (adjusted hazard ratio 1.42, 95% confidence interval 1.11–1.83, p = 0.01). In patients with HFrEF, greater pain severity was associated with worse HRQoL and clinical outcomes. Trial Registration: NCT00047437

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Beck Depression Inventory-II


Canadian Cardiovascular Society


Cardiopulmonary exercise




Heart failure


Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training


Health-related quality of life


Kansas City Cardiomyopathy Questionnaire


New York Heart Association


Respiratory exchange ratio


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HF-ACTION was funded by the National Institutes of Health. This manuscript was funded internally by the Duke Clinical Research Institute, Durham, NC.

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Corresponding author

Correspondence to Kent Y. Feng.

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Informed Consent Statement

The protocol was approved by the institutional review board or ethics committee at each participating institution and all patients provided written informed consent. No animal studies were carried out by the authors for this article.

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Clinical Significance

In patients with chronic heart failure with reduced ejection fraction, greater pain severity was associated with worse composite endpoint of all-cause mortality and all-cause hospitalizations.

Associate Editor Ana Barac oversaw the review of this article

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Feng, K.Y., O’Connor, C.M., Clare, R. et al. Greater Pain Severity Is Associated with Worse Outcomes in Patients with Heart Failure. J. of Cardiovasc. Trans. Res. (2021).

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  • Pain
  • Exercise
  • Health-related quality of life
  • Heart failure