Interleukin-1 (IL-1) blockade with anakinra significantly reduces perceptions of exertion and dyspnea independent of workload during submaximal exercise among patients with recently decompensated systolic heart failure (HF), according to a study in the American Journal of Cardiology.
Researchers evaluated the use of patient ratings of perceived exertion (RPE) and dyspnea on exertion (DOE) at standardized times during cardiopulmonary exercise testing (CPET) as a measure of treatment response in post hoc analysis of the Recently Decompensated Heart Failure Anakinra Response Trial (Clinicaltrials.gov identifier: NCT01936909) of patients with systolic HF.
Patients (N=60) were randomly assigned in a 1:1:1 fashion to subcutaneous injections of anakinra 100 mg per day for 12 weeks, anakinra 100 mg for 2 weeks followed by placebo for the remaining 10 weeks, or placebo for 12 weeks. CPET was performed at baseline and 2, 4, and 12 weeks.
Among the cohorts, 18 patients received placebo for 12 weeks (aged mean, 61 years; 72% men), 16 received anakinra for 2 weeks (aged mean, 57 years; 75% men), and 18 patients received anakinra for 12 weeks (aged mean, 55; 72% men).
The participants were asked to indicate their RPE (on a scale from 6 to 20) and DOE (on a scale from 0 to 10, modified Borg scale) throughout the exercise protocol. All patients completed the Duke Activity Status Index (DASI) and the Minnesota Living with HF questionnaire (MLHFQ).
After 12 weeks of treatment, patients treated with anakinra reported significantly lower RPE values compared with patients who received placebo at 3 minutes (7.00 [IQR, 6.00-8.75] vs 9.00 [IQR, 7.00-11.00], P =.003 for time × group interaction from baseline) and at 6 minutes (8.00 [IQR, 7.00-9.50] vs 11.00 [IQR 7.00-13.00], P =.039 for time × group interaction from baseline).
For patients treated with anakinra, a trend was observed toward lower DOE values compared with patients who received placebo at 3 minutes (0.00 [IQR, 0.00-0.875] vs 0.50 [IQR 0.00-1.00], P =.083 for time × group interaction from baseline) and at 6 minutes (0.25 [IQR 0.00-2.00] vs 1.00 [IQR, 0.00-3.00], P =.19 for time × group interaction from baseline), although the difference was not statistically significant.
DOE at 3 minutes (1.50 [IQR, 0.125-2.75] to 0.00 [IQR, 0.00-0.875], P =.012) and DOE at 6 minutes (2.00 [IQR, 2.00-4.00] to 0.25 [IQR, 0.00-2.00], P =.007) were significantly reduced in patients treated with anakinra.
In the assessment of all CPETs in the treatment groups, RPE (3 minutes), RPE (6 minutes), DOE (3 minutes), and DOE (6 minutes) all had significant positive correlations with MLHFQ (physical domain) scores, which suggests that increased perceptions of exertion and dyspnea correlate with greater HF burden.
In multivariate regression analysis that included RPE (3 minutes), RPE (6 minutes), DOE (3 minutes), and DOE (6 minutes), peak oxygen consumption, and the ventilation/carbon dioxide production slope, only RPE (6 minutes) was an independent predictor for both DASI and MLWHF (physical domain) scores.
The researchers noted that whether the potential changes in perception after IL-1 blockade lead to better outcomes in reducing hospital readmissions through physical, psychologic, or cognitive effects remains unknown and further investigation is needed.
“Patient perceptions of exertion and dyspnea during submaximal effort correlate with patient-reported quality of life measures and may therefore provide an additional opportunity to assess patients with systolic HF,” the researchers wrote.
Mihalick V, Wohlford G, Talasaz AH, et al. Patient perceptions of exertion and dyspnea with interleukin-1 blockade in patients with recently decompensated systolic heart failure. Am J Cardiol. Published online April 24, 2022. doi: 10.1016/j.amjcard.2022.03.026