Patient Perceptions of Exertion and Dyspnea With Interleukin-1 Blockade in Patients With Recently Decompensated Systolic Heart Failure

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Interleukin-1 (IL-1) blockade is an anti-inflammatory treatment that may affect exercise capacity in heart failure (HF). We evaluated patient-reported perceptions of exertion and dyspnea at submaximal exercise during cardiopulmonary exercise testing (CPET) in a double-blind, placebo-controlled, randomized clinical trial of IL-1 blockade in patients with systolic HF (REDHART [Recently Decompensated Heart Failure Anakinra Response Trial]). Patients underwent maximal CPET at baseline, 2, 4, and 12 weeks and rated their perceived level of exertion (RPE, on a scale from 6 to 20) and dyspnea on exertion (DOE, on a scale from 0 to 10) every 3 minutes throughout exercise. Patients also answered 2 questionnaires to assess HF-related quality of life: the Duke Activity Status Index and the Minnesota Living with Heart Failure Questionnaire. From baseline to the 12-week follow-up, IL-1 blockade significantly reduced RPE and DOE at 3- and 6-minutes during CPET without changing values for heart rate, oxygen consumption, and cardiac workload at 3- and 6-minutes. Linear regression identified 6-minute RPE to be a strong independent predictor of both physical symptoms (Minnesota Living with Heart Failure Questionnaire; β = 0.474, p = 0.002) and perceived exercise capacity (Duke Activity Status Index; β = −0.443, p = 0.008). In conclusion, patient perceptions of exertion and dyspnea at submaximal exercise may be valuable surrogates for quality of life and markers of response to IL-1 blockade in patients with HF.

Introduction

Cardiopulmonary exercise testing (CPET) is the gold standard assessment of cardiorespiratory fitness (CRF) in heart failure (HF).1, 2, 3, 4 CPET offers a unique opportunity to measure objective parameters that are both “disease-oriented” prognostic markers and “patient-oriented” functional assessments. Peak oxygen consumption (VO2) and the minute ventilation/carbon dioxide production (VE/VCO2) slope represent powerful independent predictors of adverse cardiovascular outcomes that have been widely used to measure prognosis, disease progression, exercise capacity, and more broadly, CRF.5 Despite these important insights, however, these metrics do not directly incorporate patient perceptions of dyspnea and exertion during submaximal exercise. Given that patients with HF spend the majority of their lives and experience the majority of clinical symptoms at submaximal levels of physical exertion, we investigated the utility of patient ratings of perceived exertion (RPE) and dyspnea on exertion (DOE) at standardized times during CPET as a measure of treatment response within the setting of the REDHART (Recently Decompensated Heart Failure Anakinra Response Trial) clinical trial, a study of targeted interleukin-1 (IL-1) blockade in patients with systolic HF.6,7

Section snippets

Methods

The design of the REDHART clinical trial was previously presented elsewhere.7 In brief, REDHART was a randomized, placebo-controlled, double-blinded, experimental trial to evaluate the use of recombinant IL-1 receptor antagonist (anakinra) on CRF (in particular, the peak VO2 and the VE/VCO2 slope) in 60 patients enrolled within 2 weeks of hospitalization for acute decompensated systolic HF. Patients were randomized (1: 1: 1) to subcutaneous injections of anakinra 100 mg per day for 12 weeks,

Results

The clinical characteristic of the patients in the 3 groups have been already described.7 All CPETs were completed to maximal exertion and 92% of all CPETs achieved peak RER ≥1.00 (median peak RER = 1.13 [interquartile range [IQR] 1.06 to 1.20]). Patient demographic data including cardiovascular risk factors did not show a significant difference between groups (Table 1). There were no significant differences in the use of HF medications among groups, except for the use of hydralazine/isosorbide

Discussion

Improving the burden of HF symptoms remains an unmet medical need. Even in the absence of symptoms at rest, many patients with HF experience frequent symptoms of dyspnea and fatigue with low levels of exertion that disrupt activities of daily living and significantly impair quality of life. Patient-reported outcomes, measured with the MLHFQ and DASI, capture the severity of HF symptoms and carry important prognostic information.9,15 CPET is a noninvasive test that assesses a broad array of

Disclosures

Dr. Van Tassell and Dr. Abbate were co-prinicpal investigators on the NIH funding for this study. Please list both of them as receiving financial support from NIH.

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  • This study was supported by R34HL117026 and UL1TR000058 for NIH (Bethesda, Maryland).

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