Advertisement

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

      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.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Del Buono MG
        • Arena R
        • Borlaug BA
        • Carbone S
        • Canada JM
        • Kirkman DL
        • Garten R
        • Rodriguez-Miguelez P
        • Guazzi M
        • Lavie CJ
        • Abbate A.
        Exercise intolerance in patients with heart failure: JACC state-of-the-art review.
        J Am Coll Cardiol. 2019; 73: 2209-2225
        • Arena R
        • Canada JM
        • Popovic D
        • Trankle CR
        • Del Buono MG
        • Lucas A
        • Abbate A.
        Cardiopulmonary exercise testing - refining the clinical perspective by combining assessments.
        Expert Rev Cardiovasc Ther. 2020; 18: 563-576
        • van Wezenbeek J
        • Canada JM
        • Ravindra K
        • Carbone S
        • Kadariya D
        • Trankle CR
        • Wohlford G
        • Buckley L
        • Del Buono MG
        • Billingsley H
        • Viscusi M
        • Tchoukina I
        • Shah KB
        • Arena R
        • Van Tassell B
        • Abbate A.
        Determinants of cardiorespiratory fitness in patients with heart failure across a wide range of ejection fractions.
        Am J Cardiol. 2020; 125: 76-81
        • van Wezenbeek J
        • Canada JM
        • Ravindra K
        • Carbone S
        • Trankle CR
        • Kadariya D
        • Buckley LF
        • Del Buono M
        • Billingsley H
        • Viscusi M
        • Wohlford GF
        • Arena R
        • Van Tassell B
        • Abbate A.
        C-reactive protein and N-terminal pro-brain natriuretic peptide levels correlate with impaired cardiorespiratory fitness in patients with heart failure across a wide range of ejection fraction.
        Front Cardiovasc Med. 2018; 5: 178
        • Tashiro H
        • Tanaka A
        • Ishii H
        • Motomura N
        • Arai K
        • Adachi T
        • Okajima T
        • Iwakawa N
        • Kojima H
        • Mitsuda T
        • Hirayama K
        • Hitora Y
        • Hayashi M
        • Furusawa K
        • Yoshida R
        • Imai H
        • Ogawa Y
        • Kawaguchi K
        • Murohara T.
        Reduced exercise capacity and clinical outcomes following acute myocardial infarction.
        Heart Vessels. 2020; 35: 1044-1050
        • Abbate A
        • Toldo S
        • Marchetti C
        • Kron J
        • Van Tassell BW
        • Dinarello CA.
        Interleukin-1 and the inflammasome as therapeutic targets in cardiovascular disease.
        Circ Res. 2020; 126: 1260-1280
        • Van Tassell BW
        • Canada J
        • Carbone S
        • Trankle C
        • Buckley L
        • Oddi Erdle C
        • Abouzaki NA
        • Dixon D
        • Kadariya D
        • Christopher S
        • Schatz A
        • Regan J
        • Viscusi M
        • Del Buono M
        • Melchior R
        • Mankad P
        • Lu J
        • Sculthorpe R
        • Biondi-Zoccai G
        • Lesnefsky E
        • Arena R
        • Abbate A
        Interleukin-1 blockade in recently decompensated systolic heart failure: results From REDHART (Recently Decompensated Heart Failure Anakinra Response Trial).
        Circ Heart Fail. 2017; 10e004373
        • Arena R
        • Humphrey R
        • Peberdy MA.
        Using the Duke Activity Status Index in heart failure.
        J Cardiopulm Rehabil. 2002; 22: 93-95
        • Bilbao A
        • Escobar A
        • García-Perez L
        • Navarro G
        • Quirós R.
        The Minnesota Living with Heart Failure Questionnaire: comparison of different factor structures.
        Health Qual Life Outcomes. 2016; 14: 23
        • Arena R
        • Humphrey R
        • Peberdy MA
        • Madigan M.
        Predicting peak oxygen consumption during a conservative ramping protocol: implications for the heart failure population.
        J Cardiopulm Rehabil. 2003; 23: 183-189
        • Arena R
        • Myers J
        • Abella J
        • Pinkstaff S
        • Brubaker P
        • Moore B
        • Kitzman D
        • Peberdy MA
        • Bensimhon D
        • Chase P
        • Forman D
        • West E
        • Guazzi M.
        Determining the preferred percent-predicted equation for peak oxygen consumption in patients with heart failure.
        Circ Heart Fail. 2009; 2: 113-120
        • Chase PJ
        • Kenjale A
        • Cahalin LP
        • Arena R
        • Davis PG
        • Myers J
        • Guazzi M
        • Forman DE
        • Ashley E
        • Peberdy MA
        • West E
        • Kelly CT
        • Bensimhon DR
        Effects of respiratory exchange ratio on the prognostic value of peak oxygen consumption and ventilatory efficiency in patients with systolic heart failure.
        JACC Heart Fail. 2013; 1: 427-432
        • Arena R
        • Myers J
        • Guazzi M.
        Cardiopulmonary exercise testing is a core assessment for patients with heart failure.
        Congest Heart Fail. 2011; 17: 115-119
        • Carvalho VO
        • Bocchi EA
        • Guimarães GV.
        The Borg scale as an important tool of self-monitoring and self-regulation of exercise prescription in heart failure patients during hydrotherapy. A randomized blinded controlled trial.
        Circ J. 2009; 73: 1871-1876
        • Huang W
        • Teng TK
        • Tay WT
        • Richards AM
        • Kadam U
        • Lawson CA
        • Shimizu W
        • Loh SY
        • Anand I
        • Lam CSP.
        Patient-reported outcomes in heart failure with preserved vs. reduced ejection fraction: focus on physical independence.
        ESC Heart Fail. 2020; 7: 2051-2062
        • Albouaini K
        • Egred M
        • Alahmar A
        • Wright DJ.
        Cardiopulmonary exercise testing and its application.
        Postgrad Med J. 2007; 83: 675-682
        • Dominguez-Rodriguez A
        • Abreu-Gonzalez P.
        Cardiopulmonary exercise testing versus 6-Min walk test as clinically meaningful endpoints in HF trials.
        J Am Coll Cardiol. 2017; 69: 2251-2252
        • Guazzi M
        • Myers J
        • Peberdy MA
        • Bensimhon D
        • Chase P
        • Arena R.
        Maximal dyspnea on exertion during cardiopulmonary exercise testing is related to poor prognosis and echocardiography with tissue Doppler imaging in heart failure.
        Congest Heart Fail. 2009; 15: 277-283
        • Guazzi M
        • Myers J
        • Peberdy MA
        • Bensimhon D
        • Chase P
        • Arena R.
        Ventilatory efficiency and dyspnea on exertion improvements are related to reduced pulmonary pressure in heart failure patients receiving sildenafil.
        Int J Cardiol. 2010; 144: 410-412
        • Lala A
        • Shah KB
        • Lanfear DE
        • Thibodeau JT
        • Palardy M
        • Ambardekar AV
        • McNamara DM
        • Taddei-Peters WC
        • Baldwin JT
        • Jeffries N
        • Khalatbari S
        • Spino C
        • Richards B
        • Mann DL
        • Stewart GC
        • Aaronson KD
        • Mancini DM
        • Investigators REVIVAL
        Predictive value of cardiopulmonary exercise testing parameters in ambulatory advanced heart failure.
        JACC Heart Fail. 2021; 9: 226-236
        • Abbate A
        • Trankle CR
        • Buckley LF
        • Lipinski MJ
        • Appleton D
        • Kadariya D
        • Canada JM
        • Carbone S
        • Roberts CS
        • Abouzaki N
        • Melchior R
        • Christopher S
        • Turlington J
        • Mueller G
        • Garnett J
        • Thomas C
        • Markley R
        • Wohlford GF
        • Puckett L
        • Medina de Chazal H
        • Chiabrando JG
        • Bressi E
        • Del Buono MG
        • Schatz A
        • Vo C
        • Dixon DL
        • Biondi-Zoccai GG
        • Kontos MC
        • Van Tassell BW.
        Interleukin-1 blockade inhibits the acute inflammatory response in patients with ST-segment-elevation myocardial infarction.
        J Am Heart Assoc. 2020; 9e014941
        • Abbate A
        • Wohlford GF
        • Del Buono MG
        • Chiabrando JG
        • Markley R
        • Turlington J
        • Kadariya D
        • Trankle CR
        • Biondi-Zoccai G
        • Lipinski MJ
        • Van Tassell BW.
        Interleukin-1 blockade with anakinra and heart failure following ST-segment elevation myocardial infarction: results from a pooled analysis of the VCUART clinical trials.
        Eur Heart J Cardiovasc Pharmacother. 2021; (])https://doi.org/10.1093/ehjcvp/pvab075
        • Trankle CR
        • Canada JM
        • Cei L
        • Abouzaki N
        • Oddi-Erdle C
        • Kadariya D
        • Christopher S
        • Viscusi M
        • Del Buono M
        • Kontos MC
        • Arena R
        • Van Tassell B
        • Abbate A.
        Usefulness of canakinumab to improve exercise capacity in patients with long-term systolic heart failure and elevated C-reactive protein.
        Am J Cardiol. 2018; 122: 1366-1370
        • Van Tassell BW
        • Arena RA
        • Toldo S
        • Mezzaroma E
        • Azam T
        • Seropian IM
        • Shah K
        • Canada J
        • Voelkel NF
        • Dinarello CA
        • Abbate A.
        Enhanced interleukin-1 activity contributes to exercise intolerance in patients with systolic heart failure.
        PLoS One. 2012; 7: e33438
        • Alpert CM
        • Smith MA
        • Hummel SL
        • Hummel EK.
        Symptom burden in heart failure: assessment, impact on outcomes, and management.
        Heart Fail Rev. 2017; 22: 25-39
        • Karshikoff B
        • Sundelin T
        • Lasselin J.
        Role of inflammation in human fatigue: relevance of multidimensional assessments and potential neuronal mechanisms.
        Front Immunol. 2017; 8: 21
        • Roerink ME
        • van der Schaaf ME
        • Dinarello CA
        • Knoop H
        • van der Meer JW.
        Interleukin-1 as a mediator of fatigue in disease: a narrative review.
        J Neuroinflammation. 2017; 14: 16
        • Carmichael MD
        • Davis JM
        • Murphy EA
        • Brown AS
        • Carson JA
        • Mayer EP
        • Ghaffar A.
        Role of brain IL-1beta on fatigue after exercise-induced muscle damage.
        Am J Physiol Regul Integr Comp Physiol. 2006; 291: R1344-R1348
        • Van Tassell BW
        • Arena R
        • Biondi-Zoccai G
        • Canada JM
        • Oddi C
        • Abouzaki NA
        • Jahangiri A
        • Falcao RA
        • Kontos MC
        • Shah KB
        • Voelkel NF
        • Dinarello CA
        • Abbate A.
        Effects of interleukin-1 blockade with anakinra on aerobic exercise capacity in patients with heart failure and preserved ejection fraction (from the D-HART pilot study).
        Am J Cardiol. 2014; 113: 321-327
        • Wohlford GF
        • Van Tassell BW
        • Billingsley HE
        • Kadariya D
        • Canada JM
        • Carbone S
        • Mihalick VL
        • Bonaventura A
        • Vecchié A
        • Chiabrando JG
        • Bressi E
        • Thomas G
        • Ho AC
        • Marawan AA
        • Dell M
        • Trankle CR
        • Turlington J
        • Markley R
        • Abbate A.
        Phase 1B, randomized, double-blinded, dose escalation, single-center, repeat dose safety and pharmacodynamics study of the oral NLRP3 inhibitor dapansutrile in subjects with NYHA II-III systolic heart failure.
        J Cardiovasc Pharmacol. 2020; 77: 49-60
        • Sinagra G
        • Iorio A
        • Merlo M
        • Cannatà A
        • Stolfo D
        • Zambon E
        • Di Nora C
        • Paolillo S
        • Barbati G
        • Berton E
        • Carriere C
        • Magrì D
        • Cattadori G
        • Confalonieri M
        • Di Lenarda A
        • Agostoni P.
        Prognostic value of cardiopulmonary exercise testing in idiopathic dilated cardiomyopathy.
        Int J Cardiol. 2016; 223: 596-603