Author Archives: Paul Older

Two-day cardiopulmonary exercise testing in long COVID post-exertional malaise diagnosis.

Gattoni C; The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
Abbasi A; Ferguson C; Lanks CW; Decato TW; Rossiter HB; Casaburi R; Stringer WW;

Respiratory physiology & neurobiology [Respir Physiol Neurobiol] 2024 Oct 28; Vol. 331, pp. 104362. Date of Electronic Publication: 2024 Oct 28.

Background: Long COVID patients present with a myriad of symptoms that can include fatigue, exercise intolerance and post exertional malaise (PEM). Long COVID has been compared to other post viral syndromes, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), where a reduction in day 2 cardiopulmonary exercise test (CPET) performance of a two-day CPET protocol is suggested to be a result of PEM. We investigated cardiopulmonary and perceptual responses to a two-day CPET protocol in Long COVID patients.
Methods: 15 Long COVID patients [n=7 females; mean (SD) age: 53(11) yr; BMI = 32.2(8.5) kg/m 2 ] performed a pulmonary function test and two ramp-incremental CPETs separated by 24 hr. CPET variables included gas exchange threshold (GET), peak oxygen uptake (V̇O 2peak ) and peak work rate (WR peak ). Ratings of perceived dyspnoea and leg effort were recorded at peak exercise using the modified 0-10 Borg Scale. PEM (past six months) was assessed using the modified DePaul Symptom Questionnaire (mDSQ). One-sample t-tests were used to test significance of mean difference between days (p<0.05).
Results: mDSQ revealed PEM in 80 % of patients. Lung function was normal. Responses to day 1 CPET were consistent with the presence of aerobic deconditioning in 40 % of patients (V̇O 2peak <80 % predicted, in the absence of evidence of cardiovascular and pulmonary limitations). There were no differences between day-1 and day-2 CPET responses (all p>0.05).
Conclusion: PEM symptoms in Long COVID patients, in the absence of differences in two-day CPET responses separated by 24 hours, suggests that PEM is not due to impaired recovery of exercise capacity between days.
Competing Interests: Declaration of Competing Interest Chiara Gattoni has no conflict of interest to declare. Asghar Abbasi is supported by awards from Johnny Carson Foundation and NIH (1R43 HL167289–01). Carrie Ferguson is supported by grants from NIH (R01HL166850). She reports consulting fees from Respira Therapeutics. She is involved in contracted clinical research with United Therapeutics, Genentech, Regeneron and Respira Therapeutics. She has received honoraria for teaching on the ACCP CPET live-learning course. She is a visiting Associate Professor at the University of Leeds, UK. Charles W. Lanks has no conflict of interest to declare. Thomas DeCato is supported by a grant from the NIH (R01HL166850). He reports consulting fees from MannKind Corporation and has received honoraria for teaching on the ACCP CPET live-learning course. Harry Rossiter is supported by grants from NIH (R01HL151452, R01HL166850, R01HL153460, P50HD098593, R01DK122767) and the Tobacco Related Disease Research Program (T31IP1666). He reports consulting fees from the NIH RECOVER-ENERGIZE working group (1OT2HL156812) and is involved in contracted clinical research with United Therapeutics, Genentech, Regeneron, Respira and Intervene Immune. He is a visiting Professor at the University of Leeds, UK. Richard Casaburi is involved in contracted research and is a consultant with Regeneron. He is an advisory board member for Inogen and a speaker bureau member for GlaxoSmithKline. William Stringer is involved in contracted clinical research with Genentech, Regeneron, Roche, AstraZeneca and the NIH Recover-Vital and Recover-Neuro clinical trials. He performs CPET Data Center activities for the NIH funded PETRACT study (UG3HL155798–01A1). He is a co-investigator on an NIH Small Business Innovation Award (1R43HL167289–01) and has been a site PI for the NIH RETHINC (5U01HL128954-04) and BLOCK-COPD (W81XWH-15–1–0705) studies. He performs Data Safety Monitoring Board activities for SYNEOS and CAPRICOR. He receives royalty payments from a CPET book from Wolters Kluwer. He is a paid consultant for Genentech, Verona and Regeneron. He owns stock in HIA. The current study was funded by the Pulmonary Education and Research Foundation.

Unveiling the link between physical parameters and safety in cardiac rehabilitation: Longitudinal observational study: Physical parameters and cardiac adverse events.

Vanzella LM; São Paulo State University, São Paulo, Brazil.
Ribeiro F; Laurino MJL; Takahashi C;Vanderlei FM; da Silva AKF; Dagostinho DBB; Silva JPLN;
Vanderlei LCM;

Current problems in cardiology [Curr Probl Cardiol] 2024 Nov 01; Vol. 50 (1), pp. 102916.
Date of Electronic Publication: 2024 Nov 01.

Objective: To identify the associations between cardiorespiratory fitness and quadriceps muscle strength and the occurrence of minor adverse events in a cardiac rehabilitation (CR) program.
Design: Prospective cohort study.
Setting: Output of a CR programme for primary or secondary prevention of cardiovascular disease (CVD).
Patients: Seventy individuals who were diagnosed with CVD and/or risk factors and 7 who were excluded due to a low adherence rate in exercise sessions (<70%), 4 due to errors in oxygen consumption recorded during the cardiopulmonary exercise test (CPET) and 11 because they decided to withdraw from the study. The data of 38 participants were analyzed.
Interventions: Not applicable.
Main Outcome Measures: Quadriceps muscle strength was assessed by an isokinetic dynamometer and by a manual dynamometer. Functional capacity was assessed by the CPET and by a six-minute walk test (6MWT). Participants were monitored by a physiotherapist during 24 exercise sessions to identify and register adverse events.
Results: Significant associations were detected between adverse events and quadriceps muscle strength assessed by an isokinetic dynamometer (peak torque, B=-2.0(-2.0;0.0), p=0.047), between functional capacity assessed by the CPET (peak torque, B=-0.3(-2.4;0.0), p=0.019), between fatigue and functional capacity assessed by the CPET (VO2max, B=-1.3(-2.9;0.0), p=0.005) and between quadriceps muscle strength assessed by an isokinetic dynamometer (peak torque, B=-10.0(-2.7;0.0); p=0.010).
Conclusions: Lower functional capacity and quadriceps muscle strength seem to be associated with a greater incidence of adverse events during exercise sessions.

Use of Cardiopulmonary Exercise Testing to Predict Outcomes for Female Patients Undergoing Abdominal Aortic Aneurysm Surgery.

Hodge S; Division of Cardiovascular Sciences, University of Manchester,  UK;
Bryan A; Quraishi-Akhtar T; Ghosh J;Haque A

European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery [Eur J Vasc Endovasc Surg] 2024 Nov 01.
Date of Electronic Publication: 2024 Nov 01.

Letter

No abstract available

Preventing Allogeneic Stem Cell Transplant-Related Cardiovascular Dysfunction: ALLO-Active Trial.

Dillon HT; Baker Heart and Diabetes Institute, Melbourne, Australia & other centres
Saner NJ; Ilsley T; Kliman DS; Foulkes SJ; Brakenridge CJ;Spencer A; Avery S; Dunstan DW; Daly RM; Fraser SF; Owen N; Lynch BM; Kingwell BA; La Gerche A; Howden EJ;

Circulation [Circulation] 2024 Nov 04.
Date of Electronic Publication: 2024 Nov 04.

Background: Allogeneic stem cell transplantation (allo-SCT) is an efficacious treatment for hematologic malignancies but can be complicated by cardiac dysfunction and exercise intolerance impacting quality of life and longevity. We conducted a randomized controlled trial testing whether a multicomponent activity intervention could attenuate reductions in cardiorespiratory fitness and exercise cardiac function (co-primary end points) in adults undergoing allo-SCT.
Methods: Sixty-two adults scheduled for allo-SCT were randomized to a 4-month activity program (n=30) or usual care (UC; n=32). Activity comprised multicomponent exercise training (3 days/week) and sedentary time reduction (≥30 min/day) program and was delivered throughout hospitalization (≈4 weeks) and for 12 weeks after discharge. Physiological assessments conducted before admission and at 12 weeks after discharge included cardiopulmonary exercise testing to quantify peak oxygen uptake ([Formula: see text]), exercise cardiac magnetic resonance imaging for peak cardiac volume (CI peak ) and stroke volume (SVI peak ) index, echocardiography-derived left ventricular ejection fraction and global longitudinal strain, and cardiac biomarkers (cTn-I [troponin-I] and BNP [B-type natriuretic peptide]).
Results: Fifty-two participants (84%) completed follow-up (25 activity and 27 UC); median (interquartile range [IQR]) adherence to the activity program was 74% (41-96%). There was a marked decline in [Formula: see text] in the UC program (-3.4 mL‧kg -1 ‧min -1 [95% CI, -4.9 to -1.8]) that was attenuated with activity (-0.9 mL‧kg -1‧ min -1 [95% CI, -2.5 to 0.8]; interaction P =0.029). Activity preserved exercise cardiac function, with preservation of CI peak (0.30 L‧min -1 ‧m 2 [95% CI, -0.34 to 0.41]) and SVI peak (0.6 mL/m 2 [95% CI, -1.3 to 2.5]), both of which declined with UC (CI peak , -0.68 L‧min -1 ‧m 2 [95% CI, -1.3 to -0.32]; interaction P =0.008; SVI peak , -2.7 mL/m 2 [95% CI, -4.6 to -0.9]; interaction P= 0.014). There were no treatment effects of activity on cardiac biomarkers or echocardiographic indices.
Conclusions: Multicomponent activity intervention during and after allo-SCT is beneficial for preserving patient cardiorespiratory fitness and exercise cardiac function. These results may have important implications for cardiovascular morbidity and mortality after allo-SCT.

Maximal exercise capacity, peripheral muscle strength, sleep quality, and quality of life in adult patients with stable asthma.

Özdemir F; Faculty of Health Sciences, Çankırı Karatekin University, Çankırı, Türkiye.
Boşnak Güçlü M;Göktaş HE; Oğuzülgen IK;

The Journal of asthma : official journal of the Association for the Care of Asthma [J Asthma] 2024 Nov 12, pp. 1-13.
Date of Electronic Publication: 2024 Nov 12.

Objective: The prevalence of asthma is increasing gradually worldwide. The pathophysiological process of asthma causes some alterations in the respiratory system and decreases oxygen-carbon dioxide exchange and respiration volume. These alterations may affect maximal exercise capacity, peripheral muscle strength, sleep quality, and disease-specific quality of life but have yet to be comprehensively investigated. To compare maximal exercise capacity, pulmonary function, peripheral muscle strength, dyspnea, sleep quality, and quality of life in adult patients with asthma, healthy controls were aimed.
Methods: Forty-one adult stable asthmatic patients (GINA I-III) and 41 healthy subjects were compared. Exercise capacity (cardiopulmonary exercise test [CPET]), pulmonary function (spirometry), peripheral muscle strength (dynamometer), dyspnea (modified Medical Research Council [mMRC] dyspnea scale), quality of life (Asthma Quality of Life Questionnaire [AQLQ]) and sleep quality (Pittsburgh Sleep Quality Index [PSQI]) were evaluated.
Results: Peak VO 2 , VO 2 kg, MET, VE, HR, %VE, %HR, VCO 2 parameters of CPET, FVC, FEV 1 , FEF 25-75% , and FEV 1 /FVC and quadriceps femoris, shoulder abductors, and hand grip muscle strength were significantly decreased in patients with asthma ( p  < 0.05). MMRC dyspnea scale score was increased, and AQLQ and PSQI scores decreased in asthma patients ( p  < 0.05).
Conclusions: Cardiac and pulmonary system responses to peak exercise worsened, and maximal exercise capacity and peripheral muscle strength decreased in adult patients with stable asthma. In addition, dyspnea during daily activities increases, and quality of life and sleep quality are impaired. A variety of exercise training that would benefit asthmatic patients’ outcomes should be investigated.

Neurovascular dysregulation in systemic sclerosis: novel insights into pathophysiology, diagnosis, and treatment utilizing invasive cardiopulmonary exercise testing.

Tarras E; Division of Pulmonary, Critical Care, and Sleep Medicine, Yale University,  Connecticut, USA.
Joseph P;

Current opinion in rheumatology [Curr Opin Rheumatol] 2024 Nov 11.
Date of Electronic Publication: 2024 Nov 11.

Purpose of Review: Pathologic abnormalities in skeletal muscle and the systemic vasculature are common in patients with systemic sclerosis (SSc). These abnormalities may lead to impaired systemic peripheral oxygen extraction (EO 2 ), known as neurovascular dysregulation, which may be because of abnormal blood flow distribution in the vasculature, microvascular shunting, and/or skeletal muscle mitochondrial dysfunction. Findings from invasive cardiopulmonary exercising testing (iCPET) provide important insights and enable diagnosis and treatment of this SSc disease manifestation.
Recent Findings: Recent findings from noninvasive cardiopulmonary exercise testing (niCPET) support the existence of neurovascular dysregulation in patients with SSc. Invasive cardiopulmonary exercise testing (iCPET) has pointed to reduced systemic vascular distensibility as a possible mechanism for neurovascular dysregulation in patients with connective tissue diseases, including SSc.
Summary: Neurovascular dysregulation is likely an underappreciated cause of exercise impairment and dyspnea in patients with SSc in the presence or absence of underlying cardiopulmonary disease. It is posited to be related to microcirculatory and muscle dysfunction. Further studies are needed to clarify the pathophysiology of neurovascular dysregulation in SSc and to identify novel treatment targets and additional therapies.

How to evaluate exertional breathlessness using normative reference equations in research.

Ekström M; Faculty of Medicine,  Lund University, Lund, Sweden.
Lewthwaite H; Jensen D; M

Current opinion in supportive and palliative care [Curr Opin Support Palliat Care] 2024 Dec 01; Vol. 18 (4), pp. 191-198.
Date of Electronic Publication: 2024 Oct 30.

Purpose of Review: Breathlessness is a common, distressing and limiting symptom in people with advanced disease, but is challenging to assess as the symptom intensity depends on the level of exertion (symptom stimulus) during the assessment. This review outlines how to use recently developed normative reference equations to evaluate breathlessness responses, accounting for level of exertion, for valid assessment in symptom research.
Recent Findings: Published normative reference equations are freely available to predict the breathlessness intensity response (on a 0-10 Borg scale) among healthy people after a 6-minute walking test (6MWT) or an incremental cycle cardiopulmonary exercise test (iCPET). The predicted normal values account for individual characteristics (including age, sex, height, and body mass) and level of exertion (walk distance for 6MWT; power output, oxygen uptake, or minute ventilation at any point during the iCPET). The equations can be used to (1) construct a matched healthy control dataset for a study; (2) determine how abnormal an individual’s exertional breathlessness is compared with healthy controls; (3) identify abnormal exertional breathlessness (rating > upper limit of normal); and (4) validly compare exertional breathlessness levels across individuals and groups.
Summary: Methods for standardized and valid assessment of exertional breathlessness have emerged for improved symptoms research.

The effect of a standardized verbal encouragement protocol on peak oxygen uptake during incremental treadmill testing in healthy individuals: A randomized cross-over trial.

Van Hooren B; Department of Nutrition and Movement Sciences, NUTRIM, Maastricht University, Maastricht, The Netherlands.
Van Der Lee P; Plasqui G;Bongers BC;

European journal of sport science [Eur J Sport Sci] 2024 Jan; Vol. 24 (1), pp. 16-25.

Peak oxygen uptake (V̇O 2peak ) is considered a vital indicator of health and physical fitness that is often measured during incremental exercise testing. While previous research has shown that the attained V̇O 2peak during exercise testing can be influenced by verbal encouragement, no or limited details were provided on the verbal encouragement protocol, hereby hampering implementation in clinical practice or research. Moreover, it remains unknown whether motivation modulates the effect of verbal encouragement. This study aimed to develop and examine the influence of a standardized verbal encouragement protocol on the achieved V̇O 2peak , time to exhaustion (TTE), peak heart rate (HR peak ), and peak respiratory exchange ratio (RER peak ) during incremental treadmill testing. As a secondary aim, we investigated whether motivation modulated the effect of verbal encouragement on V̇O 2peak . 24 healthy volunteers performed two incremental treadmill runs with 1 week in between and received verbal encouragement during only one of the tests. Motivation toward exercise was measured using the behavioral regulation in exercise questionnaire-2 (BREQ-2) questionnaire. V̇O 2peak (Δ 2.10 mL/kg/min, p < 0.001) and RER peak (Δ 2%, p = 0.042) were significantly higher with verbal encouragement. In contrast, HR peak (Δ 1.5 beats/min, p = 0.225) and TTE (Δ 1.5%, p = 0.348) were not significantly different between conditions. Exercise motivation showed a weak and nonsignificant association with the change in V̇O 2peak between tests (r -0.19, R 2 0.037, SEE 2.88, and p = 0.367). These findings show that verbal encouragement leads to higher physiological outcomes during incremental treadmill testing, but the magnitude of this effect is not higher for individuals with lower levels of pretest motivation.

Association Between Subclinical Right Ventricular Alterations and Aerobic Exercise Capacity in Type 2 Diabetes.

Dattani A; Department of Cardiovascular Sciences, University of Leicester UK.
Yeo JL;Brady EM; Cowley A; Marsh AM; Sian M; Bilak JM; Graham-Brown MPM; Singh A; Arnold JR; Adlam D;Yates T; McCann GP; Gulsin GS;

Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance [J Cardiovasc Magn Reson] 2024 Oct 28, pp. 101120.
Date of Electronic Publication: 2024 Oct 28.

Background: Type 2 Diabetes (T2D) leads to cardiovascular remodeling, and heart failure has emerged as a major complication of T2D. There is a limited understanding of the impact of T2D on the right heart. This study aimed to assess subclinical right heart alterations and their contribution to aerobic exercise capacity (peak VO 2 ) in adults with T2D.
Methods: Single center, prospective, case-control comparison of adults with and without T2D, and no prevalent cardiac disease. Comprehensive evaluation of the left and right heart was performed using transthoracic echocardiography and stress cardiovascular magnetic resonance. Cardiopulmonary exercise testing on a bicycle ergometer with expired gas analysis was performed to determine peak VO 2 . Between group comparison was adjusted for age, sex, race and body mass index using ANCOVA. Multivariable linear regression including key clinical and left heart variables, was undertaken in people with T2D to identify independent associations between measures of right ventricular (RV) structure and function with peak VO 2 .
Results: 340 people with T2D (median age 64 years, 62% male, mean HbA1c 7.3%) and 66 controls (median age 58 years, 58% male, mean HbA1c 5.5%) were included. T2D participants had markedly lower peak VO 2 (adjusted mean 20.3(95% CI: 19.8-20.9) vs. 23.3(22.2-24.5) mL/kg/min, P<0.001) than controls and had smaller left ventricular (LV) volumes and LV concentric remodeling. Those with T2D had smaller RV volumes (indexed RV end-diastolic volume: 84(82-86) vs. 100(96-104) mL/m, P<0.001) with evidence of hyperdynamic RV systolic function (global longitudinal strain: 26.3(25.8-26.8) vs. 23.5(22.5-24.5) %, P<0.001) and impaired RV relaxation (longitudinal peak early diastolic strain rate: 0.77(0.74-0.80) vs. 0.92(0.85-1.00) s -1 , P<0.001). Multivariable linear regression demonstrated that RV end-diastolic volume (β=-0.342, P=0.004) and RV cardiac output (β=0.296, P=0.001), but not LV parameters, were independent determinants of peak VO 2 .
Conclusions: In T2D, markers of RV remodeling are associated with aerobic exercise capacity, independent of left heart alterations.