Milne KM; Cowan J; Schaeffer MR; Voduc N; Chirinos JA; Abdallah SJ; Guenette JA;

ERJ open research [ERJ Open Res] 2023 Jun 19; Vol. 9 (3).
Date of Electronic Publication: 2023 Jun 19 (Print Publication: 2023).

Objectives: Dyspnoea is a common persistent symptom post-coronavirus disease 2019 (COVID-19) illness. However, the mechanisms underlying dyspnoea in the post-COVID-19 syndrome remain unclear. The aim of our study was to examine dyspnoea quality and intensity, burden of mental health symptoms, and differences in exercise responses in people with and without persistent dyspnoea following COVID-19.
Methods: 49 participants with mild-to-critical COVID-19 were included in this cross-sectional study 4 months after acute illness. Between-group comparisons were made in those with and without persistent dyspnoea (defined as modified Medical Research Council dyspnoea score ≥1). Participants completed standardised dyspnoea and mental health symptom questionnaires, pulmonary function tests, and incremental cardiopulmonary exercise testing.
Results: Exertional dyspnoea intensity and unpleasantness were increased in the dyspnoea group. The dyspnoea group described dyspnoea qualities of suffocating and tightness at peak exercise (p<0.05). Ventilatory equivalent for carbon dioxide ( V ‘ _E / V ‘ _{CO 2} ) nadir was higher (32±5 versus 28±3, p<0.001) and anaerobic threshold was lower (41±12 versus 49±11% predicted maximum oxygen uptake, p=0.04) in the dyspnoea group, indicating ventilatory inefficiency and deconditioning in this group. The dyspnoea group experienced greater symptoms of anxiety, depression and post-traumatic stress (all p<0.05). A subset of participants demonstrated gas-exchange and breathing pattern abnormalities suggestive of dysfunctional breathing.
Conclusions: People with persistent dyspnoea following COVID-19 experience a specific dyspnoea quality phenotype. Dyspnoea post-COVID-19 is related to abnormal pulmonary gas exchange and deconditioning and is linked to increased symptoms of anxiety, depression and post-traumatic stress.
Competing Interests: Conflict of interest: K.L. Lavoie reports consulting fees from AbbVie, Takeda, Astellas, Boehringer Ingelheim, AstraZeneca, Janssen, Novartis, GSK, Bausch and Sojecci Inc., outside the submitted work; payment or honoraria from AbbVie, Boehringer Ingelheim, Takeda, Pfizer, Merck, GSK, Astra-Zeneca, Novartis, Janssen, Bayer, Mundi Pharma, Bayer, Air Liquide, Astellas and Xfacto, outside the submitted work; and participation on a Data Safety Monitoring Board or Advisory Board for Astra-Zeneca, GSK and Bausch, outside the submitted work. Conflict of interest: J. Cowan reports support for the present manuscript from The Ottawa Hospital Foundation; grants or contracts from Octapharma and Takeda, outside the submitted work; payment or honoraria from GSK, Sanofi, EMD Serono, Alexion and Takeda, outside the submitted work; and support for attending meetings and/or travel from Octapharma, outside the submitted work. Conflict of interest: J.A. Chirinos reports grants or contracts from University of Pennsylvania research grants from National Institutes of Health, Fukuda-Denshi, Bristol-Myers Squibb, Microsoft and Abbott, outside the submitted work; consulting fees from Bayer, Sanifit, Fukuda-Denshi, Bristol-Myers Squibb, JNJ, Edwards Life Sciences, Merck, NGM Biopharmaceuticals and the Galway-Mayo Institute of Technology, outside the submitted work; patents planned, issued or pending: inventor in a University of Pennsylvania patent for the use of inorganic nitrates/nitrites for the treatment of Heart Failure and Preserved Ejection Fraction and for the use of biomarkers in heart failure with preserved ejection fraction, outside the submitted work; participant on advisory board for BMS, outside the submitted work; Vice President of North American Artery Society, outside the submitted work; received research device loans from Atcor Medical, Fukuda-Denshi, Uscom, NDD Medical Technologies, Microsoft and MicroVision Medical, outside the submitted work; received payments for editorial roles from the American Heart Association, the American College of Cardiology and Wiley, outside the submitted work. Conflict of interest: J.A. Guenette is an associate editor of this journal. Conflict of interest: The remaining authors have nothing to disclose.

Ahmed B; Shaw S; Pratt O; Forde C; Lal S; Carlson Cbe G;

Clinical nutrition ESPEN [Clin Nutr ESPEN] 2023 Aug; Vol. 56, pp. 152-157.
Date of Electronic Publication: 2023 May 19.

Background: Parenteral nutrition (PN) deficient in mitochondrial substrates and thiamine may lead to acidosis. This, combined with fatigue seen in patients with intestinal failure (IF), may suggest suboptimal oxidative metabolism. We therefore studied oxygen utilisation in otherwise apparently well-nourished individuals with intestinal failure receiving long term PN.
Methods: This was a retrospective analysis conducted in a tertiary IF institution, from 2010 to 2019, comparing treadmill/bicycle cardiopulmonary exercise test (CPET) derived variables including peak oxygen consumption (VO _{2 peak} ), anaerobic threshold (AT) and ventilatory efficiency (minute ventilation (VE)/CO ₂ output (VCO ₂ ) of patients with IF (cases) to those without (controls), matched in a 1:2 ratio for age ( ± 3 years), gender, use of beta-blockers and physiology parameters of p-POSSUM score ( ± 5). All subjects were free of sepsis and metastatic malignancy. Mann-Whitney or Student’s t-test for continuous and Fisher’s exact or chi-squared test for categorical variables were used as appropriate. Data shown represent mean or median values.
Results: Participants (31 cases, 62 controls) were comparable in age (65.4 vs. 65.3, p = 0.98); p-POSSUM parameters (18.0 vs. 17.0, p = 0.45); gender (p = 1.00); smoking status (p = 0.52); use of beta-blockers (p = 1.00) and ≤10 mg/day of oral steroids (p = 0.34). Participants had been on PN for 11.0 (6.0-24.0) months and were adequately nourished (requirements 27.6 kcal/kg/day, replacement 23.5 kcal/kg/day). No differences were found between VO _{2 peak} (15.2 vs. 14.6 ml/kg/min, p = 0.96), AT (10.4 vs. 11.0 ml/kg/min, p = 0.44) and VE/VCO ₂ (33.0 vs. 33.0, p = 0.96) of the examined groups.
Conclusion: Patients with intestinal failure receiving PN who are apparently well-nourished also appear to have normal oxygen utilisation, suggesting alternative causes for fatigue. More studies will be required to determine whether CPET could reliably be used to assess perioperative risk in this group of patients.

Wernhart S; Balcer B; Rassaf T; Luedike P;

Journal of clinical medicine [J Clin Med] 2023 May 25; Vol. 12 (11).
Date of Electronic Publication: 2023 May 25.

(1) Background: The exercise capacity of patients with a left ventricular assist device (LVAD) remains limited despite mechanical support. Higher dead space ventilation (V _D /V _T ) may be a surrogate for right ventricular to pulmonary artery uncoupling (RV-PA) during cardiopulmonary exercise testing (CPET) to explain persistent exercise limitations.
(2) Methods: We investigated 197 patients with heart failure and reduced ejection fraction with ( n = 89) and without (HFrEF, n = 108) LVAD. As a primary outcome NTproBNP, CPET, and echocardiographic variables were analyzed for their potential to discriminate between HFrEF and LVAD. As a secondary outcome CPET variables were evaluated for a composite of hospitalization due to worsening heart failure and overall mortality over 22 months.
(3) Results: NTproBNP (OR 0.6315, 0.5037-0.7647) and RV function (OR 0.45, 0.34-0.56) discriminated between LVAD and HFrEF. The rise of endtidal CO ₂ (OR 4.25, 1.31-15.81) and V _D /V _T (OR 1.23, 1.10-1.40) were higher in LVAD patients. Group (OR 2.01, 1.07-3.85), VE/VCO ₂ (OR 1.04, 1.00-1.08), and ventilatory power (OR 0.74, 0.55-0.98) were best associated with rehospitalization and mortality.
(4) Conclusions: LVAD patients displayed higher V _D /V _T compared to HFrEF. Higher V _D /V _T as a surrogate for RV-PA uncoupling could be another marker of persistent exercise limitations in LVAD patients.

Mounsey LA; Witkin AS; Hardin CC; Rodriguez-Lopez J;

Annals of the American Thoracic Society [Ann Am Thorac Soc] 2023 Jun 13.
Date of Electronic Publication: 2023 Jun 13.

NO abstract available

Keteyian SJ; Steenson K; Grimshaw C; Mandel N; Koester-Qualters W; Berry R; Kerrigan DJ;Ehrman JK;
Peterson EL; Brawner CA;

Journal of cardiopulmonary rehabilitation and prevention [J Cardiopulm Rehabil Prev] 2023 Jun 14.
Date of Electronic Publication: 2023 Jun 14.

Purpose: Among patients in cardiac rehabilitation (CR) on beta-adrenergic blockade (βB) therapy, this study describes the frequency for which target heart rate (THR) values computed using a predicted maximal heart rate (HRmax), correspond to a THR computed using a measured HRmax in the guideline-based heart rate reserve (HRreserve) method.
Methods: Before CR, patients completed a cardiopulmonary exercise test to measure HRmax, with the data used to determine THR via the HRreserve method. Additionally, predicted HRmax was computed for all patients using the 220 – age equation and two disease-specific equations, with the predicted values used to calculate THR via the straight percent and HRreserve methods. The THR was also computed using resting heart rate (HR) +20 and +30 bpm.
Results: Mean predicted HRmax using the 220 – age equation (161 ± 11 bpm) and the disease-specific equations (123 ± 9 bpm) differed (P < .001) from measured HRmax (133 ± 21 bpm). Also, THR computed using predicted HRmax resulted in values that were infrequently within the guideline-based HRreserve range calculated using measured HRmax. Specifically, 0 to ≤61% of patients would have had an exercise training HR that fell within the guideline-based range of 50-80% of measured HRreserve. Use of standing resting HR +20 or +30 bpm would have resulted in 100% and 48%, respectively, of patients exercising below 50% of HRreserve.
Conclusions: A THR computed using either predicted HRmax or resting HR +20 or +30 bpm seldom results in a prescribed exercise intensity that is consistent with guideline recommendations for patients in CR.

Amedro P; Mura T; Matecki S;  Guillaumont S; Requirand A; Jeandel C; Kollen L; Gavotto A;

European journal of preventive cardiology [Eur J Prev Cardiol] 2023 Jun 14.
Date of Electronic Publication: 2023 Jun 14.

Aims: Overweight and obesity in children with congenital heart disease (CHD) represent an alarming cardiovascular risk. Promotion of physical activity and cardiac rehabilitation in this population requires assessing the level of aerobic fitness (VO2max) by a cardiopulmonary exercise test (CPET). Nevertheless, the interpretation of CPET in overweight/obese children with CHD remains challenging as VO2max is affected by both the cardiac condition and the body mass index (BMI). The new paediatric VO2max Z-score reference equations, based on a logarithmic function of VO2max, height and BMI, were applied to overweight/obese children with a CHD, and compared to overweight/obese children without any other chronic condition.
Methods and Results: In this cross-sectional controlled study, 344 children with a BMI>85th percentile underwent a CPET (54% boys; mean age 11.5±3.1 years; 100 CHD; 244 controls). Using the VO2max Z-score equations, aerobic fitness was significantly lower in obese/overweight CHD children than in matched obese/overweight control children (-0.43±1.27 vs. -0.01±1.09; p=0.02, respectively) and the proportion of children with impaired aerobic fitness was significantly more important in obese/overweight CHD children than in matched controls (17% vs.6%, p=0.02, respectively). The paediatric VO2max Z-score reference equations also identified specific complex CHD at risk of aerobic fitness impairment (univentricular heart, right outflow tract anomalies). Using Cooper’s weight and height-based linear equations, similar matched-comparisons analyses found no significant group differences.
Conclusions: As opposed to the existing linear models, the new paediatric VO2max Z-score equations can discriminate the aerobic fitness of obese/overweight children with CHD from that of obese/overweight children without any chronic disease.

Omar M; Omote K; Sorimachi H; Popovic D; Kanwar A; Alogna A; Reddy YNV; Lim KG;Shah SJ; Borlaug BA;

European journal of heart failure [Eur J Heart Fail] 2023 Jun 14.
Date of Electronic Publication: 2023 Jun 14.

Background & Aims: It is widely held that heart failure (HF) does not cause exertional hypoxemia, based upon studies in HF with reduced ejection fraction (EF), but this may not apply to patients with HF and preserved EF (HFpEF). Here, we characterize the prevalence, pathophysiology, and clinical implications of exertional arterial hypoxemia in HFpEF.
Methods & Results: Patients with HFpEF (n=539) and no coexisting lung disease underwent invasive cardiopulmonary exercise testing with simultaneous blood and expired gas analysis. Exertional hypoxemia (oxyhemoglobin saturation <94%) was observed in 136 patients (25%). As compared to those without hypoxemia (n=403), patients with hypoxemia were older and more obese. Patients with HFpEF and hypoxemia had higher cardiac filling pressures, higher pulmonary vascular pressures, greater alveolar-arterial O ₂ difference, increased dead space fraction, and greater physiologic shunt compared to those without hypoxemia. These differences were replicated in a sensitivity analysis where patients with spirometric abnormalities were excluded. Regression analyses revealed that increases in pulmonary arterial and capillary pressures were related to lower PaO ₂ , especially during exercise. BMI was not correlated with the arterial PaO ₂ , and hypoxemia was associated with increased risk for death over 2.8 (IQR 0.7-5.5) years of follow up, even after adjusting for age, sex, and BMI (HR 2.00 (95%CI: 1.01-3.96), p=0.046).
Conclusion: Between 10-25% of patients with HFpEF display arterial desaturation during exercise that is not ascribable to lung disease. Exertional hypoxemia is associated with more severe hemodynamic abnormalities and increased mortality. Further study is required to better understand the mechanisms and treatment of gas exchange abnormalities in HFpEF.

Collins B; Gordon B; Wundersitz D; Hunter J; Hanson LC; O’Doherty AF;Hayes A; Kingsley M;

BMJ open [BMJ Open] 2023 Jun 15; Vol. 13 (6), pp. e070872.
Date of Electronic Publication: 2023 Jun 15.

Introduction: Exercise-based cardiac rehabilitation programmes (ExCRP) promote recovery and secondary prevention for individuals with cardiovascular disease (CVD). Despite this, enrolment and adherence to ExCRP in rural locations is low. Telehealth programmes provide a convenient, home-based intervention, but concerns remain about compliance to exercise prescription. This paper presents the rationale and protocol design to determine if telehealth delivered ExCRP is not inferior to supervised ExCRP for improving cardiovascular function and exercise fidelity.
Method and Analysis: A non-inferiority, parallel (1:1), single-blinded randomised clinical trial will be conducted. Fifty patients with CVD will be recruited from a rural phase II ExCRP. Participants will be randomly assigned to telehealth or supervised ExCRP and prescribed three weekly exercise sessions for 6 weeks. Exercise sessions will include a 10 min warm up, up to 30 min of continuous aerobic exercise at a workload equivalent to the ventilatory anaerobic threshold and a 10 min cool down. The primary outcome will be change in cardiorespiratory fitness as measured by cardiopulmonary exercise test. Secondary outcome measures will include change in blood lipid profile, heart rate variability, pulse wave velocity, actigraphy measured sleep quality and training fidelity. Non-inferiority will be confirmed if intention-to-treat and per-protocol analyses conclude the same outcome following independent samples t-test with p<0.025.
Ethics and Dissemination: Research ethics committees at La Trobe University, St John of God Health Care and Bendigo Health approved the study protocol and informed consent. Findings will be published in peer-reviewed journals and disseminated among stakeholders.

Uwase E; Caru M; Curnier D; Abasq Meng M; Andelfinger G; Krajinovic M; Laverdière C; Sinnett D; Périé D;

Journal of pediatric hematology/oncology [J Pediatr Hematol Oncol] 2023 May 16.
Date of Electronic Publication: 2023 May 16.

Background: There is a shortage of relevant studies interested in cardiac mechanical performance. Thus, it is clinically relevant to study the impact of cancer treatments on survivors’ cardiac mechanical performance to improve our knowledge. The first objective of this study is to assess survivors’ cardiac mechanical performance during a cardiopulmonary exercise test (CPET) using both ventricular-arterial coupling (VAC) and cardiac work efficiency (CWE) from cardiac magnetic resonance (CMR) acquisitions. The second objective is to assess the impact of doxorubicin and dexrazoxane (DEX) treatments.
Methods: A total of 63 childhood acute lymphoblastic leukemia survivors underwent a CMR at rest on a 3T magnetic resonance imaging system, followed by a CPET on ergocycle. The CircAdapt model was used to study cardiac mechanical performance. At different levels of exercise, arterial elastance, end-systolic elastance, VAC, and CWE were estimated.
Results: We observed significant differences between the different levels of exercise for both VAC (P<0.0001) and CWE parameters (P=0.001). No significant differences were reported between prognostic risk groups at rest and during the CPET. Nevertheless, we observed that survivors in the SR group had a VAC value slightly lower than heart rate (HR)+DEX and HR groups throughout the CPET. Moreover, survivors in the SR group had a CWE parameter slightly higher than HR+DEX and HR groups throughout the CPET.
Conclusions: This study reveals that the combination of CPET, CMR acquisitions and CircAdapt model was sensitive enough to observe slight changes in the assessment of VAC and CWE parameters. Our study contributes to improving survivors’ follow-up and detection of cardiac problems induced by doxorubicin-related cardiotoxicity.

Cantone A; Serenelli M; Sanguettoli F; Maio D; Fabbri G; Dal Passo B; Agostoni P; Grazzi G; Campo G; Rapezzi C;

ESC heart failure [ESC Heart Fail] 2023 Jun 01.
Date of Electronic Publication: 2023 Jun 01.

Background: The clinical value of cardiopulmonary exercise testing (CPET) in cardiac amyloidosis (CA) is uncertain. Due to the growing prevalence of the disease and the current availability of disease-modifying drugs, prognostic stratification is becoming fundamental to optimizing the cost-effectiveness of treatment, patient phenotyping, follow-up, and management. Peak VO ₂ and VE/VCO ₂ slope are currently the most studied CPET variables in clinical settings, and both demonstrate substantial, independent prognostic value in several cardiovascular diseases. We aim to study the association of peak VO ₂ and VE/VCO ₂ slope with prognosis in patients with CA.
Methods and Results: We performed a systematic review and searched for clinical studies performing CPET for prognostication in patients with transthyretin-CA and light-chain-CA. Studies reporting hazard ratio (HR) for mortality and peak VO ₂ or VE/VCO ₂ slope were further selected for quantitative analysis. HRs were pooled using a random-effect model. Five studies were selected for qualitative and three for quantitative analysis. A total of 233 patients were included in the meta-analysis. Mean peak VO ₂ resulted consistently depressed, and VE/VCO ₂ slope was increased. Our pooled analysis showed peak VO ₂ (pooled HR 0.89, 95% CI 0.84-0.94) and VE/VCO ₂ slope (pooled HR 1.04, 95% CI 1.01-1.07) were significantly associated with the risk of death in CA patients, with no significant statistical heterogeneity for both analyses.
Conclusions: CPET is a valuable tool for prognostic stratification in CA, identifying patients at increased risk of death. Large prospective clinical trials are needed to confirm this exploratory finding.