Durstenfeld MS; Sun K; Tahir PM; Peluso MJ; Deeks SG; Aras MA; Grandis DJ; Long CS; Beatty A; Hsue PY

MedRxiv : the preprint server for health sciences [medRxiv] 2022 Jun 16.
Date of Electronic Publication: 2022 Jun 16.

Importance: Reduced exercise capacity is commonly reported among individuals with Long COVID (LC). Cardiopulmonary exercise testing (CPET) is the gold-standard to measure exercise capacity to identify causes of exertional intolerance.
Objectives: To estimate the effect of SARS-CoV-2 infection on exercise capacity including those with and without LC symptoms and to characterize physiologic patterns of limitations to elucidate possible mechanisms of LC.
Data Sources: We searched PubMed, EMBASE, and Web of Science, preprint severs, conference abstracts, and cited references in December 2021 and again in May 2022.
Study Selection: We included studies of adults with SARS-CoV-2 infection at least three months prior that included CPET measured peak VO ₂ . 3,523 studies were screened independently by two blinded reviewers; 72 (2.2%) were selected for full-text review and 36 (1.2%) met the inclusion criteria; we identified 3 additional studies from preprint servers.
Data Extraction and Synthesis: Data extraction was done by two independent reviewers according to PRISMA guidelines. Data were pooled with random-effects models.
Main Outcomes and Measures: A priori primary outcomes were differences in peak VO ₂ (in ml/kg/min) among those with and without SARS-CoV-2 infection and LC.
Results: We identified 39 studies that performed CPET on 2,209 individuals 3-18 months after SARS-CoV-2 infection, including 944 individuals with LC symptoms and 246 SARS-CoV-2 uninfected controls. Most were case-series of individuals with LC or post-hospitalization cohorts. By meta-analysis of 9 studies including 404 infected individuals, peak VO ₂ was 7.4 ml/kg/min (95%CI 3.7 to 11.0) lower among infected versus uninfected individuals. A high degree of heterogeneity was attributable to patient and control selection, and these studies mostly included previously hospitalized, persistently symptomatic individuals. Based on meta-analysis of 9 studies with 464 individuals with LC, peak VO ₂ was 4.9 ml/kg/min (95%CI 3.4 to 6.4) lower compared to those without symptoms. Deconditioning was common, but dysfunctional breathing, chronotropic incompetence, and abnormal oxygen extraction were also described.
Conclusions and Relevance: These studies suggest that exercise capacity is reduced after SARS-CoV-2 infection especially among those hospitalized for acute COVID-19 and individuals with LC. Mechanisms for exertional intolerance besides deconditioning may be multifactorial or related to underlying autonomic dysfunction.

Van de Wiel HJ; Groen WG; Kampshoff CS; Buffart LM; van Mechelen W; van Harten WH; Aaronson PDNK;
Stuiver PDMM;

Archives of physical medicine and rehabilitation [Arch Phys Med Rehabil] 2022 Jun 19.
Date of Electronic Publication: 2022 Jun 19.

Objective: To investigate the construct validity of the Steep Ramp Test by longitudinally comparing the correlation between Maximum Short Exercise Capacity (MSEC) of the Steep Ramp Test (SRT) and direct measurements of VO ₂ peak during or shortly after treatment in patients with breast cancer and the potential impact of chemotherapy-induced symptom burden.
Design: Cross-sectional SETTING: Multicenter PARTICIPANTS: We used data from two studies that included women with breast cancer treated with chemotherapy, resulting in 274 observations. 161 patients performed the Cardiopulmonary Exercise Test (CPET) and the Steep Ramp Test in two test sessions on different time points around chemotherapy treatment.
Interventions: Not Applicable MAIN OUTCOME MEASURES: Fatigue was assessed with the Multidimensional Fatigue Inventory, and nausea and vomiting and pain by the EORTC Quality of Life Questionnaire -Core 30. The longitudinal correlation between the Maximum Short Exercise Capacity and VO ₂ peak was investigated using a linear mixed model. Interaction terms were added to the model, to investigate whether the correlation varied by symptom burden.
Results: We found a statistically significant moderate correlation between VO₂peak and Maximum Short Exercise Capacity (.61, 95% CI; .51 .70, p < .01) over time. This correlation was slightly attenuated (-.07, 95% CI; -.13 .00, p = .04) in patients’ with chemotherapy-related nausea and vomiting, indicating smaller correlations of VO ₂ peak with the Maximum Short Exercise Capacity with increasing symptom burden. Pain and fatigue did not significantly modify the correlation.
Conclusion: The Steep Ramp Test can only be used as a proxy for changes in aerobic capacity with great caution and with attention for the level of nausea and vomiting.

Salvioni E; Mapelli M; Bonomi A; Magrì D; Piepoli M; Frigerio M; Paolillo S; Corrà U; Raimondo R; Lagioia R; Badagliacca R; Filardi PP; Senni M; Correale M; Cicoira M; Perna E; Metra M; Guazzi M; Limongelli G; Sinagra G; Parati G; Cattadori G; Bandera F; Bussotti M; Vignati C; Lombardi C; Scardovi AB; Sciomer S; Passantino A; Emdin M; Passino C; Santolamazza C; Girola D; Zaffalon D; De Martino F; Agostoni P;

Chest [Chest] 2022 Jun 23.
Date of Electronic Publication: 2022 Jun 23.

Background: In clinical practice, anaerobic threshold (AT), is used to guide training and rehabilitation programs, to define risk of major thoracic or abdominal surgery, and to assess prognosis in heart failure (HF). VO ₂ AT has been reported as absolute value (VO ₂ ATabs), as percentage of predicted peak VO ₂ (VO ₂ AT%peak&#95;pred) or as percentage of observed peak VO ₂ value (VO ₂ AT%peak&#95;obs). A direct comparison of the prognostic power among these different ways to report AT is missing.
Research Question: What is the prognostic power of these different ways to report AT?
Study Design and Methods: Observational cohort study. We screened data of 7746 HF patients with history of reduced ejection fraction (<40%), recruited between 1998 and 2020 and enrolled in the MECKI register. All patients underwent a maximal cardiopulmonary exercise test (CPET), executed using a ramp protocol on an electronically braked cycle ergometer.
Results: In this study we considered 6157HF patients with identified AT. Follow up was 4.2 years (1.9-5.0). Both VO ₂ ATabs (823(305 mL/min)) and VO ₂ AT%peak&#95;pred (39.6(13.9%)) but not VO ₂ AT%peak&#95;obs (69.2(17.7%)) well stratified the population as regards prognosis (composite endpoint: cardiovascular death, urgent heart transplant or left ventricular assist device). Comparing AUC values, VO ₂ ATabs (0.680) and VO ₂ AT%peak&#95;pred (0.688) performed similarly, while VO ₂ AT%peak&#95;obs (0.538) was significantly weaker (P<0.001). Moreover, VO ₂ AT%peak&#95;pred AUC value was the only performing as well as AUC based on peakVO ₂ (0.710), with even a higher AUC (0.637 vs. 0.618 respectively) in the group with severe HF (peakVO ₂ <12mL/min/kg). Finally, the combination of VO ₂ AT%peak&#95;pred with Peak VO ₂ and VE/VCO ₂ shows the highest prognostic power.
Interpretation: In HF, VO ₂ AT%peak&#95;pred is the best way to report VO ₂ at AT in relation to prognosis, with a prognostic power comparable to that of peak VO ₂ and, remarkably, in severe HF patients.

Antoniou V; Xanthopoulos A; Giamouzis G; Davos C; Batalik L; Stavrou V; Gourgoulianis KI; Kapreli E; Skoularigis J; Pepera G;

BMJ open [BMJ Open] 2022 Jun 23; Vol. 12 (6), pp. e059945.
Date of Electronic Publication: 2022 Jun 23.

Introduction: Exercise-based cardiac rehabilitation (CR) is a beneficial tool for the secondary prevention of cardiovascular diseases with, however, low participation rates. Telerehabilitation, intergrading mobile technologies and wireless sensors may advance the cardiac patients’ adherence. This study will investigate the efficacy, efficiency, safety and cost-effectiveness of a telerehabilitation programme based on objective exercise telemonitoring and evaluation of cardiorespiratory fitness.
Methods and Analysis: A supervised, parallel-group, single-blind randomised controlled trial will be conducted. A total of 124 patients with coronary disease will be randomised in a 1:1 ratio into two groups: intervention telerehabilitation group (TELE-CR) (n=62) and control centre-based cardiac rehabilitation group (CB-CR) (n=62). Participants will receive a 12-week exercise-based rehabilitation programme, remotely monitored for the TELE-CR group and standard supervised for the CB-CR group. All participants will perform aerobic training at 70% of their maximal heart rate, as obtained from cardiopulmonary exercise testing (CPET) for 20 min plus 20 min for strengthening and balance training, three times per week. The primary outcomes will be the assessment of cardiorespiratory fitness, expressed as peak oxygen uptake assessed by the CPET test and the 6 min walk test. Secondary outcomes will be the physical activity, the safety of the exercise intervention (number of adverse events that may occur during the exercise), the quality of life, the training adherence, the anxiety and depression levels, the nicotine dependence and cost-effectiveness. Assessments will be held at baseline, end of intervention (12 weeks) and follow-up (36 weeks).
Ethics and Dissemination: The study protocol has been reviewed and approved by the Ethics Committee of the University of Thessaly (1108/1-12-2021) and by the Ethics Committee of the General University Hospital of Larissa (3780/31-01-2022). The results of this study will be disseminated through manuscript publications and conference presentations.
Trial Registration Number: NCT05019157.

de Vries JT; Wiggers TGH; Goedegebuure S; Reurink G;

Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine [Clin J Sport Med] 2022 Jul 01; Vol. 32 (4), pp. 387-395.
Date of Electronic Publication: 2022 Jan 25.

Objective: To evaluate the number of medical conditions detected by periodic health evaluations (PHEs) in elite athletes, and their consequences for management and medical clearance.
Design: Retrospective design.
Participants: Elite athletes of various sports in a high-performance program in The Netherlands, in the period between 2009 and 2020.
Interventions: The PHEs consisted of a questionnaire, general and musculoskeletal physical examination, laboratory blood test, electrocardiogram, pulmonary function testing, and (cardiopulmonary) exercise test.
Main Outcome Measures: We extracted and analyzed the medical conditions that led to advice, clinical follow-up, further diagnostic investigation or treatment, and the medical clearance status of the athlete (clearance, temporarily no clearance, or permanently no clearance).
Results: We included 721 PHEs of 451 elite athletes. We found 1389 medical conditions that led to advice (n = 923, 66%), clinical follow-up (n = 124, 9%), further diagnostic investigation (n = 190, 14%), treatment (n = 132, 10%), or sports restriction (n = 20, 1%). Only 20 cases (3%) led to temporarily no medical clearance. After further investigation or treatment, no permanent sports restriction was imposed on any of the athletes.
Conclusions: We found a high number of medical conditions detected with a PHE in elite athletes. However, the vast majority of detected conditions were mild, with consequences limited to preventive advice and follow-up. The yield of PHE to detect (potentially) severe pathological conditions seems low. Clinical relevance of PHE in elite athletes and potential future health benefits remain unclear.

Salzano A; D’Assante R; Iacoviello M; Triggiani V; Rengo G; Cacciatore F; Maiello C; Limongelli G; Masarone D; Sciacqua A; Filardi PP; Mancini A; Volterrani M; Vriz O; Castello R; Passantino A; Campo M; Modesti PA; De Giorgi A; Arcopinto M; Gargiulo P; Perticone M; Colao A; Milano S; Garavaglia A; Napoli R; Suzuki T; Bossone E; Marra AM; Cittadini A;

Cardiovascular diabetology [Cardiovasc Diabetol] 2022 Jun 16; Vol. 21 (1), pp. 108.
Date of Electronic Publication: 2022 Jun 16.

Background: Findings from the T.O.S.CA. Registry recently reported that patients with concomitant chronic heart failure (CHF) and impairment of insulin axis (either insulin resistance-IR or diabetes mellitus-T2D) display increased morbidity and mortality. However, little information is available on the relative impact of IR and T2D on cardiac structure and function, cardiopulmonary performance, and their longitudinal changes in CHF.
Methods: Patients enrolled in the T.O.S.CA. Registry performed echocardiography and cardiopulmonary exercise test at baseline and at a patient-average follow-up of 36 months. Patients were divided into three groups based on the degree of insulin impairment: euglycemic without IR (EU), euglycemic with IR (IR), and T2D.
Results: Compared with EU and IR, T2D was associated with increased filling pressures (E/e’ratio: 15.9 ± 8.9, 12.0 ± 6.5, and 14.5 ± 8.1 respectively, p < 0.01) and worse right ventricular(RV)-arterial uncoupling (RVAUC) (TAPSE/PASP ratio 0.52 ± 0.2, 0.6 ± 0.3, and 0.6 ± 0.3 in T2D, EU and IR, respectively, p < 0.05). Likewise, impairment in peak oxygen consumption (peak VO ₂ ) in TD2 vs EU and IR patients was recorded (respectively, 15.8 ± 3.8 ml/Kg/min, 18.4 ± 4.3 ml/Kg/min and 16.5 ± 4.3 ml/Kg/min, p < 0.003). Longitudinal data demonstrated higher deterioration of RVAUC, RV dimension, and peak VO ₂ in the T2D group (+ 13% increase in RV dimension, - 21% decline in TAPSE/PAPS ratio and - 20% decrease in peak VO ₂ ).
Conclusion: The higher risk of death and CV hospitalizations exhibited by HF-T2D patients in the T.O.S.CA. Registry is associated with progressive RV ventricular dysfunction and exercise impairment when compared to euglycemic CHF patients, supporting the pivotal importance of hyperglycaemia and right chambers in HF prognosis.

Zhou D; Li X; Yin G; Li S; Zhao S; Liu Z; Lu M;

Journal of magnetic resonance imaging : JMRI [J Magn Reson Imaging] 2022 Jun 17.
Date of Electronic Publication: 2022 Jun 17.

Background: Despite a recommended multidimensional approach for pulmonary hypertension (PH) risk stratification and guidance of treatment decisions, this may not always be achievable in patients with advanced disease. One issue is the lack of an imaging modality to assess right ventricular (RV) structure and function abnormalities.
Purpose: To explore the risk stratification and prognostic value of cardiac MR feature tracking (MR-FT)-derived RV strain.
Study Type: Retrospective.
Population: A total of 80 patients with idiopathic pulmonary artery hypertension (N = 52) or chronic thromboembolic PH (N = 28).
Field Strength: A 1.5 T or 3.0 T, balanced steady-state free precession sequence.
Assessment: All patients underwent laboratory testing, right heart catheterization, and MR imaging (and in 37 cases, a cardiopulmonary exercise test was also performed) within a 1-month period. Cardiac functional parameters and both global longitudinal strain (GLS) and global circumferential strain (GCS) were analyzed. Patients were stratified into low, intermediate, and high-risk groups by guideline suggested stratified values of risk factors. The combined endpoint was death or hospitalization for congestive heart failure assessed during follow-up since the date of MR examination.
Statistical Tests: Kolmogorov-Smirnov’s test, independent-sample t-tests, Wilcoxon’s rank-sum tests, one-way analysis of variance, χ ² tests or Fisher’s exact test, receiver operating characteristic analysis, Kaplan-Meier survival analysis, and Cox regression analysis. A P value < 0.05 was considered statistically significant.
Results: The median follow-up duration was 3.4 years. Thirty-five patients presented with combined endpoint including 10 cardiac deaths. RV structural and deformation impairments were significantly associated with combined endpoint (ejection fraction: 31.3% ± 13.2% vs. 38.0% ± 14.8%, hazard ratio [HR: 0.974; GLS: -14.5 [-18.6, -10.9] % vs. -20.4 [-26.0, -13.2] %, HR: 1.071; GCS: -9.8 [-14.5, -7.3] % vs. -12.3 [-19.9, -8.4] %, HR: 1.059). There were significant differences in RVGLS among low, intermediate, and high-risk groups (-19.3% ± 7.2% vs. -17.3% ± 9.4% vs. -11.5% ± 4.4% by cardiac functional class, -21.8% ± 7.3% vs. -19.4% ± 8.2% vs. -12.7 ± 5.3% by NT-proBNP, -19.7% ± 7.7 vs. -15.8% ± 6.5% vs. -12.6% ± 8.2% by cardiac index).
Data Conclusion: RV deformation may aid risk stratification in patients with PH, providing crucial information for RV remodeling, pulmonary hemodynamic condition and exercise capacity.

Parizher G; Emery MS;

Clinics in sports medicine [Clin Sports Med] 2022 Jul; Vol. 41 (3), pp. 441-454.

Exercise stress testing (EST) is indicated for diagnostic and prognostic purposes in the general population. In athletes, stress tests can also be useful to inform the risk of high-intensity training and competition, to assess athletic conditioning, and to refine training regimens. Many specific indications for EST are unique to athletes. Treadmill and cycle ergometer protocols each have their strengths and disadvantages; extensive protocol customization may be necessary to answer the clinical question at hand. A comprehensive understanding of the available tools for exercise testing, their strengths, and their limitations is crucial to providing cardiovascular care to athletic individuals.

Huang L; Zhou J; Li H; Wang Y; Wu X; Wu J;

BMJ open [BMJ Open] 2022 Jun 13; Vol. 12 (6), pp. e057117.
Date of Electronic Publication: 2022 Jun 13.

Introduction: Most patients with coronary heart disease experience sleep disturbances and low cardiorespiratory fitness (CRF), but their relationship during cardiac rehabilitation (CR) is still unclear. This article details a protocol for the study of sleep trajectory in patients with coronary heart disease during CR and the relationship between sleep and CRF. A better understanding of the relationship between sleep and CRF on patient outcomes can improve sleep management strategies.
Methods and Analysis: This is a longitudinal study with a recruitment target of 101 patients after percutaneous cardiac intervention from the Seventh People’s Hospital of Shanghai, China. Data collection will include demographic characteristics, medical history, physical examination, blood sampling, echocardiography and the results of cardiopulmonary exercise tests. The information provided by a 6-min walk test will be used to supplement the CPET. The Pittsburgh Sleep Quality Index will be used to understand the sleep conditions of the participants in the past month. The Patient Health Questionnaire and General Anxiety Disorder Scale will be used to assess depression and anxiety, respectively. All participants will be required to wear an actigraphy on their wrists for 72 hours to monitor objective sleep conditions. This information will be collected four times within 6 months of CR, and patients will be followed up for 1 year. The growth mixture model will be used to analyse the longitudinal sleep data. The generalised estimating equation will be used to examine the associations between sleep and CRF during CR.

Van Tassell B; Mihalick V; Thomas G; Marawan A; Talasaz AH;Lu J; Kang L; Ladd A; Damonte JI; Dixon DL; Markley R; Turlington J; Federmann E; Del Buono MG; Biondi-Zoccai G; Canada JM; Arena R; Abbate A;

Journal of translational medicine [J Transl Med] 2022 Jun 15; Vol. 20 (1), pp. 270.
Date of Electronic Publication: 2022 Jun 15.

Background: Heart failure (HF) is a global leading cause of mortality despite implementation of guideline directed therapy which warrants a need for novel treatment strategies. Proof-of-concept clinical trials of anakinra, a recombinant human Interleukin-1 (IL-1) receptor antagonist, have shown promising results in patients with HF.
Method: We designed a single center, randomized, placebo controlled, double-blind phase II randomized clinical trial. One hundred and two adult patients hospitalized within 2 weeks of discharge due to acute decompensated HF with reduced ejection fraction (HFrEF) and systemic inflammation (high sensitivity of C-reactive protein > 2 mg/L) will be randomized in 2:1 ratio to receive anakinra or placebo for 24 weeks. The primary objective is to determine the effect of anakinra on peak oxygen consumption (VO ₂ ) measured at cardiopulmonary exercise testing (CPX) after 24 weeks of treatment, with placebo-corrected changes in peak VO ₂ at CPX after 24 weeks (or longest available follow up). Secondary exploratory endpoints will assess the effects of anakinra on additional CPX parameters, structural and functional echocardiographic data, noninvasive hemodynamic, quality of life questionnaires, biomarkers, and HF outcomes.
Discussion: The current trial will assess the effects of IL-1 blockade with anakinra for 24 weeks on cardiorespiratory fitness in patients with recent hospitalization due to acute decompensated HFrEF.
Trial Registration: The trial was registered prospectively with ClinicalTrials.gov on Jan 8, 2019, identifier NCT03797001.