Palau P; Domínguez E; Seller J; Sastre C; Sanchis J; Bodí V; Llàcer P; Miñana G; Espriella R; Bayés-Genís A; Núñez J;

Revista espanola de cardiologia (English ed.) [Rev Esp Cardiol (Engl Ed)] 2022 Aug 26.
Date of Electronic Publication: 2022 Aug 26.

Introduction and Objectives: Little is known about the usefulness of heart rate (HR) response to exercise for risk stratification in heart failure with preserved ejection fraction (HFpEF). Therefore, this study aimed to assess the association between HR response to exercise and the risk of total episodes of worsening heart failure (WHF) in symptomatic stable patients with HFpEF.
Methods: This single-center study included 133 patients with HFpEF (NYHA II-III) who performed maximal cardiopulmonary exercise testing. HR response to exercise was evaluated using the chronotropic index (CI _x ) formula. A negative binomial regression method was used.
Results: The mean age of the sample was 73.2 ± 10.5 years; 56.4% were female, and 51.1% were in atrial fibrillation. The median for CI _x was 0.4 [0.3-0.55]. At a median follow-up of 2.4 [1.6-5.3] years, a total of 146 WHF events in 58 patients and 41 (30.8%) deaths were registered. In the whole sample, CI _x was not associated with adverse outcomes (death, P = .319, and WHF events, P = .573). However, we found a differential effect across electrocardiographic rhythms for WHF events (P for interaction = .002). CI _x was inversely and linearly associated with the risk of WHF events in patients with sinus rhythm and was positively and linearly associated with those with atrial fibrillation.
Conclusions: In patients with HFpEF, CI _x was differentially associated with the risk of total WHF events across rhythm status. Lower CI _x emerged as a risk factor for predicting higher risk in patients with sinus rhythm. In contrast, higher CI _x identified a higher risk in those with atrial fibrillation.

Mart MF; Ely EW; Tolle JJ; Patel MB; Brummel NE;

Intensive care medicine experimental [Intensive Care Med Exp] 2022 Aug 26; Vol. 10 (1), pp. 35.
Date of Electronic Publication: 2022 Aug 26.

Background: ICU survivors suffer from impaired physical function and reduced exercise capacity, yet the underlying mechanisms are poorly understood. The goal of this exploratory pilot study was to investigate potential mechanisms of exercise limitation using cardiopulmonary exercise testing (CPET) and 6-min walk testing (6MWT).
Methods: We enrolled adults aged 18 years or older who were treated for respiratory failure or shock in medical, surgical, or trauma ICUs at Vanderbilt University Medical Center (Nashville, TN, United States). We excluded patients with pre-existing cardiac dysfunction, a contraindication to CPET, or the need for supplemental oxygen at rest. We performed CPET and 6MWT 6 months after ICU discharge. We measured standard CPET parameters in addition to two measures of oxygen utilization during exercise (VO ₂ -work rate slope and VO ₂ recovery half-time).
Results: We recruited 14 participants. Low exercise capacity (i.e., VO _2Peak  < 80% predicted) was present in 11 out of 14 (79%) with a median VO _2Peak of 12.6 ml/kg/min [9.6-15.1] and 6MWT distance of 294 m [240-433]. In addition to low VO _2Peak , CPET findings in survivors included low oxygen uptake efficiency slope, low oxygen pulse, elevated chronotropic index, low VO ₂ -work rate slope, and prolonged VO ₂ recovery half-time, indicating impaired oxygen utilization with a hyperdynamic heart rate and ventilatory response, a pattern seen in non-critically ill patients with mitochondrial myopathies. Worse VO ₂ -work rate slope and VO ₂ recovery half-time were strongly correlated with worse VO _2Peak and 6MWT distance, suggesting that exercise capacity was potentially limited by impaired muscle oxygen utilization.
Conclusions: These exploratory data suggest ICU survivors may suffer from impaired muscular oxygen metabolism due to mitochondrial dysfunction that impairs exercise capacity long-term. These findings should be further characterized in future studies that include direct assessments of muscle mitochondrial function in ICU survivors.

Qasim A; Doan TT; Dan Pham T; Reaves-O’Neal D; Sachdeva S; Mery CM; Binsalamah Z; Molossi S

Seminars in thoracic and cardiovascular surgery [Semin Thorac Cardiovasc Surg] 2022 Aug 27.
Date of Electronic Publication: 2022 Aug 27.

Data on maximal exercise-stress-testing (m-EST) in anomalous-aortic-origin-of-coronary-arteries (AAOCA) is limited and correlation with stress perfusion imaging has not been demonstrated. AAOCA patients ≤20 years were prospectively enrolled from 6/2014-01/2020. A m-EST was defined as heart rate >85%ile on ECG-EST and respiratory-exchange-ratio (RER) ≥1.05 on cardiopulmonary-exercise-testing (CPET). Abnormal m-EST included significant ST-changes or high-grade arrhythmia, ໿V̇O _2max and/or O ₂ pulse <85% predicted, or abnormal O ₂ pulse curve. A (+) dobutamine-stress cardiac-magnetic-resonance-imaging (+DS-CMR) had findings of inducible-ischemia. Outcomes: 1) Differences in m-EST based on AAOCA-type; 2) Assuming DS-CMR as gold-standard for detection of inducible ischemia, determine agreement between m-EST and DS-CMR. A total of 155 AAOCA (right, AAORCA = 126; left, AAOLCA = 29) patients with a median (IQR) age of 13 (11 – 15) years were included; 63% were males and a m-EST was completed in 138 (89%). AAORCA and AAOLCA had similar demographic and m-EST characteristics, although AAOLCA had more frequently evidence of inducible ischemia on m-EST (p=0.006) and DS-CMR (p=0.007). Abnormal O ₂ pulse was significantly associated with +DS-CMR (OR 5.3, 95% CI 1.6 -18, p=0.005). Sensitivity was increased with addition of CPET to ECG-EST (to 58% from 19%). There was no agreement between m-EST and DS-CMR for detection of inducible ischemia. A m-EST has very low sensitivity for detection of inducible ischemia in AAOCA, and sensitivity is increased with addition of CPET. Stress perfusion abnormalities on DS-CMR were not concordant with m-EST findings and adjunctive testing should be considered for clinical decision making in AAOCA.

Peterman JE; Arena R; Myers J;Harber MP;Squires RW; Kaminsky LA;

Medicine and science in sports and exercise [Med Sci Sports Exerc] 2022 Aug 12.
Date of Electronic Publication: 2022 Aug 12.

Introduction: Peak rating of perceived exertion (RPE) is measured during clinical cardiopulmonary exercise testing (CPX) and is commonly used as a subjective indicator of maximal effort. However, no study to date has reported reference standards or the distribution of peak RPE across a large cohort of apparently healthy individuals.
Purpose: To determine reference standards for peak RPE when using the 6 – 20 Borg scale for both treadmill and cycle tests.
Methods: The analysis included 9,551 tests (8,821 treadmill, 730 cycle ergometer) from 13 laboratories within the Fitness Registry and Importance of Exercise National Database (FRIEND). Using data from tests conducted January 1, 1980, through January 1, 2021, percentiles of peak RPE for males and females were determined for each decade from 20 through 89 years of age for treadmill and cycle exercise modes. Two-way analysis of variance was used to compare differences in peak RPE values between sexes and across age groups.
Results: There were statistically significant differences in RPE between age groups whether the test was performed on a treadmill or cycle ergometer (P < 0.05). However, the mean and median RPE for each sex, age group, and test mode was between 18 and 19. Additionally, 83% of participants met the traditional RPE criteria of ≥18 for indicating sufficient maximal effort.
Conclusions: This report provides the first normative reference standards for peak RPE in both males and females performing CPX on a treadmill or cycle ergometer. Further, these reference standards highlight the general consistency of peak RPE responses during CPX.

Longobardi I; Prado DMLD; Goessler KF; Meletti MM; de Oliveira Júnior GN; de Andrade DCO; Gualano B; Roschel H;

American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2022 Aug 19. Date of Electronic Publication: 2022 Aug 19.

The post-acute phase of COVID-19 is often marked by several persistent symptoms and exertional intolerance, which compromise survivors’ exercise capacity. This was a cross-sectional study aiming to investigate the impact of COVID-19 on oxygen uptake (VO ₂ ) kinetics and cardiopulmonary function in survivors of severe COVID-19 three to six months after intensive care unit (ICU) hospitalization. Thirty-five COVID-19 survivors previously admitted to ICU (5±1 months after hospital discharge) and 18 controls matched for sex, age, comorbidities, and physical activity level with no prior history of SARS-CoV-2 infection were recruited. Subjects were submitted to a maximal graded cardiopulmonary exercise test (CPX) with an initial 3-minute period of a constant, moderate-intensity walk (i.e., below ventilatory threshold, VT). VO ₂ kinetics was remarkably impaired in COVID-19 survivors as evidenced at the on-transient by an 85% (P=0.008) and 28% (P=0.001) greater oxygen deficit and mean response time (MRT), respectively. Furthermore, COVID-19 survivors showed a 11% longer (P=0.046) half-time of recovery of VO ₂ (T _1/2 VO ₂ ) at the off-transient. CPX also revealed cardiopulmonary impairments following COVID-19. VO _2peak , percent-predicted VO _2peak and VO _2VT were reduced by 17%, 17% and 12% in COVID-19 survivors, respectively (all P<0.05). None of the ventilatory parameters differed between groups (all P>0.05). Additionally, COVID-19 survivors also presented with blunted chronotropic responses (i.e., chronotropic index, maximum heart rate, and heart rate recovery; all P<0.05). These findings suggest that COVID-19 negatively affects central (chronotropic) and peripheral (metabolic) factors that impair the rate at which VO ₂ is adjusted to changes in energy demands.

Waterland JL; Ismail H; Granger CL; Patrick C; Denehy L; Riedel B;

Perioperative medicine (London, England) [Perioper Med (Lond)] 2022 Aug 23; Vol. 11 (1), pp. 32.
Date of Electronic Publication: 2022 Aug 23.

Background: Patients presenting for major surgery with low cardiorespiratory fitness (deconditioning) and other modifiable risk factors are at increased risk of postoperative complications. This study investigated the feasibility of delivering prehabilitation in high-risk patients scheduled for major abdominal cancer surgery.
Methods: Eligible patients in this single-center cohort study included patients with poor fitness (objectively assessed by cardiopulmonary exercise testing, CPET) scheduled for elective major abdominal cancer surgery. Patients were recruited to participate in a prehabilitation program that spanned up to 6 weeks pre-operatively and comprised aerobic and resistance exercise training, breathing exercise, and nutritional support. The primary outcome assessed pre-specified feasibility targets: recruitment >70%, retention >85%, and intervention adherence >70%. Secondary outcomes were assessed for improved pre-operative functional status and health-related quality of life and for postoperative complications.
Results: Eighty-two (34%) out of 238 patients screened between April 2018 and December 2019 were eligible for recruitment. Fifty (61%) patients (52% males) with a median age of 71 (IQR, 63-77) years participated in the study. Baseline oxygen consumption the at anaerobic threshold and at peak exercise (mean±SD: 9.8±1.8 and 14.0±2.9 mL/kg/min, respectively) confirmed the deconditioned state of the study cohort. The retention rate within the prehabilitation program was 84%, with 42 participants returning for repeat CPET testing. While >60% of participants preferred to do home-based prehabilitation, adherence to the intervention was low-with only 12 (28%) and 15 (35%) of patients having self-reported compliance >70% with their exercise prescriptions.
Conclusion: Our prehabilitation program in high-risk cancer surgery patients did not achieve pre-specified targets for recruitment, retention, and self-reported program adherence. These findings underpin the importance of implementation research and strategies for the prehabilitation programs in major surgery.

Blumberg Y; Edelstein M; Abu Jabal K; Golan R; Tuvia N; Perets Y; Saad M; Levinas T; Saleem DIsraeli Z; Alaa AR; Elbaz Greener G; Amital A; Halabi M;

Journal of clinical medicine [J Clin Med] 2022 Jul 29; Vol. 11 (15).
Date of Electronic Publication: 2022 Jul 29.

Patients previously infected with acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may experience post-acute adverse health outcomes, known as long COVID. The most reported symptoms are fatigue, headache and attention/concentration issues, dyspnea and myalgia. In addition, reduced aerobic capacity has been demonstrated in both mild and moderate COVID-19 patients. It is unknown whether COVID-19 vaccination mitigates against reduced aerobic capacity. Our aim was to compare the aerobic capacity of vaccinated and unvaccinated individuals previously infected with SARS-CoV-2.
Methods: Individuals aged 18 to 65 years with laboratory-confirmed mild to moderate COVID-19 disease were invited to Ziv Medical Centre, Israel, three months after SARS-CoV-2 infection. We compared individuals unvaccinated at the time of infection to those vaccinated in terms of aerobic capacity, measured using symptom-limited cardiopulmonary exercise test (CPET).
Results: We recruited 28 unvaccinated and 22 vaccinated patients. There were no differences in baseline demographic and pulmonary function testing (PFT) parameters. Compared with unvaccinated individuals, those vaccinated had higher V’O ₂ /kg at peak exercise and at the anaerobic threshold. The V’O ₂ /kg peak in the unvaccinated group was 83% of predicted vs. 100% in the vaccinated ( p &lt; 0.002). At the anaerobic threshold (AT), vaccinated individuals had a higher V’O ₂ /kg than those unvaccinated.
Conclusions: Vaccinated individuals had significantly better exercise performance. Compared with vaccinated individuals, a higher proportion of those unvaccinated performed substantially worse than expected on CPET. These results suggest that vaccination at the time of infection is associated with better aerobic capacity following SARS-CoV-2 infection.

Phillips DB; James MD;O’Donnell CJD; Vincent SG; Webb KA; de-Torres JP; Neder JA; O’Donnell DE;

Journal of applied physiology (Bethesda, Md. : 1985) [J Appl Physiol (1985)] 2022 Aug 11.
Date of Electronic Publication: 2022 Aug 11.

Low resting inspiratory capacity (IC) and low maximal inspiratory pressure (MIP) have previously been linked to exertional dyspnea, exercise limitation and poor survival in chronic obstructive pulmonary disease (COPD). The interaction and relative contributions of these two related variables to important clinical outcomes are unknown. The objective of the current study was to examine the interaction between resting IC and MIP (both % predicted), exertional dyspnea, exercise capacity and long-term survival in patients with COPD. Two hundred and eighty-five patients with mild to advanced COPD completed standard lung function testing and a cycle cardiopulmonary exercise test. Multiple regression determined predictors of the exertional dyspnea-ventilation slope and peak oxygen uptake (V̇O _2peak ). Cox regression determined predictors of 10-year mortality. IC was associated with the dyspnea-ventilation slope (standardized β=-0.44, p<0.001), while MIP was excluded from the regression model (p=0.713). IC and MIP were included in the final model to predict V̇O _2peak . However, the standardized β was greater for IC (0.49) than MIP (0.22). After adjusting for age, sex, body mass index, cardiovascular risk, airflow obstruction and diffusing capacity, resting IC was independently associated with 10-year all-cause mortality (hazard ratio=1.25, confidence interval _5-95% =1.16-1.34, p<0.001), while MIP was excluded from the final model (all p=0.829). Low resting IC was consistently linked to heightened dyspnea intensity, low V̇O _2peak and worse survival in COPD even after accounting for airway obstruction, inspiratory muscle strength, and diffusing capacity. These results support the use of resting IC as an important physiological biomarker closely linked to key clinical outcomes in COPD.

Mazur A; Brat K; Homolka P; Merta Z; Svoboda M; Bratova M; Sramek V; Republic.; Olson LJ; Cundrle I;

PloS one [PLoS One] 2022 Aug 12; Vol. 17 (8), pp. e0272984.
Date of Electronic Publication: 2022 Aug 12 (Print Publication: 2022).

Introduction: Ventilatory efficiency (VE/VCO2 slope) has been shown superior to peak oxygen consumption (VO2) for prediction of post-operative pulmonary complications in patients undergoing thoracotomy. VE/VCO2 slope is determined by ventilatory drive and ventilation/perfusion mismatch whereas VO2 is related to cardiac output and arteriovenous oxygen difference. We hypothesized pre-operative VO2 predicts post-operative cardiovascular complications in patients undergoing lung resection.
Methods: Lung resection candidates from a published study were evaluated by post-hoc analysis. All of the patients underwent preoperative cardiopulmonary exercise testing. Post-operative cardiovascular complications were assessed during the first 30 post-operative days or hospital stay. One-way analysis of variance or the Kruskal-Wallis test, and multivariate logistic regression were used for statistical analysis and data summarized as median (IQR).
Results: Of 353 subjects, 30 (9%) developed pulmonary complications only (excluded from further analysis), while 78 subjects (22%) developed cardiovascular complications and were divided into two groups for analysis: cardiovascular only (n = 49) and cardiovascular with pulmonary complications (n = 29). Compared to patients without complications (n = 245), peak VO2 was significantly lower in the cardiovascular with pulmonary complications group [19.9 ml/kg/min (16.5-25) vs. 16.3 ml/kg/min (15-20.3); P<0.01] but not in the cardiovascular only complications group [19.9 ml/kg/min (16.5-25) vs 19.0 ml/kg/min (16-23.1); P = 0.18]. In contrast, VE/VCO2 slope was significantly higher in both cardiovascular only [29 (25-33) vs. 31 (27-37); P = 0.05] and cardiovascular with pulmonary complication groups [29 (25-33) vs. 37 (34-42); P<0.01)]. Logistic regression analysis showed VE/VCO2 slope [OR = 1.06; 95%CI (1.01-1.11); P = 0.01; AUC = 0.74], but not peak VO2 to be independently associated with post-operative cardiovascular complications.
Conclusion: VE/VCO2 slope is superior to peak VO2 for prediction of post-operative cardiovascular complications in lung resection candidates.

Nir V; Bentur L; Zucker-Toledano M; Gur M; Adler Z; Hanna M; Toukan Y; Masarweh K; Hakim F; Bar-Yoseph R

Pediatric pulmonology [Pediatr Pulmonol] 2022 Aug 15.
Date of Electronic Publication: 2022 Aug 15.

Background: Vascular rings are congenital anomalies of the aortic arch that compress the trachea and esophagus and may require corrective surgery. Data about the long-term effects of vascular rings are scarce. We aimed to evaluate the long-term cardiorespiratory, exercise capacity and quality of life of vascular ring patients.
Methods: A single center prospective study evaluating spirometry, echocardiography, six-minute walk test (6MWT), cardiopulmonary exercise testing (CPET) and quality of life questionnaire (SF36) in patients with a diagnosis of vascular ring, with or without corrective surgery.
Results: Twenty-seven patients participated (11.9±6 years, 52% males). The most common diagnosis was double aortic arch (16 patients, 59%). Nineteen patients had corrective surgery (O) and eight did not (NO). Pulmonary function tests were within normal range in both groups (FEV ₁ % predicted O=87.6±16.5, NO=83±10.8%). However, 11/27 had abnormal FEV ₁ , five had abnormal FVC and 13 (48%) had flattening of the expiratory curve. 6MWD and oxygen uptake were similarly mildly reduced in both groups; (6MWD O=80.1±10.7% predicted, NO=74.1±10.9% and oxygen uptake O=78.5±23.2% predicted, NO=73.4±14.3%). Peak O ₂ pulse (V̇O ₂ /HR% predicted) was mildly reduced in the NO group (O=88.4±17.3%, NO=75.8±16.2%). Echocardiogram and SF36 scores were normal in all patients.
Conclusions: Long-term evaluation of patients born with vascular rings revealed mild pulmonary impairment, reduction in 6MWD and oxygen uptake. The NO group had also mild reduced peak O ₂ pulse. Larger, long-term studies assessing functional parameters in operated and non-operated patients are needed to assess disease/surgery limitation in patients with vascular rings.