Author Archives: Paul Older

Oxygen uptake kinetics and chronotropic responses to exercise are impaired in survivors of severe COVID-19.

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.

Prehabilitation in high-risk patients scheduled for major abdominal cancer surgery: a feasibility study.

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.

Protective Effects of BNT162b2 Vaccination on Aerobic Capacity Following Mild to Moderate SARS-CoV-2 Infection: A Cross-Sectional Study Israel.

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.

Physiological Predictors of Morbidity and Mortality in COPD: The Relative Importance of Reduced Inspiratory Capacity and Inspiratory Muscle Strength.

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.

Ventilatory efficiency is superior to peak oxygen uptake for prediction of lung resection cardiovascular complications.

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.

Functional Capacity and Quality of Life in Patients With Vascular Ring.

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.

Exercise Intolerance in Post-Acute Sequelae of COVID-19 and the Value of Cardiopulmonary Exercise Testing- a Mini-Review.

Aparisi Á; Ladrón R;Ybarra-Falcón C; Tobar J; San Román JA;

Frontiers in medicine [Front Med (Lausanne)] 2022 Jul 22; Vol. 9, pp. 924819.
Date of Electronic Publication: 2022 Jul 22 (Print Publication: 2022).

Coronavirus disease (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with systemic organ damage in the most severe forms. Long-term complications of SARS-CoV-2 appear to be restricted to severe presentations of COVID-19, but many patients with persistent symptoms have never been hospitalized. Post-acute sequelae of COVID-19 (PASC) represents a heterogeneous group of symptoms characterized by cardiovascular, general, respiratory, and neuropsychiatric sequelae. The pace of evidence acquisition with PASC has been rapid, but the mechanisms behind it are complex and not yet fully understood. In particular, exercise intolerance shares some features with other classic respiratory and cardiac disorders. However, cardiopulmonary exercise testing (CPET) provides a comprehensive assessment and can unmask the pathophysiological mechanism behind exercise intolerance in gray-zone PASC. This mini-review explores the utility of CPET and aims to provide a comprehensive assessment of PASC by summarizing the current evidence.

Percentage of Age-Predicted Cardiorespiratory Fitness May Be a Stronger Risk Indicator for Incident Type 2 Diabetes Than Absolute Levels of Cardiorespiratory Fitness.

Kunutsor SK; Khan H; Seidu S; Laukkanen JA

Journal of cardiopulmonary rehabilitation and prevention [J Cardiopulm Rehabil Prev] 2022 Aug 04.
Date of Electronic Publication: 2022 Aug 04.

Purpose: There are inverse and independent associations between cardiorespiratory fitness (CRF) and several adverse cardiometabolic outcomes. The percentage of age-predicted CRF (%age-predicted CRF) is comparable to absolute CRF as a risk indicator for some of these outcomes, but the association between %age-predicted CRF and risk of type 2 diabetes (T2D) has not been previously investigated. We aimed to assess the association between %age-predicted CRF and T2D in a prospective cohort study.
Methods: Cardiorespiratory fitness, as measured directly by peak oxygen uptake, was assessed in 1901 men aged 42-60 yr who underwent cardiopulmonary exercise testing. The age-predicted CRF estimated from a regression equation for age was converted to %age-predicted CRF using (achieved CRF/age-predicted CRF) × 100. Hazard ratios (95% CI) were estimated for T2D.
Results: During a median follow-up of 26.8 yr, 227 T2D cases were recorded. The risk of T2D decreased continuously with increasing %age-predicted CRF (P value for nonlinearity = .30). A 1-SD increase in %age-predicted CRF was associated with a decreased risk of T2D in analysis adjusted for established risk factors (HR = 0.68: 95% CI, 0.59-0.79). The corresponding adjusted risk was (HR = 0.51: 95% CI, 0.35-0.75) comparing extreme tertiles of %age-predicted CRF. The respective estimates for the association between absolute CRF and T2D were-HR (95% CI)-0.71 (0.60-0.83) and 0.64 (0.44-0.95).
Conclusions: Percentage of age-predicted CRF is linearly, inversely, and independently associated with the risk of incident T2D and may be a stronger risk indicator for T2D compared to absolute CRF in a general population of middle-aged and older men.