Kimmig LM; Rako ZA; Ziegler S; Richter MJ; G S AT; Roller F; Grimminger F; Vadász I; Seeger W; Herold S; Tello K; Matt U;

Respiratory research [Respir Res] 2022 Sep 21; Vol. 23 (1), pp. 263.
Date of Electronic Publication: 2022 Sep 21.

Background: Persistent symptoms after initial COVID-19 infection are common and are frequently referred to by the umbrella terms “post-COVID syndrome” and “long COVID”. The sheer number of affected patients pose an increasing challenge to healthcare systems worldwide. To date, our understanding of the pathophysiology of the post-COVID syndrome remains poor and the extent to which persistent cardiopulmonary abnormalities contribute to the symptom complex is unclear. We sought to determine the presence and impact of cardiopulmonary sequelae after COVID-19 in longitudinal assessment.
Methods: We report on 71 patients who underwent comprehensive, longitudinal testing in regular intervals for up to 12 months after their initial COVID-19 diagnosis. Testing included pulmonary function testing, cardiopulmonary exercise testing, dedicated left and right heart echocardiography, lung ultrasonography, and cardiac MRI.
Results: Our results demonstrate that subjective quality of life after COVID-19 (EQ-5D visual acuity scale, VAS, 67.4 for patients treated as outpatient, 79.2 for patients admitted to the general floor, 71.8 for patients treated in an ICU) is not related to the severity of the initial infection. Maximal exercise capacity is also reduced (VO ₂ max 79% predicted, SD ± 19%); however, this is driven in large parts by patients who had initially required ICU-level of care. The degree of objective reduction in exertion did not correlate with quality of life scores. Pulmonary function testing revealed mild and persistent reduction in D _LCO over the first 12 months without significant restrictive or obstructive lung disease. Left and right heart function was intact with good RV function and intact RV/PA coupling, imaging findings suggestive of myocarditis were uncommon (7% of patients).
Conclusion: A reduction in exercise capacity after COVID-19 is common, but is most prominent in patients previously treated in the ICU and more likely related to deconditioning or fatigue than to cardiopulmonary impairment. Subjective quality of life scores are independent of the severity of initial infection and do not correlate with objective measures of cardiopulmonary function. In our cohort, persistent cardiopulmonary impairment after COVID-19 was uncommon. The post-COVID syndrome is unlikely to be the result of cardiopulmonary sequalae and may reflect a post-ICU syndrome in some.

James MD; Phillips DB; Vincent SG; Abdallah SJ; Donovan AA; de-Torres JP;
Neder JA; Smith BM; Jensen D; O’Donnell DE;

Journal of Physiology. 600(18):4227-4245, 2022 Sep.VI 1

In patients with chronic obstructive pulmonary disease (COPD), exertional
dyspnoea generally arises when there is imbalance between ventilatory
demand and capacity, but the neurophysiological mechanisms are unclear. We
therefore determined if disparity between elevated inspiratory neural
drive (IND) and tidal volume (VT ) responses (neuromechanical
dissociation) impacted dyspnoea intensity and quality during exercise,
across the COPD severity spectrum. In this two-centre, cross-sectional
observational study, 89 participants with COPD divided into tertiles of
FEV1 %predicted (Tertile 1 = FEV1 = 87 +/- 9%, Tertile 2 = 60 +/- 9%,
Tertile 3 = 32 +/- 8%) and 18 non-smoking controls, completed a
symptom-limited cardiopulmonary exercise test (CPET) with measurement of
IND by diaphragm electromyography (EMGdi (%max)). The association between
increasing dyspnoea intensity and EMGdi (%max) during CPET was strong (r =
0.730, P < 0.001) and not different between the four groups who showed
marked heterogeneity in pulmonary gas exchange and mechanical
abnormalities. Significant inspiratory constraints (tidal
volume/inspiratory capacity (VT /IC) >= 70%) and onset of neuromechanical
dissociation (EMGdi (%max):VT /IC > 0.75) occurred at progressively lower
minute ventilation ( V E ${\dot{V}}_{{\rm{E}}}$ ) from Control to Tertile
3. Lower resting IC meant earlier onset of neuromechanical dissociation,
heightened dyspnoea intensity and greater propensity (93% in Tertile 3) to
select qualitative descriptors of ‘unsatisfied inspiration’. We concluded
that, regardless of marked variation in mechanical and pulmonary gas
exchange abnormalities in our study sample, exertional dyspnoea intensity
was linked to the magnitude of EMGdi (%max). Moreover, onset of critical
inspiratory constraints and attendant neuromechanical dissociation
amplified dyspnoea intensity at higher exercise intensities. Simple
measurements of IC and breathing pattern during CPET provide useful
insights into mechanisms of dyspnoea and exercise intolerance in
individuals with COPD.

KEY POINTS: Dyspnoea during exercise is a common
and troublesome symptom reported by patients with chronic obstructive
pulmonary disease (COPD) and is linked to an elevated inspiratory neural
drive (IND). The precise mechanisms of elevated IND and dyspnoea across
the continuum of airflow obstruction severity in COPD remains unclear. The
present study sought to determine the mechanisms of elevated IND (by
diaphragm EMG, EMGdi (%max)) and dyspnoea during cardiopulmonary exercise
testing (CPET) across the continuum of COPD severity. There was a strong
association between increasing dyspnoea intensity and EMGdi (%max) during
CPET across the COPD continuum despite significant heterogeneity in
underlying pulmonary gas exchange and respiratory mechanical impairments.
Critical inspiratory constraints occurred at progressively lower
ventilation during exercise with worsening severity of COPD. This was
associated with the progressively lower resting inspiratory capacity with
worsening disease severity. Earlier critical inspiratory constraint was
associated with earlier neuromechanical dissociation and greater
likelihood of reporting the sensation of ‘unsatisfied inspiration’.

Pellegrino A; Casatori L; Messineo A; Ghionzoli M;Facchini F; Modesti A; Modesti PA;

Journal of hypertension [J Hypertens] 2022 Jun 01; Vol. 40 (Suppl 1), pp. e294.

Objective: Exercise training increases muscle VO2 by increasing O2 transport and O2 uptake positively affecting cardiac output. In subjects with pectus excavatum cardiac output increase during exercise might be limited by the conformation of the chest. In this condition, the psychological impact of the deformity can further reduce the propensity to physical activity, leading to a sedentary lifestyle. Surgery is the preferred choice in severe cases. However, many patients with milder deformities can benefit from exercise-based treatment. The choice of the therapeutic strategy is fundamental, but the functional parameters on which to base this choice are not yet well defined. Therefore, we investigated the relationships between habitual physical activity and functional physiological parameters obtained from the cardiopulmonary exercise test (exercise performance and stroke volume at peak exercise) in pectus excavatum.
Design and Method: A cohort of adolescents (15 with pectus excavatum and 15 age- and sex-matched healthy controls) underwent Cardiopulmonary Exercise Test to estimate exercise performance (VO2 max) and stroke volume at peak exercise (VO2/HR, O2 pulse). Habitual weekly physical activity, estimated with International Physical Activity Questionnaire – Short Form (IPAQ-SF), was expressed as METs h-1·week-1. Determinants of exercise performance and stroke volume at peak exercise were investigated in the whole group with multivariable linear regression analysis adjusted for sex, body mass index, forced expiratory volume in the first second, and presence of pectus excavatum.
Results: When compared to healthy controls, subjects with pectus excavatum had lower VO2 max (37.2 ± 6.6 vs 45.4 ± 6.4 mL·kg-1·min-1, p < 0.05), and O2 pulse (12.1 ± 2.4 vs 16.2 ± 3.6 mL·min-1·bpm-1, p < 0.05). Importantly, physical activity level was a predictor of VO2 max (B = 0.085; 95% Cl 0.010 to 0.160) while it did not affect O2 pulse (B = 0.035; 95% Cl -0.004 to 0.074).
Conclusions: Training programs should be encouraged to increase cardiopulmonary performance in subjects with pectus excavatum. A marked reduction in O2 pulse at peak exercise might be considered as a criteria to address a subject towards surgery.

Kariori M; Fragoulis C;Chrysochoou C;Leontsinis I;Mantzouranis E;Iliakis P;Konstantinidis D;Konstantinou K;Andrikou I;Kalos T;Grigoriou K;Tsioufis K

Journal of hypertension [J Hypertens] 2022 Jun 01; Vol. 40 (Suppl 1), pp. e176.

Objective: There is little data concerning the impact of arterial hypertension (HTN) on the cardiopulmonary status and right ventricle (RV) function of patients with SARS-Cov-2 infection. The purpose of our study was to investigate whether HTN affects the functional status of hospitalized for SARS-Cov-2 patients, using cardiopulmonary test and echocardiographic parameters, 3 months after the first day of infection.
Design and Method: Subjects who were hospitalized and survived Covid-19 infection were divided into two groups according to history of HTN. All subjects underwent cardiorespiratory exercise using Bruce or modified Bruce protocol evaluating all parameters. Echocardiographic findings including right ventricle strain were analyzed using an offline program.
Results: A total population of 52 hospitalized Sars-Cov-2 patients with a mean age of 57 ± 11.5 years were evaluated 3 months after the symptoms onset. Males amounted to 51.9 %. History of coronary artery disease was recorded in 15.4% of them. In hypertensive subjects, age (63 ± 8 vs. 52 ± 11 years, p < 0.001), BMI (29.9 ± 4.6 vs. 27.1 ± 5.8 kg/m2, p:0.03) and BSA (2.1 ± 0.25 vs. 2 ± 0.9 m2, p:0.04) were significantly higher. When analyzing cardiopulmonary test parameters, only maximum systolic blood pressure ((SBP, mmHg), 190 ± 21 vs.171 ± 26, p: 0.02) at peak and during the 1st minute of recovery (180 ± 23 vs. 157 ± 27 mmHg, p: 0.005) were higher comparing to normotensive subjects. Furthermore, diameter of left atrium ((LA, mm), 42 ± 6 vs.38 ± 6 p: 0.009), left ventricle ejection fraction ((LVEF,%), 48 ± 11 vs. 57 ± 6, p:0.004) and the absolute mean value of right ventricle strain ((RVLS, %), 9.1 ± 4 vs. 12.7 ± 5.4, p:0.04) differed significantly between two groups. Using linear regression analysis adjusted for age, gender, HTN, coronary heart disease and LVEF, HTN.
Conclusions: Our study highlighted negative impact of HTN both in right and left ventricle functionality, implying HTN as a negative independent predictive factor for right ventricle strain in patients hospitalized for SARS-Cov-2.

Crisci G; De Luca M; D’Assante R; Ranieri B; D’Agostino A; IValente V; Giardino F;Capone V; Chianese S; Rega S; Cocchia R; Israr MZ; Debiek R; Heaney LM; Salzano A;

Journal of cardiovascular development and disease [J Cardiovasc Dev Dis] 2022 Jul 28; Vol. 9 (8).
Date of Electronic Publication: 2022 Jul 28.

Heart failure with preserved ejection fraction (HFpEF) represents the most common HF phenotype of patients aged &gt; 65 years, with an incidence and a prevalence that are constantly growing. The HFpEF cardinal symptom is exercise intolerance (EI), defined as the impaired ability to perform physical activity and to reach the predicted age-related level of exercise duration in the absence of symptoms-such as fatigue or dyspnea-and is associated with a poor quality of life, a higher number of hospitalizations, and poor outcomes. The evidence of the protective effect between exercise and adverse cardiovascular outcomes is numerous and long-established. Regular exercise is known to reduce cardiovascular events and overall mortality both in apparently healthy individuals and in patients with established cardiovascular disease, representing a cornerstone in the prevention and treatment of many cardio-metabolic conditions. Several studies have investigated the role of exercise in HFpEF patients. The present review aims to dwell upon the effects of exercise on HFpEF. For this purpose, the relevant data from a literature search (PubMed, EMBASE, and Medline) were reviewed. The analysis of these studies underlines the fact that exercise training programs improve the cardiorespiratory performance of HFpEF patients in terms of the increase in peak oxygen uptake, the 6 min walk test distance, and the ventilatory threshold; on the other hand, diastolic or systolic functions are generally unchanged or only partially modified by exercise, suggesting that multiple mechanisms contribute to the improvement of exercise tolerance in HFpEF patients. In conclusion, considering that exercise training programs are able to improve the cardiorespiratory performance of HFpEF patients, the prescription of exercise training programs should be encouraged in stable HFpEF patients, and further research is needed to better elucidate the pathophysiological mechanisms underpinning the beneficial effects described.

Gobbo S; Favro F; Bullo V; Cugusi L; Blasio AD; Bortoletto A; Bocalini DS; Gasperetti A;Ermolao A; Bergamin M;

Frontiers in physiology [Front Physiol] 2022 Aug 08; Vol. 13, pp. 967817.
Date of Electronic Publication: 2022 Aug 08 (Print Publication: 2022).

Background: Left ventricular assist devices (LVAD) are increasingly being used as a therapy for advanced heart failure, both as a bridge to heart transplant and, given the rapid advances in the LVAD’s functionality and safety, and constant lack in availability of donor organs, as long-term destination therapy. With the diffusion of such therapy, it is crucial to assess patients’ muscle strength, aerobic capacity and exercise tolerance, to improve their functional capacity.
Methods: 38 LVAD recipients (33 men and five women) were included. Exercise testing including a maximal cardiopulmonary exercise test (CPET), handgrip, isometric and isokinetic strength testing of knee and ankle flexion/extension, and Romberg balance test in three conditions (eyes open, eyes closed, double task). Given the small and heterogeneous final sample size, a mostly descriptive statistical approach was chosen.
Results: 12 participants were classified as “Obese” (BMI>29.9). The most common comorbidities were type II diabetes and chronic kidney disease. Only 12 participants were able to successfully complete all the assessments. CPET and isokinetic strength trials were the least tolerated tests, and the handgrip test the best tolerated. Mean VO ₂ peak was 12.38 ± 3.43 ml/kg/min, with 15 participants below 50% of predicted VO ₂ max, of which 6 below 30% VO ₂ max. Mean handgrip strength was 30.05 ± 10.61 Kg; 25 participants were below the 25° percentile of their population’s normative reference values for handgrip strength, 10 of which were below the 5° percentile. Issues with the management of the external pack of the LVAD and its influence on the test limited the validity of the balance tests data, therefore, no solid conclusions could be drawn from them. VO ₂ peak did not correlate with handgrip strength or with any of the lower limb strength measures.
Conclusion: LVAD recipients show greatly reduced functional capacity and tolerance to exercise and exercise testing, with low overall strength levels. As strength variables appear to be independent from VO ₂ peak, different lower limbs strength tests should be explored to find a tolerable alternative in this population, which is subjected to muscle wasting due to old age, reduced tissue perfusion, side effects from the pharmacological therapies, and prolonged periods of bedrest.

Yang TH; Chen PC; Lin YC; Lee YY; Tseng YH; Chang WH;Chang LS; Lin CH; Kuo HC;

International journal of environmental research and public health [Int J Environ Res Public Health] 2022 Aug 18; Vol. 19 (16).
Date of Electronic Publication: 2022 Aug 18.

Background: Sweating and increased skin temperature caused by exercise can reduce physical activity and the willingness to exercise in adolescents with atopic dermatitis. This study was conducted to investigate the exercise load capacity of adolescents with atopic dermatitis and analyzed their exercise behavior and motivation.
Methods: Adolescents with and without atopic dermatitis were assigned to the atopic dermatitis group and control group ( n = 27 each). Both groups completed a cardiopulmonary exercise test and questionnaires to assess their exercise capacity, weekly exercise volume, exercise motivation, and self-efficacy, respectively.
Results: The ratio of measured forced vital capacity to the predicted forced vital capacity and the peak oxygen consumption of the atopic dermatitis group were significantly lower than those of the control group. The Godin Leisure-Time Exercise Questionnaire scores of the atopic dermatitis group were significantly lower than those of the control group. As for the Behavioral Regulation in Exercise Questionnaire 2, the scores for the introjected and identified regulations of the atopic dermatitis group were significantly lower than those of the control group. Regarding the Multidimensional Self-Efficacy for Exercise Scale, the scheduling efficacy and total scores of the atopic dermatitis group were significantly lower than those of the control group.
Conclusions: Adolescents with atopic dermatitis had lower peak exercise capacity and lower weekly exercise volume. Furthermore, they lacked the negative feelings toward inactivity and the self-confidence to plan regular exercise independently. The results of this study suggest that adolescents with atopic dermatitis should be encouraged to engage in regular indoor exercise.

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.