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Abstract Background The effects of post‐coronavirus disease 2019 (COVID‐19) syndrome on the cardiorespiratory and muscular fitness in older people are of utmost relevance. This study aimed to evaluate the effects of a 12‐week telerehabilitation programme on cardiorespiratory and muscular fitness and body composition in older patients with post‐COVID‐19 syndrome. Methods One hundred twenty older patients with post‐COVID‐19 syndrome were randomly assigned to one of two groups: patients who carried out the telerehabilitation programme (n = 60; age: 65.0 ± 5.2; female: 14.2%) and a control group (n = 60; age: 64.3 ± 5.0; female: 24.5%). An incremental cardiopulmonary exercise testing, isokinetic strength test, and bioelectrical impedance analysis were performed to compare cardiorespiratory and muscle strength responses and body composition between telerehabilitation and control groups. Results A significant increase in the cardiopulmonary exercise testing duration was found in the telerehabilitation group compared to the control group (mean difference = 88.9 s, P = 0.001). Peak oxygen uptake increased in the telerehabilitation group (mean difference = 3.0 mL·kg−1·min−1, P

Abstract Background In patients with chronic obstructive pulmonary disease (COPD), the clinical use of the minute ventilation-carbon dioxide production ( $$\rm{\dot V}$$ E- $$\rm{\dot V}$$ CO2) slope has been reported as a measure of exercise efficiency, but the oxygen uptake efficiency slope (OUES), i.e., the slope of oxygen uptake ( $$\rm{\dot V}$$ O2) versus the logarithmically transformed $$\rm{\dot V}$$ E, has rarely been reported. Methods We hypothesized that the $$\rm{\dot V}$$ E- $$\rm{\dot V}$$ CO2 slope is more useful than OUES in clinical use for the pathophysiological evaluation of COPD. Then, we investigated the cardiopulmonary exercise testing parameters affecting each of these slopes in 122 patients with all Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD grades selected from our database. Results Compared with the GOLD I-II group (n = 51), peak $$\rm{\dot V}$$ O2 (p

Aim: Poor cardiorespiratory fitness has been suggested to increase the risk of chronic diseases in obesity. We investigated the ability of key variables from cardiopulmonary exercise testing (CPET) to predict all‐cause mortality in an obese cohort. Methods: The sample included 469 participants of both sexes (mean age 40 ± 13 years) who underwent a CPET for clinical reasons between 1 March 2009 and 1 December 2023. All‐cause mortality was the prognostic endpoint. A receiver operating characteristic analysis was performed to establish optimal cut‐points for CPET variables. Kaplan–Meier and Cox regression analyses were used to determine the association between CPET variables and all‐cause mortality. Results: There were 46 deaths during a mean follow‐up period of 69 ± 48 months, resulting in an annual mortality rate of 2%. Despite the sample being made up of mostly women (70%), there were more deaths in men (18 vs. 6%, p < 0.001).The optimal thresholds for discrimination of survival were as follows: (a) peak oxygen uptake (pVO2) ≤16 mL/kg/min; (b) minute ventilation/carbon dioxide production (VE/VCO2) slope ≥31; (c) ventilatory power ≤5.8 mmHg; and (d) circulatory power ≤2980 mmHg/mL O2/min. Kaplan–Meier survival plots revealed a significant positive association between lower pVO2, circulatory power and ventilatory power values and survival (log‐rank, p < 0.001) and higher mortality for men than women. Adjusted Cox regression models showed that a pVO2 ≤16 mL/kg/min had a 20‐fold higher risk of mortality when compared with >16 mL/kg/min. Conclusion: Given the strong association of VO2, ventilatory efficiency, circulatory and ventilatory power with all‐cause mortality, our findings support the notion that poorer cardiorespiratory fitness is associated with a poor prognosis in patients with obesity. [ABSTRACT FROM AUTHOR]

We sought the cardiopulmonary exercise testing (CPET) parameter that most accurately reflected therapeutic efficacy in patients with hypertrophic cardiomyopathy (HCM). Well-being questionnaire, N-terminal brain natriuretic peptide measurements, echocardiography, and CPET were performed in patients with symptomatic non-obstructive HCM during phase II, randomized, open-label multicentre study, before and after 16 weeks of traditional or sacubitril/valsartan treatment. Patients were followed 36 months after the initial CPET. Primary endpoints were changes in: 1) peak oxygen consumption (VO 2); 2) VO 2 at anaerobic threshold (AT); 3) oxygen pulse; 4) minute ventilation (VE)/carbon-dioxide (CO 2) production slope; 5) VE/VCO 2 at AT (VE/VCO 2 _AT); 6) VE/VCO 2 nadir; 7) VE/VCO 2 intercept; and 8) partial end-tidal pressure of carbon-dioxide (P ET CO 2) change during CPET. Of 115 screened patients, 61 (52 ± 14 years, 43 % women) were included. Within subject therapy effects were detected only by the VE/VCO 2 intercept and P ET CO 2 change, whereas the differences between medical regimens were detected by differences in VE/VCO 2 nadir and VE/VCO 2 _AT changes after the treatment. The best predictors of the change in well-being were left ventricular outflow tract maximal gradient and VE/VCO 2 intercept (B = 0.41,0.36; SE = 0.16,0.30; CI = 0.14–0.79, 0.15–1.14; p = 0.006,0.016, respectively). Adverse cardiac events were best predicted by the initial VE/VCO 2 nadir. Ventilatory efficiency parameters outperform peak VO 2 in gauging therapy effects in patients with HCM. [ABSTRACT FROM AUTHOR]

Background: In patients with chronic obstructive pulmonary disease (COPD), the clinical use of the minute ventilation-carbon dioxide production ( E- CO2) slope has been reported as a measure of exercise efficiency, but the oxygen uptake efficiency slope (OUES), i.e., the slope of oxygen uptake ( O2) versus the logarithmically transformed E, has rarely been reported. Methods: We hypothesized that the E- CO2 slope is more useful than OUES in clinical use for the pathophysiological evaluation of COPD. Then, we investigated the cardiopulmonary exercise testing parameters affecting each of these slopes in 122 patients with all Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD grades selected from our database. Results: Compared with the GOLD I-II group (n = 51), peak O2 (p < 0.0001), OUES (p = 0.0161), E at peak exercise (p < 0.0001), and percutaneous oxygen saturation (SpO2) at peak exercise (p = 0.0004) were significantly lower in the GOLD III-IV group (n = 71). The GOLD III-IV group was divided into two groups by the exertional decrease in SpO2 from rest to peak exercise: 3% or less (the non-desaturation group: n = 23), or greater than 3% (the desaturation group: n = 48). OUES correlated only weakly with peak O2, E at peak exercise, and the difference between inspired and expired mean O2 concentrations (ΔFO2) at peak exercise, i.e., an indicator of oxygen consumption ability throughout the body, in the GOLD III-IV group with exertional hypoxemia. In contrast, the E- CO2 slope was significantly correlated with ΔFO2 at peak exercise, regardless of the COPD grade and exertional desaturation. Across all COPD stages, there was no correlation between the E- CO2 slope and E at peak exercise, and stepwise analysis identified peak O2 (p = 0.0345) and ΔFO2 (p < 0.0001) as variables with a greater effect on the E- CO2 slope. Conclusions: The OUES may be less useful in advanced COPD with exertional hypoxemia. The E- CO2 slope, which is independent of E, focuses on oxygen consumption ability and exercise tolerance in COPD, regardless of the exertional hypoxemia level and COPD grade. Therefore, the E- CO2 slope might be useful in establishing or evaluating tailor-made therapies for individual patient's pathologies in COPD as an indicator focusing on oxygen consumption ability. [ABSTRACT FROM AUTHOR]

Background: Supramaximal constant work rate tests (CWR) elicit intense hyperventilation, thus potentially up-shifting ventilation (⩒E)-to-carbon dioxide (CO2) responses when compared to graded exercise tests (GXT) in athletes. We predicted higher ventilatory efficiency on supramaximal CWR using a new method, challenging the classic orthodox interpretation of an increased ⩒E-⩒CO2 as ventilatory inefficiency. This misinterpretation could make difficult to differentiate between physiological hyperventilation from heart disease conditions in athletes. Methods: On different days, a GXT and a CWR at 110% of the maximal velocity achieved in the GXT were performed. Twenty-seven athletes completed the two tests and were compared for usual (linear regression) and log-transformed new variables for ventilatory efficiency through paired t-Student statistics. Results: The ⩒E-⩒CO2 slope (31.4 ± 4.9 vs. 26.2 ± 3.4, p < .001), ⩒E-⩒CO2 intercept (7.2 ± 7.5 vs. 2.8 ± 4.2, p < .007), ⩒E/⩒CO2 nadir (33.0 ± 3.6 vs. 25.4 ± 2.2, p < .001), ⩒CO2-log⩒E slope (10.8 ± 2.9 vs. 6.9 ± 2.2 L*logL−1, p < .001), and η⩒E (36.0 ± 12 vs. 22.8 ± 8.1%, p < .001) values were all significantly higher in the CWR compared to the GXT. We registered a bi-modal nadir response for ⩒E/⩒CO2 on CWR for 22 out of 27 subjects for the first time. A weak association was observed between ⩒E/⩒CO2 nadir (coefficient of determination ~ 27%) and time to exhaustion. Conclusions: The new method allows us to improve the quantification and interpretation of ventilatory efficiency in athletes, avoiding misinterpretation due to the up-shifting elicited by the usual ⩒E-⩒CO2 slope and ⩒E/⩒CO2 nadir indices, which may be confounded with ventilatory inefficiency. This study suggests that ventilatory changes underpin better ventilatory efficiency during CWR. [ABSTRACT FROM AUTHOR]

Background: Given the high prevalence of stage A or B heart failure (HF), comprehensive screening for new-onset HF is cost-prohibitive. Therefore, further risk stratification is warranted to identify at-risk patients. This study aimed to evaluate the prognostic utility of cardiopulmonary exercise test (CPET) with bicycle stress echocardiography (BSE) in patients with stage A or B HF. Methods: Among 687 consecutive patients who underwent CPET-BSE, 410 with stage A or B HF were analyzed. The association between the CPET-BSE parameters and adverse cardiac events (hospitalization for HF or cardiac-related death) was analyzed using the Cox proportional hazard model under univariate and multivariate analyses. Results: After a median 9 years of follow-up, 47 (11.5 %) of the 410 patients had events. In the univariable analysis, age, diuretics, BUN, creatinine, peak oxygen uptake (VO2), ventilatory efficiency (VE/VCO2), time to VT and peak exercise, left atrial volume index, rest and exercise E/e′, and tricuspid regurgitation velocity demonstrated significant parameters. In multivariate analysis, VE/VCO2 (hazard ratio [HR] 1.205, 95 % CI 1.095–1.327) and VO2 at peak exercise (HR 1.164, 95 % CI 1.022–1.325), time to VT (HR 0.993, 95 % CI 0.989–0.997), and exercise E/e′ (HR 1.582, 95 % CI 1.199–2.087) were only independent predictors for events. Conclusions: In patients with stage A or B HF, four parameters of CPET-BSE were good predictors of future development of HF or cardiac death. If patients are unable to perform complete exercise, the time to VT may serve as a sufficiently predictive parameter for clinical events.

Major surgery is associated with high complication rates. Several risk scores exist to assess individual patient risk before surgery but have limited precision. Novel prognostic factors can be included as additional building blocks in existing prediction models. A candidate prognostic factor, measured by cardiopulmonary exercise testing, is ventilatory efficiency (VE/VCO 2). The aim of this systematic review was to summarise evidence regarding VE/VCO 2 as a prognostic factor for postoperative complications in patients undergoing major surgery. A medical library specialist developed the search strategy. No database-provided limits, considering study types, languages, publication years, or any other formal criteria were applied to any of the sources. Two reviewers assessed eligibility of each record and rated risk of bias in included studies. From 10,082 screened records, 65 studies were identified as eligible. We extracted adjusted associations from 32 studies and unadjusted from 33 studies. Risk of bias was a concern in the domains 'study confounding' and 'statistical analysis'. VE/VCO 2 was reported as a prognostic factor for short-term complications after thoracic and abdominal surgery. VE/VCO 2 was also reported as a prognostic factor for mid- to long-term mortality. Data-driven covariable selection was applied in 31 studies. Eighteen studies excluded VE/VCO 2 from the final multivariable regression owing to data-driven model-building approaches. This systematic review identifies VE/VCO 2 as a predictor for short-term complications after thoracic and abdominal surgery. However, the available data do not allow conclusions about clinical decision-making. Future studies should select covariables for adjustment a priori based on external knowledge. PROSPERO (CRD42022369944). [ABSTRACT FROM AUTHOR]

Administering sodium bicarbonate (NaHCO3) to patients with respiratory acidosis breathing spontaneously is contraindicated because it increases carbon dioxide load and depresses pulmonary ventilation. Nonetheless, several studies have reported salutary effects of NaHCO3 in patients with respiratory acidosis but the underlying mechanism remains uncertain. Considering that such reports have been ignored, we examined the ventilatory response of unanesthetized dogs with respiratory acidosis to hypertonic NaHCO3 infusion (1 N, 5 mmol/kg) and compared it with that of animals with normal acid-base status or one of the remaining acid-base disorders. Ventilatory response to NaHCO3 infusion was evaluated by examining the ensuing change in PaCO2 and the linear regression of the PaCO2 vs. pH relationship. Strikingly, PaCO2 failed to increase and the ΔPaCO2 vs. ΔpH slope was negative in respiratory acidosis, whereas PaCO2 increased consistently and the ΔPaCO2 vs. ΔpH slope was positive in the remaining study groups. These results cannot be explained by differences in buffering-induced decomposition of infused bicarbonate or baseline levels of blood pH, PaCO2, and pulmonary ventilation. We propose that NaHCO3 infusion improved the ventilatory efficiency of animals with respiratory acidosis, i.e., it decreased their ratio of total pulmonary ventilation to carbon dioxide excretion (VE/VCO2). Such exclusive effect of NaHCO3 infusion in animals with respiratory acidosis might emanate from baseline increased VD/VT (dead space/tidal volume) caused by bronchoconstriction and likely reduced pulmonary blood flow, defects that are reversed by alkali infusion. Our observations might explain the beneficial effects of NaHCO3 reported in patients with acute respiratory acidosis. [ABSTRACT FROM AUTHOR]

Background and Objectives: The aim of the study was to evaluate the health status of professional athletes after recovering from COVID-19 and the impact that SARS-CoV-2 had on their overall cardiorespiratory fitness, which was done by conducting cardiopulmonary exercise testing (CPET). Materials and Methods: A total of twenty-seven professional basketball players (Euroleague Basketball and the ABA League) participated in the study. CPET was performed before (as part of their regular preparticipation exam, during the pre-season period), as well as after SARS-CoV-2 infection (after two weeks of home isolation, during the competitive part of the season). CPET was performed on a treadmill, while cardiovascular, respiratory, and metabolic functions were evaluated by using a breath-by-breath analysis technique (Quark CPET system manufactured by Cosmed, Rome, Italy). Results: Maximal oxygen consumption and aerobic efficiency were significantly reduced after SARS-CoV-2 infection (p = 0.000). An obvious decrease in oxygen pulse was observed during CPET after recovering from COVID-19 (p = 0.001), as was deterioration of ventilatory efficiency. Internal respiration was the most negatively affected. An early transition from aerobic to anaerobic mechanisms of creating energy for work and intensive metabolic fatigue were obvious after SARS-CoV-2 infection. Conclusions: Although it was believed that SARS-CoV-2 only affects the cardiopulmonary status of the elderly population and people with associated comorbidities, it is clear from this research that professional athletes can also be at certain risk. Even though no pathological cardiovascular and respiratory changes were found in athletes after COVID-19, results showed significantly decreased cardiorespiratory fitness, with an emphasis on internal respiration. [ABSTRACT FROM AUTHOR]

• Correlation between peripheral endothelial function and VO 2peak after HTx. • Correlation between LnRHI and VE/VCO 2slope in HTx recipients. • Findings emphasize the importance of the prevention of cardiovascular risk. Endothelial dysfunction and peak oxygen uptake (VO 2peak) are also predictors of increased risk of cardiovascular events in heart transplantation (HTx) recipients. The preservation of endothelial function may contribute to exercise tolerance. To investigate the correlation between peripheral endothelial function and exercise tolerance through VO 2peak and ventilation to carbon dioxide production slope (VE / VCO 2 slope) in HTx recipients. A pilot cross-sectional study was conducted with adult individuals aged 18-65 years, HTx ≥ six months after surgery, who had a stable medical condition and no changes over the last three months of immunosuppressive treatment. The patients underwent an assessment of endothelial function through PAT (EndoPAT-2000®) and performed a cardiopulmonary exercise test (CPET). A total of 41% of the studied population presented endothelial dysfunction. The individuals were divided into two groups: the endothelial dysfunction (GED; n=9) group and the normal endothelial function (GNEF; n=13) group according to the logarithm of the reactive hyperemia index (LnRHI). There was a positive and moderate correlation between the LnRHI and VO 2 peak (r=0.659, p=0.013) and a negative and moderate correlation between the LnRHI and VE/VCO 2 slope (r= -0.686, p= 0.009) in the GNEF. However, no significant correlations were found in the GED. The results showed that the preservation of peripheral endothelial function is significantly correlated with an increase in exercise tolerance in individuals after HTx. These findings bring important considerations for cardiovascular risk prevention and emphasize that therapeutic strategies with physical training programs must be implemented early. [ABSTRACT FROM AUTHOR]

This pilot study aimed to evaluate if peak VO2 and ventilatory efficiency in combination would improve preoperative risk stratification beyond only relying on peak VO2. This was a single‐center retrospective cohort study including all patients who underwent cardiopulmonary exercise testing (CPET) as part of preoperative risk evaluation before major upper abdominal surgery during years 2008–2021. The primary outcome was any major cardiopulmonary complication during hospitalization. Forty‐nine patients had a preoperative CPET before decision to pursue to surgery (cancer in esophagus [n = 18], stomach [6], pancreas [16], or liver [9]). Twenty‐five were selected for operation. Patients who suffered any major cardiopulmonary complication had lower ventilatory efficiency (i.e., higher VE/VCO2 slope, 37.3 vs. 29.7, p = 0.031) compared to those without complications. In patients with a low aerobic capacity (i.e., peak VO2 < 20 mL/kg/min) and a VE/VCO2 slope ≥ 39, 80% developed a major cardiopulmonary complication. In this pilot study of patients with preoperative CPET before major upper abdominal surgery, patients who experienced a major cardiopulmonary complication had significantly lower ventilatory efficiency compared to those who did not. A low aerobic capacity in combination with low ventilatory efficiency was associated with a very high risk (80%) of having a major cardiopulmonary complication. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the effects of a 15‐week telerehabilitation program and a detraining period on cardiorespiratory fitness and mechanical efficiency in patients with post‐COVID‐19 sequelae. Methods: 131 patients with post‐COVID‐19 sequelae were randomly assigned to one of two groups: patients who carried out the supervised telerehabilitation program (TRG, n = 66) and a control group (CG, n = 65). An incremental cardiopulmonary exercise testing (CPET) was performed on cycle ergometer to compare cardioventilatory responses between experimental groups. Results: A significant increase in the CPET duration, peak power output, and mechanical efficiency was observed in TRG compared to CG after the telerehabilitation program (p ≤ 0.001). A significant increase in the CPET duration, peak power output, and mechanical efficiency was verified at 3 months compared to the pretest and after detraining in TRG (p < 0.001). A significant increase in peak oxygen uptake (V̇O2peak) was identified after the intervention and in the detraining period compared to the pretest in both experimental groups (p < 0.001). A higher ventilatory efficiency was observed after the telerehabilitation program (p = 0.021) than in pretest only in TRG. Conclusions: A 15‐week supervised home telerehabilitation program improved exercise capacity, power output, and mechanical efficiency in TRG compared to a CG. The telerehabilitation program was not more effective in improving V̇O2peak than the activities of the CG. However, ventilatory efficiency was improved only after the telerehabilitation program. The reported results after the detraining period highlight the need to maintain the rehabilitation program over time. [ABSTRACT FROM AUTHOR]

Background: The effects of coronavirus disease 2019 (COVID-19) on the cardiorespiratory fitness of hospitalized and obese patients are of utmost relevance. This study aimed to analyze how hospital and intensive care unit (ICU) stay together with body mass index affect cardiorespiratory fitness in patients with COVID-19. Methods: 251 participants (males, n = 118; females, n = 133) were assigned to four groups: non-hospitalized COVID-19 patients (n = 65, age: 45.3 years), hospitalized COVID-19 patients (n = 63, age: 57.6 years), COVID-19 patients admitted to the ICU (n = 61, age: 56.9 years), and control group (n = 62, age: 49.8 years). An incremental cardiopulmonary exercise test was performed between 3 and 6 weeks after medical discharge from hospital. Results: Higher peak oxygen uptake (VO2peak), ventilatory efficiency and power output were found in ICU patients with normal weight (NW) than in overweight (OW) (Mean difference: 0.1 L·min−1, −5.5, 29.0 W, respectively) and obese (OB) ICU patients (Mean difference: 0.1 L·min−1, −5.0, 26.2 W, respectively) (p <.05). In NW, OW and OB participants, higher VO2peak and power output were observed in control group compared with non-hospitalized (Mean difference: NW: 0.2 L·min−1, 83.3 W; OW: 0.2 L·min−1, 60.0 W; OB: 0.2 L·min−1, 70.9 W, respectively), hospitalized (Mean difference: NW: 0.2 L·min−1, 72.9 W; OW: 0.1 L·min−1, 58.3 W; OB: 0.2 L•min−1, 91.1 W, respectively) and ICU patients (Mean difference: NW: 0.1 L·min−1, 70.9 W; OW: 0.2 L·min−1, 91.1 W; OB: 0.3 L·min−1; 65.0 W, respectively) (p <.05). Conclusions: The degree of severity of COVID-19, especially identified by hospitalization and ICU stay, together with obesity and overweight were key factors in reducing cardiorespiratory fitness in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Background: Optimal noninvasive respiratory support for patients with hypoxemic respiratory failure should minimize work of breathing without increasing the transpulmonary pressure. Recently, an asymmetrical high flow nasal cannula (HFNC) interface (Duet, Fisher & Paykel Healthcare Ltd), in which the caliber of each nasal prong is different, was approved for clinical use. This system might reduce work of breathing by lowering minute ventilation and improving respiratory mechanics. Methods: We enrolled 10 patients ≥ 18 years of age who were admitted to the Ospedale Maggiore Policlinico ICU in Milan, Italy, and had a PaO2/FiO2 < 300 mmHg during HFNC support with a conventional cannula. We investigated whether the asymmetrical interface, compared to a conventional high flow nasal cannula, reduces minute ventilation and work of breathing. Each patient underwent support with the asymmetrical interface and the conventional interface, applied in a randomized sequence. Each interface was provided at a flow rate of 40 l/min followed by 60 l/min. Patients were continuously monitored with esophageal manometry and electrical impedance tomography. Results: Application of the asymmetrical interface resulted in a −13.5 [−19.4 to (−4.5)] % change in minute ventilation at a flow rate of 40 l/min, p = 0.006 and a −19.6 [−28.0 to (−7.5)] % change at 60 l/min, p = 0.002, that occurred despite no change in PaCO2 (35 [33–42] versus 35 [33–43] mmHg at 40 l/min and 35 [32–41] versus 36 [32–43] mmHg at 60 l/min). Correspondingly, the asymmetrical interface lowered the inspiratory esophageal pressure–time product from 163 [118–210] to 140 [84–159] (cmH2O*s)/min at a flow rate of 40 l/min, p = 0.02 and from 142 [123–178] to 117 [90–137] (cmH2O*s)/min at a flow rate of 60 l/min, p = 0.04. The asymmetrical cannula did not have any impact on oxygenation, the dorsal fraction of ventilation, dynamic lung compliance, or end-expiratory lung impedance, suggesting no major effect on PEEP, lung mechanics, or alveolar recruitment. Conclusions: An asymmetrical HFNC interface reduces minute ventilation and work of breathing in patients with mild-to-moderate hypoxemic respiratory failure supported with a conventional interface. This appears to be primarily driven by increased ventilatory efficiency due to enhanced CO2 clearance from the upper airway. [ABSTRACT FROM AUTHOR]

Introduction: We assessed the cardiorespiratory optimal point (COP)--the minimal VE/V O2 in a given minute of an incremental cardiopulmonary exercise test--in patients with heart failure (HF) and aimed to determine 1) its association with patient and disease characteristics, 2) changes after an exercise-based cardiac rehabilitation program (CR), and 3) the association with clinical outcomes. Methods: We studied 277 HF patients (67 (58-74) yr, 30% female, 72% HF with restricted ejection fraction) between 2009 and 2018. Patients participated in a 12- to 24-wk CR program, and COP was assessed pre- and post-CR. Patient and disease characteristics and clinical outcomes (mortality and cardiovascular-related hospitalization) were extracted from patient files. The incidence of clinical outcomes was compared across COP tertiles (low, <26.0; moderate, 26.0-30.7; high, >30.7). Results:Median COP was 28.2 (24.9-32.1) and was reached at 51%± 15%of VO2peak. Lower age, female sex, higher body mass index, the absence of a pacemaker or the absence of chronic obstructive pulmonary disease, and lower N-terminal prohormone brain natriuretic peptide concentrations were associated with a lower COP. Participation in CR reduced COP (-0.8; 95% confidence interval, -1.3 to -0.3). Low COP had a reduced risk (adjusted hazard ratio, 0.53; 95% confidence interval, 0.33-0.84) for adverse clinical outcomes as compared with high COP. Conclusions: Classic cardiovascular risk factors are associated with a higher, more unfavorable, COP. CR-based exercise training reduces COP, whereas a lower COP is associated with a better clinical prognosis. As COP can be established during a submaximal exercise test, this may offer novel risk stratification possibilities for HF care programs. [ABSTRACT FROM AUTHOR]

Limitation in exercise capacity has not been described in athletes affected by SARS‐CoV‐2 infection. However, patients who have recovered from COVID‐19 without cardiopulmonary impairment show exaggerated ventilatory response during exercise. Therefore, we aimed to evaluate the ventilatory efficiency (VEf) in competitive athletes recovered from COVID‐19 and to characterize the ventilation versus carbon dioxide relationship (VE/VCO2) slope in this population. Thirty‐seven competitive athletes with COVID‐19 were recruited for this study. All participants underwent spirometry, echocardiography, and cardiopulmonary exercise testing (CPET). z‐FVC values and end‐title pressure of CO2 (PETCO2) were lower in the third tertile compared with the first tertile: −0.753 ± 0.473 vs. 0.037 ± 0.911, p = 0.05; 42.2 ± 2.7 vs. 37.1 ± 2.5 mmHg, p < 0.01. VE/VCO2 slope was significantly correlated to maximal VCO2/VE and maximal VO2/VE: coefficient = −0.5 R2 = 0.58, p < 0.0001 and coefficient = −0.3 R2 = 0.16, p = 0.008. Competitive athletes affected by SARS‐CoV‐2 infection, without cardio‐respiratory disease sequel, may present ventilatory inefficiency (ViE), without exercise capacity limitation. FVC is higher in athletes with better ventilatory performance during exercise, and increased VE/VCO2 slope is inversely correlated to max VCO2/VE and max VO2/VE. [ABSTRACT FROM AUTHOR]

Abstract Background Optimal noninvasive respiratory support for patients with hypoxemic respiratory failure should minimize work of breathing without increasing the transpulmonary pressure. Recently, an asymmetrical high flow nasal cannula (HFNC) interface (Duet, Fisher & Paykel Healthcare Ltd), in which the caliber of each nasal prong is different, was approved for clinical use. This system might reduce work of breathing by lowering minute ventilation and improving respiratory mechanics. Methods We enrolled 10 patients ≥ 18 years of age who were admitted to the Ospedale Maggiore Policlinico ICU in Milan, Italy, and had a PaO2/FiO2

Background and Objectives: The aim of the study was to evaluate the health status of professional athletes after recovering from COVID-19 and the impact that SARS-CoV-2 had on their overall cardiorespiratory fitness, which was done by conducting cardiopulmonary exercise testing (CPET). Materials and Methods: A total of twenty-seven professional basketball players (Euroleague Basketball and the ABA League) participated in the study. CPET was performed before (as part of their regular preparticipation exam, during the pre-season period), as well as after SARS-CoV-2 infection (after two weeks of home isolation, during the competitive part of the season). CPET was performed on a treadmill, while cardiovascular, respiratory, and metabolic functions were evaluated by using a breath-by-breath analysis technique (Quark CPET system manufactured by Cosmed, Rome, Italy). Results: Maximal oxygen consumption and aerobic efficiency were significantly reduced after SARS-CoV-2 infection (p = 0.000). An obvious decrease in oxygen pulse was observed during CPET after recovering from COVID-19 (p = 0.001), as was deterioration of ventilatory efficiency. Internal respiration was the most negatively affected. An early transition from aerobic to anaerobic mechanisms of creating energy for work and intensive metabolic fatigue were obvious after SARS-CoV-2 infection. Conclusions: Although it was believed that SARS-CoV-2 only affects the cardiopulmonary status of the elderly population and people with associated comorbidities, it is clear from this research that professional athletes can also be at certain risk. Even though no pathological cardiovascular and respiratory changes were found in athletes after COVID-19, results showed significantly decreased cardiorespiratory fitness, with an emphasis on internal respiration.

Objective: We aimed to evaluate whether or not using the slope of the increase in minute ventilation in relation to carbon dioxide (VE/VCo2-slope), with a cutoff value of 35, could improve risk stratification for major pulmonary complications or death following lobectomy in lung cancer patients at moderate risk (Vo2peak = 10-20 mL/kg/min). Methods: Single center, retrospective analysis of 146 patients with lung cancer who underwent lobectomy and preoperative cardiopulmonary exercise testing in 2008-2020. The main outcome was any major pulmonary complication or death within 30 days of surgery. Patients were categorized based on their preoperative cardiopulmonary exercise testing as: low-risk group, peak oxygen uptake >20 mL/kg/min; low-moderate risk, peak oxygen uptake 10 to 20 mL/kg/min and VE/VCo2-slope

Background An elevated ventilatory efficiency slope during exercise (minute ventilation/volume of expired CO2; VE/VCO2 slope) is a strong prognostic indicator in heart failure. It is elevated in people with heart failure with preserved ejection, many of whom have hypertension. However, whether the VE/VCO2 slope is also elevated in people with primary hypertension versus normotensive individuals is unknown. We hypothesize that there is a spectrum of ventilatory inefficiency in cardiovascular disease, reflecting an increasingly abnormal physiological response to exercise. The aim of this study was to evaluate the VE/VCO2 slope in patients with hypertension compared with age‐, peak oxygen consumption–, and sex‐matched healthy subjects. Methods and Results Ramped cardiovascular pulmonary exercise tests to peak oxygen consumption were completed on a bike ergometer in 55 patients with primary hypertension and 24 normotensive controls. The VE/VCO2 slope was assessed from the onset of exercise to peak oxygen consumption. Data were compared using unpaired Student t test. Age (mean±SD, 66±6 versus 64±6 years; P=0.18), body mass index (25.4±3.5 versus 24±2.4 kg/m2; P=0.13), and peak oxygen consumption (23.2±6.6 versus 24±7.3 mL/min per kg; P=0.64) were similar between groups. The VE/VCO2 slope was elevated in the hypertensive group versus controls (31.8±4.5 versus 28.4±3.4; P=0.002). Only 27% of the hypertensive group were classified as having a normal VE/VCO2 slope (20–30) versus 71% in the control group. Conclusions Ventilatory efficiency is impaired people with hypertension without a diagnosis of heart failure versus normotensive individuals. Future research needs to establish whether those patients with hypertension with elevated VE/VCO2 slopes are at risk of developing future heart failure.

Background The symptom for identification of pulmonary arterial hypertension (PAH) is dyspnea on exertion, with a concomitant decrease in exercise capacity. Even patients with hemodynamically improved PAH may have impaired exercise tolerance; however, the effect of central and peripheral factors on exercise tolerance remains unclear. We explored the factors contributing to exercise capacity and ventilatory efficiency in patients with hemodynamically normalized PAH after medical treatment. Methods and Results In total, 82 patients with PAH (age: median 46 [interquartile range, 39–51] years; male:female, 23:59) and mean pulmonary arterial pressure ≤30 mm Hg at rest were enrolled. The exercise capacity, indicated by the 6‐minute walk distance and peak oxygen consumption, and the ventilatory efficiency, indicated by the minute ventilation versus carbon dioxide output slope, were assessed using cardiopulmonary exercise testing with a right heart catheter. The mean pulmonary arterial pressure was 21 (17–25) mm Hg, and the 6‐minute walk distance was 530 (458–565) m, whereas the peak oxygen consumption was 18.8 (14.8–21.6) mLꞏmin−1ꞏkg−1. The multivariate model that best predicted 6‐minute walk distance included peak arterial mixed venous oxygen content difference (β=0.46, P

Background: Heart failure (HF) has become increasingly difficult to manage given its increasing incidence. Despite the availability of novel treatment target relieving inhibition and congestions for neurohormonal activation, heart failure is one of leading health conditions associated with high hospitalization and readmission rates, resulting in poor quality of life. In light of this, this article serves to demonstrate the effect of anakinra as one of the treatment paradigms for HF to explore the need for advanced novel interventions. Methods: We conducted a search in five electronic databases, including Embase, MEDLINE, Cochrane, Scopus, and PubMed, for RCTs (randomized controlled trials) evaluating the effects of anakinra against placebo in HF. Meta-analysis was performed using RevMan version 5.4. Results: Eight RCTs were obtained and included for analysis in this study. The results demonstrate that anakinra significantly reduces the levels of CRP (C-reactive protein), with significant difference between anakinra- and placebo-treated groups. Analyses also show that CRP failed to cause an improvement in peak oxygen consumption and ventilatory efficiency. Additionally, the treatment-related adverse events were insignificant. Some considerable limitations are that the same set of researchers were involved in most of the studies; hence, more independent studies need to be encouraged. Conclusion: Anakinra was associated with a reduction in CRP levels, indicating some anti-inflammatory effects but no effect on function, exercise capacity, and adverse effects. [ABSTRACT FROM AUTHOR]

Background: Left atrial (LA) myopathy is an established component of hypertrophic cardiomyopathy (HCM); however, the data about its association with exercise incapacity or ventilatory inefficiency that may be seen in HCM patients are limited. This study aimed to explore the association between LA myopathy, evaluated by echocardiography LA strain, and exercise capacity and ventilatory efficiency, evaluated by cardiopulmonary exercise testing (CPET), in HCM patients.Methods: This study included 241 consecutive HCM patients (aged 51.2±15.7 years 67.2% male) in sinus rhythm who underwent CPET and transthoracic echocardiography at the same visit. Exercise incapacity (maximal/predicted oxygen consumption [%peakVO2] <80%) and ventilatory inefficiency (ventilation/carbon dioxide output [VE/VCO2] slope >34) were assessed by CPET. Left atrial myopathy was examined by speckle-tracking myocardial deformation parameters: LA reservoir, conduit and booster strain.Results: All three LA strain values were univariate predictors of exercise capacity and ventilatory efficiency. Among them, LA reservoir strain had the higher r correlation coefficient for predicting both %peakVO2 and VE/VCO2 slope. Left atrial reservoir strain, presence of angina and family history of HCM were independent predictors of exercise capacity. Left atrial reservoir strain, male gender and non-sustained ventricular tachycardia were independent predictors of ventilatory efficiency. Left atrial reservoir strain was a significant predictor of %peakVO2<80% with an optimal cut-off value of 27% (sensitivity 87% and specificity 31%) and VE/VCO2>34 with an optimal cut-off value of 18% (sensitivity 71% and specificity 83%).Conclusion: Left atrial myopathy, as reflected by the LA strain values, was associated with exercise incapacity and ventilatory inefficiency in HCM individuals. Left atrial reservoir strain was the only common independent predictor of %peakVO2 and VE/VCO2 slope. [ABSTRACT FROM AUTHOR]

Abstract Aims The minute ventilation–carbon dioxide production relationship (VE/VCO2 slope) is widely used for prognostication in heart failure (HF) with reduced left ventricular ejection fraction (LVEF). This study explored the prognostic value of VE/VCO2 slope across the spectrum of HF defined by ranges of LVEF. Methods and results In this single‐centre retrospective observational study of 1347 patients with HF referred for cardiopulmonary exercise testing, patients with HF were categorized into HF with reduced (HFrEF, LVEF

Background and objective: Along with impaired aerobic capacity, increased slope of the relationship between ventilation (VE) and pulmonary CO2 output (VCO2), i.e., VE-VCO2 slope is a common finding in patients with cardiac amyloidosis (CA), which suggests ventilatory inefficiency. Little is known about mechanisms leading to ventilatory inefficiency in CA patients. The purpose of this investigation was to examine the factors that underlie the abnormal ventilatory efficiency in transthyretin hereditary CA patients, such as excessive ventilatory drive, inability of pulmonary blood flow to increase adequately during exercise and excessive sympathetic stimulation, which are known mechanisms of VE-VCO2 slope increase. Methods: In this single-center retrospective observational study, consecutive patients (n = 41) with known familial transthyretin amyloidosis p.Val142Ile mutation carriers with confirmed cardiac phenotype were included. Results: Compared with CA patients without ventilatory inefficiency (VEVCO2 slope < 36), patients with ventilatory inefficiency (VE-VCO2 slope = 36) had increased inter-ventricular septum thickness, lower VO2 peak along with hyperventilation, and prolonged post-exercise heart rate recovery. By multivariate analysis, only excess of minute-ventilation at anaerobic threshold (ß = 0.127; p = 0.011) remained an independent predictor of ventilatory inefficiency. Conclusion: Our data suggest that high ventilatory stimulation during exercise leading to hyperventilation is the main determinant of ventilatory inefficiency in hereditary transthyretin cardiac amyloidosis patients. This novel finding helps to better understand the mechanism of exercise intolerance in these patients where physiological limitation may be related to both heart dysfunction and abnormal pulmonary response. [ABSTRACT FROM AUTHOR]

Background: The association between cardiorespiratory fitness (CRF) and metabolic syndrome (MetSyn) is well established. Additional variables derived from cardiopulmonary exercise testing (CPET) have shown prognostic value in some chronic diseases, however, there is limited information on how cardiopulmonary responses to exercise may be altered in individuals with MetSyn. Thus, the purpose of this study was to examine the association between cardiopulmonary variables derived from CPET and MetSyn. Methods: A cohort of 3181 participants (1714 men, 1467 women), aged 20–79 years, completed CPET and metabolic risk factor assessment between January 1, 1971, and November 1, 2020. Cardiopulmonary variables assessed included CRF defined as the maximum volume of oxygen uptake (VO2max), ventilatory threshold (VO2@VT), oxygen uptake efficiency slope (OUES), the ratio of ventilation to VO2 at peak exercise (peak VE/VO2) and the VE/VCO2slope. MetSyn was defined using the National Cholesterol Education Program/Adult Treatment Panel. Results: VO2max, VO2@VT, and OUES were lower (P < 0.001) and VE/VCO2slope was higher (P < 0.001) in individuals with MetSyn (n = 774), whereas no difference between groups existed for peak VE/VO2. Logistic regression analysis revealed that VO2max [0.91, 0.89–0.93; odds ratio (OR), 95% confidence interval (CI)], VO2@VT (0.91, 0.87–0.95; OR, 95% CI), OUES (0.32, 0.20–0.52; OR, 95% CI), and VE/VCO2slope (1.03, 1.01–1.05 OR, 95% CI) were all associated with the presence of MetSyn (P ≤ 0.001). Conclusion: These results indicate that MetSyn is associated with altered cardiopulomary function that may provide insight into the underlying pathophysiology of MetSyn. [ABSTRACT FROM AUTHOR]

Background and objective: Along with impaired aerobic capacity, increased slope of the relationship between ventilation (VE) and pulmonary CO2 output (VCO2), i.e., VE-VCO2 slope is a common finding in patients with cardiac amyloidosis (CA), which suggests ventilatory inefficiency. Little is known about mechanisms leading to ventilatory inefficiency in CA patients. The purpose of this investigation was to examine the factors that underlie the abnormal ventilatory efficiency in transthyretin hereditary CA patients, such as excessive ventilatory drive, inability of pulmonary blood flow to increase adequately during exercise and excessive sympathetic stimulation, which are known mechanisms of VE-VCO2 slope increase.Methods: In this single-center retrospective observational study, consecutive patients (n = 41) with known familial transthyretin amyloidosis p.Val142Ile mutation carriers with confirmed cardiac phenotype were included.Results: Compared with CA patients without ventilatory inefficiency (VE-VCO2 slope < 36), patients with ventilatory inefficiency (VE-VCO2 slope ≥ 36) had increased inter-ventricular septum thickness, lower VO2 peak along with hyperventilation, and prolonged post-exercise heart rate recovery. By multivariate analysis, only excess of minute-ventilation at anaerobic threshold (β = 0.127; p = 0.011) remained an independent predictor of ventilatory inefficiency.Conclusion: Our data suggest that high ventilatory stimulation during exercise leading to hyperventilation is the main determinant of ventilatory inefficiency in hereditary transthyretin cardiac amyloidosis patients. This novel finding helps to better understand the mechanism of exercise intolerance in these patients where physiological limitation may be related to both heart dysfunction and abnormal pulmonary response.

Rationale: Impaired exercise ventilatory efficiency (high ventilatory requirements for CO2 [[Formula: see text]e/[Formula: see text]co2]) provides an indication of pulmonary gas exchange abnormalities in chronic obstructive pulmonary disease (COPD). Objectives: To determine 1) the association between high [Formula: see text]e/[Formula: see text]co2 and clinical outcomes (dyspnea and exercise capacity) and its relationship to lung function and structural radiographic abnormalities; and 2) its prevalence in a large population-based cohort. Methods: Participants were recruited randomly from the population and underwent clinical evaluation, pulmonary function, cardiopulmonary exercise testing, and chest computed tomography. Impaired exercise ventilatory efficiency was defined by a nadir [Formula: see text]e/[Formula: see text]co2 above the upper limit of normal (ULN), using population-based normative values. Measurements and Main Results: Participants included 445 never-smokers, 381 ever-smokers without airflow obstruction, 224 with Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 COPD, and 200 with GOLD 2-4 COPD. Participants with [Formula: see text]e/[Formula: see text]co2 above the ULN were more likely to have activity-related dyspnea (Medical Research Council dyspnea scale ⩾ 2; odds ratio [5-95% confidence intervals], 1.77 [1.31 to 2.39]) and abnormally low peak [Formula: see text]o2 ([Formula: see text]o2peak below the lower limit of normal; odds ratio, 4.58 [3.06 to 6.86]). The Kco had a stronger correlation with nadir [Formula: see text]e/[Formula: see text]co2 (r = -0.38; P < 0.001) than other relevant lung function and computed tomography metrics. The prevalence of [Formula: see text]e/[Formula: see text]co2 above the ULN was 24% in COPD (similar in GOLD 1 and 2 through 4), which was greater than in never-smokers (13%) and ever-smokers (12%). Conclusions: [Formula: see text]e/[Formula: see text]co2 above the ULN was associated with greater dyspnea and low [Formula: see text]o2peak and was present in 24% of all participants with COPD, regardless of GOLD stage. The results show the importance of recognizing impaired exercise ventilatory efficiency as a potential contributor to dyspnea and exercise limitation, even in mild COPD. [ABSTRACT FROM AUTHOR]

Cardiac amyloidosis (CA) is a myocardial disease characterized by extracellular amyloid infiltration throughout the heart, resulting in increased myocardial stiffness, and restrictive heart wall chamber behavior. Its diagnosis among patients hospitalized for cardiovascular diseases is becoming increasingly frequent, suggesting improved disease awareness, and higher diagnostic capacities. One predominant functional manifestation of patients with CA is exercise intolerance, objectified by reduced peak oxygen uptake (VO2 peak), and assessed by metabolic cart during cardiopulmonary exercise testing (CPET). Hemodynamic adaptation to exercise in patients with CA is characterized by low myocardial contractile reserve and impaired myocardial efficiency. Rapid shallow breathing and hyperventilation, in the absence of ventilatory limitation, are also typically observed in response to exercise. Ventilatory inefficiency is further suggested by an increased VE-VCO2 slope, which has been attributed to excessive sympathoexcitation and a high physiological dead space (VD/VT) ratio during exercise. Growing evidence now suggests that, in addition to well-established biomarker risk models, a reduced VO2 peak is potentially a strong and independent predictive factor of adverse patient outcomes, both for monoclonal immunoglobulin light chain (AL) or transthyretin (ATTR) CA. Besides generating prognostic information, CPET can be used for the evaluation of the impact of therapeutic interventions in patients with CA.

Aims: The minute ventilation–carbon dioxide production relationship (VE/VCO2 slope) is widely used for prognostication in heart failure (HF) with reduced left ventricular ejection fraction (LVEF). This study explored the prognostic value of VE/VCO2 slope across the spectrum of HF defined by ranges of LVEF. Methods and results: In this single‐centre retrospective observational study of 1347 patients with HF referred for cardiopulmonary exercise testing, patients with HF were categorized into HF with reduced (HFrEF, LVEF < 40%, n = 598), mid‐range (HFmrEF, 40% ≤ LVEF < 50%, n = 164), and preserved (HFpEF, LVEF ≥ 50%, n = 585) LVEF. Four ventilatory efficiency categories (VC) were defined: VC‐I, VE/VCO2 slope ≤ 29; VC‐II, 29 < VE/VCO2 slope < 36; VC‐III, 36 ≤ VE/VCO2 slope < 45; and VC‐IV, VE/VCO2 slope ≥ 45. The associations of these VE/VCO2 slope categories with a composite outcome of all‐cause mortality or HF hospitalization were evaluated for each category of LVEF. Over a median follow‐up of 2.0 (interquartile range: 1.9, 2.0) years, 201 patients experienced the composite outcome. Compared with patients in VC‐I, those in VC‐II, III, and IV demonstrated three‐fold, five‐fold, and eight‐fold increased risk for the composite outcome. This incremental risk was observed across HFrEF, HFmrEF, and HFpEF cohorts. Conclusions: Higher VE/VCO2 slope is associated with incremental risk of 2 year all‐cause mortality and HF hospitalization across the spectrum of HF defined by LVEF. A multilevel categorical approach to the interpretation of VE/VCO2 slope may offer more refined risk stratification than the current binary approach employed in clinical practice. [ABSTRACT FROM AUTHOR]

Low forced vital capacity (FVC) is associated with decreased exercise capacity in CHD. Multiple prior cardiac surgeries have been associated with low FVC. We seek to understand the relationship between low FVC, number of cardiac surgeries and cardiopulmonary response leading to decreased exercise capacity. Retrospective chart review of demographics, surgical history and exercise testing including spirometry was performed in patients with CHD. Single ventricle patients were excluded. Low FVC was defined as a Z-score below the lower limit of normal. Exercise parameters were expressed as a percent of predicted. There were 93 patients with 2 ventricle CHD identified over 34 months with cardiopulmonary exercise testing. The FVC Z-score directly correlated with peak V̇O2% (R2 = 0.07, p < 0.05), and the O2 pulse% (R2 = 0.25, p < 0.0001). The VE/VCO2 was inversely related to the FVC Z-score (R2 = 0.11, p < 0.01). Patients with minimum three prior surgeries had decreased peak VO2% (63.7 vs. 72.8, p < 0.05), decreased peak O2 pulse% (80.8 vs. 97.9, p < 0.01) and a lower mean FVC Z-score (− 1.9 vs − 0.38, p < 0.01). The FVC Z-score and number of surgeries both predicted peak V̇O2% in multivariate analysis. Our study demonstrated that low FVC and three or more prior cardiac surgeries were associated with lower exercise capacity and lower stroke volume response. More cardiac surgeries were also associated with low FVC. However, both low FVC and the number of surgeries were independent predictors of exercise capacity. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) has become increasingly difficult to manage given its increasing incidence. Despite the availability of novel treatment target relieving inhibition and congestions for neurohormonal activation, heart failure is one of leading health conditions associated with high hospitalization and readmission rates, resulting in poor quality of life. In light of this, this article serves to demonstrate the effect of anakinra as one of the treatment paradigms for HF to explore the need for advanced novel interventions. Methods: We conducted a search in five electronic databases, including Embase, MEDLINE, Cochrane, Scopus, and PubMed, for RCTs (randomized controlled trials) evaluating the effects of anakinra against placebo in HF. Meta-analysis was performed using RevMan version 5.4. Results: Eight RCTs were obtained and included for analysis in this study. The results demonstrate that anakinra significantly reduces the levels of CRP (C-reactive protein), with significant difference between anakinra- and placebo-treated groups. Analyses also show that CRP failed to cause an improvement in peak oxygen consumption and ventilatory efficiency. Additionally, the treatment-related adverse events were insignificant. Some considerable limitations are that the same set of researchers were involved in most of the studies; hence, more independent studies need to be encouraged. Conclusion: Anakinra was associated with a reduction in CRP levels, indicating some anti-inflammatory effects but no effect on function, exercise capacity, and adverse effects.

To achieve this with an appropriately powered sample size, an international registry that includes high-quality CPX laboratories conducting tests in patients with COVID-19 and tracking outcomes would be ideal. Pleguezuelos et al. [[8]] performed CPX on healthy controls, patients diagnosed with ischemic heart disease (IHD), patients diagnosed with chronic obstructive pulmonary disease (COPD) and patients hospitalized for COVID-19; CPX was performed two months post-hospital discharge in the COVID-19 group. Keywords: Aerobic capacity; cardiorespiratory fitness; prognosis; pulmonary hemodynamics; ventilatory efficiency EN Aerobic capacity cardiorespiratory fitness prognosis pulmonary hemodynamics ventilatory efficiency 877 880 4 11/30/21 20211001 NES 211001 Countries around the world continue to address the large-scale health and wellbeing impacts and the broader societal burden associated with the coronavirus disease 2019 (COVID-2019). [Extracted from the article]

Aims: In contrast to cardiovascular disease, low rather than high ventilatory inefficiency, evaluated by the minute ventilation-carbon dioxide output (V'E-V'CO2)-slope, has been recognized as being related to greater disease severity in chronic obstructive pulmonary disease (COPD). To better care for patients with cardiopulmonary disease, understanding the physiological correlation between ventilatory inefficiency and exercise limitation is necessary, but remains inadequate. Given that oxygen uptake (V'O2) evaluated by cardiopulmonary exercise testing (CPET) depends on both the ventilatory capability and oxygen extraction, i.e., the difference between inspiratory and expiratory oxygen concentration (ΔFO2), the aim of this study was to investigate the correlations between V'E-V'CO2-slope and the ΔFO2 during exercise and their physiological implications in patients with COPD.Methods: A total of 156 COPD patients (mean age, 70.9 ± 7.2 years) with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I–IV and 16 controls underwent CPET with blood gas analysis.Results: With the progression of COPD, mechanical ventilatory constraints together with a slower respiratory frequency led to exertional respiratory acidosis. In GOLD IV cases, (1) decrease in the dependence of reduced peak V'O2 on V'E led to an increase in its dependence on peak ΔFO2 during exercise; and (2) the ΔFO2-V'CO2-slope became steeper, correlating with the severity of exertional respiratory acidosis (r = 0.6359, p < 0.0001). No significant differences in peak exercise ΔFO2 or V'E-V'CO2-slope were observed among the various GOLD stages. In all subjects, including controls, peak exercise ΔFO2 had the strongest correlation with the V'E-V'CO2-slope (r = −0.8835, p < 0.0001) and correlated well with body mass index (r = 0.3871, p < 0.0001), although it did not correlate with the heart rate-V'CO2-relationship and V'E.Conclusions: Ventilatory efficiency related to CO2 clearance might depend on exertional oxygen extraction in the body. Measuring ΔFO2 might be a key component for identifying ventilatory inefficiency and oxygen availability. Increasing ΔFO2 would help to improve ventilatory inefficiency and exercise tolerance separately from cardiac and ventilatory capability in COPD patients.

Background and objective: The combination of both reduced resting diffusing capacity of the lung for carbon monoxide (DLCO) and ventilatory efficiency (increased ventilatory requirement for CO2 clearance [V˙E/V˙CO2]) has been linked to exertional dyspnoea and exercise intolerance in chronic obstructive pulmonary disease (COPD) but the underlying mechanisms are poorly understood. The current study examined if low resting DLCO and higher exercise ventilatory requirements were associated with earlier critical dynamic mechanical constraints, dyspnoea and exercise limitation in patients with mild COPD. Methods: In this retrospective analysis, we compared V˙E/V˙CO2, dynamic inspiratory reserve volume (IRV), dyspnoea and exercise capacity in groups of patients with Global Initiative for Chronic Obstructive Lung Disease stage 1 COPD with (1) a resting DLCO at or greater than the lower limit of normal (≥LLN; Global Lung Function Initiative reference equations [n = 44]) or (2) below the

Aims: In contrast to cardiovascular disease, low rather than high ventilatory inefficiency, evaluated by the minute ventilation-carbon dioxide output (V' E- V' CO2)-slope, has been recognized as being related to greater disease severity in chronic obstructive pulmonary disease (COPD). To better care for patients with cardiopulmonary disease, understanding the physiological correlation between ventilatory inefficiency and exercise limitation is necessary, but remains inadequate. Given that oxygen uptake (V' O2) evaluated by cardiopulmonary exercise testing (CPET) depends on both the ventilatory capability and oxygen extraction, i.e., the difference between inspiratory and expiratory oxygen concentration (ΔFO2), the aim of this study was to investigate the correlations between V' E- V' CO2-slope and the ΔFO2 during exercise and their physiological implications in patients with COPD. Methods: A total of 156 COPD patients (mean age, 70.9 ± 7.2 years) with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I–IV and 16 controls underwent CPET with blood gas analysis. Results: With the progression of COPD, mechanical ventilatory constraints together with a slower respiratory frequency led to exertional respiratory acidosis. In GOLD IV cases, (1) decrease in the dependence of reduced peak V' O2 on V' E led to an increase in its dependence on peak ΔFO2 during exercise; and (2) the ΔFO2- V' CO2-slope became steeper, correlating with the severity of exertional respiratory acidosis (r = 0.6359, p < 0.0001). No significant differences in peak exercise ΔFO2 or V' E- V' CO2-slope were observed among the various GOLD stages. In all subjects, including controls, peak exercise ΔFO2 had the strongest correlation with the V' E- V' CO2-slope (r = −0.8835, p < 0.0001) and correlated well with body mass index (r = 0.3871, p < 0.0001), although it did not correlate with the heart rate- V' CO2-relationship and V' E. Conclusions: Ventilatory efficiency related to CO2 clearance might depend on exertional oxygen extraction in the body. Measuring ΔFO2 might be a key component for identifying ventilatory inefficiency and oxygen availability. Increasing ΔFO2 would help to improve ventilatory inefficiency and exercise tolerance separately from cardiac and ventilatory capability in COPD patients. [ABSTRACT FROM AUTHOR]

Rationale: Obesity presents a mechanical load to the thorax, which could perturb the generation of minute ventilation (V̇e) during exercise. Because the respiratory effects of obesity are not homogenous among all individuals with obesity and obesity-related effects could vary depending on the magnitude of obesity, we hypothesized that the exercise ventilatory response (slope of the V̇e and carbon dioxide elimination [V̇co2] relationship) would manifest itself differently as the magnitude of obesity increases.Objectives: To investigate the V̇e/V̇co2 slope in an obese population that spanned across a wide body mass index (BMI) range.Methods: A total of 533 patients who presented to a surgical weight loss center for pre-bariatric surgery testing performed an incremental maximal cycling test and were studied retrospectively. The V̇e/V̇co2 slope was calculated up to the ventilatory threshold. Patients were examined in groups based on BMI (category 1: 30-39.9 kg/m2, category 2: 40-49.9 kg/m2, and category 3: ≥50 kg/m2). Because the respiratory effects of obesity could be sex and/or age specific, we further examined patients in groups by sex and age (younger: <50 yr and older: ≥50 yr). Differences in the V̇e/V̇co2 slope were then compared between BMI category, age, and sex using a three-way ANOVA.Results: No significant BMI category by sex by age interactions was detected (P = 0.75). The V̇e/V̇co2 slope decreased with increases in BMI (category 1, 29.1 ± 4.0; category 2, 28.4 ± 4.1; and category 3, 27.1 ± 3.3) and was elevated in women (28.9 ± 4.1) compared with men (26.7 ± 3.2) (BMI category by sex interaction, P < 0.05). No age-related differences were observed (BMI category by age interaction, P = 0.55). The partial pressure for end-tidal CO2 was elevated at the ventilatory threshold in BMI category 3 compared with BMI categories 1 and 2 (both P < 0.01).Conclusions: These findings suggest that obesity presents a unique challenge to augmenting ventilatory output relative to CO2 elimination, such that the increase in the exercise ventilatory response becomes blunted as the magnitude of obesity increases. Further studies are required to investigate the clinical consequences and the mechanisms that may explain the attenuation of exercise ventilatory response with increasing BMI in men and women with obesity. [ABSTRACT FROM AUTHOR]

Smokers without airflow obstruction have reduced exercise capacity, but the underlying physiological mechanisms are not fully understood. We aimed to compare quadriceps function assessed using nonvolitional measures and ventilatory requirements during exercise, between smokers without airway obstruction and never-smoker controls. Adult smokers (n = 20) and never-smoker controls (n = 16) aged 25–50 yr with normal spirometry, underwent incremental cycle cardiopulmonary exercise testing to exhaustion with measurement of symptoms and dynamic lung volumes. Quadriceps strength and endurance were assessed nonvolitionally using single and repetitive magnetic stimulation. Quadriceps bulk was assessed using ultrasound, as rectus-femoris cross-sectional area. Physical activity level was quantified using the SenseWear armband worn for 5 days. Smokers had lower peak exercise workload, peak oxygen consumption, and anaerobic threshold than controls (170 ± 46 vs. 256 ± 57 W, 2.20 ± 0.56 vs. 3.18 ± 0.72 L/min, 1.38 ± 0.33 vs. 2.09 ± 0.7 L/min, respectively; P < 0.01 for all). Quadriceps endurance was lower in smokers (Δforce-time integral 54.9% ± 14.7% vs. 40.4% ± 14.7%; P = 0.007), but physical activity, quadriceps strength, and bulk were similar between groups. Smokers displayed higher ventilation (120 W: 52.6 ± 11.8 vs. 40.7 ± 6.0 L/min; P < 0.001), decreased ventilatory efficiency (higher V̇e/V̇co2), and were more breathless with greater leg fatigue at iso-workloads and iso-ventilation levels compared with never-smoker controls. Smokers showed no mechanical constraints on tidal volume expansion during exercise or ventilatory limitation at peak exercise. Adult smokers without airflow obstruction have reduced skeletal muscle endurance and ventilatory efficiency compared with never-smoker controls, despite similar daily physical activity levels, which contributed to reduced peak exercise capacity. NEW & NOTEWORTHY In adult smokers without airflow obstruction, the contributions of pulmonary and skeletal muscle functions to reduced exercise capacity are unclear. We found that non-COPD smokers had decreased exercise capacity and muscle endurance although strength was preserved compared with never-smoking controls. Exercise endurance was associated with quadriceps endurance and CO transfer factor. Despite similar physical activity levels, smokers developed leg fatigue, breathlessness, and displayed increased ventilation with reduced ventilatory efficiency at lower workloads, without exhibiting ventilatory constraint. [ABSTRACT FROM AUTHOR]

Introduction: Cardiopulmonary exercise testing (CPET) is nowadays used to study the exercise response in healthy subjects and in disease. Ventilatory efficiency is one of the main determinants in exercise tolerance, and its main variables are a useful tool to guide pathophysiologists toward specific diagnostic pathways, providing prognostic information and improving disease management, treatment, and outcomes., Areas Covered: This review will be based on today's available scientific evidence, describing the main physiological determinants of ventilatory efficiency at rest and during exercise, and focusing also on how CPET variables are modified in specific diseases, leading to the possibility of early diagnosis and management., Expert Opinion: Growing knowledge on CPET interpretation and a wider use of this clinical tool is expected in order to offer more precise diagnostic and prognostic information to patients and clinicians, helping in the management of therapeutic decisions. Future research could be able to identify new and more simple markers of ventilatory efficiency, and to individuate new interventions for the improvement of symptoms, such as exertional dyspnea.

Cardiopulmonary exercise testing (CPET) is a method for evaluating pulmonary and cardiocirculatory abnormalities, dyspnea, and exercise tolerance in healthy individuals and patients with chronic conditions. During exercise, ventilation (V˙E) increases in proportion to metabolic demand [i.e., carbon dioxide production (V˙CO2)] to maintain arterial blood gas and acid-base balance. The response of V˙E relative to V˙CO2 (V˙E/V˙CO2) is commonly termed ventilatory efficiency and is becoming a common physiological tool, in conjunction with other key variables such as operating lung volumes, to evaluate exercise responses in patients with chronic conditions. A growing body of research has shown that the V˙E/V˙CO2 response to exercise is elevated in conditions such as chronic heart failure (CHF), pulmonary hypertension (PH), interstitial lung disease (ILD), and chronic obstructive pulmonary disease (COPD). Importantly, this potentiated V˙E/V˙CO2 response contributes to dyspnea and exercise intolerance. The clinical significance of ventilatory inefficiency is demonstrated by findings showing that the elevated V˙E/V˙CO2 response to exercise is an independent predictor of mortality in patients with CHF, PH, and COPD. In this article, the underlying physiology, measurement, and interpretation of exercise ventilatory efficiency during CPET are reviewed. Additionally, exercise ventilatory efficiency in varying disease states is briefly discussed.

• Reference values of ventilator efficiency variables in a normal Japanese population. • Cardiopulmonary exercise testing was performed using a cycle ergometer. • Tidal volume and minute ventilation (V̇E) during ramp exercise testing were evaluated. • Slope of V̇E versus carbon dioxide (V̇E vs. V̇CO 2 slope), minimum V̇E/V̇CO 2 , and oxygen uptake efficiency slope were also determined. The current understanding of ventilator efficiency variables during ramp exercise testing in the normal Japanese population is insufficient, and the responses of tidal volume (VT) and minute ventilation (V̇E) to the ramp exercise test in the normal Japanese population are not known. A total of 529 healthy Japanese subjects aged 20–78 years underwent cardiopulmonary exercise testing using a cycle ergometer with ramp protocols. VT and V̇E at rest, at anaerobic threshold, and at peak exercise were determined. The slope of V̇E versus carbon dioxide (V̇CO 2) (V̇E vs. V̇CO 2 slope), minimum V̇E/V̇CO 2 , and oxygen uptake efficiency slope (OUES) were determined. For males and females in their 20 s, peak VT (VTpeak) was 2192 ± 376 and 1509 ± 260 mL (p < 0.001), peak V̇E (V̇Epeak) was 80.6 ± 18.7 and 57.7 ± 13.9 L/min (sex differences p < 0.001), the V̇E vs. V̇CO 2 slope was 24.4 ± 3.2 and 25.7 ± 3.2 (p = 0.035), the minimum V̇E/V̇CO 2 was 24.2 ± 2.3 and 27.0 ± 2.8 (p < 0.001), and the OUES was 2452 ± 519 and 1991 ± 315 (p < 0.001), respectively. VTpeak and V̇Epeak decreased with age and increased with weight and height. The V̇E vs. V̇CO 2 slope and minimum V̇E/V̇CO 2 increased with age, while conversely, the OUES decreased with age. We have established the normal range of VT and V̇E responses, the V̇E vs. V̇CO 2 slope, the minimum V̇E/V̇CO 2 , and the OUES for a healthy Japanese population. Some of these parameters were influenced by weight, height, sex, and age. These results provide useful reference values for interpreting the results of cardiopulmonary exercise testing in cardiac patients. [ABSTRACT FROM AUTHOR]

Cardiopulmonary exercise test (CPET) is becoming a key examination to assess physical capacity and disease severity in pediatric cardiology. The V̇e/V̇co2 slope has been increasingly used as a surrogate marker for morbidity and mortality in adult heart failure, pulmonary arterial hypertension, and for adult patients with congenital heart disease (CHD). Nevertheless, the use of the V̇e/V̇co2 slope in children remains limited in the absence of reference values and clearly identified clinical determinants. This study aimed to compare the V̇e/V̇co2 slope in a pediatric cohort with CHD to that of age- and gender-adjusted healthy controls. We also intended to identify the clinical and CPET variables associated with V̇e/V̇co2 slope in this population. This cross-sectional study was carried out between November 2010 and September 2015 in two tertiary care pediatric cardiology reference centers. A total of 700 children were enrolled (399 CHD and 301 healthy controls). The mean V̇e/V̇co2 slope was significantly higher in the CHD subjects than in healthy subjects (31.6 ± 4.8 vs. 29.3 ± 4.8; P < 0.001). The V̇e/V̇co2 slope was higher in children with significant pulmonary regurgitation, tricuspid regurgitation, right ventricular hypertension, and right ventricle outflow tract (RVOT) obstacle. In the CHD group, V̇e/V̇co2 slope increase was associated with body mass index, the presence of a RVOT obstacle, the number of cardiac catheter procedures, as well as low age, forced vital capacity, tidal volume, and PETCO2 . Increased V̇e/V̇co2 slope was predominantly in children with single ventricle and/or residual right heart abnormalities, suggesting that maldistribution of pulmonary blood flow during exercise is an important CHD-unique determinant of V̇e/V̇co2 slope. NEW & NOTEWORTHY Using V̇e/V̇co2 slope is useful for children with congenital heart disease. V̇e/V̇co2 slope is sensitive to pulmonary blood flow maldistribution during exercise, this concerns congenital heart disease with pulmonary regurgitation, tricuspid regurgitation, right ventricular hypertension, and right ventricle outflow tract obstacle. V̇e/V̇co2 slope is a good parameter to follow single ventricles and right heart residual lesions (tetralogy of Fallot; pulmonary atresia; truncus arteriosus…). [ABSTRACT FROM AUTHOR]

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Cardiorespiratory fitness (CRF) is now established as a vital sign. Cardiopulmonary exercise testing (CPX) is the gold-standard approach to assessing CRF. A body of literature spanning several decades clearly supports the clinical utility of CPX in those who are apparently health and at risk for chronic disease as well as numerous patient populations. While CPX, in and of itself, is a valid and reliable clinical assessment, combining findings with other available assessments may provide a more comprehensive perspective that enhances clinical decision making and outcomes. The current review will accomplish the following: (1) define key CPX measures based upon current evidence; and (2) describe the current evidence addressing the relationships between CPX and echocardiography, serum biomarkers, and cardiovascular magnetic resonance. Cardiopulmonary exercise testing provides prognostic and diagnostic information in apparently healthy individuals, those at risk for one or more chronic conditions, as well as numerous patient populations. Moreover, if the goal of an intervention is to improve one or more systems integral to the physiologic response to exercise, CPX should be considered as a central assessment to gauge therapeutic efficacy. To further refine the information obtained from CPX, combining other assessments has demonstrated promise. [ABSTRACT FROM AUTHOR]

Cardiopulmonary exercise testing (CPET) is a method for evaluating pulmonary and cardiocirculatory abnormalities, dyspnea, and exercise tolerance in healthy individuals and patients with chronic conditions. During exercise, ventilation (V˙ E) increases in proportion to metabolic demand [i.e., carbon dioxide production (V˙ CO2)] to maintain arterial blood gas and acid-base balance. The response of V˙ E relative to V˙ CO2 (V˙ E/ V˙ CO2) is commonly termed ventilatory efficiency and is becoming a common physiological tool, in conjunction with other key variables such as operating lung volumes, to evaluate exercise responses in patients with chronic conditions. A growing body of research has shown that the V˙ E/ V˙ CO2 response to exercise is elevated in conditions such as chronic heart failure (CHF), pulmonary hypertension (PH), interstitial lung disease (ILD), and chronic obstructive pulmonary disease (COPD). Importantly, this potentiated V˙ E/ V˙ CO2 response contributes to dyspnea and exercise intolerance. The clinical significance of ventilatory inefficiency is demonstrated by findings showing that the elevated V˙ E/ V˙ CO2 response to exercise is an independent predictor of mortality in patients with CHF, PH, and COPD. In this article, the underlying physiology, measurement, and interpretation of exercise ventilatory efficiency during CPET are reviewed. Additionally, exercise ventilatory efficiency in varying disease states is briefly discussed. [ABSTRACT FROM AUTHOR]