Grinstein J; Sawalha Y; Medvedofsky DA; Ahmad S;Hofmeyer M;  Rodrigo M; Kadakkal A; Barnett C; Kalantari S; Talati I; Zaghol R; Molina EJ; Sheikh FH; Najjar SS;

Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs [J Artif Organs] 2021 Apr 01. Date of Electronic Publication: 2021 Apr 01.

Preoperative cardiopulmonary exercise testing (CPET) is well validated for prognostication before advanced surgical heart failure therapies, but its role in prognostication after LVAD surgery has never been studied. VE/VCO2 slope is an important component of CPET which has direct pathophysiologic links to right ventricular (RV) performance. We hypothesized that VE/VCO ₂ slope would prognosticate RV dysfunction after LVAD. All CPET studies from a single institution were collected between September 2009 and February 2019. Patients who ultimately underwent LVAD implantation were selectively analyzed. Peak VO2 and VE/VCO2 slope were measured for all patients. We evaluated their association with hemodynamic, echocardiographic and clinical markers of RV dysfunction as well mortality. Patients were stratified into those with a ventilatory class of III or greater. (VE/VCO2 slope of ≥ 36, n = 43) and those with a VE/VCO2 slope < 36 (n = 27). We compared the mortality between the 2 groups, as well as the hemodynamic, echocardiographic and clinical markers of RV dysfunction. 570 patients underwent CPET testing. 145 patients were ultimately referred to the advanced heart failure program and 70 patients later received LVAD implantation. Patients with VE/VCO2 slope of ≥ 36 had higher mortality (30.2% vs. 7.4%, p = 0.02) than patients with VE/VCO2 slope < 36 (n = 27). They also had a higher incidence of clinically important RVF (Acute severe 9.3% vs. 0%, Severe 32.6% vs 25.9%, p = 0.03). Patients with a VE/VCO2 slope ≥ 36 had a higher CVP than those with a lower VE/VCO2 slope (11.2 ± 6.1 vs. 6.0 ± 4.8 mmHg, p = 0.007), and were more likely to have a RA/PCWP ≥ 0.63 (65% vs. 19%, p = 0.008) and a PAPI ≤ 2 (57% vs. 13%, p = 0.008). In contrast, peak VO2 < 12 ml/kg/min was not associated with postoperative RV dysfunction or mortality. Elevated preoperative VE/VCO2 slope is a predictor of postoperative mortality, and is associated with postoperative clinical and hemodynamic markers of impaired RV performance.

Grinstein J; Sawalha Y; Medvedofsky DA; Ahmad S; Hofmeyer M; Rodrigo M; Kadakkal A; Barnett C; Kalantari S; Talati I; Zaghol R; Molina EJ; Sheikh FH; Najjar SS;

Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs [J Artif Organs] 2021 Apr 01. Date of Electronic Publication: 2021 Apr 01.

Preoperative cardiopulmonary exercise testing (CPET) is well validated for prognostication before advanced surgical heart failure therapies, but its role in prognostication after LVAD surgery has never been studied. VE/VCO2 slope is an important component of CPET which has direct pathophysiologic links to right ventricular (RV) performance. We hypothesized that VE/VCO ₂ slope would prognosticate RV dysfunction after LVAD.
All CPET studies from a single institution were collected between September 2009 and February 2019. Patients who ultimately underwent LVAD implantation were selectively analyzed. Peak VO2 and VE/VCO2 slope were measured for all patients. We evaluated their association with hemodynamic, echocardiographic and clinical markers of RV dysfunction as well mortality. Patients were stratified into those with a ventilatory class of III or greater. (VE/VCO2 slope of ≥ 36, n = 43) and those with a VE/VCO2 slope < 36 (n = 27). We compared the mortality between the 2 groups, as well as the hemodynamic, echocardiographic and clinical markers of RV dysfunction. 570 patients underwent CPET testing. 145 patients were ultimately referred to the advanced heart failure program and 70 patients later received LVAD implantation. Patients with VE/VCO2 slope of ≥ 36 had higher mortality (30.2% vs. 7.4%, p = 0.02) than patients with VE/VCO2 slope < 36 (n = 27). They also had a higher incidence of clinically important RVF (Acute severe 9.3% vs. 0%, Severe 32.6% vs 25.9%, p = 0.03). Patients with a VE/VCO2 slope ≥ 36 had a higher CVP than those with a lower VE/VCO2 slope (11.2 ± 6.1 vs. 6.0 ± 4.8 mmHg, p = 0.007), and were more likely to have a RA/PCWP ≥ 0.63 (65% vs. 19%, p = 0.008) and a PAPI ≤ 2 (57% vs. 13%, p = 0.008). In contrast, peak VO2 < 12 ml/kg/min was not associated with postoperative RV dysfunction or mortality.
Elevated preoperative VE/VCO2 slope is a predictor of postoperative mortality, and is associated with postoperative clinical and hemodynamic markers of impaired RV performance.

Kobayashi Y; Christle JW; Contrepois K; Nishi T; Moneghetti K; Cauwenberghs N; Myers J; Kuznetsova T; Palaniappan L; Haddad F;

The American journal of cardiology [Am J Cardiol] 2021 Mar 20. Date of Electronic Publication: 2021 Mar 20.

Patients with diabetes mellitus (DM) frequently present reduced exercise capacity. We aimed to explore the extent to which peripheral extraction relates to exercise capacity in asymptomatic patients with DM. We prospectively enrolled 98 asymptomatic patients with type-2 DM (mean age of 59±11 years and 56% male sex), and compared with 31 age, sex and body mass index (BMI)-matched normoglycemic controls. Cardiopulmonary exercise testing (CPX) with resting echocardiography was performed. Exercise response was assessed using peak oxygen uptake (peak VO ₂ ) and ventilatory efficiency was measured using the slope of the relationship between minute ventilation and carbon dioxide production (VE/VCO ₂ ). Peripheral extraction was calculated as the ratio of VO ₂ to cardiac output. Cardiac function was evaluated using left ventricular longitudinal strain (LVLS), E/e’, and relative wall thickness (RWT). Among patients with DM, 26 patients (27%) presented reduced percent-predicted-peak VO ₂ (<80%) and 18 (18%) presented abnormal VE/VCO ₂ slope (>34). There was no significant difference in peak cardiac output; peripheral extraction was lower in patients with DM compared to controls. Higher peak E/e’ (beta=-0.24, p=0.004) was associated with lower peak VO ₂ along with age, sex and BMI (R ² =0.53). A network correlation map revealed the connectivity of peak VO ₂ as a central feature and cluster analysis found LVLS, E/e’, RWT and peak VO ₂ in different clusters.
In conclusion, impaired peripheral extraction may contribute to reduced peak VO ₂ in asymptomatic patients with DM. Furthermore, cluster analysis suggests that CPX and echocardiography may be complementary for defining subclinical heart failure in patients with DM.

Baratto C; Caravita S; Faini A; Perego GB; Senni M;Badano LP; Parati G;

Journal of applied physiology (Bethesda, Md. : 1985) [J Appl Physiol (1985)] 2021 Mar 25. Date of Electronic Publication: 2021 Mar 25.

Background: Survivors from COVID-19 pneumonia can present with persisting multisystem involvement (lung, pulmonary vessels, heart, muscle, red blood cells) that may negatively affect exercise capacity.
Methods: We sought to determine the extent and the determinants of exercise limitation in COVID-19 patients at the time of hospital discharge.
Results: Eighteen consecutive patients with COVID-19 and 1:1 age-, sex-, and body mass index- matched controls underwent: spirometry, echocardiography, cardiopulmonary exercise test and exercise echocardiography for the study of pulmonary circulation. Arterial blood was sampled at rest and during exercise in COVID-19 patients. COVID-19 patients lie roughly on the same oxygen consumption isophlets than controls both at rest and during submaximal exercise, thanks to supernormal cardiac output (p<0.05). Oxygen consumption at peak exercise was reduced by 30% in COVID-19 (p<0.001), due to a peripheral extraction limit. Additionally, within COVID-19 patients, hemoglobin content was associated with peak oxygen consumption (R ² =0.46, p=0.002)Respiratory reserve was not exhausted (median [IRQ], 0.59 [0.15]) in spite of moderate reduction of forced vital capacity (79±40%)Pulmonary artery pressure increase during exercise was not different between patients and controls. Ventilatory equivalents for carbon dioxide were higher in COVID-19 patients than in controls (39.5 [8.5] vs 29.5 [8.8], p<0.001), and such an increase was mainly explained by increased chemosensitivity.
Conclusions: When recovering from COVID-19, patients present with reduced exercise capacity and augmented exercise hyperventilation. Peripheral factors, including anemia and reduced oxygen extraction by peripheral muscles were the major determinants of deranged exercise physiology. Pulmonary vascular function seemed unaffected, despite restrictive lung changes.

Winkert K; Kirsten J; Kamnig R; Steinacker JM; Treff G

International journal of sports physiology and performance [Int J Sports Physiol Perform] 2021 Mar 26, pp. 1-6. Date of Electronic Publication: 2021 Mar 26.

Purpose: Automated metabolic analyzers are frequently utilized to measure maximal oxygen consumption (V˙O2max). However, in portable devices, the results may be influenced by the analyzer’s technological approach, being either breath-by-breath (BBB) or dynamic micro mixing chamber mode (DMC). The portable metabolic analyzer K5 (COSMED, Rome, Italy) provides both technologies within one device, and the authors aimed to evaluate differences in V˙O2max between modes in endurance athletes.
Methods: Sixteen trained male participants performed an incremental test to voluntary exhaustion on a cycle ergometer, while ventilation and gas exchange were measured by 2 structurally identical COSMED K5 metabolic analyzers synchronously, one operating in BBB and the other in DMC mode. Except for the flow signal, which was measured by 1 sensor and transmitted to both devices, the devices operated independently. V˙O2max was defined as the highest 30-second average.
Results: V˙O2max and V˙CO2@V˙O2max were significantly lower in BBB compared with DMC mode (-4.44% and -2.71%), with effect sizes being large to moderate (ES, Cohen d = 0.82 and 1.87). Small differences were obtained for respiratory frequency (0.94%, ES = 0.36), minute ventilation (0.29%, ES = 0.20), and respiratory exchange ratio (1.74%, ES = 0.57).
Conclusion: V˙O2max was substantially lower in BBB than in DMC mode. Considering previous studies that also indicated lower V˙O2 values in BBB at high intensities and a superior validity of the K5 in DMC mode, the authors conclude that the DMC mode should be selected to measure V˙O2max in athletes.

Lammi MR; Ghonim MA; Johnson J; D’Aquin J; Zamjahn JB; Pellett A; Okpechi SC; Romaine C; Pyakurel K; Luu HH; Shellito JE; Boulares AH; deBoisblanc BP;

Respiratory medicine [Respir Med] 2021 Mar 08; Vol. 180, pp. 106354. Date of Electronic Publication: 2021 Mar 08.

Background and Objective: We tested whether the prostacyclin analog inhaled iloprost modulates dead space, dynamic hyperinflation (DH), and systemic inflammation/oxidative stress during maximal exercise in subjects with chronic obstructive pulmonary disease (COPD) who were not selected based on pulmonary hypertension (PH).
Methods: Twenty-four COPD patients with moderate-severe obstruction (age 59 ± 7 years, FEV ₁ 53 ± 13% predicted) participated in a randomized, double-blind, placebo-controlled crossover trial. Each subject received a single nebulized dose of 5.0 μg iloprost or placebo on non-consecutive days followed by maximal cardiopulmonary exercise tests. The primary outcome was DH quantified by end-expiratory lung volume/total lung capacity ratio (EELV/TLC) at metabolic isotime.
Results: Inhaled iloprost was well-tolerated and reduced submaximal alveolar dead-space fraction but did not significantly reduce DH (0.70 ± 0.09 vs 0.69 ± 0.07 following placebo and iloprost, respectively, p = 0.38). Maximal exercise time (9.1 ± 2.3 vs 9.3 ± 2.2 min, p = 0.31) and peak oxygen uptake (17.4 ± 6.3 vs 17.9 ± 6.9 mL/kg/min, p = 0.30) were not significantly different following placebo versus iloprost.
Conclusions: A single dose of inhaled iloprost was safe and reduced alveolar dead space fraction; however, it was not efficacious in modulating DH or improving exercise capacity in COPD patients who were not selected for the presence of PH.

Dun Y; Olson TP; Li C; Qiu L; Fu S; Cao Z; Ripley-Gonzalez JW; You B; Li Q; Deng L; Li Q; Liu S;

International journal of cardiology [Int J Cardiol] 2021 Mar 12. Date of Electronic Publication: 2021 Mar 12.

Background: Reference values of cardiopulmonary exercise testing (CPX) vary with race/ethnicity. Chinese Americans are the fastest-growing racial/ethnic group in the United States. However, there is limited information about the reference values of cardiopulmonary exercise testing (CPX) variables in the Chinese population.
Methods: As part of the Xiangya Hospital Exercise Testing project (the X-ET project), this cross-sectional study screened 20,696 consecutive CPXs performed by 17,802 unique individuals at Xiangya Hospital of Central South University, China, from January 1, 2002, to December 31, 2019. A total of 964 unique healthy adults/tests (42% female) aged 49 ± 12 who completed a maximal ramp incremental CPX with cycle ergometry were included in this study. The reference values of primary CPX variables were expressed as the lower limit or upper limit of normal. Stepwise linear regression was used to fit the equations of key CPX variables. Predictive accuracy analysis for the equations with a comparison between present and previous studies were performed.
Results: Peak oxygen consumption (V̇O ₂ ), carbon dioxide production, ventilation/min, work rate, and V̇O ₂ at the anaerobic threshold were regressed on age, height, weight, and sex. These predictive equations showed good in- and out-sample predictive accuracy. Comparison with prior research revealed that prediction equations of peak V̇O ₂ resultant from studies in which populations were entirely or primarily Caucasian had overestimated our subjects’ actual values.
Conclusion: The reference values and predicted equations of CPX variables in this study may provide a more appropriate framework to interpret the response to maximal ramp incremental cycle ergometry in the Chinese adult population.

Schindel CS; Schiwe D; Heinzmann-Filho JP; Campos NE; Pitrez PM; Donadio MVF;

World journal of pediatrics : WJP [World J Pediatr] 2021 Mar 17. Date of Electronic Publication: 2021 Mar 17.

Background: Lower exercise tolerance is an important component of asthma and the possible effects of non-invasive ventilation on exercise capacity in individuals with severe therapy-resistant asthma (STRA) are unknown. This study aimed to evaluate the immediate effect of continuous positive airway pressure (CPAP) on exercise tolerance in children with STRA.
Methods: We performed a controlled, randomized, crossover clinical trial including subjects aged 6 to 18 years old diagnosed with STRA. Clinical, anthropometric and lung function data were collected. The participants in the intervention group (IG) used CPAP (PEEP 10cmH ₂ O and FiO ₂ 0.21) for a period of 40 min. Subjects in the control group (CG) used CPAP with minimum PEEP at 1 cmH ₂ 0 also for 40 min. Afterwards, subjects from both groups underwent cardiopulmonary exercise testing (CPET). After a 15-day washout period, on a subsequent visit, subjects participated in the opposite group to the initial one.
Results: Thirteen subjects with a mean age of 12.30 ± 1.7 years were included. The variables of peak expiratory flow (PEF) and forced expiratory volume in the first second (FEV ₁ ) before using CPAP and after performing CPET did not show significant differences. Regarding CPET results, there was no significant difference (P = 0.59) between groups at peak exercise for oxygen consumption-VO ₂ (CG: 33.4 ± 6.3 and IG: 34.5 ± 5.9, mL kg ^-1  min ^-1 ). However, the IG (12.4 ± 2.1) presented a total test time (min) significantly (P = 0.01) longer than the CG (11.5 ± 1.3).
Conclusion: The results suggest that the use of CPAP before physical exercise increases exercise duration in children and adolescents with STRA.

Debeaumont D; Boujibar F; Ferrand-Devouge E; Artaud-Macari E; Tamion F; Gravier FE; Smondack A; Cuvelier A; Muir JF; Alexandre K; Bonnevie T;

Physical therapy [Phys Ther] 2021 Mar 18. Date of Electronic Publication: 2021 Mar 18.

Objective: The aim of this pilot study was to assess physical fitness and its relationship with functional dyspnea in survivors of Covid-19, 6 months after their discharge from the hospital.
Methods: Data collected routinely from people referred for cardiopulmonary exercise testing (CPET) following hospitalization for Covid-19 were retrospectively analyzed. Persistent dyspnea was assessed using the modified Medical Research Council dyspnea (mMRC) scale.
Results: Twenty-three people with persistent symptoms were referred for CPET. Mean mMRC dyspnea score was 1 (SD = 1) and was significantly associated with VO2peak (%) (rho = -0.49). At 6 months, those hospitalized in the general ward had a slightly reduced VO2peak (87% [SD = 20]), whereas those who had been in the intensive care unit (ICU) had a moderately reduced VO2peak (77% [SD = 15]). Of note, the results of the CPET revealed that, in all patients, respiratory equivalents were high, power-to-weight ratios were low, and those who had been in the ICU had a relatively low ventilatory efficiency (mean VE/VCO2 slope = 34 [SD = 5]). Analysis of each individual showed that none had a breathing reserve <15% or 11 L/min, all had a normal exercise electrocardiogram, and 4 had a heart rate above 90%.
Conclusion: At 6 months, persistent dyspnea was associated with reduced physical fitness. This study offers initial insights into the mid-term physical fitness of people who required hospitalization for Covid-19. It also provides novel pathophysiological clues about the underlaying mechanism of the physical limitations associated with persistent dyspnea. Those with persistent dyspnea should be offered a tailored rehabilitation intervention, which should probably include muscle reconditioning, breathing retraining, and perhaps respiratory muscle training.
Impact: This study is the first to show that a persistent breathing disorder (in addition to muscle deconditioning) can explain persistent symptoms 6 months after hospitalization for Covid-19 infection and suggests that a specific rehabilitation intervention is warranted.