Peterman JE; Whaley MH; Harber MP; Fleenor BS; Imboden MT; Myers J; Arena R; Kaminsky LA;

European journal of preventive cardiology [Eur J Prev Cardiol] 2021 Apr 10; Vol. 28 (2), pp. 142-148.

Aims: A recent scientific statement suggests clinicians should routinely assess cardiorespiratory fitness using at least non-exercise prediction equations. However, no study has comprehensively compared the many non-exercise cardiorespiratory fitness prediction equations to directly-measured cardiorespiratory fitness using data from a single cohort. Our purpose was to compare the accuracy of non-exercise prediction equations to directly-measured cardiorespiratory fitness and evaluate their ability to classify an individual’s cardiorespiratory fitness.
Methods: The sample included 2529 tests from apparently healthy adults (42% female, aged 45.4 ± 13.1 years (mean±standard deviation). Estimated cardiorespiratory fitness from 28 distinct non-exercise prediction equations was compared with directly-measured cardiorespiratory fitness, determined from a cardiopulmonary exercise test. Analysis included the Benjamini-Hochberg procedure to compare estimated cardiorespiratory fitness with directly-measured cardiorespiratory fitness, Pearson product moment correlations, standard error of estimate values, and the percentage of participants correctly placed into three fitness categories.
Results: All of the estimated cardiorespiratory fitness values from the equations were correlated to directly measured cardiorespiratory fitness (p < 0.001) although the R2 values ranged from 0.25-0.70 and the estimated cardiorespiratory fitness values from 27 out of 28 equations were statistically different compared with directly-measured cardiorespiratory fitness. The range of standard error of estimate values was 4.1-6.2 ml·kg-1·min-1. On average, only 52% of participants were correctly classified into the three fitness categories when using estimated cardiorespiratory fitness.
Conclusion: Differences exist between non-exercise prediction equations, which influences the accuracy of estimated cardiorespiratory fitness. The present analysis can assist researchers and clinicians with choosing a non-exercise prediction equation appropriate for epidemiological or population research. However, the error and misclassification associated with estimated cardiorespiratory fitness suggests future research is needed on the clinical utility of estimated cardiorespiratory fitness.

Tanaka S; Miyamoto T; Mori Y; Harada T; Tasaki H;

Heart and vessels [Heart Vessels] 2021 Mar 30. Date of Electronic Publication: 2021 Mar 30.

This study aimed to examine the factors that contribute to improvement of exercise tolerance in patients with heart failure (HF) and atrial fibrillation (AF) following cardiac rehabilitation. Our hypothesis is that parasympathetic values are important for recovering exercise tolerance in those patients. We included 84 consecutive patients with HF and AF (mean age: 69 ± 15 years, 80% men). All of the patients underwent a cardiopulmonary exercise test and had pre and post 5 month cardiac rehabilitation assessed. After 155 ± 11 days and 44 ± 8 sessions, 73 patients (86%) showed an increase in peak oxygen uptake (VO ₂ ) and VO ₂ at the anaerobic threshold. In univariate linear regression analysis, the % change in heart rate recovery, plasma B-type natriuretic peptide levels, resting heart rate, and the minute ventilation /carbon dioxide output slope were significantly related to that of peak VO ₂ (p < 0.01, p = 0.03, p = 0.02, p < 0.01, respectively). Stepwise multivariate linear regression analysis showed that the % change in heart rate recovery was independently related to that of peak VO ₂ (p < 0.05). Our results suggest that heart rate recovery is closely associated with recovery of exercise tolerance in patients with HF and AF after CR.

Tooba R; Mayuga KA; Wilson R; Tonelli AR;

Annals of the American Thoracic Society [Ann Am Thorac Soc] 2021 Apr; Vol. 18 (4), pp. 573-581.

Dyspnea in low-preload states is an underrecognized but growing diagnosis in patients with unexplained dyspnea. Patients can often experience debilitating symptoms at rest and with exertion, as low measured preload often leads to decreased cardiac output and ultimately dyspnea. In the present article, we performed a review of the literature and a multidisciplinary evaluation to understand the pathophysiology, diagnosis, and treatment of dyspnea in low-preload states. We explored selected etiologies and suggested an algorithm to approach unexplained dyspnea. The mainstay of diagnosis remains as invasive cardiopulmonary exercise testing. We concluded with a variety of nonpharmacological and pharmacological therapies, highlighting that a multifactorial approach may lead to the best results.

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.