Category Archives: Publications

Rest and exercise oxygen uptake and cardiac output changes 6 months after successful transcatheter mitral valve repair.

Vignati C; De Martino F; Muratori M; Salvioni E; Tamborini G; Bartorelli A; Pepi M; Alamanni F; Farina S;
Cattadori G;Mantegazza V; Agostoni P;

ESC heart failure [ESC Heart Fail] 2021 Sep 22. Date of Electronic Publication: 2021 Sep 22.

Aims: Changes in peak exercise oxygen uptake (VO 2 ) and cardiac output (CO) 6 months after successful percutaneous edge-to-edge mitral valve repair (pMVR) in severe primary (PMR) and functional mitral regurgitation (FMR) patients are unknown. The aim of the study was to assess the efficacy of pMVR at rest by echocardiography, VO 2 and CO (inert gas rebreathing) measurement and during cardiopulmonary exercise test with CO measurement.
Methods and Results: We evaluated 145 and 115 patients at rest and 98 and 66 during exercise before and after pMVR, respectively. After successful pMVR, significant reductions in MR and NYHA class were observed in FMR and PMR patients. Cardiac ultrasound showed reverse remodelling (left ventricular end-diastolic volume from 158 ± 63 mL to 147 ± 64, P < 0.001; ejection fraction from 51 ± 15 to 48 ± 14, P < 0.001; pulmonary artery systolic pressure (PASP) from 43 ± 13 to 38 ± 8 mmHg, P < 0.001) in the entire population. These changes were significant in PMR (n = 62) and a trend in FMR (n = 53), except for PASP, which decreased in both groups. At rest, CO and stroke volume (SV) increased in FMR with a concomitant reduction in arteriovenous O 2 content difference [ΔC(a-v)O 2 ]. Peak exercise, CO and SV increased significantly in both groups (CO from 5.5 ± 1.4 L/min to 6.3 ± 1.5 and from 6.2 ± 2.4 to 6.7 ± 2.0, SV from 57 ± 19 mL to 66 ± 20 and from 62 ± 20 to 69 ± 20, in FMR and PMR, respectively), whereas peak VO 2 was unchanged and ΔC(a-v)O 2 decreased.
Conclusions: These data confirm pMVR-induced clinical improvement and reverse ventricular remodelling at a 6-month analysis and show, in spite of an increase in CO, an unchanged exercise performance, which is achieved through a ‘more physiological’ blood flow distribution and O 2 extraction behaviour. Direct rest and exercise CO should be measured to assess pMVR efficacy.

Sub-maximal aerobic exercise training reduces hematocrit and ameliorates symptoms in Andean highlanders with Chronic Mountain Sickness.

Macarlupú JL; Vizcardo-Galindo G; Figueroa-Mujíca R; Voituron N; Richalet JP; Villafuerte FC;

Experimental physiology [Exp Physiol] 2021 Sep 23. Date of Electronic Publication: 2021 Sep 23.

New Findings: What is the central question of this study? What is the effect of sub-maximal aerobic exercise training on signs and symptoms of chronic mountain sickness (CMS) in Andean highlanders? What is the main finding and its importance? Aerobic exercise training effectively reduces hematocrit, ameliorates symptoms, and improves aerobic capacity in CMS patients, suggesting that a regular aerobic exercise training program might be used as a low-cost non-invasive/non-pharmacological management strategy of this syndrome.
Abstract: Excessive erythrocytosis (EE) is the hallmark sign of Chronic Mountain Sickness (CMS), a debilitating syndrome associated with neurological symptoms and increased cardiovascular risk. We have shown that unlike sedentary residents at the same altitude, trained individuals maintain hematocrit within sea-level range, and thus we hypothesize that aerobic exercise training (ET) might reduce excessive hematocrit and ameliorate CMS signs and symptoms. Eight highlander men (38 ± 12y) with CMS (hematocrit: 70.6 ± 1.9%, CMS score: 8.8 ± 1.4) from Cerro de Pasco-Peru (4340m) participated in the study. Baseline assessment included hematocrit, CMS score, pulse oximetry, maximal cardiopulmonary exercise testing, and in-office plus 24h ambulatory blood pressure (BP) monitoring. Blood samples were collected to assess erythropoietic, hemolysis, and cardiometabolic markers. ET consisted of pedaling exercise in a cycloergometer at 60% of VO 2peak for 1h/day, 4 days/week for 8 weeks, and participants were assessed at weeks 4 and 8. Hematocrit and CMS score decreased significantly by week 8 (to 65.6 ± 6.6%, and 3.5 ± 0.8, respectively, p<0.05), while VO 2peak and maximum workload increased with ET (33.8 ± 2.4 vs. 37.2 ± 2.0ml/min/kg, p<0.05; and 172.5 ± 9.4 vs 210.0 ± 27.8W, p<0.01; respectively). Except for an increase in HDL-C, other blood markers and BP showed no differences. Our results suggest that reduction of hematocrit and CMS symptoms result mainly from hemodilution due to plasma volume expansion rather than to hemolysis. In conclusion, we show that ET can effectively reduce hematocrit, ameliorate symptoms, and improve aerobic capacity in CMS patients, suggesting that regular aerobic exercise might be used as a low-cost non-invasive/non-pharmacological management strategy.

Is the modified shuttle test a maximal effort test in children and adolescents with asthma?

Reimberg MM; Ritti-Dias R; Selman JP; Scalco RS; Wandalsen GF; Solé D; Hulzebos HJ; Takken T; Corso SD;
Lanza FC;

Pediatric pulmonology [Pediatr Pulmonol] 2021 Sep 27. Date of Electronic Publication: 2021 Sep 27.

Purpose: Whether modified shuttle teste (MST) achieves maximal effort in children and adolescents with asthma is unclear. The aim was to compare the physiological responses of MST to the cardiopulmonary exercise test (CPET) in pediatric patients with asthma, to observe its convergent validity.
Patients and Methods: cross sectional study, volunteers with asthma (6 to 17 years of age) under regular treatment. The MST is an external-paced test, and the participants were allowed to walk/run. CPET was performed on a cycle ergometer to compare with MST. Gas exchange (VO 2 , VCO 2 , and VE) and heart rate (HR) were the outcomes, and continuously assessed in both tests.
Results: 47 volunteers were included, normal lung function FEV1/FVC 88.6 (7.7). VO 2peak was higher at MST (2.0 ± 0.6 L/min) compared to CPET (1.6 ± 0.5 L/min), p< 0.001. Similar to VE at MST (50 ± 16 L/min) vs at CPET (40 ± 13 L/min), and VCO 2 , at MST (2.1 ± 0.8 L/min) vs CPET (1.7 ± 0.6 L/min), p < 0.001. HR was also higher at MST (94 ± 6%pred) vs CPET (87 ± 8%pred), p=0.002. VO 2peak in MST correlated to the CPET (r = 0.78, p < 0.001). The ICC of VO 2peak between tests was 0.73 (0.06 – 0.89), p<0.001, and VO2peak Bland-Altman analysis showed bias of 0.46L/min.
Conclusion: the MST showed maximal physiologic response in children and adolescents with asthma. It is valid test, and can be used as an alternative to evaluate exercise capacity.

Does Becoming Fit Mean Feeling (f)it? A Comparison of Physiological and Experiential Fitness Data From the iReAct Study.

Gropper H; Mattioni Maturana F; Nieß AM; Thiel A;

Frontiers in sports and active living [Front Sports Act Living] 2021 Sep 01; Vol. 3, pp. 729090.
Date of Electronic Publication: 2021 Sep 01 (Print Publication: 2021).

Regular exercise fosters fitness-enhancing benefits. We assume that exercise interventions become successful and sustainable if physiological benefits of exercise are also subjectively perceivable. The goal of this study was to examine how young inactive adults physiologically respond to an exercise intervention and how those responses are subjectively experienced . Furthermore, we aimed to assess whether the sequence of two distinct endurance-based exercise modes has an impact on physiological and subjectively experienced physical fitness. Thirty-one young inactive adults were assessed for this substudy of the larger iReAct study. Participants were randomly assigned to a high-intensity interval training (HIIT) or a moderate-intensity continuous training (MICT) group for 6 weeks and subsequently switched groups for a second training period. Physiological fitness data was collected at baseline, follow-up I, and follow-up II using a graded cardiopulmonary exercise test. Subjectively reconstructed (i.e., retrospective constructions) experiences relating to physical fitness were assessed at follow-up II using a biographical mapping method. A repeated-measures one-way ANOVA on each training group was performed to see whether physiological and subjectively experienced fitness differed across training periods. The rate of change between all variables was calculated for the first and the second training period in order to compare the agreement between physiological and subjective fitness improvements. Participants increased their fitness across the intervention period both physiologically and subjectively. However, the rate of change depended on the sequence of the two training modes. While VO 2max increased significantly in both training periods in the MICT-HIIT sequence, a significant increase in VO 2max in the HIIT-MICT sequence was only observed in the HIIT period. Participants similarly perceived those increases subjectively in their exercise-related physical fitness, although they experienced a significant decrease in the second period of the HIIT-MICT sequence. For subjectively perceived physical fitness relating to everyday activities, significant increases were only observed for the first period of the MICT-HIIT sequence. Young inactive adults can improve both their physiological and their subjectively perceived fitness through regular exercise. However, exercise modes and their sequence can make a substantial difference regarding measured and perceived physical fitness. Additionally, despite a favorable tendency toward HIIT over MICT, inter- and intra-individual variability, particularly in the subjective experiences of fitness, reiterates the necessity of individualized approaches to exercise.

Exploring the Anthropometric, Cardiorespiratory, and Haematological Determinants of Marathon Performance.

Christou GA; Pagourelias ED; Deligiannis AP; Kouidi EJ;

Frontiers in physiology [Front Physiol] 2021 Sep 03; Vol. 12, pp. 693733.
Date of Electronic Publication: 2021 Sep 03 (Print Publication: 2021).

Aim: We aimed to investigate the main anthropometric, cardiorespiratory and haematological factors that can determine marathon race performance in marathon runners.
Methods: Forty-five marathon runners (36 males, age: 42 ± 10 years) were examined during the training period for a marathon race. Assessment of training characteristics, anthropometric measurements, including height, body weight ( n = 45) and body fat percentage (BF%) ( n = 33), echocardiographic study ( n = 45), cardiopulmonary exercise testing using treadmill ergometer ( n = 33) and blood test ( n = 24) were performed. We evaluated the relationships of these measurements with the personal best marathon race time (MRT) within a time frame of one year before or after the evaluation of each athlete.
Results: The training age regarding long-distance running was 9 ± 7 years. Training volume was 70 (50-175) km/week. MRT was 4:02:53 ± 00:50:20 h. The MRT was positively associated with BF% ( r = 0.587, p = 0.001). Among echocardiographic parameters, MRT correlated negatively with right ventricular end-diastolic area (RVEDA) ( r = -0.716, p < 0.001). RVEDA was the only independent echocardiographic predictor of MRT. With regard to respiratory parameters, MRT correlated negatively with maximum minute ventilation indexed to body surface area (VEmax/BSA) ( r = -0.509, p = 0.003). Among parameters of blood test, MRT correlated negatively with haemoglobin concentration ( r = -0.471, p = 0.027) and estimated haemoglobin mass (Hbmass) ( r = -0.680, p = 0.002). After performing multivariate linear regression analysis with MRT as dependent variable and BF% (standardised β = 0.501, p = 0.021), RVEDA (standardised β = -0.633, p = 0.003), VEmax/BSA (standardised β = 0.266, p = 0.303) and Hbmass (standardised β = -0.308, p = 0.066) as independent variables, only BF% and RVEDA were significant independent predictors of MRT (adjusted R 2 = 0.796, p < 0.001 for the model).
Conclusions: The main physiological determinants of better marathon performance appear to be low BF% and RV enlargement. Upregulation of both maximum minute ventilation during exercise and haemoglobin mass may have a weaker effect to enhance marathon performance.

Minute ventilation/carbon dioxide production in congenital heart disease.

Hager A;

European respiratory review : an official journal of the European Respiratory Society [Eur Respir Rev] 2021 Sep 15; Vol. 30 (161). Date of Electronic Publication: 2021 Sep 15 (Print Publication: 2021).

This review summarises various applications of how ventilatory equivalent (ventilatory efficiency or better still ventilatory inefficiency) and the minute ventilation ( VE )/carbon dioxide production ( VCO 2 ) slope obtained from cardiopulmonary exercise testing (CPET) can be used in the diagnostic or prognostic workup of patients with congenital heart disease.The field of congenital heart disease comprises not only a very heterogeneous patient group with various heart diseases, but also various conditions in different stages of repair, as well as the different residuals seen in long-term follow-up. As such, various physiologic disarrangements must be considered in the analysis of increased VE / VCO 2 slope from CPET in patients with congenital heart disease. In addition to congestive heart failure (CHF), cyanosis, unilateral pulmonary stenosis and pulmonary hypertension (PH) provide the background for this finding. The predictive value of increased VE / VCO 2 slope on prognosis seems to be more important in conditions where circulatory failure is associated with failure of the systemic ventricle. In cyanotic patients, those with Fontan circulation, or those with substantial mortality from arrhythmia, the impact of VE / VCO 2 on prognosis is not that important.

Cardiopulmonary Exercise Test in the Detection of Unexplained Post-COVID-19 Dyspnea.

Djokovic D; Nikolic M; Muric N; Nedeljkovic I;Simovic S; Novkovic L; Cupurdija V; Savovic Z; Vuckovic-Filipovic J; Susa R; Cekerevac I;

International heart journal [Int Heart J] 2021 Sep 17. Date of Electronic Publication: 2021 Sep 17.

There is emerging evidence of prolonged recovery in survivors of coronavirus disease 2019 (COVID-19), even in those with mild COVID-19. In this paper, we report a case of a 39-year-old male with excessive body weight and a history of borderline values of arterial hypertension without therapy, who was mainly complaining of progressive dyspnea after being diagnosed with mild COVID-19. According to the recent guidelines on the holistic assessment and management of patients who had COVID-19, all preferred diagnostic procedures, including multidetector computed tomography (CT), CT pulmonary angiogram, and echocardiography, should be conducted. However, in our patient, no underlying cardiopulmonary disorder has been established. Therefore, considering all additional symptoms our patient had beyond dyspnea, our initial differential diagnosis included anxiety-related dysfunctional breathing. However, psychiatric evaluation revealed that our patient had only a mild anxiety level, which was unlikely to provoke somatic complaints. We decided to perform further investigations considering that cardiopulmonary exercise test (CPET) represents a reliable diagnostic tool for patients with unexplained dyspnea. Finally, the CPET elucidated the diastolic dysfunction of the left ventricle, which was the most probable cause of progressive dyspnea in our patient. We suggested that, based on uncontrolled cardiovascular risk factors our patient had, COVID-19 triggered a subclinical form of heart failure (HF) with preserved ejection fraction (HFpEF) to become clinically manifest. Recently, the new onset, exacerbation, or transition from subclinical to clinical HFpEF has been associated with COVID-19. Therefore, in addition to the present literature, our case should warn physicians on HFpEF among survivors of COVID-19.

Minute ventilation/carbon dioxide production in congenital heart disease

Hager A;

Eur Respir Rev 2021; 30: 200178 [DOI: 10.1183/16000617.0178-2020].

This review summarises various applications of how ventilatory equivalent (ventilatory efficiency or better
still ventilatory inefficiency) and the minute ventilation (VʹE)/carbon dioxide production (VʹCO2) slope
obtained from cardiopulmonary exercise testing (CPET) can be used in the diagnostic or prognostic
workup of patients with congenital heart disease.
The field of congenital heart disease comprises not only a very heterogeneous patient group with various
heart diseases, but also various conditions in different stages of repair, as well as the different residuals
seen in long-term follow-up. As such, various physiologic disarrangements must be considered in the
analysis of increased VʹE/VʹCO2 slope from CPET in patients with congenital heart disease. In addition to
congestive heart failure (CHF), cyanosis, unilateral pulmonary stenosis and pulmonary hypertension (PH)
provide the background for this finding. The predictive value of increased VʹE/VʹCO2 slope on prognosis
seems to be more important in conditions where circulatory failure is associated with failure of the
systemic ventricle. In cyanotic patients, those with Fontan circulation, or those with substantial mortality
from arrhythmia, the impact of VʹE/VʹCO2 on prognosis is not that important.

Effects of the exercise training on skeletal muscle oxygen consumption in heart failure patients with reduced ejection fraction.

Guimarães GV; Ribeiro F; Castro RE; Roque JM; Machado ADT; Antunes-Correa LM; Ferreira SA; Bocchi EA;

International journal of cardiology [Int J Cardiol] 2021 Sep 07. Date of Electronic Publication: 2021 Sep 07.

Aims: Skeletal muscle dysfunction is a systemic consequence of heart failure (HF) that correlates with functional capacity. However, the impairment within the skeletal muscle is not well established. We investigated the effect of exercise training on peripheral muscular performance and oxygenation in HF patients.
Methods and Results: HF patients with ejection fraction ≤40% were randomized 2:1 to exercise training or control for 12 weeks. Muscle tissue oxygen was measured noninvasively by near-infrared spectroscopy (NIRS) during rest and a symptom-limited cardiopulmonary exercise test (CPET) before and after intervention. Measurements included skeletal muscle oxygenated hemoglobin concentration, deoxygenated hemoglobin concentration, total hemoglobin concentration, VO 2 peak, VE/VCO 2 slope, and heart rate. Muscle sympathetic nerve activity by microneurography, and muscle blood flow by plethysmography were also assessed at rest pre and post 12 weeks. Twenty-four participants (47.5 ± 7.4 years, 58% men, 75% no ischemic) were allocated to exercise training (ET, n = 16) or control (CG, n = 8). At baseline, no differences between groups were found. Exercise improved VO 2 peak, slope VE/VCO 2 , and heart rate. After the intervention, significant improvements at rest were seen in the ET group in muscle sympathetic nerve activity and muscle blood flow. Concomitantly, a significant decreased in Oxy-Hb (from 29.4 ± 20.4 to 15.7 ± 9.0 μmol, p = 0.01), Deoxi-Hb (from 16.3 ± 8.2 to 12.2 ± 6.0 μmol, p = 0.003) and HbT (from 45.7 ± 27.6 to 27.7 ± 13.4 μmol, p = 0.008) was detected at peak exercise after training. No changes were observed in the control group.
Conclusion: Exercise training improves skeletal muscle function and functional capacity in HF patients with reduced ejection fraction. This improvement was associated with increased oxygenation of the peripheral muscles, increased muscle blood flow, and decreased sympathetic nerve activity.

Cardiorespiratory Abnormalities in Patients Recovering from COVID-19.

Szekely Y; Lichter Y; Sadon S; Lupu L; Taieb P; Banai A; Sapir O; Granot Y; Hochstadt A;Friedman S; Laufer-Perl M; Banai S; Topilsky Y;

Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography [J Am Soc Echocardiogr] 2021 Sep 08. Date of Electronic Publication: 2021 Sep 08.

Background: Large number of patients around the world are recovering from COVID-19; many of them report persistence of symptoms.
Objectives: We sought to test pulmonary, cardiovascular and peripheral responses to exercise in patients recovering from COVID-19.
Methods: We prospectively evaluated patients who recovered from COVID-19 using a combined anatomic/functional assessment. All patients underwent clinical examination, laboratory tests, and a combined stress echocardiography and cardiopulmonary exercise test. We measured left ventricular volumes, ejection fraction, stroke volume, heart rate, E/e’ ratio, right ventricular function, VO 2 , lung volumes, Ventilatory efficiency, O 2 saturation and muscle O 2 extraction in all effort stages and compared them to historical controls.
Results: A total of 71 patients were assessed 90.6±26 days after onset of COVID-19 symptoms. Only 23 (33%) were asymptomatic. The most common symptoms were fatigue (34%), muscle weakness/pain (27%) and dyspnea (22%). VO 2 was lower among post-COVID-19 patients compared to controls (p=0.03, group by time interaction p=0.007). Reduction in peak VO 2 was due to a combination of chronotropic incompetence (75% of post-COVID-19 patients vs. 8% of controls, p<0.0001) and insufficient increase in stroke volume during exercise (p=0.0007, group by time interaction p=0.03). Stroke volume limitation was mostly explained by diminished increase in left ventricular end-diastolic volume (p=0.1, group by time interaction p=0.03) and insufficient increase in ejection fraction (p=0.01, group by time interaction p=0.01). Post-COVID-19 patients had higher peripheral O 2 extraction (p=0.004) and did not have significantly different respiratory and gas exchange parameters compared to controls.
Conclusions: Patients recovering from COVID-19 have symptoms associated with objective reduction in peak VO 2 . The mechanism of this reduction is complex and mainly involves a combination of attenuated heart rate and stroke volume reserve.