Astley C; Children and Adolescent Institute: University of Sao Paulo, Sao Paulo, Brazil.
Prado DMLD; Sieczkowska SM; Esteves GP; Suguita P; Fink T; Lindoso L; Matsuo O; Martins F; Bain V; Badue MF; Marques HH; Malluf A; Leal G; Silva CA; Roschel H; Gualano B;

Journal of applied physiology (Bethesda, Md. : 1985) [J Appl Physiol (1985)] 2023 Nov 02.
Date of Electronic Publication: 2023 Nov 02.

Purpose: This study aimed to describe cardiopulmonary fitness and endothelial function 6 months after hospital diagnosis in a sample mainly comprising immunocompromised patients with confirmed SARS-Cov-2 infection vs. controls.
Methods: Youth (n=30; 14; 60% females) with confirmed SARS-CoV-2 seen in a tertiary hospital of Sao Paulo, Brazil, were matched by propensity score based on BMI, age, sex and pre-existing diseases with a control group who had not been tested positive for SARS-CoV-2 (n=30; age: 15; 50% females). Cardiopulmonary fitness (by means of a cardiopulmonary exercise test: CPET) and brachial flow-mediated dilation (%b-FMD) were assessed 6 months after diagnosis.
Results: Patients were similar for pre-existing diseases, sex, age and body mass index (all p>.05). Compared with controls, COVID-19 patients showed reduced VAT and peak exercise time (all p>.01), and VE/MVV (p<0.1). Brachial endothelial function variables were all adjust for body surface area (BSA). COVID-19 patients had decreased %b-FMD (3.6 vs. 5.4; p=.03) mean and positive flow (p=.02 and p=.03, respectively) vs. controls. Adjusted linear regression models exploring associations between CPET variables, %b-FMD and the potential predictors post-COVID-19 syndrome, number of symptoms, hospitalization and COVID severity did not detect significant associations, except for total shear rate in hospitalization (Coefficient: -65.07 [95%CI -119.5;-10.5], p=0.02).
Conclusion: In a sample of mainly immunocompromised youth with COVID-19, we found impaired exercise performance and endothelial function. These findings reinforce the need for preventive measures against infection in this vulnerable population and suggest that proper monitoring and treatment for these patients are warranted.

Kosmidis D; AHEPA University Hospital,  Thessaloniki, Greece.
Arvanitaki A; Farmakis IT; Liakos A; Giannopoulos A; Ziakas A; First Giannakoulas G;

Heart (British Cardiac Society) [Heart] 2023 Nov 02.
Date of Electronic Publication: 2023 Nov 02.

Objective: In Fontan circulation, pulmonary arterial hypertension (PAH)-targeted therapies could improve the patients’ exercise capacity. This study aimed to investigate the effects of PAH agents on different exercise parameters in stable Fontan patients by synthesising evidence of randomised controlled trials (RCTs).
Methods: A systematic search of PubMed, Cochrane Central Register of Controlled Trials and Web of Science databases, as well as of ClinicalTrials.gov, was performed. Primary outcomes were specific cardiopulmonary exercise test parameters: peak oxygen uptake (peak VO ₂ ), peak heart rate (peak HR), the minute ventilation/produced carbon dioxide (VE/VCO ₂ ) slope and the oxygen uptake, both measured at the anaerobic threshold (VO ₂ @AT).
Results: Five RCTs were included in the analysis including 573 Fontan patients (mean age 21.2 years, 60% male). PAH-targeted therapies did not affect peak VO ₂ (mean difference (MD) 0.72, 95% CI -0.25 to 1.70) or peak HR (MD -0.67, 95% CI -3.81 to 2.47), but resulted in a small, significant improvement in VO ₂ @AT (standardised MD 0.24, 95% CI 0.02 to 0.47). VE/VCO ₂ slope at the anaerobic threshold was also reduced (MD -1.13, 95% CI -2.25 to -0.01).
Conclusions: Although PAH-targeted therapies did not affect exercise parameters at maximal effort, they induced slight improvements in indices of submaximal effort, measured at the anaerobic threshold. Pharmacological improvement of submaximal exercise seems to be a more suitable indicator of Fontan individuals’ exercise capacity. Larger RCTs, recruiting specific subpopulations and focusing also on the anaerobic threshold, are warranted to draw more robust conclusions.

Stavrou VT;  Faculty of Medicine, University of Thessaly, 41100 Larissa, Greece.
Karetsi E; Gourgoulianis KI;

Children (Basel, Switzerland) [Children (Basel)] 2023 Sep 27; Vol. 10 (10).
Date of Electronic Publication: 2023 Sep 27.

Background: The performance of young swimmers is the result of a multifactorial process that is influenced by anthropometric characteristics and biological maturation. The purpose of our study was to investigate the effect of stages of biological maturation and body surface area on cardiopulmonary fitness indicators in preadolescent female swimmers, for whom menstruation has not started.
Methods: Thirty female preadolescent swimmers (age 13.4 ± 1.0 years) participated in this study. We recorded anthropometric and morphological characteristics, stages of biological maturation, and pulmonary function parameters, and the swimmers underwent cardiopulmonary exercise testing.
Results: The cut-off was set for body surface area (BSA) at 1.6 m ² and for biological maturation stages at score 3. The BSA results showed differences in variabilities in maximal effort oxygen pulse ( p < 0.001), oxygen uptake ( p < 0.001), ventilation ( p = 0.041), tidal volume ( p < 0.001), and oxygen breath ( p < 0.001). Tanner stage score results showed differences in variabilities in maximal effort breath frequency ( p < 0.001), tidal volume ( p = 0.013), and oxygen breath ( p = 0.045). Biological maturation stages and BSA were correlated during maximal effort with oxygen breath ( p < 0.001; p < 0.001), oxygen uptake ( p = 0.002; p < 0.001), and oxygen pulse ( p < 0.001; p < 0.001).
Conclusions: In conclusion, the findings of our study showed that the girls who had a smaller body surface area and biological maturation stage presented lower values in maximal oxygen uptake and greater respiratory work.

Honceriu C; Faculty of Physical Education and Sports, ‘Alexandru-Ioan Cuza’ University, 700115 Iasi, Romania.
Roca M;Costache AD; Abălașei B; Popescu L; Puni AR; Maștaleru A; Oancea A; Drugescu A; ‘, Adam C; Mitu O; , Costache II; Leon MM; Roca IC; ‘Mocanu V;Mitu F;

Medicina (Kaunas, Lithuania) [Medicina (Kaunas)] 2023 Sep 27; Vol. 59 (10).
Date of Electronic Publication: 2023 Sep 27.

Background and Objectives : Cortisol is a valuable marker for assessing the body’s response to any form of stress. We conducted this study in order to evaluate the variations of salivary and serum cortisol levels in professional football players in relation to cardiopulmonary exercise testing (CPET) and their significance in potentially evaluating overtraining in athletes. Also, the question of whether salivary cortisol determination could fully substitute serum sampling was addressed.
Materials and Methods : A total of 19 male professional football players were evaluated by measuring serum cortisol levels at rest (T0) and immediately after a CPET (T1) and salivary cortisol levels at rest (T0), 10 min after a CPET (T2), and 30 min after a CPET (T3).
Results : T0 serum cortisol showed a statistically significant correlation with the oxygen uptake at the anaerobic threshold divided by the body weight (VO ₂ -AT/weight), as did the T2 salivary cortisol with the maximum oxygen uptake at the anaerobic threshold (VO ₂ -AT) and VO ₂ -AT/weight. T0 salivary cortisol was significantly correlated with the subjects’ height and the predicted O ₂ pulse.
Conclusions : While some correlations were discovered, they are insufficient to recommend cortisol as a routine biomarker in athletes’ evaluation. However, significant correlations were established between salivary and serum determinations, meaning that the non-invasive procedure could substitute venous blood sampling.

Garcia Brás P; Central Lisbon Hospital University Center, 1169-024 Lisbon, Portugal.
Gonçalves AV; Reis JF; Moreira RI; Pereira-da-Silva T; Rio P; Timóteo AT; Silva S; Soares RM; Ferreira R

Life (Basel, Switzerland) [Life (Basel)] 2023 Sep 29; Vol. 13 (10).
Date of Electronic Publication: 2023 Sep 29.

Background: Exercise testing is key in the risk stratification of patients with heart failure (HF). There are scarce data on its prognostic power in women. Our aim was to assess the predictive value of the heart transplantation (HTx) thresholds in HF in women and in men.
Methods: Prospective evaluation of HF patients who underwent cardiopulmonary exercise testing (CPET) from 2009 to 2018 for the composite endpoint of cardiovascular mortality and urgent HTx.
Results: A total of 458 patients underwent CPET, with a composite endpoint frequency of 10.5% in females vs. 16.0% in males in 36-month follow-up. Peak VO ₂ (pVO ₂ ), VE/VCO ₂ slope and percent of predicted pVO ₂ were independent discriminators of the composite endpoint, particularly in women. The International Society for Heart Lung Transplantation recommended values of pVO ₂ ≤ 12 mL/kg/min or ≤14 if the patient is intolerant to β-blockers, VE/VCO ₂ slope > 35, and percent of predicted pVO ₂ ≤ 50% showed a higher diagnostic effectiveness in women. Specific pVO ₂ , VE/VCO ₂ slope and percent of predicted pVO ₂ cut-offs in each sex group presented a higher prognostic power than the recommended thresholds.
Conclusion: Individualized sex-specific thresholds may improve patient selection for HTx. More evidence is needed to address sex differences in HF risk stratification.

Magrì D; ‘Sapienza’ Università degli Studi di Roma, Roma, Italy, Centro Cardiologico Monzino, IRCCS, Milano, Italy & others in Italy
Gallo G;  Piepoli M;Salvioni E; Mapelli M; Vignati C; Fiori E; Muthukkattil ML; Corrà U; Me Tra M; Paolillo S; Filardi PP; Maruotti A;Di Loro PA; Senni M; Lagioia R; Scrutinio D; Emdin M; Passino C; Parati G; Sinagra G; Correale M; Badagliacca R; Sciomer S; Di Lenarda A; Agostoni P;

European journal of preventive cardiology [Eur J Prev Cardiol] 2023 Oct 27.
Date of Electronic Publication: 2023 Oct 27.

Aims: Chronotropic incompetence (CI) is a strong predictor of outcome in heart failure with reduced ejection fraction (HFrEF), however no data on its clinical and prognostic impact in heart failure with mildly reduced ejection fraction (HFmrEF). Therefore, the study aims to investigate, in a large multicenter HFmrEF cohort, the prevalence of CI as well as its relationship with exercise capacity and its prognostic role over the cardiopulmonary exercise testing (CPET) parameters.
Methods: Within the Metabolic Exercise combined with Cardiac and Kidney Indexes (MECKI) database, we analyzed data of 864 HFmrEF out of 1164 stable outpatients who performed a maximal CPET at the cycle ergometer and who had no significant rhythm disorders or comorbidities. The primary study endpoint was cardiovascular (CV) death. All-cause death was also explored.
Results: CI prevalence differed depending on the method (peak heart rate, pHR% versus pHR reserve, pHRR%) and the cut-off adopted (pHR% from ≤75% to ≤60% and pHRR%≤65% to ≤50%), ranging from 11% to 62%. A total of 84 (9.7%) CV deaths were collected, with 39 (4.5%) occurring within 5 year. At multivariate analysis, both pHR% [Hazard Ratio 0.97(0.95-0.99), p < 0.05] and pHRR% [Hazard Ratio 0.977(0.961-0.993), p < 0.01) were associated with the primary end-point. A pHR%≤75% and a pHRR%≤50% represented the most accurate cut-off values in predicting the outcome.
Conclusions: The study suggests an association between blunted exercise-HR response, functional capacity, and CV death risk among patients with HFmrEF. Whether the CI presence might be adopted in daily HFmrEF management needs to be addressed in larger prospective studies.

Elliott JA; St. James’s Hospital, Dublin, Ireland;
Guinan E; Reynolds JV;

Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus [Dis Esophagus] 2023 Oct 28. Date of Electronic Publication: 2023 Oct 28.

Esophagectomy is an exemplar of complex oncological surgery and is associated with a relatively high risk of major morbidity and mortality. In the modern era, where specific complications are targeted in prevention and treatment pathways, and where the principles of enhanced recovery after surgery are espoused, optimum outcomes are targeted via a number of approaches. These include comprehensive clinical and physiological risk assessment, specialist perioperative care by a high-volume team, and multimodal inputs throughout the patient journey that aim to preserve or restore nutritional deficits, muscle mass and function.

J. Afoke, J. Mohal, G. S. Kanaganayagam, R. Casula, V. Bruno, L. Howard, et al;

Perfusion 2023 Pages 26765912312077

INTRODUCTION: Our aim is to describe the use of cardiopulmonary exercise testing in watchful waiting for asymptomatic severe primary mitral regurgitation.
METHODS: Between October 2016 and October 2017, ten patients with asymptomatic severe primary mitral regurgitation underwent watchful waiting in a single centre. Baseline assessment included history, physical examination, transthoracic echocardiogram and cardiopulmonary exercise testing. Patients were re-evaluated every 6 months with history, physical examination and transthoracic echocardiogram; and at 12 months with cardiopulmonary exercise testing.
RESULTS: At 1 year follow up, five patients remained asymptomatic with no significant change in left ventricular ejection fraction (p = 0.18). This was associated with no significant change in cardiopulmonary exercise testing parameters. However, five patients developed early new symptoms or changes in echocardiographic parameters with a significant fall in left ventricular ejection fraction (p < 0.01). This was associated with a significant fall in anaerobic threshold (p = 0.04) and four of the five patients having an abnormal percentage predicted peak VO2 at 1 year follow up.
CONCLUSIONS: Changes in symptomatic status or echocardiographic parameters during a watchful waiting approach for asymptomatic severe primary mitral regurgitation is associated with a significant reduction in cardiopulmonary exercise testing parameters.

Argirò A; Careggi University Hospital, Florence, Italy.
Silverii MV; Burgisser C; Fattirolli F; Baldasseroni S; Di Mario C; Zampieri M; Biagioni G; Mazzoni C; Chiti C; Allinovi M; Ungar A; Perfetto F; Cappelli F;

The Canadian journal of cardiology [Can J Cardiol] 2023 Oct 02.
Date of Electronic Publication: 2023 Oct 02.

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is associated with a progressive reduction of functional capacity. The progression of cardiopulmonary exercise testing (CPET) parameters over time is still unknown.
Methods: In this study 55 patients with ATTR-CM underwent two serial cardiological evaluation and CPET in a National Referral Center for cardiac amyloidosis (Careggi University hospital, Florence).
Results: Forty-three patients (78%) had wild type ATTR. Median age was 80 (76-83) years, 50 patients (91%) were men. At baseline median peak oxygen consumption (pVO2) was 15 (12-18) ml/kg/min, percentage of predicted pVO2 (%ppVO2) was 71 (60-83) % and VE/VCO2 slope was 31 (26-34). After a median follow-up of 14 (13-16) months, pVO2, %ppVO2 and VE/VCO2 slope were significantly worsened (-1.29ml/kg/min, CI -1.85 to -0.74, p<0.01, -4.5% CI -6.9 to -2.02, p<0.01, 8.6 CI 6 to 11, p<0.01, respectively). Furthermore, exercise time (-39 seconds, CI -59 to -19, p<0.01), exercise tolerance (-0.47 METs, CI -0.69 to -0.2, p<0.01) and peak systolic pressure (-10.8 mmHg, CI -16.2 to -5.4, p<0.01) were significantly reduced. The worsening in CPET variables did not correspond to a significant change in echocardiographic parameters.
Conclusions: Cardiorespiratory response to exercise significantly worsened over a short period of time in patients with ATTR-CM. Serial CPET may be useful to identify early disease progression.

Goldberg CS; C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor. (C.S.G.) ; Toronto, Cincinatti, Bethesda, New York & many other centres
Trachtenberg F; William Gaynor J; Mahle WT; Ravishankar C; Schwartz SM; Cnota JF; Ohye RG;
Gongwer R; Taylor M; Paridon S; Frommelt PC; Afton K; Atz AM; Burns KM; Detterich JA;Hill KD; Cabrera AG; Lewis AB; Pizarro C;Shah A; Sharma B; Newburger JW;

Circulation [Circulation] 2023 Oct 05.
Date of Electronic Publication: 2023 Oct 05.

Objective: In the SVR trial (Single Ventricle Reconstruction), newborns with hypoplastic left heart syndrome were randomly assigned to receive a modified Blalock-Taussig-Thomas shunt (mBTTS) or a right ventricle-to-pulmonary artery shunt (RVPAS) at Norwood operation. Transplant-free survival was superior in the RVPAS group at 1 year, but no longer differed by treatment group at 6 years; both treatment groups had accumulated important morbidities. In the third follow-up of this cohort (SVRIII [Long-Term Outcomes of Children With Hypoplastic Left Heart Syndrome and the Impact of Norwood Shunt Type]), we measured longitudinal outcomes and their risk factors through 12 years of age.
Methods: Annual medical history was collected through record review and telephone interviews. Cardiac magnetic resonance imaging (CMR), echocardiogram, and cycle ergometry cardiopulmonary exercise tests were performed at 10 through 14 years of age among participants with Fontan physiology. Differences in transplant-free survival and complication rates (eg, arrhythmias or protein-losing enteropathy) were identified through 12 years of age. The primary study outcome was right ventricular ejection fraction (RVEF) by CMR, and primary analyses were according to shunt type received. Multivariable linear and Cox regression models were created for RVEF by CMR and post-Fontan transplant-free survival.
Results: Among 549 participants enrolled in SVR, 237 of 313 (76%; 60.7% male) transplant-free survivors (mBTTS, 105 of 147; RVPAS, 129 of 161; both, 3 of 5) participated in SVRIII. RVEF by CMR was similar in the shunt groups (RVPAS, 51±9.6 [n=90], and mBTTS, 52±7.4 [n=75]; P =0.43). The RVPAS and mBTTS groups did not differ in transplant-free survival by 12 years of age (163 of 277 [59%] versus 144 of 267 [54%], respectively; P =0.11), percentage predicted peak Vo ₂ for age and sex (74±18% [n=91] versus 72±18% [n=84]; P =0.71), or percentage predicted work rate for size and sex (65±20% versus 64±19%; P =0.65). The RVPAS versus mBTTS group had a higher cumulative incidence of protein-losing enteropathy (5% versus 2%; P =0.04) and of catheter interventions (14 versus 10 per 100 patient-years; P =0.01), but had similar rates of other complications.
Conclusions: By 12 years after the Norwood operation, shunt type has minimal association with RVEF, peak Vo ₂ , complication rates, and transplant-free survival. RVEF is preserved among the subgroup of survivors who underwent CMR assessment. Low transplant-free survival, poor exercise performance, and accruing morbidities highlight the need for innovative strategies to improve long-term outcomes in patients with hypoplastic left heart syndrome.