Vishram-Nielsen JKK; Peter Munk Cardiac Centre, Division of Cardiology, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.; and Department of Cardiology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark.
Scolari FL;Steve Fan CP; Moayedi Y;Ross HJ; Manlhiot C; Allwood MA; Alba AC; Brunt KR; Simpson JA; Billia F

CJC open [CJC Open] 2024 Jan 24; Vol. 6 (5), pp. 745-754.
Date of Electronic Publication: 2024 Jan 24 (Print Publication: 2024).

Background: Diaphragm atrophy can contribute to dyspnea in patients with heart failure (HF) with its link to central neurohormonal overactivation. HF medications that cross the blood-brain barrier could act centrally and improve respiratory function, potentially alleviating diaphragmatic atrophy. Therefore, we compared the benefit of central- vs peripheral-acting HF drugs on respiratory function, as assessed by a single cardiopulmonary exercise test (CPET) and outcomes in HF patients.
Methods: A retrospective study was conducted of 624 ambulatory adult HF patients (80% male) with reduced left ventricular ejection fraction ≤ 40% and a complete CPET, followed at a single institution between 2001 and 2017. CPET parameters, and the outcomes all-cause death, a composite endpoint (all-cause death, need for left ventricular assist device, heart transplantation), and all-cause and/or HF hospitalizations, were compared in patients receiving central-acting (n = 550) vs peripheral-acting (n = 74) drugs.
Results: Compared to patients who receive peripheral-acting drugs, patients who receive central-acting drugs had better respiratory function (peak breath-by breath oxygen uptake [VO ₂ ], P  = 0.020; forced expiratory volume in 1 second [FEV1], P  = 0.007), and ventilatory efficiency (minute ventilation / carbon dioxide production [VE/VCO ₂ ], P < 0.001; end-tidal carbon dioxide tension [PETCO ₂ ], P  = 0.015; and trend for forced vital capacity [FVC], P  = 0.056). Many of the associations between the CPET parameters and drug type remained significant after multivariate adjustment. Moreover, patients receiving central-acting drugs had fewer composite events ( P  = 0.023), and HF hospitalizations ( P  = 0.044), although significance after multivariant correction was not achieved, despite the hazard ratio being 0.664 and 0.757, respectively.
Conclusions: Central-acting drugs were associated with better respiratory function as measured by CPET parameters in HF patients. This could extend to clinically meaningful composite outcomes and hospitalizations but required more power to be definitive in linking to drug effect. Central-acting HF drugs show a role in mitigating diaphragm weakness.

Kershner CE; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
Hardie WD; Chin C; Opotowsky AR; Aronoff EB; Mays WA; Knecht SK; TPowell AW

Frontiers in surgery [Front Surg] 2024 May 20; Vol. 11, pp. 1356501.
Date of Electronic Publication: 2024 May 20 (Print Publication: 2024).

Introduction: Patients with congenital heart disease (CHD) often have pulmonary abnormalities and exercise intolerance following cardiac surgery. Cardiac rehabilitation (CR) improves exercise capacity in patients with CHD, but minimal study has been performed to see if resting and dynamic pulmonary performance improves following CR in those with prior cardiac surgery.
Methods: This was a retrospective cohort study of all patients who completed ≥12 weeks of CR from 2018 through 2022. Demographic, cardiopulmonary exercise test (CPET), spirometry, 6-minute walk, functional strength measures, and outcomes data were collected. Data are presented as median[IQR]. A Student’s t -test was used for comparisons between groups and serial measurements were measured with a paired t -test. A p  < 0.05 was considered significant.
Results: There were a total of 37 patients [age 16.7 (14.2-20.1) years; 46% male] included. Patients with prior surgery ( n  = 26) were more likely to have abnormal spirometry data than those without heart disease ( n  = 11) (forced vital capacity [FVC] 76.7 [69.1-84.3]% vs. 96.4 [88.1-104.7]%, p  = 0.002), but neither group experienced a significant change in spirometry. On CPET, peak oxygen consumption increased but there was no change in other pulmonary measures during exercise. Percent predicted FVC correlated with hand grip strength ( r  = 0.57, p  = 0.0003) and percent predicted oxygen consumption ( r  = 0.43, p  = 0.009). The number of prior sternotomies showed negative associations with both percent predicted FVC ( r  = -0.43, p  = 0.04) and FEV ₁ ( r  = -0.47, p  = 0.02).
Discussion: Youth and young adults with a prior history of cardiac surgery have resting and dynamic pulmonary abnormalities that do not improve following CR. Multiple sternotomies are associated with worse pulmonary function.

Piamonti D; Department of Public Health and Infectious Diseases, Sapienza University of Rome, Italy.
Panza L; Flore R;Baccolini V;Pellegrino D; Sanna A;Lecci A;Lo Muzio G; Angelone D; Mirabelli FM; Morviducci M;Onorati P; Messina E;Panebianco V; Catalano C; Bonini M; Palange P

Respiratory physiology & neurobiology [Respir Physiol Neurobiol] 2024 May 31; Vol. 327, pp. 104285.
Date of Electronic Publication: 2024 May 31.

Background: Long COVID is defined as persistency of symptoms, such as exertional dyspnea, twelve weeks after recovery from SARS-CoV-2 infection.
Objectives: To investigate ventilatory efficiency by the use of cardiopulmonary exercise testing (CPET) in patients with exertional dyspnea despite normal basal spirometry after 18 (T ₁₈ ) and 36 months (T ₃₆ ) from COVID-19 pneumonia.
Methods: One hundred patients with moderate-critical COVID-19 were prospectively enrolled in our Long COVID program. Medical history, physical examination and lung high-resolution computed tomography (HRCT) were obtained at hospitalization (T ₀ ), 3 (T ₃ ) and 15 months (T ₁₅ ). All HRCTs were revised using a semi-quantitative CT severity score (CSS). Pulmonary function tests were obtained at T ₃ and T ₁₅ . CPET was performed in a subset of patients with residual dyspnea (mMRC ≥ 1), at T ₁₈ and at T ₃₆ .
Results: Remarkably, at CPET, ventilatory efficiency was reduced both at T ₁₈ (V’ _E /V’CO ₂ slope = 31.4±3.9 SD) and T ₃₆ (V’ _E /V’CO ₂ slope = 31.28±3.70 SD). Furthermore, we identified positive correlations between V’ _E /V’CO ₂ slope at T ₁₈ and T ₃₆ and both percentage of involvement and CSS at HRCT at T ₀ , T ₃ and T ₁₅ . Also, negative linear correlations were found between V’ _E /V’CO ₂ slope at T ₁₈ and T ₃₆ and DL _CO at T ₃ and T ₁₅ .
Conclusions: At eighteen months from COVID-19 pneumonia, 20 % of subjects still complains of exertional dyspnea. At CPET this may be explained by persistently reduced ventilatory efficiency, possibly related to the degree of lung parenchymal involvement in the acute phase of infection, likely reflecting a damage in the pulmonary circulation.

Kjesbu IE; Department of Cardiology, Bispebjerg Frederiksberg University Hospital, Denmark. (also from Italy, Spain, Switzerland, Germany & France)
Sibilitz KL; Petersen J; Houben VJG; Wilhelm M; Pena-Gil C;Iliou MC; Zeymer U; IArdissino D; Van ‘t Hof AWJ; van der Velde AE;de Kluiver EP; Prescott E;

European journal of preventive cardiology [Eur J Prev Cardiol] 2024 Jun 05.
Date of Electronic Publication: 2024 Jun 05.

Aims: The ability to be physically active is pivotal to the quality of life in elderly patients. This study aims to describe the association between exercise capacity and health-related quality of life (HRQoL), anxiety, and depression following an exercise-based cardiac rehabilitation (CR) program in elderly cardiac patients.
Methods: Patients aged ≥65 years with acute and chronic coronary syndrome or heart valve surgery were consecutively included from 8 CR centers in 7 European countries. Exercise capacity (VO2peak(ml/kg/min)) was assessed with a cardiopulmonary exercise test (97%) or a six-minute walk test. Outcome variables included HRQoL (SF-36 physical and mental component scores (PCS and MCS)), anxiety (GAD-7), and depression (PHQ-9). Mixed models were used to address the association between baseline and the development in VO2peak, and outcome variables stratified on sex, and adjusted for baseline values, age, and CR center.
Results: A total of 1,633 patients were included (T0), 1,523 (93%) completed end-of-CR assessment (T1), and 1,457 (89%) 1-year follow-up (T2). Women had higher % of predicted VO2peak, but poorer scores in HRQoL, anxiety and depression at all time-points. All scores improved in both sexes at follow-up. We found significant associations between VO2peak at baseline as well as development in VO2peak and all outcome variables at T1 and T2 in men (all p < 0.001). In women, VO2peak was only associated with PCS scores (p < 0.001).
Conclusions: Improvements in exercise capacity was strongly associated with improvements in HRQoL and mental health, however with stronger associations in men. The results highlight the importance of physical fitness for HRQol and mental health. The findings from this study might be useful to better target individual CR programs

Jiang S; Department of Physical Education, Health and Exercise Science Laboratory, Institute of Sports Science, Seoul National University, Seoul, Korea.
Li X; Seo JW; Ahn S; Sung Y; Jamrasi P;Song W

The Journal of sports medicine and physical fitness [J Sports Med Phys Fitness] 2024 Jun 06.
Date of Electronic Publication: 2024 Jun 06.

Background: Alterations caused by face masks on physiological responses vary among different population groups. This study aimed to investigate whether physically active and sedentary individuals respond differently to face mask use during exercise.
Methods: Sixteen healthy college students were divided into two groups: Physically active group (N.=10; 26.50±2.80 years) and Sedentary group (N.=6; 26.33±2.81 years). They performed three maximal cardiopulmonary exercise test (CPET)s following the Bruce protocol: one without a face mask (NON), one with a surgical mask (SUR) and one with a cloth mask (CLO). Cardiorespiratory parameters and heart rate were monitored continuously during the test. Blood pressure, oxygen saturation and lactate level were measured immediately before and after exertion.
Results: Significant differences were found between the Physically active and the Sedentary group in peak VO<inf>2</inf> (VO<inf>2peak</inf>) in NON (P=0.030). However, this difference disappeared when the face masks were used. Furthermore, VO<inf>2</inf>/kg (P=0.002) and METs (P=0.002) decreased significantly at the respiratory compensation point (RCP) only in the Physically active group with face masks. No significant differences were found between the two groups for exercise time, lactate level and dyspnea (P>0.05).
Conclusions: The decrease in exercise tolerance and cardiorespiratory responses, particularly VO<inf>2peak</inf>, due to face mask use was greater in physically active individuals compared to sedentary individuals. Population group characteristics should be considered when adapting face masks to daily life.

Naito A; Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan.;
Kagami K; Yuasa N; Harada T;Sorimachi H; Murakami F; Saito Y; Tani Y; Kato T; Wada N; Adachi T; Ishii H; Obokata M;

European journal of heart failure [Eur J Heart Fail] 2024 Jun 06.
Date of Electronic Publication: 2024 Jun 06.

Aims: Cardiopulmonary exercise testing (CPET) combined with exercise echocardiography (CPETecho) allows simultaneous assessments of cardiac, pulmonary, and ventilation in heart failure (HF) with preserved ejection fraction (HFpEF). This study sought to determine whether simultaneous assessment of CPET variables could provide additive predictive value over exercise stress echocardiography in patients with dyspnoea.
Methods and Results: CPETecho was performed in 443 patients with suspected HFpEF (240 HFpEF and 203 controls without HF). Patients with HFpEF were divided based on peak oxygen consumption (VO ₂ , ≥10 or <10 ml/min/kg) or the slope of minute ventilation to carbon dioxide production (V _E vs. VCO ₂ slope ≥45.0 or <45.0). The primary endpoint was defined as a composite of all-cause mortality, HF hospitalization, unplanned hospital visits requiring intravenous diuretics, or intensification of oral diuretics. During a median follow-up of 399 days, the composite outcome occurred in 57 patients. E/e’ ratio during peak exercise was associated with adverse outcomes. Patients with HFpEF and lower peak VO ₂ had increased risks of the composite event (hazard ratio [HR] 5.05, 95% confidence interval [CI] 2.65-9.62, p < 0.0001 vs. controls; HR 3.14, 95% CI 1.69-5.84, p = 0.0003 vs. HFpEF with higher peak VO ₂ ). Elevated V _E versus VCO ₂ slope was also associated with adverse events in HFpEF. The addition of either the presence of abnormal peak VO ₂ or V _E versus VCO ₂ slope increased the predictive ability over the model based on age, sex, atrial fibrillation, left atrial volume index, and exercise E/e’ (p < 0.05).
Conclusion: These data provide new insights into the role of CPETecho in patients with HFpEF.

Bokov P; Université de Paris, AP-HP, Hôpital Robert Debré, Service de Physiologie Pédiatrique Paris, France.
Dudoignon B; Fikiri Bavurhe R; Couque N; Matrot B; Delclaux C;

Pediatric research [Pediatr Res] 2024 Jun 08.
Date of Electronic Publication: 2024 Jun 08.

Background: It has been stated that patients with congenital central hypoventilation syndrome (CCHS) do not perceive dyspnea, which could be related to defective CO ₂ chemosensitivity.
Methods: We retrospectively selected the data of six-minute walk tests (6-MWT, n = 30), cardiopulmonary exercise test (CPET, n = 5) of 30 subjects with CCHS (median age, 9.3 years, 17 females) who had both peripheral (controller loop gain, CG0) and central CO ₂ chemosensitivity (hyperoxic, hypercapnic response test [HHRT]) measurement.
Main Results: Ten subjects had no symptom during the HHRT, as compared to the 20 subjects exhibiting symptoms, their median ages were 14.7 versus 8.8 years (p = 0.006), their maximal PETCO ₂ were 71.6 versus 66.7 mmHg (p = 0.007), their median CO ₂ response slopes were 0.28 versus 0.30 L/min/mmHg (p = 0.533) and their CG0 values were 0.75 versus 0.50 L/min/mmHg (p = 0.567). Median dyspnea Borg score at the end of the 6-MWT was 1/10 (17/30 subjects >0), while at the end of the CPET it was 3/10 (sensation: effort). This Borg score positively correlated with arterial desaturation at walk (R = 0.43; p = 0.016) and did not independently correlate with CO ₂ chemosensitivities.
Conclusion: About half of young subjects with CCHS do exhibit mild dyspnea at walk, which is not related to hypercapnia or residual CO ₂ chemosensitivity.
Impact: Young subjects with CCHS exhibit some degree of dyspnea under CO ₂ exposure and on exercise that is not related to residual CO ₂ chemosensitivity. It has been stated that patients with CCHS do not perceive sensations of dyspnea, which must be tempered. The mild degree of exertional dyspnea can serve as an indicator for the necessity of breaks.

D’Hulst G; Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland.
Hodžić D; Leuenberger R; Arnet J; Westerhuis E; Roth R; Schmidt-Trucksäss A; Knaier R; Wagner J

International journal of sports physiology and performance [Int J Sports Physiol Perform] 2024 Jun 07, pp. 1-12.
Date of Electronic Publication: 2024 Jun 07.

Objective: To (1) establish extensive physiological profiles of highly trained CrossFit® athletes using gold-standard tests and (2) investigate which physiological markers best correlate with CrossFit Open performance.
Methods: This study encompassed 60 participants (30 men and 30 women), all within the top 5% of the CrossFit Open, including 7 CrossFit semifinalists and 3 CrossFit Games finalists. Isokinetic dynamometers were employed to measure maximum isometric and isokinetic leg and trunk strength. Countermovement-jump height and maximum isometric midthigh-pull strength were assessed on a force plate. Peak oxygen uptake (VO2peak) was measured by a cardiopulmonary exercise test, and critical power and W’ were evaluated during a 3-minute all-out test, both on a cycle ergometer.
Results: Male and female athletes’ median (interquartile range) VO2peak was 4.64 (4.43, 4.80) and 3.21 (3.10, 3.29) L·min-1, critical power 314.5 (285.9, 343.6) and 221.3 (200.9, 238.9) W, and midthigh pull 3158 (2690, 3462) and 2035 (1728, 2347) N. Linear-regression analysis showed strong evidence for associations between different anthropometric variables and CrossFit Open performance in men and women, whereas for markers of cardiorespiratory fitness such as VO2peak, this was only true for women but not men. Conventional laboratory evaluations of strength, however, manifested minimal evidence for associations with CrossFit Open performance across both sexes.
Conclusions: This study provides the first detailed insights into the physiology of high-performing CrossFit athletes and informs training optimization. Furthermore, the results emphasize the advantage of athletes with shorter limbs and suggest potential modifications to CrossFit Open workout designs to level the playing field for athletes across different anthropometric characteristics.

Sarullo FM; U.O.S.D. di Riabilitazione Cardiovascolare Ospedale Buccheri La Ferla Fatebenefratelli, Palermo, Italy.
Nugara C; Sarullo S; Iacoviello M; Di Gesaro G; Miani D; Driussi M; Correale M; Bilato C; Passantino A; Carluccio E; Villani A; Degli Esposti L; D’Agostino C; Peruzzi E; Poli S; Di Lenarda A;

Frontiers in cardiovascular medicine [Front Cardiovasc Med] 2024 May 10; Vol. 11, pp. 1347908.
Date of Electronic Publication: 2024 May 10 (Print Publication: 2024).

Background: Heart failure (HF) significantly affects the morbidity, mortality, and quality of life of patients. New therapeutic strategies aim to improve the functional capacity and quality of life of patients while controlling HF-related risks. Real-world data on both the functional and cardiopulmonary exercise capacities of patients with HF with reduced ejection fraction upon sacubitril/valsartan use are lacking.
Methods: A multicenter, retrospective, cohort study, called REAL.IT, was performed based on the data collected from the electronic medical records of nine specialized HF centers in Italy. Cardiopulmonary exercise testing was performed at baseline and after 12 months of sacubitril/valsartan therapy, monitoring carbon dioxide production (VCO ₂ ) and oxygen consumption (VO ₂ ).
Results: The functional capacities of 170 patients were evaluated. The most common comorbidities were hypertension and diabetes (i.e., 53.5 and 32.4%, respectively). At follow-up, both the VO ₂ peak (from 15.1 ± 3.7 ml/kg/min at baseline to 17.6 ± 4.7 ml/kg/min at follow-up, p  < 0.0001) and the predicted % VO ₂ peak (from 55.5 ± 14.1 to 65.5 ± 16.9, p  < 0.0001) significantly increased from baseline. The VO ₂ at the anaerobic threshold (AT-VO ₂ ) increased from 11.5 ± 2.6 to 12.5 ± 3.3 ml/kg/min ( p  = 0.021), and the rate ratio between the oxygen uptake and the change in work (ΔVO ₂ /Δwork slope) improved from 9.1 ± 1.5 to 9.9 ± 1.6 ml/min/W ( p  < 0.0001).
Conclusions: Sacubitril/valsartan improves the cardiopulmonary capacity of patients with HFrEF in daily clinical practice in Italy.
Competing Interests: MI: Lectures or consultant for Novartis, Vifor Pharma, Boehringer, Lilly, Bayer, AstraZeneca, Roche Diagnostics, Neopharmed Gentili. ADL: Lectures for Novartis, Vifor Pharma, Boheringer, Daiichi, Bayer, Pfizer, AstraZeneca, Research Funds from Novartis, Amgen, AstraZeneca, Vifor Pharma, Bayer. CDA, EP, and SP are employees of Novartis. LDE was employed by company CliCon S.r.l. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. The authors declare that this study received funding from Novartis Farma. The funder had the following involvement in the study: study design, data collection and analysis, supporting manuscript preparation.