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.

Abbasi A; Division of Respiratory and Critical Care Physiology and Medicine, Harbor-UCLA Medical Center,
Ahmad K; Ferguson C; Soriano A; Calmelat R;Rossiter HB; Casaburi R; Stringer WW; Porszasz J

European journal of applied physiology [Eur J Appl Physiol] 2023 Oct 06.
Date of Electronic Publication: 2023 Oct 06.

Purpose: Pathogen transmission during cardio-pulmonary exercise testing (CPET) is caused by carrier aerosols generated during respiration.
Methods: Ten healthy volunteers (age range: 34 ± 15; 4 females) were recruited to see if the physiological reactions to ramp-incremental CPET on a cycle ergometer were affected using an in-line filter placed between the mouthpiece and the flow sensor. The tests were in random order with or without an in-line bacterial/viral spirometer filter. The work rate aligned, time interpolated 10 s bin data were compared throughout the exercise period.
Results: From rest to peak exercise, filter use increased only minute ventilation ([Formula: see text] _E ) (Δ[Formula: see text] _E  = 1.56 ± 0.70 L/min, P < 0.001) and tidal volume (V _T ) (ΔV _T  = 0.10 ± 0.11 L, P = 0.014). Over the entire test, the slope of the residuals for [Formula: see text]CO ₂ was positive (0.035 ± 0.041 (ΔL/L), P = 0.027). During a ramp-incremental CPET in healthy subjects, an in-line filter increased [Formula: see text] _E and V _T but not metabolic rate.
Conclusion: In conclusion, using an in-line filter is feasible, does not affect appreciably the physiological variables, and may mitigate risk of aerosol dispersion during CPET.

Eser P;  University of Bern, Switzerland & other centres in Netherlands, Italy, France & Spain
Marcin T; Prescott E; Prins LF; Kolkman E; Bruins W; van der Velde AE; Gil CP; Iliou MC; Ardissino D; Zeymer U; Meindersma EP;
Van’t Hof AWJ; de Kluiver EP; Wilhelm M;

Frontiers in cardiovascular medicine [Front Cardiovasc Med] 2023 Sep 01; Vol. 10, pp. 1219589.
Date of Electronic Publication: 2023 Sep 01 (Print Publication: 2023).

Background: Inefficient ventilation is an established prognostic marker in patients with heart failure. It is not known whether inefficient ventilation is also linked to poor prognosis in patients with left ventricular dysfunction (LVD) but without overt heart failure.
Objectives: To investigate whether inefficient ventilation in elderly patients with LVD is more common than in patients without LVD, whether it improves with exercise-based cardiac rehabilitation (exCR), and whether it is associated with major adverse cardiovascular events (MACE).
Methods: In this large multicentre observational longitudinal study, patients aged ≥65 years with acute or chronic coronary syndromes (ACS, CCS) without cardiac surgery who participated in a study on the effectiveness of exCR in seven European countries were included. Cardiopulmonary exercise testing (CPET) was performed before, at the termination of exCR, and at 12 months follow-up. Ventilation (VE), breathing frequency (BF), tidal volume (VT), and end-expiratory carbon dioxide pressure (P _ET CO ₂ ) were measured at rest, at the first ventilatory threshold, and at peak exercise. Ventilatory parameters were compared between patients with and without LVD (based on cardio-echography) and related to MACE at 12 month follow-up.
Results: In 818 patients, age was 72.5 ± 5.4 years, 21.9% were women, 79.8% had ACS, and 151 (18%) had LVD. Compared to noLVD, in LVD resting VE was increased by 8%, resting BF by 6%, peak VE _, peak VT, and peak P _ET CO ₂ reduced by 6%, 8%, and 5%, respectively, and VE/VCO ₂ slope increased by 11%. From before to after exCR, resting VE decreased and peak P _ET CO ₂ increased significantly more in patients with compared to without LVD. In LVD, higher resting BF, higher nadir VE/VCO ₂ , and lower peak P _ET CO ₂ at baseline were associated with MACE.
Conclusions: Similarly to patients with HF, in elderly patients with ischemic LVD, inefficient resting and exercise ventilation was associated with worse outcomes, and ExCR alleviated abnormal breathing patterns and gas exchange parameters.

Brochhagen J;Faculty of Sport Science, Leipzig University,  Germany.
Coll Barroso MT; Baumgart C; Wasmus DT; Freiwald J; Hoppe MW;

Frontiers in sports and active living [Front Sports Act Living] 2023 Sep 05; Vol. 5, pp. 1218948.
Date of Electronic Publication: 2023 Sep 05 (Print Publication: 2023).

Introduction: It is known that maximum oxygen uptake depends on age, sex, endurance capacity, and chronic heart failure. However, due to the required invasive or often applied non-continuous approaches, less is known on underlying central and peripheral factors. Thus, this study aimed to investigate the effects of age, sex, endurance capacity, and chronic heart failure on non-invasively and continuously measured central and peripheral factors of oxygen uptake.
Methods: 15 male children (11 ± 1 years), 15 male (24 ± 3 years) and 14 female recreationally active adults (23 ± 2 years), 12 male highly trained endurance athletes (24 ± 3 years), and 10 male elders (59 ± 6 years) and 10 chronic heart failure patients (62 ± 7 years) were tested during a cardiopulmonary exercise test on a cycling ergometer until exhaustion for: blood pressure, heart rate, stroke volume, cardiac output, cardiac power output, vastus lateralis muscle oxygen saturation, and (calculated) arterio-venous oxygen difference. For the non-invasive and continuous measurement of stroke volume and muscle oxygen saturation, bioreactance analysis and near-infrared spectroscopy were used, respectively. A two-factor repeated measure ANOVA and partial eta-squared effect sizes ( η p 2 ) were applied for statistical analyses at rest, 80, and 100% of oxygen uptake.
Results: For the age effect, there were statistically significant group differences for all factors ( p  ≤ .033; η p 2 ≥ .169 ). Concerning sex, there were group differences for all factors ( p  ≤ .010; η p 2 ≥ .223 ), except diastolic blood pressure and heart rate ( p  ≥ .698; η p 2 ≤ .006 ). For the effect of endurance capacity, there were no group differences for any of the factors ( p  ≥ .065; η p 2 ≤ .129 ). Regarding chronic heart failure, there were group differences for the heart rate and arterio-venous oxygen difference ( p  ≤ .037; η p 2 ≥ .220 ).
Discussion: Age, sex, endurance capacity, and chronic heart failure affect central and peripheral factors of oxygen uptake measured by non-invasive and continuous technologies. Since most of our findings support pioneer work using invasive or non-continuous measures, the validity of our applied technologies is indirectly confirmed. Our outcomes allow direct comparison between different groups serving as reference data and framework for subsequent studies in sport science and medicine aiming to optimise diagnostics and interventions in athletes and patients.

Mistry MS; Boston Children’s Hospital, Department of Cardiology.
Gauvreau K; Alexander ME; Jenkins K; Gauthier N;

The Journal of pediatrics [J Pediatr] 2023 Sep 18, pp. 113742.
Date of Electronic Publication: 2023 Sep 18.

Objectives: To determine socioeconomic status (SES) has a greater effect than standard demographic values on predicted peak oxygen consumption (pVO ₂ ).
Study Design: We conducted a single-institution, retrospective analysis of maximal cardiopulmonary exercise test (CPET) data from 2010 to 2020 for healthy patients age <19 years with BMI percentile (BMI%) between 5-95. Data were sorted by self-identified race, BMI%, and adjusted gross income (AGI); AGI served as a surrogate for SES. Mean percent predicted pVO ₂ (%ppVO ₂ ) was compared between groups. Linear regression was used to adjust for differences.
Results: 541 CPETs met inclusion criteria. Mean %ppVO ₂ was 97% ± 22.6 predicted (p<0.01) with 30% below criterion standard for normal (85% predicted). After excluding unknown AGI and race, 418 CPETs remained. Mean %ppVO ₂ was lower for Blacks (n=36) and LatinX (n=26) compared with Whites (n=333, p<0.01). Mean %ppVO ₂ declined as AGI decreased (p<0.01). The differences in %ppVO ₂ between racial categories remained significant when adjusted for BMI% (Black r=-7.3, p=0.035; LatinX r=-15.4, p<0.01). These differences both decreased in magnitude and were no longer significant when adjusted for AGI (Black r=-6.0, p=0.150; LatinX r=-9.3, p=0.06).
Conclusions: Lower SES correlates with lower measured cardiovascular fitness and may confound data interpretation. When using normative reference ranges in clinical decision making, providers should recognize that social determinants of health may influence predicted fitness. Social inequities should be considered when assessing pediatric cardiovascular fitness.

De Biase N; (Department of Clinical and Experimental Medicine, University of Pisa, Italy.)
Mazzola M; Del Punta L; Di Fiore V;De Carlo M; Giannini C; Costa G; Paneni F; Mengozzi A; Nesti L; Gargani L; Masi S; Pugliese NR;

European journal of heart failure [Eur J Heart Fail] 2023 Sep 01.
Date of Electronic Publication: 2023 Sep 01.

Aims: Degenerative aortic valve stenosis with preserved ejection fraction (ASpEF) and heart failure with preserved ejection fraction (HFpEF) display intriguing similarities. This study aimed to provide a non-invasive, comparative analysis of ASpEF versus HFpEF at rest and during exercise.
Methods and Results: We prospectively enrolled 148 patients with HFpEF and 150 patients with degenerative moderate-to-severe ASpEF, together with 66 age- and sex-matched healthy controls. All subjects received a comprehensive evaluation at rest and 351/364 (96%) performed a combined cardiopulmonary exercise stress echocardiography test. Patients with ASpEF eligible for transcatheter aortic valve replacement (n = 125) also performed cardiac computed tomography (CT). HFpEF and ASpEF patients showed similar demographic distribution and biohumoral profiles. Most patients with ASpEF (134/150, 89%) had severe high-gradient aortic stenosis; 6/150 (4%) had normal-flow, low-gradient ASpEF, while 10/150 (7%) had low-flow, low-gradient ASpEF. Both patient groups displayed significantly lower peak oxygen consumption (VO ₂ ), peak cardiac output, and peak arteriovenous oxygen difference compared to controls (all p < 0.01). ASpEF patients showed several extravalvular abnormalities at rest and during exercise, similar to HFpEF (all p < 0.01 vs. controls). Epicardial adipose tissue (EAT) thickness was significantly greater in ASpEF than HFpEF and was inversely correlated with peak VO ₂ in all groups. In ASpEF, EAT was directly related to echocardiography-derived disease severity and CT-derived aortic valve calcium burden.
Conclusion: Functional capacity is similarly impaired in ASpEF and HFpEF due to both peripheral and central components. Further investigation is warranted to determine whether extravalvular alterations may affect disease progression and prognosis in ASpEF even after valve intervention, which could support the concept of ASpEF as a specific sub-phenotype of HFpEF.