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Background: The one-minute sit-to-stand test (1STST) is an easy-to-administer, space and time-saving test for determining functional exercise capacity in cardiac disease. This study aimed to investigate the 1STST -test-retest reliability and convergent validity and compare its physiological responses to the six-minute walk test (6MWT) in patients with Atrial fibrillation (AF)., Methods: Forty-five patients with AF were included in this study. Functional exercise capacity was evaluated using the 1STST and 6MWT. For assessing test-retest reliability, the intraclass correlation coefficient and Bland-Altman plots were utilised. Convergent validity was determined by correlation analysis 1 STST and 6MWT, age, European Heart Rhythm Association score, ejection fraction, and quality of life. The cut-off point of 1STST was defined using ROC analysis., Results: With an intraclass correlation coefficient value of 0.975 [95 % confidence interval (CI) 0.954-0.986], the 1STST demonstrated excellent-test-retest reliability. Physiological responses after tests were similar in the 1STST and 6MWT (p > 0.05). The number of 1STST repetitions was strongly associated with 6MWT distance (r = 0.809; p < 0.001). A cut-off value of ≤13 repetitions in the number of 1STST repetitions was defined as functional impairment related to an increased risk of clinical events [sensitivity: 100 %, specificity: 84.6 %; AUC:0.94; 95 % CI 0.82 to 0.98; p < 0.001]., Conclusions: The 1STST is a reliable and valid assessment tool that produced comparable hemodynamic responses to the 6MWT in patients with AF. Considering its feasibility and time efficiency, healthcare professionals can use the 1STST rather than the 6MWT test to measure functional exercise status in a constrained environment for this patient group., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Exercise Based Cardiac Rehabilitation (EBCR) is highly beneficial to improve the outcome and quality of life of patients suffering from cardiac diseases. Most of the time, it increases cardiorespiratory and muscle capacity. However, not all patients elicit these benefits because of the high variability in their response to EBCR. In this context, the present study aimed to determine the potential of a specific parameter, the Contractility index (CTi), to predict the response of cardiac patients to EBCR. This parameter is acquired during the baseline Cardiopulmonary Exercise Test (CPET), using Signal-Morphology based Impedance Cardiography (SM-ICG TM )., Methods: 58 cardiac patients (59.7 ± 10.2 years old) were retrospectively enrolled in this study and admitted to EBCR, and 57 could be analyzed., Results: The patients were divided into 2 groups based on their CTi response during CPET (normal versus altered or compromised). After the EBCR program, there was an overall increase in peak oxygen uptake (VO 2 peak) (+13.6 ± 22.9 %). EBCR induced a higher VO 2 peak improvement in patients with normal CTi response compared to their counterparts with altered or compromised CTi profiles (+24.1 ± 21.4 % vs. + 3.36 ± 19.5 %, p < 0.01) Patients with a normal CTi response during the baseline CPET were more likely to have a greater than 5% improvement in VO 2 peak (odds ratio 8.7, p = 0.012) and benefit from EBCR, as compared to the patients in the altered or compromised CTi group., Conclusion: This study demonstrated the predictive potential of the CTi profile observed during the baseline CPET to anticipate the response to EBCR in cardiac patients., Competing Interests: Declaration of competing interest Frank Bour is co-inventor of the SM-ICG(TM) technology and co-founder and managing director of Manatec Biomedical, the company that develops and manufactures the PhysioFlow® device based on this technology., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: Right ventricular (RV) output reserve, defined as increase of cardiac output during exercise, is reduced in patients with pulmonary arterial hypertension (PAH). Aim of this study was to evaluate the association of right heart size measured by echocardiography and invasively measured RV function at rest and during exercise in PAH patients., Methods: Adult PAH-patients who received routine haemodynamic assessment at rest and during exercise by right heart catheterisation and echocardiographic measurement of right heart size (right atrial (RA) and RV area) were included in this study. Clinical, echocardiographic, laboratory, exercise and invasive haemodynamic parameters were retrospectively analysed. The primary endpoint was to assess the association between right heart size and right ventricular function., Results: Data from 215 PAH patients (age 58.9 ± 15.9 years, 63.3% female, 62.2% double or triple combination treatment) were analysed in this cross-sectional study. Cardiac index was significantly lower for patients with enlarged RA-area > 18 cm 2 at rest, and at 25 and 50 W (all p < 0.001) and for patients with enlarged RV area > 20 cm 2 at rest, 25, 50 and 75 W (all p < 0.001). Furthermore, pulmonary vascular resistance and mPAP/CO slope (all p < 0.001) were significantly higher and pulmonary arterial compliance (all p < 0.05) was significantly lower in patients with enlarged RA or RV area. RA and RV area correlated with TAPSE/sPAP (both p < 0.001, R - 0.570 and - 0.530)., Conclusion: This study could underline that an enlargement of RA- and RV-area is associated with an impaired RV function at rest and during exercise in patients with PAH., Competing Interests: Declaration of competing interest BE: received travel fees, consulting fees, speaking fees, and/or honoraria from Janssen, MSD, Bayer and OMT, outside the submitted work. KFW, AMM: nothing to declare. CAE: received speaking fees from MSD outside the submitted work. SH: received honoraria for lectures, consultancy, or both from Actelion, AOP, Bayer/MSD, GSK, Novartis, OMT, Pfizer, and United Therapeutics out-side the submitted work. EG: has received grants and personal fees from Actelion, Bayer AG, and MSD; grants from GSK, Novartis, and United Therapeutics and personal fees from SCOPE, OrPha Swiss GmbH, and Zurich Heart House, outside the submitted work. PX: has received personal fees from MSD and OMT outside the submitted work. NB: received speaker fees from University Hospital Zurich and AOP., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Chronic Chagas cardiomyopathy (CCC), the most severe clinical condition of Chagas disease, often leads to a reduction in functional capacity and the appearance of symptoms such as fatigue and dyspnea on exertion. However, its determinant factors remain unclear. We aimed to evaluate the peak oxygen consumption (VO 2peak ) in patients with CCC and identify its determining factors., Methods: An observational study with 97 CCC patients was conducted. Patients underwent clinical examination, cardiopulmonary exercise test (CPET), and echocardiography as part of the standard clinical evaluation. Multivariate linear regression was used to identify independent clinical and echocardiographic predictors of VO 2peak and percentage of predicted VO 2 ., Results: Mean age of study patients was 55.9 ± 13.4 years, median left ventricle ejection fraction (LVEF) was 40 (26-61.5) % and median VO 2peak was 16.1 (12.1-20.8) ml/Kg/min. 36 patients presented preserved LVEF and 61 presented reduced LVEF. There were significant differences in almost all CPET variables (p < 0.05) between these two groups. VO 2peak was associated with age, male sex, NYHA functional class, LVEF, left atrium diameter, LV diastolic diameter, E wave, LV mass index, and pulmonary artery systolic pressure (PASP). Age, male sex, LVEF, and E wave remained independently associated with VO 2peak in the multivariate analysis (R 2  = 0.69), furthermore, only LVEF and E wave were associated with the predicted VO 2 percentage (R 2  = 0.53)., Conclusion: In patients with CCC, disease severity, male sex, LV systolic and diastolic function influence the functional capacity., Competing Interests: Declaration of competing interest All authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: The prognostic utility of comprehensive, guideline-defined assessment of diastolic measures during routine exercise echocardiography remains unclear., Objectives: The purpose of the study was to pragmatically assess the prognostic role of obtainable Doppler-derived diastolic variables during treadmill exercise echocardiography., Methods: In this retrospective study, the authors included 1910 patients undergoing exercise echocardiography. The guideline-defined diastolic measures included resting septal e' velocity, post-exercise E/e' ratio and post-exercise tricuspid regurgitant jet velocity. Since tricuspid regurgitant jet velocity is not routinely obtainable, the authors examined 2 approaches: 2 variable approach using only resting septal e' velocity and post-exercise E/e' ratio and 3 variable approach with all diastolic variables., Results: The mean age of study subjects was 57.6 ± 16 years and 1068 (56 %) were women. The tricuspid jet velocity was not reliably obtained in 501(26 %) of patients. All 3 diastolic variables were associated with the hard outcomes (mortality, acute coronary syndrome, cardiac hospitalization), soft outcomes (subsequent revascularization and cardiac testing), as well as the composite outcome. In the 2-variable approach, the presence of 2 abnormal variables was associated with a worse composite outcome. In the 3 variable approach, the presence of 2 or 3 abnormal variables was associated with a worse composite outcome. The associations persisted after multivariable adjustment and in the propensity matched subgroups., Conclusions: Guideline-defined diastolic variables during treadmill exercise echocardiography offer prognostic utility when used in combination, especially if all 3 variables are obtainable., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: We aimed to investigate the role of feature-tracking (FT) strain in long-term risk stratification of patients with known or suspected coronary artery disease (CAD) who underwent stress cardiac MRI with dipyridamole; to determine if contrast-free stress cardiac MRI with strain measurements could provide comparable prognostic value to myocardial perfusion., Materials and Methods: This retrospective study included consecutive patients with stable symptoms suggesting possible cardiac ischemia who underwent stress cardiac MRI with dipyridamole. The mean follow-up period was 5.8 years ±1.2 [SD]. FT cardiac MRI analysis was performed for each patient to obtain 2D global peak circumferential strain (GCS). The primary outcome measure was major adverse cardiac events (MACE), defined as nonfatal myocardial infarction and cardiac death., Results: A total of 729 patients (mean age, 63 years ±10 [SD]; 616 males) were included. MACE occurred in 70 (9.6%) patients. The presence of late gadolinium enhancement (LGE) ([HR] 2.74, [95% CI: 1.53, 4.88]; P < .001) and stress GCS (HR, 1.06 [95% CI: 1.01, 1.12]; P = .016) were independently associated with MACE. A model based on contrast-free assessment of LVEF and stress GCS showed similar performance for predicting MACE than LVEF and perfusion (P = .056)., Conclusions: In patients with known or suspected CAD undergoing stress cardiac MRI with dipyridamole, GCS and LGE presence were independent predictors of MACE. Contrast-free stress cardiac MRI with stress GCS measurement offered prognostic value akin to myocardial perfusion assessment., Clinical Relevance Statement: Stress global circumferential strain represented an additional method to predict major adverse cardiac events in patients undergoing stress cardiac MRI, even without the use of contrast agents. This would be of particular significance in patients with severe renal impairment., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)

Background: Reliable change indices can determine pre-post intervention changes at an individual level that are greater than chance or practice effect. We applied previously developed minimal meaningful change (MMC RCI ) scores for oxygen uptake (V̇O 2 ) values associated with estimated lactate threshold (θ LT ), respiratory compensation point (RCP), and peak oxygen uptake (V̇O 2peak ) to evaluate the effectiveness of exercise training in cardiovascular disease patients., Methods: 303 patients (65 ± 11 yrs.; 27% female) that completed a symptom-limited cardiopulmonary exercise test (CPET) before and after 6-months of guideline-recommended exercise training were assessed to determine absolute and relative V̇O 2 at θ LT , RCP, and V̇O 2peak . Using MMC RCI ∆V̇O 2 scores of ±3.9 mL·kg -1 ·min -1 , ±4.0 mL·kg -1 ·min -1 , and ± 3.6 mL·kg -1 ·min -1 for θ LT , RCP, and V̇O 2peak , respectively, patients were classified as "positive" (Δθ LT , ΔRCP, and/or ΔV̇O 2peak  ≥ +MMC RCI ), "non-" (between ±MMC RCI ), or "negative" responders (≤ -MMC RCI )., Results: Mean RCP (n = 86) and V̇O 2peak (n = 303) increased (p < 0.05) from 19.4 ± 3.6 mL·kg -1 ·min -1 and 18.0 ± 6.3 mL·kg -1 ·min -1 to 20.1 ± 3.8 mL·kg -1 ·min -1 and 19.2 ± 7.0 mL·kg -1 ·min -1 at exit, respectively, whereas θ LT (n = 140) did not change (15.5 ± 3.4 mL·kg -1 ·min -1 versus 15.7 ± 3.8 mL·kg -1 ·min -1 , p = 0.324). For changes in θ LT , 6% were classified as "positive" responders, 90% as "non-responders", and 4% as "negative" responders. For RCP, 10% exhibited "positive" changes, 87% were "non-responders", and 2% were "negative" responders. For ΔV̇O 2peak , 57 patients (19%) were classified as "positive" responders, 229 (76%) as "non-responders", and 17 (6%) as "negative" responders., Conclusion: Most patients that completed the exercise training program did not achieve reliable improvements greater than that of chance or practice at an individual level in θ LT , RCP and V̇O 2peak ., Competing Interests: Declaration of competing interest No conflicts of interest, financial or otherwise, are declared by the authors., (Copyright © 2024. Published by Elsevier B.V.)

Background and aims of the study A functionally single ventricle (FSV) refers to a group of congenital heart defects that are not amenable for biventricular correction. The Fontan operation is utilized as surgical treatment for most of FSV patients. The evaluation of FSV function is extremely difficult due to its unique pathophysiology. This study aimed to explore the efficacy of speckle tracking echocardiography (STE) parameters measured at rest and during exercise for comprehensive assessment of univentricular heart., Methods: We enrolled 37 patients with a functionally single ventricle after the Fontan operation, hospitalized in the Department of Congenital Heart Defects between years 2019 and 2021.The echocardiographic stress tests were performed in the Echocardiography Laboratory of the Congenital Heart Defects Department. The study was conducted on a bicycle ergometer in a semi-recumbent position. The parameters obtained by speckle tracking echocardiography (STE): the longitudinal strain of the FSV free wall (Ɛ) and the longitudinal strain of myocardial layers: subendocardial, medial and subepicardial were analyzed. A transmural longitudinal strain gradient (TG) was calculated as the difference between longitudinal deformation of the subendocardial and subepicardial layers. Current results of cardiac magnetic resonance imaging (CMR) and cardio-pulmonary test (CPET) were also incorporated. Demographic data, past interventions, pharmacological treatment and comorbidities were extracted from medical records., Results: Ɛ at rest and during exercise were not related to the parameters of physical capacity obtained on CPET nor to the CMR results. The transmural strain gradient was dependent on physical performance parameter- peak oxygen uptake- and related to the FSV ejection fraction calculated by magnetic resonance imaging., Conclusions: The transmural strain gradient and FSV free wall strain are readily measurable and suitable for evaluating single ventricle function. The TG is positively correlated with peak oxygen uptake during the cardiopulmonary test and with the ejection fraction derived from cardiac magnetic resonance imaging. The applicability of these findings in patients undergoing the Fontan procedure warrants further exploration., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: Many studies evaluated the functional response in post-Covid-19 patients; however, they systematically excluded patients with concomitant acute coronary syndrome (ACS). We evaluated the long-term functional capacity assessed by cardiopulmonary exercise test (CPET) in patients hospitalized for ACS and concomitant SARS-CoV2 infection. The secondary aim was to investigate the functional response in patients with symptoms related to "long COVID-19 syndrome" (LCS)., Methods: This cross-sectional case-control study compared 20 patients with ACS and concomitant SARS-COV2 infection with 20 patients without COVID-19. At the follow-up visit (between 6 and 12 months after revascularization procedure) all patients underwent a CPET., Results: Patients with previous ACS and concomitant COVID-19 showed a reduced O2 consumption than controls (predicted peak V̇O2 74.00% vs 86.70%; p = 0.01) with a high degree of ventilatory inefficiency (VE/ V̇CO2 slope 38.04 vs 30.31; p = 0.002). 50% of subjects with previous COVID-19 disease showed symptoms related to "LCS"; this subgroup demarcates the characteristic reduced exercise capacity found in the entire COVID + group., Conclusions: This study is the first in literature having analyzed the long-term functional capacity phenotype in a population of ACS patients and concomitant SARS-CoV2 infection. Severe ventilatory inefficiency emerged as the functional signature of these patients. Moreover, the subset of patients with symptoms related to LCS has the most compromised long term reduced exercise capacity and an altered ventilation control., Competing Interests: Declaration of Competing Interest We 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., (Published by Elsevier B.V.)

Background: In chronic heart failure (HF), exercise-induced increase in pulmonary capillary pressure may cause an increase of pulmonary congestion, or the development of pulmonary oedema. We sought to assess in HF patients the exercise-induced intra-thoracic fluid movements, by measuring plasma brain natriuretic peptide (BNP), lung comets and lung diffusion for carbon monoxide (DLCO) and nitric oxide (DLNO), as markers of hemodynamic load changes, interstitial space and alveolar-capillary membrane fluids, respectively., Methods and Results: Twenty-four reduced ejection fraction HF patients underwent BNP, lung comets and DLCO/DLNO measurements before, at peak and 1 h after the end of a maximal cardiopulmonary exercise test. BNP significantly increased at peak from 549 (328-841) to 691 (382-1207, p < 0.0001) pg/mL and almost completely returned to baseline value 1 h after exercise. Comets number increased at peak from 9.4 ± 8.2 to 24.3 ± 16.7, returning to baseline (9.7 ± 7.4) after 1 h (p < 0.0001). DLCO did not change significantly at peak (from 18.01 ± 4.72 to 18.22 ± 4.73 mL/min/mmHg), but was significantly reduced at 1 h (16.97 ± 4.26 mL/min/mmHg) compared to both baseline (p = 0.0211) and peak (p = 0.0174). DLNO showed a not significant trend toward lower values 1 h post-exercise., Conclusions: Moderate/severe HF patients have a 2-step intra-thoracic fluid movement with exercise: the first during active exercise, from the vascular space toward the interstitial space, as confirmed by comets increase, without any effect on diffusion, and the second, during recovery, toward the alveolar-capillary membrane, clearing the interstitial space but worsening gas diffusion., Competing Interests: Declaration of competing interest The Authors report no relationships that could be construed as a conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: In patients with transposition of the great arteries and an arterial switch operation (TGA-ASO) right ventricular outflow tract (RVOT) obstruction is a common complication requiring one or more RVOT interventions., Objectives: We aimed to assess cardiopulmonary exercise capacity and right ventricular function in patients stratified for type of RVOT intervention., Methods: TGA-ASO patients (≥16 years) were stratified by type of RVOT intervention. The following outcome parameters were included: predicted (%) peak oxygen uptake (peak VO2), tricuspid annular plane systolic excursion (TAPSE), tricuspid Lateral Annular Systolic Velocity (TV S'), right ventricle (RV)-arterial coupling (defined as TAPSE/RV systolic pressure ratio), and N-terminal proBNP (NT-proBNP)., Results: 447 TGA patients with a mean age of 25.0 (interquartile range (IQR) 21-29) years were included. Patients without previous RVOT intervention (n = 338, 76%) had a significantly higher predicted peak VO2 (78.0 ± 17.4%) compared to patients with single approach catheter-based RVOT intervention (73.7 ± 12.7%), single approach surgical RVOT intervention (73.8 ± 28.1%), and patients with multiple approach RVOT intervention (66.2 ± 14.0%, p = 0.021). RV-arterial coupling was found to be significantly lower in patients with prior catheter-based and/or surgical RVOT intervention compared to patients without any RVOT intervention (p = 0.029)., Conclusions: TGA patients after a successful arterial switch repair have a decreased exercise capacity. A considerable amount of TGA patients with either catheter or surgical RVOT intervention perform significantly worse compared to patients without RVOT interventions., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Cardiopulmonary exercise testing (CPET) is a recognized tool for prognostic stratification in patients with dilated cardiomyopathy (DCM). Given the lack of data currently available, the aim of this study was to test the prognostic value of repeating CPET during the follow-up of patients with DCM., Methods: This multicenter, retrospective study, analyzed DCM patients who consecutively performed two echocardiographies and CPETs during clinical stability. The study end-point was a composite of death from all causes, heart transplantation, left ventricular assist device implantation, life-threatening ventricular arrhythmias or hospitalization for heart failure., Results: 216 DCM patients were enrolled (52 years, 78% male, NYHA I-II 82%, LVEF 32%, 94% on ACE inhibitors/ARNI, 95% on beta-blockers). The interval between CPETs was 15 months. During a median follow-up of 38 months from the second CPET, 102 (47%) patients experienced the study end-point. Among them, there was stability of echocardiographic values but a significant worsening of functional capacity. Among the 173 patients (80%) who did not show echocardiographic left ventricular reverse remodeling (LVRR), the 1-year prevalence of the study-end point was higher in patients who worsened vs patients who maintained stable their functional capacity at CPET (38 vs. 15% respectively, p-value: 0.001). These results were consistent also when excluding life-threatening ventricular arrhythmias from the composite end-point., Conclusion: In clinically stable DCM patients with important depression of LVEF, the repetition of combined echocardiography and CPET might be recommended. When LVRR fails, 1-year repetition of CPET could identify higher-risk patients., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Exercise capacity is impaired in patients after arterial switch operation (ASO) for complete transposition of the great arteries. Maximal oxygen consumption is related with outcome., Objectives: This study assessed ventricular function by advanced echocardiography and cardiac magnetic resonance (CMR) imaging at rest and during exercise, to determine exercise capacity in ASO patients, and to correlate exercise capacity with ventricular function as potential early marker of subclinical impairment., Methods: Forty-four patients (71% male, mean age 25 ± 4 years - range 18-40 years) were included during routine clinical follow-up. Assessment involved physical examination, 12‑lead ECG, echocardiography, and cardiopulmonary exercise test (CPET) (day 1). On day 2 CMR imaging at rest and during exercise was performed. Blood was sampled for biomarkers., Results: All patients reported New York Heart Association class I, the overall cohort had an impaired exercise capacity (80 ± 14% of predicted peak oxygen consumption). Fragmented QRS was present in 27%. Exercise CMR showed that 20% of patients had abnormal contractile reserve (CR) of the left ventricle (LV) and 25% had reduced CR of the right ventricle (RV). CR LV and CR RV were significantly associated with impaired exercise capacity. Pathological patterns on myocardial delayed enhancement and hinge point fibrosis were detected. Biomarkers were normal., Conclusion: This study found that in some asymptomatic ASO patients electrical, LV and RV changes at rest, and signs of fibrosis are present. Maximal exercise capacity is impaired and seems to be linearly related to the CR of the LV and the RV. Therefore, exercise CMR might play a role in detecting subclinical deterioration of ASO patients., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: HFA-PEFF and cardiopulmonary exercise testing (CPET) are comprehensive diagnostic tools for heart failure with preserved ejection fraction (HFpEF). We aimed to investigate the incremental prognostic value of CPET for the HFA-PEFF score among patients with unexplained dyspnea with preserved ejection fraction (EF)., Methods: Consecutive patients with dyspnea and preserved EF (n = 292) were enrolled between August 2019 and July 2021. All patients underwent CPET and comprehensive echocardiography, including two-dimensional speckle tracking echocardiography in the left ventricle, left atrium and right ventricle. The primary outcome was defined as a composite cardiovascular event including cardiovascular-related mortality, acute recurrent heart failure hospitalization, urgent repeat revascularization/myocardial infarction or any hospitalization due to cardiovascular events., Results: The mean age was 58 ± 14.5 years, and 166 (56.8%) participants were male. The study population was divided into three groups based on the HFA-PEFF score: < 2 (n = 81), 2-4 (n = 159), and ≥ 5 (n = 52). HFA-PEFF score ≥ 5, VE/VCO 2 slope, peak systolic strain rate of the left atrium and resting diastolic blood pressure were independently associated with composite cardiovascular events. Furthermore, the addition of VE/VCO 2 and HFA-PEFF to the base model showed incremental prognostic value for predicting composite cardiovascular events (C-statistic 0.898; integrated discrimination improvement 0.129, p = 0.032; net reclassification improvement 1.043, p ≤ 0.001)., Conclusions: CPET could be exploited for the HFA-PEFF approach in terms of incremental prognostic value and diagnosis among patients with unexplained dyspnea with preserved EF., Competing Interests: Declaration of Competing Interest Jung Sun Cho has no conflicts of interest to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Exertional oscillatory breathing (EOV) represents an emerging prognostic marker in heart failure (HF) patients, however little is known about EOV meaning with respect to its disappearance/persistence during cardiopulmonary exercise test (CPET). The present single-center study evaluated EOV clinical and prognostic impact in a large cohort of reduced ejection fraction HF patients (HFrEF) and, contextually, if a specific EOV temporal behavior might be an addictive risk predictor., Methods and Results: Data from 1.866 HFrEF patients on optimized medical therapy were analysed. The primary cardiovascular (CV) study end-point was cardiovascular death, heart transplantation or LV assistance device (LVAD) implantation at 5-years. For completeness a secondary end-point of total mortality at 5- years was also explored. EOV presence was identified in 251 patients (13%): 142 characterized by EOV early cessation (Group A) and 109 by EOV persistence during the whole CPET (Group B). The entire EOV Group showed worse clinical and functional status than NoEOV Group (n = 1.615) and, within the EOV Group, Group B was characterized by a more severe HF. At CV survival analysis, EOV patients showed a poorer outcome than the NoEOV Group (events 27.1% versus 13.1%, p < 0.001) both unpolished and after matching for main confounders. Instead, no significant differences were found between EOV Group A and B with respect to CV outcome. Conversely the analysis for total mortality failed to be significant., Conclusions: Our analysis, albeit retrospective, supports the inclusion of EOV into a CPET-centered clinical and prognostic evaluation of the HFrEF patients. EOV characterizes per se a more advanced HFrEF stage with an unfavorable CV outcome. However, the EOV persistence, albeit suggestive of a more severe HF, does not emerge as a further prognostic marker., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: To evaluate the consistency on the target heart rate for exercise determined by simple target heart rate (sTHR) based on resting heart rate (HRrest) and heart rate at anaerobic threshold (HRAT) in cardiopulmonary exercise test (CPET) for patients with chronic heart failure., Methods: This is a retrospective cohort study, in which CHF patients who underwent CPET in Tongji Hospital Cardiac Rehabilitation Center Affiliated to Tongji University from March 2007 to December 2018 were enrolled. The clinical data of the patients from the electronic medical record system, HRrest and HRAT measured by CPET were collected. Patients were further divided into subgroups according to gender, age (<60 years group and ≥ 60 years group), with or without beta-blocker therapy and subgroup of heart failure (heart failure with reduced, mid-range and preserved ejection fraction). The sTHR (HRrest plus 10, 15, 20, 25 and 30 bpm) and HRAT were all calculated in each patient. Paired t-test was used for the difference between the two methods, correlation analysis was shown by pearson analysis and intraclass correlation coefficient (ICC) was calculated for consistency test., Results: A total of 547 CHF patients were enrolled, including 447 males (81.7%), aged 63 (56,69) years, with BMI of 25.2 (23.5,26.4) kg/m 2 and LVEF of 45.0 (36.0, 52.0) %. The target heart rate determined by HRAT method was (93.59 ± 13.95) bpm, and its counterpart determined by HRrest plus 20 bpm (HRrest +20 ) was (93.16 ± 7.69) bpm. There was no significant difference between the two methods (P>0.05). However, it was statistically different between HRrest plus 10, 15, 25, 30 bpm and HRAT respectively (P<0.001). And HRrest +20 was positively correlated with HRAT (r = 0.418, P<0.001). Therefore, HRrest +20 below was regarded as sTHR. The ICC of the consistency test between sTHR and HRAT was 0.523,95%CI 0.435-0.596 (P < 0.001) in all patients (n = 547). In patients with beta-blocker therapy (n = 464), the ICC of sTHR and HRAT consistency test was 0.534,95%CI 0.441-0.612, P < 0.001; The ICC of the consistency test between sTHR and HRAT of patients without beta-blocker therapy (n = 83) was 0.407,95%CI 0.083-0.616, P < 0.05. In the sinus rhythm group (n = 466), the ICC of sTHR and HRAT consistency test was 0.527,95%CI 0.433-0.606, P < 0.001; The ICC of the consistency test between sTHR and HRAT of atrial fibrillation patients in group (n = 81) was 0.482,95%CI 0.195-0.667, P < 0.05.The ICC of the consistency test between sTHR and HRAT was 0.501,95%CI 0.338-0.623 (P < 0.001) in patients under 60 years old (n = 195); The ICC of the consistency test between sTHR and HRAT in patients ≥60 years old (n = 352) was 0.533,95%CI 0.424-0.621, P < 0.001. In the male group (n = 447), the ICC of sTHR and HRAT consistency test was 0.577,95%CI 0.491-0.649, P < 0.001; The ICC of the consistency test between sTHR and HRAT of female patients in group (n = 100) was 0.344,95%CI 0.025-0.559, P < 0.05. The ICC of sTHR and HRAT consistency test in HFrEF group (n = 170) was 0.395,95%CI 0.181-0.553, P < 0.01; The ICC values of the consistency test between sTHR and HRAT was 0.543, 95%CI 0.405-0.649 (P < 0.001) in patients with HFmrEF (n = 222); In HFpEF group (n = 155), the ICC of sTHR and HRAT consistency test was 0.620,95%CI 0.478-0.723, P < 0.001., Conclusion: The exercise target heart rate calculated by HRrest is consistent with that determined by HRAT in patients with CHF. For primary hospitals without CPET, exercise prescription equivalent to AT intensity for patients with CHF can be determined by HRrest. However, the target heart rate calculated by HRrest can't replace that determined by HRAT in this patient cohort completely., Competing Interests: Declaration of Competing Interest The authors report none., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: To evaluate the change in aerobic fitness (VO 2max ), measured by cardio-pulmonary exercise test (CPET), in children with congenital heart disease (CHD), compared to matched healthy controls, and identify predictors of VO 2max change with time in this specific population., Method: This longitudinal retrospective multicentre cohort study was carried out from 2010 to 2020. We included CHD paediatric patients from the cohort of a previous cross-sectional study, who had a second CPET at least 1 year after the first one, during their follow-up., Results: We included 936 children, 296 in the CHD group and 640 controls. Mean time between baseline and final CPET was 4.4 ± 1.7 years. After matching on age and gender and adjustment for age and BMI, the mean VO2 max group difference was 10.5% ± 1.0% of percent-predict VO 2max at baseline and increased to 19.1% ± 1.3% at final assessment. In the CHD group, the proportion of children with impaired aerobic fitness was significantly higher at final than at baseline CPET assessment (51.4% vs 20.3%; P < 0.01). The mean annual VO 2max decrease was significantly worse in the CHD group than in controls (-1.88% ± 0.19% of percent-predict VO 2max /year vs. -0.44% ± 0.27% of percent-predict VO 2max /year, P < 0.01, respectively). In multivariate analyse, male gender, a high initial VO 2max , a high BMI, and the number of cardiac surgical procedures ≥2, were predictors of the VO 2max decrease with time., Conclusion: The VO 2max decrease with time is more pronounced in children with CHD compared to healthy matched controls. This study highlighted the importance of serial CPET assessment in children with CHD. Trial registration NCT04815577., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Among heart failure patients diagnosed as having exertional oscillatory ventilation (OV), some present with OV at rest that persists during exercise, and others develop OV only after the onset of exercise during cardiopulmonary exercise (CPX) testing. We tested whether or not there was any difference in the prognostic significance between the two abnormal breathing patterns., Methods: Patients with New York Heart Association class III-heart failure were categorized into the following 3 groups according to their ventilation pattern during the CPX: patients with an OV pattern at rest that persisted for ≥60% of the exercise test at an amplitude of ≥15% of the average resting value (group 1), patients with the same abnormal ventilatory pattern as group 1 that was observed only during exercise (group 2), and patients without any OV (group 3). The patients were followed-up for at least 2 years to assess the composite outcome of cardiac death or hospitalization for worsening heart failure., Results: The occurrence of the composite outcome differed significantly across the groups with its highest occurrence in group 1 (21/29 [72.4%], 15/38 [39.5%] and 48/167 [28.7%]; log-rank P < 0.001). In multivariate hazard analyses, an N-terminal pro-brain natriuretic peptide of >900 pg/mL (hazard ratio [HR] = 1.72, P = 0.04), and group 1 (HR 2.03, P = 0.02) were independently associated with the composite outcome., Conclusions: Checking for the resting OV prior to incremental exercise during CPX testing may be helpful in risk-stratification among subjects with advanced heart failure., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Cardiopulmonary exercise testing (CPX) is the gold-standard approach to assessing cardiorespiratory fitness (CRF). The current study puts forth reference standards for peak oxygen (O 2 ) pulse from the "Fitness Registry and the Importance of Exercise: A National Data Base" (FRIEND) Registry., Methods: The current analysis included 13,318 tests from CPX laboratories in the United States, Canada and Europe. Inclusion criteria included CPX data on apparently healthy men and women: 1) aged ≥20 years; 2) with exercise tests performed on a treadmill; and 3) achieving a peak respiratory exchange ratio ≥ 1.00., Results: Peak O 2 pulse 50th percentile values decreased from 20.8 ml/beat in the 2nd decade to 11.2 ml/beat in the 8th decade in men and from 13.6 ml/beat in the 2nd decade to 7.9 ml/beat in the 8th decade in women. Linear regression analysis results produced the following statistically significant (p < 0.001) equation: peak O 2 pulse (ml/beat) = 23.2-0.09(age) - 6.6(sex); female = 1 and male = 0., Discussion: The assessment of CRF through CPX is an important health metric. Reference standards, such as those put forth in the current study, allow for the comparison of key measures of CRF to expected normal responses across the adult lifespan., (Copyright © 2019. Published by Elsevier B.V.)

Background: Children with repaired congenital heart disease (CHD) have impaired maximal aerobic capacity (VO2max). Determining the causes of their VO2max alteration remains challenging. Cardiac output measure using thoracic impedancemetry during cardiopulmonary exercise tests (CPET) can help to understand the determinants of VO2max in children with open-heart repaired CHD., Method: We analyzed CPET in 77 children with repaired CHD. Among them, 55 patients had residual lesions. Patients with repaired CHD were compared with 44 age-matched healthy individuals. Maximal oxygen content brought to capillaries (QO2max) and oxygen muscle diffusion capacity (DO2) were assessed using cardiac output measure, Fick principle and simplified Fick law., Results: In the 55 patients with residual lesion, VO2max, QO2max and DO2 were lower than those of controls (76.1 vs 86% of theoretical value, p < 0.01; 2.15 vs 2.81 L/mn, p < 0.001; 24.7 vs 28.8 ml/min/mmHg, p < 0.05). Decrease in QO2max was due to both impaired stroke volume and chronotropic insufficiency (48 vs 53 ml/m 2 and p < 0.05; 171 vs 185/min p < 0.001). Patients without residual lesion (22/77) had normal VO2max with lower maximal heart rate compensated by higher SV (p < 0.05)., Conclusion: Aerobic capacity was normal in children without residual lesions after CHD repair. Patients with residual lesion have impaired VO2max due to both lower central and peripheral determinants. Measuring cardiac performance during CPET allowed a better selection of patients with altered cardiac reserve that can benefit from residual lesion treatment and find the good timing for intervention. Detection of peripheral deconditioning can lead to a rehabilitation program., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: To assess the relationship between heart rate response and exercise tolerance in adults with systemic right ventricle (sRV) after atrial switch repair for Transposition of the Great Artery (TGA) in addition to other physiological parameters., Methods: All patients with a sRV after atrial switch repair for TGA followed in our institution between June 2015 and April 2018 who underwent cardiopulmonary exercise testing (CPET) were analyzed. Cardiac imaging performed within a six-month time period of the CPET were also collected. Chronotropic incompetence was defined as the inability to achieve 80% of age-predicted maximal heart rate reserve (HRR) and <62% on a beta-blocker regimen. Patient characteristics were assessed according to tertiles of the percentage of predicted pVO2 (%ppVO2)., Results: We studied 70 patients (mean of age 32.4 ± 7.6 years old, 51 males). Mean peak oxygen uptake was 21.5 ± 5.8 mL/kg/min, corresponding to a %ppVO2 of 57 ± 14.1% while mean VE/VCO2 slope was 37.1 ± 8.2. There was a trend toward more exaggerated hyperventilation in patient with lower pVO2. Mean age-adjusted HRR was 68.5 ± 19%. Chronotropic incompetence was observed in 65.7% and was correlated with %ppVO2 (r = 0.482; p < 0.001) as physical training evaluated with Ventilatory Anaerobic threshold (r = 0.571; p < 0.001), while no difference was found based on respiratory parameters. No echocardiographic or Magnetic Resonance Imaging parameters assessing sRV systolic function at rest were correlated with %ppVO2., Conclusions: Exercise limitation is related to the inability to increase cardiac output during exercise and is notably due to the degree of chronotropic incompetence., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Hypertension is common in patients with aortic stenosis (AS) and optimal blood pressure (BP) control is advised to reduce arterial load and cardiovascular events. Whether calcium channel blockers (CCB) are safe is not known., Methods: This was a retrospective analysis of 314 patients (age 65 ± 12 years, 68% men) with moderate or severe asymptomatic AS. Hypertension was defined from a history of hypertension, past or current antihypertensive treatment or a BP at the baseline clinic visit >140/90 mmHg. All patients underwent an exercise treadmill test (ETT) and echocardiography., Results: The prevalence of hypertension was 73.6%, and 65% took antihypertensive treatment. Patients who used a CCB (25%) (CCB+) were older, more likely to have hypercholesterolemia and coronary artery disease, and had higher systolic BP, stroke work, left ventricular mass compared to CCB-patients (all p < 0.05). During the baseline ETT, CCB+ patients achieved a lower peak heart rate, a shorter exercise time and were more likely to have a blunted BP response compared to CCB- patients (p < 0.05). Event-free survival was significantly lower in CCB+ than CCB- patients (all-cause mortality 16 [20.3%] versus 13 [5.6%]; p < 0.001). In a multivariable Cox regression model, CCB+ was associated with a 7-fold increased hazard ratio (HR) for all-cause mortality (HR 7.09; 95% CI 2.15-23.38, p = 0.001), independent of age, hypertension, diabetes, left ventricular ejection fraction, and aortic valve area., Conclusion: The use of CCB was associated with an adverse effect on treadmill exercise and reduced survival in asymptomatic patients with moderate or severe AS., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Despite widespread use of ETT and vasodilator-stress with myocardial perfusion imaging (MPI) for noninvasive detection of flow-limiting coronary artery disease, there is continued need to improve diagnostic accuracy. We examined whether measurement of interlead T-wave heterogeneity (TWH) during exercise tolerance testing (ETT) or pharmacologic stress testing improves detection of stenoses in large epicardial coronary arteries., Methods: All 137 patients at our institution who underwent diagnostic coronary angiography within 0 to 5 days after ETT (N = 81) or dipyridamole IV infusion (N = 58) in 2016 were studied, including 2 patients with both tests. Cases (N = 93) had angiographically significant stenosis (≥50% of left main or ≥ 70% of an epicardial coronary artery ≥2 mm in diameter); controls (N = 44) did not. TWH, i.e., interlead splay of T waves, was determined by second central moment analysis from precordial leads by an investigator blinded to angiographic results., Results: At rest, TWH levels were similar for cases and controls. ETT and dipyridamole stress testing increased TWH by 69% (p < 0.0001) and 27% (p < 0.0001), respectively, in cases. In controls, TWH did not change. Areas under the ROC curves for TWH increase for any flow-limiting coronary artery stenosis were 0.737 (p < 0.0001) for ETT and 0.818 (p < 0.0001) for dipyridamole stress testing. By contrast, neither ST-segment changes during ETT (p = 0.12) nor MPI during dipyridamole stress testing (p = 0.60) discriminated cases from controls., Conclusions: TWH measurement is a novel method that improves detection of angiographically confirmed flow-limiting stenoses in large epicardial coronary arteries during both ETT and MPI during pharmacologic stress testing with dipyridamole., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Both coronary microvascular dysfunction (CMD) and reduced exercise capacity are associated with adverse cardiovascular prognosis. The association between CMD and cardiopulmonary exercise testing (CPET) derived exercise capacity in symptomatic individuals without obstructive coronary artery disease (CAD) is not clear. We investigated whether exercise capacity was reduced in women with angina, CMD and no obstructive CAD compared with sex-matched controls. Furthermore, we assessed the association between CMD and other CPET-derived variables., Methods: All participants underwent transthoracic Doppler echocardiography of the left anterior descending artery with dipyridamole-induced vasodilation and CPET using ergometer cycle with an incremental test protocol., Results: We included 99 women with angina and no obstructive CAD (patients) and 27 asymptomatic women (controls), age (mean ± standard deviation) 61 ± 10 and 58 ± 10 years, respectively. Patients had a higher burden of risk factors compared with controls, while the weekly physical activity level was comparable between the groups (p = 0.72). CMD was present in 27 (27%) patients and 5 (19%) controls. Peak VO 2 was significantly reduced in patients with CMD compared with controls with normal coronary microvascular function ((median (IQR) 17.3 (15.5-21.3) vs. 27.3 (21.6-30.8) ml/kg/min; age-adjusted p = 0.001), independent of cardiovascular risk factors (p = 0.041). Presence of CMD in symptomatic women was also associated with diminished heart rate reserve (p < 0.001) and blunted heart rate recovery., Conclusions: Women with angina, CMD and no obstructive CAD have markedly reduced exercise capacity compared with sex-matched controls. Moreover, combination of angina and CMD is associated with impaired heart rate response and heart rate recovery., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: CT myocardial perfusion imaging (CTP) represents one of the newly developed CT-based techniques but its cost-effectiveness in the clinical pathway is undefined. The aim of the study is to evaluate the usefulness of combined evaluation of coronary anatomy and myocardial perfusion in intermediate to high-risk patients for suspected CAD or with known disease in terms of clinical decision-making, resource utilization and outcomes in a broad variety of geographic areas and patient subgroups., Methods: CTP-PRO study is a cooperative, international, multicentre, prospective, open-label, randomized controlled study evaluating the cost-effectiveness of a CCTA+CTP strategy (Group A) versus usual care (Group B) in intermediate-high risk patients with suspected or known CAD who undergo clinically indicated diagnostic evaluation. A total sample size of 2000 subjects will be enrolled and followed up for 24 months. The primary endpoint is the reclassification rate of CCTA in group A due to the addition of CTP. The secondary endpoint will be the comparison between groups in terms of non-invasive and invasive downstream testing, prevalence of obstructive CAD at ICA, revascularization, cumulative ED and overall cost during the follow-up at 1- and 2-years. The tertiary endpoint will be the comparison between each group in terms of MACE and cost-effectiveness at 1- and 2-years., Conclusions: The study will provide information to patients, health care providers and other stakeholders about which strategy could be more effective in the diagnosis of suspected CAD in intermediate to high-risk patients or in the symptomatic patients with known CAD and previous history of revascularization., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Systemic right ventricle (RV) is a rare and complex congenital heart disease (CHD). Patients with a systemic RV present with a significant decrease of their exercise capacity. We aimed at identifying clinical and paraclinical factors associated with maximum oxygen uptake (VO2 max ) in adults with a systemic RV., Methods: This multicentre cross-sectional study was performed in 2017 in three French tertiary care CHD centres. Adult patients with a D-transposition of the great artery (d-TGA) or a congenitally corrected TGA (cc-TGA) were included. Demographic, clinical, laboratory and imaging data were collected. Univariate and multivariate analyses were performed to identify predictors of impaired VO2 max , as measured by cardiopulmonary exercise test (CPET)., Results: A total of 111 patients were included in the study (85% d-TGA, median age 37.2 ± 8.2 years). Most patients presented with impaired physical capacity (mean VO2 max of 23.3 ± 6.9 ml/kg/min, representing 68.4 ± 16.6% of predicted values) and ventilatory anaerobic threshold (VAT) impaired (mean VAT of 32.7 ± 10.9% of the predicted values). In univariate analysis, VO2 max correlated with professional status, NYHA functional class, BNP level, the type of systemic RV, decreased RV function values in cardiac imaging, the severity of tricuspid regurgitation, the presence of a pacemaker or an implantable defibrillator, the VAT, the maximum load, and the maximal heart rate during exercise. In multivariate analysis, the VO2 max remained associated with the NYHA functional class. The final multivariate model explained 49% of the variability of VO2 max ., Conclusion: NYHA functional class and RV function are predictors of impaired exercise capacity in adult patients with systemic RV., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Functional aerobic capacity (FAC) determined by treadmill exercise testing (TMET) is associated with cardiovascular (CV) disease mortality independent of traditional CV risk factors and is a potentially underutilized tool. The purpose of this study was to determine added prognostic value of reduced FAC and other exercise test abnormalities beyond CV risk factors for predicting total and CV mortality., Methods: The TMET database was queried for Minnesota patients (≥30 years) without baseline CV disease from September 21, 1993, through December 20, 2010. Risk factors and exercise abnormalities including low FAC (<80% predicted), abnormal heart rate recovery (<13 bpm), and abnormal electrocardiogram (ST depression ≥1 mm regardless of baseline) were extracted. Mortality data were obtained through February 2016. Patients were divided into 9 groups by abnormality number (0, 1, or ≥2) and risk factors (0, 1, or ≥2). Cox regression was used to determine mortality risk according to exercise abnormalities/CV risk factors, adjusted for age and sex., Results: 19,551 patients met inclusion criteria; 1271 (6.5%) died over 12.4 ± 5.0 years' follow-up (405 [32%] CV deaths). Exercise abnormalities significantly modified risk for every number of CV risk factors. Hazard ratios (95% CI) for total mortality (0 vs ≥2 abnormalities) were 2.4 (1.9-2.9; P < .001) for 0 CV risk factors; 2.7 (2.2-3.3; P < .001), 1 risk factor; and 6.1 (4.8-7.7; P < .001), ≥2 risk factors. Similar results were noted for CV disease mortality., Conclusions: Exercise test abnormalities strongly predict mortality beyond traditional CV risk factors. Our results indicate that TMET should be considered for CV risk assessment., (Copyright © 2019. Published by Elsevier B.V.)

Background: Ethnicity is an important determinant of athletes' cardiovascular adaptation. Black adolescent and adult athletes exhibit a left ventricular (LV) hypertrophy with a concentric remodelling higher than their Caucasian counterparts. Scant data, however, are available on race-related differences in hemodynamic response of adolescent athletes to exercise and its relation with heart remodelling. We evaluated if race-specific, sport-related structural and electrical remodelling in adolescent athletes of Caucasian and African ethnicity exclusively depends on race itself rather than on different cardiovascular responses to physical exercise., Methods: We examined 90 adolescent athletes, 60 Caucasian (WA) and 30 Black (BA). All participants underwent thorough clinical, echocardiographic and stress test evaluations., Results: BA had greater indexed LV mass (LVM/BSA) with increased relative wall thickness (RWT) implying a concentric remodelling. BA showed higher systolic blood pressure (SBP) compared to WA during the whole exercise test. ECG data showed that BA vs WA had a significant shorter QRS duration in each step considered with a significant greater QT dispersion. BA reached a higher relative pressure peak as compared to WA. RWT was strongly influenced by ethnicity and less by SBP at peak of exercise (PE), although LVM/BSA was significantly related to SBP at PE and just marginally to age and not significantly to race., Conclusions: Black adolescent athletes showed higher SBP during all steps of exercise associated to a different trend. Ethnicity was the main determinant of RWT, suggesting that LV geometry is principally race-related rather than influenced by a different hemodynamic profile to physical activity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In the present practice review, we will explain how to perform and interpret a cardiopulmonary exercise test (CPET) in heart failure patients. Specifically, we will explain why cycle ergometer should be preferred to treadmill, the type of protocol needed, and the ideal exercise duration. Thereafter, we will discuss how to interpret CPET findings and determine the parameters that should be included. We will focus specifically on: peak VO 2 (absolute value and a percentage of its predicted value), exercise duration, respiratory exchange ratio, peak work rate, heart rate, O 2 pulse, end-tidal carbon dioxide pressure (PetCO 2 ), PetO 2 , and -if blood gas samples are obtained-dead space to tidal volume ratio. Moreover, we will discuss the physiological and clinical value of anaerobic threshold, respiratory compensation point, ventilation vs. VCO 2 and VO 2 vs. work relationships. Finally, attention will be dedicated to exercise-induced periodic breathing. We will also discuss when and why CPET should be integrated with other measurements in the so-called complex CPET. Specifically: a) when and how to use a complex non-invasive CPET, which integrates CPET measurements with non-invasive cardiac output determination, working muscle near-infrared spectroscopy, transthoracic echocardiography, thoracic ultrasound, and lung diffusion analysis; b) when and how to use a complex minimally invasive CPET, in which CPET is combined with esophageal balloon recordings or with serial arterial blood sampling for blood gas analysis; c) when and how to use a complex invasive CPET, which usually implies the presence of a Swan Ganz catheter in the pulmonary artery and an arterial line., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Exercise stress test (EST) has a moderate precision for diagnosis of CAD and could potentially obtain improved accuracy if adding a reliable cardiac biomarker to the test., Objective: We aimed to investigate resting levels and change in hs-cTnT during EST in patients with and without angiographically significant CAD. Moreover, we intended to explore the additive value of hs-cTnT to EST results in diagnosis of stable CAD. We hypothesized that hs-cTnT would be higher in CAD patients and increase diagnostic precision of EST., Method: Patients presenting with symptoms of stable CAD, performed a maximal EST on a bicycle ergometer. Venous blood samples were taken at rest and within 5 min post-exercise. All patients underwent coronary angiography. Significant CAD was defined as having ≥75% stenosis in one or more segments of the coronary arteries., Results: Out of the 297 participants, significant CAD was found in 111 (37%) patients. Patients with significant CAD compared to without, had higher resting levels of hs-cTnT (median 8.1 vs 5.0 ng/L) and no significant difference in exercise-induced change (median 0.5 vs 0.3 ng/L), p < 0.001 and p = 0.086 respectively. Combined resting hs-cTnT with EST had higher predictive value for significant CAD than EST alone, AUC = 0.751 vs. AUC = 0.637. In an adjusted multivariable regression analysis, resting hs-cTnT >6.0 ng/L was predictive for having significant CAD, OR 2.55 (CI 95% 1.40, 4.65 p = 0.002)., Conclusion: In patients with suspected stable CAD, hs-cTnT has a predictive value alone, as well as added to a diagnostic EST for CAD., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Impaired pulmonary function is an independent predictor of mortality in adult congenital heart disease (CHD), but has been scarcely studied in the paediatric CHD population., Aims: To compare the pulmonary function of children with CHD to healthy controls, and evaluate its association with clinical outcomes, exercise capacity, and quality of life., Methods: Cross-sectional multicentre study among 834 children (555 CHD and 279 control subjects) who underwent a complete spirometry and a cardiopulmonary exercise test (CPET). The 5th centile (Z-score = -1.64) was used to define the lower limit of normal. The association of clinical and CPET variables with spirometry was studied using a multivariate analysis. Children and their parents filled in the Kidscreen health-related quality of life questionnaire., Results: Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) Z-scores values were lower in children with CHD than controls (-0.4 ± 1.5 vs. 0.4 ± 1.3, P < 0.001 and -0.5 ± 1.4 vs. 0.4 ± 1.2, P < 0.001, respectively), without any obstructive airway disorder. Restrictive pattern was more frequent in CHD patients than in controls (20% vs. 4%, P < 0.0001). FVC Z-scores were predominantly impaired in complex CHD, such as heterotaxy (-1.1 ± 0.6), single ventricle (-1.0 ± 0.2), and complex anomalies of the ventricular outflow tracts (-0.9 ± 0.1). In multivariate analysis, FVC was associated with age, body mass index, peak oxygen uptake, genetic anomalies, the number of cardiac surgery and cardiac catheter procedures. FVC and FEV1 correlated with self and proxy-related quality of life scores., Conclusion: These results suggest that pulmonary function should be monitored early in life, from childhood, in the CHD population., Trial Registration Number: NCT01202916, post-results., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: This study examined the accuracy of cardiopulmonary exercise testing (CPET) on a treadmill (TM) and recumbent ergometry (RE) in the predicting coronary artery disease (CAD) severity and prognosis., Methods: Forty Caucasian subjects, mean age 63.5 ± 7.6, with significant coronary artery lesions (≥50%) were included. Within two months of coronary angiography, TM and RE CPET were performed on two visits 2-4 days apart and subsequently followed up to 32 ± 10 months., Results: Mean left ventricular ejection fraction was 56.7 ± 9.6%. TM CPET exhibited a higher occurrence of ST segment depression ≥ 1 mm (71.05% vs 28.95%, p = 0.04). Subjects with 1-2 stenotic coronary arteries (SCA) demonstrated a better CPET response compared to those with 3-SCA. ROC analysis revealed a high predictive value for the ventilation/carbon dioxide production (VE/VCO 2 ) slope obtained on TM (area 0.84, p = 0.003, Sn 88.9%, Sp 72%) in distinguishing between 1 and 2-SCA and 3-SCA. Among all CPET parameters, work efficiency (∆VO 2 /∆WR) during RE predicted cumulative cardiac events (p < 0.01)., Conclusions: CPET parameters hold predictive value for CAD severity and prognosis. CPET on a TM appears to be more reliable in the quantification of CAD compared to RE., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Pre-participation screening (PPS) of athletes aged over 35 years (master athletes, MA) is a major concern in Sports Cardiology. In this population, sports-related sudden cardiac death is rare but usually due to coronary atherosclerosis (CA). Coronary CT Angiography (CCTA) has changed the approach to diagnosis/management of CA, but its role in this context still needs to be assessed., Methods and Results: We retrospectively examined 167 MA who underwent CCTA in our hospital since 2006, analyzing symptoms, stress-test ECG, cardiovascular risk profiles (SCORE) and CCTA findings. Among the whole enrolled population, 153 (91.6%) MA underwent CCTA for equivocal/positive stress-test ECG with/without symptoms, 13 (7.8%) just for clinical symptoms, 1 (0.6%) for the family history. The CCTA showed the presence of CA in 69 MA (41.3%), congenital coronary anomalies (anomalous origin or deep myocardial bridge) in 8 (4.8%), both in 7 (4.2%). A negative CCTA was observed in 83 MA (49.7%). The risk-SCORE (age, hypertension, hypercholesterolemia, smoking) was a good indicator for the presence of moderate/severe CA on CCTA. However, mild/moderate CA was present in 17.8% of MA clinically stratified at a low risk-SCORE., Conclusion: While coronary angiography is more indicated in athletes with positive stress-test ECG and high clinical risk, the CCTA may be useful in the evaluation of MA with an abnormal stress test ECG and/or clinical symptoms engaged in competitive sports with a high cardiovascular involvement. Age, gender, presence of symptoms and clinical risk-SCORE assessment may help sports physicians and cardiologists to decide whether to request a CCTA or not., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The long-term evolution of pulmonary vascular resistance (PVR) after ventricular septal defect (VSD) repair is unknown. This study serially evaluated resting and exercise PVR after VSD repair in childhood., Methods: Patients were enrolled from the outpatient Adult Congenital Heart Disease clinic of the University Hospitals Leuven and compared to age- and gender-matched controls. Participants underwent resting and exercise echocardiography and cardiopulmonary exercise testing at baseline and follow-up. Total PVR was calculated as the ratio of mean pulmonary artery pressure (mPAP) to cardiac output (CO). The slope of the mPAP-CO curve (exercise PVR) was obtained using linear regression analysis., Results: Twenty-seven patients (mean age 31 ± 7 years, 70% male) and 18 controls were included. At baseline, patients had larger right ventricular (RV) end-diastolic areas (10 ± 2 vs 9 ± 1 cm 2 /m 2 , p = 0.001) and lower tricuspid annular plane systolic excursion (TAPSE) (17 (17-19) vs 26 (22-28) mm, p < 0.001). After 1.1 (1.0-1.5) years follow-up, similar differences in RV areas and TAPSE were found. Patients reached lower peak workload and cardiac index compared to controls at each time point. Peak total PVR was higher (Baseline: 2.7 ± 0.8 vs 2.2 ± 0.3 mm Hg/L/min, p = 0.005; Follow-up: 2.9 ± 0.9 vs 2.1 ± 0.3 mm Hg/L/min, p < 0.001) and the mPAP-CO slope was steeper (Baseline: 2.2 ± 0.8 vs 1.7 ± 0.3 mm Hg/L/min, p = 0.008; Follow-up: 2.5 ± 0.9 vs 1.6 ± 0.3 mm Hg/L/min, p < 0.001) in patients. The mPAP-CO slope in patients correlated inversely with peak oxygen uptake (R = -0.41 and - 0.45, p = 0.036 and 0.022, baseline and follow-up, respectively)., Conclusion: Despite repair, VSD patients seem to show altered pulmonary hemodynamics and RV impairment at rest and exercise, supporting life-long follow-up., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The effects of adding moderate-to-high intensity inspiratory muscle training (IMT) to short-term aerobic and resistance exercise (combined training [CT]), after coronary artery bypass grafting (CABG) are not established. This study aimed to determine the effects of moderate-to-high intensity IMT + CT on exercise capacity, respiratory muscle strength, inspiratory muscle endurance, quality of life (QoL), and laboratory biomarkers in patients after CABG who were participants of a phase II cardiac rehabilitation program., Methods: Twenty-four patients were randomly assigned to either the IMT + CT group (n = 12), who performed moderate-to-high intensity IMT with CT or the sham-IMT + CT group (n = 12). Patients completed two sessions per week for 12 weeks. Each patient underwent a cardiopulmonary exercise test, six-minute walk test (6MWT), respiratory muscle strength and endurance evaluation, QoL questionnaire, and serum advanced oxidation protein products, ferric reducing antioxidant power [FRAP], nitrate/nitrate, and high-sensitivity C-reactive protein, before and after the 12-week intervention., Results: The IMT + CT group showed significantly greater improvements in peak oxygen uptake (1.3 mL∙kg -1 ∙min -1 ; 95% confidence interval [95% CI], 0.5 to 2.2), distance covered during the 6MWT (78.8 m; 95% CI, 28.1 to 129.5), maximal inspiratory pressure (23.0 cmH 2 O; 95% CI, 9.3 to 36.7), QoL (-15.1 points; 95% CI, -26.9 to -3.3), and FRAP (83.7 μmol/L; 95% CI, 20.2 to 147.1) compared to the sham-IMT + CT group as a result of the intervention., Conclusions: Short-term moderate-to-high intensity IMT with CT provided additional benefits in exercise capacity, inspiratory muscle strength, QoL, and antioxidant profile in patients after CABG. Trial Registration clinicaltrials.gov Identifier: NCT02885077., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: In patients with heart failure, downregulation of adenosine receptor gene expression and impaired adenosine-related signal transduction may result in a diminished response to adenosine. This may have implications for cardiac stress testing. We evaluated the haemodynamic response to intravenous adenosine in patients with left ventricular systolic dysfunction (LVSD) undergoing stress cardiovascular magnetic resonance imaging (CMR)., Methods and Results: We retrospectively examined 497 consecutive patients referred for clinical stress CMR. Blood pressure and heart rate responses with intravenous adenosine were compared in patients with normal, mild-moderately impaired and severely impaired LV systolic function (ejection fraction [EF] > 55%, 36-55% and < 35%, respectively). Following 2 min of adenosine infusion, there was a significant difference between the groups in the heart rate change from baseline, with a diminished heart rate response in patients with LVSD (p < 0.001). An increase in the dose of adenosine (up to 210 μg/kg/min) was required to achieve a sufficient haemodynamic response in more patients with severe LVSD (41%) than those with mild-moderately impaired and normal LV systolic function (24% and 19%, respectively, p < 0.001). Even with increased doses of adenosine in subjects with severe LVSD, peak haemodynamic response remained blunted. With multivariate analysis age (p < 0.001) and LVEF (p = 0.031) were independent predictors of heart rate response to adenosine., Conclusion: Patients with reduced LVEF referred for stress CMR may have a blunted heart rate response to adenosine. Further study is warranted to determine whether this may be associated with reduced diagnostic accuracy and also the potential utility of further dose increases or alternative stressors., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In the summer of 2016, delegates from the German Society of Cardiology (DGK), the German Respiratory Society (DGP), and the German Society of Pediatric Cardiology (DGPK) met in Cologne, Germany, to define consensus-based practice recommendations for the management of patients with pulmonary hypertension (PH). These recommendations were built on the 2015 European Pulmonary Hypertension guidelines, aiming at their practical implementation, considering country-specific issues, and including new evidence, where available. To this end, a number of working groups was initiated, one of which was specifically dedicated to the definition, clinical classification and initial diagnosis of PH. While the European guidelines provide a detailed clinical classification and a structured approach for diagnostic testing, their application in routine care may be challenging, particularly given the changing phenotype of PH patients who are nowadays often elderly and may present with multiple potential causes of PH, as well as comorbid conditions. Specifically, the working group addresses the thoroughness of diagnostic testing, and the roles of echocardiography, exercise testing, and genetic testing in diagnosing PH. Furthermore, challenges in the diagnostic work-up of patients with various causes of PH including "PAH with comorbidities", CTEPH and coexisting conditions are highlighted, and a modified diagnostic algorithm is provided. The detailed results and recommendations of the working group on definition, clinical classification and initial diagnosis of PH, which were last updated in the spring of 2018, are summarized in this article., (Copyright © 2018. Published by Elsevier B.V.)

Background: Changes in circulatory physiology are common in Fontan patients due to suboptimal cardiac output, which may reduce the peripheral blood flow and impair the skeletal muscle. The objective of this study was to investigate the forearm blood flow (FBF), cross-sectional area (CSA) of the thigh and functional capacity in asymptomatic clinically stable patients undergoing Fontan surgery., Methods: Thirty Fontan patients and 27 healthy subjects underwent venous occlusion plethysmography, magnetic resonance imaging of the thigh musculature and maximal cardiopulmonary exercise testing. Muscle sympathetic nerve activity (MSNA), norepinephrine measures, cardiovascular magnetic resonance, handgrip strength and 6-minute walk test were also performed., Results: Fontan patients have blunted FBF (1.59 ± 0.33 vs 2.17 ± 0.52 mL/min/100 mL p < 0.001) and forearm vascular conductance (FVC) (1.69 ± 0.04 vs 2.34 ± 0.62 units p < 0.001), reduced CSA of the thigh (81.2 ± 18.6 vs 116.3 ± 26.4 cm 2 p < 0.001), lower peak VO 2 (29.3 ± 6 vs 41.5 ± 9 mL/kg/min p < 0.001), walked distance (607 ± 60 vs 701 ± 58 m p < 0.001) and handgrip strength (21 ± 9 vs 30 ± 8 kgf p < 0.001). The MSNA (30 ± 4 vs 22 ± 3 bursts/min p < 0.001) and norepinephrine concentration [265 (236-344) vs 222 (147-262) pg/mL p = 0.006] were also higher in Fontan patients. Multivariate linear regression showed FVC (β = 0.653; CI = 0.102-1.205; p = 0.022) and stroke volume (β = 0.018; CI = 0.007-0.029; p = 0.002) to be independently associated with reduced CSA of the thigh adjusted for body mass index. The CSA of the thigh adjusted for body mass index (β = 5.283; CI = 2.254-8.312; p = 0.001) was independently associated with reduced peak VO 2 ., Conclusion: Patients with Fontan operation have underdeveloped skeletal muscle with reduced strength that is associated with suboptimal peripheral blood supply and diminished exercise capacity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: There is a growing interest in exploring the concept of right ventricular functional reserve in patients with pulmonary arterial hypertension. However, it is still unclear how it should be assessed. Aim of the study was to investigate the determinants of the changes in cardiac output and in pulmonary pressure during dobutamine stress echocardiography in pulmonary arterial hypertension., Methods: Low-dose dobutamine stress echocardiography was performed in 55 patients and 28 controls. Tricuspid annular plane systolic excursion, its ratio to systolic pulmonary artery pressure, right ventricular area change, degree of tricuspid regurgitation, right ventricular end-systolic pressure-area ratio, cardiac output were assessed at rest and at peak stress., Results: According to the stress induced increase in cardiac output, patients were classified into 2 groups: above/equal to the median of 2.8 L/min (high cardiac output) or below the median (low cardiac output). High cardiac output patients were characterized by a greater increase in heart rate (+45.1 ± 17.5 vs +21.3 ± 17.7 bpm), a greater improvement in tricuspid annular plane systolic excursion (+4.2 ± 3.3 vs +1.9 ± 2.6 mm, P = 0.005) and a decrease in tricuspid regurgitation (P = 0.010) as compared to low cardiac output patients. Changes in pulmonary pressure were not associated with changes in indicators of right ventricular function but only with changes in heart rate., Conclusions: The increase in cardiac output during dobutamine is associated with an improvement in longitudinal right ventricular function, a decrease in tricuspid regurgitation and an increase in heart rate. Changes in pulmonary pressure only reflect the changes in heart rate., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The coronary sinus (CS) Reducer is a novel device designed to aid in the management and to improve quality of life of patients with severe angina symptoms refractory to optimal medical and interventional therapies. This study aims to assess the safety and efficacy of the Reducer in a real-world cohort of patients presenting with refractory angina., Methods: One hundred forty-one consecutive patients were treated with CS Reducer implantation. The primary efficacy endpoint was reduction in angina symptoms from baseline as assessed by Canadian Cardiovascular Society (CCS) class status and Seattle Angina Questionnaire (SAQ) scores. The primary safety endpoint was successful Reducer device delivery and deployment in the absence of any device-related events., Results: Procedural success was achieved in 139 (98.6%) patients. Reducer implantation was not obtained in 2 (1.4%) patients because of unfavorable anatomy of the CS. There were no CS perforations, cardiac tamponade, peri-procedural death or myocardial infarction during a median follow-up of 14 months (range from 6- to 70-month). In patients undergoing Reducer implantation, mean CCS class improved from 3.05 ± 0.53 at baseline to 1.63 ± 0.98 at follow-up (p < 0.001). Overall, 113 (81%) patients experienced at least 1 CCS improvement, and 63 (45%) patients at least 2 CCS-class improvement. All SAQ items improved significantly (p < 0.001 for all) and translated into a significant reduction in the mean number of anti-ischemic drugs prescribed (2.37 ± 0.97 vs 2.17 ± 0.95; p = 0.003)., Conclusions: In a real-world multi-center experience, implantation of the CS Reducer appears safe, and efficacious in reducing symptoms of angina and improving quality of life., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: We investigated whether increased concentrations of inspired oxygen (Fio 2 ) affects exercise tolerance in patients with heart failure and normal ejection fraction (HeFNEF)., Methods: 46 patients (mean age 75 years (63% male) and median NTproBNP 1432 (interquartile range: 543-2378 ng/l)) with HeFNEF (defined as signs or symptoms of heart failure requiring treatment with diuretics, with a left ventricular ejection fraction of >45% by echocardiography and amino terminal pro brain natriuretic peptide (NTproBNP) >220 ng/l) completed three maximal incremental exercise tests with different Fio 2 (21%, 28% and 40%) in random order. Fio 2 was controlled by investigator but blinded to patients. The primary outcome was exercise time (ET)., Results: Increasing Fio 2 significantly increased exercise time (522 ± 180 seconds for 21% to 543 ± 176 seconds, and 542 ± 177 seconds, for 28% and 40%, respectively, P = 0.04) with no difference in peak workload (57 ± 25 W, 58 ± 25 W and 57 ± 25 W, for 21%, 28% and 40%, respectively, P = 0.50). There was an increase in oxygen saturation but no change in peak heart rate with increasing Fio 2. Compared to patients with LVEF ≥50%, patients with LVEF between 45 and 49% had a significantly greater exercise time and peak workload. There was a correlation between the difference in exercise time between Fio 2 21% and 40% and age; but not with BMI, haemoglobin, creatinine or NTproBNP., Conclusion: Increasing Fio 2 during exertion leads to a small increase in exercise time in patients with HeFNEF., (Copyright © 2017. Published by Elsevier B.V.)

Background: In RCTs about revascularization, the terms "coronary artery disease" and "ischemic heart disease" are sometimes used interchangeably. This can create confusion concerning inclusion and exclusion criteria, which may lead to uncertain results., Objective: Our purpose is to investigate whether the study populations in randomized controlled trials (RCTs) which compared percutaneous coronary revascularization to medical therapy for stable ischemic heart disease specifically enrolled patients with demonstrable ischemia, and how many patients were included in trials with evidence of coronary atherosclerosis but without evidence of ischemia., Methods: Trial published data were obtained from ACME I, ACME II, RITA I, RITA II, MASS I, MASS II, AVERT, ACIP, COURAGE and FAME2. Published data were used to calculate the number of patients included in the trials with a negative stress test but significant coronary artery stenosis and the number of patients excluded from the trials with a positive stress test or angina, but without significant coronary artery stenosis at the time of angiography., Results: A total of 196,433 patients were screened between 1998 and 2011. Overall about 30% of patients were excluded if they did not meet the angiographic criteria, even though the presence of inducible ischemia or angina, and, about 20% of patients were included without inducible ischemia., Conclusion: RCTs have contributed to the confusion between coronary artery disease and ischemic heart disease. This may limit the ability to interpret the results and apply them in practice., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Percent of predicted peak VO 2 (ppVO 2 ) is considered a standard measure for establishing disease severity, however, there are known limitations to traditional normative values. This study sought to compare ppVO 2 from the newly derived "Fitness Registry and the Importance of Exercise: a National Database" (FRIEND) registry equation to conventional prediction equations in a clinical cohort of patients undergoing cardiopulmonary exercise testing (CPX)., Methods and Results: We selected 1094 patients referred for evaluation of heart failure (HF) symptoms who underwent CPX. ppVO 2 was calculated using the FRIEND, Wasserman/Hansen and Jones equations. Participants were followed for a median of 4.5 years [Interquartile range 3.5-6.0] for the composite endpoint of death, advanced HF therapy, or acute decompensated HF requiring hospital admission. Mean age was 48 ± 15 years and 62% were female. The FRIEND registry equation predicted the lowest ppVO 2 (measured/predicted; 71 ± 31%), compared to the Wasserman/Hansen (74 ± 29%) and Jones equations (83 ± 33%) (p < 0.001). All expressions of peak VO 2 were significant as univariate predictors of outcome with no significant differences between equations on pairwise analysis of receiver operating characteristic curves. When compared at a similar threshold of ppVO 2 the event rate was significantly lower in the FRIEND registry equation versus the currently used Wasserman and Jones equations., Conclusion: The use of the newly derived FRIEND registry equation predicts HF outcomes; however, it appears to predict a higher predicted VO 2 ; the clinical implication being a lower threshold of percent predicted peak VO 2 should be considered when risk stratifying patients with HF., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to investigate the effects of high intensity interval training (HIIT) versus moderate intensity continuous training (MICT) in heart failure patients with reduced ejection fraction (HFrEF)., Background: Despite the well-known positive effects of exercise in heart failure patients, the best mode of exercise is still under discussion., Methods: We searched Pubmed/MEDLINE, Cochrane Central Register of Controlled Trials, PEDro data base, and SciELO (from the earliest date available to October 2017) for randomized controlled trials that evaluated the effects of HIIT versus MICT in HFrEF patients. Weighted mean differences (WMD) with 95% confidence interval (CI) were calculated, and heterogeneity was assessed using the I 2 test., Results: 13 studies met the study criteria, including 411 patients. Compared to MICT, HIIT resulted in improvement in Peak VO 2 WMD (1.35 mL·kg -1 ·min -1 95% CI: 0.03 to 2.64 N = 411). HIIT resulted in no difference in VE/VCO 2 slope WMD (-1.21 95% CI: -3.0 to 0.58 N = 135), and quality of life measured by Minnesota Living with Heart Failure questionnaire WMD (1.19 95% CI: -5.81 to 8.19 N = 79). Sub-group analyses comparing studies with and without isocaloric exercise training protocol also showed a nonsignificant difference in peak VO 2 for participants in the HIIT group compared with MICT group., Conclusions: HIIT improves peak VO 2 and should be considered as a component of care of HFrEF patients. However, its superiority versus MICT disappears when isocaloric protocols are compared. An important caveat is uncertainty and variation of actual training intensities compared to program targets., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: To evaluate the relationship between right ventricular (RV) systolic dysfunction at rest and reduced exercise capacity in patients with a systemic RV (sRV)., Methods: All patients with congenitally corrected transposition of the great arteries (ccTGA) or complete TGA after atrial switch (TGA-Mustard/Senning) followed in our institution between July 2011 and September 2017 who underwent cardiac imaging within a six-month time period of cardiopulmonary exercise testing (CPET) were analyzed. We assessed sRV systolic function with TAPSE and fractional area change on echocardiogram and, if possible, with ejection fraction, global longitudinal and circumferential strain on cardiac magnetic resonance (CMR) imaging., Results: We studied 105 patients with an sRV (median age 34 [IQR 28-42] years, 29% ccTGA and 71% TGA-Mustard/Senning) of which 39% had either a pacemaker (n = 17), Eisenmenger physiology (n = 6), severe systemic atrioventricular valve regurgitation (n = 14), or peak exercise arterial oxygen saturation < 92% (n = 17). Most patients were asymptomatic or mildly symptomatic (NYHA class I/II/III in 71/23/6%). Sixty-four percent had evidence of moderate or severe sRV dysfunction on cardiac imaging. Mean peak oxygen uptake (pVO2) was 24.1 ± 7.4 mL/kg/min, corresponding to a percentage of predicted pVO2 (%ppVO2) of 69 ± 17%. No parameter of sRV systolic function as evaluated on echocardiography (n = 105) or CMR (n = 46) was correlated with the %ppVO2, even after adjusting for associated cardiac defects or pacemakers., Conclusions: In adults with an sRV, there is no relation between echocardiographic or CMR-derived sRV systolic function parameters at rest and peak oxygen uptake. Exercise imaging may be superior to evaluate whether sRV contractility limits exercise capacity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Exercise ECG (Ex-ECG) is advocated by guidelines for patients with low - intermediate probability of coronary artery disease (CAD). However, there are no randomized studies comparing Ex-ECG with exercise stress echocardiography (ESE) evaluating long term cost-effectiveness of each management strategy., Methods: Accordingly, 385 patients with no prior CAD and low-intermediate probability of CAD (mean pre-test probability 34%), were randomized to undergo either Ex-ECG (194 patients) or ESE (191 patients). The primary endpoint was clinical effectiveness defined as the positive predictive value (PPV) for the detection of CAD of each test. Cost-effectiveness was derived using the cumulative costs incurred by each diagnostic strategy during a mean of follow up of 3.0 years., Results: The PPV of ESE and Ex-ECG were 100% and 64% (p = 0.04) respectively for the detection of CAD. There were fewer clinic (31 vs 59, p < 0.01) and emergency visits (14 vs 30, p = 0.01) and lower number of hospital bed days (8 vs 29, p < 0.01) in the ESE arm, with fewer patients undergoing coronary angiography (13.4% vs 6.3%, p = 0.02). The overall cumulative mean costs per patient were £796 for Ex-ECG and £631 for ESE respectively (p = 0.04) equating to a >20% reduction in cost with an ESE strategy with no difference in the combined end-point of death, myocardial infarction, unplanned revascularization and hospitalization for chest pain between ESE and Ex-ECG (3.2% vs 3.7%, p = 0.38)., Conclusion: In patients with low to intermediate pretest probability of CAD and suspected angina, an ESE management strategy is cost-effective when compared with Ex-ECG during long term follow up., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Pulmonary hypertension (PH) patients show, during exercise, an excessive increase in ventilation (V E ) compared to carbon dioxide output (VCO 2 ), determining a high V E /VCO 2 slope. There are several possible causes, including an elevated dead space ventilation (V D ), V E /perfusion (Q) mismatch and/or an enhanced peripheral or central chemoreceptor activity. We evaluated the causes of exercise hyperventilation in PH patients., Methods: Eighteen group I and IV PH patients underwent cardiopulmonary exercise test with blood gas analysis at every minute. V E , alveolar ventilation (V A ) and V D vs. VCO 2 relationship were calculated. Resting chemoreceptor sensitivity was analyzed through hypoxia/hypercapnia tests., Results: PeakVO 2 and V E /VCO 2 slopes were 1.06±0.24l/min and 39.1±9.0, respectively. Throughout the exercise, 30% of V E was due to V D . V E /VCO 2 slope significantly correlated with V D /VCO 2 slope (r=0.82, p<0.001) but not with V A /VCO 2 slope (r=0.3, p=ns). Peak exercise end-tidal CO 2 (PetCO 2 ) correlated with V D /VCO 2 slope (r=-0.79, p<0.001) and V E /VCO 2 slope (r=-0.91, p<0.001). Dead space(DS)/Tidal volume and P(arterial-et)CO 2 were elevated without arterial hypoxemia suggesting a high V E /Q mismatch. Chemoreceptor peripheral response to hypoxia and central CO 2 response were both enhanced being peripheral responses to hypoxia and hypercapnia 0.416±0.402 (normal ref values=0.285±0.221) l/min/O 2 Sat and 0.076±0.047 (0.066±0.430) l/min/mmHg, respectively; central hypercapnic chemosensitivity was 4.475±3.99 (2.352±0.936) l/min/mmHg., Conclusions: Increased DS, V E /Q mismatch and chemorecptor response are among the main mechanisms involved in exercise hyperventilation in PH. ClinicalTrial.govNCT02892981., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)