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We report the case of an athlete who, despite facing the challenges of laryngectomy, underwent a comprehensive cardiopulmonary exercise test to assess both his ability to participate in sports and his cardiopulmonary fitness. We not only highlight the individualized approach to sports assessment in a challenging medical context but also emphasize the feasibility of employing cardiopulmonary testing in evaluating subjects in unusual settings.

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.)

Introduction: Risk stratification in heart failure (HF) is essential for clinical and therapeutic management. The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score is a validated prognostic model for assessing cardiovascular risk in HF patients with reduced ejection fraction (HFrEF). From the validation of the score, the prevalence of HF patients treated with direct oral anticoagulants (DOACs), such as edoxaban, for non-valvular atrial fibrillation (NVAF) has been increasing in recent years. This study aims to evaluate the reliability of the MECKI score in HFrEF patients treated with edoxaban for NVAF., Materials and Methods: This study included consecutive outpatients with HF and NVAF treated with edoxaban ( n = 83) who underwent a cardiopulmonary exercise test (CPET). They were matched by propensity score with a retrospective group of HFrEF patients with NVAF treated with vitamin K antagonists (VKAs) from the MECKI score registry ( n = 844). The study endpoint was the risk of cardiovascular mortality, urgent heart transplantation, or Left Ventricle Assist Device (LVAD) implantation., Results: Edoxaban patients were treated with a more optimized HF therapy and had different clinical characteristics, with a similar MECKI score. After propensity score, 77 patients treated with edoxaban were successfully matched with the MECKI-VKA control cohort. In both groups, MECKI accurately predicted the composite endpoint with similar area under the curves (AUC = 0.757 vs. 0.829 in the MECKI-VKA vs. edoxaban-treated group, respectively, p = 0.452). The two populations' survival appeared non-significantly different at the 2-year follow-up., Conclusions: this study confirms the prognostic accuracy of the MECKI score in HFrEF patients with NVAF treated with edoxaban, showing improved predictive power compared to VKA-treated patients.

Aims: Improvement of left ventricular ejection fraction is a major goal of heart failure (HF) treatment. However, data on clinical characteristics, exercise performance and prognosis in HF patients who improved ejection fraction (HFimpEF) are scarce. The study aimed to determine whether HFimpEF patients have a distinct clinical phenotype, biology and prognosis than HF patients with persistently reduced ejection fraction (pHFrEF)., Methods and Results: A total of 7948 patients enrolled in the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score database were evaluated (median follow-up of 1490 days). We analysed clinical, laboratory, electrocardiographic, echocardiographic, exercise, and survival data from HFimpEF (n = 1504) and pHFrEF (n = 6017) patients. The primary endpoint of the study was the composite of cardiovascular death, left ventricular assist device implantation, and urgent heart transplantation. HFimpEF patients had lower HF severity: left ventricular ejection fraction 44.0 [41.0-47.0] versus 29.7 [24.1-34.5]%, B-type natriuretic peptide 122 [65-296] versus 373 [152-888] pg/ml, haemoglobin 13.5 [12.2-14.6] versus 13.7 [12.5-14.7] g/dl, renal function by the Modification of Diet in Renal Disease equation 72.0 [56.7-89.3] versus 70.4 [54.5-85.3] ml/min, peak oxygen uptake 62.2 [50.7-74.1] versus 52.6 [41.8-64.3]% predicted, minute ventilation-to-carbon dioxide output slope 30.0 [26.9-34.4] versus 32.1 [28.0-38.0] in HFimpEF and pHFrEF, respectively (p < 0.001 for all). Cardiovascular mortality rates were 26.6 and 46.9 per 1000 person-years for HFimpEF and pHFrEF, respectively (p < 0.001). Kaplan-Meier analysis showed that HFimpEF had better a long-term prognosis compared with pHFrEF patients. After adjustment for variables differentiating HFimpEF from pHFrEF, except echocardiographic parameters, the Kaplan-Meier curves showed the same prognosis., Conclusions: Heart failure with improved ejection fraction represents a peculiar group of HF patients whose clinical, laboratory, electrocardiographic, echocardiographic, and exercise characteristics parallel the recovery of systolic function. Nonetheless, these patients remain at risk for adverse outcome., (© 2023 European Society of Cardiology.)

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.)

Cardiopulmonary exercise test (CPET) has become pivotal in the functional evaluation of patients with chronic heart failure (HF), supplying a holistic evaluation both in terms of exercise impairment degree and possible underlying mechanisms. Conversely, there is growing interest in investigating possible multiparametric approaches in order to improve the overall HF risk stratification. In such a context, in 2013, a group of 13 Italian centres skilled in HF management and CPET analysis built the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score, based on the dynamic assessment of HF patients and on some other instrumental and laboratory parameters. Subsequently, the MECKI score, initially developed on a cohort of 2716 HF patients, has been extensively validated as well as challenged with the other multiparametric scores, achieving optimal results. Meanwhile, the MECKI score research group has grown over time, involving up to now a total of 27 centres with an available database accounting for nearly 8000 HF patients. This exciting joint effort from multiple HF Italian centres allowed to investigate different HF research field in order to deepen the mechanisms underlying HF, to improve the ability to identify patients at the highest risk as well as to analyse particular HF categories. Most recently, some of the participants of the MECKI score group started to join the forces in investigating a possible additive role of CPET assessment in the cardiomyopathy setting too. The present study tells the ten-year history of the MECKI score presenting the most important results achieved as well as those projects in the pipeline, this exciting journey being far to be concluded., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cardiopulmonary exercise test (CPET) is a valuable diagnostic tool with a specific application in heart failure (HF) thanks to the strong prognostic value of its parameters. The most important value provided by CPET is the peak oxygen uptake (peak VO2), the maximum rate of oxygen consumption attainable during physical exertion. According to the Fick principle, VO2 equals cardiac output (Qc) times the arteriovenous content difference [C(a-v)O2], where Ca is the arterial oxygen and Cv is the mixed venous oxygen content, respectively; therefore, VO2 can be reduced both by impaired O2 delivery (reduced Qc) or extraction (reduced arteriovenous O2 content). However, standard CPET is not capable of discriminating between these different impairments, leading to the need for 'complex' CPET technologies. Among non-invasive methods for Qc measurement during CPET, inert gas rebreathing and thoracic impedance cardiography are the most used techniques, both validated in healthy subjects and patients with HF, at rest and during exercise. On the other hand, the non-invasive assessment of peripheral muscle perfusion is possible with the application of near-infrared spectroscopy, capable of measuring tissue oxygenation. Measuring Qc allows, by having haemoglobin values available, to discriminate how much any VO2 deficit depends on the muscle, anaemia or heart., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Hyperventilation and inadequate cardiac output (CO) increase are the main causes of exercise limitation in pulmonary hypertension (PH). Intrapulmonary blood flow partitioning between ventilated and unventilated lung zones is unknown. Thoracic impedance cardiography and inert gas rebreathing have been both validated in PH patients for non-invasive measurement of CO and pulmonary blood flow (PBF), respectively. This study sought to evaluate CO behaviour in PH patients during exercise and its partitioning between ventilated and unventilated lung areas, in parallel with ventilation partitioning between ventilated and unventilated lung zones., Methods: Eighteen PH patients (group 1 or 4) underwent a cardiopulmonary exercise test (CPET) with a three-step loaded workload protocol. The steps occurred at 0%, 20%, 40%, and 60% of peak workload reached during a preliminary maximum CPET. Ventilatory parameters, arterial blood gases, CO, PBF, and intrapulmonary shunt (calculated as the difference between CO and PBF) were obtained at each step, combining thoracic impedance cardiography and an inert gas rebreathing technique., Results: Dead space ventilation observed throughout the exercise was about 40% of total ventilation. A progressive increase of CO from 4.86 ± 1.24 L/min (rest) to 9.41 ± 2.63 L/min (last step), PBF from 3.81 ± 1.41 L/min to 7.21 ± 2.93 L/min, and intrapulmonary shunt from 1.05 ± 0.96 L/min to 2.21 ± 2.28 L/min was observed. Intrapulmonary shunt was approximately 20% of CO at each exercise step., Conclusions: Although the study population was small, the combined non-invasive CO measurement seems a promising tool for deepening our knowledge of lung exercise haemodynamics in PH patients. This technique could be applied in future studies to evaluate PH treatment influences on CO partitioning, since a secondary increase of intrapulmonary shunt is undesirable., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Farina, Pezzuto, Vignati, Laveneziana and Agostoni.)

Pulmonary arterial hypertension (PAH) is a progressive disease with a poor prognosis if left untreated. Despite remarkable achievements in understanding disease pathophysiology, specific treatments, and therapeutic strategies, we are still far from a definitive cure for the disease, and numerous evidences have underlined the importance of early diagnosis and treatment to improve the prognosis. Cardiopulmonary exercise testing (CPET) is the gold standard for assessing functional capacity and evaluating the pathophysiological mechanisms underlying exercise limitation. As effort dyspnea is the earliest and one of the main clinical manifestations of PAH, CPET has been shown to provide valid support in early detection, differential diagnosis, and prognostic stratification of PAH patients, being a useful tool in both the first approach to patients and follow-up. The purpose of this review is to present the current applications of CPET in pulmonary hypertension and to propose possible future utilization to be further investigated.

Background: Impaired iron transport (IIT) is a form of iron deficiency (ID) defined as transferrin saturation (TSAT) < 20% irrespective of serum ferritin levels. It is frequently observed in heart failure (HF) where it negatively affects prognosis irrespective of anaemia., Objectives: In this retrospective study we searched for a surrogate biomarker of IIT., Methods: We tested the predictive power of red distribution width (RDW), mean corpuscular volume (MCV) and mean corpuscular haemoglobin concentration (MCHC) to detect IIT in 797 non-anaemic HF patients., Results: At ROC analysis, RDW provided the best AUC (0.6928). An RDW cut-off value of 14.2% identified patients with IIT, with positive and negative predictive values of 48 and 80%, respectively. Comparison between the true and false negative groups showed that estimated glomerular filtration rate (eGFR) was significantly higher ( p  = 0.0092) in the true negative vs. false negative group. Therefore, we divided the study population according to eGFR value: 109 patients with eGFR ≥ 90 ml/min/1.73 m 2 , 318 patients with eGFR 60-89 ml/min/1.73 m 2 , 308 patients with eGFR 30-59 ml/min/1.73 m 2 and 62 patients with eGFR < 30 ml/min/1.73 m 2 . In the first group, positive and negative predictive values were 48 and 81% respectively, 51 and 85% in the second group, 48 and 73% in the third group and 43 and 67% in the fourth group., Conclusion: RDW may be seen as a reliable marker to exclude IIT in non-anaemic HF patients with eGFR ≥60 ml/min/1.73 m 2 ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor MM declared a shared affiliation with the authors JC, AB, FDM, CV, BP, PA at the time of review., (© 2023 Campodonico, Carulli, Doni, Russo, Junod, Gaudenzi Asinelli, Bonomi, De Martino, Vignati, Pezzuto and Agostoni.)