N. Cosentino, G. Marenzi, M. Muratori, D. Magri, G. Cattadori and P. Agostoni

Eur J Prev Cardiol 2023 Vol. 30 Issue Suppl 2 Pages ii9-ii15

Fluid retention is a major determinant of symptoms in patients with heart failure (HF), and it is closely associated with prognosis. Hence, congestion represents a critical therapeutic target in this clinical setting. The first therapeutic strategy in HF patients with fluid overload is optimization of diuretic intervention to maximize water and sodium excretion. When diuretic therapy fails to relieve congestion, renal replacement therapy represents the only alternative option for fluid removal, as well as a way to restore diuretic responsiveness. On this background, the pathophysiology of fluid balance in HF is complex, with heart, kidney, and lung being deeply involved in volume regulation and management. Therefore, the interplay between these organs should be appreciated and considered when fluid overload in HF patients is targeted.

C. Vignati, M. Contini, E. Salvioni, C. Lombardi, S. Caravita, G. Bilo, et al.

Eur J Prev Cardiol 2023 Vol. 30 Issue Suppl 2 Pages ii40-ii46

Clinical outcome and quality of life of patients with chronic heart failure (HF) have greatly improved over the last two decades. These results and the availability of modern lifts allow many cardiac patients to spend leisure time at altitude. Heart failure per se does not impede a safe stay at altitude, but exercise at both simulated and real altitudes is associated with a reduction in performance, which is inversely proportional to HF severity. For example, in normal subjects, the reduction in functional capacity is approximately 2% every 1000 m altitude increase, whereas it is 4 and 10% in HF patients with normal or slightly diminished exercise capacity and in HF patients with markedly diminished exercise capacity, respectively. Also, the on-field experience with HF patients at altitude confirms safety and shows overall similar data to that reported at simulated altitude. Even ‘optimal’ HF treatment in patients spending time at altitude or at hypoxic conditions is likely different from optimal treatment at sea level, particularly with regard to the selectivity of beta-blockers. Furthermore, high altitude, both simulated and on-field, represents a stimulating model of hypoxia in HF patients and healthy subjects. Our data suggest that spending time at altitude (<3500 m) can be safe even for HF patients, provided that subjects are free from comorbidities that may directly interfere with the adaptation to altitude and are stable. However, HF patients experience a reduction of exercise capacity directly proportional to HF severity and altitude. Finally, HF patients should be tested for functional capacity and must undergo a specific ‘hypoxic-tailored treatment’ to avoid pharmacological interference with altitude adaptation mechanisms, particularly with regard to the selectivity of beta-blockers.

I. Mattavelli, C. Vignati, S. Farina, A. Apostolo, G. Cattadori, F. De Martino, et al.

Eur J Prev Cardiol 2023 Vol. 30 Issue Suppl 2 Pages ii34-ii39

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 he

C. Banfi, P. Gugliandolo, S. Paolillo, A. Mallia, E. Gianazza and P. Agostoni

Eur J Prev Cardiol 2023 Vol. 30 Issue Suppl 2 Pages ii2-ii8

In this review, we describe the structure and function of the alveolar-capillary membrane and the identification of a novel potential marker of its integrity in the context of heart failure (HF). The alveolar-capillary membrane is indeed a crucial structure for the maintenance of the lung parenchyma gas exchange capacity, and the occurrence of pathological conditions determining lung fluids accumulation, such as HF, might significantly impair lung diffusion capacity altering the alveolar-capillary membrane protective functions. In the years, we found that the presence of immature forms of the surfactant protein-type B (proSP-B) in the circulation reflects alterations in the alveolar-capillary membrane integrity. We discussed our main achievements showing that proSP-B, due to its chemical properties, specifically binds to high-density lipoprotein, impairing their antioxidant activity, and likely contributing to the progression of the disease. Further, we found that immature proSP-B, not the mature protein, is related to lung abnormalities, more precisely than the lung function parameters. Thus, to the list of the potential proposed markers of HF, we add proSP-B, which represents a precise marker of alveolar-capillary membrane dysfunction in HF, correlates with prognosis, and represents a precocious marker of drug therapy

J. Campodonico, M. Contini, M. Alimento, M. Mapelli, E. Salvioni, I. Mattavelli, et al

Eur J Prev Cardiol 2023 Vol. 30 Issue Suppl 2 Pages ii54-ii62

In the last decades, the pharmacological treatment of heart failure (HF) become more complex due to the availability of new highly effective drugs. Although the cardiovascular effects of HF therapies have been extensively described, less known are their effects on cardiopulmonary function considered as a whole, both at rest and in response to exercise. This is a ‘holistic’ approach to disease treatment that can be accurately evaluated by a cardiopulmonary exercise test. The aim of this paper is to assess the main differences in the effects of different drugs [angiotensin-converting enzyme (ACE)-inhibitors, Angiotensin II receptor blockers, beta-blockers, Angiotensin receptor-neprilysin inhibitors, renal sodium-glucose co-transporter 2 inhibitors, iron supplementation] on cardiopulmonary function in patients with HF, both at rest and during exercise, and to understand how these differences can be taken into account when choosing the most appropriate treatment protocol for each individual patient leading to a precision medicine approach.

M. Mapelli, E. Salvioni, I. Mattavelli, P. Gugliandolo, A. Bonomi, P. Palermo, et al.

Eur J Prev Cardiol 2023 Vol. 30 Issue Suppl 2 Pages ii47-ii53

Heart failure (HF) patients traditionally report dyspnoea as their main symptom. Although the cardiopulmonary exercise test (CPET) and 6 min walking test are the standardized tools in assessing functional capacity, neither cycle ergometers nor treadmill maximal efforts do fully represent the actual HF patients’ everyday activities [activities of daily living (ADLs)] (i.e. climbing the stairs). New-generation portable metabolimeters allow the clinician to measure task-related oxygen intake (VO2) in different scenarios and exercise protocols. In the last years, we have made considerable progress in understanding the ventilatory and metabolic behaviours of HF patients and healthy subjects during tasks aimed to reproduce ADLs. In this paper, we describe the most recent findings in the field, with special attention to the relationship between the metabolic variables obtained during ADLs and CPET parameters (i.e. peak VO2), demonstrating, for example, how exercises traditionally thought to be undemanding, such as a walk, instead represent supramaximal efforts, particularly for subjects with advanced HF and/or artificial heart (left ventricular assist devices) wearers.
This article summarizes the most recent evidence on the cardiometabolic behaviours of a full spectrum of heart failure (HF) patients of different severity during their daily life activities (i.e. walking, making a bed, and taking the stairs).Heart failure patients experience symptoms (mostly dyspnoea) during daily activities that sometimes represent maximal or supramaximal exercises for them, particularly for the most severe patients.Measuring metabolic parameters (O2 intake, ventilation, and CO2 production) through appropriate devices during these activities provides a better understanding of the pathophysiological mechanisms underlying HF patients’ symptoms and their adaptation. This can lead to the detection of new parameters that can become novel patient-centred prognostic markers or therapeutic targets for drugs and rehabilitation treatments.

G. Cunha, A. Apostolo, F. De Martino, E. Salvioni, I. Matavelli and P. Agostoni

Eur J Prev Cardiol 2023 Vol. 30 Issue Suppl 2 Pages ii22-ii27

Exercise oscillatory ventilation (EOV) is a fascinating event that can be appreciated in the cardiopulmonary exercise test and is characterized by a cyclic fluctuation of minute ventilation, tidal volume, oxygen uptake, carbon dioxide production, and end-tidal pressure for oxygen and carbon dioxide. Its mechanisms stem from a dysregulation of the normal control feedback of ventilation involving one or more of its components, namely, chemoreflex delay, chemoreflex gain, plant delay, and plant gain. In this review, we intend to breakdown therapeutic targets according to pathophysiology and revise the prognostic value of exercise oscillatory ventilation in the setting of heart failure and other diagnoses.

Zavorsky, G;  Agostoni, P;

ERJ Open Res 2024 Vol. 10 Issue 1

BACKGROUND: Heart failure (HF) is a chronic condition in which the heart does not pump enough blood to meet the body’s demands. Diffusing capacity of the lung for nitric oxide (D(LNO)) and carbon monoxide (D(LCO)) may be used to classify patients with HF, as D(LNO) and D(LCO) are lung function measurements that reflect pulmonary gas exchange. Our objectives were to determine 1) if D(LNO) added to D(LCO) testing predicts HF better than D(LCO) alone and 2) whether the binary classification of HF is better when D(LNO) z-scores are combined with D(LCO) z-scores than using D(LCO) z-scores alone.
METHODS: This was a retrospective secondary data analysis in 140 New York Heart Association Class II HF patients (ejection fraction <40%) and 50 patients without HF. z-scores for D(LNO), D(LCO) and D(LNO)+D(LCO) were created from reference equations from three articles. The model with the lowest Bayesian Information Criterion was the best predictive model. Binary HF classification was evaluated with the Matthews Correlation Coefficient (MCC). RESULTS: The top two of 12 models were combined z-score models. The highest MCC (0.51) was from combined z-score models. At most, only 32% of the variance in the odds of having HF was explained by combined z-scores.
CONCLUSIONS: Combined z-scores explained 32% of the variation in the likelihood of an individual having HF, which was higher than models using D(LNO) or D(LCO) z-scores alone. Combined z-score models had a moderate ability to classify patients with HF. We recommend using the NO-CO double diffusion technique to assess gas exchange impairment in those suspected of HF.

D. Magri, G. Gallo, M. Piepoli, E. Salvioni, M. Mapelli, C. Vignati, et al.

Eur J Prev Cardiol 2024 Vol. 31 Issue 2 Pages 263-271

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