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Il tessuto adiposo epicardico (EAT) è un fattore di rischio cardiovascolare in quanto promuove la progressione della fibrillazione atriale, della malattia coronarica e dell’insufficienza cardiaca. EAT si caratterizza per rapido metabolismo, misurabilità clinica e facile modificabilità e rappresenta un bersaglio terapeutico peculiare per farmaci innovativi, quali gli agonisti del recettore del peptide glucagone-simile 1 e gli inibitori del co-trasportatore sodio-glucosio 2, che appaiono salutari dal punto di vista cardiometabolico ben oltre i loro effetti sul glucosio e sul peso corporeo (Materiale Supplementare).

IMPORTANCE: Cardiopulmonary exercise testing (CPET) has an established role in the assessment of patients with heart failure. However, data are lacking in patients with transthyretin (ATTR) amyloidosis. OBJECTIVE: To use CPET to characterize the spectrum of functional phenotypes in patients with ATTR amyloidosis and assess their association with the cardiac amyloid burden as well as the association between CPET parameters and prognosis. DESIGN, SETTING AND PARTICIPANTS: This single-center study evaluated patients diagnosed with ATTR amyloidosis from May 2019 to September 2022 who underwent CPET at the National Amyloidosis Centre. Of 1045 patients approached, 506 were included and completed the study. Patients were excluded if they had an absolute contraindication to CPET or declined participation. The mean (SD) follow-up period was 22.4 (11.6) months. MAIN OUTCOMES AND MEASURES: Comparison of CPET parameters across disease phenotypes (ATTR with cardiomyopathy [ATTR-CM], polyneuropathy, or both [ATTR-mixed]), differences in CPET parameters based on degree of amyloid infiltration (as measured by cardiovascular magnetic resonance [CMR] with extracellular volume mapping), and association between CPET parameters and prognosis. RESULTS: Among the 506 patients with ATTR amyloidosis included in this study, the mean (SD) age was 73.5 (10.2) years, and 457 participants (90.3%) were male. Impairment in functional capacity was highly prevalent. Functional impairment in ATTR-CM and ATTR-mixed phenotypes (peak mean [SD] oxygen consumption [VO2], 14.5 [4.3] mL/kg/min and 15.7 [6.2] mL/kg/min, respectively) was observed alongside impairment in the oxygen pulse, with ventilatory efficiency highest in ATTR-CM (mean [SD] ventilatory efficiency/volume of carbon dioxide expired slope, 38.1 [8.6]). Chronotropic incompetence and exercise oscillatory ventilation (EOV) were highly prevalent across all phenotypes, with both the prevalence and severity being higher than in heart failure from different etiologies. Worsening of amyloid burden on CMR was associated with decline in multiple CPET parameters, although chronotropic response and EOV remained abnormal irrespective of amyloid burden. On multivariable Cox regression analysis, peak VO2 and peak systolic blood pressure (SBP) were independently associated with prognosis (peak VO2: hazard ratio, 0.89 [95% CI, 0.81-0.99; P = .03]; peak SBP: hazard ratio, 0.98 [95% CI, 0.97-0.99; P < .001]). CONCLUSIONS AND RELEVANCE: In this study, ATTR amyloidosis was characterized by distinct patterns of functional impairment between all disease phenotypes. A high prevalence of chronotropic incompetence, EOV, and ventilatory inefficiency were characteristic of this population. CPET parameters were associated with amyloid burden by CMR and with peak VO2, and SBP, which have been shown to be independent predictors of mortality. These findings suggest that CPET may be useful in characterizing distinct patterns of functional impairment across the spectrum of amyloid infiltration and predicting outcomes, and potentially offers a more comprehensive method of evaluating functional capacity for future prospective studies.

In clinical practice, anaerobic threshold (AT) is used to guide training and rehabilitation programs, to define risk of major thoracic or abdominal surgery, and to assess prognosis in heart failure (HF). AT of oxygen uptake (V.O2; V.O2AT) has been reported as an absolute value (V.O2ATabs), as a percentage of predicted peak V.O2(V.O2AT%peak_pred), or as a percentage of observed peak V.O2(V.O2AT%peak_obs). A direct comparison of the prognostic power among these different ways to report AT is missing.

OBJECTIVE -- In type 1 diabetes, lung diffusing capacity for carbon monoxide ([DL.sub.CO]) may be impaired, and insulin has been shown to be beneficial in cases in which near-normal metabolic [...]

Placement of an interatrial shunt device reduces pulmonary capillary wedge pressure during exercise in patients with heart failure and preserved or mildly reduced ejection fraction. We aimed to investigate whether an interatrial shunt can reduce heart failure events or improve health status in these patients.

Purpose: Chest X-ray (CXR) severity score and BMI-based obesity are predictive risk factors for COVID-19 hospital admission. However, the relationship between abdominal obesity and CXR severity score has not yet been fully explored. Methods: This retrospective cohort study analyzed the association of different adiposity indexes, including waist circumference and body mass index (BMI), with CXR severity score in 215 hospitalized patients with COVID-19. Results: Patients with abdominal obesity showed significantly higher CXR severity scores and had higher rates of CXR severity scores ≥ 8 compared to those without abdominal obesity (P< 0.001; P= 0.001, respectively). By contrast, patients with normal weight, with overweight and those with BMI-based obesity showed no significant differences in either CXR severity scores or in the rates of CXR severity scores ≥ 8 (P= 0.104; P= 0.271, respectively). Waist circumference and waist-to-height ratio (WHtR) correlated more closely with CXR severity scores than BMI (r= 0.43, P< 0.001; r= 0.41, P< 0.001; r= 0.17, P= 0.012, respectively). The area under the curves (AUCs) for waist circumference and WHtR were significantly higher than that for BMI in identifying a high CXR severity score (≥ 8) (0.68 [0.60–0.75] and 0.67 [0.60–0.74] vs 0.58 [0.51–0.66], P= 0.001). A multivariate analysis indicated abdominal obesity (risk ratio: 1.75, 95% CI: 1.25–2.45, P< 0.001), bronchial asthma (risk ratio: 1.73, 95% CI: 1.07–2.81, P= 0.026) and oxygen saturation at admission (risk ratio: 0.96, 95% CI: 0.94–0.97, P< 0.001) as the only independent factors associated with high CXR severity scores. Conclusion: Abdominal obesity phenotype is associated with a high CXR severity score better than BMI-based obesity in hospitalized patients with COVID-19. Therefore, when visiting the patient in a hospital setting, waist circumference should be measured, and patients with abdominal obesity should be monitored closely.

Prognostic stratification of cardiomyopathies represents a cornerstone for the appropriate management of patients and is focused mainly on arrhythmic events and heart failure. Cardiopulmonary exercise testing provides additional prognostic information, particularly in the setting of heart failure. Cardiopulmonary exercise testing data, integrated in scores such as the Metabolism Exercise Cardiac Kidney Index score have been shown to improve the risk stratification of these patients. Cardiopulmonary exercise testing has been analysed as a potential supplier of prognostic parameters in the context of hypertrophic cardiomyopathy, for which it has been shown that a reduced oxygen consumption peak, an increased ventilation/carbon dioxide production slope and chronotropic incompetence correlate with a worse prognosis. To a lesser extent, in dilated cardiomyopathy, it has been shown that the percentage of oxygen consumption peak, not the pure value, and the ventilation/carbon dioxide production slope are associated with a greater cardiovascular risk. Few data are available about other cardiomyopathies (arrhythmogenic and restrictive). Cardiomyopathy patients should be early and routinely referred to heart failure advanced centres in order to perform a comprehensive risk stratification which should include a cardiopulmonary exercise test, with variables and cut-offs shown to improve their risk stratification.

IMPORTANCE: Myocardial injury, detected by elevated plasma troponin levels, has been associated with mortality in patients hospitalized with coronavirus disease 2019 (COVID-19). However, the initial data were reported from single-center or 2-center studies in Chinese populations. Compared with these patients, European and US patients are older, with more comorbidities and higher mortality rates. OBJECTIVE: To evaluate the prevalence and prognostic value of myocardial injury, detected by elevated plasma troponin levels, in a large population of White Italian patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: This is a multicenter, cross-sectional study enrolling consecutive patients with laboratory-confirmed COVID-19 who were hospitalized in 13 Italian cardiology units from March 1 to April 9, 2020. Patients admitted for acute coronary syndrome were excluded. Elevated troponin levels were defined as values greater than the 99th percentile of normal values. MAIN OUTCOMES AND MEASURES: Clinical characteristics and outcomes stratified as elevated or normal cardiac troponin levels at admission, defined as troponin T or troponin I at a level greater than the 99th percentile of normal values. RESULTS: A total of 614 patients with COVID-19 were included in this study (mean age [SD], 67 [13] years; 70.8% male), of whom 148 patients (24.1%) died during the hospitalization. Elevated troponin levels were found in 278 patients (45.3%). These patients were older (mean [SD] age, 64.0 [13.6] years vs 71.3 [12.0] years; P < .001) and had higher prevalence of hypertension (168 patients [50.5%] vs 182 patients [65.9%]; P < .001), heart failure (24 [7.2%]; 63 [22.8%]; P < .001), coronary artery disease (50 [15.0%] vs 87 [31.5%]; P < .001), and atrial fibrillation (33 [9.9%] vs 67 [24.3%]; P < .001). Elevated troponin levels were associated with an increased in-hospital mortality (37% vs 13%; HR, 1.71 [95% CI, 1.13-2.59]; P = .01 via multivariable Cox regression analysis), and this was independent from concomitant cardiac disease. Elevated troponin levels were also associated with a higher risk of in-hospital complications: heart failure (44 patients [19.2%] vs 7 patients [2.9%]; P < .001), sepsis (31 [11.7%] vs 21 [6.4%]; P = .03), acute kidney failure (41 [20.8%] vs 13 [6.2%]; P < .001), multiorgan failure (21 [10.9%] vs 6 [2.9%]; P = .003), pulmonary embolism (27 [9.9%] vs 17 [5.2%]; P = .04), delirium (13 [6.8%] vs 3 [1.5%]; P = .02), and major bleeding (16 [7.0%] vs 4 [1.6%]; P = .008). CONCLUSIONS AND RELEVANCE: In this multicenter, cross-sectional study of Italian patients with COVID-19, elevated troponin was an independent variable associated with in-hospital mortality and a greater risk of cardiovascular and noncardiovascular complications during a hospitalization for COVID-19.

Heart failure is characterized by pathologic hemodynamic derangements, including elevated cardiac filling pressures (“backward” failure), which may or may not coexist with reduced cardiac output (“forward” failure). Even when normal during unstressed conditions such as rest, hemodynamics classically become abnormal during stressors such as exercise in patients with heart failure. This has important upstream and downstream effects on multiple organ systems, particularly with respect to the lungs and kidneys. Hemodynamic abnormalities in heart failure are affected by processes that extend well beyond the cardiac myocyte, including important roles for pericardial constraint, ventricular interaction, and altered venous capacity. Hemodynamic perturbations have widespread effects across multiple heart failure phenotypes, ranging from reduced to preserved ejection fraction, acute to chronic disease, and cardiogenic shock to preserved perfusion states. In the lung, hemodynamic derangements lead to the development of abnormalities in ventilatory control and efficiency, pulmonary congestion, capillary stress failure, and eventually pulmonary vascular disease. In the kidney, hemodynamic perturbations lead to sodium and water retention and worsening renal function. Improved understanding of the mechanisms by which altered hemodynamics in heart failure affect the lungs and kidneys is needed in order to design novel strategies to improve clinical outcomes.

Extracorporeal membrane oxygenation is essential for the treatment of refractory cardiopulmonary failure. Its use may be complicated by worse haemorrhagic complications exacerbated by extracorporeal membrane oxygenation–related therapeutic anticoagulation. Progressive technological advancements have made extracorporeal membrane oxygenation components less thrombogenic, potentially allowing its application with temporary avoidance of systemic anticoagulants. A systematic review of all the available experiences, reporting the use of extracorporeal membrane oxygenation without systemic anticoagulation in the published literature was performed. Only patient series were included, irrespective of the clinical indication. The survival, extracorporeal membrane oxygenation system–related dysfunction and complications rates, as well as in-hospital outcome, were analysed. Six studies were selected for the analysis. Veno-arterial extracorporeal membrane oxygenation was used in 84% of patients, while veno-venous extracorporeal membrane oxygenation was applied in the remaining cases. Anticoagulation was avoided because of the high risk of bleeding after cardiac surgery (64%), active major bleeding (23%) or presence of severe traumatic injury (9%). Duration of support ranged from 0.3 to 1128 h. Heparin was antagonized by protamine in all the post-cardiotomy cases. Successfully extracorporeal membrane oxygenation weaning was achieved in 74% of the treated cases, with a hospital discharge of 58% of patients. Rates of extracorporeal membrane oxygenation malfunctioning due to clot formation and blood transfusion requirement varied remarkably in the published series. Extracorporeal membrane oxygenation without systemic anticoagulation appears feasible in selected circumstances. Further investigations are warranted to elucidate actual aspects regarding extracorporeal membrane oxygenation system performance, related adverse events and benefits associated with this management.

Background Chronotropic insufficiency (CI) is defined as the inability of the heart to increase its rate commensurate with increased demand. Exercise CI is an established predictor of major adverse cardiovascular events in patients with cardiovascular diseases.Aim The aim of this study was to evaluate how exercise CI phenotypes different levels of cardiovascular risk and how it may better perform in defining cardiovascular risk when analysed in the context of cardiopulmonary exercise test (CPET)-derived measures and standard echocardiography in a healthy population with variable cardiovascular risk profile.Methods Apparently healthy individuals (N= 702, 53.8% females) with at least one major cardiovascular risk factor (MCVRF; hypertension, diabetes, tabagism, dyslipidaemia, body mass index > 25), enrolled in the Euro-EX prevention trial, underwent CPET. CI was defined as the inability to reach 80% of the chronotropic index, that is, the ratio of peak heart rate – rest heart rate/peak heart rate – age predicted maximal heart rate (AMPHR: 220 – age), they were divided into four groups according to the heart rate reserve (<80%>) and respiratory gas exchange ratio (RER; < 1.05>) as a marker of achieved maximal performance. Subjects with a RER < 1.05 (n= 103) were excluded and the final population (n= 599) was divided into CI group (n= 472) and no-CI group (n= 177).Results Compared with no-CI, CI subjects were more frequently females with a history of hypertension in a high rate. CI subjects also exhibited a significantly lower peak oxygen uptake (VO2) and circulatory power and an echocardiographic pattern indicative of higher left atrial volume index and left ventricular mass index. An inverse stepwise relationship between heart rate reserve and number of MCVRFs was observed (one MCVRF: 0.71 ± 0.23; two MCVRFs: 0.68 ± 0.24, three MCVRFs: 0.64 ± 0.20; four MCVRFs: 0.64 ± 0.23; five MCVRFs: 0.57 ± 18; p< 0.01). In multivariate analysis the only variable found predicting CI was peak VO2(p< 0.05; odds ratio 0.91; confidence interval 0.85–0.97).Conclusions In a population of apparently healthy subjects, exercise CI is common and phenotypes the progressive level of cardiovascular risk by a tight relationship with MCVRFs. CI patients exhibit some peculiar abnormal exercise gas exchange patterns (lower peak VO2and exercise oscillatory ventilation) and echo-derived measures (higher left atrium size and left ventricle mass) that may well anticipate evolution toward heart failure.

A study was conducted to examine the impact of beta-blockade (BB) on the prognostic value of cardiopulmonary exercise (CPX) variables in a group of subjects diagnosed with heart failure (HF). The results from the study indicate that CPX maintains prognosis value irrespective of BB use.

The findings showed that adding a 4-wk course of cardiac rehabilitation to usual care for patients with cardiac syndrome X not only increased the Duke Treadmill Score and exercise test duration but also improved the resting oxygen (O2) pulse, the peak O2uptake, and the first-minute recovery heart rate.

Patients with type 2 diabetes mellitus suffer from dysregulation of a plethora of cardiovascular and metabolic functions, including dysglycaemia, dyslipidaemia, arterial hypertension, obesity and a reduced cardiorespiratory fitness. Exercise training has the potential to improve many of these functions, such as insulin sensitivity, lipid profile, vascular reactivity and cardiorespiratory fitness, particularly in type 2 diabetes mellitus patients with cardiovascular comorbidities, such as patients that suffered from an acute myocardial infarction, or after a coronary intervention such as percutaneous coronary intervention or coronary artery bypass grafting. The present position paper aims to provide recommendations for prescription of exercise training in patients with both type 2 diabetes mellitus and cardiovascular disease. The first part discusses the relevance and practical applicability of treatment targets that may be pursued, and failure to respond to these targets. The second part provides recommendations on the contents and methods to prescribe exercise training tailored to these treatment targets as well as to an optimal preparation and dealing with barriers and risks specific to type 2 diabetes mellitus and cardiac comorbidity.

The most important determinant of long-term survival in patients with idiopathic pulmonary fibrosis is the right ventricular (RV) adaptation to the increased pulmonary vascular resistance. Our aim was to explore RV contractile reserve during stress echocardiography in early-stage IPF.

The Right Heart International Network is a multicenter international study aiming to prospectively collect exercise Doppler echocardiography tests of the right heart pulmonary circulation unit (RHPCU) in large cohorts of healthy subjects, elite athletes, and individuals at risk of or with overt pulmonary hypertension. It is going to provide standardization of exercise stress echocardiography of RHPCU and explore the full physiopathologic response.

Pulmonary hypertension (PH) is a common hemodynamic evolution of heart failure (HF) with preserved or reduced ejection fraction, responsible for congestion, symptoms worsening, exercise limitation, and negative outcome. In HF of any origin, PH develops in response to a passive backward pressure transmission as result of increased left atrial pressure. Sustained pressure injury and chronic venous congestion can trigger pulmonary vasoconstriction and vascular remodeling, leading to irreversible pulmonary vascular disease, right ventricular hypertrophy, and failure. In this article, the key determinants of this “dangerous liaison” are analyzed with some digressions on related “leitmotiv” at the horizon.

Right ventricular (RV) exercise contractile reserve (RVECR), its phenotypes, and its functional correlates are among the unresolved issues with regard to the role of the right ventricle in heart failure (HF) syndrome, and understanding these issues constitutes the objective of this study.

In the past several decades, cardiopulmonary exercise testing (CPX) has seen an exponential increase in its evidence base. The growing volume of evidence in support of CPX has precipitated the release of numerous scientific statements by societies and associations. In 2012, the European Association for Cardiovascular Prevention & Rehabilitation and the American Heart Association developed a joint document with the primary intent of redefining CPX analysis and reporting in a way that would streamline test interpretation and increase clinical application. Specifically, the 2012 joint scientific statement on CPX conceptualized an easy-to-use, clinically meaningful analysis based on evidence-vetted variables in color-coded algorithms; single-page algorithms were successfully developed for each proposed test indication. Because of an abundance of new CPX research in recent years and a reassessment of the current algorithms in light of the body of evidence, a focused update to the 2012 scientific statement is now warranted. The purposes of this update are to confirm algorithms included in the initial scientific statement not requiring revision, to propose revisions to algorithms included in the initial scientific statement, to propose new algorithms based on emerging scientific evidence, to further clarify the application of oxygen consumption at ventilatory threshold, to describe CPX variables with an emerging scientific evidence base, to describe the synergistic value of combining CPX with other assessments, to discuss personnel considerations for CPX laboratories, and to provide recommendations for future CPX research.

In heart failure (HF), women show better survival despite a comparatively low peak oxygen consumption (V˙o2): this raises doubt about the accuracy of risk assessment by cardiopulmonary exercise testing (CPET) in women. Accordingly, we aimed to check (1) whether the predictive role of well-known CPET risk indexes, ie, peak V˙o2and ventilatory response (V˙e/V˙co2slope), is sex independent and (2) if sex-related characteristics that impact outcome in HF should be considered as associations that may confound the effect of sex on survival.

Introduction There has been a greater appreciation of several variables obtained by cardiopulmonary exercise testing (CPX). Exercise oscillatory ventilation (EOV) is a CPX pattern that has gained recognition as an ominous marker of poor prognosis in cardiac patients. The purpose of the present study is to characterize whether such an abnormal ventilatory pattern may also be detected in apparently healthy subjects and determine its clinical significance.Methods The study involved 510 subjects (mean age 60 ± 14 years; 49% male) with a broad cardiovascular (CV) risk factor profile who underwent CPX.Results The population was divided into two groups according to the presence (17%) or absence of EOV. Subjects with EOV were significantly older and a higher percentage was female. Risk factor profile and medication use was significantly different between subgroups, indicating subjects with EOV had a worse CV risk factor profile and were prescribed CV-focused preventive medications at a significantly higher frequency. Subjects with EOV had comparatively poorer CPX performance and gas exchange phenotype. Multivariate binary logistic regression analysis found being female was the strongest predictor of EOV (odds ratio: 2.77, 95% confidence interval (CI): 1.66-4.61, p< 0.001). A diagnosis of diabetes (odds ratio: 2.40, 95% CI: 1.34–4.15.2, p< 0.001) added significant value for predicting EOV and was retained in the regression. The likelihood for EOV for subjects who were female and diagnosed with diabetes was 3.71 (95% CI 1.88–7.30, p< 0.001).Conclusions This is the first study to examine EOV prevalence and characterization in apparently healthy persons with results supporting an in-depth definition of abnormal exercise phenotypes.

Background Oxygen uptake at the anaerobic threshold (VO2AT), a submaximal exercise-derived variable, independent of patients’ motivation, is a marker of outcome in heart failure (HF). However, previous evidence of VO2AT values paradoxically higher in HF patients with permanent atrial fibrillation (AF) than in those with sinus rhythm (SR) raised uncertainties.Design We tested the prognostic role of VO2AT in a large cohort of systolic HF patients, focusing on possible differences between SR and AF.Methods Altogether 2976 HF patients (2578 with SR and 398 with AF) were prospectively followed. Besides a clinical examination, each patient underwent a maximal cardiopulmonary exercise test (CPET).Results The follow-up was analysed for up to 1500 days. Cardiovascular death or urgent cardiac transplantation occurred in 303 patients (250 (9.6%) patients with SR and 53 (13.3%) patients with AF, p= 0.023). In the entire population, multivariate analysis including peak oxygen uptake (VO2) showed a prognostic capacity (C-index) similar to that obtained including VO2AT (0.76 vs 0.72). Also, left ventricular ejection fraction, ventilation vs carbon dioxide production slope, β-blocker and digoxin therapy proved to be significant prognostic indexes. The receiver-operating characteristic (ROC) curves analysis showed that the best predictive VO2AT cut-off for the SR group was 11.7 ml/kg/min, while it was 12.8 ml/kg/min for the AF group.Conclusions VO2AT, a submaximal CPET-derived parameter, is reliable for long-term cardiovascular mortality prognostication in stable systolic HF. However, different VO2AT cut-off values between SR and AF HF patients should be adopted.

Noncommunicable diseases (NCDs) have become the primary health concern for most countries around the world. Currently, more than 36 million people worldwide die from NCDs each year, accounting for 63% of annual global deaths; most are preventable. The global financial burden of NCDs is staggering, with an estimated 2010 global cost of $6.3 trillion (US dollars) that is projected to increase to $13 trillion by 2030. A number of NCDs share one or more common predisposing risk factors, all related to lifestyle to some degree: (1) cigarette smoking, (2) hypertension, (3) hyperglycemia, (4) dyslipidemia, (5) obesity, (6) physical inactivity, and (7) poor nutrition. In large part, prevention, control, or even reversal of the aforementioned modifiablerisk factors are realized through leading a healthy lifestyle (HL). The challenge is how to initiate the global change, not toward increasing documentation of the scope of the problem but toward true action—creating, implementing, and sustaining HL initiatives that will result in positive, measurable changes in the previously defined poor health metrics. To achieve this task, a paradigm shift in how we approach NCD prevention and treatment is required. The goal of this American Heart Association/European Society of Cardiology/European Association for Cardiovascular Prevention and Rehabilitation/American College of Preventive Medicine policy statement is to define key stakeholders and highlight their connectivity with respect to HL initiatives. This policy encourages integrated action by all stakeholders to create the needed paradigm shift and achieve broad adoption of HL behaviors on a global scale.

Pulmonary hypertension, which is related to right ventricular (RV) failure, indicates a poor prognosis in heart failure (HF). Increased ventilatory response and exercise oscillatory ventilation (EOV) also have a negative impact. We hypothesized that the severity classification of HF and risk prediction could be improved by combining functional capacity with cardiopulmonary exercise testing (CPET) and RV-pulmonary circulation coupling, as evaluated by the tricuspid annular plane systolic excursion (TAPSE)-pulmonary artery systolic pressure (PASP) relationship.

Pulmonary hypertension (PH) in left heart disease, classified as group II, is the most common form of PH that occurs in approximately 60% of cases of reduced and preserved left ventricular ejection fraction. Although relatively much is known about hemodynamic stages (passive or reactive) and their consequences on the right ventricle (RV) there is no consensus on the best hemodynamic definition of group II PH. In addition, the main pathways that lead to lung capillary injury and impaired biology of small artery remodelling processes are largely unknown. Typical lung manifestations of an increased pulmonary pressure and progressive RV-pulmonary circulation uncoupling are an abnormal alveolar capillary gas diffusion, impaired lung mechanics (restriction), and exercise ventilation inefficiency. Of several classes of pulmonary vasodilators currently clinically available, oral phosphodiesterase 5 inhibition, because of its strong selectivity for targeting the cyclic guanosine monophosphate pathway in the pulmonary circulation, is increasingly emerging as an attractive opportunity to reach hemodynamic benefits, reverse capillary injury, and RV remodelling, and improve functional capacity. Guanylate cyclase stimulators offer an additional intriguing opportunity but the lack of selectivity and systemic effects might preclude some of the anticipated benefits on the pulmonary circulation. Future trials will determine whether new routes of pharmacologic strategy aimed at targeting lung structural and vascular remodelling might affect morbidity and mortality in left heart disease populations. We believe that this therapeutic goal rather than a pure hemodynamic effect might ultimately emerge as an important challenge for the clinician.

The recent European Society of Cardiology position paper strongly advises participation of patients with stable heart failure (HF) in structured exercise training (ET) programs, and in most recent years considerable efforts have been put into standardization of exercise prescription. Up to now, 3 ET modalities are proposed for HF populations with variable combinations and extent of effects: (1) endurance aerobic (continuous and interval); (2) strength/resistance; (3) respiratory. Irrespective of ET modalities, most of the studies have clearly demonstrated significant improvements in exercise physiology (ie, oxygen consumption, muscle function, and ventilation), quality of life, and left ventricular function.

Several cardiovascular diseases are characterized by an impaired O2kinetic during exercise. The lack of a linear increase of oxygen consumption (VO2)Work Rate (WR) relationship, as assessed by expired gas analysis, is considered an indicator of abnormal cardiovascular efficiency. We aimed at describing the frequency of VO2WR flattening in a symptomatic population of cardiac patients, characterizing its functional profile, and testing the hypothesis that dynamic pulmonary hypertension and right ventricular contractile reserve play a major role as cardiac determinants.

Background We are unaware of any previous investigation that has compared the relationship of key cardiopulmonary exercise testing (CPX) variables to various measures of pathophysiology between heart failure-reduced ejection fraction (HFrEF) and HF-preserved ejection fraction (HFpEF) cohorts that are well matched with respect to baseline characteristics and their exercise response, which is the purpose of the present study.Methods Thirty-four patients with HFpEF were randomly matched to 34 subjects with HFrEF according to age and sex as well as peak oxygen consumption (VO2), ventilatory efficiency (VE/VCO2slope), and exercise oscillatory ventilation (EOV). In addition to CPX, patients also underwent echocardiography with tissue Doppler imaging (TDI) and assessment of N-terminal pro-B-type natriuretic peptide (NT-proBNP).Results When matched for age, sex, and CPX variables, the HFrEF and HFpEF cohorts had similar echocardiography with TDI and NT-proBNP values, indicating comparable disease severity. In addition, the correlations between key CPX measures (peak VO2and VE/VCO2slope) and echocardiography with TDI and NT-proBNP measures were similar between HFrEF and HFpEF groups. Of note, the correlation between the VE/VCO2slope and pulmonary artery systolic pressure and NT-proBNP was highly significant in both groups (r≥ 0.65, p< 0.01). Moreover, subjects with EOV in both groups had a significantly higher PASP (∼47 vs. ∼35 mmHg, p< 0.05).Conclusions The results of the current study indicate CPX equally represents disease severity in HFrEF and HFpEF patients. This is a novel finding supporting the key role of CPX in the clinical follow-up of HF patients irrespective of LVEF and cardiac phenotype.

Background Heart rate recovery (HRR) is becoming an important prognostic maker in heart failure (HF), but very little is known about the underlying mechanisms responsible for its clinical efficacy. Therefore, we examined echocardiographic and exercise (submaximal and maximal) characteristics to gain a better appreciation of HRR and factors responsible for the development of abnormal HRR in patients with both heart failure reduced ejection fraction (HFrEF) and heart failure preserved ejection fraction (HFpEF).Methods Cardiopulmonary exercise testing (CPX), a 6-minute walk test (6MWT), and resting 2D echocardiography were randomly performed in 240 HF patients (200 HFrEF, 40 HFpEF) after which HRR was measured. HRR was defined as the difference between heart rate at peak exercise and 1 minute following test termination.Results Bivariate correlation analyses found significant relationships among most CPX and 6MWT measurements with the highest correlations between 6MWT HRR and 6MWT peak HR (r= 0.65; p< 0.001) and CPX HRR and CPX HRreserve(r= 0.63; p< 0.001). The relationship between 6MWT HRR and CPX HRR was very good (r= 0.91; p< 001). Multivariate logistic regression of submaximal and maximal exercise found 6MWT peak HR and exercise oscillatory ventilation (EOV), respectively, were the strongest predictors (p< 0.001) of abnormal HRR. The E/E′ was a significant predictor (p< 0.001) of abnormal HRR, but EOV was the strongest predictor of abnormal HRR (OR = 6.5).Conclusions HRR after both CPX and the 6MWT is significantly related to many exercise and echocardiographic measures with the most significant predictors of abnormal HRR being related to indices of cardiorespiratory performance in patients with HFrEF and HFpEF.