Bio-Humoral and Non-Invasive Haemodynamic Correlates of Renal Venous Flow Patterns across the Heart Failure Spectrum.

Background: We evaluated the bio-humoral and non-invasive haemodynamic correlates of renal congestion evaluated by Doppler renal venous flow (RVF) across the heart failure (HF) spectrum, from asymptomatic subjects with cardiovascular risk factors (Stage A) and structural heart disease (Stage B) to patients with clinically overt HF (Stage C). Methods: Ultrasound evaluation, including echocardiography, lung ultrasound and RVF, along with blood and urine sampling, was performed in 304 patients. Results: Continuous RVF was observed in 230 patients (76%), while discontinuous RVF (dRVF) was observed in 74 (24%): 39 patients had pulsatile RVF, 18 had biphasic RVF and 17 had monophasic RVF. Stage C HF was significantly more common among patients with dRVF. Monophasic RVF was associated with worse renal function and a higher urinary albumin-to-creatinine ratio (uACR). After adjusting for hypertension, diabetes mellitus, the presence of Stage C HF and serum creatinine levels, worsening RVF patterns were associated with higher NT-proBNP levels, worse right ventricular-arterial coupling, larger inferior vena cava and higher echo-derived pulmonary artery wedge pressure. This trend was confirmed when only patients with HF Stage C were analysed after adjusting for the left ventricle ejection fraction (LVEF). Conclusion: Abnormal RVF is common across the HF spectrum. Worsening RVF patterns are independently associated with increased congestion, worse non-invasive haemodynamics and impaired RV-arterial coupling. RVF evaluation could refine prognostic stratification across the HF spectrum, irrespective of LVEF.

Mechanisms of reduced peak oxygen consumption in subjects with uncomplicated type 2 diabetes.

BACKGROUND: Type 2 diabetes mellitus (T2D) increases the risk of incident heart failure (HF), whose earliest fingerprint is effort intolerance (i.e. impaired peak oxygen consumption, or VO2peak). In the uncomplicated T2D population, however, the prevalence of effort intolerance and the underpinning mechanistic bases are uncertain. Leveraging the multiparametric characterization allowed by imaging-cardiopulmonary exercise testing (iCPET), the aim of this study is to quantify effort intolerance in T2D and to dissect the associated cardiopulmonary alterations. METHODS: Eighty-eight adults with well-controlled and uncomplicated T2D and no criteria for HF underwent a maximal iCPET with speckle tracking echocardiography, vascular and endothelial function assessment, as well as a comprehensive biohumoral characterization. Effort intolerance was defined by a VO2peak below 80% of maximal predicted oxygen uptake. RESULTS: Forty-eight patients (55%) had effort intolerance reaching a lower VO2peak than T2D controls (16.5 ± 3.2 mL/min/kg, vs 21.7 ± 5.4 mL/min/kg, p < 0.0001). Despite a comparable cardiac output, patients with effort intolerance showed reduced peak peripheral oxygen extraction (11.3 ± 3.1 vs 12.7 ± 3.3 mL/dL, p = 0.002), lower VO2/work slope (9.9 ± 1.2 vs 11.2 ± 1.4, p < 0.0001), impaired left ventricle systolic reserve (peak S' 13.5 ± 2.8 vs 15.2 ± 3.0, p = 0.009) and global longitudinal strain (peak-rest ΔGLS 1.7 ± 1.5 vs 2.5 ± 1.8, p = 0.03) than subjects with VO2peak above 80%. Diastolic function, vascular resistance, endothelial function, biohumoral exams, right heart and pulmonary function indices did not differ between the two groups. CONCLUSIONS: Effort intolerance and reduced VO2peak is a severe and highly prevalent condition in uncomplicated, otherwise asymptomatic T2D. It results from a major defect in skeletal muscle oxygen extraction coupled with a subtle myocardial systolic dysfunction.

A multicentric quality-control study of exercise Doppler echocardiography of the right heart and the pulmonary circulation. The RIGHT Heart International NETwork (RIGHT-NET).

PURPOSE: This study was a quality-control study of resting and exercise Doppler echocardiography (EDE) variables measured by 19 echocardiography laboratories with proven experience participating in the RIGHT Heart International NETwork. METHODS: All participating investigators reported the requested variables from ten randomly selected exercise stress tests. Intraclass correlation coefficients (ICC) were calculated to evaluate the inter-observer agreement with the core laboratory. Inter-observer variability of resting and peak exercise tricuspid regurgitation velocity (TRV), right ventricular outflow tract acceleration time (RVOT Act), tricuspid annular plane systolic excursion (TAPSE), tissue Doppler tricuspid lateral annular systolic velocity (S'), right ventricular fractional area change (RV FAC), left ventricular outflow tract velocity time integral (LVOT VTI), mitral inflow pulsed wave Doppler velocity (E), diastolic mitral annular velocity by TDI (e') and left ventricular ejection fraction (LVEF) were measured. RESULTS: The accuracy of 19 investigators for all variables ranged from 99.7 to 100%. ICC was > 0.90 for all observers. Inter-observer variability for resting and exercise variables was for TRV = 3.8 to 2.4%, E = 5.7 to 8.3%, e' = 6 to 6.5%, RVOT Act = 9.7 to 12, LVOT VTI = 7.4 to 9.6%, S' = 2.9 to 2.9% and TAPSE = 5.3 to 8%. Moderate inter-observer variability was found for resting and peak exercise RV FAC (15 to 16%). LVEF revealed lower resting and peak exercise variability of 7.6 and 9%. CONCLUSIONS: When performed in expert centers EDE is a reproducible tool for the assessment of the right heart and the pulmonary circulation.

Assessing vulnerability to psychological distress during the COVID-19 pandemic through the analysis of microblogging content.

In recent years we have witnessed a growing interest in the analysis of social media data under different perspectives, since these online platforms have become the preferred tool for generating and sharing content across different users organized into virtual communities, based on their common interests, needs, and perceptions. In the current study, by considering a collection of social textual contents related to COVID-19 gathered on the Twitter microblogging platform in the period between August and December 2020, we aimed at evaluating the possible effects of some critical factors related to the pandemic on the mental well-being of the population. In particular, we aimed at investigating potential lexicon identifiers of vulnerability to psychological distress in digital social interactions with respect to distinct COVID-related scenarios, which could be "at risk" from a psychological discomfort point of view. Such scenarios have been associated with peculiar topics discussed on Twitter. For this purpose, two approaches based on a "top-down" and a "bottom-up" strategy were adopted. In the top-down approach, three potential scenarios were initially selected by medical experts, and associated with topics extracted from the Twitter dataset in a hybrid unsupervised-supervised way. On the other hand, in the bottom-up approach, three topics were extracted in a totally unsupervised way capitalizing on a Twitter dataset filtered according to the presence of keywords related to vulnerability to psychological distress, and associated with at-risk scenarios. The identification of such scenarios with both approaches made it possible to capture and analyze the potential psychological vulnerability in critical situations.

The assessment of pressure-volume relationship during exercise stress echocardiography predicts left ventricular remodeling and eccentric hypertrophy in patients with chronic heart failure.

BACKGROUND: The contractile response of patients with heart failure (HF) may be assessed by exercise stress echocardiography (ESE)-derived indexes. We sought to test whether ESE parameters are useful to identify the risk of adverse left ventricular (LV) remodeling in patients with chronic HF and reduced or mildly reduced LV ejection fraction (EF). METHODS: We enrolled 155 stabilized patients (age: 62 ± 11 years, 17% female, coronary artery disease 47%) with chronic HF, LV EF ≤50% and LV end-diastolic volume index > 75 ml/m2. All patients underwent a symptom-limited graded bicycle semi-supine ESE, with evaluation of peak stress LV EF, end-systolic pressure-volume relation (ESPVR, i.e. LV elastance) and cardiac power output to LV mass (CPOM). A complete echocardiographic study was performed at baseline and after 6 ± 3 months. Adverse LV remodeling was defined as the association of eccentric LV hypertrophy (LV mass: ≥115 g/m2 for male and ≥ 95 g/m2 for women, and relative wall thickness < 0.32) with an increase in LV end-systolic volume index ≥10% at six months. RESULTS: Adverse LV remodeling was detected in 34 (22%) patients. After adjustment for clinical, biochemical and echocardiographic data, peak ESPVR resulted in the most powerful independent predictor of adverse LV remodeling (OR: 12.5 [95% CI 4.5-33]; p < 0.0001) followed by ischemic aetiology (OR: 2.64 [95% 1.04-6.73]; p = 0.04). CONCLUSION: In patients with HF and reduced or mildly reduced EF, a compromised ESE-derived peak ESPVR, that reflects impaired LV contractility, resulted to be the most powerful predictor of adverse LV remodeling.

Evolving Paradigms in Transcatheter Aortic Valve Replacement: Results from a High-Volume, Single Center Experience.

Given the expanding indications toward younger patients at lower surgical risk, transcatheter aortic valve replacement (TAVR) simplification and streamlining are gaining increasing importance. Patients who underwent TAVR from the year 2015 to 2020 were prospectively enrolled. The patients were divided in time tertiles according to the date of intervention. Data on preprocedural planning, including coronary computed tomography angiography (CCTA), procedures, and outcomes, were compared between the time tertiles. A total of 771 consecutive patients from a single institution were enrolled. We observed a trend toward the use of a fully percutaneous versus surgical approach for the index access, left radial artery versus contralateral femoral artery for the secondary access, and left ventricular pacing on the stiff guidewire versus right ventricular pacing. Immediate device success significantly increased, whereas the length of hospital stay decreased. Overall, approximately 60% of the total study population underwent CCTA instead of coronary angiography, with no adverse events. One-year survival rates significantly improved over time. A simplified TAVR approach was associated with better survival, whereas low baseline functional capacity, preexisting coronary artery disease, renal impairment, periprocedural blood transfusions, and paravalvular leak were related to worse outcomes. In conclusion, our study showed a constant tendency to procedure streamlining and improve procedural success and 1-year outcomes. A strategy based on CCTA allows sparing safely almost half of the preoperative invasive coronary angiography.

Novel Techniques, Biomarkers and Molecular Targets to Address Cardiometabolic Diseases.

Cardiometabolic diseases (CMDs) are interrelated and multifactorial conditions, including arterial hypertension, type 2 diabetes, heart failure, coronary artery disease, and stroke. Due to the burden of cardiovascular morbidity and mortality associated with CMDs' increasing prevalence, there is a critical need for novel diagnostic and therapeutic strategies in their management. In clinical practice, innovative methods such as epicardial adipose tissue evaluation, ventricular-arterial coupling, and exercise tolerance studies could help to elucidate the multifaceted mechanisms associated with CMDs. Similarly, epigenetic changes involving noncoding RNAs, chromatin modulation, and cellular senescence could represent both novel biomarkers and targets for CMDs. Despite the promising data available, significant challenges remain in translating basic research findings into clinical practice, highlighting the need for further investigation into the complex pathophysiology underlying CMDs.

Guideline-Directed Medical Therapy and Survival After TEER for Secondary Mitral Regurgitation With Right Ventricular Impairment.

BACKGROUND: Right ventricular impairment is common among patients undergoing transcatheter edge-to-edge repair for secondary mitral regurgitation (SMR). Adherence to guideline-directed medical therapy (GDMT) for heart failure is poor in these patients. OBJECTIVES: The aim of this study was to evaluate the impact of GDMT on long-term survival in this patient cohort. METHODS: Within the EuroSMR (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation) international registry, we selected patients with SMR and right ventricular impairment (tricuspid annular plane systolic excursion ≤17 mm and/or echocardiographic right ventricular-to-pulmonary artery coupling <0.40 mm/mm Hg). Titrated guideline-directed medical therapy (GDMTtit) was defined as a coprescription of 3 drug classes with at least one-half of the target dose at the latest follow-up. The primary outcome was all-cause mortality at 6 years. RESULTS: Among 1,213 patients with SMR and right ventricular impairment, 852 had complete data on medical therapy. The 123 patients who were on GDMTtit showed a significantly higher long-term survival vs the 729 patients not on GDMTtit (61.8% vs 36.0%; P < 0.00001). Propensity score-matched analysis confirmed a significant association between GDMTtit and higher survival (61.0% vs 43.1%; P = 0.018). GDMTtit was an independent predictor of all-cause mortality (HR: 0.61; 95% CI: 0.39-0.93; P = 0.02 for patients on GDMTtit vs those not on GDMTtit). Its association with better outcomes was confirmed among all subgroups analyzed. CONCLUSIONS: In patients with right ventricular impairment undergoing transcatheter edge-to-edge repair for SMR, titration of GDMT to at least one-half of the target dose is associated with a 40% lower risk of all-cause death up to 6 years and should be pursued independent of comorbidities.

[Management of myocardial infarction and ischemia without obstructive coronary arteries: insights from a case series]. / Gestione dell'infarto miocardico e dell'ischemia miocardica senza ostruzione coronarica significativa: approfondimenti da una serie di casi clinici.

Acute coronary syndromes typically result from the formation of atherosclerotic lesions in a large epicardial vessel, which restrict blood flow either partially or completely. These lesions can be identified through angiography, an invasive imaging technique that enables visualization of the coronary arteries. However, a small percentage of patients, usually ranging from 5% to 10%, experience symptoms and/or signs of myocardial ischemia, either acute or chronic, without significant obstructive coronary lesions visible on angiography. This condition is particularly prevalent in young women and is characterized by two distinct forms: myocardial infarction with no obstructive coronary arteries (MINOCA) and myocardial ischemia with no obstructive coronary arteries (INOCA). MINOCA can be caused by a variety of heterogeneous mechanisms, including coronary vascular spasm, microvascular disease, spontaneous coronary dissection, and plaque rupture or erosion. Conversely, coronary vasospasm and microvascular dysfunction account for the majority of patients with INOCA. We here present three cases of MINOCA/INOCA that were evaluated using optical coherence tomography, coronary flow reserve, index of microcirculatory resistance, and acetylcholine provocative test. These diagnostic tests allowed us to identify a specific condition and adopt a targeted treatment for each patient.

Cardiometabolic Phenotyping in Heart Failure: Differences between Patients with Reduced vs. Preserved Ejection Fraction.

AIMS: We explored multiple cardiometabolic patterns, including inflammatory and congestive pathways, in patients with heart failure (HF). METHODS AND RESULTS: We enrolled 270 HF patients with reduced (<50%, HFrEF; n = 96) and preserved (≥50%, HFpEF; n = 174) ejection fraction. In HFpEF, glycated hemoglobin (Hb1Ac) seemed to be relevant in its relationship with inflammation as Hb1Ac positively correlated with high-sensitivity C-reactive protein (hs-CRP; Spearman's rank correlation coefficient ρ = 0.180, p < 0.05). In HFrEF, we found a correlation between Hb1Ac and norepinephrine (ρ = 0.207, p < 0.05). In HFpEF, we found a positive correlation between Hb1Ac and congestion expressed as pulmonary B lines (ρ = 0.187, p < 0.05); the inverse correlation, although not significant, was found in HFrEF between Hb1Ac and N-terminal pro-B-type natriuretic peptide (ρ = 0.079) and between Hb1Ac and B lines (ρ = -0.051). In HFrEF, we found a positive correlation between E/e' ratio and Hb1Ac (ρ = 0.203, p < 0.05) and a negative correlation between tricuspid annular systolic excursion (TAPSE)/echocardiographically measured systolic pulmonary artery pressure (sPAP) (TAPSE/sPAP ratio) (ρ = -0.205, p < 0.05) and Hb1Ac. In HFpEF, we found a negative correlation between TAPSE/sPAP ratio and uric acid (ρ = -0.216, p < 0.05). CONCLUSION: In HF patients, HFpEF and HFrEF phenotypes are characterized by different cardiometabolic indices related to distinct inflammatory and congestive pathways. Patients with HFpEF showed an important relationship between inflammatory and cardiometabolic parameters. Conversely, in HFrEF, there is a significant relationship between congestion and inflammation, while cardiometabolism appears not to influence inflammation, instead affecting sympathetic hyperactivation.

Prognostic Role of Sonographic Decongestion in Patients with Acute Heart Failure with Reduced and Preserved Ejection Fraction: A Multicentre Study.

BACKGROUND: We investigated the role of the dynamic changes of pulmonary congestion, as assessed by sonographic B-lines, as a tool to stratify prognosis in patients admitted for acute heart failure with reduced and preserved ejection fraction (HFrEF, HFpEF). METHODS: In this multicenter, prospective study, lung ultrasound was performed at admission and before discharge by trained investigators, blinded to clinical findings. RESULTS: We enrolled 208 consecutive patients (mean age 76 [95% confidence interval, 70-84] years), 125 with HFrEF, 83 with HFpEF (mean ejection fraction 32% and 57%, respectively). The primary composite endpoint of cardiovascular death or HF re-hospitalization occurred in 18% of patients within 6 months. In the overall population, independent predictors of the occurrence of the primary endpoint were the number of B-lines at discharge, NT-proBNP levels, moderate-to-severe mitral regurgitation, and inferior vena cava diameter on admission. B-lines at discharge were the only independent predictor in both HFrEF and HFpEF subgroups. A cut-off of B-lines > 15 at discharge displayed the highest accuracy in predicting the primary endpoint (AUC = 0.80, p < 0.0001). Halving B-lines during hospitalization further improved event classification (continuous net reclassification improvement = 22.8%, p = 0.04). CONCLUSIONS: The presence of residual subclinical sonographic pulmonary congestion at discharge predicts 6-month clinical outcomes across the whole spectrum of acute HF patients, independent of conventional biohumoral and echocardiographic parameters. Achieving effective pulmonary decongestion during hospitalization is associated with better outcomes.

Haemodynamic and metabolic phenotyping of patients with aortic stenosis and preserved ejection fraction: A specific phenotype of heart failure with preserved ejection fraction?

AIMS: Degenerative aortic valve stenosis with preserved ejection fraction (ASpEF) and heart failure with preserved ejection fraction (HFpEF) display intriguing similarities. This study aimed to provide a non-invasive, comparative analysis of ASpEF versus HFpEF at rest and during exercise. METHODS AND RESULTS: We prospectively enrolled 148 patients with HFpEF and 150 patients with degenerative moderate-to-severe ASpEF, together with 66 age- and sex-matched healthy controls. All subjects received a comprehensive evaluation at rest and 351/364 (96%) performed a combined cardiopulmonary exercise stress echocardiography test. Patients with ASpEF eligible for transcatheter aortic valve replacement (n = 125) also performed cardiac computed tomography (CT). HFpEF and ASpEF patients showed similar demographic distribution and biohumoral profiles. Most patients with ASpEF (134/150, 89%) had severe high-gradient aortic stenosis; 6/150 (4%) had normal-flow, low-gradient ASpEF, while 10/150 (7%) had low-flow, low-gradient ASpEF. Both patient groups displayed significantly lower peak oxygen consumption (VO2 ), peak cardiac output, and peak arteriovenous oxygen difference compared to controls (all p < 0.01). ASpEF patients showed several extravalvular abnormalities at rest and during exercise, similar to HFpEF (all p < 0.01 vs. controls). Epicardial adipose tissue (EAT) thickness was significantly greater in ASpEF than HFpEF and was inversely correlated with peak VO2 in all groups. In ASpEF, EAT was directly related to echocardiography-derived disease severity and CT-derived aortic valve calcium burden. CONCLUSION: Functional capacity is similarly impaired in ASpEF and HFpEF due to both peripheral and central components. Further investigation is warranted to determine whether extravalvular alterations may affect disease progression and prognosis in ASpEF even after valve intervention, which could support the concept of ASpEF as a specific sub-phenotype of HFpEF.

Exercise Stress Echocardiography of the Right Ventricle and Pulmonary Circulation.

BACKGROUND: Exercise echocardiography is used for assessment of pulmonary circulation and right ventricular function, but limits of normal and disease-specific changes remain insufficiently established. OBJECTIVES: The objective of this study was to explore the physiological vs pathologic response of the right ventricle and pulmonary circulation to exercise. METHODS: A total of 2,228 subjects were enrolled: 375 healthy controls, 40 athletes, 516 patients with cardiovascular risk factors, 17 with pulmonary arterial hypertension, 872 with connective tissue diseases without overt pulmonary hypertension, 113 with left-sided heart disease, 30 with lung disease, and 265 with chronic exposure to high altitude. All subjects underwent resting and exercise echocardiography on a semirecumbent cycle ergometer. All-cause mortality was recorded at follow-up. RESULTS: The 5th and 95th percentile of the mean pulmonary artery pressure-cardiac output relationships were 0.2 to 3.5 mm Hg.min/L in healthy subjects without cardiovascular risk factors, and were increased in all patient categories and in high altitude residents. The 5th and 95th percentile of the tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio at rest were 0.7 to 2.0 mm/mm Hg at rest and 0.5 to 1.5 mm/mm Hg at peak exercise, and were decreased at rest and exercise in all disease categories and in high-altitude residents. An increased all-cause mortality was predicted by a resting tricuspid annular plane systolic excursion to systolic pulmonary artery pressure <0.7 mm/mm Hg and mean pulmonary artery pressure-cardiac output >5 mm Hg.min/L. CONCLUSIONS: Exercise echocardiography of the pulmonary circulation and the right ventricle discloses prognostically relevant differences between healthy subjects, athletes, high-altitude residents, and patients with various cardio-respiratory conditions. (Right Heart International NETwork During Exercise in Different Clinical Conditions; NCT03041337).

Porto-pulmonary arterial hypertension: Translation of pathophysiological concepts to the bedside.

Porto-pulmonary arterial hypertension (PoPAH) is a form of pulmonary arterial hypertension (PAH) that affects patients with cirrhosis, and - to a lesser extent - patients with non-cirrhotic liver diseases. Compared with other forms of PAH, PoPAH is more prevalent in male, in older subjects, and is characterized by lower mean pulmonary arterial pressure (mPAP) and lower pulmonary vascular resistance (PVR) with higher cardiac output. Despite more favorable hemodynamics and functional class, patients with PoPAH have a significantly worse survival than patients with other forms of PAH, likely because of liver-related events and therapeutic barriers to PAH-specific therapy. Furthermore, here cardiopulmonary and hepatic complications may affect treatment efficacy. These patients have been excluded from most randomized clinical trials testing PAH-specific treatments. To date, there is only one study investigating efficacy, safety, tolerability and pharmacokinetics of PAH-specific therapy in patients with PoPAH in a randomized placebo-controlled setting. In this trial the use of the endothelin-1 receptor antagonist macitentan showed clear hemodynamic benefit without safety concerns. However, the drug effects on functional capacity and mortality remain unclear. Here we review the current knowledge on the pathophysiology and management of PoPAH and report a case vignette of a patient with PoPAH due to hepatorenal polycystic disease.

Mitral valve stenosis in the current era: a changing landscape.

Mitral stenosis results from haemodynamic obstruction at the mitral valve level because of structural abnormalities of the valve apparatus, leading to increased resistance to the transmitral flow. Although rheumatic fever remains the predominant cause of mitral stenosis worldwide, other causes are increasingly relevant in the developed countries with degenerative mitral stenosis (DMS) because of mitral annulus calcification (MAC) becoming growingly prevalent in industrialized countries with higher life expectancy. Rheumatic mitral stenosis (RMS) and DMS display dramatic differences in pathophysiology, prognosis, and disease progression. Furthermore, to date, robust evidence regarding the management of DMS because of MAC is lacking. Nevertheless, new diagnostic techniques and catheter-based interventions are changing this landscape and paving the way to a significant reduction in DMS-related morbidity and mortality. Here we briefly review the current knowledge on the pathophysiology, diagnosis and treatment of DMS and RMS, underscoring the current diagnostic and therapeutic pathways, as well as persisting uncertainties and perspectives.

Exercise-induced pulmonary hypertension in HFpEF and HFrEF: Different pathophysiologic mechanism behind similar functional impairment.

AIMS: Pathophysiological mechanisms behind cardio-pulmonary impairment in heart failure (HF) with reduced (HFrEF) and preserved (HFpEF) ejection fraction are likely different. We analysed them using combined cardiopulmonary-exercise stress echocardiography (CPET-ESE). METHODS: We matched 1:1 subjects with HFrEF (n = 90) and HFpEF (n = 90) for age, sex, body mass index (BMI), peak oxygen consumption, and minute ventilation/carbon dioxide production slope. All patients underwent a symptom-limited graded ramp bicycle CPET-ESE compared with 40 age-, sex- and BMI-matched healthy controls. RESULTS: During a median follow-up of 25 months, we observed 22 deaths and 80 HF hospitalisations, with similar distribution between HFpEF and HFrEF. Compared with HFrEF, HFpEF had a higher prevalence of metabolic syndrome (p = 0.02) with higher levels of high-sensitivity C-reactive protein and uric acid (p < 0.01). The multipoint mean pulmonary artery pressure/cardiac output (mPAP/CO) slope showed equally increased values in HFrEF and HFpEF (3.5 ± 1.8 and 3.7 ± 1.5 mmHg/L/min) compared with controls (1.8 ± 1.1 mmHg/L/min; p < 0.0001). During exercise, HFpEF displayed more adverse interaction of right ventricle-pulmonary artery (RV-PA; tricuspid annular plane systolic excursion/systolic pulmonary artery pressure: 0.40 ± 0.2 vs 0.47 ± 0.2 mm/mmHg in HFrEF; p < 0.01) and left atrium-left ventricle (LA-LV; LA reservoir strain/LV global longitudinal strain: 1.5 ± 0.8 vs 2.2 ± 1.1 in HFrEF; p < 0.01). The latter were independent predictors of mPAP/CO slope, along with hs-CRP (adjusted R2: 0.21; p < 0.0001). CONCLUSION: Despite similar disease severity, HFpEF and HFrEF show different pathophysiological mechanisms. HFpEF is characterised by a worse LA-LV and RV-PA interaction than HFrEF, with more prevalent low-grade systemic inflammation. In HFpEF, these features may have a role in exercise-induced pulmonary hypertension.

Arterial Hypertension and Cardiopulmonary Function: The Value of a Combined Cardiopulmonary and Echocardiography Stress Test.

Arterial hypertension (AH) is a global burden and the leading risk factor for mortality worldwide. Haemodynamic abnormalities, longstanding neurohormonal and inflammatory activation, which are commonly observed in patients with AH, promote cardiac structural remodeling ultimately leading to heart failure (HF) if blood pressure values remain uncontrolled. While several epidemiological studies have confirmed the strong link between AH and HF, the pathophysiological processes underlying this transition remain largely unclear. The combined cardiopulmonary-echocardiography stress test (CPET-ESE) represents a precious non-invasive aid to detect alterations in patients at the earliest stages of HF. The opportunity to study the response of the cardiovascular system to exercise, and to differentiate central from peripheral cardiovascular maladaptations, makes the CPET-ESE an ideal technique to gain insights into the mechanisms involved in the transition from AH to HF, by recognizing alterations that might be silent at rest but influence the response to exercise. Identifications of these subclinical alterations might allow for a better risk stratification in hypertensive patients, facilitating the recognition of those at higher risk of evolution towards established HF. This may also lead to the development of novel preventive strategies and help tailor medical treatment. The purpose of this review is to summarise the potential advantages of using CPET-ESE in the characterisation of hypertensive patients in the cardiovascular continuum.

Characterization of hemodynamic and metabolic abnormalities in the heart failure spectrum: the role of combined cardiopulmonary and exercise echocardiography stress test.

Heart failure (HF) is a complex clinical syndrome characterized by different etiologies and a broad spectrum of cardiac structural and functional abnormalities. Current guidelines suggest a classification based on left ventricular ejection fraction (LVEF), distinguishing HF with reduced (HFrEF) from preserved (HFpEF) LVEF. HF should also be thought of as a continuous range of conditions, from asymptomatic stages to clinically manifest syndrome. The transition from one stage to the next is associated with a worse prognosis. While the rate of HF-related hospitalization is similar in HFrEF and HFpEF once clinical manifestations occur, accurate knowledge of the steps and risk factors leading to HF progression is still lacking, especially in HFpEF. Precise hemodynamic and metabolic characterization of patients with or at risk of HF may help identify different disease trajectories and risk factors, with the potential to identify specific treatment targets that might offset the slippery slope towards overt clinical manifestations. Exercise can unravel early metabolic and hemodynamic alterations that might be silent at rest, potentially leading to improved risk stratification and more effective treatment strategies. Cardiopulmonary exercise testing (CPET) offers valuable aid to investigate functional alterations in subjects with or at risk of HF, while echocardiography can assess cardiac structure and function objectively, both at rest and during exercise (exercise stress echocardiography [ESE]). The purpose of this narrative review was to summarize the potential advantages of using an integrated CPET-ESE evaluation in the characterization of both subjects at risk of developing HF and patients with stable HF.

Exercise-induced pulmonary hypertension in HIV patients: Association with poor clinical and immunological status.

BACKGROUND AND AIM: Exercise-induced pulmonary hypertension (Ex-PH) may represent the earliest sign of pulmonary arterial hypertension (PAH) in human immunodeficiency virus (HIV) patients. We investigated its association with clinical and immunological status, virologic control, and response to antiviral therapy. METHODS: In 32 consecutive HIV patients with either low (n = 29) or intermediate probability (n = 3) of PH at rest, we evaluated the association of isolated ExPH with: time to HIV diagnosis; CD4+ T-cell count; clinical progression to acquired immunodeficiency syndrome (AIDS); development of resistance to antiretroviral therapy (ART); HIV RNA levels; time to beginning of ART; current use of protease inhibitors; combination of ART with boosters (ritonavir or cobicistat); immuno-virologic response to ART; and ART discontinuation. Isolated ExPH at stress echocardiography (ESE) was defined as absence of PH at rest and systolic pulmonary arterial pressure (sPAP) >45 mmHg or a >20 mmHg increase during low-intensity exercise cardiac output (<10 L/min). RESULTS: In our cohort, 22% (n = 7) of the enrolled population developed ExPH which was inversely related to CD4+ T-cell count (p = 0.047), time to HIV diagnosis (p = 0.014) and time to onset of ART (p = 0.041). Patients with ExPH had a worse functional class than patients without ExPH (p < 0.001). ExPH and AIDS showed a trend (p = 0.093) to a direct relationship. AIDS patients had a higher pulmonary vascular resistance compared to patients without ExPH (p = 0.020) at rest echocardiography. CONCLUSIONS: The presence of isolated ExPH associates with a worse clinical status and poor immunological control in HIV patients. Assessment of ExPH by ESE may help identify subgroups of HIV patients with a propensity to develop subclinical impairment of pulmonary circulation following poor control of HIV infection.

Impact of epicardial adipose tissue on cardiovascular haemodynamics, metabolic profile, and prognosis in heart failure.

AIMS: We evaluated the impact of echocardiographic epicardial adipose tissue (EAT) on cardiovascular haemodynamics, metabolic profile and prognosis in heart failure (HF) using combined cardiopulmonary-echocardiography exercise stress. METHODS AND RESULTS: We analysed EAT thickness of HF patients with reduced (HFrEF, n = 205) and preserved (HFpEF, n = 188) ejection fraction, including 44 controls. HFpEF patients displayed the highest EAT, while HFrEF patients had lower values than controls. EAT showed an inverse correlation with natriuretic peptides, troponin T and C-reactive protein in HFrEF, while having a direct association with troponin T and C-reactive protein in HFpEF. EAT was independently associated with peak oxygen consumption (VO2 ) and peripheral extraction (AVO2 diff), regardless of body mass index. EAT was inversely correlated with peak VO2 and AVO2 diff in HFpEF, while a direct association was observed in HFrEF, where lower EAT values were associated with worse left ventricular systolic dysfunction. In HFpEF, increased EAT was related to right ventriculo-arterial (tricuspid annular plane systolic excursion/systolic pulmonary artery pressure) uncoupling. After 21 months of follow-up, 146 HF hospitalizations and 34 cardiovascular deaths were recorded in the HF population. Cox multivariable analysis supported an independent differential role of EAT in HF cohorts (interaction P = 0.01): higher risk of adverse events for increasing EAT in HFpEF [hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.04-1.37] and for decreasing EAT in HFrEF (HR 0.75, 95% CI 0.54-0.91). CONCLUSION: In HFpEF, EAT accumulation is associated with worse haemodynamic and metabolic profile, also affecting survival. Conversely, lower EAT values imply higher left ventricular dysfunction, global functional impairment and adverse prognosis in HFrEF.