High-resolution DNA methylation changes reveal biomarkers of heart failure with preserved ejection fraction versus reduced ejection fraction.

Novel biomarkers are needed to better identify-and distinguish-heart failure with preserved ejection fraction (HFpEF) from other clinical phenotypes. The goal of our study was to identify epigenetic-sensitive biomarkers useful to a more accurate diagnosis of HFpEF. We performed a network-oriented genome-wide DNA methylation study of circulating CD4 T lymphocytes isolated from peripheral blood using reduced representation bisulfite sequencing (RRBS) in two cohorts (i.

Pulmonary arterial hypertension with left to right shunts: When to treat and/or close?

Pulmonary arterial hypertension (PAH) is defined as increase in mean pulmonary arterial pressure and pulmonary vascular resistance (PVR). It can be associated with congenital heart disease (CHD) with the following subtypes: 1) uncorrected left-to-right (L-R) intracardiac shunt leading to overload of the pulmonary circulation and a progressive increase of PVR; 2) Eisenmenger syndrome, appearing when a large post-tricuspid shunt is left uncorrected and pulmonary vascular disease (PVD) is severe, so the shunt becomes bidirectional or right-to-left, causing cyanosis; 3) PAH after shunt closure, when PVR arises after a defect correction; and 4) PAH associated with small or coincidental defects. While the treatment of patients with Eisenmenger syndrome is well established, the treatment of patients with PAH in whom there is a L-R shunt (with no cyanosis) remains unclear and requires expertise.

A pulmonary hypertension targeted algorithm to improve referral to right heart catheterization: A machine learning approach.

Background: Pulmonary hypertension (PH) is a pathophysiological problem that may involve several clinical symptoms and be linked to various respiratory and cardiovascular illnesses. Its diagnosis is made invasively by Right Cardiac Catheterization (RHC), which is difficult to perform routinely. Aim of the current study was to develop a Machine Learning (ML) algorithm based on the analysis of anamnestic data to predict the presence of an invasively measured PH.

Gaps in evidence in the treatment of prevalent patients with pulmonary arterial hypertension at intermediate risk: An expert consensus.

Despite the innovations introduced in the 2022 European Society of Cardiology/European Respiratory Society Guidelines on Pulmonary Hypertension, risk discrimination and management of pulmonary arterial hypertension (PAH) patients at intermediate risk still represents a grey zone. Additionally, clinical evidence derived from currently available studies is limited. This expert panel survey intends to aid physicians in choosing the best therapeutic strategy for patients at intermediate risk despite ongoing oral therapy.

Biomarkers of lung congestion and injury in acute heart failure.

Acute heart failure (AHF) classification and management are primarily based on lung congestion and/or hypoperfusion. The quantification of the vascular and tissue lung damage is not standard practice though biomarkers of lung injury may play a relevant role in this context. Haemodynamic stress promotes alveolar and vascular derangement with loss of functional units, impaired lung capillary permeability and fluid swelling.

Right ventricular phenotyping in incident patients with idiopathic pulmonary arterial hypertension.

Background: Right ventricular (RV) imaging has not a definite role in risk stratification of pulmonary arterial hypertension (PAH) patients. We tested the hypothesis that echocardiography-derived phenotypes, depicting different degrees of RV remodeling and dysfunction, may provide additional prognostic information to current risk stratification tools.

Methods: Consecutive incident PAH patients aged ≥18 years, diagnosed between January 2005 and December 2021, underwent clinical assessment, right heart catheterization, standard echocardiography.

Gaps in evidence in the management of patients with intermediate-risk pulmonary arterial hypertension: Considerations following the ESC/ERS 2022 guidelines.

A comprehensive evaluation of risk, using multiple indices, is necessary to provide reliable prognostic information and guide therapy in pulmonary arterial hypertension (PAH). The current ESC/ERS guidelines suggest using a three-strata model for incident (newly diagnosed) patients and a four-strata model for prevalent patients with PAH. The four-strata model serves as a fundamental risk-stratification tool and relies on a minimal dataset of indicators that must be considered during follow-up.

[ANMCO/SIC Consensus statement on pulmonary arterial hypertension].

Pulmonary hypertension (PH) is a frequent pathological condition worldwide, mainly secondary to cardiovascular and respiratory diseases, with a poor prognosis. Pulmonary arterial hypertension (PAH) is a rare form that affects the arterial pulmonary vasculature. PH and PAH are characterized by non-specific symptoms and a progressive increase of pulmonary vascular resistance that results in progressive, sometimes irreversible, right ventricular dysfunction.

Lung Ultrasound, Echocardiography, and Fluid Challenge for the Differential Diagnosis of Pulmonary Hypertension.

Objectives: The differential diagnosis between pulmonary arterial hypertension (PAH) and postcapillary pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF) is sometimes difficult despite guidelines-derived standardized step-by-step diagnostic algorithms. We therefore explored the added value of lung ultrasound to a previously validated echocardiographic score of right heart catheterization measurements.

Methods: Patients referred for PH underwent a right heart catheterization, echocardiography, and lung ultrasound before and after rapid infusion of 7 mL/kg of saline.

Idiopathic Pulmonary Arterial Hypertension in Paediatrics Represents Still a Serious Challenge: A Case Series Study.

Introduction: Paediatric pulmonary hypertension (PH) represents a heterogeneous illness that is responsible for high morbidity and mortality if left without treatment. Idiopathic pulmonary arterial hypertension (IPAH) is a subtype of PAH rarely seen in paediatrics. Limited long-term data are available.

Relevance of comorbidities on initial combination therapy in pulmonary arterial hypertension.

Rationale: Demographic characteristics of pulmonary arterial hypertension (PAH) patients have changed over time, but the effects of cardiovascular risk factors on risk status and pulmonary vascular resistance (PVR) reduction with initial oral combination therapy are not known. Therefore, we tested the relevance of cardiovascular comorbidities in this setting.

Methods: The study enrolled 181 treatment-naive PAH patients with a 6-month (IQR 144-363 days) right heart catheterisation and risk assessment after initial oral combination therapy.

Right Ventricular Contractile Reserve: A Key Metric to Identifying When Cardiorespiratory Fitness Will Improve With Pulmonary Vasodilators.

Cardiorespiratory fitness (CRF) has been proposed as a vital sign for the past several years, supported by a wealth of evidence demonstrating its significance as a predictor of health trajectory, exercise/functional capacity, and the quality of life. According to the Fick equation, oxygen consumption (VO) is the product of cardiac output (CO) and arterial-venous oxygen difference, with the former being a primary driver of one's aerobic capacity. In terms of the dependence of aerobic capacity on a robust augmentation of CO from rest to maximal exercise, left ventricular (LV) CO has been the historic focal point.

Association Between Circulating CD4 T Cell Methylation Signatures of Network-Oriented SOCS3 Gene and Hemodynamics in Patients Suffering Pulmonary Arterial Hypertension.

Pathogenic DNA methylation changes may be involved in pulmonary arterial hypertension (PAH) onset and its progression, but there is no data on potential associations with patient-derived hemodynamic parameters. The reduced representation bisulfite sequencing (RRBS) platform identified N = 631 differentially methylated CpG sites which annotated to N = 408 genes (DMGs) in circulating CD4 T cells isolated from PAH patients vs. healthy controls (CTRLs).

The paradox of pulmonary arterial hypertension in Italy in the COVID-19 era: is risk of disease progression around the corner?

Objective: The coronavirus disease 2019 (COVID-19) outbreak has led to significant restrictions on routine medical care. We conducted a multicentre nationwide survey of patients with pulmonary arterial hypertension (PAH) to determine the consequences of governance measures on PAH management and risk of poor outcome in patients with COVID-19.

Materials And Methods: The present study, which included 25 Italian centres, considered demographic data, the number of in-person visits, 6-min walk and echocardiographic test results, brain natriuretic peptide/N-terminal pro-brain natriuretic peptide test results, World Health Organization functional class assessment, presence of elective and non-elective hospitalisation, need for treatment escalation/initiation, newly diagnosed PAH, incidence of COVID-19 and mortality rates.

Echocardiographic probability of pulmonary hypertension: a validation study.

Background: According to current guidelines, the diagnosis of pulmonary hypertension (PH) relies on echocardiographic probability followed by right heart catheterisation (RHC). How echocardiography predicts PH recently redefined by mean pulmonary arterial pressure (mPAP) >20 mmHg instead of ≥25 mmHg and pulmonary vascular disease defined by pulmonary vascular resistance (PVR) ≥3 or >2 WU has not been established.

Methods: A total of 278 patients referred for PH underwent comprehensive echocardiography followed by RHC.

[Pulmonary arterial hypertension or heart failure with preserved ejection fraction? Beyond heart catheterization: a roadmap for challenging cases].

The cause of dyspnea may remain uncertain even after a complete non-invasive clinical workup, and a right heart catheterization is performed to achieve a definitive diagnosis. Although pulmonary artery wedge pressure (PAWP) is key for the differential diagnosis between pulmonary arterial hypertension (PAH) and heart failure with preserved ejection fraction (HFpEF), the diagnosis may be challenging because PAWP may be normal after diuretic administration in HFpEF patients on optimal medical therapy. In order to avoid misdiagnosis, building a pre-test probability of pre- or post-capillary pulmonary hypertension is crucial.

Feasibility of semi-recumbent bicycle exercise Doppler echocardiography for the evaluation of the right heart and pulmonary circulation unit in different clinical conditions: the RIGHT heart international NETwork (RIGHT-NET).

Exercise Doppler echocardiography (EDE) is a well-validated tool in ischemic and valvular heart diseases. However, its use in the assessment of the right heart and pulmonary circulation unit (RH-PCU) is limited. The aim of this study is to assess the semi-recumbent bicycle EDE feasibility for the evaluation of RH-PCU in a large multi-center population, from healthy individuals and elite athletes to patients with overt or at risk of developing pulmonary hypertension (PH).

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.

Hemodynamics and risk assessment 2 years after the initiation of upfront ambrisentan‒tadalafil in pulmonary arterial hypertension.

Background: Upfront combination therapy with ambrisentan and tadalafil has been reported to improve the condition of patients with pulmonary arterial hypertension (PAH) more than with either drug alone. However, little is known about the long-term associated changes in hemodynamics and risk assessment scores.

Methods: This was a multicenter, retrospective analysis of clinical data in 106 patients with newly diagnosed PAH.

Risk Reduction and Hemodynamics with Initial Combination Therapy in Pulmonary Arterial Hypertension.

An initial oral combination of drugs is being recommended in pulmonary arterial hypertension (PAH), but the effects of this approach on risk reduction and pulmonary vascular resistance (PVR) are not known. To test the hypothesis that a low-risk status would be determined by the reduction of PVR in patients with PAH treated upfront with a combination of oral drugs. The study enrolled 181 treatment-naive patients with PAH (81% idiopathic) with a follow-up right heart catheterization at 6 months (interquartile range, 144-363 d) after the initial combination of endothelin receptor antagonist + phosphodiesterase-5 inhibitor drugs and clinical evaluation and risk assessments by European guidelines and Registry to Evaluate Early and Long-Term PAH Disease Management scores.