Prognostic value of deep echocardiographic phenotyping in pulmonary arterial hypertension.

Background: A novel approach to derive prognostic information from echocardiography in pulmonary arterial hypertension (PAH) is to define a phenotype of right heart function combining standard echocardiographic parameters which describe right ventricular pump function and systemic venous congestion. We tested the hypothesis that the combination of advanced strain imaging parameters could yield high prognostic accuracy. Methods: This was a prospective observational study with a single centre derivation cohort and a second centre validation cohort. The derivation cohort included 49 naive PAH patients who underwent right heart catheterisation and echocardiographic evaluation at baseline and 4-12 months after diagnosis. The validation cohort included 83 prevalent PAH patients who underwent the same examinations at 12 months after diagnosis. We stratified the risk of the derivation cohort according to three models: Model 1, based on haemodynamic parameters; Model 2, based on standard echocardiographic parameters; and Model 3, based on advanced echocardiographic parameters. The median follow-up period was 21 months; the end point of the analysis was clinical worsening. Results: In the derivation cohort, haemodynamic and echocardiographic parameters obtained at diagnosis were not associated with outcome, whereas a significant association was observed at first reassessment. Model 3 yielded a better predictive accuracy (Harrell's C index 0.832) as compared to Model 2 (Harrell's C index 0.667), and to Model 1 (Harrell's C index 0.713). The validation cohort confirmed the accuracy of Model 3. Conclusions: A comprehensive assessment of right heart function using right ventricular strain, right atrial reservoir strain and degree of tricuspid regurgitation provides accurate prognostic information in prevalent PAH patients.

Does moderate hyperkalemia influence survival in HF? Insights from the MECKI score data base.

BACKGROUND: The prognostic role of moderate hyperkalemia in reduced ejection fraction (HFrEF) patients is still controversial. Despite this, it affects the use of renin-angiotensin-aldosterone system inhibitors (RAASi) with therapy down-titration or discontinuation. OBJECTIVES: Aim of the study was to assess the prognostic impact of moderate hyperkalemia in chronic HFrEF optimally treated patients. METHODS AND RESULTS: We retrospectively analyzed MECKI (Metabolic Exercise test data combined with Cardiac and Kidney Indexes) database, with median follow-up of 4.2 [IQR 1.9-7.5] years. Data on K+ levels were available in 7087 cases. Patients with K+ plasma level ≥ 5.6 mEq/L and < 4 mEq/L were excluded. Remaining patients were categorized into normal >4 and < 5 mEq/L (n = 4826, 68%) and moderately high ≥5.0 and ≤ 5.5 mEq/L (n = 496, 7%) K+. Then patients were matched by propensity score in 484 couplets of patients. MECKI score value was 7% [IQR 3.1-14.1%] and 7.3% [IQR 3.4-15%] (p = 0.678) in patients with normal and moderately high K+ values while cardiovascular mortality events at two years follow-up were 41 (4.2%) and 33 (3.4%) (p = 0.333) in each group respectively. CONCLUSIONS: Moderate hyperkalemia does not influence patients' outcome in a large cohort of ambulatory HFrEF patients.

Haemodynamic effects of an acute vasodilator challenge in heart failure patients with reduced ejection fraction and different forms of post-capillary pulmonary hypertension.

AIMS: The most recent European guidelines have proposed new definitions of pulmonary hypertension (PH) in left heart disease, to better approach the characteristics required to reflect the presence of pulmonary vascular disease. The purpose of this study was to assess whether different haemodynamic definitions of post-capillary PH imply a different reversibility of PH in response to acute vasodilator administration in heart failure patients with reduced ejection fraction and PH (HFrEF-PH). METHODS AND RESULTS: Right heart catheterization and reversibility testing was performed in 156 HFrEF-PH patients. Patients were classified as combined post-capillary and pre-capillary pulmonary hypertension (Cpc-PH) vs. isolated post-capillary pulmonary hypertension (Ipc-PH) and on the basis of diastolic pulmonary gradient (DPG) ≥ 7 vs. < 7 mmHg or of transpulmonary gradient (TPG) >12 vs. ≤12 mmHg. After vasodilator administration, Cpc-PH patients showed a greater per cent improvement in pulmonary vascular resistance (PVR), DPG and TPG as compared with Ipc-PH patients (all Pint < 0.001); only pulmonary compliance (PCa) improved less in Cpc-PH than in Ipc-PH patients (Pint = 0.007). However, despite vasodilatation, Cpc-PH patients remained in an unfavourable portion of the inverse hyperbolic relationship between PVR and PCa. The number of patients in whom PVR was reduced below 2.5 wood units was similar in Cpc-PH, DPG ≥7 mmHg and TPG >12 mmHg groups (28.3, 26.7 and 18.9%, respectively). CONCLUSION: Although substantial improvements in PVR, DPG and TPG were observed in Cpc-PH patients after acute vasodilator administration, this response was associated with persistent abnormalities in the PVR vs. PCa relationship. The link between baseline right heart haemodynamics and pulmonary vascular disease remains elusive.

An official European Respiratory Society statement: pulmonary haemodynamics during exercise.

There is growing recognition of the clinical importance of pulmonary haemodynamics during exercise, but several questions remain to be elucidated. The goal of this statement is to assess the scientific evidence in this field in order to provide a basis for future recommendations.Right heart catheterisation is the gold standard method to assess pulmonary haemodynamics at rest and during exercise. Exercise echocardiography and cardiopulmonary exercise testing represent non-invasive tools with evolving clinical applications. The term "exercise pulmonary hypertension" may be the most adequate to describe an abnormal pulmonary haemodynamic response characterised by an excessive pulmonary arterial pressure (PAP) increase in relation to flow during exercise. Exercise pulmonary hypertension may be defined as the presence of resting mean PAP <25 mmHg and mean PAP >30 mmHg during exercise with total pulmonary resistance >3 Wood units. Exercise pulmonary hypertension represents the haemodynamic appearance of early pulmonary vascular disease, left heart disease, lung disease or a combination of these conditions. Exercise pulmonary hypertension is associated with the presence of a modest elevation of resting mean PAP and requires clinical follow-up, particularly if risk factors for pulmonary hypertension are present. There is a lack of robust clinical evidence on targeted medical therapy for exercise pulmonary hypertension.

Heart failure in patients with human immunodeficiency virus: a review of the literature.

Coronary artery disease represents the leading cause of death for HIV patients treated with highly active antiretroviral treatment. Besides this, an extensive amount of data related to the risk of overt heart failure and consequently of atrial fibrillation and sudden cardiac death (SCD) in this population has been reported. It seems that persistent deregulation of immunity in HIV-infected patients is a common pathway related to both of these adverse clinical outcomes. Despite the fact that atrial fibrillation and heart failure are relatively common in HIV, few data are reported about screening, diagnosis, and potential treatment of these conditions.

Right heart and pulmonary vessels structure and function.

The right ventricle (RV) can be described in terms of 3 components: the inlet, the apex, and the infundibulum. In the normal adult, the RV shows an arrangement suited for pumping blood against low resistance, with a mass about one sixth that of left ventricle (LV) mass, and a larger volume than the LV. The RV is able to manage a progressive increase in the afterload by increasing contractility and remodeling. The gold standard measurement of contractility is maximal elastance (Emax), or the ratio between end-systolic pressure (ESP) and end-systolic volume (ESV), and the best measurement of afterload is arterial elastance (Ea), or the ratio between ESP and stroke volume (SV). The ratio Emax/Ea defines RV-arterial coupling. The optimal energy transfer from the RV to the pulmonary circulation is measured at Emax/Ea ratios of 1.5-2. In the presence of pulmonary hypertension, the SV/ESV ratio may be an acceptable surrogate of Emax/Ea. The right atrium (RA) has 3 anatomical components: the appendage, the venous part, and the vestibule. It is a dynamic structure having different functions: reservoir, conduit, and booster pump function. In case of increased afterload, the RA is enlarged, denoting high RA pressure, as a consequence of elevated RV diastolic pressure. RA area is a strong predictor of adverse clinical outcome in pulmonary arterial hypertension. In patients with severe pulmonary hypertension, in several congenital heart diseases, and in Eisenmenger syndrome, symptoms and prognosis are greatly dependent on RV function and its ability to adapt to a chronic increase in afterload.

Myocardial and microvascular inflammation/infection in patients with HIV-associated pulmonary artery hypertension.

BACKGROUND: Right ventricle compromise affects survival of patients with HIV-associated pulmonary artery hypertension (PAH). DESIGN: Myocardial histology with viral assessment may clarify the mechanism of right ventricular deterioration and provide clues on PAH origin. METHODS: Fifteen patients with HIV infection, PAH and right ventricular dysfunction underwent cardiac magnetic resonance, catheterization, coronary with ventricular angiography and biventricular endomyocardial biopsy. Endothelial expression of HLA-DR, ICAM-1, E-selectin and VCAM-1 was semi-quantitatively evaluated. PCR for HIV, hepatitis C virus, human herpes virus-6, human herpes virus-8, Epstein-Barr virus, adenovirus, cytomegalovirus, enterovirus, influenza A/B and parvovirus B19 was performed. In PCR-positive hearts, viral protein adenovirus-1 and TORDJI-22 were assessed by immunohistology. RESULTS: New York Heart Association class was 2.4 ±â€Š0.5, mean pulmonary artery pressure 49.93 ±â€Š10.15 mmHg and wedge pressure 9.5 ±â€Š2.19 mmHg. Coronaries were normal with slow flow. Left ventricular and/or right ventricular micro-aneurysms were seen in eight patients. Cardiac magnetic resonance documented increased right ventricular end-diastolic volume with reduced ejection fraction, normal left ventricular end-diastolic volume and left ventricular ejection fraction. Subepicardial/mesocardial oedema and delayed enhancement in the inter-ventricular junction and/or left ventricular inferolateral wall was detected in eight patients. Histology showed active lymphocytic myocarditis in 12 patients, with microvasculitis in three. Endothelial adhesion molecules were over-expressed in all patients. PCR was positive in four patients for hepatitis C virus and in two for adenovirus, and viruses localized both in cardiomyocytes and endothelial cells. CONCLUSIONS: Inflammation/infection of myocardium and intramural vessels is detectable in patients with HIV-associated PAH. It may adversely affect right ventricular function and have a role in the compromised pulmonary circulation.

Current perspectives modern hemodynamic evaluation of the pulmonary circulation. Application to pulmonary arterial hypertension and embolic pulmonary hypertension.

The hemodynamic evaluation of the pulmonary circulation normally includes the measurements of mean pulmonary artery pressure and a calculation of pulmonary vascular resistance (PVR). The definition of PVR can be improved by the measurements of pulmonary vascular pressures at several levels of flow to derive a pressure-flow line, and the site of PVR can be identified by the analysis of pulmonary artery pressure decay curves after balloon occlusion. An analysis of the morphology of pulmonary artery pressure and flow waves informs about right ventricular (RV) hydraulic load. As pulmonary hypertension is clinically a right heart failure syndrome, it is important to measure the coupling of RV to pulmonary arterial function. This can be done using a single beat method with sampling and synchronization of instantaneous pulmonary artery flow and RV pressure to calculate a ratio of end-systolic to arterial elastances. The optimal value of this ratio is depressed in minimally symptomatic pulmonary arterial hypertension patients, indicating pending right heart failure.

[Pulmonary hypertension and HIV: implementation of a Regional Registry]. / Ipertensione polmonare e HIV. Istituzione di un Registro nella Regione Lazio.

In the era of new, potent antiretroviral therapy, much more attention is being given to non-infectious complications of HIV diseases, such as cardiomyopathy, pericardial effusion and pulmonary hypertension (PH). PH diagnosis is based on a mean pulmonary artery pressure of more than 25 mmHg at rest, or more than 30 mmHg with exercise. The incidence of PH is about 0.1% per year among HIV-positive patients, while in the general population it is 1 to 2 cases per million people. The histopathology of HIV-associated PH (HAPH) is similar to that of idiopathic PH, although its pathogenesis is still unclear. In patients with HAPH secondary causes of PH must be ruled out, such as intravenous drug abuse, valvulopathy, congenital heart disease and previous tricuspid endocarditis. The treatment of HAPH is not substantially different from that of idiopathic PH and is essentially based on the use of vasodilators. The Regional Authority of Lazio (Italy) has instituted a Registry for PH in HIV-positive patients; its aims are to evaluate the real incidence and prevalence of primitive and secondary PH among patients with HIV infection, and optimise the management of patients with suspected PH through the definition of a diagnostic algorithm.