Absence Of Pulmonary Arterial Hypertension Research Articles

Diastolic function of the left and right ventricles of the heart in outpatients with arterial hypertension.

The aim of the study is to investigate the impairment of diastolic function of the left ventricle (LV) and the right ventricle (RV) in arterial hypertension outpatients. Arterial hypertension patients (n=299) and practically healthy people (n=62) were examined on an outpatient basis. Echocardiographically, diastolic dysfunctions of both ventricles were evaluated. All the arterial hypertension patients had a pattern of diastolic dysfunction (DD) of the RV of different grades (grade I RVDD and grade II RVDD), regardless of the presence or absence of pulmonary arterial hypertension. Patterns of grade I LVDD and grade I RVDD were detected in 84 patients. Patterns of grade I LVDD and grade II RVDD were detected in 77 patients. Patterns of grade II LVDD and grade II RVDD were detected in 41 patients. A pattern of grade II RVDD with normal left ventricular diastolic function was detected in 97 patients with a short duration of disease (3.92±0.48years) vs the other groups with more than 15years of hypertension. One hundred and seventy-five arterial hypertension patients had grade I or II LVDD only in 18.3% of cases according to the recommendations of the American and European societies of echocardiographers (2016). The patients with a short period of hypertensive disease have only the pseudonormal pattern of RVDD, which can be an early diagnostic marker of heart failure. Echocardiographic diagnosis of diastolic function made according to various criteria can both increase the number of chronic heart failure patients and significantly decrease it.

P5262Subclinical myocardial abnormalities in systemic sclerosis-associated versus non-connective tissue disease pulmonary hypertension by CMR multiparametric mapping

Abstract Introduction Scleroderma (SSc)-associated pulmonary arterial hypertension (PAH) has the worst prognosis of all PAH subtypes despite having relatively more favourable haemodynamic and cardiac functional profiles. Myocardial abnormalities in SSc have been demonstrated by cardiovascular magnetic resonance (CMR) multiparametric tissue mapping. However, myocardial tissue characterisation studies across distinct PAH subtypes including SSc are limited. Purpose We compared indices of tissue characterisation by CMR multiparametric mapping between patients with SSc with and without PAH, non-connective tissue disease pulmonary hypertension (non-CTD PH) and healthy volunteers. Methods One-hundred and thirty-six patients underwent a CMR study over a 30-month period: 104 patients with systemic sclerosis, of whom 39 had SSc-PAH and 65 had no PH; 32 patients with idiopathic PAH, chronic thromboembolic PH or portopulmonary PH (non-CTD PH group). Patients underwent comprehensive CMR tissue characterisation including quantification of native myocardial T1 (MOLLI), myocardial T2 and ECV from automatically generated tissue maps along with conventional late gadolinium enhancement (LGE) imaging. Twenty age-matched controls underwent the same CMR study protocol. Patients were assessed for PH by right heart catheterisation. Results Native myocardial T1 and myocardial T2 and myocardial ECV are significantly elevated in SSc-PAH versus non-CTD PH (all p<0.05, Figure 1) despite no differences in LV systolic function between these patient cohorts. Patients with SSc have similar degrees of elevated T1, T2 and ECV irrespective of the presence or absence of PAH, suggesting a diffuse myocardial process due to SSc itself. Both SSc sub-groups have significantly higher T1, T2 and ECV compared with controls (all p<0.05). All patients with SSc were subdivided by the presence or absence of ventricular insertion point LGE. Even in the absence of LGE, T1, T2 and ECV were significantly higher in SSc patients versus controls (all p<0.001). However, the presence of focal insertional LGE in SSc was not associated with different burdens of interstitial disease, as defined by median ECV. This highlights the unique role of multiparametric tissue maps in assessing diffuse myocardial involvement beyond the identification of focal LGE. Conclusion Subclinical abnormalities of the myocardium can be detected by CMR multiparametric tissue mapping in patients with SSc. The higher native myocardial T1 and T2 along with the elevated ECV in SSc-PAH are likely to be accounted for by SSc involvement itself. Abnormalities of the myocardial architecture could be a potential contributory reason for the poorer outcomes in SSc-PAH versus non-CTD PH despite the more favourable haemodynamics and right heart function observed in the former patient sub-group. Further work should be directed at determining the prognostic capacity of these metrics in SSc-PAH. Acknowledgement/Funding British Heart Foundation, Action Pharmaceuticals Ltd

PI3Kα Pathway Inhibition With Doxorubicin Treatment Results in Distinct Biventricular Atrophy and Remodeling With Right Ventricular Dysfunction.

BackgroundCancer therapies inhibiting PI3Kα (phosphoinositide 3‐kinase‐α)–dependent growth factor signaling, including trastuzumab inhibition of HER2 (Human Epidermal Growth Factor Receptor 2), can cause adverse effects on the heart. Direct inhibition of PI3Kα is now in clinical trials, but the effects of PI3Kα pathway inhibition on heart atrophy, remodeling, and function in the context of cancer therapy are not well understood.Method and ResultsPharmacological PI3Kα inhibition and heart‐specific genetic deletion of p110α, the catalytic subunit of PI3Kα, was characterized in conjunction with anthracycline (doxorubicin) treatment in female murine models. Biventricular changes in heart morphological characteristics and function were analyzed, with molecular characterization of signaling pathways. Both PI3Kα inhibition and anthracycline therapy promoted heart atrophy and a combined effect of distinct right ventricular dilation, dysfunction, and cardiomyocyte remodeling in the absence of pulmonary arterial hypertension. Congruent findings of right ventricular dilation and dysfunction were seen with pharmacological and genetic suppression of PI3Kα signaling when combined with doxorubicin treatment. Increased p38 mitogen‐activated protein kinase activation was mechanistically linked to heart atrophy and correlated with right ventricular dysfunction in explanted failing human hearts.Conclusions The PI3Kα pathway promotes heart atrophy in mice. The right ventricle is specifically at risk for dilation and dysfunction in the setting of PI3K inhibition in conjunction with chemotherapy. Inhibition of p38 mitogen‐activated protein kinase is a proposed therapeutic target to minimize this mode of cardiotoxicity.

Prospective Echocardiographic Evaluation of the Right Ventricle and Pulmonary Arterial Pressure in Hyperthyroid Patients

Pulmonary arterial hypertension (PAH) occurs in 35% to 65% of hyperthyroid patients. Despite this high frequency, only a few authors have examined the effects of hyperthyroidism treatment on PAH and the right ventricle. We evaluated the effects of hyperthyroidism and its reversal on cardiovascular structure and function using Doppler echocardiography. We prospectively evaluated 32 patients (42.5±11.9years old) with thyrotoxicosis. Exclusion criteria included previous cardiovascular disease. An echocardiogram was performed at the time of hyperthyroidism diagnosis and after normalisation of free thyroxine (T4) levels. Patients were divided into two groups according to the presence or absence of PAH at the diagnosis, or at two moments, before and after T4 normalisation. Graves' disease was the most frequent aetiology (75%) of hyperthyroidism. Pulmonary arterial hypertension was observed in 43.8% of patients. Free T4 concentration was higher in PAH than non-PAH patients. Free T4 normalised after 5 (2.0-10.5; median and percentiles) months of treatment. Cardiac chamber sizes and cardiac output were higher in PAH. Right ventricular (RV) systolic function was impaired in PAH. Cardiac output and free T4 (r=0.42; p<0.05) correlated with pulmonary artery systolic pressure (PASP). Cardiac chamber size, cardiac output, left ventricular ejection fraction, and PASP (34.0±8.6 to 21.7±4.5mmHg) reduced after treatment. Right ventricular myocardial performance index and fractional area change improved after T4 normalisation. Pulmonary arterial hypertension is highly prevalent in hyperthyroid patients and is combined with increased cardiac chambers size and cardiac output, and impaired RV function. Cardiovascular changes are reversible after T4 normalisation in patients without cardiovascular disease.

Decreased global myocardial perfusion at adenosine stress as a potential new biomarker for microvascular disease in systemic sclerosis: a magnetic resonance study

BackgroundPatients with systemic sclerosis (SSc) have high cardiovascular mortality even though there is no or little increase in prevalence of epicardial coronary stenosis. First-pass perfusion on cardiovascular magnetic resonance (CMR) have detected perfusion defects indicative of microvascular disease, but the quantitative extent of hypoperfusion is not known. Therefore, we aimed to determine if patients with SSc have lower global myocardial perfusion (MP) at rest or during adenosine stress, compared to healthy controls, quantified with CMR.MethodsNineteen SSc patients (17 females, 61 ± 10 years) and 22 controls (10 females, 62 ± 11 years) underwent CMR. Twelve patients had limited cutaneous SSc and 7 patients had diffuse cutaneous SSc. One patient had pulmonary arterial hypertension (PAH). MP was quantified using coronary sinus flow (CSF) measurements at rest and during adenosine stress, divided by left ventricular mass (LVM).ResultsThere was no difference in MP at rest between patients and controls (1.1 ± 0.5 vs. 1.1 ± 0.3 ml/min/g, P = 0.85) whereas SSc patients showed statistically significantly lower MP during adenosine stress (3.1 ± 0.9 vs. 4.2 ± 1.3 ml/min/g, P = 0.008). Three out of the 19 SSc patients showed fibrosis in the right ventricle insertion points despite absence of PAH. None had signs of myocardial infarction.ConclusionsPatients with SSc have decreased MP during adenosine stress compared to healthy controls. Thus hypoperfusion at stress may be a sensitive marker of cardiac disease in SSc patients possibly signifying microvascular myocardial disease.

Hypoxia and Cyanosis due to Unusual Right-to-Left Shunt in a Patient with an Atrial Septal Defect

Hypoxia due to an Atrial Septal Defect (ASD), without Eisenmenger physiology, is reported rarely and may be underestimated due to difficulty in its diagnosis. We report the case of a 67-year-old woman with chronic cyanosis and hypoxia, in whom a large ASD was diagnosed by cardiac catheterization after an extensive workup to clarify the aetiology of the hypoxia. The right-to-left shunt at the ASD occurred probably due to a well-developed Eustachian valve, partly directing the right atrial flow into the left atrium, in the absence of pulmonary arterial hypertension.

AB0622 Clinical Characteristics of Systemic Sclerosis Patients with Interstitial Lung Disease Who do not Require Immunosuppressive Treatment

BackgroundSystemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis of the skin and internal organs. Although interstitial lung disease (ILD) is a major cause of death in this...

Characteristic haemodynamic changes of cirrhosis may influence the diagnosis of portopulmonary hypertension.

Diagnosis of portopulmonary hypertension (POPH) is based on the presence of portal hypertension and the same haemodynamic criteria as pulmonary arterial hypertension (PAH). However, the typical hyperdynamic circulation of cirrhosis may have some impact on the diagnosis of POPH. The aim was to compare the haemodynamic pattern of the pulmonary circulation between cirrhotics and non-cirrhotics, including patients with PAH. 600 patients with cirrhosis [male 77.5%, age 54 (47-60) years, Child A: 14.7%, B: 54.3%, C: 31%] received right heart catheterization. For comparison, 118 non-cirrhotic patients [male 60%, age 64 (53-65) years] with right heart catheterization and PCWP <20 mmHg were included. Both were divided into 3 groups, A: absence of pulmonary arterial hypertension; B or intermediate group: MPAP >25 mmHg, PVR 120-240 dyn s cm(-5) and PCWP <15 mmHg (or PCWP >15 mmHg with TPG ≥12 mmHg); C: pulmonary arterial hypertension (same criteria as B except PVR ≥240 dyn s cm(-5) ). Distribution of patients with cirrhosis was A 583, B 7 and C 10. Prevalence of POPH was 1.7%. Cirrhotics had lower SVR and greater CO than non-cirrhotics (P < 0.05). Interestingly, patients with cirrhosis without PAH (groups A and B) had lower PVR (P < 0.05) when comparing with non-cirrhotics, while no differences in PVR were observed in group C. However, mean TPG was greater in group C of cirrhotics [36.6 mmHg (12.2) vs. 27.1 mmHg (10.1); P = 0.034]. Patients with cirrhosis have lower PVR. TPG is greater in POPH than PAH. Characteristic haemodynamic changes of cirrhosis may influence the diagnosis of POPH.

Platelet Distribution Width and Mean Platelet Volume in Children With Pulmonary Arterial Hypertension Secondary to Congenital Heart Disease With Left-to-Right Shunt: New Indices of Severity?

The majority of patients with congenital heart disease (CHD), particularly those with relevant systemic-to-pulmonary shunts, if left untreated, will experience the development of pulmonary arterial hypertension (PAH). Previous studies have shown that platelet activation occurs in patients with PAH. In response, this study aimed to investigate the platelet indices, including platelet distribution width (PDW) and mean platelet volume (MPV), in patients with PAH. The study was conducted in the pediatrics cardiology unit of Selcuk University Medical Faculty between July 2010 and January 2012. The patients' clinical and laboratory data were obtained retrospectively from hospital recordings. The study enrolled 57 children with CHD (all with left-to-right shunting). The patients who had undergone diagnostic cardiac catheterization were analyzed according to the presence or absence of PAH. Group 1 had CHD with PAH, and group 2 had CHD without PAH. Compared with the group 2 patients, a significant decrease in PDW (p < 0.0001) was noted in the group 1 patients (with PAH). Likewise, a significant difference was found in the MPV of group 1 (p < 0.0001). Statistically, groups 1 and 2 did not differ in terms of platelet count (p = 0.3). Patients who had pulmonary hypertension secondary to CHD with left-to-right shunting exhibited a lower PDW and MPV.

Elevated Homocysteine and Asymmetric Dimethyl Arginine Levels in Pulmonary Hypertension Associated With Congenital Heart Disease

Pulmonary arterial hypertension (PAH) is a major cause of morbidity and mortality among patients with congenital heart disease (CHD). This study was designed to determine biomarker levels in patients with PAH associated with CHD (PAH-CHD) and CHD patients without PAH and to investigate the relationship of these potential biomarkers with hemodynamic findings. In this prospective single-center study, patients with CHD were analyzed according to the presence or absence of PAH and compared with healthy control subjects. Cardiac catheterization and echocardiographs were performed. Plasma homocysteine, asymmetric dimethyl arginine (ADMA), and nitric oxide (NO) levels were determined by enzyme-linked immunosorbent assay. Homocysteine and ADMA levels were higher in the PAH-CHD group (n = 30) than among CHD patients with left-to-right shunting but no PAH (n = 20; P < 0.001) and healthy control subjects (n = 20; P < 0.001). There was no difference in NO levels. Cyanotic PAH-CHD patients had significantly higher homocysteine than acyanotic patients in the same group. No correlation was shown between echocardiographic/hemodynamic parameters and homocysteine, ADMA, and NO levels. Homocysteine and ADMA levels are increased in patients with PAH-CHD. These parameters have the potential to be used as biomarkers in the diagnosis and follow-up evaluation of patients with PAH-CHD. However, large, multicentered prospective studies are required to facilitate routine use of these biologic markers in the clinical setting.

Clinical Manifestations and Long-Term Follow-Up in Pediatric Patients Living at Altitude With Isolated Pulmonary Artery of Ductal Origin

This study's aim was to define the clinical manifestations and long-term outcome of pediatric patients living at altitude with isolated pulmonary artery (PA) of ductal origin (IPADO). This was a retrospective cohort study of 17 consecutive cases of IPADO at a single center. All patients lived at modest altitude (median 2050 m [range 1700 m to 3050 m]). Fifteen children (88%) were symptomatic at presentation. High-altitude pulmonary edema was present in 2 patients (12%) at diagnosis, and only 1 patient had episodes of hemoptysis during follow-up. Fourteen patients (82%) demonstrated evidence of pulmonary arterial hypertension (PAH). Among 14 patients with PAH, 11 patients had surgical interventions. PAH resolved in 5 of 11 patients (45%) undergoing surgical rehabilitation. One patient died during follow-up, and 7 patients are receiving oral vasodilator therapies due to residual PAH; 14 patients remained asymptomatic. Our study showed that early intervention in patients with IPADO at modest altitude can potentially rehabilitate the isolated PA and reverse PAH. Whether surgery is indicated for patients with this disorder in the absence of PAH is unknown.

Prevalence and Predictors of Pulmonary Arterial Hypertension in Hemoglobin E/ β-Thalassemia Patients.

Abstract 2015Poster Board I-1037 Introduction:Pulmonary arterial hypertension (PAH) associated with thalassemia (Thal) hemoglobinopathy is now an accepted clinical entity. Most of the reports are in sickle cell disease and splenectomized β-Thal patients. Once manifested, it connotes poor prognosis. We herein present its prevalence and predictors in hemoglobin E/β-Thal (E/β-Thal) patients. Patients and Methods:One hundred and ten clinically stable E/β-Thal outpatients, on no medication aside from folic acid and who received no blood transfusion in the preceding 4 weeks were studied. All gave written informed consent, and study protocol was approved by the institution ethics committee on studies in humans (#0774/2548). Echocardiogram was used to estimate systolic PA pressure (SPAP). PAH was defined as an estimated SPAP ≥36 mmHg. Clinical features and laboratory data were stratified according to the presence or absence of PAH, and statistical analysis was done by STATA version 10 (Stata Corp, Texas), considering a P value <0.05 as statistically significant. Predictors of PAH were considered in univariate analysis. Results:There were 110 patients, 56 of whom were female and 61 were asplenic. PAH was present in 41 patients (37.3%), all of whom had normal left ventricular ejection fraction. There was no gender difference between the 2 groups (p=0.055). Selected statistically significant results are shown in the table.ResultsWith PAH (41 Patients)Without PAH (69 Patients)P valueAge at 1st transfusion (median)6 years11.25 years0.03Total transfusions (median)37 units PRBC15 units PRBC0.04Splenectomy78%42%<0.001Cardiomegaly52.5%32.3%0.042Extramedullary hematopoiesis56.4%30.6%0.01RBC count3.24 +/- 0.93 × 106/μL3.65 +/- 0.9 × 106/μL0.034Corrected reticulocyte count (median)4%1.7%0.02Nucleated RBC (median)530/100 WBCs15.5/100 WBCs<0.001Corrected WBC count9.34 +/- 4 × 103/μL7.8 +/- 3.5 × 103/μL0.036Platelet count627.7 +/- 313.2 × 103/μL436 +/- 267.4 × 103/μL0.001Globulin4.4 +/- 1.2 g/dL3.8 +/-0.8 g/dL0.002LDH323.3 +/- 117.2 u/L243.3 +/- 85.6 u/L<0.001Free hemoglobin (median)4.42 mg/dL2.7 mg/dL0.001C-reactive protein (high sens) (median)2.9 mg/L1.3 mg/L0.008Soluble VCAM-11,896.1 +/- 553.5 ng/mL1,463 +/- 622 ng/mL0.004NT pro BNP11.7 pmol/L6.2 pmol/L0.026 Conclusions:Prevalence of PAH in E/β-Thal patients is 37.3% without gender preponderance. Predictors are asplenia, more severe hemolysis, higher number of circulating (activated) platelets and nucleated RBCs, increased chronic low grade inflammation and increased cellular adhesion between blood and endothelial cells. These changes could facilitate development of thrombotic pulmonary arteriopathy, the underlying basis of PAH. Serum NT pro BNP assay can be utilized as a predictor or a screener of PAH in these patients. Disclosures:No relevant conflicts of interest to declare.

Lack of circulating autoantibodies to bone morphogenetic protein receptor-II or activin receptor-like kinase 1 in mixed connective tissue disease patients with pulmonary arterial hypertension

To examine whether autoantibodies against bone morphogenetic protein receptor-II (BMPR-II) or activin receptor-like kinase 1 (ALK-1) are associated with pulmonary arterial hypertension (PAH) in patients with mixed connective tissue disease (MCTD). We studied sera from 37 MCTD patients with or without PAH, six patients with idiopathic PAH, and 30 healthy controls. Circulating anti-BMPR-II and anti-ALK-1 antibodies were detected using immunoprecipitation of recombinant antigens generated by in vitro transcription/translation and indirect immunofluorescence of cultured cells that were induced to express these antigens by gene transfer. Anti-BMPR-II antibodies were further examined by immunoprecipitation and immunoblotting using a recombinant fragment of the extracellular domain of BMPR-II. Serum anti-BMPR-II and anti-ALK-1 autoantibodies were not detected in MCTD patients irrespective of the presence or absence of PAH, or in patients with idiopathic PAH. Our finding does not support the hypothesis that autoantibody-mediated dysregulation of signals through BMPR-II or ALK-1 contributes to the development of PAH in patients with connective tissue diseases.

Noninvasive radiographic assessment of cardiovascular function in acute and chronic respiratory failure

Noninvasive radiographic techniques have provided a means of studying the natural history and pathogenesis of cardiovascular performance in acute and chronic respiratory failure. Chest radiography, radionuclide angiocardiography and thallium-201 imaging, and M mode and crosssectional echocardiography have been employed. Each of these techniques has specific uses, attributes and limitations. For example, measurement of descending pulmonary arterial diameters on the plain chest radiograph allows determination of the presence or absence of pulmonary arterial hypertension. Right and left ventricular performance can be evaluated at rest and during exercise using radionuclide angiocardiography. The biventricular response to exercise and to therapeutic interventions also can be assessed with this approach. Evaluation of the pulmonary valve echogram and echocardiographic right ventricular dimensions have been shown to reflect right ventricular hemodynamics and size. Each of these noninvasive techniques has been applied to the study of patients with respiratory failure and has provided important physiologic data.