Long-Term Outcomes in Adult Patients With Pulmonary Hypertension After Percutaneous Closure of Atrial Septal Defects

Background: Pulmonary hypertension (PH), recently redefined as mean pulmonary arterial pressure >20 mm Hg (PH 20 ), may be observed in patients with atrial septal defects (ASD). We aimed to determine the effect of preprocedural PH 20 status on outcomes among patients undergoing ASD closure. Methods: Study population was selected from a retrospective registry of adult patients who underwent percutaneous ASD closure from 1998 to 2016 from a single center and had right heart catheterizations during the procedure. The clinical registry was linked to administrative databases to capture short- and long-term outcomes. Results: We included a total of 632 ASD closure patients of whom 359 (56.8%) had PH 20 . The mean follow-up length was 7.6±4.6 years. Patients with PH 20 were older (mean age 56.5 versus 43.1 years, P <0.001) and a higher prevalence of comorbidities including hypertension (54.3% versus 21.6%, P <0.001) and diabetes (18.1% versus 5.9%, P <0.001) than those without PH. In a Cox proportional hazards model after covariate adjustment, patients with PH had a significantly higher risk of developing major adverse cardiac and cerebrovascular events (heart failure, stroke, myocardial infarction, or cardiovascular mortality), with hazards ratio 2.45 (95% CI, 1.4–4.4). When applying the prior, mean pulmonary arterial pressure ≥25 mm Hg (PH 25 ) cutoff, a significantly higher hazard of developing major adverse cardiac and cerebrovascular events was observed in PH versus non-PH patients. Conclusions: ASD patients with PH undergoing closure suffer from more comorbidities and worse long-term major adverse cardiac and cerebrovascular events outcomes, compared with patients without PH. The use of the new PH 20 definition potentially dilutes the effect of this serious condition on outcomes in this population.

Pulmonary Hypertension in Thalassemia Patients

Pulmonary hypertension (PH) is defined in children as a mean pulmonary arterial pressure (PAP) greater than 25 mmHg at rest or 30 mmHg during physical activity, with increased pulmonary artery capillary wedge pressure and an increased pulmonary vascular resistance greater than 3 Wood units × M2. it is the main cause of morbidity and mortality in the group of thalassemia, if no treatment leads to right ventricular heart failure and death. The development of pulmonary arterial hypertension (PAH) is assumed to be the result of many multifactorial pathogenic mechanisms including chronic hemolysis, iron overload, hypercoagulability, and erythrocyte dysfunction as a result of splenectomy, inflammation and nitric oxide (NO) depletion. PAH symptoms are non-specific, their signs consist of right ventricular lift, an accentuated pulmonary component of the second heart sound, a (gallop rhythm) right ventricular third heart sound, and parasternal heave meaning a hypertrophied right ventricle. The diagnosis of PAH requires a clinical suspicion based on symptoms and physical examination. Echocardiography is frequently used to screen for PAH, monitor progression over time and allow identification of patients for whom diagnostic right heart catheterization (RHC) is warranted and its treatment includes hemoglobinopathy specific treatment and PAH specific therapy.

Therapy for Pulmonary Arterial Hypertension: Glance on Nitric Oxide Pathway

Pulmonary arterial hypertension (PAH) is a severe disease with a resultant increase of the mean pulmonary arterial pressure, right ventricular hypertrophy and eventual death. Research in recent years has produced various therapeutic options for its clinical management but the high mortality even under treatment remains a big challenge attributed to the complex pathophysiology. Studies from clinical and non-clinical experiments have revealed that the nitric oxide (NO) pathway is one of the key pathways underlying the pathophysiology of PAH. Many of the essential drugs used in the management of PAH act on this pathway highlighting its significant role in PAH. Meanwhile, several novel compounds targeting on NO pathway exhibits great potential to become future therapy medications. Furthermore, the NO pathway is found to interact with other crucial pathways. Understanding such interactions could be helpful in the discovery of new drug that provide better clinical outcomes.

CTRP9 Mitigates the Progression of Arteriovenous Shunt-Induced Pulmonary Artery Hypertension in Rats

The present study is aimed at investigating the molecular mechanism of C1q/TNF-related protein 9 (CTRP9) and providing a new perspective in arteriovenous shunt-induced pulmonary arterial hypertension (PAH). PAH was established by an arteriovenous shunt placement performed in rats. Adenovirus(Ad)-CTRP9 and Ad-green fluorescent protein viral particles were injected into the rats through the tail vein. Following 12 weeks, the mean pulmonary arterial pressure (mPAP) and right ventricular systolic pressure (RVSP) were measured and morphological analysis was conducted to confirm the establishment of the PAH model. The systemic elevation of CTRP9 maintained pulmonary vascular homeostasis and protected the rats from dysfunctional and abnormal remodeling. CTRP9 attenuated the pulmonary vascular remodeling in the shunt group by decreasing the mPAP and RVSP, which was associated with suppressed inflammation, apoptosis, and extracellular matrix injury. In addition, CTRP9 dramatically increased the phosphorylation of AKT and p38-MAPK in the lung tissues of shunt-operated animals. These findings suggest a previously unrecognized effect of CTRP9 in pulmonary vascular homeostasis during PAH pathogenesis.

Right ventricular reverse remodeling assessed by echocardiography as a new goal-oriented treatment strategy in PAH patients

Background While in heart failure with reduced ejection fraction, left ventricular reverse remodeling assessed by transthoracic echocardiography (TTE) is associated with better prognosis, right ventricular reverse remodeling (RVRR) was less investigated in pulmonary arterial hypertension (PAH) Purpose We aimed to investigate whether RVVR assessed by echocardiography could help to stratify PAH patient's prognosis. Methods Between 2002 and 2019, all consecutive PAH patients were included, treated and followed in a single PAH center in accordance with the current ESC/ERS guidelines. In addition to regular risk stratification parameters, we measured several echocardiographic RV systolic function and size parameters, including tricuspid annular plane systolic excursion (TAPSE, mm) or RV-end diastolic area (cm2) from apical-4 chamber view both at baseline, 1-year of follow-up as well as their change. Primary composite outcome was three-year transplant-free survival and death from all cause from the 1-year evaluation. Conditional inference trees were used to determine which TTE parameters and cutoffs values were associated with primary outcome from hierarchy of multiple covariates in multivariable Cox regression analysis. Kaplan-Meier curves were then drawn and compared with log-rank test. Results 126 incident PAH patients were included (63% female, mean age 59±18 yo), mainly due to connectivite-tissue disease and idiopathic PAH (26% and 22% respectively). At baseline, mean pulmonary arterial pressure was 42 (33, 52) mmHg. At 1-y follow-up under pulmonary vasodilation therapy, NYHA (p&lt;0.01), NTproBNP (p&lt;0.01), mean pulmonary arterial pressure (p&lt;0.01) and cardiac index (p&lt;0.01) were significantly improved compared to baseline. Conditional inference trees showed that 1-year TAPSE gain &gt;1 mm and 1-year RV end-diastolic area decreased &gt;2 cm2 were associated with 3-year transplant-free survival in multivariable Cox regression analysis (HR=0.23, 95% CI [0.08–0.61] p=0,0035, HR=0.34, 95% CI [0.12–0.94], p=0.038). Simple score from 0 (absence of RVRR), 1 (partial RVRR) and 2 (complete RVRR), describing the number of TTE parameters reach at 1-year was then investigated. Patients with complete RVRR depicted better transplant-free survival than partial or absence of RVRR, log-rank p&lt;0.001 (figure). Conclusion Complete reverse remodeling from right ventricular size and function could represent a new goal-oriented treatment strategy in PAH patients. FUNDunding Acknowledgement Type of funding sources: None. RVRR survival curves

Echocardiographic parameters related to pulmonary arterial hypertension in patients with chronic myeloid leukemia under dasatinib treatment

Introduction: The use of dasatinib in patients with CML has improved life expectancy and follow-up with transthoracic echocardiography (ECOTT) for early detection of PAH allows modifications to the treatment. Objective: To determine the echocardiographic parameters and echocardiographic probability for PAH in patients with CML treated with dasatinib. Methods: Correlation, cross-sectional, retrospective, single-center study; patients with CML treated with dasatinib were included. Spearman and Pearson correlation was used. Results: 16 patients were analyzed, mean age 53.5 years; 62.5% men, 37.5% women. The dasatinib dose was 50 mg / day in 18.7%, and 100 mg / day in 81.2%, mean pulmonary arterial pressure (mPAP) 26.3 mmHg, mean maximum tricuspid regurgitation velocity (VmxRT) 2.9 m / s, mean pulmonary artery systolic pressure (PSAP) 41 mmHg. 56.2% had right ventricular diastolic dysfunction (RVDD). 43% were categorized as low probability for PAH, 18.7% intermediate, and 37.5% as high. Relationship between PAPm and VmxRT with p = 0.012. Relationship between mPAP and RV diastolic function, with p = 0.002. Relationship between probability for PAH and mPAP, with p = 0.008. Conclusion: The echocardiographic parameters PAPm, VmxRT, PSAP, DDVD and echocardiographic probability for PAH are useful and necessary for the diagnosis of PAH. The determination of all these parameters should be carried out early and as a follow-up, since a considerable positive relationship was found for each one with the presence of PAH, which is not dependent on the treatment time or the dose of dasatinib.

Hyperuricemia in patients with pulmonary hypertension: A study in a tertiary care center

Pulmonary Hypertension is one of a life-threatening disease with high rate of patient mortality. Decreased cardiac output and tissue hypoxia is measured using Uric acid as a marker for assessment of pulmonary hypertension. 75 patients who were diagnosed with a mean pulmonary arterial pressure of &#62;22mmHg were categorized as group A and 75 healthy patients were considered to be Group B. Blood was collected for Uric acid, creatinine and total Bilirubin estimation. Pulmonary arterial systolic pressure as well as the ventricular function of the patients was evaluated using Colour Doppler ECG and a value of ≥50 mmHg, or a mean pulmonary arterial pressure (at rest) of ≥25 mmHg was taken and the right arterial pressure was calculated. Using the Simpson’s formula, the right and left ventricular ejaculation factors (RVEF, LVEF) were calculated. The serum uric acid levels among the patients were 8.3±1.4mg/dL, creatinine levels were 2.1 ± 0.5 mg/dL, and the total bilirubin levels were 1.9 ± 0.8 mg/dL all of which was significantly higher than the controls. The uric acid levels were also positively correlated to the NHYA class. The blood pressure and the pulmonary arterial pressure were also higher than that of the controls. The correlation was done between the elevated uric acid and ejection fractions and the correlation coefficients of MPAP, LVEF, RVEF and the NYHA class were all significantly associated and the values were 0.394, -0.513, -0.467 and 0.38 respectively. High serum uric acid levels is significantly associated with higher blood pressure, pulmonary arterial pressure and NYHA class. High serum uric acid levels can be a reliable prognostic marker for the detection of pulmonary hypertension. Early therapy may help in the reduction of mortality rate.

The definition of pulmonary hypertension: history, practical implications and current controversies

The definition of pulmonary hypertension (PH) is based on a growing body of evidence and represents the result of ongoing discussions within the PH community over the past 50 years. In 2018, the most recent World Symposium on Pulmonary Hypertension introduced significant changes in the definition of PH by lowering the mean pulmonary arterial pressure threshold to >20 mmHg and (re)introducing the pulmonary vascular resistance ≥3 WU cut-off for all forms of pre-capillary PH. These changes and their potential clinical impact have been the subject of lively discussions in the community and some important questions and controversies have been identified.In this review we aim to present the development of the definition of PH over the past decades and discuss the main arguments that led to relevant modifications. In addition, we address the practical implications of the most recent changes and controversies that still exist.Educational aimsTo review the historical development of the definition of pulmonary hypertension.To discuss practical implications and current controversies of the currently recommended definitions of pulmonary hypertension and pulmonary arterial hypertension.

Pulmonary hypertension in systemic sclerosis: diagnosis by systematic screening and prognosis after three years follow-up

Background Systemic sclerosis (SSc) is a rare disease, and the presence of pulmonary hypertension can be a determining factor in prognosis. The aim of this study was to evaluate the diagnosis, profile, and prognosis of systemic sclerosis pulmonary hypertension (SSc-PH) diagnosed by systematic screening in a Brazilian population. Methods A cohort of SSc patients underwent systematic screening for SSc-PH. Patients were referred for right heart catheterization (RHC) according to transthoracic echocardiogram or a combination of diagnostic tools. The clinical, immunological, and hemodynamic features and prognosis after 3 years were evaluated. Results Twenty patients underwent RHC. SSc pulmonary arterial hypertension (SSc-PAH) was the most common group of SSc-PH. These patients had long disease duration, high urate levels and highly elevated mean pulmonary arterial pressure (mPAP) and peripheral vascular resistance (PVR) on hemodynamics. Patients with mPAP > 20– < 25 mmHg had hemodynamic features of intermediate disease. Patients with SSc-PH associated to interstitial lung disease (SSc-ILD-PH) had signs of vasculopathy on hemodynamics. In patients with no-SSc-PH, the survival at 1, 2, and 3 years was 96%, 92% and 92%, respectively and in patients with SSc-PH it was 86.7%, 60% and 53.3%, respectively. Conclusions Patients identified with SSc-PAH and SSc-ILD-PH in our screening had severe clinical and hemodynamic features. Mortality remains high in SSc-PH but was more related to Bo-PAH and SSc-ILD-PH, while in SSc-PAH, the prognosis was better. Trial registration: Current Controlled Trials ISRCTN 72968188, July 8th, 2021. Retrospectively registered.

Pulmonary Hypertension - A Distinct Perspective

In this review, we have discussed pulmonary hypertension including definition, classification, pathophysiology, epidemiology, diagnosis and treatment of each class of PH as per latest available data and guidelines. Pulmonary hypertension is defined as an increase in mean pulmonary arterial pressure of ≥ 20 mmHg at rest. The clinical classification of pulmonary hypertension (as per world health organization) includes five different classes constructed on the basis of clinical causes of pulmonary hypertension. The main pathophysiology involved in the development of pulmonary hypertension of all types is prolonged pulmonary vasoconstriction caused by multiple factors which ultimately leads to pulmonary vascular remodelling (structural as well as functional). The primary treatment of pulmonary hypertension comprises of correction/control of underlying cause of pulmonary hypertension. The prevalence of pulmonary hypertension is increasing in developed as well as developing countries and thus its awareness is important for timely diagnosis and management of this chronic condition. The main aim of our review is to provide all the necessary information regarding pulmonary hypertension in one document. KEYWORDS Pulmonary Hypertension, Chronic Thromboembolism, Left Heart Disease, Lung Disease, Pulmonary Arterial Hypertension