Pulmonary arterial hypertension (PAH) develops in 10-16% of patients with atrial septal defect (ASD). The determinants of occurrence of PAH in ASD are not clear. There does not appear to be a relationship between duration of exposure to increased pulmonary blood flow and the development of PAH. Once PAH develops, it is challenging to determine operability and predict outcomes after repair in borderline situations. Two illustrative cases of ASD and PAH; an infant and an adult who were evaluated for operability and factors that were considered in decision-making are discussed. Their subsequent follow-up is also presented to illustrate their modified history following closure of the ASD.

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Right ventricular hypertrophy (RVH) is a serious clinical problem that complicates many disease processes, including pulmonary arterial hypertension (PAH). PAH is a lethal syndrome of pulmonary hypertension due to the obstruction, obliteration, and constriction of small pulmonary arteries. One of the most important prognostic factors in PAH is RV function. Nowadays, surprisingly little work has been done on the change in RV function by PAH. Recent evidence suggests that there is a change in metabolism in PAH, reminiscent of the Warburg effect (i.e. increased glycolysis and decreased glucose oxidation occurs despite abundant PO ₂ ). In PAH, the increased expression of pyruvate dehydrogenase kinase (PDK) may inhibit pyruvate dehydrogenase (PDH), limiting oxidative metabolism. PDK-4, a key regulator of glucose metabolism, is activated in monocrotaline (MCT)-induced RVH. This phosphorylates and inhibits PDH, thereby decreasing oxidative metabolism. There appears to be a compensatory increase glycolysis in RVH. This is associated with an increase in the expression of the glucose transported, GLUT4. RVH-related changes in metabolism may alter cardiac repolarization, which could predispose PAH patients to arrhythmia and decreased contractile function. We have noted altered shape and duration of cardiac action potential (AP) repolarization in RVH (largely dependent on dynamic changes in K ⁺ channel expression). Our preliminary data show that there is AP prolongation in RVH. We propose the concept that altered metabolism may alter ion channel expression in RVH and that this in turn causes AP prolongation. Based on our preliminary data and the literature, we hypothesize that a Warburg effect occurs in RVH and suggest that this may constitute a new therapeutic target.

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Although the prognosis for patients with Pulmonary Hypertension (PH) has improved over recent decades, it is still difficult to predict clinical outcome in individual patients. In all forms of the disease, right ventricular (RV) function remains the most important determinant of survival and the difficulties encountered in predicting prognosis in individuals reflects the heterogeneous response of the RV. Our understanding of the mechanisms that underpin RV failure or adaptation in response to PH has greatly improved over recent years, as has our ability to accurately identify prognostically significant RV dysfunction in patients with PH. These advances have been driven by significant improvements in established RV imaging tools, such as 2-D echocardiography, and by the development of entirely new techniques, such as 3-D echocardiography, tissue Doppler imaging and cardiovascular magnetic resonance imaging. The purpose of this article is to review these techniques and to summarize these recent advances.

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According to the World Health Organization (WHO), the South East Asia Region (SEAR) consists of eleven countries with diverse population size, land area, sociopolitical environment, economy and health care systems. Each country has epidemiological and geographical factors that may contribute to risks for developing pulmonary hypertension (PH). Currently, there are no published estimates of the number of people suffering from PH in these countries. This article started as an attempt to capture a general overview of available, indexed publications on PH from the South East Asia region. Publications on PH from the SEAR originated almost entirely from India and Thailand. Further, virtually all of the Medline0 indexed research literature from the SEAR comes from these two countries. The type of available PH literature from this region were analyzed using data such as age groups in human studies, top publishing journals and topics of study (MeSH terms). A web-based tool called MedSum that provides numerical summaries of Medline literature, based on user-provided PubMed style search terms and field tags was used for this work.

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Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction A Community-Based Study Carolyn S. P. Lam, Vιronique L. Roger, Richard J. Rodeheffer, Barry A. Borlaug, Felicity T. Enders, Margaret M. Redfield, Journal of the American College of Cardiology 2009; 53:1119-26. Objectives: This study sought to define the prevalence, severity, and significance of pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF) in the general community. Background: Although HFpEF is known to cause PH, its development is highly variable. Community-based data are lacking, and the relative contribution of pulmonary venous versus pulmonary arterial hypertension (HTN) to PH in HFpEF is unknown. We hypothesized that PH would be a marker of symptomatic pulmonary congestion, distinguishing HFpEF from pre-clinical hypertensive heart disease. Methods: This community-based study of 244 HFpEF patients (age: 76±13 years; 45% male) was followed up using Doppler echocardiography over 3 years. Control subjects were 719 adults with HTN without HF (age: 66±10 years; 44% male). Pulmonary artery systolic pressure (PASP) was derived from the tricuspid regurgitation velocity and PH defined as PASP _35 mm Hg. Pulmonary capillary wedge pressure (PCWP) was estimated from the ratio of early transmitral flow velocity to early mitral annular diastolic velocity. Results: In HFpEF, PH was present in 83% and the median (25 ^th , 75 ^th percentile) PASP was 48 (37, 56) mm Hg. PASP increased with PCWP (r = 0.21; P = 0.007). Adjusting for PCWP, PASP was higher in HFpEF than HTN ( P = 0.001). The PASP distinguished HFpEF from HTN with an area under the receiver-operating characteristic curve of 0.91 ( P = 0.001) and strongly predicted mortality in HFpEF (hazard ratio: 1.3 per 10 mm Hg; P = 0.001). Conclusions: PH is highly prevalent and often severe in HFpEF. Although pulmonary venous HTN contributes to PH, it does not fully account for the severity of PH in HFpEF, suggesting that a component of pulmonary arterial HTN also takes part in the contribution.

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In recent years, much more insight has been given to the pathogenic role of HIV and to the clinical manifestations of HIV-related pulmonary hypertension (HRPH) that currently represents one of the most severe events during the HIV disease. HRPH occurs in early and late stages of HIV infection and does not seem to be related to the degree of immune deficiency. Many of the symptoms in HRPH result from right ventricular dysfunction: the first clinical manifestation is effort intolerance and exertional dyspnea that will progress to the point of breathlessness at rest. Echocardiography has been proved to be an extremely useful tool for the diagnosis of HRPH, and Doppler echocardiography may be used to estimate systolic pulmonary artery pressure and to monitor the effects of therapy. The assessment of hemodynamic measures by catheterization remains, however, the best test for evaluating the response to therapy. Cardiac catheterization is mandatory to characterize the disease and exclude an underlying cardiac shunt as etiology. Vasodilators have been extensively used in the treatment of pulmonary hypertension since vasoconstriction is a determinant characteristic of this disease. More recently, highly effective therapies for pulmonary arterial hypertension have been made available, including prostanoids, endothelin-receptor antagonists, and phosphodiesterase-5 inhibitors, allowing an amelioration of symptoms and a better prognosis. However, HRPH remains a progressive disease for which treatment is often unsatisfactory and there is no cure. As a new efficient antiretroviral treatment will be introduced, clinicians should expect to encounter an increasing number of cases of pulmonary hypertension in HIV-infected patients in the future.

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