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The function of the right ventricle (RV) determines the prognosis of patients with pulmonary hypertension. While much progress has been made in the treatment of pulmonary hypertension, therapies for the RV are less well established. In this review of treatment strategies for the RV, first we focus on ways to reduce wall stress since this is the main determinant of changes to the ventricle. Secondly, we discuss treatment strategies targeting the detrimental consequences of increased RV wall stress. To reduce wall stress, afterload reduction is the essential. Additionally, preload to the ventricle can be reduced by diuretics, by atrial septostomy, and potentially by mechanical ventricular support. Secondary to ventricular wall stress, left-to-right asynchrony, altered myocardial energy metabolism, and neurohumoral activation will occur. These may be targeted by optimising RV contraction with pacing, by iron supplement, by angiogenesis and improving mitochondrial function, and by neurohumoral modulation, respectively. We conclude that several treatment strategies for the right heart are available; however, evidence is still limited and further research is needed before clinical application can be recommended. [ABSTRACT FROM AUTHOR]

Examines the changes in main pulmonary artery flow and right ventricular mass and volumes in patients with pulmonary hypertension during epoprostenol therapy. Evaluation of 11 patients before the start of therapy and every four months thereafter; Magnetic resonance imaging; Indication that epoprostenol lowers pulmonary vascular resistance, leading to an increase in pulmonary artery flow.

The long-term outcomes of operated and nonoperated patients with chronic thromboembolic pulmonary hypertension were reported in a large, prospective, multicentre, European and Canadian registry. The long-term prognosis of operated patients was superior to that of nonoperated patients, indicating that surgery should be the first-choice treatment in this patient cohort. [ABSTRACT FROM AUTHOR]

The role of right ventricular (RV) fibrosis in pulmonary hypertension (PH) remains a subject of ongoing discussion. Alterations of the collagen network of the extracellular matrix may help prevent ventricular dilatation in the pressure-overloaded RV. At the same time, fibrosis impairs cardiac function, and a growing body of experimental data suggests that fibrosis plays a crucial role in the development of RV failure. In idiopathic pulmonary arterial hypertension and chronic thromboembolic PH, the RV is exposed to a ≈5 times increased afterload, which makes these conditions excellent models for studying the impact of pressure overload on RV structure. With this review, we present clinical evidence of RV fibrosis in idiopathic pulmonary arterial hypertension and chronic thromboembolic PH, explore the correlation between fibrosis and RV function, and discuss the clinical relevance of RV fibrosis in patients with PH. We postulate that RV fibrosis has a dual role in patients with pressure-overloaded RVs of idiopathic pulmonary arterial hypertension and chronic thromboembolic PH: as part of an adaptive response to prevent cardiomyocyte overstretch and to maintain RV shape for optimal function, and as part of a maladaptive response that increases diastolic stiffness, perturbs cardiomyocyte excitation-contraction coupling, and disrupts the coordination of myocardial contraction. Finally, we discuss potential novel therapeutic strategies and describe more sensitive techniques to quantify RV fibrosis, which may be used to clarify the causal relation between RV fibrosis and RV function in future research. [ABSTRACT FROM AUTHOR]

The article focuses on a study which looks into the relationship between pulmonary vascular resistance (PVR) and right ventricular ejection fraction (RVEF) in patients with pulmonary hypertension (PH). The study has discovered changes in the right ventricular function and hypertensive pulmonary circulation during the pulmonary hypertension's targeted therapies. It has compared the combination therapy with epoprostenol and bosentan and epoprostenol monotherapy. However, it has also identified that the preservation of PVR is not guaranteed by a small PVR reduction.

Survival in patients with pulmonary arterial hypertension (PAH) is closely related to right ventricular (RV) function. Although pulmonary load is an important determinant of RV systolic function in PAH, there remains a significant variability in RV adaptation to pulmonary hypertension. In this report, the authors discuss the emerging concepts of right heart pathobiology in PAH. More specifically, the discussion focuses on the following questions. 1) How is right heart failure syndrome best defined? 2) What are the underlying molecular mechanisms of the failing right ventricle in PAH? 3) How are RV contractility and function and their prognostic implications best assessed? 4) What is the role of targeted RV therapy? Throughout the report, the authors highlight differences between right and left heart failure and outline key areas of future investigation. [ABSTRACT FROM AUTHOR]

Irrespective of its cause, pulmonary hypertension (PH) leads to an increase in pulmonary vascular resistance (PVR). Failing adaption of the right ventricle (RV) to the increased afterload is the main cause of death in PH patients and therefore monitoring RV function during treatment is essential. However, consensus on the optimal method for serial assessment of RV function is lacking and therefore the major clinical trials on PH-specific therapies have not provided clear answers with respect to the response of the RV to treatment. This short review will give an overview of the most important load-dependent and load-independent parameters for assessing RV response to therapy in PH patients. [ABSTRACT FROM AUTHOR]

Background After lung transplantation, increased left ventricular (LV) filling can lead to LV failure, increasing the risk of post-operative complications and mortality. LV dysfunction in pulmonary arterial hypertension (PAH) is characterized by a reduced LV ejection fraction and impaired diastolic function. Objectives The pathophysiology of LV dysfunction in PAH is incompletely understood. This study sought to assess the contribution of atrophy and contractility of cardiomyocytes to LV dysfunction in PAH patients. Methods LV function was assessed by cardiac magnetic resonance imaging. In addition, LV biopsies were obtained in 9 PAH patients and 10 donors. The cross-sectional area (CSA) and force-generating capacity of isolated single cardiomyocytes was investigated. Results Magnetic resonance imaging analysis revealed a significant reduction in LV ejection fraction in PAH patients, indicating a reduction in LV contractility. The CSA of LV cardiomyocytes of PAH patients was significantly reduced (~30%), indicating LV cardiomyocyte atrophy. The maximal force-generating capacity, normalized to cardiomyocyte CSA, was significantly reduced (~25%). Also, a reduction in the number of available myosin-based cross-bridges was found to cause the contractile weakness of cardiomyocytes. This finding was supported by protein analyses, which showed an ~30% reduction in the myosin/actin ratio in cardiomyocytes from PAH patients. Finally, the phosphorylation level of sarcomeric proteins was reduced in PAH patients, which was accompanied by increased calcium sensitivity of force generation. Conclusions The contractile function and the CSA of LV cardiomyocytes is substantially reduced in PAH patients. We propose that these changes contribute to the reduced in vivo contractility of the LV in PAH patients. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to describe the long-term outcomes in idiopathic pulmonary arterial hypertension (IPAH) treated with first-line bosentan or intravenous (IV) epoprostenol, and additional therapy as needed. Methods: In a single-center, retrospective, longitudinal cohort, data on right heart catheterization, 6-minute walk distance (6MWD), disease progression and mortality were collected. Outcomes were assessed in first-line bosentan and first-line epoprostenol patients. To reduce selection bias due to differences between groups, two independent analyses were performed. First, a comparison was made of World Health Organization (WHO) Functional Class (FC) III patients. Second, to control for disease severity, a matched-pairs analysis was performed, with matching according to baseline cardiac output and exercise capacity and irrespective of FC at baseline. Results: Thirty-seven IPAH patients initiated first-line bosentan treatment and 37 first-line IV epoprostenol. Twenty-nine of the bosentan patients and 16 of the IV epoprostenol patients were in WHO FC III; demographic profiles were similar, although hemodynamic measurements and 6MWD suggested more severe disease in the IV epoprostenol group at treatment initiation. At 1 and 3 years, median change in 6MWD for patients initiating bosentan was +54 m (95% confidence interval: −3 to 76) and +71 m (−123 to 116), respectively, and +92 m (17 to 128) and +142 m (−6 to 242) for those on IV epoprostenol. Absence of disease progression of WHO FC III at 1 and 3 years was 72% and 45% with bosentan and 75% and 44% with IV epoprostenol, respectively. Survival at 1 and 3 years was 93% and 89% with bosentan and 94% and 75% with IV epoprostenol, respectively. Results were confirmed in matched-pairs analysis of 16 bosentan and 16 IV epoprostenol patients with similar disease severity. Conclusions: First-line epoprostenol treatment may lead to greater improvement in exercise capacity than first-line bosentan. However, these greater exercise improvements did not translate into longer time to disease progression or survival. [Copyright &y& Elsevier]

Background: The aim of our study was to describe the efficacy of addition of intravenous or subscutaneous prostanoids in idiopathic pulmonary arterial hypertension (PAH) patients deteriorating on bosentan or on bosentan-sildenafil. Methods: PAH treatment at our hospital is standardized with first-line oral therapy in New York Heart Association class III patients followed by addition of prostanoids on clinical worsening. Results: Mean improvement in 6-minute walk distance after 4 months of prostanoids was 86 m (p < 0.01) in the bosentan group versus 41 m (p < 0.05) in the bosentan–sildenafil group, and these improvements persisted at long-term follow-up. Conclusions: From these results we conclude that addition of subcutaneous or intravenous prostanoids can be efficacious in PAH deteriorating on oral therapy. [Copyright &y& Elsevier]

Background: Among patients with advanced pulmonary arterial hypertension (PAH) who are receiving epoprostenol treatment, complications due to the delivery system are known to be a cause of serious morbidity and mortality. In this study, we aimed to outline the complications associated with the use of a totally implantable access port (TIAP) and their consequences in continuous intravenous epoprostenol treatment. Methods: One hundred eleven pulmonary hypertension (PH) patients treated with epoprostenol through a totally implantable access port (TIAP) between May 1998 and July 2006 at three Dutch PH referral centers were retrospectively studied. Results: During a mean follow-up period of 946 ± 719 days, TIAP-related complications included local port site infections, bloodstream infections, port site skin perforations and incorrect port placement, with incidence rates of 0.11, 0.15, 0.06 and 0.04 per patient-year, respectively. Fatal, serious, moderate and minor consequences of these complications had incidence rates of 0.01, 0.50, 0.09 and 0.01 per patient-year, respectively. The median complication-free survival was 371 days. Staphylococcus aureus was the dominant infectious agent. The median TIAP life duration was 677 days. Female patients showed significantly longer first TIAP survival (p = 0.004). Conclusions: The use of a TIAP showed long-lasting port survival and relatively low complication rates. Our data suggest that the TIAP is well suited for continuous intravenous epoprostenol delivery in patients with pulmonary hypertension. [Copyright &y& Elsevier]