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In pulmonary hypertension, the right ventricle adapts to the increasing vascular load by enhancing contractility ("coupling") to maintain flow. Ventriculoarterial coupling implies that stroke volume changes little while preserving ventricular efficiency. Ultimately, a phase develops where ventricular dilation occurs in an attempt to limit the reduction in stroke volume, with uncoupling and increased wall stress as a consequence. With pressure-volume analysis, we separately describe the changing properties of the pulmonary vascular system and the right ventricle, as well as their coupling, as important concepts for understanding the changes that occur in pulmonary hypertension. On the basis of the unique properties of the pulmonary circulation, we show how all relevant physiological parameters can be derived using an integrative approach. Because coupling is maintained by hypertrophy until the end stage of the disease, when progressive dilation begins, right ventricular volume is the essential parameter to measure in follow-up of patients with pulmonary hypertension. [ABSTRACT FROM AUTHOR]

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]

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]

Objectives: The purpose of this study was to examine the relationship between changes in pulmonary vascular resistance (PVR) and right ventricular ejection fraction (RVEF) and survival in patients with pulmonary arterial hypertension (PAH) under PAH-targeted therapies. Background: Despite the fact that medical therapies reduce PVR, the prognosis of patients with PAH is still poor. The primary cause of death is right ventricular (RV) failure. One possible explanation for this apparent paradox is the fact that a reduction in PVR is not automatically followed by an improvement in RV function. Methods: A cohort of 110 patients with incident PAH underwent baseline right heart catheterization, cardiac magnetic resonance imaging, and 6-min walk testing. These measurements were repeated in 76 patients after 12 months of therapy. Results: Two patients underwent lung transplantation, 13 patients died during the first year, and 17 patients died in the subsequent follow-up of 47 months. Baseline RVEF (hazard ratio [HR]: 0.938; p = 0.001) and PVR (HR: 1.001; p = 0.031) were predictors of mortality. During the first 12 months, changes in PVR were moderately correlated with changes in RVEF (R = 0.330; p = 0.005). Changes in RVEF (HR: 0.929; p = 0.014) were associated with survival, but changes in PVR (HR: 1.000; p = 0.820) were not. In 68% of patients, PVR decreased after medical therapy. Twenty-five percent of those patients with decreased PVR showed a deterioration of RV function and had a poor prognosis. Conclusions: After PAH-targeted therapy, RV function can deteriorate despite a reduction in PVR. Loss of RV function is associated with a poor outcome, irrespective of any changes in PVR. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to explore in pulmonary arterial hypertension (PAH) whether the cause of interventricular asynchrony lies in onset of shortening or duration of shortening. Background: In PAH, leftward ventricular septal bowing (LVSB) is probably caused by a left-to-right (L-R) delay in myocardial shortening. Methods: In 21 PAH patients (mean pulmonary arterial pressure 55 ± 13 mm Hg and electrocardiogram–QRS width 100 ± 16 ms), magnetic resonance imaging myocardial tagging (14 ms temporal resolution) was applied. For the left ventricular (LV) free wall, septum, and right ventricular (RV) free wall, the onset time (Tonset) and peak time (Tpeak) of circumferential shortening were calculated. The RV wall tension was estimated by the Laplace law. Results: The Tonset was 51 ± 23 ms, 65 ± 4 ms, and 52 ± 22 ms for LV, septum, and RV, respectively. The Tpeak was 293 ± 58 ms, 267 ± 22 ms, and 387 ± 50 ms for LV, septum, and RV, respectively. Maximum LVSB was at 395 ± 45 ms, coinciding with septal overstretch and RV Tpeak. The L-R delay in Tonset was −1 ± 16 ms (p = 0.84), and the L-R delay in Tpeak was 94 ± 41 ms (p < 0.001). The L-R delay in Tpeak was not related to the QRS width but was associated with RV wall tension (p < 0.05). The L-R delay in Tpeak correlated with leftward septal curvature (p < 0.05) and correlated negatively with LV end-diastolic volume (p < 0.05) and stroke volume (p < 0.05). Conclusions: In PAH, the L-R delay in myocardial peak shortening is caused by lengthening of the duration of RV shortening. This L-R delay is related to LVSB, decreased LV filling, and decreased stroke volume. [Copyright &y& Elsevier]