Abstract Pulmonary hypertension is a common hemodynamic complication of heart failure. Interest in left-sided pulmonary hypertension has increased remarkably in recent years because its development and consequences for the right heart are now seen as mainstay abnormalities that begin in the early stages of the disease and bear unfavorable prognostic insights. However, some knowledge gaps limit our ability to influence this complex condition. Accordingly, attention is now focused on: 1) establishing a definitive consensus for a hemodynamic definition, perhaps incorporating exercise and fluid challenge; 2) implementing the limited data available on the pathobiology of lung capillaries and small arteries; 3) developing standard methods for assessing right ventricular function and, hopefully, its coupling to pulmonary circulation; and 4) searching for effective therapies that may benefit lung vessels and the remodeled right ventricle. The authors review the pathophysiology, pathobiology, and emerging clinical perspectives on pulmonary hypertension across the broad spectrum of heart failure stages.
Pulmonary hypertension (PH) is a chronic, progressive, life-threatening disease that requires expert multidisciplinary care. To facilitate this level of care, the Pulmonary Hypertension Association established across the United States a network of pulmonary hypertension care centers (PHCCs) with special expertise in PH, particularly pulmonary arterial hypertension, to raise the overall quality of care and outcomes for patients with this life-threatening disease. Since the inception of PHCCs in September 2014, to date 35 centers have been accredited in the United States. This model of care brings together physicians and specialists from other disciplines to provide care, facilitate basic and clinical research, and educate the next generation of providers. PHCCs also offer additional opportunities for improvements in PH care. The patient registry offered through the PHCCs is an organized system by which data are collected to evaluate the outcomes of patients with PH. This registry helps in detecting variations in outcomes across centers, thus identifying opportunities for improvement. Multiple tactics were undertaken to implement the strategic plan, training, and tools throughout the PHCC network. In addition, strategies to foster collaboration between care center staff and individuals with PH and their families are the cornerstone of the PHCCs. The Pulmonary Vascular Network of the American College of Chest Physicians believes this to be a positive step that will improve the quality of care delivered in the United States to patients with PH.
Background Pulmonary hypertension (PH) is a severe progressive disease. Though five subgroups are recognised, reports on survival focus mainly on pulmonary arterial hypertension (PAH). Methods Long-term transplant-free survival, and its determinants, were investigated in patients with PH (diagnosed by right heart catheterization) within a prospective registry at a single referral center in Giessen, Germany. Results In total, 2067 patients were enrolled (PAH, 685 patients [33.1%]; pulmonary venous hypertension, 307 patients [14.9%]; PH due to lung diseases (LD-PH), 546 patients [26.4%; mainly interstitial lung disease and chronic obstructive pulmonary disease]; chronic thromboembolic PH, 459 patients [22.2%]; PH owing to miscellaneous/unknown causes, 70 patients [3.4%]). Median follow-up was 37 months. Differences in transplant-free survival between etiological groups were highly significant ( p < 0.001), with 1-, 3-, and 5-year survival rates of 88.2%, 72.2%, and 59.4%, respectively, for those with PAH compared with 79.5%, 52.7%, and 38.1%, respectively, for patients with LD-PH. Patients’ age, sex, and 6-minute walk distance (6MWD), but not New York Heart Association (NYHA) functional class, associated significantly with survival across all PH subtypes in multivariate Cox regression analyses. Conclusions This is the largest reported single-center PH cohort. Some parameters used in clinical practice do not independently predict survival. Age, sex, and 6MWD outperformed NYHA functional class in predicting survival across all etiologic groups.
Management and outcome of patients with operable chronic thromboembolic pulmonary hypertension (CTEPH) who underwent pulmonary endarterectomy (PEA) at a large German referral center were investigated. In Germany, 394 PEAs were performed in 2014 and 2015 with an in-hospital mortality rate of 5.8%. Of these, 253 patients (64.2%) were treated at the Kerckhoff Clinic, Bad Nauheim, and 237 (93.7%; median age, 62 years [interquartile range [IQR], 52–72 years]; 46.0% female) were included in the present analysis. On referral, 52 patients (22.0%) were treated with pulmonary arterial hypertension–specific drugs and 95 (40.4%) were treated with non–vitamin K–dependent oral anticoagulants, and 14 (5.9%) had mean pulmonary artery pressure <25 mm Hg and were classified as having chronic thromboembolic pulmonary vascular disease. PEA was feasible in 236 (99.6%) patients with median duration of surgery of 397 minutes (IQR, 363–431 minutes). Periprocedural (0%) and in-hospital (2.5%) mortality rates were very low. Forty-two patients (17.7%) had intraoperative complications, and 60 (25.3%) had post-operative complications. The duration of surgery was the only predictor of in-hospital mortality (≥500 minutes; odds ratio [OR], 32.0; 95% confidence interval [CI], 5.5–187.6) and the only independent predictor of intraoperative (≥440 minutes; OR, 10.8; 95% CI, 4.4–26.5) and post-operative (≥390 minutes; OR, 2.4; 95%CI, 1.1–5.7) complications. Only intraoperative complications independently predicted a longer duration of surgery (≥397 minutes; OR, 5.0; 95% CI, 2.2–11.2). In an experienced center with multidisciplinary diagnostic and therapeutic approaches, PEA is safe. Prognosis was mainly determined by occurrence of intraoperative complications and duration of surgery rather than patients’ pre-operative status.
Pulmonary hypertension (PH) is a heterogeneous disorder associated with a poor prognosis. Thus, the development of novel treatment strategies is of great interest. The enzyme arginase (Arg) is emerging as important player in PH development. The aim of the current study was to determine the expression of ArgI and ArgII as well as the effects of Arg inhibition in a rat model of PH. PH was induced in 35 Sprague-Dawley rats by monocrotaline (MCT, 60 mg/kg as single-dose). There were three experimental groups: sham-treated controls (control group, n = 11), MCT-induced PH (MCT group, n = 11) and MCT-induced PH treated with the Arg inhibitor Nω-hydroxy-nor-l-arginine (nor-NOHA; MCT/NorNoha group, n = 13). ArgI and ArgII expression was determined by immunohistochemistry and Western blot. Right ventricular systolic pressure (RVPsys) was measured and lung tissue remodeling was determined. Induction of PH resulted in an increase in RVPsys (81 ± 16 mmHg) compared to the control group (41 ± 15 mmHg, p = 0.002) accompanied by a significant elevation of histological sum-score (8.2 ± 2.4 in the MCT compared to 1.6 ± 1.6 in the control group, p < 0.001). Both, ArgI and ArgII were relevantly expressed in lung tissue and there was a significant increase in the MCT compared to the control group (p < 0.01). Arg inhibition resulted in a significant reduction of RVPsys to 52 ± 19 mmHg (p = 0.006) and histological sum-score to 5.8 ± 1.4 compared to the MCT group (p = 0.022). PH leads to increased expression of Arg. Arg inhibition leads to reduction of RVPsys and diminished lung tissue remodeling and therefore represents a potential treatment strategy in PH.
ObjectivesTo determine the prevalence and factors associated with persistent pulmonary hypertension (PH) following transcatheter aortic valve replacement (TAVR) and its relationship with long-term mortality.MethodsConsecutive patients who underwent TAVR from July 2011 through January 2016 were studied. The prevalence of baseline PH (mean pulmonary artery pressure ≥25 mm Hg on right heart catheterisation) and the prevalence and the predictors of persistent≥moderate PH (pulmonary artery systolic pressure (PASP)>45 mm Hg on 1 month post-TAVR transthoracic Doppler echocardiography) were collected. Cox models quantified the effect of persistent PH on subsequent mortality while adjusting for confounders.ResultsOf the 407 TAVR patients, 273 (67%) had PH at baseline. Of these, 102 (25%) had persistent≥moderate PH. Mortality at 2 years in patients with no baseline PH versus those with PH improvement (follow-up PASP≤45 mm Hg) versus those with persistent≥moderate PH was 15.4%, 16.6% and 31.3%, respectively (p=0.049). After adjusting for Society of Thoracic Surgeons Predicted Risk of Mortality and baseline right ventricular function (using tricuspid annular plane systolic excursion), persistent≥moderate PH remained associated with all-cause mortality (HR=1.82, 95% CI 1.06 to 3.12, p=0.03). Baseline characteristics associated with increased likelihood of persistent≥moderate PH were ≥moderate tricuspid regurgitation, ≥moderate mitral regurgitation, atrial fibrillation/flutter, early (E) to late (A) ventricular filling velocities (E/A ratio) and left atrial volume index.ConclusionsPersistency of even moderate or greater PH at 1 month post-TAVR is common and associated with higher all-cause mortality.