Chronic thromboembolic pulmonary hypertension (CTEPH) is an uncommon disease that is the most serious complication associated with unresolved pulmonary embolism. This disease has several risk factors, but no familial pattern has been described. Few thrombophilic conditions have been reported to increase risk of CTEPH, and none of the hereditary thrombophilias causes this disease. The reason CTEPH develops in some patients after pulmonary embolism remains unknown. We describe a 54-year-old woman and her maternal aunt who both underwent pulmonary thromboendarterectomy for CTEPH. This represents the first description of familial CTEPH.
Anomalous origin of the pulmonary artery from the ascending aorta can lead to congestive heart failure in infancy, and with advancing age many patients will experience severe pulmonary hypertension. Surgical intervention has high mortality and morbidity risks if this happens. Strategies to manage these patients seem only limited to heart–lung transplantation or lung transplantation. Here, we successfully performed surgical intervention in an adult patient who had anomalous origin of the right pulmonary artery from the ascending aorta with high pressures in the ascending aorta and normally originating pulmonary artery.
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.
Objective Pulmonary endarterectomy is the treatment of choice for chronic thromboembolic pulmonary hypertension. In many patients hemodynamics are normalized early after surgical intervention. However, the effect of residual pulmonary hypertension on postoperative clinical status and survival is unknown. Methods Data were collected prospectively on all patients who underwent pulmonary endarterectomy in a continuous national series between 1997 and December 2007. Postoperatively, patients underwent scheduled reinvestigation, including functional testing and right heart catheterization, at 3 months after the operation. They were divided into 2 groups based on mean pulmonary artery pressure: group 1, less than 30 mm Hg; group 2, 30 mm Hg or greater. Results Three hundred fourteen patients underwent pulmonary endarterectomy, survived to hospital discharge, and completed the 3-month follow-up period. At 3 months after pulmonary endarterectomy, there was a significant reduction in mean pulmonary artery pressure for the whole cohort (48 ± 12 to 26 ± 10 mm Hg, P < .001). However, 31% of the patients had residual pulmonary hypertension. Group 1 patients enjoyed significantly better exercise capacity and improved symptoms compared with group 2 patients. In addition, there were significantly fewer patients receiving targeted medical therapy in group 1 versus group 2 (0% vs 25%, P < .001). Conditional survival after discharge from the hospital for the whole cohort was 90.0% at 5 years and was not different between groups (90.3% for group 1 vs 89.9% for group 2, P = .36). Conclusions For patients undergoing pulmonary endarterectomy, survival after hospital discharge is excellent. Residual pulmonary hypertension significantly compromised symptom status and functional capacity but did not appear to adversely affect medium-term survival. The effect of targeted medical therapy in patients with residual pulmonary hypertension after pulmonary endarterectomy needs to be evaluated further.
Background A subset of patients with hereditary hemorrhagic telangiectasia (HHT) develops pulmonary hypertension (PH) by mechanisms including pulmonary arterial hypertension, high flow, and elevated pulmonary arterial wedge pressure (PAWP). We aimed to describe echocardiographic and hemodynamic characteristics of patients with coexisting HHT and PH. Methods We conducted a single-center cohort study of patients with confirmed HHT who underwent right-sided heart catheterization (RHC) and transthoracic two-dimensional echocardiography for suspected PH between June 1, 2003 and September 1, 2013 at Mayo Clinic Rochester, Minnesota. Results Of 38 patients with confirmed HHT who underwent RHC and echocardiography, 28 (74%) had a mean pulmonary artery pressure (MPAP) ≥ 25 mm Hg. Of those 28, 12 (43%) had pulmonary arterial hypertension. Two patients had normal PAWP and pulmonary vascular resistance (PVR), with PH secondary to either an atrial septal defect or high cardiac flow. Fourteen patients (50%) had elevated PAWP (≥ 15 mm Hg), nine with evidence of high flow. RHC in all 28 patients demonstrated a MPAP of 41 ± 11 mm Hg, PAWP of 17 ± 10 mm Hg, and PVR of 4.5 ± 4.2 Wood units. Echocardiography demonstrated moderate/severe right ventricular dysfunction in nine patients (32%). The presence of PH trended toward worse survival ( P = .06). Conclusions PH in patients with HHT occurs by different mechanisms, and there is a trend toward worse survival in patients who develop PH despite the mechanism. The equal predilection toward all subtypes of PH illustrates the necessity of RHC to clarify the hemodynamics.
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 artery remodeling triggered by alveolar hypoxia is considered the main mechanism of pulmonary hypertension (PH) in COPD patients. We hypothesized that the risk for PH in COPD is increased by an elevation in the proinflammatory cytokines interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), and IL-1β, as well as by specific genetic polymorphisms of these cytokines. We assessed cytokine plasma levels and the polymorphisms G(−174)C IL-6, C(−511)T IL-1β, and A(−2518)G MCP-1 in 148 COPD patients (recruited at two centers) with right heart catheterization data and 180 control subjects including smokers and nonsmokers. Human pulmonary artery smooth muscle cells (PA-SMCs) were cultured for IL-6 messenger RNA assays under normoxic and hypoxic conditions. Patients with PH (mean pulmonary artery pressure [PAP], ≥ 25 mm Hg) had lower Pa and higher plasma IL-6 values than those without PH; there were no differences in terms of pulmonary function test results or CT scan emphysema scores. Plasma IL-6 correlated with mean PAP ( = 0.39; p < 0.001) and was included in a multiple stepwise regression analysis, with mean PAP as the dependent variable. In patients with the GG genotype, the mean PAP value was significantly higher and PH was more common than in CG or CC patients (adjusted odds ratio, 4.32; 95% confidence interval, 1.96 to 9.54). Exposure to 4 h of hypoxia led to an about twofold increase in IL-6 messenger RNA in cultured human PA-SMCs. Inflammation, most likely involving IL-6, may contribute substantially to PH complicating COPD.
Background Osteopontin (OPN) is a pleiotropic cytokine that has been postulated to play a role in the pathogenesis of idiopathic pulmonary arterial hypertension (IPAH). OPN plasma levels may be related to disease severity and mortality in patients with PAH. Methods OPN plasma levels obtained during right-sided heart catheterization were assessed by a commercially available enzyme-linked immunosorbent assay and related to hemodynamics, exercise capacity, N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level, uric acid level, C-reactive protein level, and survival in two cohorts of patients with IPAH: a 4-year retrospective cohort (n = 70) and a prospective cohort (n = 25) followed for 3 months after initiation of therapy. Forty apparently healthy individuals served as control subjects. Results Baseline OPN levels were elevated in patients with IPAH compared with healthy control subjects (50.2 ± 35.9 vs 23.7 ± 2.8 ng/mL, P < .0001). In the retrospective as well as in the prospective cohort, OPN levels correlated with mean right atrial pressure and NT-BNP. In the retrospective cohort, OPN levels also correlated with age ( r = 0.3, P = .02), 6-min walking distance ( r =−0.4, P = .05), and New York Heart Association class ( r = 0.4, P = .001). Multivariate Cox analysis demonstrated that baseline OPN levels were independent predictors of mortality ( P = .02). When patients were divided according to their baseline OPN values, being normal or elevated at baseline (below or above 34.5 ng/mL), proportional survival rates were 100% vs 80% after 1 year and 77% vs 51% after 3 years, respectively. Conclusion Circulating OPN predicts survival in patients with IPAH and is associated with a higher New York Heart Association class. OPN, thus, may be useful as a biomarker in IPAH.