Luciana Tamie Kato Morinaga

The Role of Target Therapies in Schistosomiasis-Associated Pulmonary Arterial Hypertension

BACKGROUND Schistosomiasis-associated pulmonary arterial hypertension (Sch-PAH) may be one of the most prevalent forms of pulmonary arterial hypertension (PAH) worldwide. However, the clinical and hemodynamical response to specific PAH therapy in Sch-PAH is not known. METHODS We retrospectively analyzed the charts of all patients with Sch-PAH who initiated specific PAH treatment between June 2003 and June 2010 in a single PAH reference center in São Paulo, Brazil. Clinical and hemodynamical data were retrospectively collected and evaluated in two periods: baseline and posttreatment. RESULTS The study population consisted of 12 patients with Sch-PAH. They were treated with phosphodiseterase-5 inhibitors (seven patients), endothelin receptor antagonists (four patients), or combination therapy (one patient). Mean treatment period was 34.9 ± 15.5 months. Patients with Sch-PAH presented significant improvements in terms of functional class, 6-min walk test distance (439 ± 85 to 492 ± 79 m, P = .032), cardiac index (2.66 ± 0.59 to 3.08 ± 0.68 L/min/m(2), P = .028), and indexed pulmonary vascular resistance (20.7 ± 11.6 to 15.9 ± 9 W/m(2), P = .038) with the introduction of specific PAH treatment. CONCLUSIONS We conclude that specific PAH therapy may be of benefit to patients with Sch-PAH, considering clinical, functional, and hemodynamic parameters.

Pulmonary Arterial Hypertension in the Southern Hemisphere

BACKGROUND Pulmonary arterial hypertension (PAH) is a rare and ultimately fatal disorder of the pulmonary vasculature. There is increasing interest in the worldwide characteristics of patients with PAH, although data coming from the Southern Hemisphere remain scarce. The objective of this study was to describe a cohort of incident patients with PAH from a large reference center in Brazil. METHODS All consecutive patients who received a diagnosis of PAH by right-sided heart catheterization between 2008 and 2013 were included in the study. RESULTS A total of 178 patients with newly diagnosed PAH were enrolled in the study (mean age, 46 years; female/male ratio, 3.3:1; 45.5% in New York Heart Association functional class III or IV). Idiopathic PAH (IPAH), connective tissue disease (CTD), and schistosomiasis-associated PAH (Sch-PAH) accounted for 28.7%, 25.8%, and 19.7% of all cases, respectively. The patients were treated with phosphodiesterase type 5 inhibitors (66%), endothelin receptor antagonists (27%), or a combination of both (5%). For the PAH group as a whole, the estimated survival rate 3 years after diagnosis was 73.9%. The prognosis for the patients with CTD was worse than that for the patients with IPAH and Sch-PAH (P = .03). CONCLUSIONS The distribution of PAH causes and the baseline characteristics in our registry clearly differ from the previously published European and US-based registries. These differences highlight the importance of regional registries and also raise questions regarding the need to better account for such differences in future clinical trials.

Quality of life as a prognostic marker in pulmonary arterial hypertension

BackgroundImprovement in quality of life together with better survival are the ultimate goals in the treatment of pulmonary arterial hypertension (PAH) patients. The objective of this study was to evaluate the health-related quality of life (HRQL) of pulmonary arterial hypertension (PAH) patients with the SF-36 generic questionnaire and to identify the prognostic implication of this assessment.MethodsFifty-four consecutive newly diagnosed PAH patients (WHO classification group I) in a single PAH reference center were included. Patients were evaluated at baseline for clinical and hemodynamic parameters, and they subsequently received first-line therapy with either an endothelin receptor antagonist or a phosphodiesterase-5 inhibitor. After 16 weeks of specific PAH therapy, all patients were re-evaluated using a 6MWT and a SF 36 questionnaire, and then they were followed up for at least 36 months.ResultsAfter treatment, the patients demonstrated an improved 6MWT (414 ± 124 m vs. 440 ± 113 m, p = 0.001). Specific PAH therapy also improved the HRQL scores.Patients with a baseline Physical Component Score (PCS) higher than 32 had a better survival rate than those who had a score under 32 (p = 0.04). Similarly, patients with a PCS of at least a 38 after the 16 week therapy period had a better survival rate when compared with those who did not achieve this value (p = 0.016). Unlike the absolute PCS values, the post-treatment PCS variability was unable to predict better survival rates (p = 0.58).ConclusionsOur findings suggest that HRQL is associated with prognosis in PAH. Furthermore, achieving pre-determined PCS scores might represent a specific goal to be reached in treatment-to-target strategies.

Schistosomiasis and pulmonary hypertension

Schistosomiasis is one of the most prevalent chronic infectious diseases in the world. One of its most severe complications, pulmonary hypertension, occurs in up to 5% of patients with hepatosplenic schistosomiasis. The prevalence of schistosomiasis is so overwhelming that schistosomiasis-associated pulmonary hypertension (Sch-PH) may be the most prevalent cause of pulmonary hypertension around the world. Multiple pathways have been described as potential mechanisms of disease in Sch-PH, such as egg embolism, inflammatory disease or pulmonary blood overflow. The possible physiopathological mechanisms will be discussed in this article, as well the disease’s clinical course and response to the treatment available.

Left ventricular dysfunction in patients with suspected pulmonary arterial hypertension

OBJECTIVE: To evaluate the role of right heart catheterization in the diagnosis of pulmonary arterial hypertension (PAH). METHODS: We evaluated clinical, functional, and hemodynamic data from all patients who underwent right heart catheterization because of diagnostic suspicion of PAH-in the absence of severe left ventricular dysfunction (LVD), significant changes in pulmonary function tests, and ventilation/perfusion lung scintigraphy findings consistent with chronic pulmonary thromboembolism-between 2008 and 2013 at our facility. RESULTS: During the study period, 384 patients underwent diagnostic cardiac catheterization at our facility. Pulmonary hypertension (PH) was confirmed in 302 patients (78.6%). The mean age of those patients was 48.7 years. The patients without PH showed better hemodynamic profiles and lower levels of B-type natriuretic peptide. Nevertheless, 13.8% of the patients without PH were categorized as New York Heart Association functional class III or IV. Of the 218 patients who met the inclusion criteria, 40 (18.3%) and 178 (81.7%) were diagnosed with PH associated with LVD (PH-LVD) and with PAH, respectively. The patients in the HP-LVD group were significantly older than were those in the PAH group (p < 0.0001). CONCLUSIONS: The proportional difference between the PAH and PH-LVD groups was quite significant, considering the absence of echocardiographic signs suggestive of severe LVD during the pre-catheterization investigation. Our results highlight the fundamental role of cardiac catheterization in the diagnosis of PAH, especially in older patients, in whom the prevalence of LVD that has gone undiagnosed by non-invasive tests is particularly relevant.

Skeletal muscle abnormalities in pulmonary arterial hypertension.

Background Pulmonary arterial hypertension is a progressive disease that is characterized by dyspnea and exercise intolerance. Impairment in skeletal muscle has recently been described in PAH, although the degree to which this impairment is solely determined by the hemodynamic profile remains uncertain. The aim of this study was to verify the association of structural and functional skeletal muscle characteristics with maximum exercise in PAH. Methods The exercise capacity, body composition, CT area of limb muscle, quality of life, quadriceps biopsy and hemodynamics of 16 PAH patients were compared with those of 10 controls. Results PAH patients had a significantly poorer quality of life, reduced percentage of lean body mass, reduced respiratory muscle strength, reduced resistance and strength of quadriceps and increased functional limitation at 6MWT and CPET. VO2 max was correlated with muscular variables and cardiac output. Bivariate linear regression models showed that the association between muscular structural and functional variables remained significant even after correcting for cardiac output. Conclusion Our study showed the coexistence of ventilatory and quadriceps weakness in face of exercise intolerance in the same group of PAH patients. More interestingly, it is the first time that the independent association between muscular pattern and maximum exercise capacity is evidenced in PAH, independently of cardiac index highlighting the importance of considering rehabilitation in the treatment strategy for PAH.

New anticoagulants for the treatment of venous thromboembolism

Worldwide, venous thromboembolism (VTE) is among the leading causes of death from cardiovascular disease, surpassed only by acute myocardial infarction and stroke. The spectrum of VTE presentations ranges, by degree of severity, from deep vein thrombosis to acute pulmonary thromboembolism. Treatment is based on full anticoagulation of the patients. For many decades, it has been known that anticoagulation directly affects the mortality associated with VTE. Until the beginning of this century, anticoagulant therapy was based on the use of unfractionated or low-molecular-weight heparin and vitamin K antagonists, warfarin in particular. Over the past decades, new classes of anticoagulants have been developed, such as factor Xa inhibitors and direct thrombin inhibitors, which significantly changed the therapeutic arsenal against VTE, due to their efficacy and safety when compared with the conventional treatment. The focus of this review was on evaluating the role of these new anticoagulants in this clinical context.

Use of direct oral anticoagulants for chronic thromboembolic pulmonary hypertension

OBJECTIVES: Chronic thromboembolic pulmonary hypertension is one of the most prevalent forms of pulmonary hypertension and is a major complication of acute pulmonary embolism. One mainstay of chronic thromboembolic pulmonary hypertension treatment is lifelong anticoagulation. The recent advent of direct oral anticoagulants for acute pulmonary embolism treatment has provided a viable and effective alternative for treating this condition. However, little is known about the efficacy of this new class of drugs for treating chronic thromboembolic pulmonary hypertension. We aimed to evaluate the safety and efficacy of direct oral anticoagulants in the treatment of chronic thromboembolic pulmonary hypertension. METHODS: A cohort of chronic thromboembolic pulmonary hypertension patients who initiated treatment with direct oral anticoagulants between June 2015 and November 2016 were enrolled in this study. RESULTS: Sixteen patients used rivaroxaban, three used dabigatran and one used apixaban for a mean follow-up of 20.9 months. The mean age was 51 years, and eighteen patients were classified as functional class II/III. Eight patients underwent a pulmonary endarterectomy and exhibited clinical, hemodynamic and functional improvement and currently continue to use direct oral anticoagulants. No episode of venous thromboembolism recurrence was identified during the follow-up period, but there was one episode of major bleeding after a traumatic fall. CONCLUSIONS: Although direct oral anticoagulants appear to be a safe and effective alternative for treating chronic thromboembolic pulmonary hypertension, larger studies are needed to support their routine use.