Francisca Gavilanes

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.

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.

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.

Pulmonary arterial hypertension in schistosomiasis.

Purpose of review Schistosomiasis is one of the most prevalent parasitic diseases in the world, being present in more than 70 countries. Pulmonary hypertension is one of the several chronic complications of schistosomiasis; particularly in developing countries, schistosomiasis-associated pulmonary arterial hypertension might represent one of the most prevalent causes of pulmonary arterial hypertension. Recent findings New epidemiological data reinforce the importance of schistosomiasis in the context of pulmonary hypertension; furthermore, the inflammatory components of the pathophysiology of pulmonary hypertension associated with schistosomiasis have been recently explored, opening the perspective of new targets to be explored. Clinical and hemodynamic features of this particular complication of schistosomiasis, and the role of targeted therapies in this setting, have been better described in recent years. Summary The importance of schistosomiasis-associated pulmonary hypertension is now recognized with better knowledge about its pathophysiology and management. Nevertheless, there is a need for better understanding the predisposal factors (genetic, environmental and so on) for the development of pulmonary hypertension in schistosomiasis as a way to prevent it from occurring. Furthermore, better control programs to decrease disease transmission are still missing, ensuring that we will have to face this devastating complication of schistosomiasis for a long future.

Incidence of spontaneous subdural hematoma in incident cases of pulmonary arterial hypertension: a registry of cases occurring over a five-year period

Imatinib, a tyrosine-kinase inhibitor, has recently been tested to determine its safety and efficacy for the treatment of pulmonary arterial hypertension (PAH), specifically in a study entitled Imatinib in Pulmonary Arterial Hypertension, a Randomized, Efficacy Study (IMPRES).(1) Experimental data suggest that imatinib plays a role in controlling pulmonary vascular remodeling, and this hypothesis had been previously tested in isolated case reports. (2) Nevertheless, the results of the IMPRES, a randomized, double-blind, placebo-controlled trial of imatinib mesylate as add-on therapy for pulmonary arterial hypertension, clearly demonstrated an increase in the occurrence of one severe side effect—spontaneous subdural hematoma.(1) The authors reported eight separate cases in which patients developed spontaneous subdural hematoma: two during the core study (in which 103 patients were enrolled in the treatment group) and six during the open-label, long-term extension study (in which 144 patients opted to be treated with imatinib). All of the patients were using oral anticoagulants at target levels. In patients with chronic myeloid leukemia, the first study to investigate the efficacy of imatinib showed no spontaneous subdural hematoma but did identify thrombocytopenia in 4-24% of the patients, depending on the dosage.(3) After the use of imatinib became widespread, there were some reports of spontaneous bleeding and (more rarely) spontaneous subdural hematoma.(4) A recent review of two randomized controlled trials of targeted therapies in PAH, collectively involving 564 patients, reported the occurrence of two events of spontaneous subdural hematoma among those patients, which translates to an incidence of 0.3% (95% CI: 0.1-1.3).(5) In both of those cases, the patients were using oral anticoagulants. The risk of bleeding in PAH patients was further evaluated in a study involving 218 patients with chronic thromboembolic pulmonary hypertension, connective tissue disease-associated PAH, and idiopathic PAH.(6) All of the patients evaluated in that study were receiving vitamin K antagonists. The authors found that the incidence of bleeding was highest in the patients with connective tissue disease-associated PAH, although central nervous system bleeding occurred in only one case (0.4%). We have recently created a registry of incident cases of PAH treated at a large referral center in Brazil over a five-year period (2008-2013).(7,8) During that period, 178 newly diagnosed cases were included in the registry. During follow-up, two patients presented with spontaneous subdural hematoma, corresponding to an incidence of 1.1% (95% CI: 0.3-4.0): one was a female patient with idiopathic PAH (baseline mean pulmonary artery pressure of 50 mmHg; cardiac output of 4.3 L/min) who was using bosentan, and one was a male patient with schistosomiasis-associated PAH (baseline mean pulmonary artery pressure of 55 mmHg; cardiac output of 2.71 L/min) who was using sildenafil. Neither of those patients were using an oral anticoagulant. Our data provide the first prospectively collected data on the incidence of spontaneous subdural hematoma in patients with PAH managed at a tertiary referral center. Our results underscore the assertion that the events reported in the IMPRES are not trivial and truly represent a major cause for concern regarding the safety of imatinib for use in PAH.