Carlos Jardim

Splenectomy and chronic thromboembolic pulmonary hypertension

Background: An increased prevalence of splenectomy has been reported in patients with idiopathic pulmonary arterial hypertension. Examination of small pulmonary arteries from these subjects has revealed multiple thrombotic lesions, suggesting that thrombosis may contribute to this condition. Based on these findings, we hypothesised that splenectomy could be a risk factor for chronic thromboembolic pulmonary hypertension (CTEPH), a condition defined by the absence of thrombus resolution after acute pulmonary embolism that causes sustained obstruction of the pulmonary arteries and subsequent pulmonary hypertension. Methods: The medical history, clinical characteristics, thrombotic risk factors and haemodynamics of 257 patients referred for CTEPH between 1989 and 1999 were reviewed. In a case-control study the prevalence of splenectomy in patients with CTEPH was compared with that of patients evaluated during the same period for idiopathic pulmonary hypertension (n = 276) or for lung transplantation in other chronic pulmonary conditions (n = 180). Results: In patients with CTEPH, 8.6% (95% CI 5.2 to 12.0) had a history of splenectomy compared with 2.5% (95% CI 0.7 to 4.4) and 0.56% (95% CI 0 to 1.6) in cases of idiopathic pulmonary arterial hypertension and other chronic pulmonary conditions, respectively (p<0.01). Conclusion: Splenectomy may be a risk factor for chronic thromboembolic pulmonary hypertension.

Cardiopulmonary Manifestations of Hepatosplenic Schistosomiasis

Background— Schistosomiasis is a highly prevalent disease with >200 million infected people. Pulmonary hypertension is one of the pulmonary manifestations in this disease, particularly in its hepatosplenic presentation. The aim of this study was to determine the prevalence of pulmonary hypertension in schistosomiasis patients with the hepatosplenic form of the disease. Methods and Results— All patients with hepatosplenic schistosomiasis followed up at the gastroenterology department of our university hospital underwent echocardiographic evaluation to search for pulmonary hypertension. Patients presenting with systolic pulmonary artery pressure >40 mm Hg were further evaluated through right heart catheterization. Our study showed an 18.5% prevalence of patients with elevated systolic pulmonary artery pressure at echocardiography. Invasive hemodynamics confirmed the presence of pulmonary hypertension in 7.7% (95% confidence interval, 3.3 to 16.7) of patients, with a prevalence of precapillary (arterial) pulmonary hypertension of 4.6% (95% confidence interval, 1.5 to 12.7). Conclusions— Our study reinforces the role of echocardiography as a screening tool in the investigation of pulmonary hypertension, together with the need for invasive monitoring for a proper diagnosis. We conclude that hepatosplenic schistosomiasis may account for one of the most prevalent forms of pulmonary hypertension worldwide, justifying the development of further studies to evaluate the effect of specific pulmonary hypertension treatment in this particular form of the disease.

Características clínicas dos pacientes com hipertensão pulmonar em dois centros de referência em São Paulo

OBJECTIVES Describe the clinical profile of PH patients from two pulmonary hypertension centers. METHODS Retrospective chart analysis. RESULTS One hundred and twenty three PH patients were included in the study; 62% of these presented functional class III or IV (NYHA). Mean right ventricle systolic pressure (RVSP) was 83.48+/-24.61 mmHg. There was no correlation between functional class and RVSP. About 50% of the patients were diagnosed as IPAH; 30% as pulmonary hypertension associated to schistosomiasis; 10% as PH associated to connective tissue diseases. Mean time of dyspnea until diagnosis was variable with no correlation with functional class (p>0.05). No difference was found in the clinical presentation in spite of the diverse etiologies. CONCLUSION Based upon our findings, we stressed the need for an active investigation of PH patients prior to administration of any therapeutic alternative. We emphasized that a better understanding of PH related to schistosomiasis is needed due to the high prevalence of this condition among PH patients as shown in the Brazilian population.

Effect of bosentan treatment on surrogate markers in pulmonary arterial hypertension.

ABSTRACT Objective: The aim of this study was to evaluate the effect of the oral dual ETA/ETB receptor antagonist bosentan on different surrogate markers in patients with pulmonary arterial hypertension (PAH). Design and setting: Prospective, open label, uncontrolled study in a University Hospital in Brazil. Population: Fifteen PAH patients (11 females) with mean age of 40 ± 11 years (5 in WHO functional class II, 10 in class III). Methods: All patients were investigated at baseline and after 16 weeks of bosentan treatment. We used the following surrogate markers for patients’ evaluation: 6‐min walk test, quality of life questionnaire (Short Form SF‐36) and N‐terminal proBNP (B type natriuretic peptide) fraction levels in blood. Results: Between the evaluation at baseline and week 16, the 6‐min walk test distance changed from 396 ± 135 to 434 ± 137 m ( p < 0.05). Each of the eight domains of the SF‐36 was significantly improved. Mean NT‐proBNP levels were decreased from a mean of 1670 pg/mL to 1010 pg/mL ( p = 0.01). Conclusion: The study suggests that bosentan treatment results in the improvement of different kinds of surrogate markers independently of their specificity to reflect functional capacity, quality of life and myocardial stress. It is concluded that the combined use of these different markers may be an alternative endpoint for future short duration clinical trials.

Validação de um protocolo para o teste de caminhada de seis minutos em esteira para avaliação de pacientes com hipertensão arterial pulmonar

OBJETIVO: Elaborar e validar um protocolo para teste de caminhada de seis minutos em esteira (TC6est) para a avaliacao de pacientes com hipertensao arterial pulmonar (HAP). METODOS: A populacao do estudo foi composta por 73 pacientes com HAP diagnosticados atraves de cateterismo cardiaco direito, com ou sem inalacao de NO. Todos os pacientes realizaram um TC6 em solo e tres TC6est baseados em um protocolo de incremento de velocidade pre-determinado e intercalados por um periodo de repouso. Os pacientes que haviam realizado o teste hemodinâmico com inalacao de NO realizaram o terceiro TC6est com a inalacao da mesma dose de NO utilizada durante o cateterismo. RESULTADOS: Os resultados mostraram uma correlacao da distância caminhada no TC6est com os dados hemodinâmicos, assim como com a classe funcional e com a distância caminhada no solo. Alem disso, a distância percorrida no TC6est apresentou uma correlacao significativa com a sobrevida, confirmando, portanto, sua correlacao com a gravidade da doenca. A inalacao de NO durante o TC6est levou a variacoes compativeis com as variacoes hemodinâmicas frente a mesma dose de NO, sugerindo que o protocolo em questao pode refletir o efeito de intervencoes terapeuticas. CONCLUSOES: Concluimos que a distância percorrida no TC6est e um marcador funcional e prognostico na avaliacao de rotina de pacientes com HAP.

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.

Diagnóstico e tratamento da hipertensão pulmonar: uma atualização

Over the last five years, knowledge in the field of pulmonary hypertension has grown consistently and significantly. On the basis of various clinical studies showing the usefulness of new diagnostic tools, as well as the efficacy of new medications and drug combinations, new diagnostic and treatment algorithms have been developed. Likewise, in order to simplify the clinical management of patients, the classification of pulmonary hypertension has been changed in an attempt to group the various forms of pulmonary hypertension in which the diagnostic and therapeutic approaches are similar. The objective of this review was to discuss these modifications, based on the 2005 Brazilian guidelines for the management of pulmonary hypertension, emphasizing what has been added to the international guidelines.Over the last five years, knowledge in the field of pulmonary hypertension has grown consistently and significantly. On the basis of various clinical studies showing the usefulness of new diagnostic tools, as well as the efficacy of new medications and drug combinations, new diagnostic and treatment algorithms have been developed. Likewise, in order to simplify the clinical management of patients, the classification of pulmonary hypertension has been changed in an attempt to group the various forms of pulmonary hypertension in which the diagnostic and therapeutic approaches are similar. The objective of this review was to discuss these modifications, based on the 2005 Brazilian guidelines for the management of pulmonary hypertension, emphasizing what has been added to the international guidelines.

Immunopathological aspects of schistosomiasis-associated pulmonary arterial hypertension

OBJECTIVES Pulmonary hypertension is a lethal complication of chronic hepatosplenic schistosomiasis. Little is known of the underlying (immuno-)histopathological characteristics of lung vasculopathy. METHODS We characterized vasculopathy and inflammation in lung tissue of 10 patients with Schistosomiasis-associated PH (SCH-PH) in comparison to 22 idiopathic pulmonary arterial hypertension (IPAH) patients and 10 normal controls. SCH-PH cases were younger than controls. RESULTS Plexiform lesions and/or angiomatoid lesions were found in 10/10 SCH-PH, and 19/22 IPAH patients (χ² p = 0.22). Lung granulomas with Schistosoma eggs were found in 2/10 of SCH-PH cases. PAH cases had increased peri-arterial density of CD3+ T cells, chymase+ and tryptase+ mast cells when compared to controls (p ≤ 0.047). SCH-PH showed increased density of CD4+ cells when compared to controls (p = 0.025), paralleled by an increased density of dendritic CD83+ cells when compared to both controls and IPAH patients (p ≤ 0.022). CONCLUSION Both SCH-PH and IPAH feature plexogenic arteriopathy and increased periarterial T cell and mast cell density. SCH-PH and IPAH differ only with respect to the density of dendritic CD83+ cells. These findings imply ongoing antigenic stimulation in SCH-PH, yet a pattern of pulmonary vasculopathy similar to IPAH, suggestive of a final common pathway in their pathogenesis of PAH.

Lesão por inalação de fumaça

A lesao inalatoria e hoje a principal causa de morte nos pacientes queimados, motivo pelo qual se justifica o grande numero de estudos publicados sobre o assunto. Os mecanismos envolvidos na genese da lesao inalatoria envolvem tanto os fatores de acao local quanto os de acao sistemica, o que acaba por aumentar muito as repercussoes da lesao. Atualmente, buscam-se ferramentas que permitam o diagnostico cada vez mais precoce da lesao inalatoria e ainda estrategias de tratamento que minimizem as consequencias da lesao ja instalada. Esta revisao aborda os mecanismos fisiopatologicos, os metodos diagnosticos e as estrategias de tratamento dos pacientes vitimas de lesao inalatoria. Ressalta ainda as perspectivas terapeuticas em desenvolvimento.

Tadalafil para o tratamento da hipertensão arterial pulmonar idiopática

Phosphodiesterase inhibitors like sildenafil have already been shown to improve functional capacity and hemodynamics in the treatment of pulmonary arterial hypertension. Few studies address the effects of new phosphodiesterase inhibitors as tadalafil. We report a case of a patient with idiopathic pulmonary arterial hypertension in functional class IV (New York Heart Association) with significant response to treatment with tadalafil.