Atualização no Tratamento da Hipertensão Arterial Pulmonar / Update on the Treatment of Pulmonary Arterial Hypertension

Resumo Muitos avanços ocorreram nas últimas décadas na terapêutica da hipertensão arterial pulmonar (HAP), uma doença grave, progressiva, incurável e potencialmente fatal. Para seu tratamento adequado, são fundamentais o diagnóstico hemodinâmico e a classificação de sua etiologia, em que várias delas (colagenoses, hipertensão portal, cardiopatia congênitas, esquistossomose) requerem medidas específicas, além do tratamento farmacológico característico para HAP. O tratamento com fármacos-alvo para HAP baseia-se em produtos farmacêuticos que interferem em três vias fisiopatológicas moleculares: da prostaciclina, da endotelina e do óxido nítrico. Tais fármacos apresentam múltiplas apresentações (oral, endovenosa, subcutânea e inalatória) e mudaram a história da HAP. Essas medicações e suas estratégias de uso, assim como particularidades das diferentes formas de HAP, são o foco desta revisão.

Abstract In the last decades, important advances have been made in the treatment of pulmonary arterial hypertension (PAH), a severe, progressive, incurable, and potentially fatal disease. For an adequate therapy, correct hemodynamic diagnosis and etiology classification are fundamental. Many etiologies - rheumatic disease, portal hypertension, congenital heart diseases, schistosomiasis - require specific measures, in addition to drug therapy for PAH. The specific therapy for PAH is based on medications that act on three pathophysiological pathways - prostacyclin, endothelin, and nitric oxide pathways. These drugs have multiple presentations (oral, intravenous, subcutaneous, and inhaled) and have changed the history of PAH. This review presents an overview of drug therapy strategies and different forms and peculiarities of PAH.

Lung cavities in chronic thromboembolic pulmonary hypertension

OBJECTIVES: Chronic thromboembolic pulmonary hypertension (CTEPH) is a unique form of pulmonary hypertension (PH) that arises from obstruction of the pulmonary vessels by recanalized thromboembolic material. CTEPH has a wide range of radiologic presentations. Commonly, it presents as main pulmonary artery enlargement, peripheral vascular obstructions, bronchial artery dilations, and mosaic attenuation patterns. Nevertheless, other uncommon presentations have been described, such as lung cavities. These lesions may be solely related to chronic lung parenchyma ischemia but may also be a consequence of concomitant chronic infectious conditions. The objective of this study was to evaluate the different etiologies that cause lung cavities in CTEPH patients. METHODS: A retrospective data analysis of the medical records of CTEPH patients in a single reference PH center that contained or mentioned lung cavities was conducted between 2013 and 2016. RESULTS: Seven CTEPH patients with lung cavities were identified. The cavities had different sizes, locations, and wall thicknesses. In two patients, the cavities were attributed to pulmonary infarction; in 5 patients, an infectious etiology was identified. CONCLUSION: Despite the possibility of being solely associated with chronic lung parenchyma ischemia, most cases of lung cavities in CTEPH patients were associated with chronic granulomatous diseases, reinforcing the need for active investigation of infectious agents in this setting.

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.

Left ventricular dysfunction in patients with suspected pulmonary arterial hypertension / Disfunção ventricular esquerda em pacientes com suspeita de hipertensão arterial pulmonar

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. .

OBJETIVO: Avaliar o papel do cateterismo de câmaras cardíacas direitas no diagnóstico de hipertensão arterial pulmonar (HAP). MÉTODOS: Entre 2008 e 2013, foram avaliadas as características clínicas, funcionais e hemodinâmicas de todos os pacientes que realizaram cateterismo cardíaco direito por suspeita de HAP em nosso laboratório, depois de afastada a presença de disfunção ventricular esquerda (DVE) grave, de alterações significativas nos testes de função pulmonar ou de resultados de cintilografia pulmonar de inalação/perfusão compatíveis com tromboembolismo pulmonar crônico. RESULTADOS: Durante o período de estudo, 384 pacientes foram submetidos a cateterismo cardíaco diagnóstico. A hipertensão pulmonar (HP) foi confirmada em 302 pacientes (78,6%). A média de idade desses pacientes foi de 48,7 anos. Os pacientes sem HP apresentaram melhor perfil hemodinâmico e menores níveis de peptídio natriurético do tipo B que aqueles diagnosticados com HP. No entanto, 13,8% dos pacientes sem HP apresentavam-se em classe funcional III/IV do New York Heart Association. Dos 218 pacientes que cumpriam os critérios de inclusão, 40 (18,3%) e 178 (81,7%) foram diagnosticados como portadores de HP associada à DVE (HP-DVE) e HAP, respectivamente. O grupo HP-DVE tinha idade significativamente mais avançada que aqueles com HAP (p < 0,0001). CONCLUSÕES: A diferença proporcional entre os grupos HAP e HP-DVE foi bastante significativa, considerando a inexistência de sinais ecocardiográficos sugestivos de DVE importante como parte da investigação que antecedeu ...

Avaliação do ventrículo direito nos pacientes com hipertensão pulmonar / Right ventricle evaluation in pulmonary hypertension

Introdução: A fração de ejeção do ventrículo direito (FEVD) é um importante fator prognóstico em pacientes com hipertensão pulmonar (HP), porém a sua medida é complicada e demorada devido à complexidade anatômica do ventrículo direito (VD). O TAPSE (Tricuspid Annular Plane Systolic Excursion) é um bom índice da FEVD, mas ele avalia apenas o componente longitudinal da contração ventricular direita. A RVFAC (Right Ventricular Fractional Area Change) parece ser um melhor índice da FEVD por incluir os componentes longitudinal e transversal da contração ventricular direita. O objetivo deste estudo foi avaliar a performance da RVFAC de acordo com a gravidade do acometimento hemodinâmico em dois grupos distintos de pacientes portadores de HP pré-capilar: hipertensão arterial pulmonar (HAP) e tromboembolismo pulmonar crônico hipertensivo (TEPCH). Métodos: 62 pacientes realizaram cateterismo cardíaco direito e ressonância magnética cardíaca em ±72h. As áreas sistóica e diastólica finais do ventrículo direito (ASFVD, ADFVD), a área diastólica final do ventrículo esquerdo (ADFVE) e o TAPSE foram medidos nas imagens de quatro cavidades. A RVFAC (ADFVD-ASFVD/ADFVD) e a relação entre as áreas diastólica finais ventriculares (ADFVD/ADFVE) foram calculadas. Os diâmetros entre as paredes livre e septal (dL-S) e antero-posterior (dA-P) do ventículo esquerdo (VE) foram medidos nas imagens em eixo curto e o índice de excentricidade do VE (IE) foi calculado (=dA-P/dL-S). A FEVD foi calculada a partir de imagens consecutivas de 6mm no eixo curto. . Resultados: A população tinha 58 anos em média, a maioria era do sexo feminino e estava em classe funcional III, 23 tinham HAP e 39 TEPCH. A FEVD apresentou correlações fracas com as medidas hemodinâmicas de sobrecarga e de função do VD. A RVFAC apresentou melhor correlação (R2=0,65, p < 0,001) do que o TAPSE (R2=0,35, p<0,001) com a FEVD e melhor capacidade para estimar FEVD<35% do que o TAPSE (TAPSE: AUC 0,73 e RVFAC: AUC 0,93,...

Introduction: The right ventricular ejection fraction (RVEF) is a surrogate marker in pulmonary hypertension (PH), but its measurement is complicated and time consuming. The TAPSE (Tricuspid Annular Plane Systolic Excursion) is a good index of RVEF, though it measures only the longitudinal component of right ventricular contraction. The RVFAC (Right Ventricular Fractional Area Change) seems to be a better index of RVEF because it takes into account the longitudinal and the transversal components of right ventricular contraction. The aim of our study was to evaluate the RVFAC performance according to hemodynamic severity in two groups of patients with PH: pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Methos: Sixty-two patients with PAH and CTEPH underwent right heart catheterization and cardiac MR in a 72-hour delay. The right and left ventricle end diastolic areas (RVEDA, LVEDA), the right ventricle end systolic area (RVESA) and TAPSE were measured in the four chamber view. The RVFAC (=RVEDARVESA/RVEDA) and the RVEDA/LVEDA relationship were calculated. The diameter between the left ventricle (LV) free wall and the septum (dF-S) and the diameter between the LV anterior and posterior walls (dA-P) were measured and the LV eccentricity index (EI) was calculated (=dA-P/dF-S). The RVEF was calculated by using 6 mm RV short axis cines. Results: The population had mean age of 58 years with female majority, most of the patients were in functional class III, 23 had PAH and 39 CTEPH. The RVEF was weakly correlated to the hemodynamic variables of RV afterload and function. The RVFAC was more strongly correlated to RVEF (R2=0.65, p<0.001) than TAPSE (R2=0.35, p<0.001). RVEF<35% was better predicted by RVFAC than TAPSE (TAPSE: AUC 0.73 and RVFAC: AUC 0.93, p=0.0065). We divided the population by the median of the pulmonary vascular resistance (PVR) and we observed that in the group with worse hemodynamic severity...

O papel dos exames de imagem na avaliação da circulação pulmonar / The role of imaging techniques in the assessment of pulmonary circulation

O conhecimento sobre a estrutura e a função da circulação pulmonar evoluiu sensivelmente nas últimas décadas. A utilização de exames de imagem não invasivos para a avaliação da anatomia e da função dos vasos pulmonares e do coração ganhou ainda mais importância com o advento de tratamentos até então indisponíveis. Além do auxílio para o diagnóstico, as informações obtidas têm se mostrado fundamentais para o estabelecimento de prognósticos e como parâmetro de sucesso dos tratamentos. A presente revisão discute os diversos métodos que podem ser utilizados para a avaliação da circulação pulmonar por imagens existentes nos dias de hoje, desde técnicas amplamente disponíveis e de relativa baixa complexidade técnica, como a radiografia de tórax, até métodos complexos e promissores, como a tomografia de impedância elétrica.

Knowledge of the structure and function of pulmonary circulation has evolved considerably in the last few decades. The use of non-invasive imaging techniques to assess the anatomy and function of the pulmonary vessels and heart has taken on added importance with the recent advent of novel therapies. Imaging findings not only constitute a diagnostic tool but have also proven to be essential for prognosis and treatment follow-up. This article reviews the myriad of imaging methods currently available for the assessment of pulmonary circulation, from the simple chest X-ray to techniques that are more complex and promising, such as electrical impedance tomography.

Diagnóstico e tratamento da hipertensão pulmonar: uma atualização / Diagnosis and treatment of pulmonary hypertension: an update

Ao longo dos últimos cinco anos, o conhecimento na área de hipertensão pulmonar evoluiu de forma consistente e significativa. Novos algoritmos diagnósticos e de tratamento foram desenvolvidos com base no resultado de diversos estudos clínicos que evidenciaram a utilidade de novas ferramentas, assim como a eficácia de novos medicamentos e de combinações. Da mesma forma, a classificação da hipertensão pulmonar evoluiu, na tentativa de agrupar as diferentes formas de hipertensão pulmonar que apresentam abordagens diagnósticas e terapêuticas semelhantes a fim de facilitar a condução clínica dos pacientes. Esta revisão visa discutir cada uma dessas modificações, tendo por base as diretrizes brasileiras para manejo da hipertensão pulmonar de 2005, ressaltando aquilo que foi acrescentado às diretrizes internacionais.

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.