ABSTRACT Idiopathic pulmonary arterial hypertension (PAH) patients with a positive response to acute vasodilator challenge and a clinical response to calcium channel blockers (CCBs) for at least one year are traditionally designated true responders. Nevertheless, little is known about a sustained response to CCBs over longer periods of time. We evaluated the loss of response to CCBs after long-term treatment in a cohort of idiopathic PAH patients previously classified as being true responders. Our data suggest that idiopathic PAH patients can lose clinical response to CCBs even after one year of clinical stability, reinforcing the need for constant multidimensional reevaluation to assess the need for targeted PAH therapies and to classify these patients correctly.

RESUMO Pacientes com hipertensão arterial pulmonar (HAP) idiopática com resposta positiva ao teste de vasorreatividade aguda e resposta clínica a bloqueadores dos canais de cálcio (BCC) durante no mínimo um ano são tradicionalmente denominados “respondedores verdadeiros”. No entanto, pouco se sabe sobre a manutenção da resposta a BCC durante períodos mais longos. Avaliamos a perda de resposta a BCC após tratamento prolongado em uma coorte de pacientes com HAP idiopática previamente considerados respondedores verdadeiros. Nossos dados sugerem que pacientes com HAP idiopática podem deixar de apresentar resposta clínica a BCC mesmo depois de um ano de estabilidade clínica, reforçando a necessidade de reavaliação multidimensional constante para avaliar a necessidade de terapias específicas para HAP e classificar esses pacientes corretamente.

RESUMO A hipertensão pulmonar tromboembólica crônica (HPTEC) é uma doença grave e debilitante, causada pela oclusão do leito arterial pulmonar por êmbolos hemáticos e por material fibroso induzido pela presença desses êmbolos. Essa oclusão eleva a resistência vascular e, por consequência, a pressão do território arterial pulmonar, caracterizando a presença de hipertensão pulmonar. Esse aumento da carga imposta ao ventrículo direito leva a progressiva insuficiência do mesmo e, finalmente, ao óbito. No entanto, ao contrário das outras formas de hipertensão pulmonar, a HPTEC possui uma particularidade muito significativa: a existência de tratamento potencialmente curativo através da tromboendarterectomia pulmonar. Dessa forma, o objetivo primordial do manejo deve ser a avaliação do potencial cirúrgico do paciente em um centro de referência em HPTEC. Entretanto, nem todos os pacientes podem ser submetidos à cirurgia. Para esses pacientes outras alternativas terapêuticas viáveis são a angioplastia de artérias pulmonares e o tratamento farmacológico. Nestas recomendações, discutir-se-ão as bases fisiopatológicas para o surgimento de HPTEC, a partir da embolia pulmonar aguda, bem como o quadro clínico apresentado pelo paciente, o algoritmo diagnóstico a ser seguido e as alternativas terapêuticas disponíveis.

ABSTRACT Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious and debilitating disease caused by occlusion of the pulmonary arterial bed by hematic emboli and by the resulting fibrous material. Such occlusion increases vascular resistance and, consequently, the pressure in the region of the pulmonary artery, which is the definition of pulmonary hypertension. The increased load imposed on the right ventricle leads to its progressive dysfunction and, finally, to death. However, CTEPH has a highly significant feature that distinguishes it from other forms of pulmonary hypertension: the fact that it can be cured through treatment with pulmonary thromboendarterectomy. Therefore, the primary objective of the management of CTEPH should be the assessment of patient fitness for surgery at a referral center, given that not all patients are good candidates. For the patients who are not good candidates for pulmonary thromboendarterectomy, the viable therapeutic alternatives include pulmonary artery angioplasty and pharmacological treatment. In these recommendations, the pathophysiological bases for the onset of CTEPH, such as acute pulmonary embolism and the clinical condition of the patient, will be discussed, as will the diagnostic algorithm to be followed and the therapeutic alternatives currently available.

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.

RESUMO O tromboembolismo pulmonar (TEP) agudo é uma condição altamente prevalente (104-183 por 100.000 pessoas-ano) e potencialmente fatal. Aproximadamente 20% dos pacientes com TEP agudo apresentam-se hipotensos, sendo considerados pacientes com alto risco de morte. Nesses casos, a necessidade de reperfusão pulmonar imediata é mandatória para reduzir a pós-carga do ventrículo direito e restaurar a condição hemodinâmica do paciente. Visando a redução da resistência vascular pulmonar no TEP agudo e, por consequência, a melhora na função ventricular direita, estratégias de reperfusão pulmonar foram desenvolvidas com passar do tempo e vêm sendo muito estudadas nos últimos anos. Avanços na indicação e no uso de trombolíticos sistêmicos, reperfusão pulmonar via abordagem endovascular ou abordagem cirúrgica clássica no TEP agudo são os focos desta revisão.

ABSTRACT Acute pulmonary thromboembolism (APTE) is a highly prevalent condition (104-183 cases per 100,000 person-years) and is potentially fatal. Approximately 20% of patients with APTE are hypotensive, being considered at high risk of death. In such patients, immediate lung reperfusion is necessary in order to reduce right ventricular afterload and to restore hemodynamic stability. To reduce pulmonary vascular resistance in APTE and, consequently, to improve right ventricular function, lung reperfusion strategies have been developed over time and widely studied in recent years. In this review, we focus on advances in the indication and use of systemic thrombolytic agents, as well as lung reperfusion via endovascular and classical surgical approaches, in APTE.

O tromboembolismo venoso (TEV) está entre as principais causas de morte por doenças cardiovasculares no mundo, atrás apenas do infarto agudo do miocárdio e do acidente vascular cerebral. O TEV possui espectro de apresentação que vai desde a trombose venosa profunda até o tromboembolismo pulmonar agudo, de acordo com gravidade crescente de acometimento, sendo seu tratamento baseado na anticoagulação plena dos pacientes. Há muitas décadas, sabe-se que a anticoagulação interfere diretamente na mortalidade associada ao TEV. Até o início deste século a terapia anticoagulante se baseava no uso de heparina, em suas formas não fracionada ou de baixo peso molecular, e de antagonistas da vitamina K, principalmente a varfarina. Ao longo das últimas décadas, foram desenvolvidos novas classes de medicamentos anticoagulantes, inibidores do fator Xa e inibidores diretos da trombina, que mudaram significativamente o arsenal terapêutico do TEV, em função de suas características de eficácia e segurança em relação ao tratamento convencional, sendo o foco principal de esta revisão avaliar seu papel neste contexto clínico.

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.