Loss of response to calcium channel blockers after long-term follow-up treatment in patients with idiopathic pulmonary arterial hypertension.

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.

Loss of response to calcium channel blockers after long-term follow-up treatment in patients with idiopathic pulmonary arterial hypertension / Perda de resposta a bloqueadores dos canais de cálcio após acompanhamento prolongado em pacientes com hipertensão arterial pulmonar idiopática

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.

Brazilian Thoracic Society recommendations for the diagnosis and treatment of chronic thromboembolic pulmonary hypertension.

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.

Association between pulmonary artery to aorta diameter ratio with pulmonary hypertension and outcomes in diffuse cystic lung diseases.

ABSTRACT: To investigate the importance of pulmonary vascular measurements on computed tomography (CT) in predicting pulmonary hypertension (PH) and worse outcomes in diffuse cystic lung diseases (DCLDs).We conducted a cross-sectional study of patients with DCLDs. Patients underwent pulmonary function tests, a six-minute walk test (6MWT), chest CT, transthoracic echocardiography, and right heart catheterization. Pulmonary artery (PA) diameter and PA-ascending aorta ratio (PA-Ao ratio) were obtained from CT. Mean pulmonary artery pressure (mPAP) from right heart catheterization was correlated with tomographic, functional, and echocardiographic variables. The association between the PA-Ao ratio with outcomes was determined by Kaplan-Meier curves.Thirty-four patients were included (18 with pulmonary Langerhans cell histiocytosis and 16 with lymphangioleiomyomatosis, mean age 46 ±â€Š9 years). Forced expiratory volume in the first second and lung diffusing capacity for carbon monoxide were 47 ±â€Š20% and 38 ±â€Š21% predicted, respectively. PA diameter and PA-Ao ratio were 29 ±â€Š6 mm and 0.95 ±â€Š0.24, respectively. PA-Ao ratio > 1 occurred in 38.2% of patients. PA-Ao ratio was a good predictor of PH. mPAP correlated best with PA-Ao ratio, PA diameter, oxygen desaturation during six-minute walk test, and echocardiographic variables. Patients with PA-Ao ratio > 1 had greater mPAP, and a higher risk of death or lung transplantation (log-rank, P < .001) than those with PA-Ao ratio ≤ 1.The PA-Ao ratio measured on CT scan has a potential role as a non-invasive tool to predict the presence of PH and as a prognostic parameter in patients with DCLDs.

Mechanisms of Exercise Limitation and Prevalence of Pulmonary Hypertension in Pulmonary Langerhans Cell Histiocytosis.

BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) determines reduced exercise capacity. The speculated mechanisms of exercise impairment in PLCH are ventilatory and cardiocirculatory limitations, including pulmonary hypertension (PH). RESEARCH QUESTION: What are the mechanisms of exercise limitation, the exercise capacity, and the prevalence of dynamic hyperinflation (DH) and PH in PLCH? STUDY DESIGN AND METHODS: In a cross-sectional study, patients with PLCH underwent an incremental treadmill cardiopulmonary exercise test with an evaluation of DH, pulmonary function tests, and transthoracic echocardiography. Those patients with lung diffusing capacity for carbon monoxide (Dlco) < 40% predicted and/or transthoracic echocardiogram with tricuspid regurgitation velocity > 2.5 m/s and/or with indirect PH signs underwent right heart catheterization. RESULTS: Thirty-five patients were included (68% women; mean age, 47 ± 11 years). Ventilatory and cardiocirculatory limitations, impairment suggestive of PH, and impaired gas exchange occurred in 88%, 67%, 29%, and 88% of patients, respectively. The limitation was multifactorial in 71%, exercise capacity was reduced in 71%, and DH occurred in 68% of patients. FEV1 and Dlco were 64 ± 22% predicted and 56 ± 21% predicted. Reduction in Dlco, an obstructive pattern, and air trapping occurred in 80%, 77%, and 37% of patients. FEV1 and Dlco were good predictors of exercise capacity. The prevalence of PH was 41%, predominantly with a precapillary pattern, and mean pulmonary artery pressure correlated best with FEV1 and tricuspid regurgitation velocity. INTERPRETATION: PH is frequent and exercise impairment is common and multifactorial in PLCH. The most prevalent mechanisms are ventilatory, cardiocirculatory, and suggestive of PH limitations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02665546; URL: www.clinicaltrials.gov.

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.

Brazilian Thoracic Society recommendations for the diagnosis and treatment of chronic thromboembolic pulmonary hypertension / Recomendações para o diagnóstico e tratamento da hipertensão pulmonar tromboembólica crônica da Sociedade Brasileira de Pneumologia e Tisiologia

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.

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.

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.

Pulmonary Hypertension in General Cardiology Practice.

The finding of pulmonary hypertension (PH) by echocardiography is common and of concern. However, echocardiography is just a suggestive and non-diagnostic assessment of PH. When direct involvement of pulmonary circulation is suspected, invasive hemodynamic monitoring is recommended to establish the diagnosis. This assessent provides, in addition to the diagnostic confirmation, the correct identification of the vascular territory predominantly involved (arterial pulmonary or postcapillary). Treatment with specific medication for PH (phosphodiesterase type 5 inhibitors, endothelin receptor antagonists and prostacyclin analogues) has been proven effective in patients with pulmonary arterial hypertension, but its use in patients with PH due to left heart disease can even be damaging. In this review, we discuss the diagnosis criteria, how etiological investigation should be carried out, the clinical classification and, finally, the therapeutic recommendations for PH.

Pulmonary Hypertension in General Cardiology Practice / Hipertensão Pulmonar na Prática do Cardiologista

Abstract The finding of pulmonary hypertension (PH) by echocardiography is common and of concern. However, echocardiography is just a suggestive and non-diagnostic assessment of PH. When direct involvement of pulmonary circulation is suspected, invasive hemodynamic monitoring is recommended to establish the diagnosis. This assessent provides, in addition to the diagnostic confirmation, the correct identification of the vascular territory predominantly involved (arterial pulmonary or postcapillary). Treatment with specific medication for PH (phosphodiesterase type 5 inhibitors, endothelin receptor antagonists and prostacyclin analogues) has been proven effective in patients with pulmonary arterial hypertension, but its use in patients with PH due to left heart disease can even be damaging. In this review, we discuss the diagnosis criteria, how etiological investigation should be carried out, the clinical classification and, finally, the therapeutic recommendations for PH.

Resumo O achado de hipertensão pulmonar (HP) em avaliação ecocardiográfica é frequente e preocupante. No entanto, o ecocardiograma é apenas um exame sugestivo e não diagnóstico de HP. Quando se suspeita de acometimento direto da circulação pulmonar, está indicada medida hemodinâmica invasiva para estabelecer o diagnóstico. Essa avaliação permite, além da confirmação diagnóstica, a correta identificação do território vascular predominantemente acometido (arterial pulmonar ou pós-capilar). O tratamento com as medicações específicas de HP (inibidores da fosfodiestarese 5, antagonistas do receptor de endotelina, análogos da prostaciclina e estimulador da guanilil ciclase solúvel) é comprovadamente eficaz para pacientes com hipertensão arterial pulmonar, mas seu uso em pacientes com HP decorrente de doença cardíaca de câmaras esquerdas pode até mesmo ser prejudicial. Discutiremos nesta revisão o critério diagnóstico, a maneira de proceder a investigação etiológica, a classificação clínica e, finalmente, as recomendações terapêuticas na HP.

Reperfusion in acute pulmonary thromboembolism.

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.

Reperfusion in acute pulmonary thromboembolism / Reperfusão no tromboembolismo pulmonar agudo

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.

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.

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.

New anticoagulants for the treatment of venous thromboembolism / Os novos anticoagulantes no tratamento do tromboembolismo venoso

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.

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.

Pulmonary arterial hypertension in the southern hemisphere: results from a registry of incident Brazilian cases.

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.

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.