Risk assessment validation in patients with pulmonary arterial hypertension: Data from a Southern Brazil registry (RESPHIRAR study).

Pulmonary arterial hypertension (PAH) is a severe and progressive disease characterized by increased pulmonary vascular resistance, ultimately leading to right heart failure and death. Registries are a valuable tool in the research of rare conditions such as PAH. Moreover, the risk assessment strategy has been validated in European and North American registries and has been reported to provide an accurate prediction of mortality and the clinical advantage of reaching low-risk status. However, there is no available data from Brazil. Thus, the aim of the present study was to describe the characteristics of a sample of PAH from Southern Brazil and to retrospectively validate the risk assessment at our population. The RESPHIRAR is a retrospective and multicentric registry on pulmonary hypertension. With a join collaboration from nine centers in Southern Brazil, demographics, clinical presentation, and hemodynamics data of PAH were collected between 2007 and 2017. Moreover, the REVEAL 2.0 and REVEAL 2.0 Lite risk assessments were validated in our population. Overall, 370 PAH patients were included in the present study. Patients were predominantly female (78.5%) and had a mean age of 41.8 ± 18.8 years. Most patients (33.4%) had idiopathic PAH, 30.2% had PAH associated with congenital heart disease, and 23.5% had PAH associated with connective tissue disease. The low-risk group showed significantly lower mortality than the intermediated- or high-risk group at diagnosis (p < 0.05). In conclusion, our data suggest that REVEAL 2.0 and REVEAL 2.0 Lite risk assessments can predict mortality risk in PAH patients in Southern Brazil.

Soluble Guanylate Cyclase Stimulators (Riociguat) in Pulmonary Hypertension: Data from Real-Life Clinical Practice in a 3-Year Follow-Up. / Estimuladores de Guanilato Ciclase Solúvel (Riociguate) na Hipertensão Pulmonar: Dados da Prática Clínica Real em 3 Anos de Acompanhamento.

BACKGROUND: Pulmonary hypertension (PH) is a rare and complex disease with poor prognosis, which requires lifelong treatment. OBJECTIVE: To describe 3-year follow-up real-life data on treatment with soluble guanylate cyclase stimulators (Riociguat) of patients with PH, measuring current risk assessment parameters. METHODS: This study retrospectively collected clinical and epidemiological data of patients with PH of group 1 (pulmonary arterial hypertension) and group 4 (chronic thromboembolic PH). Non-invasive and invasive parameters corresponding to the risk assessment were analyzed at baseline and follow-up. Statistical analyses were performed using the SPSS 18.0 software, and p-values < 0.050 were considered statistically significant. RESULTS: In total, 41 patients receiving riociguat were included in the study. Of them, 31 had already completed 3 years of treatment and were selected for the following analysis. At baseline, 70.7% of patients were in WHO functional class III or IV. After 3 years of treatment, the WHO functional class significantly improved in all patients. In addition, the median of the 6-minute walk test (6MWT) significantly increased from 394 ± 91 m at baseline to 458 ± 100 m after 3 years of follow-up (p= 0.014). The three-year survival rate was 96.7%. CONCLUSION: In our real-life cohort, most patients with PH treated with riociguat showed stable or improved risk parameters, especially in the 6MWT, at 3 years of follow-up.

FUNDAMENTO: A hipertensão pulmonar (HP) é uma doença rara e complexa com prognóstico ruim, que exige tratamento pela vida toda. OBJETIVO: Descrever dados de 3 anos de acompanhamento da vida real sobre o tratamento com estimuladores de guanilato ciclase solúvel (Riociguate) de pacientes com HP, medindo parâmetros atuais de avaliação de risco. MÉTODOS: Coletamos dados clínicos e epidemiológicos retrospectivamente de pacientes com HP do grupo 1 (hipertensão arterial pulmonar) e do grupo 4 (HP tromboembólica crônica). Parâmetros não invasivos e invasivos correspondentes à avaliação de risco foram analisados na linha de base e no acompanhamento. Foram realizadas análises estatísticas usando o software SPSS 18.0, e os p-valores <0,050 foram considerados estatisticamente significativos. RESULTADOS: No total, 41 pacientes tratados com riociguate foram incluídos no estudo. Entre eles, 31 já concluíram 3 anos de tratamento e foram selecionados para a seguinte análise. Na linha de base, 70,7% dos pacientes estavam nas classes funcionais III ou IV da OMS. Depois de 3 anos de tratamento, a classe funcional da OMS melhorou significativamente em todos os pacientes. Além disso, a mediana do teste de caminhada de 6 minutos (TC6M) aumentou significativamente de 394 ± 91 m na linha de base para 458 ± 100 m após 3 anos de acompanhamento (p= 0,014). O índice de sobrevida após três anos foi de 96,7%. CONCLUSÃO: Em nossa coorte de vida real, a maioria dos pacientes com HP tratados com riociguate demonstraram parâmetros de risco estáveis ou melhores, especialmente no TC6M, aos 3 anos de acompanhamento.

Estimuladores de Guanilato Ciclase Solúvel (Riociguate) na Hipertensão Pulmonar: Dados da Prática Clínica Real em 3 Anos de Acompanhamento / Soluble Guanylate Cyclase Stimulators (Riociguat) in Pulmonary Hypertension: Data from Real-Life Clinical Practice in a 3-Year Follow-Up

Resumo Fundamento A hipertensão pulmonar (HP) é uma doença rara e complexa com prognóstico ruim, que exige tratamento pela vida toda. Objetivo Descrever dados de 3 anos de acompanhamento da vida real sobre o tratamento com estimuladores de guanilato ciclase solúvel (Riociguate) de pacientes com HP, medindo parâmetros atuais de avaliação de risco. Métodos Coletamos dados clínicos e epidemiológicos retrospectivamente de pacientes com HP do grupo 1 (hipertensão arterial pulmonar) e do grupo 4 (HP tromboembólica crônica). Parâmetros não invasivos e invasivos correspondentes à avaliação de risco foram analisados na linha de base e no acompanhamento. Foram realizadas análises estatísticas usando o software SPSS 18.0, e os p-valores <0,050 foram considerados estatisticamente significativos. Resultados No total, 41 pacientes tratados com riociguate foram incluídos no estudo. Entre eles, 31 já concluíram 3 anos de tratamento e foram selecionados para a seguinte análise. Na linha de base, 70,7% dos pacientes estavam nas classes funcionais III ou IV da OMS. Depois de 3 anos de tratamento, a classe funcional da OMS melhorou significativamente em todos os pacientes. Além disso, a mediana do teste de caminhada de 6 minutos (TC6M) aumentou significativamente de 394 ± 91 m na linha de base para 458 ± 100 m após 3 anos de acompanhamento (p= 0,014). O índice de sobrevida após três anos foi de 96,7%. Conclusão Em nossa coorte de vida real, a maioria dos pacientes com HP tratados com riociguate demonstraram parâmetros de risco estáveis ou melhores, especialmente no TC6M, aos 3 anos de acompanhamento.

Abstract Background Pulmonary hypertension (PH) is a rare and complex disease with poor prognosis, which requires lifelong treatment. Objective To describe 3-year follow-up real-life data on treatment with soluble guanylate cyclase stimulators (Riociguat) of patients with PH, measuring current risk assessment parameters. Methods This study retrospectively collected clinical and epidemiological data of patients with PH of group 1 (pulmonary arterial hypertension) and group 4 (chronic thromboembolic PH). Non-invasive and invasive parameters corresponding to the risk assessment were analyzed at baseline and follow-up. Statistical analyses were performed using the SPSS 18.0 software, and p-values < 0.050 were considered statistically significant. Results In total, 41 patients receiving riociguat were included in the study. Of them, 31 had already completed 3 years of treatment and were selected for the following analysis. At baseline, 70.7% of patients were in WHO functional class III or IV. After 3 years of treatment, the WHO functional class significantly improved in all patients. In addition, the median of the 6-minute walk test (6MWT) significantly increased from 394 ± 91 m at baseline to 458 ± 100 m after 3 years of follow-up (p= 0.014). The three-year survival rate was 96.7%. Conclusion In our real-life cohort, most patients with PH treated with riociguat showed stable or improved risk parameters, especially in the 6MWT, at 3 years of follow-up.

Parasympathetic modulation withdrawal improves functional capacity in pulmonary arterial hypertension.

In 15 pulmonary arterial hypertension patients, the relation of functional capacity to their peripheral endothelial function and sympathaovagal modulation was studied by carrying out brachial artery ultrasound and electrocardiogram spectral analysis, respectively. The functional capacity was assessed by cardiopulmonary exercise testing and six-minute walking test. The sympathovagal modulation was correlated with the predicted peak oxygen consumption (peak VO2 %; r = 0.692, P < 0.05), peak O2 pulse (mL/beat; r = 0.661, P < 0.05), VE, minute ventilation, VCO2 carbon dioxide production (VE/VCO2 slope; r=-0.806, P < 0.01) and distance walked predicted (%6MWT; r = 0.694, P < 0.05). Moreover, there were negative correlations between parasympathetic modulation with peak VO2 (r = 0.755, P < 0.01), peak VO2% (r=-0.727, P < 0.01) and peak O2 pulse (r = 0.615, P < 0.05), %6MWT (r=-0.834, P < 0.01). Collectively these correlations indicate that parasympathetic withdrawal is crucial for improving functional capacity. This conclusion is supported by both positive and negative correlations of parasympathetic modulation with the functional capacity parameters. The sympathetic modulation predominance, although increases the cardiovascular risk, is probably crucial to facilitate the bronchodilation and the oxygen uptake.

Hipertensão pulmonar devido à doença cardíaca esquerda / Pulmonary hypertension due to Heart Disease Left

A hipertensão pulmonar associada à doença cardíaca esquerda (HP-DCE) é a forma mais comum de hipertensão pulmonar encontrada na prática clínica atual. Embora freqüentemente alvo de terapia, a sua fisiopatologia permanece mal compreendida e seu tratamento permanece indefinido. Hipertensão pulmonar no contexto da doença cardíaca esquerda é um marcador de pior prognóstico e de gravidade da doença. Porém, desconhecemos se o seu tratamento primário é benéfico ou prejudicial. Um passo importante para o estudo futuro deste problema clínico será a padronização das definições e critérios diagnóstico...

Pulmonary hypertension associated with left heart disease (HP-ECD) is the most common form of pulmonary hypertension found in current clinical practice. Although often being target of therapy, its pathophysiology remains poorly understood and its treatment remains undefined. Pulmonary hypertension in the context of left heart disease is a marker of poor prognosis and severity of the disease. However, its primary treatment is not known to be beneficial or harmful. An important step for the future study of this clinical problem is the standardization of definitions and diagnostic criteria...