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1.
N Engl J Med ; 384(13): 1204-1215, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33789009

RESUMO

BACKGROUND: Pulmonary arterial hypertension is characterized by pulmonary vascular remodeling, cellular proliferation, and poor long-term outcomes. Dysfunctional bone morphogenetic protein pathway signaling is associated with both hereditary and idiopathic subtypes. Sotatercept, a novel fusion protein, binds activins and growth differentiation factors in the attempt to restore balance between growth-promoting and growth-inhibiting signaling pathways. METHODS: In this 24-week multicenter trial, we randomly assigned 106 adults who were receiving background therapy for pulmonary arterial hypertension to receive subcutaneous sotatercept at a dose of 0.3 mg per kilogram of body weight every 3 weeks or 0.7 mg per kilogram every 3 weeks or placebo. The primary end point was the change from baseline to week 24 in pulmonary vascular resistance. RESULTS: Baseline characteristics were similar among the three groups. The least-squares mean difference between the sotatercept 0.3-mg group and the placebo group in the change from baseline to week 24 in pulmonary vascular resistance was -145.8 dyn · sec · cm-5 (95% confidence interval [CI], -241.0 to -50.6; P = 0.003). The least-squares mean difference between the sotatercept 0.7-mg group and the placebo group was -239.5 dyn · sec · cm-5 (95% CI, -329.3 to -149.7; P<0.001). At 24 weeks, the least-squares mean difference between the sotatercept 0.3-mg group and the placebo group in the change from baseline in 6-minute walk distance was 29.4 m (95% CI, 3.8 to 55.0). The least-squares mean difference between the sotatercept 0.7-mg group and the placebo group was 21.4 m (95% CI, -2.8 to 45.7). Sotatercept was also associated with a decrease in N-terminal pro-B-type natriuretic peptide levels. Thrombocytopenia and an increased hemoglobin level were the most common hematologic adverse events. One patient in the sotatercept 0.7-mg group died from cardiac arrest. CONCLUSIONS: Treatment with sotatercept resulted in a reduction in pulmonary vascular resistance in patients receiving background therapy for pulmonary arterial hypertension. (Funded by Acceleron Pharma; PULSAR ClinicalTrials.gov number, NCT03496207.).


Assuntos
Hipertensão Arterial Pulmonar/tratamento farmacológico , Proteínas Recombinantes de Fusão/uso terapêutico , Fator de Crescimento Transformador beta/antagonistas & inibidores , Resistência Vascular/efeitos dos fármacos , Adulto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Tolerância ao Exercício/efeitos dos fármacos , Feminino , Humanos , Injeções Subcutâneas , Análise dos Mínimos Quadrados , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Hipertensão Arterial Pulmonar/sangue , Hipertensão Arterial Pulmonar/fisiopatologia , Proteínas Recombinantes de Fusão/efeitos adversos , Proteínas Recombinantes de Fusão/farmacologia , Trombocitopenia/induzido quimicamente , Teste de Caminhada
2.
BMC Surg ; 21(1): 3, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397333

RESUMO

BACKGROUND: We aimed to explore the relationship between the neutrophil to lymphocyte ratio (NLR) and the early clinical outcomes in children with congenital heart disease (CHD) associated with pulmonary arterial hypertension (PAH) after cardiac surgery. METHODS: A retrospective observational study involving 190 children from January 2013 to August 2019 was conducted. Perioperative clinical and biochemical data were collected. RESULTS: We found that pre-operative NLR was significantly correlated with AST, STB, CR and UA (P < 0.05), while post-operative NLR was significantly correlated with ALT, AST, BUN (P < 0.05). Increased post-operative neutrophil count and NLR as well as decreased lymphocyte count could be observed after cardiac surgery (P < 0.05). Level of pre-operative NLR was significantly correlated with mechanical ventilation time, ICU stay time and total length of stay (P < 0.05), while level of post-operative NLR was only significantly correlated to the first two (P < 0.05). By using ROC curve analysis, relevant areas under the curve for predicting prolonged mechanical ventilation time beyond 24 h, 48 h and 72 h by NLR were statistically significant (P < 0.05). CONCLUSION: For patients with CHD-PAH, NLR was closely related to early post-operative complications and clinical outcomes, and could act as a novel marker to predict the occurrence of prolonged mechanical ventilation.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Cardiopatias Congênitas/cirurgia , Linfócitos/patologia , Neutrófilos/patologia , Hipertensão Arterial Pulmonar/cirurgia , Biomarcadores/sangue , Criança , Feminino , Cardiopatias Congênitas/sangue , Cardiopatias Congênitas/complicações , Humanos , Contagem de Linfócitos , Masculino , Período Pré-Operatório , Prognóstico , Hipertensão Arterial Pulmonar/sangue , Hipertensão Arterial Pulmonar/complicações , Estudos Retrospectivos , Volume Sistólico , Função Ventricular Esquerda
3.
Biomed Pharmacother ; 133: 110910, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378990

RESUMO

Pulmonary arterial hypertension (PAH) is a type of high morbidity and mortality disease. Currently, the intrinsic metabolic alteration and potential mechanism of PAH are still not fully uncovered. Previously, we have found that polyphenol resveratrol (Rev) reversed the remodeling of the pulmonary vasculature and decreased the number of mitochondria in pulmonary arterial smooth muscle cells (PASMCs) (Lei Yu et al. (2017)). However, potential effects of Rev on the changed metabolic molecules derived from lung tissue and serum have no fully elucidated. Thus, we conducted a systematic elaboration through the metabonomics method. Various of metabolites in different pathways including amino acid metabolism, tricarboxylic acid cycle (TCA), acetylcholine metabolism, fatty acid metabolism and biosynthesis in male Wistar rats' sera and lung tissues were explored in three groups (normal group, PAH group, PAH and Rev treatment group). We found that leucine and isoleucine degradation, valine, leucine and isoleucine biosynthesis, tryptophan metabolism and aminoacyl-tRNA biosynthesis were involved in the development of PAH. Hydroxyphenyllactic, isopalmitic acid and cytosine might be significant key metabolites. Further work in this area may inform personalized treatment approaches in clinical practice of PAH through elucidating pathophysiology mechanisms of experimental verification.


Assuntos
Metabolismo Energético/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Metabolômica , Hipertensão Arterial Pulmonar/tratamento farmacológico , Resveratrol/farmacologia , Animais , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Hipóxia/complicações , Pulmão/metabolismo , Masculino , Hipertensão Arterial Pulmonar/sangue , Hipertensão Arterial Pulmonar/etiologia , Ratos Wistar , Espectrometria de Massas por Ionização por Electrospray
4.
Clin Biochem ; 89: 58-62, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33382999

RESUMO

BACKGROUND: Carbohydrate antigen 125 (CA 125), known as a tumor marker for ovarian cancer, has been reported to increase and be associated with severity in heart failure and chronic obstructive pulmonary disease. Patients with pulmonary arterial hypertension may also die due to developing right heart failure. The aim of this study is to evaluate the prognostic role of CA-125 in PAH patients. METHODS: A total of 40 consecutive patients with PAH were evaluated prospectively. The mean age of patients was 52 ± 11 years (12% males, 88% females) with a median follow-up period of 16 months. RESULTS: After follow-up period, 12 out of 40 patients (30%) died. CA-125 levels were higher among those who died compared to those who survived [78.5 (11.0-292) vs. 27.5 (2.10-138) U/ml, p = 0.001]. The optimal cut-off value of CA-125 to predict mortality was found as 35.29 U/ml, with 85.7% specificity and 75% sensitivity. In multivariable Cox proportional-hazards model with forward stepwise method; CA-125 > 35.32 U/ml on admission (HR = 7.645, 95% CI: 1.356-43.121, p = 0.021), age (HR = 1.132, 95% CI: 1.040-1.233, p = 0.004), TAPSE (HR = 0.740, 95% CI: 0.549-0.998, p = 0.048) and uric acid (HR = 1.444, 95% CI: 1.022-2.042, p = 0.037) remained associated with an increased risk of death. CONCLUSION: In this study, we showed for the first time that serum CA-125 values were an independent predictor for the long-term mortality in PAH patients.


Assuntos
Biomarcadores/sangue , Antígeno Ca-125/sangue , Hipertensão Arterial Pulmonar/mortalidade , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Hipertensão Arterial Pulmonar/sangue , Hipertensão Arterial Pulmonar/patologia , Fatores de Risco , Taxa de Sobrevida
5.
J Pediatr ; 223: 164-169.e1, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32711743

RESUMO

OBJECTIVE: To assess whether circulating interleukin-6 (IL-6) is associated with measures of disease severity and clinical worsening in pediatric pulmonary arterial hypertension (PAH). STUDY DESIGN: IL-6 was measured by enzyme-linked immunosorbent assay in serum samples from a cross-sectional cohort from the National Heart, Lung, and Blood Institute Pulmonary Arterial Hypertension Biobank (n = 175) and a longitudinal cohort from Children's Hospital Colorado (CHC) (n = 61). Associations between IL-6, disease severity, and outcomes were studied with regression and Kaplan-Meier analysis. RESULTS: In analyses adjusted for age and sex, each log-unit greater IL-6 was significantly associated in the Pulmonary Arterial Hypertension Biobank cohort with greater pulmonary vascular resistance indices, lower odds of having idiopathic PAH or treatment with prostacyclin, and greater odds of having PAH associated with a repaired congenital shunt. In the CHC cohort, each log-unit greater IL-6 was significantly associated with greater mean pulmonary arterial pressure over time. Kaplan-Meier analysis in the CHC cohort revealed that IL-6 was significantly associated with clinical worsening (a composite score of mortality, transplant, or palliative surgery) (P = .037). CONCLUSIONS: IL-6 was significantly associated with worse hemodynamics at baseline and over time and may be associated with clinical worsening. IL-6 may provide a less-invasive method for disease monitoring and prognosis in pediatric PAH as well as a potential therapeutic target.


Assuntos
Interleucina-6/sangue , Hipertensão Arterial Pulmonar/sangue , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Estudos Transversais , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Pressão Propulsora Pulmonar/fisiologia
7.
Adv Ther ; 37(5): 2199-2209, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32239458

RESUMO

INTRODUCTION: To explore the relationship between serum high-density lipoprotein cholesterol (HDL-C) levels and the presence and severity of pulmonary arterial hypertension (PAH). METHODS: A total of 177 patients with PAH and 103 patients without pulmonary hypertension (PH) were enrolled in this study. All patients underwent right heart catheterization (RHC) for diagnosing and assessing the severity of PAH. Demographics, comorbidities, and laboratory data including serum HDL-C levels were collected. RESULTS: Plasma HDL-C levels in patients with PAH were significantly lower compared with patients without PH (1.08 ± 0.36 vs 1.49 ± 0.36, p < 0.001). HDL-C levels positively correlated with cardiac output (r = 0.360, p < 0.001), cardiac index (r = 0.337, p < 0.001), and mixed venous oxygen saturation (r = 0.426, p < 0.001), and negatively with mean pulmonary arterial pressure (r = - 0.529, p < 0.001), right atrial pressure (r = - 0.421, p < 0.001), and pulmonary vascular resistance (r = - 0.583, p < 0.001). Multivariate logistic regression analysis indicated that HDL-C was a significant independent predictor of PAH (OR 0.042, 95% CI 0.006-0.304, p = 0.002). The receiver operating characteristic curve analysis showed that the optimal cutoff value of the serum HDL-C concentration for predicting PAH was 1.32 mmol/L, with a sensitivity of 83.6% and a specificity of 72.8% (area under the curve 0.803, 95% confidence interval 0.750-0.856, p < 0.001). CONCLUSIONS: Serum HDL-C is a simple biomarker that might be used for prediction and assessment of PAH in Chinese Han ethnicity, and the mechanism underlying the association needs further study.


Assuntos
Grupo com Ancestrais do Continente Asiático , Biomarcadores/sangue , HDL-Colesterol/sangue , Hipertensão Arterial Pulmonar/sangue , Hipertensão Arterial Pulmonar/fisiopatologia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença
8.
J Pediatr ; 220: 139-145, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32113658

RESUMO

OBJECTIVE: To assess the association between serially measured N-terminal pro-B-type natriuretic peptide (NT-proBNP) serum levels and disease severity in children with pulmonary arterial hypertension (PAH), and to assess its predictive value for death or (heart-)lung transplantation. STUDY DESIGN: This was a longitudinal cohort study of the Dutch National Network for Pediatric Pulmonary Hypertension conducted between 2003 and 2017. Data on NT-proBNP and disease severity markers (World Health Organization Functional Class [WHO-FC], 6-minute walking distance [6MWD], and tricuspid annular plane systolic excursion [TAPSE]) were collected every 3 to 6 months from 82 children with PAH. The outcome measure was death or (heart-)lung transplantation. Also, NT-proBNP levels over time were compared between survivors and nonsurvivors. RESULTS: The median patient age was 8.8 years (IQR, 4.6-13.5 years), and 61% were female. The median duration of follow-up was 4.8 years (IQR, 1.9-10.0 years). At all times during the course of disease, higher NT-proBNP levels were associated with higher WHO-FC (ß = 0.526; 95% CI, 0.451-0.600), lower 6MWD z-score (ß = -0.587; 95% CI, -0.828 to -0.346), lower TAPSE z-score (ß = -0.783; 95% CI, -1.016 to -0.549), and elevated risk of death or (heart-)lung transplantation (hazard ratio 16.61; 95% CI, 7.81-35.33). Compared with survivors, nonsurvivors had NT-proBNP levels that were higher at first measurement and increased exponentially over time (P = .005). Changes in NT-proBNP serum level over time were predictive of outcome. CONCLUSIONS: Throughout the disease course of pediatric PAH, serial measurements of NT-proBNP are associated with disease severity and transplant-free survival. Monitoring NT-proBNP levels over time provides important prognostic information that can support clinical decision making in combination with other established prognostic markers.


Assuntos
Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Hipertensão Arterial Pulmonar/sangue , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Testes Hematológicos/métodos , Humanos , Estudos Longitudinais , Masculino , Monitorização Fisiológica , Valor Preditivo dos Testes , Índice de Gravidade de Doença
9.
Rev Soc Bras Med Trop ; 53: e20190418, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32049203

RESUMO

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a serious pulmonary circulation disease caused by several etiologies, including schistosomiasis. The present study retrospectively evaluated the clinical and hemodynamic characteristics of patients with schistosomal PAH (PAH-Sch) compared to those of non-Sch PAH patients (non-Sch PAH). METHODS: Patients treated at the Pronto-Socorro Cardiológico de Pernambuco and diagnosed by right cardiac catheterization were divided into PAH-Sch and non-Sch PAH groups. Their socio-demographic and clinical characteristics, N-terminal-pro B-type natriuretic peptide (NT-proBNP), and echocardiography and hemodynamic parameters were retrospectively reviewed. RESULTS: Among the included 98 patients (mean age, 45 ± 14 years; 68 women [69.4%]), we found 56 PAH-Sch and 42 non-Sch PAH. The age distribution was heterogeneous in the PAH-Sch group, with patients predominantly ranging from 50-59 (p <0.004). Dyspnea was the most common symptom, reported by 92 patients (93.8%), and commonly present for over two years prior to diagnosis. Clinical symptoms were similar in both groups, with no differences in functional class, pulmonary artery systolic pressure (p = 0.102), 6-minute walk test score (p = 0.234), NT-proBNP serum levels (p = 0.081), or hemodynamic parameters. CONCLUSIONS: Patients with PAH-Sch present clinical, laboratory, and hemodynamic profiles similar to those with PAH resulting from other etiologies of poor prognosis. PAH is an important manifestation of schistosomiasis in endemic regions that is often diagnosed late.


Assuntos
Fator Natriurético Atrial/sangue , Precursores de Proteínas/sangue , Hipertensão Arterial Pulmonar/etiologia , Esquistossomose/complicações , Adulto , Idoso , Biomarcadores/sangue , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hipertensão Arterial Pulmonar/sangue , Estudos Retrospectivos , Fatores Socioeconômicos
10.
Clin Transl Gastroenterol ; 11(1): e00118, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31977452

RESUMO

INTRODUCTION: Hepatic involvement in hereditary hemorrhagic telangiectasia (HHT) is common and can be associated with severe clinical consequences, including portal hypertension, cardiac failure, and encephalopathy. However, there are no reliable clinical predictors of hepatic involvement and its associated complications, limiting appropriate identification of these patients. In this work, we define the utility of serum ammonia and liver biochemical tests (LFTs) in predicting hepatic HHT involvement and its complications. METHODS: We performed a retrospective study examining a well-characterized cohort of patients with HHT. Clinical characteristics, laboratory tests, liver imaging, transthoracic echocardiography assessment of right ventricular systolic pressure (RVSP), and history of other HHT-related outcomes were assessed. Patients were followed for the development of encephalopathy. RESULTS: Of 45 patients with definite HHT, 18 (40%) had elevated ammonia levels. An elevated ammonia associated with the presence of hepatic arteriovenous malformations (AVMs) on imaging (P < 0.03) and when combined with elevated liver tests increased the sensitivity for hepatic AVMs by 18% (55% for LFTs vs 73% for LFTs plus ammonia). Furthermore, an elevated serum ammonia in patients with HHT associated with an elevated RVSP (>35 mm Hg), providing an 80% sensitivity and 71% specificity for predicting the presence of pulmonary hypertension. In contrast, there was no association with an elevated serum ammonia and encephalopathy over a total of 859 months of follow-up. DISCUSSION: Elevated ammonia in a cohort of patients with HHT was associated with the presence of hepatic AVMs and elevated RVSP, but no other complications of HHT, including encephalopathy.


Assuntos
Malformações Arteriovenosas/sangue , Hiperamonemia/sangue , Hepatopatias/sangue , Hipertensão Arterial Pulmonar/sangue , Telangiectasia Hemorrágica Hereditária/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Amônia/sangue , Malformações Arteriovenosas/diagnóstico por imagem , Malformações Arteriovenosas/etiologia , Aspartato Aminotransferases/sangue , Estudos de Coortes , Ecocardiografia , Feminino , Humanos , Hiperamonemia/etiologia , Hepatopatias/diagnóstico por imagem , Hepatopatias/etiologia , Masculino , Pessoa de Meia-Idade , Hipertensão Arterial Pulmonar/diagnóstico por imagem , Hipertensão Arterial Pulmonar/etiologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Telangiectasia Hemorrágica Hereditária/complicações , Adulto Jovem
11.
Heart Lung Circ ; 29(1): 142-148, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30686644

RESUMO

BACKGROUND: Precapillary pulmonary hypertension (PH) is characterised by compromised functional capacity and impaired quality of life. Assessment of haemodynamics is routinely used for initial diagnosis, follow-up, and risk stratification in these patients. The purpose of this study was to investigate the relation of health-related quality of life (HRQoL) as assessed by emPHasis-10 score, a self-assessment questionnaire assessing breathlessness, fatigue, control, and confidence, to haemodynamic and neurohormonal indices in patients with precapillary PH. METHOD: This was a prospective cross-sectional study which included stable patients with precapillary PH. All patients underwent right heart catheterisation, 6-minute walk test, N-terminal pro-brain natriuretic peptide (NT-proBNP) measurement, and assessment of HRQoL with the emPHasis-10 scale. RESULTS: Overall, 54 patients were included (32 women; mean age, 58.4 ± 14.6 yr). Mean emPHasis-10 score was 19.2 ± 12.0. EmPHasis-10 score correlated with World Health Organization functional class (r = 0.52, p < 0.001), 6-minute walk distance (r=-0.56, p < 0.001), and log10(NT-proBNP) (r = 0.41, p < 0.01). A positive correlation of emPHasis-10 score with mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) and a negative correlation with mixed venous oxygen saturation and cardiac index was observed, after adjustment for age, sex, body mass index, and PH group. In a subgroup analysis of patients with pulmonary arterial hypertension (n = 34) there was a stronger correlation of emPHasis-10 score with mPAP (r = 0.86, p < 0.001) and PVR (r = 0.69, p < 0.01), but no correlation with cardiac index and mixed venous oxygen saturation. CONCLUSIONS: Self-assessment of quality of life with the use of the emPHasis-10 score reflects functional capacity and is correlated with haemodynamic and neurohormonal indices of right heart dysfunction in patients with precapillary PH.


Assuntos
Hemodinâmica , Hipertensão Arterial Pulmonar/fisiopatologia , Qualidade de Vida , Resistência Vascular , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Estudos Prospectivos , Hipertensão Arterial Pulmonar/sangue , Hipertensão Arterial Pulmonar/terapia
12.
Clin Rheumatol ; 39(1): 49-56, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31129792

RESUMO

OBJECTIVE: Our goal was to determine if whole blood viscosity (WBV) can be used to predict the risk of pulmonary arterial hypertension (PAH) in patients with systemic sclerosis (SSc). METHODS: Patients with SSc were analyzed. Out of 107 patients, 26 patients, found to have confirmed diagnosis of PAH, were classified as those with (n = 26, PAH group) and without PAH (n = 81, non-PAH group). We calculated estimated WBV at both high (HSR) and low shear rates (LSR) from hematocrit and total serum protein levels. RESULTS: Total protein levels were significantly higher and the anti-centromere antibody (ACA) was more frequent in the PAH group. Furthermore, anti-topoisomerase antibody (anti-scl-70) was significantly less frequent in the PAH group. The WBV values were significantly higher at HSR (16.68 ± 0.38 vs. 16.24 ± 0.58; p < 0.001) and at LSR (51.81 ± 7.21 vs. 42.97 ± 11.76; p < 0.001) in PAH group. The multivariate analysis revealed that the WBV at both shear rates independently designated the presence of PAH in SSc patients. The ROC curve showed that the sensitivity and specificity of LSR and HSR were 92.3% and 61.7% (AUC 0.759, p < 0.001), and 88.5% and 65.4% (AUC 0.770, p < 0.001) with a cutoff value of 43.56 and 16.32 for WBV, respectively. CONCLUSION: Higher WBV levels in SSc patients were an independent indicator for PAH development in this cohort. WBV-LSR and WBV-HSR values might help exclude the PAH possibility in patients diagnosed with SSc and remain as an independently associated biomarker for follow-up of these patients for future risk of PAH development. Findings remain to be confirmed by other cohorts.Key Points• The most important cause of morbidity and mortality in systemic sclerosis patients is considered to be pulmonary arterial hypertension.• When the symptoms of PAH are not recognized earlier in the course of the SSc, the prognosis might be worse.• Higher whole blood viscosity levels in scleroderma patients with PAH was an independent indicator for PAH development.


Assuntos
Viscosidade Sanguínea , Hipertensão Arterial Pulmonar/etiologia , Escleroderma Sistêmico/complicações , Adulto , Idoso , Biomarcadores/sangue , Ecocardiografia , Feminino , Hematócrito , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Hipertensão Arterial Pulmonar/sangue , Hipertensão Arterial Pulmonar/diagnóstico por imagem , Curva ROC , Estudos Retrospectivos , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/diagnóstico por imagem , Sensibilidade e Especificidade
13.
Chest ; 157(2): 376-383, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31563498

RESUMO

BACKGROUND: Combinations of therapies are currently recommended for patients with severe pulmonary arterial hypertension (PAH), and excellent results have been reported with triple upfront combination of these drugs. We evaluated the effects of this approach on right ventricular (RV) function and outcome in patients with severe PAH. METHODS: Twenty-one patients (age, 44 ± 15 years) with newly diagnosed high-risk idiopathic PAH that was nonreversible by the inhalation of nitric oxide were treated upfront with a combination of ambrisentan, tadalafil, and subcutaneous treprostinil between 2014 and 2018. Clinical evaluation, World Health Organization functional class, 6-min walk distance, biomarkers, echocardiography, and right-sided heart catheterization data were recorded at baseline and during follow-up. RESULTS: At a median follow-up of 2 years, all patients were still alive. The Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management score decreased from 10 ± 1 to 5 ± 1, right-sided atrial pressure decreased from 13 ± 3 to 5 ± 2 mm Hg, mean pulmonary artery pressure decreased from 60 ± 9 to 42 ± 5 mm Hg, pulmonary vascular resistance (PVR) decreased from 16.4 ± 4.4 to 5.5 ± 1.3 Wood units, N-terminal pro-brain natriuretic peptide decreased from 3,379 ± 1,921 to 498 ± 223 pg/mL, and World Health Organization functional class decreased from 3.4 ± 0.5 to 2.0 ± 0.4 (all P < .001). Cardiac index increased from 1.8 ± 0.3 to 3.5 ± 0.8 L/min/m2 and 6-min walk distance increased from 158 ± 130 to 431 ± 66 m (both P < .001). Echocardiography showed decreased right-sided atrial and RV areas, improved left ventricular eccentricity index, and increased fractional area change (all P < .001) in proportion to treatment-induced decrease in PVR. CONCLUSIONS: Triple upfront combination therapy with ambrisentan, tadalafil, and subcutaneous treprostinil in severe nonreversible PAH is associated with considerable clinical and hemodynamic improvement and right-sided heart reverse remodeling.


Assuntos
Anti-Hipertensivos/uso terapêutico , Remodelamento Atrial , Epoprostenol/análogos & derivados , Fenilpropionatos/uso terapêutico , Hipertensão Arterial Pulmonar/tratamento farmacológico , Piridazinas/uso terapêutico , Tadalafila/uso terapêutico , Vasodilatadores/uso terapêutico , Remodelação Ventricular , Adulto , Cateterismo Cardíaco , Quimioterapia Combinada , Ecocardiografia , Epoprostenol/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Hipertensão Arterial Pulmonar/sangue , Hipertensão Arterial Pulmonar/diagnóstico por imagem , Hipertensão Arterial Pulmonar/fisiopatologia , Estudos Retrospectivos , Comportamento de Redução do Risco , Resultado do Tratamento , Resistência Vascular , Função Ventricular Direita , Teste de Caminhada
14.
BMC Pediatr ; 19(1): 502, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31847901

RESUMO

BACKGROUND: Pulmonary arterial hypertension (PAH) caused by congenital heart disease (CHD) is very common in clinics. Some studies have shown that PAH is related to the number of endothelial progenitor cells (EPCs), but there is no report on the relationship between PAH and the number of EPCs in children with CHD. METHODS: In this study, a total of 173 cases with CHD (from 0 to 6 years old) were collected. According to the mean pulmonary arterial pressure (mPAP) measured by right heart catheterization, these cases were divided into PAH groups (including high PAH group, mPAP> 25 mmHg, n = 32, and the middle PAH group, 20 mmHg ≤ mPAP≤25 mmHg, n = 30) and non-PAH group (mPAP< 20 mmHg, n = 111). Peripheral blood was taken for flow cytometry, and the number of EPCs (CD133+/KDR+ cells) was counted. The number of EPCs /µL of peripheral blood was calculated using the following formula: EPCs /µL = WBC /L × lymphocytes % × EPCs % × 10- 6. RESULTS: The median EPCs of the non-PAH group, middle PAH group and high PAH group is 1.86/µL, 1.30 /µL and 0.98/µL, respectively. The mPAP decreases steadily as the level of EPCs increases (P < 0.05). After adjustment of gender, age and BMI, the number of EPCs was significantly associated with a decreased risk of high PAH (OR = 0.37, 95% CI: 0.16-0.87, P < 0.05). However, EPCs was not significantly associated with middle PAH (P > 0.05). CONCLUSION: The findings revealed that the EPCs and high PAH in patients with CHD correlate significantly and EPCs may become an effective treatment for PAH in patients with CHD. EPCs may be a protective factor of high PAH for children with CHD.


Assuntos
Células Progenitoras Endoteliais , Cardiopatias Congênitas/sangue , Cardiopatias Congênitas/complicações , Hipertensão Arterial Pulmonar/sangue , Hipertensão Arterial Pulmonar/etiologia , Contagem de Células , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino
15.
Respir Res ; 20(1): 250, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703589

RESUMO

BACKGROUND: Balloon pulmonary angioplasty (BPA) has been demonstrated to improve cardiac function and exercise capacity in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH), but its instant impact on cardiopulmonary function has seldom been evaluated. This study aims to determine the safety and efficacy of BPA and its immediate and lasting effects on cardiopulmonary function among CTEPH patients. METHODS: From May 2018 to January 2019, patients with inoperable CTEPH who underwent BPA sessions were consecutively enrolled. Hemodynamics were measured by right heart catheterization, selective pulmonary angiography and BPA were successively conducted. Hemodynamic variables, WHO functional class (WHO-FC), 6-min walk distance (6MWD) and serum NT-proBNP were evaluated before and after BPA sessions during hospitalization. Pulmonary function testing (PFT) and cardiopulmonary exercise testing (CPET) were performed within 1-3 days pre and post BPA to evaluate the effect of BPA on cardiopulmonary function. RESULTS: Twenty-five patients with inoperable CTEPH who underwent a total of forty BPA sessions were consecutively enrolled. A total of 183 segmental or subsegmental vessels (4.6 ± 1.9 vessels per session) in 137 segments (3.4 ± 1.6 segments per session) were dilated. No procedure-related complications occurred. Instant hemodynamics, WHO-FC, 6MWD and NT-proBNP were all significantly improved after a single BPA session. Significant improvement in cardiopulmonary function was also evident as assessed by PFT indexes (forced vital capacity, forced expiratory volume in the first second, maximal voluntary ventilation) and CPET parameters (peak work rate, peak VO2, oxygen uptake efficiency slope). Further analysis among ten CTEPH patients receiving multiple BPA sessions (2-4 sessions) indicated BPA resulted in lasting improvements in hemodynamics and cardiopulmonary function. CONCLUSIONS: BPA, a safe and effective approach, can bring instant improvements after a single session and lasting benefits after multiple sessions to hemodynamics and cardiopulmonary function for patients with inoperable CTEPH.


Assuntos
Angioplastia com Balão , Hemodinâmica , Hipertensão Arterial Pulmonar/terapia , Artéria Pulmonar/fisiopatologia , Circulação Pulmonar , Embolia Pulmonar/terapia , Idoso , Angioplastia com Balão/efeitos adversos , Biomarcadores/sangue , Doença Crônica , Tolerância ao Exercício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Hipertensão Arterial Pulmonar/sangue , Hipertensão Arterial Pulmonar/diagnóstico , Hipertensão Arterial Pulmonar/fisiopatologia , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/fisiopatologia , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento
16.
Am J Physiol Heart Circ Physiol ; 317(5): H1093-H1101, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31490732

RESUMO

Pulmonary arterial hypertension (PAH) is a fatal disease with a median survival of only 5-7 yr. PAH is characterized by remodeling of the pulmonary vasculature causing reduced pulmonary arterial compliance (PAC) and increased pulmonary vascular resistance (PVR), ultimately resulting in right ventricular failure and death. Better therapies for PAH will require a paradigm shift in our understanding of the early pathophysiology. PAC decreases before there is an increase in the PVR. Unfortunately, present treatment has little effect on PAC. The loss of compliance correlates with extracellular matrix remodeling and fibrosis in the pulmonary vessels, which have been linked to chronic perivascular inflammation and immune dysregulation. However, what initiates the perivascular inflammation and immune dysregulation in PAH is unclear. Alteration of the gut microbiota composition and function underlies the level of immunopathogenic involvement in several diseases, including atherosclerosis, obesity, diabetes mellitus, and depression, among others. In this review, we discuss evidence that raises the possibility of an etiologic role for changes in the gut and circulating microbiome in the initiation of perivascular inflammation in the early pathogenesis of PAH.


Assuntos
Pressão Arterial , Bactérias/metabolismo , Microbioma Gastrointestinal , Mediadores da Inflamação/sangue , Intestinos/microbiologia , Hipertensão Arterial Pulmonar/microbiologia , Artéria Pulmonar/microbiologia , Animais , Bactérias/imunologia , Disbiose , Interações Hospedeiro-Patógeno , Humanos , Mediadores da Inflamação/imunologia , Hipertensão Arterial Pulmonar/sangue , Hipertensão Arterial Pulmonar/imunologia , Hipertensão Arterial Pulmonar/fisiopatologia , Artéria Pulmonar/imunologia , Artéria Pulmonar/metabolismo , Artéria Pulmonar/fisiopatologia , Fatores de Risco , Transdução de Sinais
17.
Int Immunopharmacol ; 76: 105874, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31499270

RESUMO

Pulmonary arterial hypertension (PAH) is a severe complication of systemic lupus erythematosus (SLE), with unclear etiopathogenesis. We evaluated the role of macrophage migration inhibitory factor (MIF), which has been implicated in idiopathic pulmonary hypertension (PH), in SLE-associated PAH. Circulating MIF was measured in SLE patients, SLE-PAH patients, and healthy donors. In situ pulmonary artery MIF protein expression was determined in spontaneous SLE mice (MRL/lpr) and hypoxia-induced C57BL/6J mice. Daily MIF098 was administered to C57BL/6J mice, and these mice were maintained in a hypoxic chamber for 4 weeks. The right ventricular systolic pressure (RVSP) and pathological characteristics of the pulmonary artery (PA), such as hyperproliferation, muscularization, and fibrosis were then measured in each group of mice. Data were also obtained in vitro using pulmonary smooth muscle cells (PASMC) challenged with platelet-derived growth factor (PDGF)-BB or 1% O2 hypoxia. As a result, circulating MIF was elevated in SLE-PAH patients compared with SLE patients or healthy donors. Higher RVSP SLE mice produced more MIF protein than lower RVSP SLE mice in the pulmonary artery. MIF098 decreased RVSP and inhibited distal pulmonary artery hyperproliferation, muscularization, and collagen deposition in hypoxia challenged mice. In addition, MIF098 inhibited PASMC proliferation and migration by regulating mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 (MAPK/ERK1/2) signal- and cell-cycle-related proteins. MIF098 also reduced collagen synthesis by inhibiting the TGFß1/Smad2/Smad3 pathway in cell-based experiments. In conclusion, MIF may serve as a biomarker and a therapeutic target of SLE-associated PAH. Pharmacologic MIF antagonism may be an effective means to ameliorate SLE-PAH.


Assuntos
Benzoxazóis/uso terapêutico , Oxirredutases Intramoleculares/antagonistas & inibidores , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Fatores Inibidores da Migração de Macrófagos/antagonistas & inibidores , Hipertensão Arterial Pulmonar/tratamento farmacológico , Adulto , Animais , Benzoxazóis/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Colágeno/metabolismo , Modelos Animais de Doenças , Feminino , Fibrose , Humanos , Oxirredutases Intramoleculares/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/patologia , Fatores Inibidores da Migração de Macrófagos/sangue , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/fisiologia , Hipertensão Arterial Pulmonar/sangue , Hipertensão Arterial Pulmonar/etiologia , Hipertensão Arterial Pulmonar/patologia , Artéria Pulmonar/citologia , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia
18.
J Cardiovasc Med (Hagerstown) ; 20(11): 771-779, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31397686

RESUMO

AIMS: Systemic sclerosis (SSc) is an autoimmune disease characterized by micro/macrovascular damage due to the underlying fibrosis. Markers able to predict the progression of cardiovascular damage, including digital ulcers, in SSc are warranted. We aimed at characterizing the relevance of N-terminal proatrial natriuretic peptide (NT-proANP) and N-terminal probrain natriuretic peptide plasma levels in relation to cardiovascular damage and digital ulcers in a cohort of Italian SSc patients. METHODS: Seventy patients were enrolled (64 women and six men; mean age 56.7 ±â€Š14 years) with a disease duration of 11.1 ±â€Š8.3 years. Clinical, instrumental (nailfold videocapillaroscopy, ECG, transthoracic echocardiography, pulmonary function test with diffusion lung CO), NT-proANP and N-terminal probrain natriuretic peptide plasma levels measurement were performed at baseline. The clinical follow-up lasted 24 months. The statistical approach used to achieve the study objectives included multivariate analysis, receiver operating characteristic curve, Kaplan-Meier and Cox regression analyses. RESULTS: Both NT-proNPs levels correlated with systolic pulmonary arterial pressure, but only the NT-proANP level correlated with right heart dimension. Both NT-proNPs levels were higher in patients experiencing events at follow-up but only the NT-proANP level significantly predicted the progression of cardiovascular damage, including development of pulmonary arterial hypertension (PAH). NT-proANP levels were higher in patients with digital ulcers and strongly predicted their development. CONCLUSION: Our results show that the NT-proANP plasma level significantly correlates with disease progression such as new onset of PAH, worsening of pulmonary hypertension and development of digital ulcers in a cohort of SSc Italian patients. If future studies will confirm our findings, the plasma NT-proANP level could be used in clinical practice as a novel sensitive marker for PAH and digital ulcers development in SSc.


Assuntos
Fator Natriurético Atrial/sangue , Fragmentos de Peptídeos/sangue , Hipertensão Arterial Pulmonar/sangue , Escleroderma Sistêmico/sangue , Úlcera Cutânea/sangue , Adulto , Idoso , Biomarcadores/sangue , Progressão da Doença , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Valor Preditivo dos Testes , Prognóstico , Hipertensão Arterial Pulmonar/diagnóstico , Hipertensão Arterial Pulmonar/etiologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Úlcera Cutânea/diagnóstico , Úlcera Cutânea/etiologia , Regulação para Cima
19.
Int J Mol Sci ; 20(14)2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31323735

RESUMO

The impact of high-density lipoprotein (HDL) cholesterol on the development of atherosclerosis and diseases of systemic circulation has been well documented both in experimental and registry studies. Recent discoveries in pulmonary arterial hypertension (PAH) revealed a significant impact of HDL on pulmonary artery vasoreactivity and patients' prognosis. The vasoprotective activity of HDL primarily involves vascular endothelium that also plays a central role in pulmonary arterial hypertension (PAH) pathobiology. However, the exact mechanism in which this lipoprotein fraction exerts its effect in pulmonary circulation is still under investigation. This paper reviews potential vasoprotective mechanisms of HDL in pulmonary circulation and presents current clinical reports on the role of HDL in PAH patients.


Assuntos
Biomarcadores/sangue , HDL-Colesterol/sangue , Hipertensão Arterial Pulmonar/sangue , Humanos , Inflamação/sangue , Inflamação/patologia , Prognóstico , Hipertensão Arterial Pulmonar/patologia
20.
Hypertens Pregnancy ; 38(3): 163-170, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31204528

RESUMO

Objective: This study aimed to analyze the perinatal changes of plasma estradiol (E2) and angiotensin II (Ang II) in pregnant women with pulmonary arterial hypertension before and after cesarean section. Methods: Depending on pulmonary arterial pressure, the subjects were divided into two groups, moderate group, and severe group. Plasma concentrations of E2 and Ang II were determined at different time points using electrochemiluminescence immunoassay and ELISA, respectively. The correlation between E2 and Ang II concentrations was analyzed. Results: Intragroup comparison indicated that E2 levels at different time points after surgery decreased in the two groups than before, with a greater reduction in the severe group. Besides, both groups showed a reduction in Ang II concentrations after surgery. As indicated by intragroup comparison, there was a significant difference at each time point in the two groups. The reduction in Ang II concentrations was more conspicuous at 48 h and 72 h after surgery (cesarean section) than before for the two groups. Moreover, E2 concentrations were correlated positively with AngII concentrations. Conclusion: Plasma concentrations of E2 and Ang II decreased after delivery. The plasma concentrations of E2 and Ang II were correlated with each other.


Assuntos
Angiotensina II/sangue , Estradiol/sangue , Parto/sangue , Complicações Cardiovasculares na Gravidez/sangue , Hipertensão Arterial Pulmonar/sangue , Adolescente , Adulto , Pressão Sanguínea/fisiologia , Feminino , Humanos , Gravidez , Adulto Jovem
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