Familial Primary Pulmonary Hypertension ; Humans ; Hypertension, Pulmonary ; Pulmonary Arterial Hypertension

Familial Primary Pulmonary Hypertension ; Humans ; Hypertension, Pulmonary ; therapy

Bone Morphogenetic Protein 7 ; Familial Primary Pulmonary Hypertension ; Humans

Algorithms ; Familial Primary Pulmonary Hypertension ; Humans ; Hypertension, Pulmonary/diagnosis* ; Pulmonary Arterial Hypertension

Anastomosis, Surgical ; Child ; Familial Primary Pulmonary Hypertension ; Humans ; Hypertension, Pulmonary/surgery* ; Pulmonary Arterial Hypertension ; Pulmonary Artery/surgery*

Pathogenic variants of bone morphogenic protein receptor type 2 gene (BMPR2) are related to the majority of cases of heritable pulmonary arterial hypertension (PAH). Over 400 pathogenic variants have been identified. However, clinical characterization of PAH is still incomplete. We present a case of heritable PAH in a Korean family showing serious clinical presentation with high penetrance. Genetic sequencing revealed a known heterozygous BMPR2 pathogenic variant, c.418+5G>A, at a splice site of intron 3. Serious clinical presentation with high penetrance suggested that the interplay of other factors with pathologic variants might be in genotype-phenotype correlation. Further studies are needed to clarify these issues for the development of personalized medicine approaches for PAH.
Familial Primary Pulmonary Hypertension ; Genetic Association Studies ; Humans ; Hypertension* ; Hypertension, Pulmonary ; Introns* ; Penetrance* ; Precision Medicine ; Pulmonary Artery

OBJECTIVEThe objective of this study is to review the research on the prognostic markers of idiopathic pulmonary arterial hypertension (IPAH).

DATE SOURCESWe searched literature from PubMed and CNKI databases both in English and Chinese up to 2013.

STUDY SELECTIONData about mortality and cut-off value are from clinical trials and identified by analysis.

RESULTSIPAH is an unexplained, progressive, and rare disease characterized by increased pulmonary artery pressure and pulmonary vascular resistance. The diagnosis is difficult, mortality of IPAH is high, and the survival periods are only 2-3 years after diagnosis. Investigations in recent years have identified a range of prognostic markers for IPAH, including the 6-minute walking test, red blood cell distribution width, and platelet levels, as well as imaging findings. Changes in these markers are important sources of information to predict the prognosis of patients with IPAH, which carries significant benefits for treatment planning.

CONCLUSIONEven though the prognosis of IPAH has been investigated, the mortality is also high. More accurate and meaningful assessment for the prognosis of IPAH is required.

Humans ; Pulmonary Arterial Hypertension ; Bone Morphogenetic Protein Receptors, Type II/metabolism* ; Pedigree ; Mutation ; Familial Primary Pulmonary Hypertension

Objective: To explore the risk factors for death in patients with pulmonary arterial hypertension related to congenital heart disease (PAH-CHD) and the clinical characteristics of different subtypes in patients with PAH-CHD. Methods: It was a retrospective study. A total of 507 PAH-CHD patients, who were hospitalized in the Department of Pediatric Cardiology of Beijing Anzhen Hospital between September 2005 and May 2019, were included. Patients were divided into 4 subgroups: (1) Eisenmenger syndrome(ES) group. (2) PAH associated with prevalent systemic-to-pulmonary shunts(SP) group. (3) PAH associated with small defects(SD) group. (4) PAH after defect correction(CD) group. According to the complexity of cardiac malformation, patients were divided into simple-medium complex malformation group and complex malformation group. According to the location of shunts, patients were divided into pre-tricuspid group, post-tricuspid group, and mixed group or complex deformity group. Baseline clinical data of patients were collected from the electronic medical record system. Demographic data (age, gender, etc.), percutaneous oxygen saturation(SPO(2)), New York Heart Association(NYHA) cardiac function classification, 6 minutes walking distance(6MWD), and B type natriuretic peptide(BNP), systolic pulmonary arterial pressure(sPAP) estimated by echocardiography and mean pulmonary artery pressure (mPAP), mean right atrial pressure(mRAP), cardiac index(CI), and calculated pulmonary vascular resistance (PVR) estimated by right heart catheterization were compared among various groups. The results of regular follow-up of all enrolled patients were collected, including the status of monotherapy or combination of PAH-targeted drugs during the follow-up period, cardiac-related adverse events(hemopysis, syncope, edema, arrhythmia, etc.) and primary endpoint event(all-cause death) were obtained and analyzed. Risk factors for all-cause death were analyzed using univariate and multivariate Cox regression analysis model. Results: The median age at diagnosis was 23.1(13.9,32.1) years, 345 cases(68.0%) were female. Two hunderds and thirty-five cases(46.4%) were diagnosed with ES; 193 cases(38.1%) were diagnosed with CD, 47 cases (9.3%) were diagnosed with SD. Among them, 32 cases(6.3%) were in the SP group. All 507 patients underwent echocardiography examination, there were significant differences in sPAP among different clinical subgroups(P<0.001). A total of 289 patients(57.0%) received right heart catheterization examination, the results showed that the ES group had the highest mPAP and PVR and the lowest mRAP(all P<0.001), the CD group had the highest mRAP and CI(both P<0.001). The 6MWD in the ES group was significantly shorter than that in the SP, SD, and CD groups(all P<0.001). The proportion of patients with NYHA class Ⅲ/Ⅳ was higher in SD group than in SP group(P<0.001), which was similar between SD, ES and CD groups (P values were 0.077 and 0.072, respectively). At admission, the proportion of patients with NYHA class Ⅰ/Ⅱwas the highest in SP group(96.9% (31/32) ), followed by CD group (85.5%(165/193)) and the ES group(85.1%(200/235)), and the SD group(75.0%(35/47)). The BNP level at admission was also higher in SD group than in SP, ES and CD groups(P<0.001). Of the 507 patients, 379(74.8%) patients received PAH-targeted drug therapy at the last follow-up, and the treatment plan was mainly monotherapy(75.7%(287/379)). The median follow-up time was 3.6(2.0, 5.6) years and 37(7.3%) patients died, including 13 in the CD group, 17 in the ES group, and 7 in the SD group. No deaths occurred in the SP group. Right heart failure was the most common cause of death(11(29.7%)), followed by severe hemoptysis dyspnea(7(18.9%)), sudden cardiac death(6(16.2%)), and pulmonary hypertensive crisis(4(10.8%)). Kaplan-Meier curve showed that survival rates of end-point-free events at 1, 3, 5 and 10 years after diagnosis of PAH were 98.0%, 95.4%, 89.9%, and 84.4%, respectively; there were statistically significant differences in survival among the subgroups(P=0.026); there was no significant difference in the survival rate between the ES group and the CD group(P=0.918), and both were higher than the SD group(P values were 0.011 and 0.013, respectively). Univariate Cox regression analysis showed that NYHA class Ⅲ/Ⅳ and BNP>100 ng/L at admission were the risk factors for all-cause death in patients with PAH-CHD(HR=6.452, 95%CI 3.378-12.346, P<0.001, and HR=2.481, 95%CI 1.225-5.025, P=0.012). Multivariate Cox regression analysis showed that NYHA class Ⅲ/Ⅳ was an independent risk factor for all-cause death in patients with PAH-CHD(HR=4.998, 95%CI 1.246-20.055, P=0.023). Conclusions: PAH-CHD patients with different clinical subtypes have different clinical symptoms, cardiac functional class, hemodynamic characteristics, and mid to long-term survival rates. SP patients have the best prognosis, outcome of ES and CD patients is similar, and SD patients have the worst prognosis. NYHA class Ⅲ/Ⅳ is an independent risk factor for all-cause death in patients with PAH-CHD.
Adolescent ; Adult ; Familial Primary Pulmonary Hypertension ; Female ; Heart Defects, Congenital ; Humans ; Hypertension, Pulmonary ; Pulmonary Arterial Hypertension ; Retrospective Studies ; Risk Factors ; Young Adult

Objective: To explore the short-term efficacy of fenestrated atrial septal defect (ASD) occulders in the treatment of pulmonary arterial hypertension (PAH). Methods: Thirty-six healthy dogs were divided into the balloon atrial septostomy (BAS)+fenestrated ASD occulders group (n=12), BAS group (n=12) and non-septostomy group (n=12). PAH was induced by intra-atrial injection of dehydrogenized monocrotaline (1.5 mg/kg) in all dogs. Animals in the BAS+fenestrated ASD occulders group underwent atrial septal puncture and fenestrated ASD occulders implantation. Animals in the BAS group underwent balloon atrial septostomy. The non-septostomy group received no surgical intervention. The hemodynamic indexes and blood N-terminal pro-B-type natriuretic peptide (NT-proBNP) of dogs were measured before modeling, 2 months after modeling, 1, 3, and 6 months after surgery, respectively. Echocardiography was performed to observe the patency of the shunt and atrial septostomy of the dogs in the BAS+fenestrated ASD occulders group and BAS group at 1, 3, and 6 months after surgery. Three dogs were sacrificed in each group at 1, 3, and 6 months after surgery, respectively. Atrial septal tissue and fenestrated ASD occulders were removed to observe the patency and endothelialization of the device. Lung tissues were obtained for hematoxylin-eosin (HE) staining to observe the inflammatory cells infiltration and the thickening and narrowing of the pulmonary arterials. Results: Among 36 dogs, 2 dogs died within 24 hours after modeling, and 34 dogs were assigned to BAS+fenestrated ASD occulders group (n=12), BAS group (n=11), and non-septostomy group (n=11). Compared with BAS group, the average right atrial pressure (mRAP) and NT-proBNP of dogs in the BAS+fenestrated ASD occulders group were significantly reduced at 3 months after surgery (P<0.05), and the cardiac output (CO) was significantly increased at 6 months after surgery, arterial oxygen saturation (SaO₂) was also significantly reduced (P<0.05). Compared with non-septostomy group, dogs in the BAS+fenestrated ASD occulders group had significantly lower mRAP and NT-proBNP at 1, 3, and 6 months after surgery (P<0.05), and higher CO and lower SaO₂ at 6 months after surgery (P<0.05). Compared with the non-septostomy group, the dogs in the BAS group had significantly lower mRAP and NT-proBNP at 1 month after surgery (P<0.05), and there was no significant difference on mRAP and NT-proBNP at 3 and 6 months after surgery (P>0.05). Echocardiography showed that there was a minimal right-to-left shunt in the atrial septum in the BAS group at 1 month after the surgery, and the ostomy was closed in all the dogs in the BAS group at 3 months after the surgery. There was still a clear right-to-left shunt in the dogs of BAS+fenestrated ASD occulders group. The shunt was well formed and satisfactory endothelialization was observed at 1, 3 and 6 months after surgery. The results of HE staining showed that the pulmonary arterials were significantly thickened, stenosis and collapse occurred in the non-septostomy group. Pulmonary microvascular stenosis and inflammatory cell infiltration in the pulmonary arterials were observed in the non-septostomy group. Pulmonary arterial histological results were comparable between BAS+fenestrated ASD occulders group and non-septostomy group at 6 months after surgery . Conclusions: The fenestrated ASD occulder has the advantage of maintaining the open fistula hole for a longer time compared with simple balloon dilation. The fenestrated ASD occulder can improve cardiac function, and it is safe and feasible to treat PAH in this animal model.
Animals ; Atrial Septum/surgery* ; Cardiac Catheterization/methods* ; Dogs ; Familial Primary Pulmonary Hypertension ; Heart Septal Defects, Atrial/surgery* ; Hypertension, Pulmonary ; Pulmonary Arterial Hypertension