Rationale and design of the SPRING trail: effectivity and safety of Pfo closuRe vs medIcine in alleviatiNg migraine, a multicenter, randomized and open-label trail.

BACKGROUND: Migraine is a leading cause of disability worldwide. Several retrospective studies have suggested that the closure of the Patent Foramen Ovale (PFO) may provide relief from migraines. However, three randomized controlled trials did not meet their primary endpoints regarding migraine cessation, reduction in monthly migraine days, and responder rates. METHODS: The SPRING study is a multicenter, prospective, randomized, and open-label trial designed to compare the effectiveness and safety of PFO closure versus medication in the relief of migraines. The primary endpoint is the total cessation of migraines, as recorded in patient headache diaries during the follow-up period. Additional diagnostic tools include echocardiography with agitated saline contrast, transcranial Doppler, and routine laboratory measurements. CONCLUSION: The SPRING trial aims to assess the effectiveness and safety of PFO closure versus medication in mitigating migraines in real-world settings. (Clinical Trails ID: NCT04946734).

ACE2 gene polymorphisms are associated with elevated pulmonary artery pressure in congenital heart diseases.

BACKGROUNDS: Angiotensin converting enzyme 2 (ACE2) polymorphisms are related to the occurrence and prognosis of cardiovascular disease. However, whether ACE2 polymorphisms also affect pulmonary circulation in congenital heart disease (CHD) remains unclear. Thus, we investigated the relationship between ACE2 single nucleotide polymorphism (SNPs) and pulmonary circulation in CHD patients of Chinese Han ethnicity. METHODS: Enrolled CHD patients (n = 367) underwent gene sequencing of ACE2 SNPs rs2074192, rs2285666, and rs2106809. Patients with pulmonary hypertension were further examined for detailed hemodynamics. RESULTS: Female heterozygous patients had worse pulmonary circulation hemodynamic parameters compared to those of homozygotes. Female CHD patients with the CCA (OR = 0.53, 95% CI: 0.32-0.88) or CCG (OR = 0.59, 95% CI: 0.35-0.99) haplotype had a lower risk of elevated pulmonary artery pressure. CONCLUSION: In female CHD patients, ACE2 SNPs are related to pulmonary circulation hemodynamics. Female CHD patients with the CCA and CCG haplotype had a lower risk of pulmonary hypertension.

Model for screening adult congenital heart disease surgery eligibility with echocardiography parameters.

OBJECTIVES: This study aimed to screen for the eligibility of correction in cases of adult congenital heart disease (CHD). Pulmonary to systemic flow ratios (Qp/Qs) > 1.5 and pulmonary to systemic vascular resistance ratios (Rp/Rs) < 1/3, acquired by right heart catheterization (RHC), are two essential parameters. Nonetheless, performing RHC at every follow-up is impractical and even harmful. Thus, it is important to establish a model to predict Qp/Qs and Rp/Rs status before a RHC confirmation, using echocardiography parameters. METHODS: A total of 1,785 patients with adult CHD were enrolled and randomly assigned to the derivation or validation groups. Echocardiogram parameters of the 974 patients in the derivation group were considered candidate predictors for surgery eligibility (Qp/Qs > 1.5 and Rp/Rs < 1/3). Binary logistic regression analyses were performed to identify the independent predictors and establish a scoring system. The scoring system was further examined in the validation group using a receiver operating characteristic (ROC) analysis. RESULTS: Estimated pulmonary artery systolic pressure, velocity through the pulmonary valve, and diameters of the left and right atria were identified as independent predictors. The area under the ROC curve of the predictive value in the validation group and its pre- and post-tricuspid valve malformation subgroups were 0.87 (95% confidence interval [CI]: 0.84-0.90, p < 0.01), 0.86 (95% CI: 0.82-0.91, p < 0.01), and 0.85 (95% CI: 0.79-0.90, p < 0.01), respectively. CONCLUSIONS: This scoring system could augment flexibility and convenience for pre-screening CHD patients' eligibility for surgery, before RHC.

Carcinoembryonic antigen levels are increased with pulmonary output in pulmonary hypertension due to congenital heart disease.

OBJECTIVE: Pulmonary artery hypertension (PAH) is a severe complication of congenital heart disease (CHD). Monitoring of pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) is essential during follow-up. This retrospective study aimed to examine carcinoembryonic antigen (CEA) as an additional marker for evaluation by investigating the correlation between CEA levels and hemodynamics in CHD-PAH. METHODS: Seventy-six patients with CHD-PAH (mean PAP [mPAP] >25 mmHg and PVR >3 Wood units, group A), 71 patients with CHD and pulmonary hypertension (CHD-PH, mPAP >25 mmHg and PVR ≤3 Wood units, group B), and 102 patients with CHD without PH (mPAP ≤25 mmHg, group C) were enrolled. Serum CEA levels and the relationships between CEA levels and hemodynamic data were assessed. RESULTS: Mean serum CEA levels were 1.99±1.61, 2.44±1.82, and 1.58±1.07 ng/mL, mPAP was 58.66±20.21, 30.2±4.83, and 17.31±4.51 mmHg, and PVR was 10.12±7.01, 2.19±0.56, and 2.2±1.1 Wood units in groups A, B, and C, respectively. Mean pulmonary output (PO) was 7.24±3.07, 15.79±5.49, 10.18±4.72 L/minute, respectively. CEA levels were positively correlated with PO and negatively correlated with PVR in all of the patients. CONCLUSION: CEA levels are increased with PO and decreased with PVR in CHD-PH.

Cardiac operation and interventional therapy during pregnancy： an analysis of outcome / 中华妇产科杂志

Objective:To explore the efficacy and safety of open cardiac operation and interventional therapy in pregnant patients and describe the feto-neonatal and maternal outcomes.Methods:A retrospective study of 39 cases of women undergoing open cardiac operation or interventional therapy during pregnancy was conducted in Guangdong Provincial People′s Hospital from Jan. 2014 to Oct. 2019.Results:The age of 39 pregnant women with gestational heart disease was (30±6) years old (21-43 years old). Among them, 37 cases were single and 2 cases were twin pregnancy. Modified World Health Organization (mWHO) pregnancy risk classification were all level Ⅳ. There were 22 women receiving cardiac operation under cardiopulmonary bypass during pregnancy, 14 patients undergoing percutaneous balloon mitral valvuloplasty, 2 patients accepting percutaneous balloon pulmonary valvuloplasty, and 1 case receiving atrial septal defect occluder with ultrasound guidance. Three were no maternal deaths during and after the operation. One patient had an inevitable abortion. Four fetuses died in the uterine after open cardiac surgery. There patients chose termination of the pregnancy after cardiac operation. There were 31 live birth, in which 7 cases were preterm live birth and 24 patients were term live birth. The total number of newborns were 33. Two fetuses suffered neonatal intracranial hemorrhage and died after birth. Thirty-one fetuses were alive and born without any abnormity.Conclusion:For pregnant women with high risk of cardiovascular disease and classified as mWHO pregnancy risk level Ⅳ, cardiopulmonary bypass and interventional therapy during pregnancy could be used as an alternative for better materal and fetal outcomes.

Serum uric acid is associated with disease severity and an important predictor for clinical outcome in patients with pulmonary hypertension / 中华心血管病杂志

Objective@#The growing body of literature showed a link between uric acid and pulmonary hypertension (PH), but the impact of hyperuremia on outcome of patients with PH has not been well defined. Therefore, the present study was performed to analyze the impact of uric acid on outcome of PH patients.@*Methods@#One hundred seventy-three PH patients (112 females, mean age 38 years old), who were hospitalized in our department between January 2010 and December 2015, were included in our study, the PH diagnosis was made based on right heart catheterization examination result (mean pulmonary artery pressure≥25 mmHg(1 mmHg=0.133 kPa)). PH patients were divided into mild to moderate PH group (Rp/Rs≤0.6, n=97) and severe PH group (Rp/Rs>0.6, n=76). Fifty-one patients (33 females, mean age 45 years old) without PH based on right heart catheterization were included as control subjects. All participants were followed up for a median of 24 months(6-71 months). Clinical endpoints were defined as cardiogenic death or heart-and-lung transplantation.@*Results@#Uric acid was positively correlated with pulmonary vascular resistance(r=0.398, P<0.01), systemic vascular resistance(r=0.244, P<0.01) and mean right atrial pressure (r=0.26, P<0.01), and was negatively correlated with cardiac index(r=-0.278, P<0.01)and mixed venous oxygen saturation (r=-0.322, P<0.01)in PH patients. Serum uric acid level was significantly higher in patients with severe PH than in patients with mild-to-moderate PH and the control subjects (both P<0.05). According to the receiver operating characteristic curve (ROC), 425.5 μmol/L was found to be the best cut-off value of serum uric acid level to predict the outcome of PH patients (sensitivity 50%, specificity 72%). During follow-up, patients with higher level of uric acid (>425.5 μmol/L) were linked with poorer clinical outcome compared to patients with uric acid <425.5 μmol/L(P=0.027).@*Conclusion@#Our findings suggests that uric acid is associated with the severity of PH and higher uric acid level serves as an important predictor for poor clinical outcome of PH patients.

Effects of iloprost combined with low dose tadalafil in adult congenital heart disease patients with severe pulmonary arterial hypertension: a single-center, open-label controlled study / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the therapy efficacy of iloprost combined with low dose tadalafil in adult congenital heart disease (CHD) patients with severe pulmonary arterial hypertension (PAH).</p><p><b>METHODS</b>Adult CHD patients with severe PAH were included and divided into the sequential combination therapy group [iloprost: 10 µg/inhalation, 6 times per day for 6 months, and then add oral tadalafil (5 mg/d) till 12 months, n = 32] and upfront combination therapy group [iloprost: 10 µg/inhalation, 6 times per day combined with oral tadalafil (5 mg) for 12 months, n = 36]. Data on 6 min walking test (6MWT), Borg dyspnea score, oxygen saturation measurement, WHO classification, and cardiac catheterization were obtained at baseline, 6 and 12 months.</p><p><b>RESULTS</b>Seventy-two patients were enrolled in the study and 68 patients completed the study. Pulmonary vascular resistance (PVR) was significantly reduced in the sequential combination therapy group[ (12.96 ± 6.48 ) Wood U vs. (16.94 ± 8.11) Wood U, P < 0.05] and in the upfront combination therapy group [(12.45 ± 7.32) Wood U vs. (16.73 ± 9.28) Wood U, P < 0.05] while pulmonary blood flow [(6.77 ± 3.17) L/min vs. (5.08 ± 2.36) L/min, P < 0.05; (6.95 ± 3.32) L/min vs. (5.03 ± 2.32) L/min, P < 0.05], the 6 MWD were significantly increased [(458 ± 59) m vs. (427 ± 65) m, P < 0.05; (494 ± 59) m vs. (436 ± 62) m, P < 0.01], the Borg dyspnea score (2.04 ± 0.72 vs. 2.52 ± 0.79, P < 0.05; 1.72 ± 0.73 vs. 2.51 ± 0.77, P < 0.01) was significantly improved in both groups at 6 months compared to baseline levels. In the upfront combination therapy group, venous oxygen saturation [(68.4 ± 9.3)% vs. (62.9 ± 9.5)%, P < 0.05] and systemic oxygen saturation during exercise[ (87.2 ± 9.7)% vs. (83.1 ± 15.6)%, P < 0.05]at 6 months were also significantly improved compared to baseline. At month 12, significantly lowered pulmonary artery pressure, PVR, Rp/Rs and increased pulmonary blood flow and cardiac index were evidenced in both groups compared to baseline.</p><p><b>CONCLUSION</b>Iloprost combined with low dose tadalafil regimen can effectively reduce PVR, increase 6MWD, and improve cardiopulmonary function in adults CHD patients with severe PAH. Compared with the sequential therapy regimen, the upfront combination therapy regimen can more rapidly improve the clinical symptoms of patients.</p>

Inaccuracy of doppler echocardiographic estimates of pulmonary artery pressures in adult atrial septal defect patients with pulmonary arterial hypertension / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>While echocardiography has been a pivotal screening test in pulmonary arterial hypertension (PAH), the presence of structural cardiac defects may affect the ability to reliably predict pulmonary artery pressures (PAPs). This study sought to evaluate the accuracy of Doppler echocardiography (DE) for estimating PAPs in adult atrial septal defect (ASD) patients with PAH.</p><p><b>METHODS</b>A prospective study was carried out to compare the echocardiographic assessment of PAP with the same pressures obtained by right heart catheterization (RHC) in adult ASD patients with PAH who underwent simultaneous DE and RHC. Bland-Altman analyses were performed to evaluate the agreement between DE and RHC measurements of PAPs.</p><p><b>RESULTS</b>Two hundred and fifty-seven patients were included in the study. A significant overestimation of the systolic pulmonary arterial pressure (sPAP) and mean pulmonary artery pressure (mPAP) was reported by echocardiography compared with those by catheterization ((81.8 ± 26.9) mmHg vs. (72.9 ± 26.9) mmHg, P < 0.01; (51.9 ± 16.4) mmHg vs. (41.4 ± 17.2) mmHg, P < 0.01, respectively). Twenty-one percent (55/257) of the patients had PAH when estimated by echocardiography whereas showed normal results in the subsequent catheterization test. Using Bland-Altman analytic methods, the bias for the echocardiographic assessment of the sPAP was 9.1 mmHg with 95% limits of agreement ranging from -24.4 to 42.6 mmHg. For mPAP measurement, the bias was 10.5 mmHg with 95% limits of agreement ranging from -12.4 to 33.4 mmHg. On multiple linear regression analysis, age, gender, body surface area, ASDs' diameter, PVR, diastolic blood pressure, and echocardiographic assessment of right atrial pressure (RAP) explained 68.8% of the total variability in the model (r(2) = 0.688, P < 0.01).</p><p><b>CONCLUSION</b>Inaccuracy was frequently reported in Doppler echocardiographic assessment of the PAP in adult ASD patients with PAH and was often associated with age, gender, body surface area, ASDs' diameter, pulmonary vascular resistance, diastolic blood pressure and echocardiographic estimation of RAP.</p>

Comparison of acute hemodynamic effects of aerosolized iloprost and inhaled nitric oxide in adult congenital heart disease with severe pulmonary arterial hypertension.

OBJECTIVE: To compare the acute hemodynamic effects of aerosolized iloprost and inhaled nitric oxide (NO) in adult congenital heart disease (CHD) patients with severe pulmonary arterial hypertension (PAH). METHODS: One hundred and eighty five adult CHDs with severe PAH were nonrandomized into two groups (iloprost, n=127; NO, n=58). Various hemodynamic parameters were measured before and after iloprost or NO inhalation. RESULTS: Iloprost and NO inhalation resulted in significant reductions in pulmonary arterial pressure (from 110.6±21.8 mmHg to 105.5±22.3 mmHg, p<0.05; from 113.1±18.7 mmHg to 107.2±19.9 mmHg, p<0.05, respectively) and pulmonary vascular resistance (PVR) (from 13.4±8.3 Wood units to 9.6±6.4 Wood units, p<0.01; from 13.7±7.1 Wood units to 9.3±4.9 Wood units, p<0.01, respectively) and increases in pulmonary blood flow (from 6.7±3.3 L/min to 9.4±5.8 L/min, p<0.05; from 6.6±3.1 L/min to 9.6±5.9 L/min, p<0.01, respectively) and the Qp/Qs ratio (from 1.5±0.8 to 2.1±1.4, p<0.01; from 1.5±0.8 to 2.0±1.3, p<0.01, respectively). When the effects of inhaled iloprost and NO were compared, similar reductions in pulmonary arterial pressure and pulmonary vascular resistance were observed. Aerosolized iloprost and inhaled nitric oxide (iNO) were generally well tolerated and no patient experienced any side effects during inhalation. CONCLUSION: Aerosolized iloprost can be effectively and safely used and might be an alternative to NO for testing pulmonary vascular reactivity and treating severe PAH in adult CHD patients.