Congenital Heart Disease-associated Pulmonary Hypertension Research Articles

The impact of right atrial volume on ablation outcomes in patients with pulmonary hypertension and atrial flutter

BackgroundCatheter ablation has evolved as a safe treatment for atrial flutter (AFL) in patients with pulmonary hypertension (PH), and the recurrence of AFL may accelerate clinical decompensation. The aim of this study was to determine the recurrence rate and risk factors for recurrent AFL in PH patients after ablation.MethodsAll PH patients who underwent AFL ablation at Fuwai Hospital between May 2015 and December 2020 were followed up. The recurrence rate and risk factors for recurrence were analyzed.ResultsA total of 68 PH patients (mean age 44.0 ± 13.0 years, 36.8% male) were enrolled. The majority patients diagnosed PH had congenital heart disease-associated PH (63.2%), and 30.9% had idiopathic pulmonary arterial hypertension. At baseline, most patients (80.9%) had only cavotricuspid isthmus (CTI)-related AFL; the occurrence of non-CTI-related AFL among patients was 8.8%, and 10.3% of the patients had both types of AFL. During a median follow-up of 17.5 months, 22 patients developed at least one recurrent AFL episode (AFL-free survival: 76.5% at 1 year). The immediate success of ablation (HR 0.061, 95% CI 0.009 to 0.438; P = 0.005) and the right atrial volume index (RAVi, per 10 ml/m2; HR 1.064, 95% CI 1.011 to 1.120; P = 0.018) were associated with long-term ablation outcomes in PH patients. With 166.64 ml/m2 as a cutoff value, AFL-free survival was significantly greater in patients whose RAVi was < 166.64 ml/m2 (log-rank P = 0.024).ConclusionThe immediate success of ablation and the RAVi are associated with recurrent AFL. Patients with a RAVi ≥ 166.64 ml/m2 are likely experience recurrence.

Left main coronary artery compression in precapillary pulmonary hypertension.

Pulmonary hypertension (PH) is a progressive and invalidating condition despite available therapy. Addressing complications such as left main coronary artery compression (LMCo) due to the dilated pulmonary artery (PA) may improve symptoms and survival. Nevertheless, clear recommendations are lacking. The aim of this study is to analyze the prevalence, characteristics, predictive factors and impact of LMCo in a heterogenous precapillary PH population in a single referral center. Two hundred sixty-five adults with various etiologies of precapillary PH at catheterization were reviewed. Coronary angiography (CA) was performed for LMCo suspicion. Revascularization was performed in selected cases. Outcomes were assessed at a mean follow-up of 3.9 years. LMCo was suspected in 125 patients and confirmed in 39 (31.2%), of whom 21 (16.8%) had 50%-90% stenoses. Nine revascularizations were performed, with clinical improvement. The only periprocedural complication was a stent migration. LMCo was associated with PH etiology (p 0.003), occuring more frequently in congenital heart disease-associated PH (61.5% of all LMCo cases, 66.6% of LMCo ≥ 50%). Predictors of LMCo ≥50% were PA ≥ 37.5 mm (Sn 81%, Sp 74%) and PA-to-aorta ≥1.24 (Sn 81%, Sp 69%), with increased discrimination when considering RV end-diastolic area. LMCo ≥ 50% without revascularization presented clinical deterioration and worse survival (p 0.019). This analysis of a heterogeneous pre-capillary PH population provides LMCo prevalence estimation, predictive factors (PA size, PA-to-aorta, RV end-diastolic area and PH etiology) and long-term impact. While LMCo impact on survival is inconclusive, untreated LMCo ≥ 50% has worse prognosis. LMCo revascularization may be performed safely and with good outcomes.

Maternal Outcomes Among Pregnant Women With Congenital Heart Disease-Associated Pulmonary Hypertension.

Studies focused on pregnant women with congenital heart disease (CHD)-associated pulmonary hypertension (PH) are scarce and limited by small sample sizes and single-center design. This study sought to describe the pregnancy outcomes in women with CHD with and without PH. Outcomes for pregnant women with CHD were evaluated retrospectively from 1993 to 2016 and prospectively from 2017 to 2019 from 7 tertiary hospitals. PH was diagnosed on the basis of echocardiogram or catheterization. The incidence of maternal death, cardiac complications, and obstetric and offspring complications was compared for women with CHD and no PH, mild, and moderate-to-severe PH. A total of 2220 pregnant women with CHD had completed pregnancies. PH associated with CHD was identified in 729 women, including 398 with mild PH (right ventricle to right atrium gradient 30-50 mm Hg) and 331 with moderate-to-severe PH (right ventricle to right atrium gradient >50 mm Hg). Maternal mortality occurred in 1 (0.1%), 0, and 19 (5.7%) women with CHD and no, mild, or moderate-to-severe PH, respectively. Of the 729 patients with PH, 619 (85%) had CHD-associated pulmonary arterial hypertension, and 110 (15%) had other forms of PH. Overall, patients with mild PH had better maternal outcomes than those with moderate-to-severe PH, including the incidence of maternal mortality or heart failure (7.8% versus 39.6%; P<0.001), other cardiac complications (9.0% versus 32.3%; P<0.001), and obstetric complications (5.3% versus 15.7%; P<0.001). Brain natriuretic peptide >100 ng/L (odds ratio, 1.9 [95% CI, 1.0-3.4], P=0.04) and New York Heart Association class III to IV (odds ratio, 2.9 [95% CI, 1.6-5.3], P<0.001) were independently associated with adverse maternal cardiac events in pregnancy with PH, whereas follow-up with a multidisciplinary team (odds ratio, 0.4 [95% CI, 0.2-0.6], P<0.001) and strict antenatal supervision (odds ratio, 0.5 [95% CI, 0.3-0.7], P=0.001) were protective. Women with CHD-associated mild PH appear to have better outcomes compared with women with CHD-associated moderate-to-severe PH, and with event rates similar for most outcomes with women with CHD and no PH. Multimodality risk assessment, including PH severity, brain natriuretic peptide level, and New York Heart Association class, may be useful in risk stratification in pregnancy with PH. Follow-up with a multidisciplinary team and strict antenatal supervision during pregnancy may also help to mitigate the risk of adverse maternal cardiac events.

The Heroic Chamber – an Outlook on the Right Ventricle in Eisenmenger Syndrome

Abstract Despite being at the extreme spectrum of congenital heart disease-associated pulmonary hypertension, patients with Eisenmenger syndrome have better outcomes compared to other types of pulmonary arterial hypertension, especially in the case of post-tricuspid shunts. This survival advantage seems to be at least partly due to significant resilience of the right ventricle and a relative resistance to failure. This paper aims to review the concept of right ventricular adaptive remodeling in Eisenmenger syndrome, its impact on prognosis and the role of multimodality imaging in the right ventricle's assessment in this setting.

High plasma adiponectin is associated with increased pulmonary blood flow and reduced right ventricular function in patients with pulmonary hypertension

BackgroundAdiponectin is a biomarker closely related to heart failure. However, its role in pulmonary hypertension remains unclear. In this study, we investigated the association between adiponectin and hemodynamic abnormalities, right ventricular function in patients with congenital heart disease associated pulmonary hypertension (CHD-PH).MethodsPatients with CHD-PH were enrolled in this cross-sectional study. Linear regression analysis was performed to assess the association between adiponectin, N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) and different clinical parameters. Results were depicted as beta-estimates(ß) with 95%-confidence intervals (95% CI). In addition, mediation and receiver operating characteristic curve analyses were used to analyze the relationships among adiponectin, NT-proBNP and right ventricular function.ResultsA total of 86 CHD-PH patients were included. The overall mean adiponectin concentration was 7.9 ± 5.8 μg/ml. Log adiponectin was positively correlated with pulmonary circulation index (ß = 2.2, 95% CI 0.5, 4.0), log NT-proBNP (ß = 0.22, 95% CI 0.04, 0.41) and inversely with the tricuspid annular plane systolic excursion (TAPSE, ß = -4.7, 95% CI -8.6, − 0.8). The mediation analysis revealed the association between NT-proBNP and TAPSE was fully mediated by adiponectin (total effect c = − 5.4, 95% CI -9.4, − 1.5, p = 0.013; direct effect c’ = − 3.7, 95% CI -7.5, 0.1, p = 0.067). Additionally, the efficiency of adiponectin for detecting right ventricular dysfunction was not inferior to NT-proBNP (AUC = 0.84, 95% CI 0.67–1.00 vs AUC = 0.74, 95% CI 0.51–0.97, p = 0.23).ConclusionsAdiponectin is closely correlated with pulmonary blood flow and right ventricular function and may be a valuable biomarker for disease assessment in patients with pulmonary hypertension.

Up-regulated lipocalin-2 in pulmonary hypertension involving in pulmonary artery SMC resistance to apoptosis.

A key feature of pulmonary hypertension (PH) is the remodeling of small pulmonary arteries due to abnormal pulmonary artery smooth muscle cell (PASMC) proliferation and resistance to apoptosis. However, the cellular mechanisms underlying how PASMCs in the pathological condition of pulmonary hypertension become resistant to apoptosis remain unknown. It was recently reported that lipocalin 2 (Lcn2) is up-regulated in a wide array of malignant conditions, which facilitates tumorigenesis partly by inhibiting cell apoptosis. In this study, we observed that the expression levels of Lcn2 were significantly elevated in a rat PH model induced with monocrotaline and in patients with congenital heart disease-associated PH (CHD-PH) when compared with respective control. Therefore, we hypothesize that Lcn2 could regulate human PASMC (HPASMC) apoptosis through a mechanism. By the detection of DNA fragmentation using the TUNEL assay, the detection of Annexin V/PI-positive cells using flow cytometry, and the detection of cleaved caspase-3 and caspase-3 activity, we observed that Lcn2 significantly inhibited HPASMC apoptosis induced by serum withdrawal and H2O2 treatment. We also observed that Lcn2 down-regulated the proapoptotic protein Bax, decreased the levels of cellular ROS, and up-regulated the expression of superoxide dismutases (SOD1 and SOD2). In conclusion, Lcn2 significantly inhibits HPASMC apoptosis induced by oxidative stress via decreased intracellular ROS and elevated SODs. Up-regulation of Lcn2 in a rat PH model and CHD-PH patients may be involved in the pathological process of PH.

Prevalence of iron deficiency in pulmonary hypertension and comparison according etiology

Background and objectives: Although iron is a pivotal player in several critical enzymes, limited data is available on the prevalence of iron deficiency in pulmonary hypertension (PH). We sought to assess the prevalence of iron deficiency in a population with PH. Methods: We performed a clinical, hemodynamic and echocardiographic characterization of all PH patients currently being followed in PH clinic between 2008 and 2012. We have assessed the prevalence of iron deficiency in this population by the evaluation of ferritin and transferrin saturation at baseline, nadir values and latest assessment on outpatient clinic. We also compared the different groups of PH. A total of 114 patients (68.4% female, mean age 44±18.3 years) were included. Results: Most patients were from group 1 PH (40.6%) whereas chronic thromboembolic PH comprised 23.8% patients, followed by congenital heart disease-associated PH in 22,8% (18.3% with Eisenmenger's Syndrome). At baseline, most patients were in NYHA 3 (44%) and NYHA 4 (28.4%). Mean brain natriuretic peptide was 355 pg/mL, mean pulmonary artery pressure was 51 mmHg, mean capillary wedge pressure was 9 mmHg and cardiac output was 3.0 L/min. Approximately one-third of patients were receiving warfarin and 14% patients required continuous oxygen. We have found that all the three groups showed transferrin saturation values lower than the reference values. The difference between the groups was statistically significant (DADOS p=0,009). The lowest values were found in group 1, with a mean value of 12%. Serial ferritin values were normal or elevated and no difference between groups was found. After follow-up, there was a favorable outcome when assessing the final transferrin saturation with respect to the minimum value (p<0,0001). Conclusion: The prevalence of iron deficiency is significantly high in PH, particularly in groups 1 and 2. However, there is a good response to treatment.

Pulmonary Hypertension in Latin America: Pulmonary Vascular Disease: The Global Perspective

Latin America is here defined as all of the Americas south of the United States. In the setting of pulmonary hypertension, there are social inequalities and geophysical aspects in this region that account for a high prevalence of certain etiologies. This review aimed to analyze some of these factors. Data were collected from the existing literature. Information also was obtained from local tertiary-care centers to where patients with pulmonary hypertension generally are referred. Further, local experience and expertise was taken into consideration. Three etiologies of pulmonary hypertension were found to be the most prevalent: schistosomiasis (approximately 1 million affected people in Brazil), high altitude (particularly in the Andes), and congenital heart disease (late diagnosis of congenital left-to-right shunts leading to development of pulmonary vasculopathy). The diversity in terms of ancestries and races probably accounts for the differences in phenotype expression of pulmonary hypertension when a given region is considered (eg, schistosomiasis-, high-altitude-, or congenital heart disease-associated pulmonary hypertension). Governmental measures are needed to improve social and economic inequalities with an obvious impact on certain etiologies, such as schistosomiasis and congenital heart disease. Early diagnosis of pulmonary hypertension and access to medication remain important challenges all over Latin America.

Pulmonary hypertension complicating congenital heart disease

Congenital heart disease can predispose individuals to pulmonary vascular remodeling as a result of the abnormality in pulmonary blood flow and pressure that accompanies the specific congenital defect being considered. Pulmonary arterial hypertension associated with congenital heart defects is an important determinant of functional capacity and survival, especially when the Eisenmenger's state of reversed shunt is present. The likelihood of right ventricular dysfunction and failure increases with the degree of pulmonary artery pressure. Thus, the aim of disease management in this patient population should be to prevent or improve right heart failure. Current therapies that modify the progression of pulmonary vascular disease-including endothelin-1 receptor antagonists, phosphodiesterase-5 inhibitors, and prostanoids-should be considered carefully in patients with congenital heart disease-associated pulmonary hypertension. The risks and benefits of altering the balance of pulmonary vascular resistance to systemic vascular resistance must be weighed for each patient.

Endothelial cell dysfunction correlates differentially with survival in primary and secondary pulmonary hypertension

Background Plasma von Willebrand factor antigen (vWF:Ag) has been used as a marker of endothelial perturbation in a number of vascular disorders. In this study, vWF:Ag was determined as an attempt to evaluate the severity of endothelial cell dysfunction in primary pulmonary hypertension (PPH) and congenital heart disease-associated pulmonary hypertension (CHD-PH) comparatively and to determine its impact on short-term survival. Methods and Results Clinical, hemodynamic, and biochemical data were obtained from 11 patients with PPH and 24 with CHD-PH. Patient groups were similar in terms of age and pulmonary artery pressure. vWF:Ag was measured by electroimmunodiffusion. Patients were followed up for 1 year and at that time, data collected at the beginning of the study were subjected to univariate and multivariate analyses. vWF:Ag was increased in patients (normal reference value 87% ± 23% activity, mean ± SD), with higher levels in the PPH group (231% ± 89%) in comparison with the CHD-PH group (127% ± 68%) ( P < .001). Multivariate analysis showed that survival was influenced by the underlying cause of pulmonary hypertension and vWF:Ag levels but not by patient age, sex, or pulmonary artery pressure. Seven of 10 nonsurvivors but only 4 of 25 survivors had PPH ( P = .007). vWF:Ag was 255 ± 90% in the nonsurvivor group and 121% ± 54% in the survivors ( P < .001). Conclusions Our findings suggest that short-term survival is related to the severity of endothelial cell dysfunction in pulmonary hypertension. In addition, exceedingly high vWF:Ag levels in PPH might reflect a particular pattern of endothelial cell dysfunction that could be associated with decreased short-term life expectancy in this disorder compared with secondary forms of pulmonary hypertension.