Pulmonary Hypertension Induced by Right Pulmonary Artery Occlusion: Hemodynamic Consequences of Bmpr2 Mutation.

BACKGROUND: The primary genetic risk factor for heritable pulmonary arterial hypertension is the presence of monoallelic mutations in the BMPR2 gene. The incomplete penetrance of BMPR2 mutations implies that additional triggers are necessary for pulmonary arterial hypertension occurrence. Pulmonary artery stenosis directly raises pulmonary artery pressure, and the redirection of blood flow to unobstructed arteries leads to endothelial dysfunction and vascular remodeling. We hypothesized that right pulmonary artery occlusion (RPAO) triggers pulmonary hypertension (PH) in rats with Bmpr2 mutations. METHODS AND RESULTS: Male and female rats with a 71 bp monoallelic deletion in exon 1 of Bmpr2 and their wild-type siblings underwent acute and chronic RPAO. They were subjected to full high-fidelity hemodynamic characterization. We also examined how chronic RPAO can mimic the pulmonary gene expression pattern associated with installed PH in unobstructed territories. RPAO induced precapillary PH in male and female rats, both acutely and chronically. Bmpr2 mutant and male rats manifested more severe PH compared with their counterparts. Although wild-type rats adapted to RPAO, Bmpr2 mutant rats experienced heightened mortality. RPAO induced a decline in cardiac contractility index, particularly pronounced in male Bmpr2 rats. Chronic RPAO resulted in elevated pulmonary IL-6 (interleukin-6) expression and decreased Gdf2 expression (corrected P value<0.05 and log2 fold change>1). In this context, male rats expressed higher pulmonary levels of endothelin-1 and IL-6 than females. CONCLUSIONS: Our novel 2-hit rat model presents a promising avenue to explore the adaptation of the right ventricle and pulmonary vasculature to PH, shedding light on pertinent sex- and gene-related effects.

Monitoring of Hemodynamics With Right Heart Catheterization in Children With Pulmonary Arterial Hypertension.

Background Right heart catheterization (RHC) is a high-risk procedure in children with pulmonary arterial hypertension without clear guidelines for the indications and targets of invasive reassessment. Our objectives are to define the aims of repeated RHC and evaluate the correlation between noninvasive criteria and hemodynamic parameters. Methods and Results Clinical and hemodynamic characteristics from 71 incident treatment-naïve children (median age 6.2 years) with pulmonary arterial hypertension who had a baseline and reevaluation RHC were analyzed. Correlations between noninvasive predictors and hemodynamic parameters were tested. Adverse outcomes were defined as death, lung transplantation, or Potts shunt. At baseline, pulmonary vascular resistance index (hazard ratio [HR] 1.07 per 1 WU·m2 increase [95% CI, 1.02-1.12], P=0.002), stroke volume index (HR 0.95 per 1 L·min-1·m-2 increase [95% CI, 0.91-0.99], P=0.012), pulmonary artery compliance index (HR 0.16 per 1 mL·mm Hg-1·m-2 increase [95% CI, 0.051-0.52], P=0.002), and right atrial pressure (HR, 1.31 per 1 mm Hg increase [95% CI, 1.01-1.71], P=0.043) were associated with adverse outcomes. Pulmonary vascular resistance index, pulmonary artery compliance index, and right atrial pressure were still associated with a worse outcome at second RHC. Noninvasive criteria accurately predicted hemodynamic evolution; however, 70% of the patients who had improved based on noninvasive criteria still presented at least 1 "at risk" hemodynamics at second RHC. Conclusions Pulmonary vascular resistance index, pulmonary artery compliance index, and right atrial pressure are solid predictors of adverse outcomes in pediatric pulmonary arterial hypertension and potential therapeutic targets. Noninvasive criteria accurately predict the evolution of hemodynamic parameters, but insufficiently. Repeated RHC are helpful to identify children with persistent higher risk after treatment introduction.

[Fetal aortic valvuloplasty in critical aortic stenosis: indication, technique and postnatal outcomes]. / Valvuloplastie aortique fœtale pour sténose aortique critique : indications, technique et devenir postnatal.

Aortic stenosis is a complex heart disease that involves the aortic valve and the left ventricle. Impairment of the left ventricle, abnormalities in its size, systolic and diastolic function determine the postnatal outcomes in the same way as the aortic valve. In the most severe forms, the left ventricle cannot provide systemic circulation at birth and the physiology is that of hypoplastic left heart syndrome. Fetal aortic valvuloplasty has been developed in the 90s to prevent in utero progression of aortic stenosis to hypoplastic left heart syndrome. In the present article, the most recently reported data about indications, procedure details and postnatal outcomes were reviewed.

Pericarditis as a rare complication of pneumococcal pneumonia in a young infant.

Purulent pericarditis is an exceptionally rare complication of pneumococcal pneumonia in infants but a rapidly fatal disease if left untreated. A previously healthy 4-month-old boy presented at our emergency department with a 10-day history of fever and non-productive cough. No signs of heart failure or cardiac friction rub were evidenced. Chest radiography showed lobar pneumonia, right pleural effusion and cardiomegaly. Echocardiography revealed a massive pericardial effusion, and an emergency drainage was performed. Streptococcus pneumoniae grew up from purulent pericardial fluid and blood cultures. After intravenous antibiotherapy, the outcome was favourable. The introduction of the pneumococcal vaccine may favour an increase in the incidence of non-vaccine serotypes which most commonly cause empyaema and perhaps pericarditis. Therefore, pericarditis should always be considered a possible complication in patients with pneumococcal pneumonia and empyaema.

Chronotropic impairment after surgical or percutaneous closure of atrial septal defect.

BACKGROUND: In previous studies, an attenuated heart rate response to exercise has been noted in patients after surgical closure of atrial septal defect. The aim of this study was to compare the prevalence of chronotropic impairment after surgical and percutaneous closure of atrial septal defect. METHODS: Thirty-eight pediatric patients who underwent a surgical (group A, n = 18) or transcatheter closure (group B, n = 20) of atrial septal defect in our institution were prospectively included in the study. Treadmill exercise testing was performed using the Bruce walking treadmill protocol to voluntary exhaustion, with continuous monitoring of heart rate and oxygen consumption. RESULTS: All the children were in sinus rhythm, and had normal values for peak oxygen uptake and endurance time. Exercise heart rate was significantly lower than normal in group A at the end of stage 2 (Z-score = -0.71 +/- SD 1.02), and in both groups at the end of stage 3 (Z-score = -2.06 +/- 1.76 in A and -1.00 +/- 0.71 in B) and at peak exercise (Z-score = -2.78 +/- 2.14 in A and -0.81 +/- 0.75 in B). However, the heart rate response to exercise was significantly less attenuated in group B than in group A. Moreover, maximal heart rate was <-2 SD in 8/18 surgical patients but in no patient of the group B. CONCLUSION: The chronotropic impairment is significantly less important after transcatheter closure of atrial septal defect than after surgical closure. It is an additional argument in favor of the interventional catheterization.