Circulation: Heart Failure Editors’ Picks

The Early Diagnosis of Pulmonary Arterial Hypertension: Can We Do Better?

The Registry of the International Society for Heart and Lung Transplantation: Thirty-third Adult Lung and Heart–Lung Transplant Report—2016; Focus Theme: Primary Diagnostic Indications for Transplant

Pediatric pulmonary arterial hypertension (PAH) can present with a wide spectrum of disease severity. Pulmonary hypertension (PH) crises can lead to acute decompensation requiring extracorporeal membrane oxygenation (ECMO) support, including extracorporeal cardiopulmonary resuscitation (eCPR). We evaluated outcomes for pediatric PH patients requiring ECMO. A single‐institution retrospective review of pediatric PAH patients with World Symposium on PH (WSPH) groups 1 and 3 requiring ECMO cannulation from 2010 through 2022 (n = 20) was performed. Primary outcome was survival to hospital discharge. Secondary outcomes were survival to decannulation and 1‐year survival. Of 20 ECMO patients, 16 (80%) survived to decannulation and 8 (40%) survived to discharge and 1 year follow up. Of three patients who had two ECMO runs; none survived. There were five patients who had eCPR for the first run; one survived to discharge. The univariate logistic regression model showed that venovenous ECMO was associated with better survival to hospital discharge than venoarterial ECMO, (OR: 0.12, 95% CI: 0.01–0.86, p = 0.046). PH medications (administered before, during, or after ECMO) were not associated with survival to discharge. For children with decompensated PAH requiring ECMO, mortality rate is high, and management is challenging. While VA ECMO is the main configuration for decompensated PH, VV ECMO could be considered if there is adequate ventricular function, presence of a systemic to pulmonary shunt, or an intercurrent treatable illness to improve survival to discharge. A multidisciplinary approach with requisite expertise should be utilized on a case‐by‐case basis until more reliable data is available to predict outcomes.

EDITORIAL article Front. Pediatr., 30 November 2015Sec. Pediatric Cardiology Volume 3 - 2015 | https://doi.org/10.3389/fped.2015.00105

Summary : Lifelong exercise training maintains a youthful compliance of the left ventricle (LV), whereas a year of exercise training started later in life fails to reverse LV stiffening, possibly because of accumulation of irreversible advanced glycation end products. Alagebrium is a novel drug that breaks advanced glycation end product crosslinks and improves LV stiffness in aged animals. In this study, the authors prescribed alagebrium (200 mg daily) or placebo combined with aerobic exercise training or contact control in healthy, sedentary older individuals for 1 year. The authors evaluated overall cardiac function by the use of several modalities, including invasive pressure–volume measurements, exercise testing, and cardiac MRI before and after the training. To the authors’ knowledge, this is the first study to evaluate the effects of alagebrium and exercise training in healthy aged humans. After intervention, exercise training significantly increased exercise capacity, LV mass, and LV end-diastolic volume. Conversely, alagebrium had little effect on exercise capacity or LV geometry. However, alagebrium showed a modest improvement in LV stiffness compared with placebo. This favorable effect of alagebrium on LV stiffness was most prominent in individuals with combined alagebrium and exercise training. Conclusions : Alagebrium had no effect on hemodynamics, LV geometry, or exercise capacity in healthy, previously sedentary seniors. However, it did show a modestly favorable effect on age-associated LV stiffening.1 Summary : Maximum oxygen consumption (peak VO2) and efficiency of ventilation (VE) during exercise (VE/VCO2 slope) are known to stratify adults in heart failure for 1-year survival. On the basis of adult data, a recent American Heart Association scientific statement suggested that peak VO2<50% predicted for age and sex should be considered substantial impairment in exercise performance in children with heart disease and therefore a class I indication for heart transplant listing. This single-center study examined the association of …

Pulmonary arterial hypertension (PAH) is a rare disease in adults, with an estimated prevalence of approximately 30–50 per million.1 2 It is even less frequent in children, with an estimated...

<i>Circulation:</i> Clinical Summaries

ObjectiveThe aim of study was to estimate outcomes of recipients with non-ischaemic chronic heart failure (CHF) after heart transplantation (HT).MethodsFrom 2010 to 2016 we heart transplanted 80 recipients: 52.5% (n=42)...

<b>Introduction:</b> Heritable forms of paediatric pulmonary arterial hypertension (hPAH) include familial forms with or without identified mutations, and sporadic forms carrying a mutation. So far, 17 genes have been identified as playing a causal role in PAH with variable level of evidence. Children with PAH or pulmonary hypertension (PH) may also present other genetic diseases or chromosomal anomalies. <b>Aims:</b> Describe the prevalence and phenotypes of children with hPAH and PH with associated genetic disorder. <b>Methods:</b> Children with idiopathic PAH, hPAH, PAH associated with congenital heart disease (APAH-CHD) or with genetic disorders diagnosed at our institution between January 2000 and October 2021 were included. <b>Results:</b> A hundred and nineteen patients had confirmed precapillary PH at right heart catheterization. Forty-one patients (34,4%) had hPAH, 17 patients (14,3%) had a genetic disorder associated with PH, including 7 and 5 patients respectively with APAH CHD (table 1) <b>Conclusion:</b> Prevalence of genetic disorders and hPAH in children with PH/PAH appears higher than previously described, being almost observed in half of the children. Systematic genetic testing in apparently idiopathic PAH as well as in newly diagnosed patients with PH should not be solely limited to the current panel of known genes but may include larger sets of genes as well as exome/genome sequencing to increase detection of new genes in this condition.

57 - Childhood Pulmonary Arterial Hypertension

Background: We performed a meta-analysis to evaluate the efficacy and safety of pulmonary vasodilators in pediatric pulmonary hypertension (PH) patients. Methods: We searched electronic databases including PubMed, EMBASE, and the Cochrane Library up to May 2020, and conducted a subgroup analysis for pulmonary vasodilators or underlying disease. Results: Fifteen studies with 719 pediatric PH patients were included in the meta-analysis. Adverse events did not differ (p = 0.11, I 2 = 15%) between the pulmonary vasodilators group and the control group, neither in the subgroups. In total, compared with the control group treatment, pulmonary vasodilators significantly decreased the mortality (p = 0.002), mean pulmonary artery pressure (mPAP, p = 0.02), and mechanical ventilation duration (p = 0.03), also improved the oxygenation index (OI, p = 0.01). In the persistent pulmonary hypertension of the newborn (PPHN) subgroup, phosphodiesterase type 5 inhibitors (PDE5i) significantly reduced mortality (p = 0.03), OI (p = 0.007) and mechanical ventilation duration (p = 0.004). Administration of endothelin receptor antagonists (ERAs) improved OI (p = 0.04) and mechanical ventilation duration (p < 0.00001) in PPHN. We also found that in the pediatric pulmonary arterial hypertension (PPAH) subgroup, mPAP was pronouncedly declined with ERAs (p = 0.006). Systolic pulmonary artery pressure (sPAP, p < 0.0001) and pulmonary arterial/aortic pressure (PA/AO, p < 0.00001) were significantly relieved with PDE5i, partial pressure of arterial oxygen (PaO2) was improved with prostacyclin in postoperative PH (POPH) subgroup (p = 0.001). Compared with the control group, pulmonary vasodilators could significantly decrease PA/AO pressure (p < 0.00001) and OI (p < 0.00001) in the short-term (duration <7 days) follow-up subgroup, improve mPAP (p = 0.03) and PaO2 (p = 0.01) in the mid-term (7–30 days) follow-up subgroup, also decrease mortality, mPAP (p = 0.0001), PA/AO pressure (p = 0.0007), duration of mechanical ventilation (p = 0.004), and ICU stay (p < 0.00001) in the long-term follow subgroup (>30 days). Conclusion: Pulmonary vasodilators decrease the mortality in pediatric PH patients, improve the respiratory and hemodynamic parameters, reduce the mechanical ventilation duration.

Pulmonary hypertension (PH) is a rare disease in newborns, infants, and children that is associated with significant morbidity and mortality. In the majority of pediatric patients, PH is idiopathic or associated with congenital heart disease and rarely is associated with other conditions such as connective tissue or thromboembolic disease. Incidence data from the Netherlands has revealed an annual incidence and point prevalence of 0.7 and 4.4 for idiopathic pulmonary arterial hypertension and 2.2 and 15.6 for pulmonary arterial hypertension, respectively, associated with congenital heart disease (CHD) cases per million children. The updated Nice classification for PH has been enhanced to include a greater depth of CHD and emphasizes persistent PH of the newborn and developmental lung diseases, such as bronchopulmonary dysplasia and congenital diaphragmatic hernia. The management of pediatric PH remains challenging because treatment decisions continue to depend largely on results from evidence-based adult studies and the clinical experience of pediatric experts. (J Am Coll Cardiol 2013;62:D117–26) a 2013 by the American College of Cardiology Foundation Pulmonary hypertension (PH) can present at any age from infancy to adulthood. The distribution of etiologies in children is quite different than that of adults, with a predominance of idiopathic pulmonary arterial hypertension (IPAH) and PAH associated with congenital heart disease (APAH-CHD) (1–5). In pediatric populations, IPAH is usually diagnosed in its later stages due to nonspecific symptoms. Without appropriate treatments, median survival rate after diagnosis of children with IPAH appears worse when compared with that of adults (6). Therapeutic strategies for adult PAH have not been sufficiently studied in children, especially regarding potential toxicities, formulation, or optimal dosing, and appropriate treatment targets for goal-oriented therapy in children are lacking. Nevertheless, children with PAH are currently treated with targeted PAH drugs and may benefit from these new therapies. This review provides an overview of recent information regarding the current approach and diagnostic classification of PAH in children as based on discussions and recommendations from the Pediatric Task Force of the 5th World Symposium on Pulmonary Hypertension (WSPH) in Nice, France (2013).

The Registry of the International Society for Heart and Lung Transplantation: Twenty-seventh official adult heart transplant report—2010

Since the recognition of nitric oxide (NO) as a key endothelial-derived vasodilator molecule in 1987, the field of NO research has expanded to encompass many areas of biomedical research. It is now well established that NO is an important signaling molecule throughout the body. The therapeutic potential of inhaled NO as a selective pulmonary vasodilator was suggested in a lamb model of pulmonary hypertension and in patients with pulmonary hypertension in 1991.1,2 Because NO is scavenged by hemoglobin (Hb) on diffusing into the blood and is thereby rapidly inactivated, the vasodilatory effect of inhaled NO is limited largely to the lung. This is in contrast to intravenously infused vasodilators that can cause systemic vasodilation and severe systemic arterial hypotension. Recent data indicate that inhaled NO can be applied in various diseases. For example, studies suggest that inhaled NO is a safe and effective agent to determine the vasodilatory capacity of the pulmonary vascular bed. This article summarizes the pharmacology and physiology of inhaled NO and reviews the current uses of inhaled NO for the treatment, evaluation, and prevention of cardiovascular and respiratory diseases. ### Chemistry of NO Gas NO is a colorless, odorless gas that is only slightly soluble in water.3 NO and its oxidative byproducts (eg, NO2 and N2O4) are produced by the partial oxidation of atmospheric nitrogen in internal combustion engines, in the burning cinder cones of cigarettes, and in lightning storms. Medical-grade NO gas is produced under carefully controlled conditions, diluted with pure nitrogen, and stored in the absence of oxygen. The recent article by Williams4 provides a review of the chemistry of NO. ### Therapeutic Versus Endogenous NO Concentrations in the Airway Although early studies of inhaled NO in the treatment of pulmonary hypertension used concentrations of 5 to 80 ppm, it has since been realized that concentrations >20 ppm provide little additional …

Objective: Several studies showed that N-terminal pro-brain type natriuretic peptide (NT-pro-BNP) as the reliable marker both in diagnostic and prognostic workup of pediatric patients with congenital heart disease complicated by pulmonary hypertension. Furthermore, it has well assisted both in therapeutic and surgical management of children with congenital heart diseases. In this review, we aimed to analyze recent studies concerning the role of the NT-pro-BNP in pediatric cardiac patients with pulmonary hypertension. Methods: PubMed, Cochrane, Science Direct and Google Scholar databases were used with the searching of the following words: “amino terminal pro brain type natriuretic peptide”, “pediatric pulmonary hypertension”, “congenital heart diseases”, emphasizing on original research articles published within recent 15 years and in English language. We critically analyzed and summarized the retrieved studies. Conclusion: NT-pro-BNP remains as the reliable diagnostic and prognostic marker of pulmonary hypertension and congenital heart diseases in pediatric patients. NT-pro-BNP and BNP remain as the universal marker of cardiovascular pathology in pediatric population. Improvement of their effectiveness in diagnostic workup in patients with CHD and PH undergoing surgery needs further clarification. Key words: pediatric pulmonary hypertension, N-terminal pro brain type natriuretic peptide, congenital heart disease