Heiner Latus

Executive summary. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK

The European Paediatric Pulmonary Vascular Disease (PVD) Network is a registered, non-profit organisation that strives to define and develop effective, innovative diagnostic methods and treatment options in all forms of paediatric pulmonary hypertensive vascular disease, including specific forms such as pulmonary arterial hypertension (PAH)-congenital heart disease, pulmonary hypertension (PH) associated with bronchopulmonary dysplasia, persistent PH of the newborn, and related cardiac dysfunction. Methods The writing group members conducted searches of the PubMed/MEDLINE bibliographic database (1990–2015) and held five face-to-face meetings with votings. Clinical trials, guidelines, and reviews limited to paediatric data were searched using the terms ‘pulmonary hypertensioń’ and 5–10 other keywords, as outlined in the other nine articles of this special issue. Class of recommendation (COR) and level of evidence (LOE) were assigned based on European Society of Cardiology/American Heart Association definitions and on paediatric data only, or on adult studies that included >10% children. Results A total of 9 original consensus articles with graded recommendations (COR/LOE) were developed, and are summarised here. The topics included diagnosis/monitoring, genetics/biomarker, cardiac catheterisation, echocardiography, cardiac magnetic resonance/chest CT, associated forms of PH, intensive care unit/ventricular assist device/lung transplantation, and treatment of paediatric PAH. Conclusions The multipaper expert consensus statement of the European Paediatric PVD Network provides a specific, comprehensive, detailed but practical framework for the optimal clinical care of children with PH.

Treatment of pulmonary arterial hypertension in children

Pulmonary arterial hypertension (PAH) is an important cause of morbidity and mortality in children. Improved understanding of the pathophysiological mechanisms of the underlying diseases has resulted in the development of effective, but not yet curative, therapies. Currently, drugs from three main pharmacological groups targeting specific aberrant pathways (endothelin, nitric oxide, and prostacyclin) and four routes of administration (inhaled, intravenous, oral, and subcutaneous) have been approved for adult patients with PAH. However, only a minority of these drugs has been officially approved for children, mainly because randomized controlled studies are limited by the small number of paediatric patients with PAH worldwide. In children with progressive, severe PAH and an inadequate response to drug therapy, advances in interventional and surgical approaches have provided promising new strategies to avoid right ventricular deterioration. These techniques can delay or even avoid the need for lung transplantation. In this Review, we present an update on developments in drug therapy for patients with PAH and highlight the current status of these treatments in children. We also describe the new surgical, interventional, and hybrid procedures, as well as their practical application in children with severe PAH.

Hybrid therapy for hypoplastic left heart syndrome: Myth, alternative, or standard?

OBJECTIVE This retrospective study presents our operative results, mortality, and morbidity with regard to pulmonary artery growth and reinterventions on the pulmonary artery and aortic arch, including key features of our institutional standards for the 3-stage hybrid palliation of patients with hypoplastic left heart syndrome. METHODS Between June 1998 and February 2015, 182 patients with hypoplastic left heart structures underwent the Giessen hybrid stage I procedure. Among these, 126 patients with hypoplastic left heart syndrome who received a univentricular palliation or heart transplantation were included in the main analysis. Median age and body weight of patients at hybrid stage I were 6 days (0-237) and 3.2 kg (1.2-7), respectively. Comprehensive stage II operation was performed at 4.5 months (2.9-39.5), and Fontan completion was established at 33.7 months (21.1-108.2). Operative and interstage mortality, morbidity, growth and reinterventions on the pulmonary arteries, and long-term operative results of the aortic arch reconstruction were assessed. RESULTS Median follow-up time after Giessen hybrid stage I palliation was 4.6 years (0-16.8). Operative mortality at hybrid stage I, comprehensive stage II, and Fontan completion was 2.5%, 4.9%, and 0%, respectively. Cumulative interstage mortality was 14.2%. At 10 years, the probability of survival is 77.8%. Body weight (<2.5 kg) and aortic atresia had no significant impact on survival. McGoon ratio did not differ at comprehensive stage II and Fontan completion (P = .991). Freedom from pulmonary artery intervention was estimated to be 32.2% at 10 years. Aortic arch reinterventions were needed in 16.7% of patients; 2 reoperations on the aortic arch were necessary. CONCLUSIONS In view of the early results and long-term outcome, the hybrid approach has become an alternative to the conventional strategy to treat neonates with hypoplastic left heart syndrome and variants. Further refinements are warranted to decrease patient morbidity.

Potts Shunt and Atrial Septostomy in Pulmonary Hypertension Caused by Left Ventricular Disease

We report a 20-year-old patient with Shones complex and severe diastolic dysfunction of his small left ventricle (LV) in whom severe pulmonary hypertension and biventricular failure developed while he was awaiting combined heart-lung transplantation. We performed a percutaneous balloon atrial septostomy and a modified Potts shunt (13-mm graft from left pulmonary artery to descending aorta), with the aim of decompressing the hypertensive right ventricle (RV) by reducing left ventricular preload and left atrial hypertension. The procedures were uneventful. The patients condition improved rapidly and biventricular function was restored. In contrast to a Potts shunt in other conditions, patients with pulmonary hypertension caused by left ventricular disease may benefit from an additional atrial left-to-right shunt.

Assessment of pulmonary endothelial function during invasive testing in children and adolescents with idiopathic pulmonary arterial hypertension.

OBJECTIVES The purpose of our study was to assess pulmonary endothelial function by vasodilator response to acetylcholine (Ach) administered in segmental pulmonary arteries in children with idiopathic pulmonary arterial hypertension (IPAH). We hypothesized that there was a relationship among pulmonary endothelial response to Ach, severity of the disease, and clinical outcome. BACKGROUND IPAH may be associated with pulmonary endothelial dysfunction; however, data regarding the impact of endothelial dysfunction on severity and prognosis of this disease are limited. METHODS Forty-three children and adolescents (mean age: 10.4 ± 5.5 years) with IPAH were included in the study. Changes in pulmonary blood flow in response to Ach were determined using intravascular Doppler flow measurements. Pulmonary flow reserve (PFR) was calculated as the ratio of pulmonary blood flow velocity in response to Ach relative to baseline values. RESULTS Mean PFR of all patients was 1.58 ± 0.67. Mean follow-up after catheterization was 55.7 ± 41.9 months. Freedom from serious cardiovascular events (lung transplantation or death) was 83% after 2 years, 76% after 3 years, and 57% after 5 years. PFR was related significantly to World Health Organization functional class. Receiver-operating characteristic curves revealed a PFR of 1.4 as the best cutoff value. Kaplan-Meier analysis demonstrated that a PFR of <1.4 was highly predictive for cardiovascular events (log-rank [Mantel Cox] chi-square: 12.49, p < 0.0001). CONCLUSIONS Our study demonstrates a strong relationship between pulmonary endothelial response to Ach and prognosis of children with IPAH. As an adjunct to the usual testing protocol, this method provides additional information for therapeutic guidance.

Aortopulmonary Collateral Flow Is Related to Pulmonary Artery Size and Affects Ventricular Dimensions in Patients after the Fontan Procedure

Background Aortopulmonary collaterals (APCs) are frequently found in patients with a single-ventricle (SV) circulation. However, knowledge about the clinical significance of the systemic-to-pulmonary shunt flow in patients after the modified Fontan procedure and its potential causes is limited. Accordingly, the aim of our study was to detect and quantify APC flow using cardiovascular magnetic resonance (CMR) and assess its impact on SV volume and function as well as to evaluate the role of the size of the pulmonary arteries in regard to the development of APCs. Methods 60 patients (mean age 13.3 ± 6.8 years) after the Fontan procedure without patent tunnel fenestration underwent CMR as part of their routine clinical assessment that included ventricular functional analysis and flow measurements in the inferior vena cava (IVC), superior vena cava (SVC) and ascending aorta (Ao). APC flow was quantified using the systemic flow estimator: (Ao) - (IVC + SVC). Pulmonary artery index (Nakata index) was calculated as RPA + LPA area/body surface area using contrast enhanced MR angiography. The patient cohort was divided into two groups according to the median APC flow: group 1 < 0.495 l/min/m2 and group 2 > 0.495 l/min/m2. Results Group 1 patients had significant smaller SV enddiastolic (71 ± 16 vs 87 ± 25 ml/m2; p=0.004) and endsystolic volumes (29 ± 11 vs 40 ± 21 ml/m2; p=0.02) whereas ejection fraction (59 ± 9 vs 56 ± 13%; p=0.38) differed not significantly. Interestingly, pulmonary artery size showed a significant inverse correlation with APC flow (r=-0.50, p=0.002). Conclusions Volume load due to APC flow in Fontan patients affected SV dimensions, but did not result in an impairment of SV function. APC flow was related to small pulmonary artery size, suggesting that small pulmonary arteries represent a potential stimulus for the development of APCs.

Cardiac MR and CT imaging in children with suspected or confirmed pulmonary hypertension/pulmonary hypertensive vascular disease. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK

Childhood pulmonary hypertension (PH) is a heterogenous disease associated with considerable morbidity and mortality. Invasive assessment of haemodynamics is crucial for accurate diagnosis and guidance of medical therapy. However, adequate imaging is increasingly important in children with PH to evaluate the right heart and the pulmonary vasculature. Cardiac MR (CMR) and computed tomography (CT) represent important non-invasive imaging modalities that may enable comprehensive assessment of right ventricular (RV) function and pulmonary haemodynamics. Here, we present graded consensus recommendations for the evaluation of children with PH by CMR and CT. The article provides a structured approach for the use of CMR and CT imaging, emphasises non-invasive variables of RV function, myocardial tissue and afterload parameters that may be useful for initial diagnosis and monitoring. Furthermore, assessment of pulmonary perfusion and characterisation of the lung parenchyma provides structural information about processes that may cause or be due to PH.

Creation of a transcatheter fenestration in children with failure of fontan circulation: Focus on extracardiac conduit connection

We report our experience with a transcatheter technique to bypass the lung and to thus improve single‐ventricle preload and reduce venous congestion in Fontan patients.

Diagnostics in Children and Adolescents with Suspected or Confirmed Pulmonary Hypertension

We provide a practical approach on the initial assessment and diagnostic work-up of children and adolescents with pulmonary hypertension (PH). Transthoracic echocardiography (TTE) often serves as initial study tool before invasive cardiac catheterization. Misinterpretation of TTE variables may lead to missed or delayed diagnosis with devastating consequences, or unnecessary invasive diagnostics that have inherited risks. In addition to clinical and biochemical markers, serial examination of patients with PH using a standardized TTE approach, determining conventional and novel echocardiographic variables, may allow early diagnosis and treatment in paediatric PH. Cardiac magnetic resonance imaging and computed tomography represent important non-invasive imaging modalities, that together with TTE may enable comprehensive assessment of ventricular function and pulmonary hemodynamics. Invasive assessment of haemodynamics (ventricular, pulmonary) and testing of acute vasoreactivity in the catheterization laboratory is still the gold standard for the diagnosis of PH and pulmonary hypertensive vascular disease (PHVD) in children and for the initiation of specific PH therapy. We suggest the regular assessment of prognostic TTE variables as part of a standardized approach for initial diagnosis of children with PH. Overreliance on any single TTE variable should be avoided as it detracts from the overall diagnostic potential of a standardized TTE examination for PH.

Transcatheter interatrial communications for the treatment of left heart disease: Application in the pediatric population

Reduction of left atrial pressure by transcatheter creation of an interatrial communication in patients who present with left ventricular (LV) failure has recently been introduced. Such an approach allows left-to-right shunting at the atrial level aiming to reduce pulmonary congestion. Although “hard” outcome parameters were not assessed, a marked improvement in functional status and cardiac output, accompanied by a significant reduction in pulmonary capillary wedge pressure (PCWP), was observed. The reported strategy can be extended to other forms of LV diseases. On the basis of our long-term experience with manipulation of the interatrial septum in neonates born with various forms of hypoplastic left heart to decompress the left atrium, we expanded this knowledge to children and young adults with restrictive cardiomyopathy (RCM) and to those with dilated cardiomyopathy (DCM). We report the use of transcatheter atrial septostomy in 5 patients, aged 6.6 years (range, 0.9–32.0 years), with RCM in New York Heart Association Functional Classification III and IV (unknown cause in 3 and a positive family history in 1 patient) with pulmonary hypertension (mean pulmonary artery pressure [PAP] 34 10 mm Hg, mean PCWP, 22 7 mm Hg, mean right atrial pressure [RAP] 6 3 mm Hg), and four patients, aged 2.9 years (range, 2.3–4.0 years), with DCM in New York Heart Association III and IV (2 patients each with idiopathic DCM and chronic lymphocytic myocarditis), who presented with severely impaired LV function (mean LV ejection fraction, 21% 7 %; mean PAP, 17 3 mm Hg; mean PCWP, 13 3 mm Hg; and mean RAP, 5 3 mm Hg). In all cases, a percutaneous atrial septostomy using Brockenbrough technique was created without adverse events. Immediately after the procedure, PCWP dropped to 14 3 mm Hg in the RCM group and to 8 2 mm Hg in the DCM group, whereas RAP remained stable (6 2 mmHg).