Medical treatment of pulmonary hypertension in adults with congenital heart disease: updated and extended results from the International COMPERA-CHD Registry

Abstract

Background: Pulmonary arterial hypertension (PAH) is common in congenital heart disease (CHD).Because clinical-trial data on PAH associated with CHD (PAH-CHD) remain limited, registry data on the long-term course are essential. This analysis aimed to update information from the COMPERA-CHD registry on management strategies based on real-world data.Methods: The prospective international pulmonary hypertension registry COMPERA has since 2007 enrolled more than 10,000 patients. COMPERA-CHD is a sub-registry for patients with PAH-CHD Results: A total of 769 patients with PAH-CHD from 62 specialized centers in 12 countries were included into COMPERA-CHD from January 2007 through September 2020. At the last follow-up in 09/2020, patients [mean age 45.3±16.8 years; 512 (66%) female] had either post-tricuspid shunts (n=359; 46.7%), pre-tricuspid shunts (n=249; 32.4%), complex CHD (n=132; 17.2%), congenital left heart or aortic valve or aortic disease (n=9; 1.3%), or miscellaneous CHD (n=20; 2.6%). The mean 6-minute walking distance was 369±121 m, and 28.2%, 56.0%, and 3.8% were in WHO functional class I/II, III or IV, respectively (12.0% unknown). Compared with the previously published COMPERA-CHD data, after 21 months of followup, the number of included PAH-CHD patients increased by 91 (13.4%). Within this group the number of Eisenmenger patients rose by 39 (16.3%), the number of "Non-Eisenmenger PAH" patients by 45 (26.9%).Currently, among the 674 patients from the PAH-CHD group with at least one follow-up, 450 (66.8%) received endothelin receptor antagonists (ERA), 416 (61.7%) PDE-5 inhibitors, 85 (12.6%) prostacyclin analogues, and 36 (5.3%) the sGC stimulator riociguat. While at first inclusion in the COMPERA-CHD registry, treatment was predominantly monotherapy (69.3%), this has shifted to favoring combination therapy in the current group (53%). For the first time, the nature, frequency, and treatment of significant comorbidities requiring supportive care and medication are described.Conclusions: Analyzing "real life data" from the international COMPERA-CHD registry, we present a comprehensive overview about current management modalities and treatment concepts in PAH-CHD.There was an trend towards more aggressive treatment strategies and combination therapies. In the future, particular attention must be directed to the "Non-Eisenmenger PAH" group and to patients with complex CHD, including Fontan patients.

Long-term course of pulmonary arterial hypertension in adults with congenital heart disease under targeted therapy: a retrospective analysis of a single tertiary center

“…Although only limited data were available, the use of targeted PAH medication has become widespread in PAH-CHD. The therapeutic approach has even shifted in the last decade towards more aggressive use of targeted PAH medication and combination therapy, along with recognition of the effectiveness of combination therapy ( 39 , 40 ). In one small study, initial combination therapy in PAH-CHD patients was found to improve clinical course compared with monotherapy ( 41 ).…”

“…The most extensive data on the use of PAH-specific drugs in ES patients are available for ERA, which have demonstrated a clear reduction of morbidity and mortality ( 44 ). Accordingly, in larger PAH registry studies such as COMPERA, more patients were on ERA than on PDE5 inhibitors at latest observation ( 39 ). The slight divergence in our study, in which PDE5 inhibitors remained the most common medication, may be due to the fact that some of our patients were minors and already on medication before study inclusion.…”

Normal reference values of tricuspid annular dimensions and functional properties in healthy adults using three-dimensional speckle-tracking echocardiography (insights from the MAGYAR-Healthy Study)

“…Mean ± standard deviation of the difference in values obtained by two observers in case of the measurements of end-diastolic and end-systolic TAD, TAA and TAP with a correlation coefficient between these independent values for TA dimensions during the cardiac cycle. Moreover, there is an increasing interest in the non-invasive evaluation of the right heart as recently new treatment options have become available in case of pulmonary hypertension (20). Unfortunately, only limited data are available regarding the normal values of TA dimensions assessed by non-invasive cardiovascular imaging (21)(22)(23).…”

Healthcare status of adults with pulmonary hypertension due to congenital heart disease

“…Medical records were reviewed for healthcare-related information, sociodemographic parameters, relevant VSD [13] Ebstein anomaly [29] d-TGA [81] d-TGA [7] PS [27] CoA [71] PA + VSD [5] Aortic aneurysm [14] TOF [69] ASD [4] MVPS [13] VSD [56] AVSD [4] IAA [1] ASD [49] ccTGA [2] ccTGA [27] Mitral valve disease [2] Connective tissue disease [23] CoA [2] AVSD [19] Ebstein anomaly [2] TA [17] PAPVC [2] PA + VSD [15] TOF [2] DIV [12] TA [2] Mitral valve disease [12] DIV [1] Cardiomyopathy, congenital [11] DORV (Fallot-Type) [1] PDA [10] DORV + TGA [1] AVSD, partial [9] AVSD, partial [1] Subaortic stenosis [9] PA + IVS [8] PAS [7] DORV (Fallot-Type) [7] TAC [6] DORV + TGA [5] HCM [4] PAPVC [4] TAPVC [4] HLHS [1] Others* [12] *…”

“…There is a gap in knowledge regarding the awareness level of patients and their primary care providers about their own disease and, the appropriate level of care needed. In addition, there is a great need for targeted medical advice (10)(11)(12).…”