Pulmonary Hypertension in Adults with Congenital Heart Disease: Real-World Data from the International COMPERA-CHD Registry

Kaemmerer H, Gorenflo M, Huscher D, Pittrow D, Apitz C, Baumgartner H, Berger F, Bruch L, Brunnemer E, Budts W, Claussen M, Coghlan G, Dähnert I, D’Alto M, Delcroix M, Distler O, Dittrich S, Dumitrescu D, Ewert R, Faehling M, Germund I, Ghofrani HA, Grohé C, Grossekreymborg K, Halank M, Hansmann G, Harzheim D, Nemes A, Havasi K, Held M, Hoeper MM, Hofbeck M, Hohenfrost-Schmidt W, Jurevičienė E, Gumbienè L, Kabitz HJ, Klose H, Köhler T, Konstantinides S, Köestenberger M, Kozlik-Feldmann R, Kramer HH, Kropf-Sanchen C, Lammers A, Lange T, Meyn P, Miera O, Milger-Kneidinger K, Neidenbach R, Neurohr C, Opitz C, Perings C, Remppis BA, Riemekasten G, Scelsi L, Scholtz W, Simkova I, Skowasch D, Skride A, Stähler G, Stiller B, Tsangaris I, Vizza CD, Vonk Noordegraaf A, Wilkens H, Wirtz H, Diller GP, Grünig E, Rosenkranz S.J Clin Med. 2020 May 13;9(5):E1456. doi: 10.3390/jcm9051456.PMID: 32414075 Free article.


Take Home Points:


  • Adults with congenital heart disease and pulmonary hypertension have better survival compared to those with idiopathic pulmonary arterial hypertension
  • Treatment patterns changed over time, with more patients receiving combination targeted pulmonary arterial hypertension therapy
  • Despite the lack of evidence, some patients with congenital heart disease and pulmonary hypertension continued to receive anticoagulant and antiplatelets


Commentary from Dr. MC Leong (Kuala Lumpur), section editor of ACHD Journal Watch:  The COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension) registry is a prospective European registry of all patients with various forms of pulmonary hypertension. It started in Dresden, Germany in July 2007 and soon grew to include 49 pulmonary hypertension centers across 11 European countries. Understandably, the majority of the centers are from Germany. The registry has since collected some 8200 adult patients and become one of the largest pulmonary hypertension registries.


Baseline demographics


This study looks at the subset of 680 (8.3% from the total patients in the registry) adult patients (median age: 44 years, range 18-87 years and 66.6% females) in the registry with congenital heart disease. The median age of the patient is comparatively higher than the mean age of other registries of patients with congenital heart disease (CHD). This registry included 7 patients who were palliated with a Fontan circuit and received targeted pulmonary arterial hypertension (PAH) medications. Patient demographics and baseline characteristics of these patients were summarized in Table 1. Of the 680 patients, 487 (71.6%) patients had cardiac catheterization to confirm the diagnosis of pulmonary hypertension. The rest of the patients were diagnosed through non-invasive investigations.

Figure 1. showed the age distribution of this cohort of patients.


Types of congenital heart disease


Simple lesions such as ventricular septal defects (29.3%) and patent ductus arteriosus (5.9%) constitute the majority of the cases. Atrial septal defects constitute 27.4% of all patients. 264 patients had their congenital heart disease operated. A summary of the types of congenital heart disease was tabulated in table 4.



 Medication and treatment strategies


600 (88.2%) patients received targeted PAH therapy. 389 (65%) received endothelin receptor antagonists while 353 (59%) received phosphodiesterase type-5 inhibitors. Tables 2 & 3 showed the treatment characteristics and the distribution of targeted PAH medications used in different types of PAH in this cohort. 80 patients with Eisenmenger syndrome were treatment-naïve. These patients, according to the authors, were younger and had milder clinical symptoms. Treatment pattern changed over time. In the initial period, monotherapy was seen in the majority of patients (70% of total patients). After a median observation time of 45.3 months, more patients (50%) were on combination therapy in all groups except for patients with Fontan palliation (Figure 3). This was in line with the emergence of recent studies demonstrating the effects of goal-targeted therapy as well as combination therapies towards improved survival.

The use of anticoagulants or platelet was varied. It was interesting to note that 13.4% of patients with Eisenmenger were on antiplatelets as there is no reliable data to support the beneficial effects of antiplatelet in this group of patients (Figure 4). There was also a substantial amount of patients receiving vitamin K or novel anticoagulants.






Of the 511 patients who received targeted PAH therapy, 91 died during the 5-year follow-up period, compared to 41 deaths in 1326 patients with idiopathic PAH. Patients with CHD had a better 5-year survival compared to patients with idiopathic PAH (Figure 5). Among patients with Eisenmenger syndrome, those with a simple CHD had a better survival compared to those with complex CHD (81% vs 64% survival at 5-year, p=0.063). These findings were in accord with previous studies.


This is an audit of a large registry. Like many multi-center registries, it is a mammoth task to validate all the data that is being entered and hence there may be inherent error in the data entry. The authors should be commended for being able to verify registry data in up to 70% of the participating centers. Pulmonary hypertension in CHD is often not easy to group and analyze. For example, patients with atrial septal defect and PAH may be classified as a simple lesion but the underlying pathogenesis is complex and often associated with idiopathic form of PAH. To include these patients in the simple lesion group and analyze their survival with other truly simple lesions changes the survival trajectory. Also, patients with single ventricle physiology with and without palliation may have a different cause of death. Patients with fenestrated Fontan circuits have complex physiology preventing accurate assessment of its pulmonary hypertension. Lastly, time 0 in survival curves in patients with CHD and pulmonary hypertension usually arbitrarily taken as the date the patients are included into the registry. Often, patients with bad disease would have died prior to being included into the registry and by natural selection, the survived patients are the ones with better and more stable disease. This gives the false impression that patients with CHD and pulmonary hypertension have better survival than patients of other causes of pulmonary hypertension. It will be interesting to see the “real” survival curve of this group of patients if time 0 be taken during infancy or childhood when the pulmonary hypertension starts to develop.