En person håller en modell av ett hjärta i sin hand
Photo: iStock Photo

International research collaboration expands understanding of rare heart defect


NEW STUDY. By collaborating with researchers at Rigshospitalet and the University of Copenhagen, researchers at Sahlgrenska University Hospital and Sahlgrenska Academy have been able to create the largest cohort of patients to date with the rare heart defect Ebstein anomaly. The collaboration enables completely new opportunities for studying comorbidity and survival over time.

In Sweden more than four babies are born annually with the heart defect Ebstein anomaly. Those with Ebstein anomaly have a congenital defect in the valve separating the right atrium and right ventricle, which results in a smaller right ventricle than normal. The severity of the congenital defect of the heart valve varies. Severe malformations are associated with symptoms early in life, some even before birth, while a mild malformation might live without any inconvenience at all. Ebstein anomaly often occurs along with other congenital heart defects, which also complicates opportunities to study the long-term consequences of living with the defect. 

Researchers at Sahlgrenska University Hospital and the Institute of Medicine at the University of Gothenburg have joined colleagues at Rigshospitalet and the University of Copenhagen to create the largest cohort of patients with Ebstein anomaly so they can follow their comorbidity and survival over time. The cohort includes 530 patients–both those who have had surgical correction of their defect and those who have not. The patients are  born from 1970 to 2017, and have been followed for a median period of 11 years. They have been matched with 5,300 individuals in a control group for age and sex. 

Zacharias Mandalenakis and Filip Eckerström
Zacharias Mandalenakis andFilip Eckerström
Photo: Privat

“It is challenging to study rare diseases such as the Ebstein anomaly why collaborations with other countries to collect sufficient data are necessary,” says Filip Eckerström, postdoctoral researcher and resident physician in internal medicine and cardiology at Sahlgrenska University Hospital/Östra Hospital. “In the Nordic countries, we have a unique opportunity to do so, especially at the epidemiological level, as we have similar health care systems and similar nationwide medical registries.” Eckerström is first author of the article recently published in one of the highest ranking journals in cardiology (Journal of the American College of Cardiology, JACC). 

Improved survival 

The study is based on registry data from Denmark and Sweden. Up until now, international research has focused on patients who have undergone surgery for their heart defect; this is the first study to include both those who have undergone surgery and those who have not. The study shows that 79 percent of patients survived until age 40, representing a significant excess cumulative mortality compared with the general population. 

“Upon closer examination of the data, we found that patients surviving for 10 years after diagnosis had a mortality rate fairly similar to that of the general population . From a trend perspective, we found that the survival have improved markedly since the turn of the millennium,” says Filip Eckerström. 

Diagnostics of the heart defect has also improved confirmed by the greater number of patients diagnosed after 2000. Implementation of cardiac ultrasound has probably played a crucial role in this respect. During the follow-up period, 43 percent of the patients underwent heart surgery, mostly because of their Ebstein anomaly. 

Filip Eckerström
Filip Eckerström
Photo: Privat

“This is the largest cohort of surgical and non-surgical patients with the Ebstein anomaly ever published. Our research material has already attracted a lot of attention. It has been praised at two of the world’s largest conferences on congenital heart defects, in Rotterdam and in Philadelphia in 2022,” says Zacharias Mandalenakis, chief physician in cardiology at the GUCH Center at Sahlgrenska University Hospital/Östra Hospital. Mandalenakis, an associate professor at Sahlgrenska Academy at the University of Gothenburg, helped initiate collection of the study material. 

Expanded collaboration and clinical trials are next 

The researchers plan to expand collaboration and involve other Nordic countries  and conduct clinical trials. 

“The combination of epidemiological and clinical research across institutional and country borders will expand our knowledge and understanding of Ebstein anomaly,” says Filip Eckerström. 

He has already begun the next project, which aims to investigate the comorbidity in patients with Ebstein anomaly, followed by clinical cardiac examinations in Sweden, Denmark, and the United States. 

“Eventually this collaboration can pave the way to  future systematic studies of other rare congenital heart defects. If the collaboration succeeds, the concept can be applied in other categories of rare diseases, which would benefit both patients and their attending physicians. 

Title: Mortality in patients with Ebstein anomaly; DOI: 10.1016/j.jacc.2023.04.037.

The Journal has also published an editorial about the study; DOI: 10.1016/j.jacc.2023.05.009