A tool to evaluate cardiac risk in patients with mitochondrial disease – Interview with Karim Wahbi

Prof. Karim Wahbi, a cardiologist, has just published the results of an international study that he coordinated with his “Registries and databases” team at the Institute. The article relates to the prediction of cardiac consequences (complications) in adult patients with mitochondrial diseases*.

What is the background to your conduct of this work?
We have been working for several years on mitochondrial diseases, which are a heterogeneous group of rare genetic diseases that can affect several different organs, including the muscles. Thus, a certain number of these patients are affected by myopathy, cardiomyopathy and various cardiac complications. We started originally by conducting studies involving small numbers of patients (a few dozen), then, five years ago, we enrolled more patients and analysed the data for 250 patients residing mainly in the Île-de-France region, based on the registry of French patients with mitochondrial diseases, coordinated by Pascal Laforêt, and on the Cardiomyopathy database managed by my team.
In this study, we have increased the number to 600 European patients, making it the most detailed study in existence, to date, for the cardiac aspects of these diseases.

What was the study objective and how did you proceed?
Our objective was to better understand the risk, for patients, of developing long-term complications, and to improve the prediction and evaluation of this risk, in order to offer them suitable treatment.
The 600 patients enrolled in the study have proven mitochondrial disease, with mutations. They are being followed up in centres located in France, England (London), Denmark (Copenhagen), Germany (Münster) and Greece (Thessaloniki). Having a greater number of patients for analyses helps us to be statistically more precise and to conduct more detailed studies, especially on rarer types of mitochondrial disease.

What have you demonstrated based on these data?
We have demonstrated that approximately a third of these patients present abnormalities during electrocardiogram (ECG) and ultrasound examinations.
We have also demonstrated that, once treated in a reference centre, during follow up, at 5 years, approximately 10% of patients presented a severe cardiac complication (either heart failure, or electrical dysfunction: an electrical conduction abnormality, which required the implantation of a pacemaker, or sometimes cardiac arrest).
Finally, we developed statistical models that help to evaluate the risk, for patients, of having cardiac complications with fairly simple investigations (ECG, ultrasound, Holter ECG).

What conclusions did you draw from this study?
It is the first time that such statistical tools have been offered, allowing risk stratification. They can be used by any doctor seeing, in consultation, a patient with a mitochondrial disease, and they make it possible, depending on the risk level, to offer a tailored therapeutic approach: for low-risk patients, follow up can occur at longer intervals (examinations every 2 or 3 years), and for high-risk patients, it is very important that cardiac follow ups occur at shorter intervals (once a year or every 6 months), and preventive treatments are sometimes required.
Studies of this type are important in the preparation of therapeutic trials. Indeed, it is essential to be able to perform a cardiac evaluation of the effects of possible emerging treatments (pharmacological treatments or innovative therapies). This study, therefore, provides us with precious data in understanding which measures should be undertaken in the context of protocols and trials.


Cardiac Outcomes in Adults With Mitochondrial Diseases, K. Savvatis, C. Rasmus Vissing, L. Klouvi, et al., J Am Coll Cardiol. 2022 Oct, 80 (15) 1421–1430