Identifying predictors for heart failure outcomes in phospholamban p.(Arg14del)-positive individuals

Background

Patients with a change in the phospholamban (PLN) p.(Arg14del) gene (a variant a gene variant found mainly in the Netherlands) have a high risk of developing a cardiomyopathy, a  disease of the heart muscle, which can lead to heart failure (a reduced pumping function of the heart) that does not respond well to standard treatments. New therapies, including gene therapies, are being developed for patients with inherited heart diseases, but it can be hard to identify which patients will benefit from or depend on these therapies. This is because the PLN gene can affect the heart in different ways with different severity.

Objective

The goal of this study is to find signs in patients with the PLN p.(Arg14del) gene change that can help predict heart failure.

Methods

We collected data from 904 patients with the PLN gene change, from the PLN/ACM Registry. The main goal was to predict heart failure, which included being admitted to hospital for heart failure, needing an external heart pump (LVAD/BiVAD), getting a heart transplantation, or dying from heart failure. The predictors, or clinical signs, for heart failure were analyzed using specific statistical methods.

Results

The median follow-up period was 5.4 years (with a range from 2.3-9.7 years). During this time, 116 patients developed heart failure. Of these, 75% were admitted to hospital for heart failure, 10.3% had a heart transplantation, 9.5% needed a heart pump, and 5.2% died from heart failure. The main factors that were found to be predict heart failure were a lower left ventricular ejection fraction, a low-voltage ECG (visible in low peaks on the ECG) and a New York Heart Association class ≥2 (which means that patients develop shortness of breath at least during strenuous physical activity or even at light physical activity or at rest), all measured during the first heart evaluation.

Conclusions

This study found factors which can help predict heart failure in patients with the PLN gene change. This can make it easier to estimate a patient’s risk. Identifying patients who are at risk for heart failure is very important, as gene therapy is developing quickly. These new therapies may offer potential treatments for patients with inherited heart disease.

Translated by Myrthe van der Heide and Ruth Biller