Prospective Analysis of Cardiac Function in Patients with CLN2 Disease: Do We Need a Different Management Because of Cardiac Co-morbidities

Background: Therapy induced longer life expectancy leads to an increased number of co-morbidities in neurodegenerative diseases. A cardiac impairment is known in neuronal ceroid lipofuscinoses (NCLs) but there is limited data about the onset and clinical relevance. The positive effect of intraventricular enzyme replacement therapy (ICV-ERT) on CNS degeneration is proven. Data about the impact on cardiac function is still missing. The purpose of this ongoing longitudinal prospective study is to analyze cardiac function in pediatric patients with CLN2 disease receiving intraventricular enzyme replacement therapy (ICV-ERT).

Methods: A total of 46 CLN2 patients with a median age of 106 months (range 41–214 m) were investigated (m = 27, f = 19). All patients received ICV-ERT. Examination included echocardiography, electrocardiogram (ECG), and cardiac serum biomarkers proBNP and high-sensitive troponin I. Until now 10 patients had a follow up at 6 months, 3 patients at 12 months, 1 patient at 15 months.

Results: Echocardiography showed normal left and right systolic function in 46 (100%) patients, characterized by LV ejection fractions (EF) within the range of male 52–72% and female 54–74%, myocardial strain values of male -16.7% and female -17.8% and for the right ventricle TAPSE measurements exceeding 17mm. s No patient had relevant myocardial hypertrophy. Diastolic function parameters demonstrated borderline normal function in 11 patients (24%). 43 patients had normal sinus rhythm, three had coordinated atrio-ventricular rhythm. In 8 patients non pathologic incomplete right bundle branch blocks were observed, including one case of complete right bundle branch block. Cardiac biomarker levels remained within standard limits, with hsTrop I values below 34.2 ng/L for males and 15.6 ng/L for females. Follow-up assessments after 6, 12, and 15 months showed no substantial deviations in parameters.

Conclusion: ICV-ERT related longer life-expectancy does not lead to any relevant cardiac impairment in pediatric patients. Occurrence of borderline diastolic function should be followed. More important we did not see any negative effect caused by therapy at short to midterm follow-up. A continuous cardiac follow-up is required to accompany these complex patients into adulthood.

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Artikel online veröffentlicht:
13. Februar 2024