Outcome in phospholamban R14del carriers: results of a large multicentre cohort study.
Circ Cardiovasc Genet
; 7(4): 455-65, 2014 Aug.
Article
in En
| MEDLINE
| ID: mdl-24909667
ABSTRACT
BACKGROUND:
The pathogenic phospholamban R14del mutation causes dilated and arrhythmogenic right ventricular cardiomyopathies and is associated with an increased risk of malignant ventricular arrhythmias and end-stage heart failure. We performed a multicentre study to evaluate mortality, cardiac disease outcome, and risk factors for malignant ventricular arrhythmias in a cohort of phospholamban R14del mutation carriers. METHODS ANDRESULTS:
Using the family tree mortality ratio method in a cohort of 403 phospholamban R14del mutation carriers, we found a standardized mortality ratio of 1.7 (95% confidence interval, 1.4-2.0) with significant excess mortality starting from the age of 25 years. Cardiological data were available for 295 carriers. In a median follow-up period of 42 months, 55 (19%) individuals had a first episode of malignant ventricular arrhythmias and 33 (11%) had an end-stage heart failure event. The youngest age at which a malignant ventricular arrhythmia occurred was 20 years, whereas for an end-stage heart failure event this was 31 years. Independent risk factors for malignant ventricular arrhythmias were left ventricular ejection fraction <45% and sustained or nonsustained ventricular tachycardia with hazard ratios of 4.0 (95% confidence interval, 1.9-8.1) and 2.6 (95% confidence interval, 1.5-4.5), respectively.CONCLUSIONS:
Phospholamban R14del mutation carriers are at high risk for malignant ventricular arrhythmias and end-stage heart failure, with left ventricular ejection fraction <45% and sustained or nonsustained ventricular tachycardia as independent risk factors. High mortality and a poor prognosis are present from late adolescence. Genetic and cardiac screening is, therefore, advised from adolescence onwards.Key words
Full text:
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Calcium-Binding Proteins
/
Arrhythmogenic Right Ventricular Dysplasia
Type of study:
Clinical_trials
/
Etiology_studies
/
Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limits:
Adult
/
Aged
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Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
Circ Cardiovasc Genet
Journal subject:
ANGIOLOGIA
/
CARDIOLOGIA
/
GENETICA MEDICA
Year:
2014
Document type:
Article