Clinicopathological implications of prkar1a mutation in patients with cardiac myxoma: Pooled data analysis from 101 myxoma cases
Altibi A, Al Jebbawi L, Patel BD, Vuong HG, and Masri AM. Clinicopathological implications of prkar1a mutation in patients with cardiac myxoma: Pooled data analysis from 101 myxoma cases. Journal of the American College of Cardiology 2020; 75(11):1195.
J Am Coll Cardiol
Background PRKAR1A is a novel genetic mutation traditionally linked to Carney Complex (CNC) and cardiac myxoma. We hypothesized that presence of PRKAR1A mutation (Mut+) identifies a subset of cardiac myxoma patients with distinct clinicopathologic features from those without the mutation (Mut-). Methods We searched PubMed, Web of Science, and Scopus from inception to September 2019 to identify individual patient data of cardiac myxoma cases. Cases were included if the mutational status of PRKAR1A gene was reported. Extracted data included: mutational status, age at diagnosis, gender, location of myxoma, multifocality, recurrence, and concomitant extra-cardiac myxomas. Results Twenty-six articles reporting on 101 individual myxoma cases with known PRKAR1A mutational status were identified. Mean age at diagnosis was 36.6 ± 16.1 years. Two-third of the cases were females (n=62), 82% of cases were Mut+ (n=83), and 93.9% (n=78) met criteria for CNC. Mean age at diagnosis for the Mut+ group and Mut- group were 35.2 and 43.3 years, retrospectively (p-value = 0.058). Overall, left atrium was the most common location for myxomas (58%). While all myxoma cases in the Mut- group were localized to the left atrium, multi-chamber myxomas occurred exclusively in patients with the mutation (p-value= 0.003). Similarly, 96% of all cases of multiple cardiac myxomas occurred in the Mut+ group. The risk of developing multiple myxomas was significantly higher in the Mut+ compared to Mut- group (RR= 4.1, p-value= 0.03). Myxoma recurrence after resection occurred in 20.8% (n=21) of all cases, 20 of them were in the Mut+ group. Time duration from surgical resection to recurrence had a mean of 7.3 ± 5.7 years. Similarly, Mut+ carried a significantly higher risk of developing extra-cardiac myxomas compared to Mut- (p-value= 0.009), as 90.6% of extra-cardiac myxomas occurred in individuals harboring the mutation. Conclusion PRKAR1A mutation identifies a subset of cardiac myxoma patients with dismal clinicopathologic features, including higher risk for multifocality, recurrence, and developing extra-cardiac myxomas. Screening for PRKAR1A mutation might need to be considered routinely at the time of diagnosis.