Abstract 4141007: Incidence of positive cardiac positron emission tomography in genotype-positive patients: A Cardiovascular Genetics Clinic lens

Background: Positron emission tomography-computed tomography (PET-CT) is widely used to diagnose cardiac sarcoidosis (CS) for treatment. There is increasing recognition of myocardial inflammation in genetic arrhythmogenic cardiomyopathy (ACM) masquerading as CS. Since our institution is a high-volume arrhythmia center that frequently utilizes cardiac PET-CT studies to assess for CS and genetic evaluation to diagnose genetic cardiomyopathy (GNC), our clinical cohort is enriched for patients with both studies. Research Question: We hypothesize cardiac PET positivity is a unique feature of ACM among GNC, accompanied by markers of myocardial injury and improvement after anti-inflammatory therapy. (Steroids currently do not play a role in ACM treatment.) Goals: This investigation seeks to delineate the potential role of PET-CT and anti-inflammatory therapy in ACM. Methods: All UCLA Cardiovascular Genetics Clinic patients who underwent a cardiomyopathy gene panel were included. Patient genotypes were classified as positive – harboring at least a pathogenic (P) or likely pathogenic (LP) variant, uncertain – at least a variant of uncertain significance, or negative. Genes were grouped into ACM or non-ACM based on the 2019 Heart Rhythm Society consensus. Patients were screened for PET-CT scans before genetic testing. PET-CT positivity was defined by cardiac FDG uptake without extracardiac uptake. Results: Forty-eight patients received a PET-CT scan, with 58% (28/48) harboring a positive genotype. Of 320 patients with P/LP variants, 28 (8.8%) underwent PET-CT scans (11 ACM, 17 non-ACM). Six scans were positive, including 3 ACM genes. PET-CT positivity rates were 27.3% (3/11) for P/LP ACM genes and 17.6% (3/17) for P/LP non-ACM genes. Among the 6 PET-CT-positive patients, 3 ( FLNC , GAA , MYH7 ) received immunosuppressive therapy with variable response. Our FLNC patient showed no improvement after 6 months of steroids. Conclusion: We recommend genetic testing for suspected CS cases with positive cardiac PET-CT without extracardiac manifestation. Cardiac PET-CT positivity led to a high genetic diagnostic yield (58%) in our clinic, where the genetic finding was enriched for but not limited to ACM gene mutations. Our limited sample of steroid treatment yielded varied results. A consortium approach to delineate patient characteristics, immunosuppressive responsiveness, and randomized control trials may help address these knowledge gaps in the future.