{
  "abstract": "Background The establishment of a Nationally commissioned Genomic Medicine Service (GMS) in the NHS has standardized genetic testing pathways for inherited cardiac conditions (ICC). We evaluated the initial experience of mainstream genetic testing in a high-volume ICC specialist centre, focusing on cardiomyopathy (CMP) patients.Methods A retrospective analysis was conducted on 180 consecutive CMP patients who underwent genetic testing from April 2020. Patient demographics, genetic test outcomes, and disease characteristics were extracted from electronic records. Testing outside national criteria occurred following multidisciplinary team (MDT) discussion. Genetic results were categorized into pathogenic/likely pathogenic variants (LP/P) and variants of uncertain significance (VUS). This study focused on hypertrophic cardiomyopathy (HCM, R131) and dilated/arrhythmogenic cardiomyopathy (DCM/ACM, R132) panels.Results Among the 180 patients, 65% were male (mean age: 52.5 years). The cohort included 100 HCM, 41 DCM, and 39 arrhythmogenic cardiomyopathy (ACM) cases. Ethnic distribution was 49% White, 10.6% Black, 10.6% Asian, 2.2% mixed-race, and 26% other. A family history of CMP was present in 29.4% of cases, and 71.7% met testing criteria (HCM: 70%, DCM: 86%, ACM: 62%).LP/P variants were identified in 27 patients (15%), while 21 (11.7%) had a VUS. Among those tested outside of criteria, 4% had an LP/P result, and 15% had either a VUS or LP/P variant (figure 1). In the HCM cohort, women had a higher positive yield (33% vs. 10%; p=0.003) (figure 2). Younger age, asymmetric septal hypertrophy, and a family history were associated with positive results (table 1). In contrast, individuals over 50 had a lower detection rate, with low prevalence of family history of CMP (9%) and a higher prevalence of cardiovascular risk factors (82%).For DCM and ACM, positive results were observed in 11% of cases (6 and 3 patients, respectively). Among DCM positives, 5 of 6 were White women, with a mean left ventricular ejection fraction (LVEF) of 38%. In ACM, all positive cases met diagnostic criteria and had sustained ventricular arrhythmias (table 2). In the overall ACM group, 15 patients (39%) had exhibited sustained arrhythmias.Abstract 1-030 Table 1Genetic results in the HCM group P/LP 18%VUS 7% Total of HCM patients (100 pts) LP/P (18 pts) Gene elusive (82 pts) p- value (95%) for test result Fulfil criteria7017 (24%)53 (75%)0.011Age5245570.001male women677 (10%)60 (89%) 3311 (33%)22 (66%)0.011White 4111 (26.8%)30 (73%)0.055Family History of CMP2510 (41%)14 (58%)0.001Cardiovascular risk factors584 (6.9%)54 (93%)<0.001Asymmetric LVH pattern4513 (30%)31 (70%)0.013MWT16,917.116.90.8HCM Risk-SCD 2,52.52.50.9CMP: Cardiomyopathy. LVH: Left ventricular hypertrophy. MWT: Maximal wall thicknessAbstract 1-030 Table 2Genetic results in DCM and ACM groups P/LP 11%VUS 17.5% Total of DCM patients DCM Positive (6 pts) p- value (95%) for test result Total of ACM patients ACM positive (3 pts) p- value (95%) for test result Fulfil criteria35 (86%)50.824 (62%)3 0.154Age48 +-1445 +-130.3852+-1253+-170.87male women 29 (75%)2 18 (44%)50.0710 (25%)10.9White 26 (63%)5 0.2722 (56%)2 0.7Family History of CMP18 (43%)30.7411 (28%)10.8Cardiovascular risk factors8 (19%)20.359 (23%)10.56LVEF38%38%0.8755%57%0,38Sustained ventricular arrhythmias4 (10%)10.3215 (39%)3 0.07CMP: Cardiomyopathy. LVEF: Left ventricular ejection fraction.Abstract 1-030 Figure 1Genetic results in patients who meet or do not meet testing criteriaAbstract 1-030 Figure 2Differences in genetic test results in HCM patients according to sexConclusions In this initial cohort, women with HCM had the highest yield of a positive genetic test, while men exhibited a similar phenotype but had a higher prevalence of cardiovascular risk factors. A genetic cause was suspected in over 25% of cases that did not fulfil diagnostic testing criteria, with 15% of these patients carrying an LP/P variant or a VUS. These findings highlight the necessity for ongoing refinement of genetic testing strategies in ICC populations and underscore the critical role of ICC expertise in identifying affected individuals outside standard criteria.",
  "authors": [
    {
      "affiliations": [
        "Inherited Cardiac Conditions Unit, St George´s University Hospital NHS Foundation Trust, London, UK"
      ],
      "name": "Pablo Martin-Marin"
    },
    {
      "affiliations": [
        "Inherited Cardiac Conditions Unit, St George´s University Hospital NHS Foundation Trust, London, UK"
      ],
      "name": "James Dargan"
    },
    {
      "affiliations": [
        "Inherited Cardiac Conditions Unit, St George´s University Hospital NHS Foundation Trust, London, UK"
      ],
      "name": "Chris Miles"
    },
    {
      "affiliations": [
        "Inherited Cardiac Conditions Unit, St George´s University Hospital NHS Foundation Trust, London, UK"
      ],
      "name": "Michael Papadakis"
    },
    {
      "affiliations": [
        "Inherited Cardiac Conditions Unit, St George´s University Hospital NHS Foundation Trust, London, UK"
      ],
      "name": "Elijah R Behr"
    },
    {
      "affiliations": [
        "Inherited Cardiac Conditions Unit, St George´s University Hospital NHS Foundation Trust, London, UK"
      ],
      "name": "Sanjay Sharma"
    },
    {
      "affiliations": [
        "Inherited Cardiac Conditions Unit, St George´s University Hospital NHS Foundation Trust, London, UK"
      ],
      "name": "Maria Teresa Tome-Esteban"
    }
  ],
  "title": "1-030 Mainstream genetic testing in an ICC specialist centre: experience under national testing criteria",
  "uid": "127f7b53-0def-5410-af91-7267064e8b6a"
}