implies that the presence of a titin truncating mutation in a patient with DCM does not preclude the possibility of func- tional recovery. 143 CLINICAL AND GENETIC CHARACTERISTICS OF FAMILIAL DILATED CARDIOMYOPATHY IN A LARGE UK PROSPECTIVE COHORT 1 Upasana Tayal*, 2 Rachel J Buchan, 3 Nicola Whiffin, 4 Simon Newsome, 3 Francesco Mazzarotto, 2 Roddy Walsh, 3 James S Ware, 5 Stuart Cook, 2 Sanjay Prasad. 1 Royal Brompton Hospital/Imperial College; 2 Royal Brompton Hospital ; 3 Imperial College, London; 4 London School of Hygiene and Tropical Medicine; 5 Duke National University Singapore; *Presenting Author 10.1136/heartjnl-2016-309890.143 Background Up to fifty percent of idiopathic dilated cardiomy- opathy (DCM) has a familial basis. Variants can occur in over 40 genes, though truncating variants in the sarcomeric gene titin account for the largest proportion (~20%). At least half of familial DCM cases are genetically orphan. We sought to study whether familial DCM was associated with distinct clini- cal characteristics, independently of the underlying genetic variant. Methods 595 prospectively recruited DCM patients underwent detailed phenotyping with cardiac MRI (Siemens scanners, 1.5T) and were sequenced using a customised panel of ~100 cardiomyopathy genes on Illumina and 5500xl platforms. Var- iants were identified and annotated using a customised bioin- formatics pipeline. Clinical information including family pedigree data, ECG, and arrhythmia status at diagnosis (pres- ence of confirmed ventricular or atrial arrhythmias) was col- lected on all patients. Familial DCM was defined as DCM occurring in 2 or more 1st or 2nd degree family members. Chi squared or Fisher’s exact test was used to compare across categorical variables and t-tests or Mann-Whitney U tests across continuous variables as appropriate. Results Overall, 16% of patients (95 out of 595) had familial DCM. Thirty individuals came from 13 families, the remain- ing were unrelated probands. Patients with familial DCM had an earlier age of disease onset (49.8 years vs 58.8 years, p < 0.0001). Non-familial DCM was characterised by a male preponderance (71% vs 56%, p = 0.004). Patients with familial DCM had less conduction disease at baseline (11% vs 36%, p < 0.0001). There was no difference in confirmed VT, NSVT or atrial fibrillation at baseline between groups. Patients with familial DCM had a milder intermediate phe- notype of DCM (left ventricular ejection fraction 45.2% vs 38.2%, p < 0.0001). Right ventricular ejection fraction was similar in both groups (39.1% familial vs 37.1% non-familial, p = 0.14). There was no difference in the presence of mid wall fibrosis detected on late gadolinium imaging (p = 0.54). There were 44 potentially disease-causing variants in DCM genes in the familial DCM cohort (Table 1). Genetic testing had a yield of 44% in familial (n = 42), and 22% in non- familial DCM (n = 117). Five patients carried 2 variants. Truncating variants in titin were the most common variant (n = 17) and were over twice as common in patients with fami- lial DCM compared to those without (18% vs 6.8%, p < 0.001). Truncating and missense variants in LMNA were ten times more frequent in familial DCM compared to non fami- lial DCM (p < 0.001). Conclusions Disease causing variants in TTN and LMNA were more commonly associated with familial DCM, but 56% of patients with familial DCM remain genetically unexplained. This highlights the need for further novel DCM disease gene discovery. Our data show that familial DCM is characterised by a younger age of disease onset and less severe ventricular dysfunction as compared to non-familial DCM. Abstract 143 Table 1 Burden of variants in DCM genes in familial and non-familial DCM Gene Percentage of variants in familial DCM patients (N=95) (=total number of variants in cohort) Percentage of variants in non familial DCM patients (N=500) (=total number of variants in cohort) P value Titin (TTN) 22.1% (21) 7.6% (38) <0.001 Lamin A/C (LMNA) 6.3% (6) 1.2% (6) 0.006 Myosin heavy chain beta (MYH7) 6.3% (6) 4.2% (21) 0.42 Plakophilin 2 (PKP2) 4.2% (4) 4.0% (20) 1.0 Troponin T 2 (TNNT2) 3.2% (3) 1.2% (6) 0.16 RNA Binding Motif Protein 20 (RBM20) 2.1% (2) 4.4% (22) 0.40 Tropomyosin1 (TPM1) 1.1% (1) 0 0.16 BCL2- Associated Athanogene 3 (BAG3) 1.1% (1) 1.6% (8) 1 Abstract 142 Table 2 Results of linear regression analysis to evaluate the effect of a truncating variant in TTN (TTNtv) on the interval change in left ventricular ejection fraction (LVEF), indexed left ventricular end diastolic volume (LVEDVi), end systolic volume (LVESVi), stroke volume (LVSVi) and mass (LVMi) Interval change in outcome variable Presence of TTNtv Unadjusted analysis Presence of TTNtv Adjusted analysis (adjusted for age, gender, heart failure medication, resting heart rate and blood pressure, NYHA status) Coefficient P value 95% confidence interval Coefficient P value 95% confidence interval LVEF (%) 1.6 0.60 -4.3 to 7.5 1.2 0.73 5.4 to 7.7 LVEDVi (mls) 2.9 0.75 15.5 to 21.1 8.9 0.38 11.0 to 28.8 LVESVi (mls) -0.9 0.92 18.8 to 17.1 3.5 0.73 16.2 to 23.3 LVSVi (mls) 3.9 0.16 1.47 to 9.37 5.3 0.08 0.67 to 11.3 LVMi (g) 1.5 0.77 8.3 to 11.3 1.6 0.78 9.4 to 12.5 Abstracts Heart 2016;102(Suppl 6):A1–A147 A103