Background: Cardiac resynchronisation therapy-defibrillator (CRT-D) implantation via the cephalic vein is feasible and safe. Recent evidence has suggested a higher implantable cardioverter defibrillator (ICD) lead failure in multi-lead defibrillator therapy via the cephalic route. We evaluated the relationship between CRT-D implantation via the cephalic and ICD lead failure. Methods: Data was collected from three CRT-D implanting centres between October 2008 – September 2017. In total 631 patients were included. Patient and lead characteristics with ICD lead failure were recorded. Comparison of ‘cephalic’ (ICD lead via cephalic) vs ‘non-cephalic’ (ICD lead via non-cephalic route) cohorts was performed. Kaplan-Meier survival and a Cox-regression analysis were applied to assess variables associated with lead failure. Results: The cephalic and non-cephalic cohorts were equally male (82.2% vs 78.3%, p=0.28), similar in age (69.7±11.5 vs 68.7 ± 11.9, p=0.33) and body mass index (BMI) (27.7±5.1 vs 27.1±5.7, p=0.33). Most ICD leads were implanted via the cephalic vein (73.7%) and patients had a median of 2.8 leads implanted via this route. The rate of ICD lead failure was low and similar between both groups (0.4%/year vs 0.14%/year, p=0.34). Female gender was more common in the lead failure cohort than non-failure (50% vs 18.2%, respectively, p=0.01) as was hypertension (90% vs 54%, respectively, p=0.03). On multivariate Cox regression, female sex (p=0.007), hypertension (p=0.041) and BMI (p=0.042) were significantly associated with ICD lead failure. Conclusion: CRT-D implantation via the cephalic route is not associated with premature ICD lead failure. Female gender, BMI and hypertension correlate with lead failure.

Background and Purpose: The neurocognitive benefits of donepezil are well recognised, but the potential side effects on cardiac conduction remain unclear. Our objectives are to investigate whether long-term donepezil therapy is associated with electrocardiographic (ECG) changes and in particular to assess its effects on the QT interval. Experimental approach: We conducted a single centre retrospective analysis of patients admitted to our institution on donepezil therapy over a 12-month period. 59 patients were identified as suitable for analysis. An admission resting 12-lead ECG was obtained and compared to their ECG prior to commencement of donepezil therapy to assess for any significant difference in ECG parameters. Key Results: Donepezil significantly prolonged the PR (P=0.04), QRS (P=0.04) and QT (P=0.002) intervals. The increase in QT intervals remained significant on correction for heart rate; resulting in 8 (13.6%) patients developing high arrhythmogenic risk based on assessment using QT nomogram plots. Concomitant use of tricyclic antidepressants was associated with significant QT prolongation, while use of rate limiting calcium channel blockers was associated with significant PR prolongation, and beta-blockers with reduction in heart rate. Conclusion and Implications: Our results clearly demonstrate that long-term use of donepezil results in prolongation of the QT interval. We suggest ECG evaluation should take place before and after donepezil initiation, and clinicians should be even more vigilant in those prescribed tricyclic antidepressants.