AT-039

Lead position is an important factor in determining response to Cardiac Resynchronization Therapy (CRT) in dyssynchronous heart failure (HF) patients. Multipoint pacing (MPP) enables pacing from multiple electrodes within the same lead, improving the potential outcome for patients. Virtual quadripolar lead designs were evaluated by simulating pacing from all combinations of 1 and 2 electrodes along the lead in each virtual patient from cohorts of HF (n = 24) and simulated reverse remodelled (RR, n = 20) patients. Electrical synchrony was assessed by the time 90% of the ventricular myocardium is activated (AT090). Optimal 1 and 2 electrode pacing configurations for AT090 were combined to identify the 4-electrode lead design that maximised benefits across all patients. LV pacing in the HF cohort in all possible single and double electrode locations reduced AT090 by 14.48 ± 5.01 ms (11.92 ± 3.51%). The major determinant of reduction in activation time was patient anatomy. Pacing with a single optimal lead design reduced AT090 more in the HF cohort than the RR cohort (12.68 ± 3.29% vs 10.81 ± 2.34%). Pacing with a single combined HF and RR population-optimised lead design achieves electrical resynchronization with near equivalence to personalised lead designs both in HF and RR anatomies. These findings suggest that although lead configurations have to be tailored to each patient, a single optimal lead design is sufficient to obtain near-optimal results across most patients. This study shows the potential of virtual clinical trials as tools to compare existing and explore new lead designs.

Bipolar disorder is a psychiatric pathology characterized by biphasic mood episodes of mania or hypomania and depression. The pharmacotherapy of bipolar disorder has significant adverse effects impairing treatment adherence and patient quality of life. The N/OFQ-NOP receptor system has been widely implicated with mood disorders. Clinical and preclinical findings suggest antidepressants actions for NOP antagonists. More recently, the administration of NOP agonists has shown to promote depressant states. The present study aimed to investigate the effects of non-peptide NOP ligands in methylphenidate-induced manic-like behavior in mice. The NOP agonist Ro 65-6570 (0.01-1 mg/kg, ip), at the higher dose, did not affect spontaneous locomotion per se, but prevented the methylphenidate (10 mg/kg, sc)-induced hyperlocomotion. The NOP partial agonist AT-090 (0.001-0.03 mg/kg, ip) and the NOP antagonist SB-612111 (1-10 mg/kg, ip) did not significantly affect the psychostimulant-induced hyperactivity. Experiments performed with mice lacking the NOP receptor (NOP(-/-)) demonstrated that the treatment with methylphenidate induced similar hyperlocomotion in NOP(-/-) and NOP(+/+) mice. In conclusion, these findings suggest a potential role for NOP agonists in the prevention of manic states, especially by counteracting the hyperactivity symptom of bipolar patients. However, more studies are necessary in order to evaluate these compounds in other features of bipolar disorder.