Drugs that suppress AF-promoting remodeling are currently lacking. Cilnidipine is a clinically available Ca²⁺ channel blocker that inhibits N-type channels which regulate autonomic function.

To assess the effect of cilnidipine on AF-related atrial remodeling.

3groups of 8dogs were followed for 3weeks:

– AF maintained by 600bpm atrial tachypacing treated with placebo (AF+P) ;

– cilnidipine 10mg twice a day (AF+C) ;

– instrumented control dogs (Sham).

At terminal open-chest study, typical electrophysiological remodeling was observed (Fig. 1A) with AF+P: reduced left atrial (LA) effective refractory period (ERP: 69±14ms vs. 126±15Sham); enhanced AF vulnerability (inducibility by single extrastimuli: (77±19 vs. 2±6%); and increased AF duration after burst pacing (12.7±10.1min vs. 0.1±0min). All these changes were suppressed in AF+C: (ERP 90±15; vulnerability 52±27%; AF duration 5.3±9.1min). Ex vivo optical mapping (Fig. 1B) showed that conduction velocity was decreased in AF+P (68±6cm/s) vs. Sham (119±9cm/s, P0.01); AF+C was protective (97±9cm/s). SCN5A was decreased in AF+P (P<0.01) but not in AF+C vs. Sham (Fig. 1C). GJA1 and Connexin43 were down regulated in AF+P (P<0.05), but not in AF+C, vs. Sham. Fibrous tissue content (Masson Trichrome) was increased in AF+P (17±4%) vs. Sham (3±1%, P<0.001) (Fig. 1D); AF+C reduced fibrosis (10±4%, P<0.01).

This study shows for the first that cilnidipine, a commercially available N-/L-type Ca²⁺ channel blocker, attenuates AF-induced electrical and structural remodeling, introducing a novel potential therapeutic target for this unmet need.