Diabetes Mellitus and Atrial Remodeling in patients with Atrial Fibrillation: role of electro-anatomical mapping and catheter ablation

Background and aim of the study Diabetes Mellitus (DM) and Atrial Fibrillation (AF) are two pandemic diseases. DM is one of the most important risk factors for AF and is a predictor of stroke and thromboembolism. The mechanisms of AF associated with DM are not fully understood and are represented by atrial autonomic, electrical, and structural remodeling, together with insulin resistance. AF ablation has become an established therapy for maintaining sinus rhythm in patients with symptomatic paroxysmal AF. This is primarily achieved through isolation of the pulmonary veins (PVI). In non-paroxysmal forms, more extensive ablations, i.e. substrate modification with complex fractionated atrial electrograms (CFAEs) ablation, may be required. The aim of this randomized study was to compare in terms of clinical outcome two strategies of catheter ablation (PVI vs PVI+CFAEs) for paroxysmal AF in DM patients. Methods The population of this study consisted of 64 patients with DM undergoing catheter ablation for AF: 32 of the them were randomized to PVI and 32 to PVI+CFAEs ablation. The study population was also compared to a historical population of non-DM patients undergone catheter ablation (PVI) for paroxysmal, symptomatic drug-refractory AF. Follow-up consisted of outpatient visits and Holter monitoring performed after 1 month and each 3 months after the ablation procedure. Results In the study population (DM patients), with respect to a historical population of non-DM patients undergone paroxysmal AF ablation, a significant higher percentage of patients showed more than 25% of atrial area interested by CFAEs (Study Population 58% vs 15% Historical Group; P <0.05). A wider CFAEs area was reported in DM patients with Hb1Ac constantly above 7.5% during the 12 months preceding ablation (Hb1Ac >7.5% 41% vs. Hb1Ac <=7.5% 24%; P <0.05). Success rate of catheter ablation in study population was similar to that of historical population (Study Population 83% vs 85% Historical Group; P = NS). During follow-up the recurrences rate was similar in the two group (PVI 27% vs. PVI + CFAEs 21%; P = NS). In patients with recurrences the AF burden, expressed as number of AF episodes/patients, was similar in the two groups (PVI 4 ± 2 vs. PVI + CFAEs 3 ± 2; P = NS). In the PVI group, recurrences occurred with similar rate in patients with Hb1Ac >7.5% compare to those with Hb1Ac <=7.5% (Hb1Ac >7.5% 30% vs. Hb1Ac <=7.5% 22%; P=NS), but a greater AF burden was observed in those with Hb1Ac >7.5% (6±2 Hb1Ac >7.5% vs. 1±2 Hb1Ac <=7.5%; P <0.05). This was not the case for PVI+CFAEs group. A significant benefit with PVI+CFAEs was identified in patients with Hb1Ac >7.5% (HR 1.28, CI 1.11-1.45, P <0.05), more than 25 years from DM diagnose (HR 1.25, CI 1.09-1.50, P <0.05) and more than 5 AF episodes/year (HR 1.2, CI 1.03-1.55, P <0.05). No significant interaction was identified for other subgroup of patient. Conclusions This is the first randomized study that investigated atrial remodeling in type 1 DM humans using electroanatomical mapping system. The main findings of this study are: a) DM patients had a more complex atrial "substrate" than non-DM patients; b) in study population at 1-year follow-up the recurrences rate was similar in the groups of patients; c) specific subgroup of patients may benefit from more complex ablations. Recurrences rate seem to be associated more with glycemic control than to simpler procedure. Upstream therapies targetting atrial remodeling may play a key role in the treatment of AF in DM pts.