Discussion
The main findings of the present study are the following:
  1. HCM patients with arrhythmia recurrence exhibit significantly wider fibrotic areas compared to those who remained in sinus rhythm;
  2. The presence of fibrotic areas greater than 13.1% (≤0.25 mV voltage criterion) or 14.1% (≤0.4 mV voltage criterion) predict arrhythmia recurrence with high sensitivity and specificity;
  3. LA fibrosis is the only predictor of arrhythmia recurrence following catheter ablation in patients with obstructive HCM;
  4. HCM patients with AF display significantly broader fibrotic areas compared to a PS matched control population of non-HCM patients and AF.
The development of AF in HCM is multifactorial and has been related to LA enlargement, increased LA pressure, LVOT obstruction, and LA fibrosis as detected by late gadolinium enhancement cardiac MR (LGE-CMR).1,13,14 This complex pathophysiology of AF in HCM possibly explains the high recurrence rates observed following catheter ablation of the arrhythmia. In a meta-analysis of five studies, the single-procedure success rate (free from any atrial arrhythmia) was only 38.7% in patients with HCM compared to 49.8% in controls.3 Outcomes after multiple procedures increased to 51.8% compared to 71.2% in controls. Repeat procedures and antiarrhythmic drugs are more frequently needed in patients with HCM to prevent arrhythmia relapse.3
Recent LGE-CMR studies have demonstrated the presence of LA fibrosis in HCM patients, and especially in those with AF.13,14The extent of LA LGE has been significantly correlated with the extent of LV LGE, suggesting that either the LA fibrosis is the result of LV fibrosis or both of them are manifestations of the same pathophysiologic process.5 Atrial fibrosis is the most important predictor of ablation failure beyond PV isolation.9 PV and posterior wall isolation alone have been shown to be insufficient to obtain satisfactory long-term results.6 In addition, non-PV triggers have been demonstrated in the majority of HCM patients with arrhythmia recurrence, a finding that supports the appropriateness of a more extensive ablation beyond PV isolation to improve the arrhythmia-free survival.6 These findings are possibly related to an extensive LA cardiomyopathy in this specific population.
In this high-density EAM study, we evaluated for the first time the extent of LA fibrosis and its impact on catheter ablation outcomes in patients with HCM and AF. Irrespective of the bipolar voltage cut-off value used for fibrosis characterization (≤0.25 mV or ≤0.4 mV), HCM patients with arrhythmia relapse exhibited wider fibrotic regions compared to those who remained in sinus rhythm. By using the ≤0.4 mV bipolar voltage criterion, the presence of low voltage areas more than 14.1% of the total LA area predicted AF recurrence with an excellent sensitivity (100%) and specificity (100%). We additionally showed that non-paroxysmal AF patients exhibit significantly wider diseased areas compared to paroxysmal AF patients. HCM patients exhibited larger low voltage areas compared to the PS matched control population of non-HCM patients. These findings have important implications in AF catheter ablation outcomes. In cases with extensive fibrosis, substrate modification aiming at scar homogenization or isolation or LA compartmentalization may be need to improve long term outcomes following catheter ablation.8,9 The existence of LA voltage areas ≤0.4 mV more than 10% of the total LA surface area has been shown to predict arrhythmia recurrence following PVAI even for paroxysmal AF patients.10 In a similar high-density EAM study, we have demonstrated that substrate modification aiming specific electrograms within low voltage areas (≤0.4 mV) leads to AF termination in 23% of patients with persistent AF and improved long-term free-survival from any atrial arrhythmia.12