Population-level evaluation of ablation therapy in patients with atrial fibrillation and comorbid heart failure

Atrial fibrillation (AF) and heart failure (HF) frequently coexist. The presence of both diseases further increases the risk of all-cause mortality, HF hospitalizations, and stroke compared to either disease individually. Pharmacologic therapy has limited effectiveness in this subpopulation, therefore a minimally invasive rhythm control strategy, catheter ablation (CA), has been used to treat AF in patients with HF. Randomized trials showed CA is safe and reduces all-cause mortality and HF hospitalizations, however, current clinical guidelines recognize the evidence for CA use in the AF-HF population is limited. The aim of the present thesis was to evaluate treatment selection patterns, safety, and long-term effectiveness of CA in a real-world AF-HF population and address methodological gaps from randomized trials. Linked hospital discharge summary [Maintenance et Exploitation des Données pour l’Étude de la Clientèle Hospitalière (Med-Echo)] and claims [la Régie de l’assurance maladie du Québec (RAMQ)] administrative databases from Quebec, Canada were used to construct the AF-HF cohort (2000-2017). The final overall cohort consisted of 112,955 AF-HF patients, of which 700 patients underwent CA. Of patients with government prescription insurance coverage, 432 patients underwent CA of 101,931 AF-HF patients. Both the overall and medication cohorts included the largest number of CA patients with AF-HF studied till date. Current clinical guidelines are nonspecific about the referral criteria for CA in the AF-HF population. Thus, the real-world treatment selection pattern is unknown. The first manuscript demonstrated that (1) CA was rarely used to treat AF in patients with HF, (2) CA patients had a minimal number of comorbidities, and (3) women had a lower probability of treatment. Structural differences in the heart of HF patients may make CA more technically challenging and potentially riskier to perform compared to patients without HF. The second manuscript showed that amongst AF-HF patients who underwent CA, the incidence of major adverse events was low and comparable to rate of major adverse events in randomized trials and real-world evaluations in the overall AF population, regardless of the presence of HF. Randomized trials demonstrated a reduction in all-cause mortality and HF hospitalizations with CA in selected patients; however, whether these results are generalizable to a real-world population and persist in the long-term remains to be shown. The third manuscript investigated the long-term effectiveness of CA in AF-HF patients in reducing the incidence of: 1) all-cause mortality, 2) HF hospitalizations, and 3) major morbidities. We found that CA was associated with a statistically significant reduction in all-cause mortality compared to non-CA patients. CA was also protective against HF hospitalizations for the first 3-years after the date of CA. Although no difference in the risk of stroke and major bleeding was detected between CA and non-CA patients, larger studies are warranted. The present thesis investigated treatment patterns, safety, and long-term effectiveness in the largest and longest cohort of AF-HF patients who underwent CA till date. In addition, the specific patient population investigated reflects those encountered real-world practice. Methodologically, this thesis advances knowledge gained from prior studies and randomized trials by illustrating the time-varying effects of CA over a long follow-up period for clinically relevant outcomes. Also, time-varying effects of medications and cardiac device use as well as the competing risk of mortality were included to better quantify the risk of a specific event, all of which fill methodological gaps present in current research on CA in AF-HF patients. Finally, results of the present thesis better informs clinical practice guidelines for the treatment of this challenging subpopulation

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