NAFLD May Predict Arrhythmia Recurrence Post-AF Ablation

Patrice Wendling

August 13, 2020

Increasingly recognized as an independent risk factor for new-onset atrial fibrillation (AF), new research suggests for the first time that nonalcoholic fatty liver disease (NAFLD) also confers a higher risk for arrhythmia recurrence after AF ablation.

Over 29 months of postablation follow-up, 56% of patients with NAFLD suffered bouts of arrhythmia, compared with 31% of patients without NAFLD, matched on the basis of age, sex, body mass index (BMI), ejection fraction within 5%, and AF type (P < .0001).

The presence of NAFLD was an independent predictor of arrhythmia recurrence in multivariable analyses adjusted for several confounders, including A1c, BMI, and AF type (hazard ratio [HR], 3.0; 95% CI 1.94 - 4.68).

The association is concerning given that one in four adults in the United States has NAFLD, and up to 6.1 million Americans are estimated to have AF.

Previous studies, such as ARREST-AF and LEGACY, however, have demonstrated the benefits of aggressive preablation cardiometabolic risk-factor modification on long-term AF ablation success.

Indeed, none of the NAFLD patients in the present study who lost at least 10% of their body weight had recurrent arrhythmia, compared with 31% who lost less than 10%, and 91% who gained weight prior to ablation (P < .0001).

All 22 patients whose A1c increased during the 12 months prior to ablation had recurrent arrhythmia, compared with 36% of patients whose A1c improved (P < .0001).

"I don't think the findings of the study were particularly surprising, given what we know. It's just further reinforcement of the essential role of risk-factor modification," lead author Eoin Donnellan, MD, Cleveland Clinic, told theheart.org | Medscape Cardiology.

The results were published August 12 in JACC Clinical Electrophysiology.

For the study, the researchers examined data from 267 consecutive patients with a mean BMI of 32.7 kg/m2 who underwent radiofrequency ablation (98%) or cryoablation (2%) at the Cleveland Clinic between January 2013 and December 2017.

All patients were followed for at least 12 months after ablation and had scheduled clinic visits at 3, 6, and 12 months after pulmonary vein isolation, and annually thereafter.

NAFLD was diagnosed in 89 patients prior to ablation on the basis of CT imaging and abdominal ultrasound or MRI. On the basis of NAFLD-Fibrosis Score (NAFLD-FS), 13 patients had a low probability of liver fibrosis (F0 to F2), 54 had an indeterminate probability, and 22 a high probability of fibrosis (F3 to F4).

Compared with patients with no or early fibrosis (F0 to F2), patients with advanced liver fibrosis (F3 to F4) had almost a threefold increase in AF recurrence (82% vs 31%; = .003).

"Cardiologists should make an effort to risk-stratify NAFLD patients either by NAFLD-FS or [an] alternative option, such as transient elastography or MR elastography, given these observations, rather than viewing it as either present or absence [sic] and involve expert multidisciplinary team care early in the clinical course of NAFLD patients with evidence of advanced fibrosis," Donnellan and colleagues write.

Coauthor Thomas G. Cotter, MD, Department of Gastroenterology and Hepatology, University of Chicago, told theheart.org | Medscape Cardiology that cardiologists could use just the NAFLD-FS as part of an algorithm for an AF.

"Because if it shows low risk, then it's very, very likely the patient will be fine," he said. "To use more advanced noninvasive testing, there are subtleties in the interpretation that would require referral to a liver doctor or a gastroenterologist and the cost of referring might bulk up the costs. But the NAFLD-FS is freely available and is a validated tool."

Although it hasn't specifically been validated in patients with AF, the NAFLD-FS has been shown to correlate with the development of coronary artery disease (CAD) and was recommended for clinical use in US multisociety guidelines for NAFLD.

The score is calculated using six readily available clinical variables (age, BMI, hyperglycemia or diabetes, aspartate aminotransferase/alanine aminotransferase, platelets, and albumin). It does not include family history or alcohol consumption, which should be carefully detailed given the large overlap between NAFLD and alcohol-related liver disease, Cotter observed.

Of note, the study excluded patients with alcohol consumption of more than 30 g/d in men and more than 20 g/d in women, chronic viral hepatitis, Wilson's disease, and hereditary hemochromatosis.

Finally, CT imaging revealed that epicardial fat volume (EFV) was greater in patients with NAFLD than in those without NAFLD (248 vs 223 mL; P = .01).

Although increased amounts of epicardial fat have been associated with CAD, there was no significant difference in EFV between patients who did and did not develop recurrent arrhythmia (238 vs 229 mL; P = .5). Nor was EFV associated with arrhythmia recurrence on Cox proportional hazards analysis (HR, 1.001; P = .17).

"We hypothesized that the increased risk of arrhythmia recurrence may be mediated in part by an increased epicardial fat volume," Donnellan said. "The existing literature exploring the link between epicardial fat volume and AF burden and recurrence is conflicting. But in both this study and our bariatric surgery study, epicardial fat volume was not a significant predictor of arrhythmia recurrence on multivariable analysis."

It's likely that the increased recurrence risk is due to several mechanisms, including NAFLD's deleterious impact on cardiac structure and function, the bidirectional relationship between NAFLD and sleep apnea, and transcription of proinflammatory cytokines and low-grade systemic inflammation, he suggested.

"Patients with NAFLD represent a particularly high-risk population for arrhythmia recurrence. NAFLD is a reversible disease, and a multidisciplinary approach incorporating dietary and lifestyle interventions should by instituted prior to ablation," Donnellan and colleagues conclude.

They noted that serial abdominal imaging to assess for preablation changes in NAFLD was limited in patients and that only 56% of control subjects underwent dedicated abdominal imaging to rule out hepatic steatosis. Also, the heterogeneity of imaging modalities used to diagnose NALFD may have influenced the results and the study's single-center retrospective design limits their generalizability.

The authors report having no relevant financial relationships

J Am Coll Cardiol EP. Published online August 12, 2020. Abstract

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