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Successful ablation of atrial fibrillation does not normalise left ventricular function, reverse impaired myocardial energetics or increase perfusion reserve: novel mechanistic insights with clinical implications
Journal of Cardiovascular Magnetic Resonance volume 18, Article number: O35 (2016)
Atrial fibrillation (AF) is associated with increased risk of heart failure and premature death, and with resistance to treatment. Animal models of pacing-induced AF indicate that AF-induced endothelial dysfunction, impaired coronary reserve, and myocardial remodelling are important in arrhythmia maintenance; however, human AF may reflect a subclinical cardiomyopathy that develops with ageing and risk factors, persists after restoration of sinus rhythm (SR), and provides a substrate for AF recurrence. To test this hypothesis, we investigated the effect of restoring SR by catheter ablation on left ventricular (LV) function, perfusion and energetics.
72 subjects were recruited: 52 patients (63 ± 8 y) referred for AF ablation, and 20 age-matched controls (62 ± 7 y) in SR. Patients had symptomatic paroxysmal (n = 27) or persistent (n = 25) AF without coronary artery disease, valve disease, diabetes, uncontrolled hypertension, inflammatory disease or inadequate ventricular rate-control. CMR-derived short axis cines were analysed by an investigator blinded to rhythm and clinical status to calculate LV volumes and ejection fraction (EF). 31Phosphorus MR spectroscopy determined LV energetics (ratio of phosphocreatine to ATP - PCr/ATP), and adenosine stress/rest CMR assessed first-pass perfusion. Ablation success was evaluated by prolonged intermittent ECG monitoring, after a 3-month blanking period. A majority of patients (n = 30) were re-assessed 7 ± 1 months post-ablation.
In patients compared to controls, LVEF and energetics (Figure 1) were both significantly impaired (59 ± 10 vs 69 ± 6%, p < 0.001, and PCr/ATP 1.48 ± 0.33 vs 1.76 ± 0.31, p = 0.001, respectively). In patients, presence of AF rather than SR at the pre-ablation scan was associated with reduced LVEF (54 ± 9 vs 66 ± 7%, p = 0.001) but not energetics (PCr/ATP 1.49 ± 0.31 vs 1.59 ± 0.39, p = 0.50).
In patients with a rhythm of AF during pre-ablation CMR and SR during post-ablation CMR (n = 10), there was modest improvement, but not normalisation, in LVEF (63 ± 7 post-ablation vs 55 ± 9% pre-ablation, p = 0.02; post-ablation/control comparison p = 0.02). However, energetics and perfusion reserve were unchanged despite recovery of SR (both p = ns). Furthermore, when patients were grouped based on presence/absence of recurrent AF on ECG monitoring post-ablation, LV function, energetics and perfusion reserve were all unchanged, irrespective of ablation success (all p = ns; Figure 2).
Even "lone" AF is associated with LV dysfunction - this is only partially explained by haemodynamic effects of AF at the time of assessment, as LV function does not normalise in patients who recover SR post-ablation. Moreover, successful ablation fails to reverse energetic impairment or increase perfusion reserve. These novel findings suggest that human AF may be the consequence (rather than the cause) of an occult cardiomyopathic process. Comprehensive therapeutic strategies that target and reverse this phenotype may reduce AF recurrence and improve clinical outcomes.
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Wijesurendra, R.S., Liu, A., Eichhorn, C. et al. Successful ablation of atrial fibrillation does not normalise left ventricular function, reverse impaired myocardial energetics or increase perfusion reserve: novel mechanistic insights with clinical implications. J Cardiovasc Magn Reson 18, O35 (2016). https://doi.org/10.1186/1532-429X-18-S1-O35
- Atrial Fibrillation
- Sinus Rhythm
- Atrial Fibrillation Ablation
- Atrial Fibrillation Recurrence
- Ablation Success