Atrial Fibrillation Ablation in Patients With Hypertrophic Cardiomyopathy: Do not Throw in the Towel too Fast!

Louisa O'Neill; Mattias Duytschaever; Sébastien Knecht


Europace. 2021;23(9):1334-1335. 

Current guidelines have emphasized the central role of catheter ablation in the management of patients with atrial fibrillation (AF). Recent advances in catheter and mapping technology and in the understanding of lesion formation have resulted in manifest progress, predominantly in the durability of ablation lesion sets and in the reduction of complications, translating into better procedural, and follow-up results.

Patients presenting with AF, however, encompass a disparate population who experience different outcomes post-ablation. At one end of the spectrum, 'healthy, normal heart' patients with paroxysmal AF have the best prognosis after ablation. At the other end are those with structural heart disease in whom ongoing atrial structural remodelling secondary to underlying cardiac pathology renders management of AF significantly more challenging. In these patient populations, multiple procedures may be needed with modest success rates, particularly in the case of persistent AF.

Within the spectrum of structural heart disease, hypertrophic cardiomyopathy (HCM) is strongly associated with the development of AF, with a prevalence of over 20%,[1] and successful management and ablation remains a significant challenge for the electrophysiologist. It is a disease with multiple components, genotypes, and structural phenotypes with increased left ventricular (LV) wall thickness and diastolic dysfunction a universal feature. Consequent increased left atrial pressure, left atrial dilatation and fibrosis create an ongoing milieu for atrial arrhythmia in these patients. Moreover, HCM often tends to progress over time and the associated evolution of the arrhythmia substrate can result in multiple recurrences of atrial arrhythmia even after apparent successful catheter ablation. Atrial fibrillation in the HCM population is often poorly tolerated due to co-existent diastolic dysfunction and rhythm control strategies may be preferable. There is a paucity of data, however, on patient selection, timing, and outcomes of catheter ablation in this population with no large scale or randomized trials in existence on this subject. Nor was there, until now, any systematic evaluation of ablation strategy in this cohort. As such, optimal treatment strategies are not well defined. Furthermore, while risk stratification scores have been developed to estimate the risk of malignant ventricular arrhythmias to guide ICD implantation, no clear prognostic schemes have been evaluated to estimate the recurrence risk after an AF ablation procedure.

Creta et al.[2] present interesting data on 137 patients with AF (57% paroxysmal) and HCM undergoing one or more ablation procedure between 2006 and 2016 in four European centres. All patients received pulmonary vein isolation with the use of radiofrequency (RF) or cryoballoon catheters and in 45% of patients, additional 'substrate modification' was performed, at operator discretion. After a mean follow-up of greater than 3 years, nearly all patients with persistent AF and 60% of patients with paroxysmal AF had a recurrence of the arrhythmia, despite the use of antiarrhythmic drug therapy in one-third of patients. The presence of an LV apical aneurysm, an enlarged left atrium, and a higher APPLE score were associated with an increased risk of AF recurrence, while the ESC HCM Risk-SCD score was not predictive of outcome. While a welcome addition to the literature on a poorly understood topic, there are some important limitations to this study which should be considered.

Although this study represents the largest cohort of patients undergoing AF ablation in HCM to date, its observational design is an inherent drawback. The rigour of a prospective study regarding follow-up and patient selection is lacking and the ablation strategy was very heterogeneous and driven by operator preference.

Furthermore, as ablation technique has dramatically improved over the last number of years, the results cannot necessarily be extrapolated to current day practice, and reported success rates may be lower than would be expected with contemporaneous ablation protocols. In the last 5 years, novel workflows for pulmonary vein isolation, utilizing cutting-edge technologies have been developed, resulting in enhanced ablation lesion durability. The robustness of such protocols has been assessed in patients undergoing pulmonary vein isolation using contiguous and optimized RF lesions with persistent isolation of all four pulmonary veins demonstrated in up to two-thirds of patients at repeat procedure.[3] Enhanced lesion durability also translates into improved post-ablation success rates. The CLOSE-to-CURE study emphasizes this point with no AF recurrence of greater than 2 minutes detected on implantable loop recorder monitoring in 87% of paroxysmal AF patients 1-year post-ablation.[4]

Novel protocols for optimization of ablation lesions have shown benefit even when employed for additional substrate ablation with RF lines in patients with persistent AF, and high rates of first-pass roofline block have been demonstrated with contiguous RF lesion delivery.[5] Further developments regarding ethanolization of the Vein of Marshal have also shown promising results, with significantly higher success rates for acute and long-term mitral line block, and when combined with catheter ablation may confer an advantage over ablation alone.[6,7]

In the present study, additional substrate ablation was not associated with improved outcomes, but again with the limitation of potentially non-durable lesion sets and possible bias from the preselection of patients with likely advanced atrial remodelling.

Pulmonary vein (PV) reconnection in the context of HCM has been shown to be very frequent (40–100%),[8] however, the pathophysiology of pulmonary vein reconnection in patients with HCM may differ with respect to the 'normal heart' cohort and may be influenced by pathological changes in the atria of these patients. Additionally, re-isolation of chronically reconnected pulmonary veins may not be associated with an improved prognosis to the extent seen in non-affected subjects.[9] This is likely to reflect an atrial arrhythmia substrate secondary to the haemodyanmic consequences of elevated LV filling pressures with pro-arrhythmic electrical and structural remodelling distant to the pulmonary veins. Supporting this point, late AF recurrence in HCM patients has been previously shown to be caused by non-pulmonary vein triggers.[10]

In this context, in the present study, data regarding left atrial fibrosis burden either on cardiac magnetic resonance imaging or intraprocedural voltage mapping are lacking and may have helped understand the low success rates seen post-ablation. It is likely that atrial fibrosis burden was significant in the population studied here given the negative prognostic factors detailed in the study (persistent AF, APPLE score, and left atrial diameter) and that metrics of atrial fibrotic remodelling may have improved patient selection for additional substrate ablation outside the pulmonary veins at index procedure.

Finally, as mentioned above, restoration of sinus rhythm is important in patients with HCM to increase ventricular filling and reduce outflow obstruction and is often associated with a clinical improvement, proportionally greater than in patients without HCM. Atrial fibrillation in HCM can be associated with deleterious clinical consequences and is a determinant of heart failure morbidity as well as disease-related mortality.[11] Furthermore, AF progression to a permanent state in HCM is not necessarily inevitable and clinical progression after AF ablation is not fully understood. While the study by Creta et al.[12] may call into question the benefit of catheter ablation in this cohort, the notably inferior results in persistent vs. paroxysmal AF patients studied here may also underscore the need for early intervention before advanced atrial remodelling has taken place. To this end, a recently published study by Dinshaw et al. reported superior post-ablation results to that of Creta et al., albeit in smaller numbers, with 84.6% of patients with paroxysmal AF remaining arrhythmia free at 4 years.[13]

In summary, AF in HCM is a challenging condition, and rhythm management strategies remain unclear reflecting a lack of randomized data in this cohort. This observational study suggests that success rates for catheter ablation are modest at best; however, it pre-dates recent advances in catheter and mapping technology with heterogeneous ablation strategies employed. Although multiple procedures may be needed in HCM patients with reduced success rates compared to those without structural heart disease, superior results may be expected with contemporary techniques and the clinical impact of even a limited reduction in AF burden may significantly improve quality of life in this population. Therefore, a personalized patient-based approach including timely AF ablation, if appropriate, is still crucial.