The New 2016 European Society of Cardiology/European Association for Cardio-Thoracic Surgery Guidelines: Enough Guidance? Enough Evidence?

Abstract

For the first time, the European Society of Cardiology and the European Association for Cardio-Thoracic Surgery have joined forces to develop consensus guidelines for the management of atrial fibrillation (AF). One of the main issues is the integrated care of patients with AF, with emphasis on multidisciplinary teams of general physicians, cardiologists, stroke specialists and surgeons, together with the patient’s involvement for better management of AF. These guidelines also help in the detection of risk factors and concomitant cardiovascular diseases, stroke prevention therapies, including anticoagulation and antiplatelet therapies after acute coronary episodes, major haemorrhages or strokes. In the field of ablation, surgery plays an important role as concomitant with other surgical procedures, and it should be considered in symptomatic patients with the highest level of evidence. Asymptomatic patients with mitral insufficiency should also be considered for combined mitral and AF surgery if they have new-onset AF. In patients with stand-alone AF, recommendations for minimally invasive ablation have an increased level of recommendation and should be considered as the same level as catheter ablation in patients with persistent or long-standing persistent AF or with paroxysmal AF who fail catheter ablation. Surgical occlusion or exclusion of the left atrial appendage may be considered for stroke prevention in patients with AF about to have surgery. Nevertheless, not enough is known to avoid long-term anticoagulation in patients at risk of stroke even if the left atrial appendage has been excluded. These Guidelines provide a full spectrum of recommendations on the management of patients with AF including prevention, treatment and complications based on the latest published evidence.

INTRODUCTION

Although cardio-thoracic surgeons participated in previous guidelines from the European Society of Cardiology (ESC), and the European Association for Cardio-Thoracic Surgery (EACTS) guidelines for AF also endorsed ESC recommendations [1–3], now, for the first time, both societies have collaborated to design a set of recommendations for the best possible management of patients with AF. These guidelines summarize all available evidence with the aim of assisting professionals to select and personalize the best treatment strategy for a patient with AF [4].

AF is probably the arrhythmia with the highest predicted increase in the number of cases in the coming years. Despite great progress in its management, AF is still an important cause of heart failure, stroke and cardiovascular morbidity and mortality. Important studies in recent years have increased knowledge about the management of this arrhythmia together with the treatment of concomitant conditions and prevention, anticoagulation and rate and rhythm control therapies. These guidelines have summarized all this new evidence in a stratified group of recommendations.

CONCOMITANT ATRIAL FIBRILLATION SURGERY

The 2016 ESC/EACTS guidelines recognized the Cox-Maze procedure as the most effective method to recover sinus rhythm in patients with AF. The guidelines also acknowledged that radiofrequency and cryothermy are the most reliable alternative methods to the cut-and-sew technique. The Cochrane Collaboration was commissioned to perform a systematic review to evaluate all evidence around surgery for AF concomitant with another cardiac procedure [5]. This review of over 21 trials and 31 reports concluded that performing surgery to correct AF significantly increased freedom from AF and other atrial arrhythmias compared to non-AF surgery. Additionally, adding surgery for AF did not produce any significant difference in all-cause mortality, 30-day mortality, cardiovascular-related mortality, adverse events as defined by the investigators, neurological or thromboembolic events or the need for surgical re-exploration. The only statistically significant complication that was associated with the addition of surgery for AF to a cardiac procedure was an increase in the rate of pacemaker implants from 4.3% to 6.4% [relative risk (RR) 1.69; 95% confidence interval 1.12–2.54; n = 1631 from 17 randomized control trials (RCT)]. Interestingly, from the 17 RCTs analysed, only 1 RCT had a significant increase in pacemaker implants, with a rate of 19.5% in the concomitant AF surgery group [6]. In view of these data, the authors of the guidelines agreed that concomitant AF ablation should be considered in symptomatic patients with AF undergoing cardiac surgery, with a level of evidence A (data derived from multiple RCTs or meta-analyses). Because evidence about increased long-term survival or freedom from stroke has been repeatedly reported in observational, non-randomized studies, a similar recommendation remains for asymptomatic patients with level of evidence C (expert consensus).

The recommendations included the suggestion of performing biatrial lesions in patients with non-paroxysmal AF, supported by RCTs and meta-analyses [7] whereas pulmonary vein isolation seems effective in patients with paroxysmal AF [8]. Left atrial dilatation, older age, >10 years history of AF and non-paroxysmal AF remain the most important predictors of AF recurrence after surgery. Nevertheless, the authors did not consider including recommendations with cut-off numbers for atrial size, age or years in AF because restrictive AF surgical recommendations may improve surgical results but may offer limited benefits to patients who are borderline.

STAND-ALONE SURGERY FOR ATRIAL FIBRILLATION

Several minimally invasive techniques are being successfully applied in patients with stand-alone AF, most of them involving radiofrequency. Nevertheless, the technique with enough evidence is thoracoscopic pulmonary vein isolation with bipolar radiofrequency with left atrial appendage (LAA) exclusion. This technique has proven to be very effective in preventing recurrence of paroxysmal AF in patients prone to fail or who have already failed catheter ablation [9]. These results have increased the previous grade of recommendation of thoracoscopic AF surgery from ‘may be’ (IIb) to ‘should be’ considered (IIa) and the level of evidence from C to B (single randomized trial or large non-randomized studies) in patients with symptomatic AF when catheter ablation has failed. Additionally, in patients with symptomatic non-paroxysmal stand-alone AF refractory to therapy with antiarrhythmic drugs, catheter and surgical ablation have now the same grade of recommendation (IIa) to improve symptoms, considering patient choice, benefit and risk, supported by an AF heart team.

To improve results, more extensive lines are being added to pulmonary vein isolation and LAA exclusion, isolating the posterior wall of the left atrium (box lesion) and towards the mitral annulus. Additionally, endoepicardial strategies (hybrid ablation) have produced excellent results that may cause heart teams to reconsider the strategies related to ablation in the future.

LEFT ATRIAL APPENDAGE MANAGEMENT

Few data are available regarding the effectiveness of the surgical exclusion of the LAA, despite the fact that it is a technique that has been performed for many decades. Non-randomized reports show a significantly low rate of stroke and thromboembolism in patients treated with a successful Maze procedure including LAA exclusion, with no anticoagulant treatment [10]. Multiple studies have shown the feasibility and safety of surgical LAA occlusion, but reports on the efficacy of LAA exclusion alone are lacking. However, residual LAA flow after incomplete closure may increase the risk of stroke [11]. RCTs on percutaneous LAA closure devices (PROTECT-AF and PREVAIL), showed that LAA occlusion was non-inferior to warfarin in resulting in a composite end point of stroke, cardiovascular death and systemic embolism, but these results were mainly due to a decreased number of haemorrhages in patients with high-risk for bleeding [12, 13]. But patients in these RCTs with LAA occlusion had a 50% higher rate of ischaemic strokes and embolisms than patients taking warfarin, even though 15% of patients with LAA occlusion continued anticoagulation therapy. One may consider that these results could have been more positive for oral anticoagulation if new oral anticoagulant drugs had been compared to LAA occlusion, since they seem to be safer than warfarin. With this evidence, authors recommend that surgical occlusion or exclusion of the LAA may be considered for stroke prevention in patients with AF undergoing cardiac surgery (IIb); however, after surgical occlusion or exclusion of the LAA, it is recommended that at-risk patients with AF continue anticoagulation therapy for stroke prevention (I).

The most significant recommendations for AF surgery are summarized in Table 1.

POSTOPERATIVE MANAGEMENT OF ATRIAL FIBRILLATION

These guidelines recommend perioperative oral beta-blocker therapy for the prevention of postoperative AF after cardiac surgery rather than amiodarone because beta-blockers may not be as effective even though it has been less closely associated with complication rates in RCT (Table 2). Despite initial reports, currently there are no data that recommend statins, magnesium, fatty acids, colchicine, corticosteroids or posterior pericardectomy to prevent postoperative AF after cardiac surgery.

There is a strong recommendation to treat patients who have postoperative AF after cardiac surgery with anticoagulant drugs, because there is evidence that these patients have an increased risk of early stroke and of increased rates of 30-day morbidity and mortality [14]. The indication for and the timing of oral anticoagulants must consider the early risk of bleeding in postoperative patients, but there is no clear evidence on when to start anticoagulants.

In contrast to unstable patients, in whom the recommendation for cardioversion is clear (I), rhythm control with antiarrhythmic drugs should be considered preferably for symptomatic stable patients (IIa), whereas asymptomatic patients should be initially managed with rate control and anticoagulants (IIa).

OTHER MAJOR NEW CONCEPTS IN THE 2016 ESC/EACTS GUIDELINES

Among the new recommendations for the general management of AF included in these guidelines, we highlight the following:

There is a slight change in the classification of AF. The new guidelines classify paroxysmal AF as having episodes that last fewer than 7 days either by spontaneous interruption or cardioversion, whereas in the previous guidelines, an episode requiring cardioversion was considered persistent AF no matter the timing of the interruption.

There is an effort to describe and emphasize the detection and control of the risk factors, like obesity, alcohol consumption, smoking and intensive sports practice, among others. There is a complete review of which treatments lower the risk of AF in patients with cardiac insufficiency compared with others that do not influence its incidence.

These guidelines recommend limiting the term ‘valvular’ AF to patients with rheumatic mitral disease or patients with a mechanical prosthesis, the 2 conditions with an increased risk for stroke. Indeed, there is no evidence that patients in AF with non-rheumatic mitral insufficiency, aortic stenosis or aortic insufficiency have an increased risk for stroke over patients with non-valvular disease. Therefore, these guidelines also recommend replacing the term ‘non-valvular’ AF with a reference to the specific underlying conditions.

Stroke prevention is an important part of these guidelines. The CHA₂DS₂-VASc scale strengthens our ability to predict thromboembolic risk, lowering the level of anticoagulation to CHA₂DS₂-VASc 1 (IIa, B). In contrast, no bleeding scale is recommended, but a list of modifiable and non-modifiable risk factors for haemorrhage is provided, emphasizing the need to control the modifiable risk factors as much as possible.

There is a clear preference for the new oral anticoagulants and for maintaining the recommendation for warfarin for patients with AF and rheumatic mitral disease or a mechanical prosthesis. We strongly recommend avoiding antiplatelet monotherapy alone or combined with oral anticoagulants for stroke prevention in patients with AF, regardless of the risk of stroke. Evidence shows that antiplatelet therapy significantly increases the risk of bleeding with no stroke prevention benefits in patients with AF.

The guidelines contain a detailed strategy for the secondary prevention of stroke or bleeding with new recommendations and flow charts, including the reintroduction of anticoagulant therapy, depending on the severity of the ischaemic or haemorrhagic episode.

The guidelines also describe the preferred combination of antiplatelet and anticoagulant therapies to use after an acute coronary syndrome or an elective percutaneous coronary intervention with a stent, both with recommendations and flow charts. In both situations, triple therapy (clopidogrel, aspirin and oral anticoagulants) is limited in time depending upon the patient’s risk of bleeding, the goal being to downscale to double therapy (clopidogrel or aspirin plus oral anticoagulation) 1–6 months after the episode and to oral anticoagulation only within 6–12 months.

LIMITS OF THE GUIDELINES: GAPS OF EVIDENCE

All published evidence has been evaluated to best develop these guidelines, but like most evidence-based recommendations, randomized trials and meta-analyses are much more important than all other types of studies. In the case of surgery for AF, most RCTs have a small number of patients and 1–2 years of follow-up. These studies have basically demonstrated an important improvement in sinus rhythm maintenance and, in one case, a quality-of-life benefit, but they have not demonstrated the advantages in survival rates and freedom from stroke suggested in multiple observational studies with much longer follow-up. Additionally, there is a great heterogeneity in both randomized and non-randomized studies in the types of lesions and energies applied. We still need a randomized trial on AF surgery concomitant with a cardiac procedure with a uniform set of lines, performed with energies known to be capable of producing consistent transmural lines and with long-term follow-up, to determine whether the benefits of the Maze procedure expand beyond sinus rhythm maintenance.

In the area of isolated AF, evidence is clear that thoracoscopic surgery is more efficient than catheter ablation, both in patients with paroxysmal AF and those with non-paroxysmal AF, but with a higher degree of invasiveness and possibly more complication rates. Thoracoscopic surgery, despite being introduced around 2003, is still not consistently performed in cardiothoracic centres, and only a few of the best centres report their experience. New trials are under way to determine whether minimally invasive surgery, alone or in combination with a catheter in a 1- or 2-stage procedure, is more effective than repeated catheter ablation.

Finally, there is evidence that LAA exclusion reduces stroke rates in patients undergoing cardiac surgery in which the Maze procedure is successfully performed. But we do not have enough evidence to recommend avoiding anticoagulation in these patients, especially in those who remain in AF. The publication of the LAOOS III randomized trial will provide some insights into this issue [15].

SIMILARITIES AND DIFFERENCES WITH THE SOCIETY OF THORACIC SURGEONS 2017 CLINICAL PRACTICE GUIDELINES AND THE 2017 HRS/EHRA/ECAS/APHRS/SOLAECE EXPERT CONSENSUS STATEMENT ON CATHETER AND SURGICAL ABLATION OF ATRIAL FIBRILLATION

Two new guideline/expert consensus statements were published in 2017 [16, 17]. Whereas the 2016 ESC guidelines comprise a general document well disseminated among all physicians involved in AF diagnosis and management, the STS guidelines and the HRS/EHRA/ECAS/APHRS/SOLAECE Expert Consensus Statement are specific documents written by and for surgeons and electrophysiologists involved in the treatment of AF. The STS guidelines increase the rate of recommendation for surgical ablation concomitant with other surgical procedures to class I, with levels of evidence A for concomitant mitral disease and B for other concomitant procedures, specifically mentioning that ablation adds no risk of mortality or morbidity. Although both the ESC and the STS guidelines are based on the same published evidence, the authors of the ESC guidelines considered that the added risk for pacemaker implantation described in meta-analyses made the recommendation for concomitant ablation IIa instead of I. Another difference between the documents was the importance given in the ESC guidelines to symptoms, giving a higher recommendation grade to symptomatic patients, whereas the STS gives the same level of recommendation regardless of the symptoms. Although this author was a member of the 2016 ESC/EACTS Guidelines for the Management of AF Committee, he agrees with the STS Guidelines authors that symptoms are not so important in the setting of AF concomitant with other cardiac conditions for 3 reasons. First, in most patients, it is difficult to elucidate which symptoms are due to AF and which are due to their concomitant disease. Second, the Cox-Maze procedure is the most efficacious procedure to treat AF, and for most patients who undergo cardiac surgery, whether symptomatic or not, it is a unique opportunity to return to sinus rhythm with no added risk of death and a low probability of pacemaker implantation. Third, the success of the ablation has no relationship with symptoms.

The 2017 consensus statements by the most important heart rhythm societies redefine the term ‘early persistent’ AF as AF that continues for more than 7 days but for less than 3 months. They recommend concomitant surgical ablation only in symptomatic patients. Moreover, whereas the level of recommendation for ‘open ablation’’ such as for concomitant mitral disease is class I, level of evidence B, the level of recommendation for ‘closed ablation’ (i.e. coronary artery bypass graft, aortic valve replacement) depends on whether the patients is refractory or intolerant to antiarrhythmic medication (class I, level of evidence B) or if ablation occurs prior to initiation of antiarrhythmic therapy (class 2A, level of evidence B). In our opinion, the distinction of recommendation based on antiarrhythmic therapy is difficult to understand when compared to a Cox-Maze procedure in a patient who already has the indications for open-heart surgery and the morbidity caused by such medication. On the other hand, recommendations for stand-alone surgery are similar in all 3 guidelines: ESC, STS and HRS/EHRA/ECAS/APHRS/SOLAECE.

CONCLUSIONS

The 2016 ESC/EACTS guidelines is a clinically oriented document that includes all evidence on AF management published through 2015. It highlights the importance of integrated teams to offer personalized treatment options for each patient. Among these options, the level of recommendation of surgical therapies is increased for patients with isolated as well as concomitant AF. LAA exclusion is also recommended in patients with AF undergoing cardiac surgery, although current evidence does not support the avoidance of anticoagulation in patients with LAA exclusion and at risk of stroke.

Conflict of interest: The author is consultant to AtriCure, Medtronic, Edwards Lifesciences.

REFERENCES