The year in cardiology 2018: arrhythmias and cardiac devices
Year: 2018
Type: article
Abstract: As in the previous years,1 numerous relevant contributions on cardiac arrhythmias and devices were presented and published in 2018. For this traditional look back on the past year, the authors identified a selected group of studies, abstracts, and articles with potential impact in daily practice. During 2018, a number of important trials have been presented or published concerning the important topic of atrial fibrillation (AF) and catheter ablation of AF. After its presentation at ESC 2017, the long awaited CASTLE-AF study was finally published in 2018.2 As previously discussed,1 CASTEL-AF randomized a total of 363 patients to AF ablation vs. conventional care (of the 3013 screened patients). Only heart failure patients [left ventricular ejection fraction (LVEF) ≤ 35%, all with an implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT)] with both paroxysmal and persistent AF were included The primary composite endpoint of all-cause death or worsening heart failure was reduced by 38% in the ablation compared to the conventional group [hazard ratio (HR) 0.62, 95% confidence interval (95% CI) 0.43–0.87; P = 0.007]. Both components of the primary endpoint were significantly reduced by AF ablation, i.e. worsening heart failure (HR 0.56, 95% CI 0.37–0.83; P = 0.004) as well as all-cause mortality (HR 0.53, 95% CI 0.32–0.86; P = 0.011). Left ventricular ejection fraction improved by 7% after 12 months in the ablation group compared to the conventional treatment group, and ablated patients were twice as likely to be free from AF as individuals in the conventional group over the 5 year duration of the trial. On the downside, 1.7% pericardial effusion were observed in the ablation group.2 The most anticipated presentation this year was the presentation of the results of the CABANA trial at the Heart Rhythm Society Meeting in May 2018.3 While the manuscript has not been published as of the time this article was written, most of the primary results are available. The CABANA trial was a prospective randomized clinical trial that compared the outcomes of catheter ablation vs. medical therapy in 2204 patients ≥ 65 years of age or less than 65 years of age with one or more stroke risk factor. The primary endpoint was a composite endpoint of death, disabling stroke, serious bleeding, or cardiac arrest. The mean patient age was 67.5 years, 43% had paroxysmal AF, 47% had persistent AF and 10% had long standing persistent AF. In the pre-specified intention to treat analysis the primary outcome did not differ in the two groups (8% for ablation vs. 9.2% for drugs, P = NS). Secondary endpoints included all-cause mortality, which also did not differ (5.2 vs. 6.1% respectively, P = NS) and the composite of death or cardiovascular (CV) hospitalization which favoured ablation (51.7% vs. 58.1%, P = 0.001). Ablation was associated with a 47% reduction in AF with 60% of patients in the ablation arm free of AF. The major complication rate of catheter ablation was 9% as compared with 4% in the drug arm. At the end of the day this was a negative trial. However, intention to treat analysis was influenced by high rate of cross overs (27.5% of subjects in medical therapy arm actually underwent catheter ablation and 9.2% of patients in ablation arm did not have catheter ablation). In any case, the results do not negate the clinical value of AF ablation. The 2017 AF Ablation Consensus Document as well as the ESC and ACC AF Guidelines make it clear that the primary indication for AF ablation is for improvement of quality of life.4–6 The results of CASTLE-AF and CABANA support these guideline recommendations, but no not fully defence the concept that catheter ablation of AF lowers the composite of death, disabling strike, serious bleeding, or cardiac arrest. However, while waiting for the results of the pending final outcome study (EAST), evidence is accumulating which indicates that AF may in fact play a much more causal role rather than that of a ‘nuisance bystander’ in the pathophysiology of CV diseases and, as a result, AF ablation may possibly serve more than just symptomatic relief.1 Another study to be aware of examined temporal trends in AF recurrence after ablation between 2005 and 2014, based on the nationwide Danish cohort study.7 Five thousand four hundred twenty-five patients undergoing a first time AF ablation were included. The rates of AF recurrence at 1 year post ablation fell from 45% in 2005–2006 to 31% in 2013–2014. Factors associated with a higher recurrence rate of AF included AF duration > 2 years, female gender, hypertension, and cardioversion within 1 year of ablation. These findings are not surprising, they are important as they provide a ‘real world’ look at the efficacy of AF ablation and how it continues to improve over time. The POWDER AF Trial8 was a prospective randomized clinical trial that examined the clinical value of continuing or stopping antiarrhythmic drug therapy three months post-AF ablation. AF recurrence post the 3 month blanking period occurred markedly less frequently when antiarrhythmic drugs were continued (2/74, 2.7%) vs. when antiarrhythmic drug therapy was stopped at 3 months (16/73, 16.9%). These data support the view that etiopathogenesis of AF is complex and catheter ablation itself may not control all the mechanisms. And the final trial to draw your attention to is the Race 3 Trial.9 This trial randomized patients with early persistent AF and mild to moderate heart failure to targeted therapy of underlying conditions or conventional therapy. Both groups received rhythm control therapy. In the intervention group additional therapies that were started included mineralocorticoid receptor antagonists, statins, angiotensin converting enzyme (ACE) inhibitors, and cardiac rehabilitation including physical activity, dietary restrictions, and counselling. The primary endpoint was sinus rhythm on a 7 day Holter monitor at 1 year. At 1 year, sinus rhythm was present in 89 (75%) of the intervention group vs. 79 (63%) in the conventional group (P = 0.042). This study is important as it calls attention to the chorus of voices and data worldwide emphasizing the importance of risk factor modification in patients with AF. At the European Society of Cardiology Meeting 2009 in Barcelona, the first trial investigating a modern Non-Vitamin K antagonist oral anticoagulant (NOAC) in AF was presented.10 What followed was a paradigm shift in the prevention of stroke in AF with similar (if not better) efficacy as well as safety (particularly regarding the most feared complication of intracranial Haemorrhage). In order to answer questions arising during daily clinical practice the European Heart Rhythm Association (EHRA) ‘Practical Guide’ was realized by Hein Heidbüchel and co-workers in 2013,11 followed by an update in 2015.12 A fully reworked and expanded version of the EHRA practical guide was presented and published in March 2018.13 Some good examples of situations without evidence in the beginning which were essentially solved over the years were those of perioperative management of NOACs around cardioversion, cardiac device implantations as well as AF ablation. For cardioversion, latest evidence from the EMANATE trial indicates that also with apixaban, the risk of stroke and systemic embolism is very low [0/753 patients, vs. 6/747 with heparin/vitamin K antagonist (VKA)] with equally very low risk of major bleeding events.14 Those findings are much in line with the X-Vert and Ensure-AF study using rivaroxaban15 and edoxaban,16 respectively, as well as with findings from the Re-LY trial using dabigatran.17 Taken together, these findings indicate that cardioversion can safely be performed with NOACs provided the necessary prerequisites are met (comparable to those with VKA).13 For AF ablation, uninterrupted (or only a brief interruption) had been demonstrated to be the therapy of choice for dabigatran18 and rivaroxaban,19 which was this year supplemented by the AXAFA study with apixaban (Figure 1).20 Indeed, also for apixaban, uninterrupted NOAC therapy resulted in a low number of ischaemic and bleeding events in 674 patients receiving either continuous apixaban or warfarin (composite of death, stroke, or Bleeding Academic Research Consortium (BARC) 2–5 bleeding: 6.9% vs. 7.3%). A substudy of 335 subjects examined the impact of these two anticoagulation strategies on asymptomatic cerebral emboli detected by magnetic resonance imaging (MRI). There was no difference in the primary outcome, being observed in 22 of 318 patients randomized to apixaban vs. 23/315 randomized to VKA. There were two strokes or TIAs in the trial, both in the apixaban arm. Major bleeding was observed in 3.1% of patients receiving apixaban vs. 4.4% on VKA therapy (P = NS). The incidence of asymptomatic cerebral emboli lesions also did not differ based on the anticoagulation strategy. This study further supports the safety and efficacy of performing AF ablation on uninterrupted NOAC therapy. Main outcome of the AXAFA trial.20 Cumulative primary outcome since randomization until 90 days after randomization. VKA, vitamin K antagonist therapy. Reproduced from reference 20. In the BRUISE CONTROL-2 study, both uninterrupted (median time from last intake to operation = 12 h) as well as interrupted (median time from last intake to operation = 72 h) NOAC therapy resulted in a low number of bleeding and even fewer ischaemic events, indicating that either strategy may be employed in perioperative management of these patients.21 Another notable study examined the relationship between dementia and oral anticoagulation in patients with AF. This was a retrospective study based on the large Swedish National Registry.22 The study included 444 106 patients with a hospital diagnosis of AF and no prior history of dementia. During over 1.5 million years of follow-up, patients on anticoagulant therapy at baseline had a 29% lower risk of dementia than patients without anticoagulation treatment. While this study is by no means definitive, it does support the hypothesis that anticoagulation of AF patients reduces the risk of dementia. Novel oral anticoagulants have revolutionized the management of stroke prevention in AF, based on the randomized clinical trials and ‘real world’ evidence. When interpreting the wealth of information stemming from the latter it is important to keep in mind which type of data sources should be used to answer which type of research questions—and where to be careful due.23 Has the introduction of NOACs translated into measurable effects? In English national databases, the number of patients with known AF increased linearly from 692 054 to 983 254 (prevalence 1.29% vs. 1.71%) from 2006 to 2016. At the same time, hospital episodes of AF-related stroke/100 000 AF patients increased from 80/week in 2006 to 98/week in 2011 and declined to 86/week in 2016 [2006–2011 difference 18.0, 95% CI 17.9–18.1, 2011–2016 difference −12.0, 95% CI −12.1 to −11.9]. In parallel, anticoagulant use in at-risk patients (CHA2DS2-VASc ≥ 2) increased from 48.0% to 78.6% and anti-platelet use declined from 42.9% to 16.1%, especially in the period from 2011 to 2016. These data indicate that the introduction of the NOACs, its inclusion in official guidelines,5 and the substantial increase in teaching activities and awareness were indeed paralleled by a reduction in hard clinical endpoints (Figure 2).24 Conversely, the authors predict that if the use of anticoagulants had remained stable at the levels of 2009, 4068 (95% CI 4046–4089) more strokes would have occurred in 2015/2016. A great example of a successful joint effort ‘to reduce the burden of cardiovascular disease’—the official ESC mission. Atrial fibrillation-related stroke in England and its association with uptake of oral anticoagulation.24 Temporal trend in finished consultant episodes of atrial fibrillation-related stroke per 100 000 patients with atrial fibrillation and uptake of oral anticoagulants and anti-platelet drugs for patients with atrial fibrillation and a CHA2DS2-VASc score ≥ 2.24 The anticoagulant timeline is a weighted trend derived from Holt et al., GRASP AF, and Quality and Outcomes Framework.24 Reproduced from reference 24. How can we increase adherence to NOACs even more? Telemonitoring-based feedback may be the answer, according to an innovative Belgian pilot study in 48 patients.25 Whether this also holds true in larger sample sizes as well as the question of cost-effectiveness in a larger scale setting remains to be proven. Since the two landmark studies (DINAMITE and IRIS) demonstrated no reduction of mortality with ICD within first 40 days after acute myocardial infarction (MI), a strategy of bridging this time period with wearable cardioverter-defibrillator (WCD) has been introduced. To evaluate the efficacy of this approach, the large, randomized Vest Prevention of Early Sudden Death Trial (VEST) screened 13 774 patients between 2008 to 2017, of whom 2302 with acute MI and LVEF ≤ 35% were 2:1 randomized within 7 days of hospital discharge to open-label WCD or usual care.26 During a median follow-up of 84 days, 1.6% of the WCD group and 2.4% of the control group experienced the primary Endpoint of sudden cardiac death or death from ventricular arrhythmia (HR 0.67; 0.37–1.21; P = 0.18). Of 1524 patients in the WCD arm, 20 patients (1.3%) received an appropriate shock, of which 14 survived to 90 days. Nine patients experienced an inappropriate shock, and 70 patients had aborted shocks. Surprisingly, all-cause death occurred more frequently in the control arm (4.9%, mainly due non-sudden death) as compared to 3.1% in treatment arm (P = 0.04). The overall mortality difference of 36% was announced as a positive trial documenting significant benefit of WCD. However, since the trial did not meet its primary endpoint, the results—overall—did not demonstrate a clinically meaningful reduction of arrhythmic mortality. Also in the light of significant cost of the technology, it remains questionable in whom the use of a WCD early after MI is justified. Recent studies suggested that complex evaluation of apparently unexplained cardiac arrests has a substantial potential to unmask specific aetiology.27 A large ongoing prospective registry of sudden cardiac arrest in the Paris area was used to describe characteristics of patients with a diagnosis of idiopathic ventricular fibrillation and evaluate the completeness of investigations in this population. Investigations performed during the index hospitalization or planned after hospital discharge were recorded to evaluate the completeness of assessment of unexplained cardiac arrest. Out of 18 622 cases of out-of-hospital cardiac arrests in a period from 2011 to 2016, 717 survivors at hospital discharge fulfilled the definition of sudden cardiac arrest. Among them, 88 (12.3%) remained unexplained after initial investigation using ECG, echocardiography, and coronary angiography. Magnetic resonance imaging and other investigations yielded the diagnosis in additional 39 patients (5.9%). Genetic testing and family screening, recommended in ESC guidelines, were initiated in only 9 (18.4%) and 12 (24.5%) cases, respectively. These findings emphasize the importance of referring victims of cardiac arrest to expert centres offering a comprehensive assessment—something still substantially underused in many clinical scenarios and areas today, and clearly a call for action. Catheter ablation has become current state-of-the-art strategy for management of ventricular tachycardia (VT) resistant to antiarrhythmic drugs. With the advent of electroanatomical mapping, various strategies of substrate mapping have been developed with different procedural endpoints and outcomes. A recent meta-analysis included 6 studies for the comparison of standard ablation of stable VT vs. substrate modification, with a total of 396 patients (mean age 63 ± 10 years, 87% males).28 In addition, seven studies were selected to assess the impact of complete vs. incomplete substrate modification, with a total of 391 patients (mean age 64 ± years, 90% males). The results suggested that substrate modification is associated with decreased composite VA recurrence/all-cause mortality compared to standard ablation of stable VTs [risk ratio (RR) 0.57, 95% CI 0.40–0.81]. Complete substrate modification was associated with decreased VA recurrence as compared to incomplete substrate modification (RR 0.39, 95% CI 0.27–0.58). Needless to say that different strategies of substrate modification may be combined together to provide even better benefit. Another question is about the role of percutaneous support for VT ablation. Recently, multicentre observational, real-world data from experienced centres, comparing 105 pts on hemodynamic support with 1650 VT ablations without the support, were published.29 As subjects with support were had lower LVEF and more outcome in hospital mortality, or 12 was than in patients ablated without the When cohort of patients with LVEF and and was was no significant difference in clinical outcomes when compared with no These results do not support the use of percutaneous support in ablation strategies substantial modification of a substrate even without a for of VT or without the strategy used in results of catheter ablation for of the arrhythmia substrate may not be A has been suggested of was in subjects had either at one traditional ablation that or a to ablation underwent a combined imaging study and tachycardia was in four to more VT This information together with data from previous mapping were used for of the for a blanking period of 6 a reduction in total VT burden was from the baseline in all subjects In to these in the safety was data in this have been provided by very recent of the trial from the same This was a trial of cardiac in with episodes of VT or to ventricular patients were for and mapping was used to the for ablation. was associated with markedly reduced ventricular arrhythmia burden (median number of VT episodes reduced from to P with patients developed a serious failure and However, events were much more 5 patients had pericardial 2 patients developed and The treatment reduction in antiarrhythmic drug use and improvement in quality of Taken together, this strategy for patients or those with myocardial substrate the safety and efficacy have to be in further of ventricular of ventricular tachycardia in a patient with a history of myocardial infarction and of ventricular tachycardia from substrate in the that was during two previous catheter ablation electroanatomical of the a large to the for and at with for the of the substrate during and line of of The for both regarding standard as well as for In a randomized 1 on with at the EHRA in Barcelona, patients were and followed for 6 with a reduction in were randomized to vs. traditional While was no difference in from to between the two groups with vs. in the conventional arm, P = the rate was much in those patients with studies are to further the of to reduce On this study more the importance of expert device frequently in daily clinical but which should a of care of these the Some studies over the year of indicate that this may be the last year, we have to that until results from randomized outcome trials are these studies have to be with for cardiac has that data have to be as until a randomized clinical trial can a clear studies are and are high that may to be an important in Another question to the role of ablation with of device for rate control of AF in population. The results of the multicentre randomized trial further support for this The study of subjects with symptomatic AF, ≤ and at one hospitalization for heart failure in previous year. In the patients were in the intention to treat analysis in the ablation and in the drug treatment arm. significant improvement in the study a significant reduction in primary endpoint or hospitalization due heart failure or worsening of heart in of ablation with of device The difference between treatment was even more in patients with LVEF ≤ 35% reduction of primary endpoint, P of from and for in has received from and to and from and and research support from has received consultant from and of has received support from and
Source: European Heart Journal
Authors: Josef Kautzner, Hugh Calkins, Jan Steffel
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2915621024