|Year : 2017 | Volume
| Issue : 1 | Page : 1-4
Top ten studies of cardiac arrhythmia in 2016
Arrhythmia Center, National Center for Cardiovascular Diseases and Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China
|Date of Web Publication||19-Jun-2017|
Arrhythmia Center, National Center for Cardiovascular Diseases and Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Zhang S. Top ten studies of cardiac arrhythmia in 2016. Int J Heart Rhythm 2017;2:1-4
| Introduction|| |
The annual summary of the top ten most influential studies in cardiac arrhythmia and electrophysiology has been going through an increasingly thrilling time since its debut 5 years ago. There are a lot to say about the happenings and findings in year 2016, from which we list the key findings of the ten most important studies with potential direction for clinical practice and research innovation. By looking back at the achievements in 2016, let us instil enthusiasm for further scientific endeavors in the years to come!
NO. 1: Cryoballoon ablation is noninferior to radiofrequency ablation with respect to efficacy and safety for paroxysmal atrial fibrillation. (N Engl J Med 2016;374:2235-45).
In June 2016, the New England Journal of Medicine issued the outcomes of the FIRE AND ICE Trial. As a multicenter, prospective, randomized, and noninferiority trial to compare cryoballoon ablation with radiofrequency ablation, the FIRE AND ICE trial enrolled a total of 762 patients who were randomly assigned to Arctic Front ™ cryoballoon group (n = 374) and radiofrequency group guided by CARTO mapping system (n = 376), and all received isolation of pulmonary veins. The primary efficacy end point was the first documented clinical failure occurring more than 90 days after the ablation procedure, which included the recurrence of atrial fibrillation (AF), occurrence of atrial flutter or atrial tachycardia, prescription of antiarrhythmic drugs, or repeat ablation. The primary safety end point was composed of all-cause death, cerebrovascular events including stroke or transient ischemic attack from any cause, and serious adverse events. After a mean follow-up of 18 months, the primary efficacy end point occurred in 138 patients in the cryoballoon group and in 143 in the radiofrequency group (1-year Kaplan–Meier event rate was 34.6% and 35.9%, respectively, hazard ratio (HR) was 0.96; P< 0.001 for noninferiority). The primary safety end point occurred in 40 patients in the cryoballoon group and 51 in the radiofrequency group (1-year Kaplan–Meier event rate was 10.2% and 12.8%, respectively, HR was 0.78; P= 0.24).
The outcomes of the FIRE AND ICE trial indicated that in the treatment of patients with drug-refractory paroxysmal AF, cryoballoon ablation was noninferior to radiofrequency ablation in terms of general safety. Compared with radiofrequency ablation, the relative simplicity and shorter learning curve of cryoballoon ablation make it be a handiest tool for the treatment of paroxysmal AF.
NO. 2: DANISH Trial: Benefits from ICD primary prevention are limited in patients with nonischemic cardiomyopathy. (N Engl J Med 2016;375:1221-30).
In the 2016 ESC conference, the results of the DANISH trial were presented and simultaneously published in N Engl J Med. In this randomized controlled trial, 556 patients with symptomatic systolic heart failure (left ventricular ejection fraction [LVEF] ≤35%) not caused by coronary artery disease were assigned to receive an implantable cardioverter defibrillator (ICD), and 560 patients were assigned to receive usual clinical care as the control group. In both groups, 58% of the patients received cardiac resynchronization therapy. The primary outcome of the trial was all-cause mortality. The secondary outcomes were sudden cardiac death and cardiovascular death. After a median follow-up period of 67.6 months, there were no significant differences in all-cause mortality (21.6% vs. 23.4%, P= 0.28) and device infection (4.9% vs. 3.6%, P= 0.29) between ICD group and control group. However, the incidence of sudden cardiac death was significantly reduced in the ICD group when compared with the control group (4.3% vs. 8.2%, P= 0.005). Results of subgroup analyses showed that the curative effect of ICD group is better than the control group among patients younger than 68 years of age, which suggests that younger patients may have a survival benefit in association with ICD implantation.
This trial suggests that for patients with nonischemic cardiomyopathy, the primary prevention of ICD should be comprehensively assessed with the risk of complication, age, and so on.
NO. 3: VANISH trial: For recurrent ventricular tachycardia after ICD implantation, catheter ablation is superior to escalated drug therapy. (N Engl J Med 2016;375:111-21).
About 50% deaths among survivors of myocardial infarction were attributed to sudden cardiac death caused by ventricular tachycardia and ventricular fibrillation. The implantation of ICD could effectively terminate ventricular arrhythmias and significantly reduce the risk of sudden cardiac death. If ventricular tachycardia reoccurs despite ICD implantation, which strategy should be chosen, catheter ablation or escalation of drugs? In June 2016, N Engl J Med issued the results of VANISH trial. The VANISH trial was a multicenter, randomized controlled trial involving 259 patients with ischemic cardiomyopathy. One hundred and thirty-two patients were randomly assigned to the catheter ablation group receiving continuation of baseline antiarrhythmic medications and 127 were assigned to the escalated therapy group and were treated with amiodarone or amiodarone plus mexiletine. The primary outcome was a composite of death, ventricular tachycardia storm (three or more documented episodes within 24 h), or appropriate ICD shock. During a mean follow-up of 28 months, the rate of the primary outcome was significantly lower in the ablation group than in the escalated therapy group (59.1% vs. 68.5%, P= 0.04). There was no significant difference in mortality between the two groups. In the escalated therapy group, treatment-related adverse events were more frequent including three deaths attributed to antiarrhythmic drugs (two from pulmonary injury and one from hepatic dysfunction). In the ablation group, there were more frequent procedural complications than in the escalated therapy group including two cardiac perforations and three major bleeding.
The outcomes of VANISH trial have indicated that for the ischemic cardiomyopathy patients with ICD and recurrent ventricular tachycardia, catheter ablation was superior to escalated drugs because it was more effective in reducing the recurrences of ventricular arrhythmias and had a lower rate of treatment-related adverse events.
NO. 4: Wearable cardioverter defibrillator, data from the Europe. (Circulation 2016;134:635-43).
Wearable cardioverter defibrillator (WCD), as a new alternative of ICD, can prevent sudden cardiac death effectively. The prospective registry WEARIT-II study initiated in 2015 has reported the real-world safety and efficacy of the WCD. However, the large-scale evaluation of WCD use in patients beside the US health-care system remained unclear.
A large, nationwide study including 6043 WCD patients in 404 German medical centers was published on Circulation in August 2016. Patients were grouped into 8 cardiovascular indications: ICD explantation with delayed reimplantation (11.9%), congestive heart failure (0.4%), heart transplantation awaits (0.7%), ischemic cardiomyopathy (26.9%), dilated cardiomyopathy (36.7%), nonischemic cardiomyopathy (12.2%), myocarditis (9.8%), and genetic disease (1.4%). The leading cause for WCD prescription was ischemic cardiomyopathy in male, with dilated cardiomyopathy and myocarditis in female. In total, 1.6% of the patients received appropriate treatment and 89% of all treatment occurred within the first 90 days after wear. Patients with ICD explantation and a delayed reimplantation had an incidence rate of 19.3/100 patient-years. In contrast, an incidence rate of 8.2 was observed in the remaining cardiac diagnosis groups. Among 120 shocked patients, 112 (93%) survived 24 h after treatment, indicating an extensive benefit among patients.
This study was the first large, nationwide study in Europe confirming the overall value of WCD in the detection and termination of VT/VF among outpatients. The study also pitched a prospective of further extensive utilization of WCD.
NO. 5: Subcutaneous versus transvenous ICD therapy, noninferior in long-term clinical outcomes. (J Am Coll Cardiol 2016;68:2047-55).
Transvenous ICDs (TV-ICDs) improve survival in patients at high risk for sudden cardiac death, but complications related to TV leads are common and troublesome. The subcutaneous ICD (S-ICD) was developed to eliminate these complications. However, direct comparison of clinical outcomes of both device types is limited due to varying patient characteristics.
The authors compared long-term clinical outcomes of TV-ICD and S-ICD therapy. In total, 1160 patients who underwent ICDs implantation in two hospitals in the Netherlands were analyzed, and 140 patients were included after propensity matching for 16 baseline characteristics including diagnosis. Clinical outcomes were device-related complications requiring surgical intervention and appropriate and inappropriate ICD interventions in the 5-year follow-up. The complication rates in the S-ICD group and TV-ICD group were similar (13.7% vs. 18.0%, P= 0.80), but the S-ICD group had less lead complications than TV-ICD group (0.8% vs. 11.5%, P= 0.03). Nonlead-related complications were more common among S-ICD patients compared with the TV-ICD patients (9.9% vs. 2.2%, P= 0.047). The S-ICD group and the TV-ICD group had a similar incidence of the appropriate intervention (17% vs. 21.3%) and inappropriate interventions (20.5% vs. 29.7%).
This study demonstrated that long-term clinical outcomes of TV-ICD and S-ICD therapies had no significant difference, and therefore S-ICD therapy might be more advantageous among patients for primary prevention and those without the need of pacing or antitachycardia pacing therapy in the future.
NO. 6: BELIEF trial: Electrical isolation of left atrial appendage improves the success rate of catheter ablation in long-standing persistent atrial fibrillation. (J Am Coll Cardiol 2016;68:1929-40).
Right now, long-standing persistent AF (LSPAF) is the most challenging type in terms of AF ablation. Although there were reports about the electrical isolation of the left atrial appendage (LAA), whether the empirical electrical isolation of LAA could improve the success rate of AF ablation is unknown. In November 2016, J Am Coll Cardiol published the results of BELIEF trial which aimed at assessing the effectiveness of empirical electrical isolation of LAA. This open-label and randomized trial enrolled 173 patients with LSPAF and randomly assigned them to undergoing empirical electrical LAA isolation along with standard ablation (Group 1; n = 85) or standard ablation alone (Group 2; n = 88). There were no significant differences between the two groups in baseline characteristics. The primary end point was a recurrence of atrial arrhythmias, and the secondary end points included cardiac-related hospitalization, all-cause mortality, and stroke. At 12-month follow-up, 56% patients in Group 1 and 28% patients in Group 2 were free of recurrence after a single procedure (HR: 1.92; 95% confidence interval [CI]: 1.3–2.9; P= 0.001). After adjusting for age, sex, and left atrial size, the standard ablation approach was a predictive factor of recurrence (HR: 2.22; 95% CI: 1.29-3.81; P= 0.004). All recurrent patients received empirical electrical isolation of LAA. At 24-month follow-up, the cumulative success rate in Group 1 was significantly higher than in Group 2 (76% vs. 56%; HR: 2.24; 95% CI: 1.3–3.8; P= 0.003).
The results of BELIEF trial showed that standard ablation plus empirical electrical isolation of the LAA may become the standard procedure for the treatment of patients with LSPAF.
NO. 7: The US experience of Watchman for stroke prevention in atrial fibrillation patients. (J Am Coll Cardiol 2016; pii: S0735-1097(16) 36641-4).
LAA closure (LAAC) using the Watchman device was food and drug administration-approved as a stroke prevention alternative for patients with nonvalvular AF. However, clinical decision-making is confounded by the fact that while LAAC avoids the anticoagulant-related lifetime risk of bleeding, implantation is associated with upfront complications. Thus, enthusiasm for LAAC as a treatment option has been appropriately tempered, particularly as the therapy is introduced beyond the clinical trial sites into general clinical practice.
In November 2016, J Am Coll Cardiol published the results of the clinical data with respect to the Watchman experience in the US. In 3822 consecutive cases, implantation was successful in 3653 (95.6%) with a median procedure time of 50 min. Procedural complication rates included 39 pericardial tamponade (1.02%; 24 treated percutaneously, 12 surgically, and 3 fatal), 3 procedure-related strokes (0.078%), 9 device embolizations (0.24%; 6 requiring surgical removal), and 3 procedure-related deaths (0.078%). This initial clinical experience with LAAC using the Watchman device was performed in 3822 consecutive patients by 382 physicians that 71% of the operators were newly implanting physicians, and these physicians performed 50% of the procedures.
The data indicate that in the real world, procedural success rates remain high with a low procedural complication. Watchman may become a new safe choice to reduce the risk of stroke for patients with nonvalvular AF in the near future.
NO. 8: Coronary revascularization did not reduce the risk of recurrent sustained ventricular arrhythmias. (Heart Rhythm 2016;13:1221-7).
Ventricular arrhythmia (VA) is a common complication of myocardial infarction. It remains unknown whether coronary revascularization can reduce recurrent VAs in patients with prior myocardial infarction and relatively preserved LVEF. This cohort study aims to determine the impact of coronary revascularization on recurrent VAs and all-cause mortality. A total of 274 patients with prior myocardial infarction and LVEF ≥ 40% who presented with first clinical sustained VAs in the absence of an acute ischemic event were included in the study. Eighty-eight patients (32.1%) underwent revascularization. During a mean follow-up period of (6.2 ± 5.1) years, 140 patients (51.1%) died or had recurrent sustained VAs or appropriate ICD therapy. Coronary revascularization did not significantly reduce the incidence of recurrent VAs or mortality (HR 0.86; 95% CI: 0.60–1.24; P= 0.43), regardless of complete or incomplete revascularization or by percutaneous or surgical means. However, the mortality reduction conferred by ICDs is significant (HR 0.23; 95% CI: 0.09–0.55; P= 0.001). Patients with prior myocardial infarction and LVEF ≥ 40% presenting with first sustained VAs were at high risk for recurrent VAs and death, but coronary revascularization did not reduce this risk.
NO. 9: Anticoagulation therapy in patients with atrial fibrillation undergoing PCI, dual or triple? (N Engl J Med 2016;375:2423-34).
In December 2016, N Engl J Med published the results of the PIONEER AF- percutaneous coronary intervention (AF-PCI) study, which provides the impressive data for the clinical anticoagulation decision for patients with AF undergoing PCI with stenting. PIONEER AF-PCI was an international, multicenter, randomized, open-label trial. Nearly 2124 participants with nonvalvular AF who had undergone PCI with stenting were randomly assigned in a 1:1:1 ratio, low-dose rivaroxaban (15 mg once daily) plus a P2Y12 inhibitor for 12 months (Group 1), very-low-dose rivaroxaban (2.5 mg twice daily) plus DAPT for 1, 6, or 12 months (Group 2), or standard therapy with a dose-adjusted vitamin K antagonist (once daily) plus DAPT for 1, 6, or 12 months (Group 3). The primary safety outcome was clinically significant bleeding (a composite of major bleeding or minor bleeding according to thrombolysis in myocardial infarction criteria or bleeding requiring medical attention). The rate of clinically significant bleeding was lower in the two groups receiving rivaroxaban than in the group receiving standard therapy (16.8% in Group 1, 18.0% in Group 2, and 26.7% in Group 3; HR for Group 1 vs. Group 3, 0.59; 95% CI: 0.47–0.76; P< 0.001; HR for Group 2 vs. Group 3, 0.63; 95% CI: 0.50–0.80; P< 0.001). The rate of death from cardiovascular causes, myocardial infarction, or stroke was similar in the three groups (P values for all comparisons were nonsignificant). In participants with AF undergoing PCI with placement of stents, the administration of either low-dose rivaroxaban plus a P2Y12 inhibitor for 12 months or very low-dose rivaroxaban plus DAPT for 1, 6, or 12 months was associated with a lower rate of clinically significant bleeding than was standard therapy with a Vitamin K antagonist plus DAPT for 1, 6, or 12 months.
The data indicate that rivaroxaban plus either one or two antiplatelet agents will both be the optimal choice for these patients.
NO. 10: Breakthrough in biological pacemakers: A new differentiation protocol for SAN-like pacemaker cells. (Nat Biotechnol 2016). [Doi: 10.1038/nbt. 3745].
Biological pacemaker, as an intriguing alternative to electronic pacemakers, was a hotspot in the 20th century; however, it fell into a significant bottleneck in the beginning of the 21st century. A recent study of biological pacemaker was published on Nature Biotechnology in December 2016. The latest study used a developmental-biology-guided approach to establish a transgene-independent differentiation protocol for generating sino-atrial-node-like pacemaker cells (SANLPCs) from human pluripotent stem cells (hPSCs). SANLPCs are regulated by stage-specific activation of the bone morphogenic protein and retinoic acid signaling pathways. Inhibition of FGF (fibroblast growth factor) signaling at the cardiac mesoderm stage completely abolishes the development of NKX2.5+ in working cardiomyocytes, allowing for the isolation of SANLPCs from differentiated populations based on the pan-cardiomyocyte surface marker SIRPA and lack of CD90 expression. SANLPCs with a similar gene expression profile to fetal SAN tissue were generated through this protocol and provided appropriate functional properties of pacemaker cells including action potential, ion current profiles, and chronotropic responses. Furthermore, the researchers demonstrated a pacemaker activity of SANLPCs in human ventricular cardiomyocytes in vitro and in the rat ventricle in vivo.
| Conclusion|| |
In year 2016, many fascinating studies with promising implications have emerged in the field of cardiac arrhythmia and electrophysiology, most of which may have important influence on scientific research and clinical practice. These results are worth learning and will enlighten us for years.
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There are no conflicts of interest.