Latest innovations designed to optimize arrhythmia care
Investigators in four late-breaking trials revealed findings in arrhythmia care during Sunday’s “Innovations to Optimize Arrhythmia Care.” They found:
- Left bundle branch pacing beats standard-of-care pacemaker implantation for atrioventricular block.
- PVI + LVA ablation is more effective than standard-of-care PVI alone for patients with detected LVAs.
- ARNI is superior to ARB to reduce atrial arrhythmia after catheter ablation in select patients.
- Promising benefits for out-of-hospital cardiac arrest survival with comprehensive community/EMS intervention.
Left bundle branch pacing showed better outcomes vs. right ventricular pacing for atrioventricular block
Individuals with atrioventricular block are typically given an implanted pacemaker using right ventricular pacing (RVP). The global OptimPacing Study found that using left bundle branch pacing (LBBP) in place of RVP decreased a composite endpoint by 59% with similar rates of adverse events. The independent data monitoring committee recommended terminating the study early for superiority during a planned interim analysis.
Jiangang Zou, MD, PhD
“Not all pacing options are the same, and people who need a pacemaker to keep their heart beating properly should talk with their healthcare team about which pacing approach is appropriate for their condition,” said Jiangang Zou, MD, PhD, professor of cardiology at First Affiliated Hospital at Nanjing Medical University, in Nanjing, China. “Our findings show that left bundle branch pacing helped the heart beat in a more natural way and was linked to fewer serious heart-related events than the standard approach of right ventricular pacing.”
RVP has been the standard of care for decades but is associated with cardiac desynchrony and left ventricular systolic dysfunction, which can increase the risk of pacing-induced cardiomyopathy, heart failure and death. LBBP preserves left ventricular electrical and mechanical synchrony, but the clinical benefits compared to RVP for patients with atrioventricular block were uncertain.
OptimPacing was an investigator-initiated, international, randomized controlled, multicenter study of patients with an indication for a permanent pacemaker, second-degree or complete atrioventricular block, persistent or permanent AFib with a mean heart rate <50 beats per minute. The trial randomized 685 patients to standard-of-care RVP (343 patients) and LBBP (342 patients) across 17 sites in China, Poland, the United Kingdom and the United States.
For RVP, the active lead was implanted in the RV septum or apex using standard-of-care techniques. For LBBP, a 3830 lumenless lead was fixed into the interventricular septum to reach the left ventricular. The mean age of patients was 68.4, and 57.5 were male. Mean LVEF was similar: 62.5 in the RVP group and 63.2 in the LBBP group.
The primary outcome was time to first occurrence of all-cause death, hospitalization for heart failure or cardiomyopathy induced by pacing. Secondary outcomes included echocardiographic measurements, pacing parameters and clinical evaluations.
A planned interim analysis after 51 primary outcome events had a median follow-up of 35.1 months. The composite primary outcome was seen in 35 RVP patients compared to 16 LBBP patients, a four-year rate of 19.2% vs. 8.5%, hazard ratio (HR) 0.41 (95% CI: [0.23, 0.75], p=0.0027). The data monitoring committee recommended early termination for superiority of LBBP, although early termination may lead to an overestimation of treatment effects.
No patients in the LBBP group developed pacing-induced cardiomyopathy compared to 11.7% of patients in the RVP group. Heart failure was seen in 2.9% of the RVP group vs. 1.5% of LBBP group, and all-cause mortality was similar in both groups. Rates of procedure- and pacing system-related complications and lead revisions were similar in the groups.
“We expected that the group with left bundle branch pacing would do better than the group with right ventricular pacing,” Zou said. “However, the difference between the groups was greater than we expected. This study shows that left bundle branch pacing should be the first choice for patients with heart block who need a pacemaker.”
OptimPacing was published simultaneously in the New England Journal of Medicine.
Double ablation more effective than conventional approach for reducing persistent AFib
Persistent atrial fibrillation is a consistent problem despite continuing improvements in catheter ablation. An extended comparison of standard care for persistent AFib in a subgroup of patients with detectable low-voltage areas, pulmonary vein isolation (PVI) alone, vs. PVI +atrial low-voltage area (LVA) ablation, showed a 23% reduction in the risk of subsequent AFib for the combination approach for a subset of patients with detectable LVAs. Combination treatment showed a nonsignificant 18% advantage in the overall COAST-AF population.
Pablo Nery, MD
“We know that PVI, while it is very effective for the management of paroxysmal atrial fibrillation, often leads to suboptimal results in patients with persistent AFib,” said Pablo Nery, MD, cardiac electrophysiologist at the University of Ottawa Heart Institute and associate professor of medicine at the University of Ottawa, Canada. “We set out to design and conduct the COAST-AF trial to determine whether or not catheter ablation beyond pulmonary vein isolation, specifically the identification and ablation of low voltage areas, could improve outcomes for patients with persistent AFib.”
The trial included 505 patients with persistent AFib to either PVI alone (254 patients) or PVI + LVI ablation (251 patients) at 14 tertiary care centers across Canada. A subset of 268 patients had detectable LVAs at baseline. The mean age of patients was 65 years; 24% were female, and 23% had long-standing persistent AFib. The median follow-up was 21 months. Patients were followed for up to 36 months and at least 18 months.
The primary endpoint was time to recurrence of first documented atrial arrhythmia (AA), defined as AFib, atrial tachycardia or atrial flutter, occurring >90 days after ablation. Secondary endpoints included arrhythmia efficacy, resource utilization and safety events, including stroke, pulmonary vein stenosis, pericarditis, cardiac perforation, major bleeding or death.
The cumulative rate of AA recurrence in the PVI only group was 57.5% vs. 49.4% for the PVI + LVA ablation group in the overall trial population for a hazard ratio (HR) of 0.82 (95% CI: [0.65, 1.04], p=0.106). In the subset of patients with detected LVA, PVI alone had an AA recurrence rate of 69.2% vs. 49.3% for PVI + LVA ablation, HR 0.77 (95% CI: [0.66, 0.91], p=0.002). There was no significant difference in safety outcomes between the groups.
“Combined with other recently completed trials, our findings suggest that catheter ablation using this combined strategy of pulmonary vein isolation plus low voltage area ablation is beneficial in the subgroup of patients with detectable low voltage areas and should be considered in patients with comparable characteristics,” Nery said.
COAST-AF was published simultaneously in the Journal of the American Medical Association.
ARNI beat ARB to reduce atrial fibrillation after catheter ablation in older patients with hypertension
Treatment with sacubitril/valsartan significantly reduced the risk of recurrent atrial fibrillation compared with valsartan alone during the first year after catheter ablation for AFib in a select population of older patients with hypertension. Primary results from the open-label SUPERIOR trial showed a 42% reduction in any atrial tachyarrhythmia for the angiotensin-receptor neprilysin inhibitor (ARNI) sacubitril/valsartan vs. the angiotensin receptor blocker (ARB) valsartan. Valsartan is a commonly prescribed ARB for the treatment of hypertension and was used as the active comparator in the trial.
“The SUPERIOR trial was designed to answer a very practical question we often face after catheter ablation for atrial fibrillation,” said Wei Zhang, MD, PhD, Shanghai Institute of Hypertension and the Centre for Epidemiological Studies and Clinical Trials at Ruijin Hospital, and Shanghai JiaoTong University School of Medicine in Shanghai, China.
Wei Zhang, MD, PhD
“Hypertension is one of the most important modifiable risk factors for atrial fibrillation and its recurrence. Even after a successful catheter ablation, the underlying atrial changes associated with hypertension may persist,” Zhang said. “We compared sacubitril/valsartan with valsartan alone for 12 months to determine whether the choice of antihypertensive therapy could influence the risk of recurrent atrial arrhythmias after ablation.”
The trial randomized 320 patients across three centers in China to receive either sacubitril/valsartan (161 patients) or valsartan (159 patients) for 12 months after catheter ablation. Treatment was initiated at 100 mg or 80 mg once daily, respectively, with dose adjustments based on blood pressure control. All patients were scheduled to undergo catheter ablation before randomization.
The mean age of the patients was 68 years; 41.2% were female and 66.6% had paroxysmal AFib.
Between three and 12 months after ablation, documented atrial tachyarrhythmia occurred in 29 patients in the ARNI group (18.0%) and 45 patients in the ARB group (28.3%), corresponding to a hazard ratio of 0.58 (95% CI: [0.36, 0.95], p=0.03). The corresponding incidence rates of documented atrial tachyarrhythmia were 20.9 and 36.1 per 100 person-years for the two groups, respectively.
There were no significant between-group differences in the reductions in clinic or 24-hour ambulatory blood pressure. There were no serious adverse events in either group, Zhang said, and the few mild adverse events were similar across groups.
“The findings are clinically relevant and important, but I would not interpret just one trial as supporting routine replacement of conventional ARBs with sacubitril/valsartan for every patient after atrial fibrillation ablation,” Zhang said. “Our findings suggest that the choice of antihypertensive therapy may be relevant to arrhythmia outcomes in selected older patients with hypertension. The results need confirmation in broader populations and with longer follow-up.”
The follow-up period for SUPERIOR has been extended to three years, he added. Later analyses will assess hard clinical outcomes including multiple cardiovascular events and mortality.
Major trial shows promising benefits but not significant improvement in survival for out-of-hospital cardiac arrest
What may be the largest randomized trial of early cardiopulmonary resuscitation and defibrillation for out-of-hospital cardiac arrest failed to show a statistically significant improvement in hospital survival with favorable neurologic outcomes. An exploratory analysis showed a significant increase in bystander CPR in the final year of the five-year trial, an important benefit suggesting that longer intervention may have the potential to improve bystander response. 
Carolina Malta Hansen, MD, PhD
“In the U.S. alone, about 350,000 people have an EMS-treated out-of-hospital cardiac arrest, and only about 10% survive,” said Carolina Malta Hansen, MD, PhD, clinical research associate professor of cardiology at the University of Copenhagen in Denmark. “We know that survival decreases about 10% per minute after cardiac arrest without any help. We also know that if the patient receives CPR and defibrillation within minutes, we can increase survival chances up to 70%-75%. We know what needs to be done; we just don’t know how to do it in our communities.”
RACE-CARS was a pragmatic trial comparing a comprehensive intervention for out-of-hospital cardiac arrest to usual care for more than 22,000 patients across 60 counties in North Carolina representing a population of over 8.5 million people. Counties were grouped into clusters with similar demographic characteristics. Interventions included 9-1-1 center training to improve rapid cardiac arrest recognition and bystander CPR instruction by 9-1-1 telecommunicators, community CPR training and enhanced automated external defibrillator use by first responders.
Data were collected using the preexisting Cardiac Arrest Registry to Enhance Survival (CARES). The primary outcome was survival to hospital discharge with good neurologic outcome.
A total of 22,459 out-of-hospital cardiac arrest patients from across North Carolina were included in the trial, 11,615 (28 clusters) in the intervention group and 10,844 (27 clusters) in the usual care group.
Results showed no difference in hospital survival with good neurologic outcome, 9.0% in the intervention group and 9.4% in the usual care group, adjusted odds ratio (aOR) 0.97 (95% CI: [0.75, 1.26], p=0.80). Bystander CPR or defibrillation before EMS arrival were likewise similar, 44.8%/13.5% in the intervention group and 42.3%/15.3% in the usual care group, aOR 1.06 (95% CI: [0.87, 1.29]) and aOR 0.79 (95% CI: [0.42, 1.49]).
An exploratory analysis showed a significant increase in bystander CPR in the final year of the trial. The fidelity of intervention components varied widely by county. More than 200,000 people were trained in CPR by the end of year 4.
“When we trained nearly 5% of the intervention population in CPR, we started to see a difference in outcomes,” Hansen said. “Based on this and what we’ve seen in other communities, this intervention may need to be intensified and sustained for a longer period of time to have a substantial effect on survival. We plan to continue looking at the impact on the population for a longer period. We know that improving survival is all about the first minutes after cardiac arrest. Everyone can administer CPR and save a life. It only takes two hands.”
RACE-CARS was published simultaneously in the New England Journal of Medicine.
