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Rethinking AF treatment to prevent life-threatening conditions – Canadian studies

A Canadian study is shedding light on how to more effectively treat atrial fibrillation (AF), showing that early intervention with cryoballoon catheter ablation (cryoablation) is more effective at reducing the risk of serious long-term health impacts, compared with the current first step in treatment – antiarrhythmic drugs.

“By treating patients with cryoablation right from the start, we see fewer people advancing to persistent, more life-threatening forms of atrial fibrillation,” said Dr Jason Andrade, an associate professor of medicine at the University of British Columbia and director of Heart Rhythm Services at Vancouver General Hospital. “In the short term, this can mean less recurrences of arrhythmia, improved quality of life and fewer visits to the hospital. In the long run, this can translate into a reduced risk of stroke and other serious heart problems.”

Cryoablation is a minimally invasive procedure that involves guiding a small tube into the heart to kill problematic tissue with cold temperatures. Historically, the procedure has been reserved as a secondary treatment when patients don’t respond to antiarrhythmic drugs.

“This study adds to the growing body of evidence that early intervention with cryoablation may be a more effective initial therapy in the appropriate patients,” Andrade added.

Early intervention halts disease progression

While AF starts as an isolated electrical disorder, each recurring incident can cause electrical and structural changes in the heart that can lead to longer-lasting events, known as persistent AF (episodes lasting more than seven continuous days).

“Atrial fibrillation is like a snowball rolling down a hill. With each atrial fibrillation episode there are progressive changes in the heart, and the heart rhythm problem gets worse,” said Andrade.

The new findings, stemming from a multi-site clinical trial, show that cryoablation can stop this snowball effect.

For the trial, the pan-Canadian research team enrolled 303 patients with AF at 18 sites across Canada. Half of the patients were randomly selected to receive antiarrhythmic drugs, while the other half were treated with cryoablation. All patients received an implantable monitoring device that recorded their cardiac activity throughout the study period.

After three years, the researchers found that patients in the cryoablation group were less likely to progress to persistent AF compared with patients treated with antiarrhythmic drugs. Over the follow-up period, the cryoablation patients also had lower rates of hospitalisation and experienced fewer serious adverse health events that resulted in death, functional disability or prolonged hospitalisation.

Addressing the root cause

Because cryoablation targets and destroys the cells that initiate and perpetuate AF, the researchers say it can lead to longer-lasting benefits.

“With cryoablation, we’re treating the cause of the condition, instead of using medications to cover up the symptoms,” said Andrade. “If we start with cryoablation, we may be able to fix atrial fibrillation early in its course.”

The new study, published in the New England Journal of Medicine, builds on a previous paper in which he and his team demonstrated that cryoablation was more effective than antiarrhythmic drugs at reducing the short-term recurrence of atrial fibrillation.

The researchers say that more effective early interventions would benefit patients as well as the healthcare system. Currently, costs associated with the provision of atrial fibrillation-associated care are estimated at 2.5% of overall annual healthcare expenditures.

Those costs are expected to rise to 4% within the next two decades.

“The evidence shows increasingly that it’s time to rethink how we approach the treatment of atrial fibrillation. With effective early intervention, we can keep people healthy, happy, and out of hospital, which would be a tremendous benefit for patients and their families, and also our entire health system.”

In another study, published the day before the above-mentioned one, also in the New England Journal of Medicine, the researchers conducted a cluster-randomised trial with crossover among six Canadian paramedic services to evaluate DSED and VC defibrillation compared with standard defibrillation in adult patients with refractory ventricular fibrillation during out-of-hospital cardiac arrest.

They concluded that among patients with refractory ventricular fibrillation, survival to hospital discharge occurred more frequently among those who received DSED or VC defibrillation than among those who received standard defibrillation.

In an accompany editorial in the journal, Dr Comilla Sasson and Dr Jason Haukoos posed the question, Defibrillation after Cardiac Arrest — Is It Time to Change Practice?

They wrote: “Treatment of patients in ventricular fibrillation is challenging. Despite heroic efforts, including performance of high-quality chest compressions with minimal interruptions, placement of advanced airways, multiple standard defibrillation attempts, and other interventions for advanced cardiac life support, some patients will remain in refractory ventricular fibrillation. Unfortunately, this results in a major gap in care, with emergency care personnel left with few therapeutic options, coupled with a decreasing likelihood of successful resuscitation with increasing numbers of defibrillation attempts.”

They said that ultimately, this trial added important new effectiveness data from a multi-agency prehospital clinical trial in support of the use of DSED and VC defibrillation for refractory ventricular fibrillation.

“In light of the challenges of performing high-quality prehospital resuscitation research, this trial is an important step forward in understanding the effectiveness of these treatment methods. However, additional research is needed to further define the effects of DSED and VC defibrillation for refractory ventricular fibrillation, including trials specifically powered to test the difference between the two approaches and those that incorporate details related to post-resuscitation care. Until then, such extended forms of defibrillation are not ready for usual care, although they may be considered when no further treatment options exist.”

And meanwhile, a massive study in Sweden has showed that severe or morbid obesity at the age of 18 might be linked to an increased risk of atrial fibrillation in younger middle age, according to the University of Gothenburg research comprising data on some 1.7m men in Sweden, whose health was tracked for 32 years

The study, published in the Journal of the American Heart Association, is based on analysis of nationwide register data on 1 704 467 men who signed up for military service in Sweden between 1969 and 2005. The average age at enrolment was 18.

The enrolment data included height, weight, blood pressure, fitness and muscle strength. Using data on inpatient care and from cause-of-death records, the researchers were then able to determine the prevalence of atrial fibrillation and track the outcomes.

Atrial fibrillation is characterised by an irregular and often rapid heartbeat, sometimes accompanied by the heart’s inability to pump blood around the body as it should. The symptoms vary in severity and the disease may be chronic or consist of sporadic attacks. Hospitalisation is often required, and the risks of heart failure and ischaemic stroke (cerebral infarction) increase.

Atrial fibrillation at age 43

Over a median follow-up period of 32 years, 36 693 cases of atrial fibrillation were registered. For the whole group of participants, the average age at diagnosis was 52.4 years.

The rise in the risk of future atrial fibrillation began, in the men who signed up for military service, at what is usually classified as low normal weight, and continued with rising body mass index (BMI).

For men with severe or morbid obesity (a BMI of 35 or higher) at enrolment, the risk of atrial fibrillation in younger middle age was between three- and fourfold. Here, the average age at diagnosis was 43.4 years.

BMI on enrolment was also strongly linked to mortality risk irrespective of cause, and to risks of heart failure and ischaemic stroke.

According to the study, higher than normal BMI in adolescents was strongly linked to early atrial fibrillation, and their subsequent clinical outcomes were relatively poor. Long-term exposure to overweight and obesity among individuals with atrial fibrillation was associated with increased risk of death, heart failure and ischaemic stroke.

More active follow-up in long term

The first author of the study, Demir Djekic, is engaged in research in molecular and clinical medicine at Sahlgrenska Academy, University of Gothenburg, and is also a specialist physician at Sahlgrenska University Hospital.

He sees screening for atrial fibrillation, and more active follow-up and treatment, as feasible in the long term if future studies can demonstrate better survival rates among individuals with obesity. At the same time, Djekic gives a pointer as to when it might be time to have one’s heart tested.

“If you’ve been overweight for a long time and are getting symptoms of atrial fibrillation, such as palpitations, shortness of breath, or an irregular pulse, you should have an ECG done,” he advised.

Study 1 details

Progression of Atrial Fibrillation after Cryoablation or Drug Therapy

Published in the New England Journal of Medicine on 7 November 2022

Jason Andrade, Marc Deyell, Laurent Macle, George Wells, Matthew Bennett, Vidal Essebag, Jean Champagne, Jean-Francois Roux, Derek Yung, Allan Skanes, Yaariv Khaykin, Carlos Morillo, Umjeet Jolly, Paul Novak, Evan Lockwood, Guy Amit, Paul Angaran, John Sapp, Stephan Wardell, Sandra Lauck, Julia Cadrin-Tourigny, Simon Kochhäuser, Atul Verma.

Abstract

Background
Atrial fibrillation is a chronic, progressive disorder, and persistent forms of atrial fibrillation are associated with increased risks of thromboembolism and heart failure. Catheter ablation as initial therapy may modify the pathogenic mechanism of atrial fibrillation and alter progression to persistent atrial fibrillation.

Methods
We report the 3-year follow-up of patients with paroxysmal, untreated atrial fibrillation who were enrolled in a trial in which they had been randomly assigned to undergo initial rhythm-control therapy with cryoballoon ablation or to receive antiarrhythmic drug therapy. All the patients had implantable loop recorders placed at the time of trial entry, and evaluation was conducted by means of downloaded daily recordings and in-person visits every 6 months. Data regarding the first episode of persistent atrial fibrillation (lasting ≥7 days or lasting 48 hours to 7 days but requiring cardioversion for termination), recurrent atrial tachyarrhythmia (defined as atrial fibrillation, flutter, or tachycardia lasting ≥30 seconds), the burden of atrial fibrillation (percentage of time in atrial fibrillation), quality-of-life metrics, health care utilisation, and safety were collected.

Results
A total of 303 patients were enrolled, with 154 patients assigned to undergo initial rhythm-control therapy with cryoballoon ablation and 149 assigned to receive antiarrhythmic drug therapy. Over 36 months of follow-up, 3 patients (1.9%) in the ablation group had an episode of persistent atrial fibrillation, as compared with 11 patients (7.4%) in the antiarrhythmic drug group (hazard ratio, 0.25; 95% confidence interval [CI], 0.09 to 0.70). Recurrent atrial tachyarrhythmia occurred in 87 patients in the ablation group (56.5%) and in 115 in the antiarrhythmic drug group (77.2%) (hazard ratio, 0.51; 95% CI, 0.38 to 0.67). The median percentage of time in atrial fibrillation was 0.00% (interquartile range, 0.00 to 0.12) in the ablation group and 0.24% (interquartile range, 0.01 to 0.94) in the antiarrhythmic drug group. At 3 years, 8 patients (5.2%) in the ablation group and 25 (16.8%) in the antiarrhythmic drug group had been hospitalized (relative risk, 0.31; 95% CI, 0.14 to 0.66). Serious adverse events occurred in 7 patients (4.5%) in the ablation group and in 15 (10.1%) in the antiarrhythmic drug group.

Conclusions
Initial treatment of paroxysmal atrial fibrillation with catheter cryoballoon ablation was associated with a lower incidence of persistent atrial fibrillation or recurrent atrial tachyarrhythmia over 3 years of follow-up than initial use of antiarrhythmic drugs.

Study 2 details

Defibrillation Strategies for Refractory Ventricular Fibrillation

Sheldon Cheskes, Richard Verbeek, Ian Drennan, Shelley McLeod, Linda Turner, Ruxandra Pinto, Michael Feldman, Matthew Davis, Christian Vaillancourt, Laurie Morrison, Paul Dorian, and Damon Scales.

Published in the New England Journal of Medicine on 6 November 2022

Background
Despite advances in defibrillation technology, shock-refractory ventricular fibrillation remains common during out-of-hospital cardiac arrest. Double sequential external defibrillation (DSED; rapid sequential shocks from two defibrillators) and vector-change (VC) defibrillation (switching defibrillation pads to an anterior–posterior position) have been proposed as defibrillation strategies to improve outcomes in patients with refractory ventricular fibrillation.

Methods
We conducted a cluster-randomised trial with crossover among six Canadian paramedic services to evaluate DSED and VC defibrillation as compared with standard defibrillation in adult patients with refractory ventricular fibrillation during out-of-hospital cardiac arrest. Patients were treated with one of these three techniques according to the strategy that was randomly assigned to the paramedic service. The primary outcome was survival to hospital discharge. Secondary outcomes included termination of ventricular fibrillation, return of spontaneous circulation, and a good neurologic outcome, defined as a modified Rankin scale score of 2 or lower (indicating no symptoms to slight disability) at hospital discharge.

Results
A total of 405 patients were enrolled before the data and safety monitoring board stopped the trial because of the coronavirus disease 2019 pandemic. A total of 136 patients (33.6%) were assigned to receive standard defibrillation, 144 (35.6%) to receive VC defibrillation, and 125 (30.9%) to receive DSED. Survival to hospital discharge was more common in the DSED group than in the standard group (30.4% vs. 13.3%; relative risk, 2.21; 95% confidence interval [CI], 1.33 to 3.67) and more common in the VC group than in the standard group (21.7% vs. 13.3%; relative risk, 1.71; 95% CI, 1.01 to 2.88). DSED but not VC defibrillation was associated with a higher percentage of patients having a good neurologic outcome than standard defibrillation (relative risk, 2.21 [95% CI, 1.26 to 3.88] and 1.48 [95% CI, 0.81 to 2.71], respectively).

Conclusions
Among patients with refractory ventricular fibrillation, survival to hospital discharge occurred more frequently among those who received DSED or VC defibrillation than among those who received standard defibrillation.

Study 3 details

Body Mass Index in Adolescence and Long‐Term Risk of Early Incident Atrial Fibrillation and Subsequent Mortality, Heart Failure, and Ischemic Stroke

Demir Djekic, Martin Lindgren, David Åberg, Maria Åberg, Espen Fengsrud, Dritan Poci, Martin Adiels and Annika Rosengren.

Published in Journal of American Heart Association on 19 October 2022

Abstract

Background
We sought to determine the role of obesity in adolescent men on development of atrial fibrillation (AF) and subsequent associated clinical outcomes in subjects diagnosed with AF.

Methods and Results
We conducted a nationwide, register‐based, cohort study of 1 704 467 men (mean age, 18.3±0.75 years) enrolled in compulsory military service in Sweden from 1969 through 2005. Height and weight, blood pressure, fitness, muscle strength, intelligence quotient, and medical disorders were recorded at baseline. Records obtained from the National Inpatient Registry and the Cause of Death Register were used to determine incidence and clinical outcomes of AF. During a median follow‐up of 32 years (interquartile range, 24–41 years), 36 693 cases (mean age at diagnosis, 52.4±10.6 years) of AF were recorded. The multivariable‐adjusted hazard ratio (HR) for AF increased from 1.06 (95% CI, 1.03–1.10) in individuals with body mass index (BMI) of 20.0 to <22.5 kg/m2 to 3.72 (95% CI, 2.44–5.66) among men with BMI of 40.0 to 50.0 kg/m2, compared with those with BMI of 18.5 to <20.0 kg/m2. During a median follow‐up of ≈6 years in patients diagnosed with AF, we identified 3767 deaths, 3251 cases of incident heart failure, and 921 cases of ischaemic stroke. The multivariable‐adjusted HRs for all‐cause mortality, incident heart failure, and ischaemic stroke in AF‐diagnosed men with baseline BMI >30 kg/m2 compared with those with BMI <20 kg/m2 were 2.86 (95% CI, 2.30–3.56), 3.42 (95% CI, 2.50–4.68), and 2.34 (95% CI, 1.52–3.61), respectively.

Conclusions
Increasing BMI in adolescent men is strongly associated with early AF, and with subsequent worse clinical outcomes in those diagnosed with AF with respect to all‐cause mortality, incident heart failure, and ischaemic stroke.

 

NEJM article – Progression of Atrial Fibrillation after Cryoablation or Drug Therapy (Open access)

 

NEJM article – Defibrillation Strategies for Refractory Ventricular Fibrillation (Open access)

 

NEJA editorial article – Defibrillation after Cardiac Arrest — Is It Time to Change Practice? (Open access)

 

AHA Journal article – Body Mass Index in Adolescence and Long‐Term Risk of Early Incident Atrial Fibrillation and Subsequent Mortality, Heart Failure, and Ischemic Stroke (Open access)

 

See more from MedicalBrief archives:

 

New shockless treatment for atrial fibrillation demonstrated

 

Bystander use of AEDs doubles cardiac arrest survival rates

 

High survival rate for elderly patients with ICD

 

Obesity link to 40% higher incidence of atrial fibrillation

 

Heart failure and the obesity paradox

 

Losing weight can reverse AFib in obese patients

 

 

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