Primary Prevention of Arrythmias Lags Behind Secondary Prevention

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More and more individuals are becoming diagnosed with atrial fibrillation. But the research to halt this crisis is not quite there yet.

One need not look far to note the sheer importance of developing optimal primary preventative measures for cardiovascular care. From remote technologies to lifestyle changes and pharmacological medications, preventive interventions are at the forefront of cardiological research and clinical care.

And while cardiologists may have a firm grasp on the risk mitigation strategies for certain cardiovascular and vascular diseases, prevention of other conditions are only slightly more elusive. 

Consider atrial fibrillation (AFib), the most common type of arrhythmia: the irregular beating of the heart signals failure of blood-flow from the atria to the heart’s 2 ventricles. Patients with AFib are at a significantly increased risk for stroke, hospitalizations, and death.

Even more, 12.1 million people in the United States may be diagnosed with new-onset AFib by 2030, according to the US Centers for Disease Control and Prevention (CDC).

A 2017 study published in the Journal of Geriatric Epidemiology forecasted it as a potential “epidemic” that could someday burden healthcare resources.

As research from last week's American College of Cardiology (ACC) 2021 Scientific Session indicates, much headway has been made in the treatment and management of arrythmias. From new medications, to surgeries, and monitoring devices, affected patients of all kinds with other co-morbidities continue to find hope in management and/or cures.

And yet, the role and importance of prevention becomes intertwined with the treatment narrative. Specialists continue to seek answers to the causes for these irregular heartbeats so that they and the patient can be one step ahead.

“A major challenge for arrhythmias in the future is to develop safe and effective approaches that prevent them (especially atrial fibrillation) before they develop,” Bruce Stambler, MD, of Piedmont Heart Institute, told HCPLive®. 

Stambler is an electrophysiologist who has dedicated much of his career to arrhythmia care and research. He has long hoped that the key to primary prevention for these conditions, particularly for AFib, can someday be attained. And the work he has done in cardiovascular care only mirrors this desire. 

“There have been tremendous advances over the last few decades in treatment and management of arrhythmias and their associated complications once they occur, but approaches that focus on prevention have been less well studied or established in cardiac electrophysiology,” he continued.

Of course, cardiology has an overall long way to go in the realm of large-scale preventative measures, and arrythmias are no exception. And as secondary prevention and management measures continue to see modest advancements, primary prevention is certainly not quite where it should be.

Mitigating New-Onset Arrhythmia

It is understood that arrythmias can be caused by other medical conditions, such as diabetes, coronary artery disease, and even surgeries. For example, older age, obesity, smoking, and chronic kidney disease are common risk factors for atrial fibrillation.

An e-poster from ACC noted an increased prevalence of AFib in patients with Marfan syndrome, while another study found an association between AFib and greater neck circumference that was independent of BMI and waist circumference.

A secondary finding from a post-hoc analysis of the STRENGTH trial showed that omega-3 fatty acids were linked to a substantial increase in new onset AFib — in what presenting author Steven Nissen, MD, of Cleveland Clinic, considered “a sad story for cardiology.”

On the flipside, data from the FIDELIO-DKD trial showed the finenerone significantly decreased risk of Afib in patients with chronic kidney disease and type 2 diabetes. Even more, this risk reduction was observed among patients with and without a history of Afib or atrial flutter.

“Preventing or delaying the onset of atrial fibrillation in patients with chronic kidney disease and diabetes is particularly important since having atrial fibrillation can worsen chronic kidney disease and having diabetes can worsen atrial fibrillation symptoms,” said study investigator Gerasimos Filippatos, MD, from the National and Kapodistrian University of Athens, in a statement.

Nevertheless, he noted that larger studies focused specifically on new-onset Afib are needed to confirm these promising findings.

This is all to say, then, that the research surrounding risk for AFib development is slowly evolving, and there are still many unknowns. Right now, however, there is certainly not enough known about the electrophysiological processes leading to the develop of arrhythmias.

“I like to use an analogy to atherosclerotic vascular disease, stroke, and heart attacks” Stambler explained. “For vascular disease, we came to understand the role of lipids and the importance of their control a number of decades ago for primary prevention.” However, he went on to argue, cardiology is not quite there yet for arrhythmia care.

Fully understanding the mechanisms behind these heart rhythm disorders can only help to ensure clinicians and patients are better equipped to handle their risk for arrythmias.

Managing Existing Arrythmias

For patients already diagnosed with Afib, or any type of arrhythmia for that matter, secondary prevention and management becomes the ultimate goal for the patient-clinician team. In many ways, the research for arrhythmia care leans heavy in this domain, as evidenced by the ACC agenda this year.

Patients with existing arrythmias have the option of ablations and new medications, for example, to help with their management—and the treatment toolbox only continues to expand.

In a late-breaking study presented by Stambler at ACC, etripamil nasal spray, a calcium channel blocker, for paroxysmal supraventricular tachycardia (PSVT), a different type of arrhythmia, was linked with a decrease in emergency room visits. Even more, such patients experienced a relief of symptoms related to their arrhythmia.

Despite this, the NODE-301 study did not meet its primary endpoint of time to conversion of PSVT to sinus rhythm compared to placebo over 5 hours.

Although the study itself speaks little to secondary prevention, it nonetheless highlights this great need among patients to have effective, convenient means for reducing or altogether terminating their arrythmia.

“Patients don’t know when or if their arrhythmia will develop,” he told HCPLive®, before underscoring the value of the drug’s convenience. “It can come out of the blue — on an airplane, in front a business meeting, or in front of classroom.”

Another clinical study sought to ask the question of causality, thus exploring the relationship between alcohol use and immediate triggering of an atrial fibrillation episode.

Led by Greg Marcus, MD, the team used a wearable technology to investigate the validity of patient-reported instances of AFib following consumption.

The trial found that a drink of alcohol was associated with a 6-fold greater odds of an atrial fibrillation episode within the next 4 hours. Further, ≥ 2 drinks were associated with a 20-fold higher odds of an episode.

Quite significantly, this trial was one of the first show a modifiable behavior associated with a triggering of an AFib event.

“It’s important for us as physicians that we acknowledge that light drinking and drinking responsibly can be important to quality of life,” Marcus told HCPLive® in an interview.

“If one has alcohol-sensitive Afib, can you take care of that completely with an ablation? Or with medications, for example? I think, in the short term, there’s a fairly clear answer for these patients who are interested in lifestyle changes to reduce their risk—and that is to recommend abstinence or minimizing alcohol use.”

He further acknowledged many questions remain in regard to this unique relationship been substance use and an arrhythmia event.

Lingering Questions

What does all this mean? For one, clinicians should continue to find novel ways to terminate and reduce risk for arrhythmia episodes in their patients. Even more, research should continue to elucidate the triggers for subsequent Afib and other arrhythmia events.

At the same time, more work needs to be done to better ascertain which populations/body types/behaviors/exposures are linked to the development of new-onset arrhythmias.

As Andrew Krahn, MD, Head of the Division of Cardiology at University of British Columbia, put it to HCPLive®, “big picture research is looking to understand why these [arrythmias] happen and why now.”

Certain patients can be genetically predisposed to conditions like Afib, and obesity is also linked to its development. Krahn indicated that the next phase of research will explore in depth patient biology and genetics.

For now, the dearth of knowledge into the physiology of these heart rhythm condition means primary prevention can only be attained through piecemeal, partially certain measures.

Stambler cited prior studies indicating that weight loss may have substantial preventative effects, although research into this area can and should go further. He himself is partaking in a study, dubbed the AVOID-HF trial, assessing high blood pressure therapy spironolactone on Afib prevention in patients undergoing ablation of atrial flutter.

On the technology front, wearables like Apple Watch are promising but can only be so reliable when it comes to the detection of Afib events for all types of patients. However, there is a long way to go before such technologies can even begin to play a role in aiding primary prevention and overall screening.

And yet, in this very moment, the questions remain clear:

What exactly are the multifaceted causes and triggers for arrhythmias, and can one be certain of them? And how can one ensure fewer and fewer patients become diagnosed with one?