‘Striking’ lack of medical therapy available for arrhythmias
Healio spoke with Jagmeet P. Singh, MD, ScM, DPhil, professor of medicine at Harvard Medical School, about anti-arrhythmic treatment options and technology’s role in cardiology practice and arrhythmia management.
Singh, an internationally recognized cardiac electrophysiologist, who has served as the clinical director of the cardiology division at Massachusetts General Hospital, also discussed the differences in treating different patient groups and the challenge of atrial fibrillation management.
Healio: What have been the most significant FDA approvals for arrhythmias and is there anything significant in the pipeline?
Singh: In the last few years there have been several anticoagulant strategies that have been approved for atrial fibrillation. These include apixaban (Eliquis, Bristol-Meyer Squibb), dabigatran (Pradaxa, Boehringer Ingelheim Pharmaceuticals Inc.), edoxaban (Savaysa, Daiichi Sankyo Inc.) and rivaroxaban. There has been limited progress on the antiarrhythmic front. The most recent FDA approvals on this front date back several years to dronedarone (Multaq, Sanofi) and dofetilide (Tikosyn, Pfizer). It’s a tad disheartening to see this as, on the other hand, there has been an exploding number of drugs and molecules being rapidly approved for cancer treatment and other disease states. More recent significant FDA approvals within the world of arrhythmias have been related to technology, and have included different catheters for atrial fibrillation ablation, along with enhancements in electro-anatomical mapping systems. There are some newer devices such as barostim (Impulse Dynamics) that have been recently approved for treating heart failure, and it remains to be seen how they directly or indirectly impact arrhythmias. There are also some digital health strategies, like an FDA cleared personal EKG monitor (AliveCor), along with Apple Watch for detecting AF. Additionally, there are a number of cloud-based artificial intelligence strategies for diagnosing arrhythmias that are being actively evaluated. As you can see, there are many facets to the management of arrhythmias, and the coming years are going to be very exciting on all of these fronts.
Regarding drugs recently evaluated by the FDA, the one that immediately comes to mind is vernakalant (Correvio Pharma), which is a chemical agent for acutely converting patients with atrial fibrillation. It went through multiple iterations, however, did not make the cut at the FDA level, on accounts of issues related to safety and efficacy. Another one currently under evaluation is etripamil (Milestone Pharmaceuticals, Inc.), a short acting calcium channel blocker. This is administered nasally for the treating supraventricular arrhythmias. It is currently being evaluated in the RAPID study. This is one of the exciting drugs that is coming down the pike that could potentially be a little bit of a game changer on the management of arrhythmias.
Healio: What patient subgroup is the most difficult to treat?
Singh: If you’re looking at arrhythmias, there are two broad categories of arrhythmias that we are commonly inundated with; one of them is atrial fibrillation and the second is ventricular tachycardia.
Atrial fibrillation is such a wide swath of patients that there are different degrees to which patients suffer. They can be categorized as mild or severe in the gravity of symptoms or the duration of occurrence. Simply put, they are characterized as paroxysmal, persistent or chronic, based on duration. We don’t have a one-size-fits-all strategy and we even lack individualized approaches to manage these patients well. Although it’s a relatively more benign arrhythmia than ventricular tachycardia, it’s the bane of our existence on a day-to-day basis in clinical practice. Again, the medications available are not very efficacious. Recurrence rates are quite high despite medical therapy.
Ventricular arrhythmias on the other hand, are less common but they’re more lethal. None of the medications here too are 100% protective. That’s why for patients who are susceptible for ventricular arrhythmias, we end up placing implantable defibrillators to prevent sudden death. These are the two big arrhythmia categories. Beyond this there are a host of other supraventricular arrhythmias that we deal with, in and outside of the EP laboratory.
Interventional therapy — be it ablation, implantable devices or surgery — is a reflection of our lack of medical therapy and our lack of adequate preventive strategies to prevent the arrhythmia from occurring in the first place. Upstream therapies are lacking for both atrial and ventricular arrhythmias.
Healio: Are there differences when treating young patients compared with older patients?
Singh: The principles remain the same. But there are some differences between the choice of medications, as that varies depending on how long that particular patient is going to need that medication. Let’s presume you have a patient who is 25 years old with ventricular arrhythmias and you have to put them on a medication. One would be very resistant to using amiodarone because of its side effect profile and the risk for facing drug adverse effects over their lifetime. On the flip side, if you are treating an older individual, who could be around 85 years old, you may not be that hesitant to try the same medication that could have these side effects because you know it’s not going to be a long term issue. Those are some individualized choices we make on daily basis across a spectrum of therapies over a wide range of demographics and comorbidities.
There’s also a lot of variability in the metabolism of medications between older and younger patients that you need to pay attention to. When you talk about interventional therapies like catheter ablation in patients, the potential for having complications is directly proportional to the age of the patient. It’s not unreasonable to be more conservative in older patients so that the risk for iatrogenic issues is less, because the resilience and reserve capacity in the elderly is also markedly less.
Healio: Is there any role for complementary therapies such as diet, yoga, etc., in the management of arrhythmias?
Singh: Complementary and lifestyle tactics as add-on approaches to clinical care are the future. There has been a recent upsurge of virtual care along with mobile health strategies to promote this. Mobile health includes sensor strategies and many apps that are promoting wellness and lifestyle.
We know that atrial fibrillation, and even ventricular arrythmias, can be lifestyle diseases. We know that atrial fibrillation is directly related to BMI, sleep apnea, the presence of hypertension and diabetes and other comorbidities. Many of these can be corrected or improved through lifestyle modification.
Even now in patients who have atrial fibrillation, I make it a point to insist that they lose weight, and they correct their sleep apnea, because oftentimes that itself may be a cure in a small proportion of patients. Why should you put patients through an invasive procedure if you can treat them with a lifestyle strategy? The same might apply even to ventricular arrhythmias. Ventricular arrhythmias that we commonly see, are acquired and related to coronary artery disease. These individuals include patients who have had myocardial infarctions that scar their ventricles and those scars then promote ventricular arrhythmias. If you could take a step back and look at it from a different vantage point, and if you could prevent a myocardial infarction, you could actually prevent that arrhythmia in that individual. This is similar to AF. Managing comorbidities and risk factors can help mitigate both atrial and ventricular arrhythmias.
There is some evidence that yoga reduces depression. It enhances the level of well-being and has been shown to reduce the burden of atrial fibrillation in small studies. And of course, most things that improve overall well-being can translate into clinical benefit.
Healio: How has COVID-19 changed treatment practices?
Singh: COVID-19 has certainly impacted our hospital treatment practices. We started categorizing things as essential and non-essential to make more bed-capacity for our COVID patients. We cancelled and postponed elective procedures, started shifting a lot of our outpatient care to telehealth. All of this to create more bed-capacity and shift our resources to look after inpatients who had COVID infections.
We subsequently have found that virtual visits are working really well and may actually persist beyond the pandemic. Much of our procedural practice during the heights of the pandemic were adjusted to the acuity of the patient.
As of now, we have begun drifting back to our normal practice patterns, except that all the workflows have been adjusted to ensure patient safety and prevent any risk for transmission of COVID among patients and our workforce. There are many lessons we have learned from the pandemic that will influence practice significantly for the coming years. The adoption of telehealth and digital health strategies are here to stay. There will be a significant amount of re-deployment and repurposing of job descriptions in the coming months. Some of our inpatient care will move to the outpatient area, while a large portion of our outpatient care will move offsite or to our patient’s homes via telehealth. The pandemic has ushered in an era that will eventually be dominated by virtual care that is sensor-aided and powered by artificial intelligence.
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