Atrial fibrillation (AF) is the most common arrhythmia, affecting an estimated 33.5 million people worldwide. If left untreated, it can lead to stroke, heart failure (HF) and cardiac arrest. AF and HF are often described as the two new epidemics of cardiovascular disease (CVD).
Apart from age, other risk factors include gender (men are slightly more likely to develop AF than women, but women tend to live longer, so they represent 50% of the overall AF population), hypertension (increases the risk of developing AF by more than 40%), coronary artery disease, valvulopathies, obesity, sleep apnoea and hypertrophic cardiomyopathy and HF.
Classification of AF
Newly diagnosed AF usually falls within the categories of paroxysmal or persistent AF:
Paroxysmal AF: Occurs in discrete episodes less than seven days in duration. In many cases, paroxysmal AF may last for only minutes to hours. Episodes of paroxysmal AF can be frequent, or rare. Some episodes may be asymptomatic and is usually discovered during cardiac monitoring. In severe cases it, can lead to stroke. Paroxysmal AF sometimes manifests as holiday heart syndrome, referring to AFib that follows a bout of heavy drinking. Recommended treatment includes lifestyle modification and pharmacological treatment or procedures aimed at controlling the patient’s heart rate. Anticoagulation might be needed to prevent stroke.
Persistent AF: Occurs in episodes that last longer than seven days. Recommended treatment includes lifestyle modification and pharmacological treatment or procedures aimed at controlling the patient’s heart rate. Anticoagulation might be needed to prevent stroke. In some patients, a pacemaker might be an option.
Permanent AF: Does not terminate, even with cardioversion attempts. Patients who are diagnosed with permanent AF are at higher risk of adverse outcomes.
The updated American Heart Association (AHA)/American College of Cardiology (ACC)/Heart Rhythm Society (HRS) guideline distinguishes between two forms of AF:
Valvular AF: Refers to AF in the setting of moderate-to-severe mitral stenosis (potentially requiring surgical intervention) or in the presence of an artificial (mechanical) heart valve.
Nonvalvular AF: Does not imply the absence of valvular heart disease.
Choosing the right treatment approach to improve outcomes
A study by Perino et al (2017) evaluated the association between treating specialty and AF outcomes among patients newly diagnosed with AF. Using data from the Retrospective Evaluation and Assessment of Therapies in AF (TREAT-AF) study from the Veterans Health Administration, patients with newly diagnosed, nonvalvular AF between were identified who had at least one outpatient encounter with primary care or cardiology within 90 days of the AF diagnosis.
Among 184 161 patients with newly diagnosed AF, 40% received cardiology care and 60% received primary care only. Cardiology care was associated with reductions in stroke and mortality and increases in hospitalisations for AF/supraventricular tachycardia and myocardial infarction. In mediation analysis, oral anticoagulation prescription within 90 days of diagnosis may have mediated reductions in stroke but did not mediate reductions in survival.
Both the AHA/ACC/HRS and the European Society of Cardiology recommend the use of anti-arrhythmic agents (AAAs) to decrease the frequency and episodes of AF, and to improve quality of life through symptom reduction.
AAAs include for example, flecainide, propafenone, ibutilide, amiodarone, digoxin and diltiazem. The two most commonly used class of AAA’s to control rhythm are Class 1c drugs and Class III drugs. Decisions on which drug to use, should be based on the comorbidities of the patient.
AAAs are classified according mechanism of action:
- Class I: Sodium channel blockers
- Class II: B-blockers
- Class III: Potassium channel blockers
- Class IV: Calcium channel blockers.
Kipp et al investigated the efficacy and safety of an initial treatment strategy with class IC or class III anti-arrhythmic drugs for newly diagnosed AF or atrial flutter using data from the TREAT-AF study. Median follow-up was 4.9 years. A total of 230 762 patients developed newly diagnosed AF or atrial flutter during the study period. In a cohort of patients with only minimal or no structural heart or coronary artery disease, 1.7% were prescribed class IC (eg flecainide and propafenone), and 3% were prescribed class III anti-arrhythmic agents (eg sotalol and dofetilide).
They found that class IC agents may be associated with a lower risk of hospitalisations for AF or atrial flutter, CV disease, HF, and a lower incidence of ischaemic stroke.
Digoxin is one of the oldest agents recommended for rate control in AF, but recent studies show that it is associated with an increased risk of mortality. In the TREAT-AF study, Turakhia et al found digoxin was associated with increased risk of death in patients with newly diagnosed AF, independent of drug adherence, kidney function, CV comorbidities, and concomitant therapies.
Novel treatments from the Treat-AF cohort
Stavrakis et al (2019) looked at the efficacy in transcutaneous electrical stimulation of the vagus nerve to decrease the AF burden compared with a sham procedure. The trial included 53 patients with paroxysmal AF. The vagus nerve runs from the brainstem throughout the chest and abdomen innervating the heart, lungs and intestines.
The stimulation group received low-level transcutaneous electrical stimulation of the auricular branch of the vagus nerve by an ear clip at the tragus (20Hz, 1mA below discomfort level) and the sham group used the ear clip on the ear lobe. The patients administered the therapy themselves for one hour per day over six months after training.
At six months, the primary outcome of median AF burden was reduced by 85% in patients assigned vagus nerve stimulation compared with those assigned the sham procedure. When the three-month and six-month time points were combined, median AF burden was reduced by 75% in the stimulation group compared with the sham group, according to the researchers. Total AF duration at six months was lower in the stimulation group and there was a trend toward total AF duration at the combined three-month and six-month time points favouring the stimulation group.
The stimulation group also had significantly altered frequency domain indices of heart rate variability and a 23% decrease in tumour necrosis factor alpha compared with the sham group. Differences in other inflammatory cytokines were not significant between the groups.
Rate vs rhythm control
Control of ventricular rate is a critical component of management of new-onset AF. Rhythm control is typically initiated when adequate rate control is not achieved or when patients have a high degree of symptoms despite achieving rate control.
However, the efficacy of a rhythm control approach is often undervalued despite offering effective treatment options. It is important to understand the rhythm control approach, whom the ‘ideal’ patient is for this approach, and how to manage these patients, according to Bhatia et al.
The AF and Congestive Heart Failure (AF-CHT) and the Danish Investigators of Arrhythmia and Mortality on Dofetilide in Congestive Heart Failure (DIAMOND-CHF trial) compared rate and rhythm control.
In AF-CHF (n=1 376) patients were randomly assigned to either rhythm control (electrical cardioversion combined with antiarrhythmic drugs) or rate control beta-blockers, digoxin, or pacemaker and AV nodal ablation). More than 80% of the patients received rhythm control, and, after a median of 47 months, 73% of patients were in sinus rhythm in the rhythm control arm versus ≈35% in the rate control arm. There was no difference in CV mortality between the groups.
In DIAMOND-CHF (n=1 518), patients were randomly assigned to dofetilide, a class III antiarrhythmic agent or placebo. At the end of follow-up, ≈65% of patients were in sinus rhythm in comparison with ≈30% in the placebo arm, and there was no difference in mortality. A subgroup analysis of the DIAMOND trial showed that patients who maintained sinus rhythm had lower mortality than those who did not and also had lower rates of hospitalisation for HF.
After deciding on a rhythm approach, it is important to realise there is no ‘one size fits all’ choice, and the selection of the AAD will depend on several factors, according to Bhatia et al.
The Canadian Society of Cardiology recommends the following:
Table 1: Factors favouring rate vs rhythm control
AF has been described as a public health crisis. The number of people with AF will increase exponentially over the three decades. Guidelines recommend the use of AAAs to decrease the frequency and episodes of AF, and to improve quality of life through symptom reduction.