Sometimes big things come in small packages.
The Aggressive Risk Factor Reduction Study for Atrial Fibrillation and Implications for the Outcome of Ablation (ARREST-AF) may be a small study, but its findings provide big gains in our understanding of the link between AF and cardiometabolic risk factors, such as high blood pressure, diabetes, obesity, alcohol excess, and sleep apnea.
I briefly wrote about this study when it was presented at the Heart Rhythm Society of America 2014 Scientific Sessions in May, mostly by telling you what Dr John Day, president of the HRS, had to say about lifestyle and AF. (He said big things.) Now that ARREST-AF has been published in the Journal of the American College of Cardiology, I wanted to revisit this practice-changing study. I believe ARREST-AF heralds the beginning of a new era in the care of patients with AF.
Setting the Stage
The team behind ARREST-AF has long been interested in how cardiometabolic risk factors figure in AF. They first showed that obesity contributed to AF in a sheep model. Then, they put the obese sheep on a diet. The leaner sheep showed favorable structural and electrical changes in their atria, including resolution of fibrosis, and AF became harder to induce.
The next question was obvious: Would weight reduction have the same effect in humans with AF? To answer this, the researchers from Adelaide studied 150 overweight and obese patients with AF. They compared a strategy of physician-led aggressive risk-factor management (RFM) with standard care.The results in humans were similar to the sheep: patients in the RFM group enjoyed more weight loss, better control of typical cardiac risk factors, less AF, and favorable structural changes as seen on echocardiograms.
In ARREST-AF, the same strategy of physician-led aggressive RFM was compared with standard care after ablation. The investigators screened 281 consecutive patients referred for AF ablation and offered RFM to 149 who had a BMI >27 kg/m2 and one or more risk factors. Those who agreed (n=61) made up the RFM group, while those who declined (n=88) served as the control group.
Risk Factor Management and Cardiometabolic Risk Factors:
Over the 41-month follow-up period before and after AF ablation, patients in the RFM group, compared with those in standard care, sustained positive changes in basic health. Body weight, blood pressure, lipid levels, glycemic control, nocturnal apnea, and (my favorite health surrogate) number of antiarrhythmic and BP pills swallowed all turned to the good in the RFM group.
BP and glycemic control stood out. In the RFM group, mean systolic blood-pressure readings fell from a mean 161 mm Hg at baseline to 127 mm Hg in follow-up. (Imagine a drug that did that!) Nine patients in the RFM group began the trial with HbA1c levels >7%. The number at follow-up: zero.
RFM also produced favorable changes in cardiac structure. Left atrial volume and LV septal thickness and size decreased. LA volume dropped from 42.5 mL/m2 at baseline to 30.4 mL/m2 at postablation follow-up in RFM patients.
Risk Factor Management and Ablation Success
The first message of ARREST-AF is basic and elegant: If patients and caregivers are motivated to do so, lifestyle-related risk factors can be reduced, pill burden lessened, and atria shrunk. Such basic health improvements relate directly to AF stroke risk. Think about it: the ability to eliminate diabetes, hypertension, and maybe heart failure (via LV remodeling), three key components of the CHA2DS2-VASC score, translates to lower stroke risk—whether or not ablation stops all AF episodes.
The second message of ARREST-AF centers on the fivefold gain in AF ablation success. Although the entry criteria required a BMI >27 kg/m2, the enrolled patients were much bigger (average BMI 33.5 kg/m2) in the RFM group, and more than a third of them had persistent AF. These were not "easy" AF patients. The fact that 87% of patients in the RFM group were free of AF at 2 years is remarkable.
It's remarkable because AF ablation is a costly and risky procedure. It's performed electively in patients at little immediate danger from their disease. We should do everything in our power to improve success rates.
I've been following AF ablation since its inception 15 years ago. The majority of research is focused on making more durable lesions or on ways to find and ablate focal drivers (now called rotors) that initiate or maintain AF. In short, these strategies seek to make AF ablation more like paroxysmal supraventricular tachycardia (PSVT) ablation.
This is flawed thinking. It misses the underlying cause of AF. When we track rotors or PV firing or autonomic ganglia, we miss the central fact that AF is most often a manifestation of a systemic atrial disease. (Here we exclude the rare AF patient with a forme fruste of an atrial tachycardia.)
I know it is a lot for a clinician to think about intracellular calcium handling, ion-channel dysfunction, autonomic neural control, and structural remodeling changes, but we must. These pathologic processes, especially fibrosis, create the milieu for atrial fibrillation, and they form the link between lifestyle-related risk factors and AF.
Consider these (oversimplified) examples: Obesity causes LV diastolic dysfunction, which in turn causes left atrial dilation and stretch. Increased atrial stretch favors reentry and AF. Sleep apnea can cause connexin dysregulationand fibrosis in animal models, which clearly promote AF. Hypertension promotes fibrosis through a variety of mechanisms. Pericardial fat produces a brew of profibrillatory inflammation mediators. I could go on, but you get the picture.
Basic health, basic science, and atrial fibrillation are all connected. While it is true that AF ablation may (expensively) buy a patient some time, the disease will return unless the underlying risk factors are treated.
The Adelaide researchers are teaching the cardiology community to view AF as a systemic disease that requires systemic—not focal—solutions. ARREST-AF may be a small nonrandomized study, but its message is huge: Taking care of atrial fibrillation means seeing and treating the person with AF.
Is this a turning point in the care of millions of patients with atrial fibrillation?
I hope so.