At this year's virtual European Society of Cardiology (ESC) Congress, a small but highly positive heart failure trial struggled for notice.
The Ablate and Pace for Atrial Fibrillation–Cardiac Resynchronization Therapy (APAF-CRT) trial compared two strategies for dealing with the common scenario of an older person with atrial fibrillation (AF) and multimorbidity who struggles with severe heart failure symptoms. Investigators randomly assigned one group to cardiac resynchronization therapy (CRT) plus atrioventricular node ablation and the other to medical therapy.
APAF-CRT Mortality Reduction
Patients (mean age, approximately 72 years) were enrolled at 11 European centers. There were three main Inclusion criteria: severely symptomatic permanent AF (>6 months) that was deemed unsuitable for primary AF ablation or that ablation had failed to resolve; narrow QRS (≤110 msec), and at least one hospitalization for heart failure.
The APAF-CRT investigators reported morbidity outcomes in 2018: at that time, CRT/ablation was superior to medical therapy in reducing heart failure hospitalizations and quality of life.
At ESC, primary investigator Michele Brignole, MD, presented the 2-year mortality results, which were stunningly positive for the ablate-and-pace strategy. The European Heart Journal published the results.
The APAF-CRT trial found a 74% reduction in death with CRT and atrioventricular node ablation. After 29 months, 7 of 63 patients in the CRT/ablation arm died vs 20 of 70 patients in the drug arm (11% vs 29%; hazard ratio, 0.26; 95% CI, 0.10 - 0.65). Keep in mind, too, that mortality is the most bias-free endpoint.
The results are even more impressive given that 18 patients in the drug arm crossed over to CRT/ablation because of recurrent heart failure. But, according to the intention-to-treat principle, these patients were counted in the drug arm.
For the secondary endpoint of all-cause death or hospitalization, there was a 60% reduction with CRT/ablation over medical therapy (hazard ratio, 0.40; 95% CI, 0.22 - 0.73; P = .002).
Left ventricular ejection fraction (LVEF) did not alter the benefit of the ablate-and-pace strategy. Patients with an LVEF greater than 35% and those with an LVEF of 35% or less had similar mortality improvements.
There was also no interaction based on resting heart rate above or below 102 beats/min—CRT/ablation was equally beneficial in both subgroups of patients.
The authors rightly concluded that CRT/ablation was superior to medical therapy in reducing mortality in patients with permanent AF and narrow QRS who were hospitalized for heart failure, irrespective of their baseline EF.
Targeting Those Dying From AF
AF is a diverse condition. Although most patients with AF are best handled with large doses of reassurance and a trial of conservative measures, elderly patients with AF who have difficult-to-control ventricular rates, lowish blood pressure, multiple comorbid conditions, and frequent heart failure admissions require action. These patients are dying from AF.
I am therefore not surprised by the stunning reduction in death seen in APAF-CRT. Electrophysiologists have long used the strategy of nodal ablation and pacing to reduce suffering. This trial shows that it also extends life.
APAF-CRT stands out not only because of its positive results but also because investigators chose to study a group of patients who are so often excluded from trials.
Many readers may wonder if a 74% reduction in death is too good to be true. How can CRT and node ablation be that amazing?
I would explain this in four ways:
First, APAF-CRT looks to have included patients sick from AF. These patients had high ventricular rates, required oodles of rate-slowing meds, had frequent heart failure hospitalizations, and had very high-effort dyspnea scores.
The second way that nodal ablation and pacing works is that it cures both the high rate and irregular rhythm of AF. That's important because many older patients have stiff ventricles that require time for diastolic filling.
Third, mechanical rate control then removes the need for high doses of medication, which can be problematic in older patients. Finally, biventricular pacing removes the downside (dyssynchrony) of right ventricular pacing. Biventricular pacing has a track record of improving death rates vs medical therapy.
Translation of this trial to the bedside requires care. Ablation of the atrioventricular node cannot be undone. It creates dependence on hardware in the bloodstream. Infection can be catastrophic for these patients. A trial of rate vs rhythm control in these patients would be wise.
But for many older patients with comorbid conditions or obvious advanced left atrial disease, primary AF ablation is foolish. It won't work, and it puts the patient at excess procedural risk. For these patients, we now have strong evidence that CRT and nodal ablation delivers both a morbidity and a mortality improvement.
The next step is to study whether we can accomplish the same benefits with one pacing lead rather than the two required in biventricular pacing. Left bundle area pacing is emerging as a promising way to resynchronize, with a single lead placed through the septum to the area of the left bundle branch. The logical extension of APAF-CRT would be to compare traditional biventricular pacing with left bundle area pacing in a similar group of patients.
My final note concerns the power of randomized trials.
APAF-CRT shows that if your intervention is truly beneficial, not just incremental, you don't need a big trial. Fewer than 200 patients took part in an experiment that can now be translated to the care of millions of people who suffer greatly from AF.
For clinicians, this trial was clearly the biggest winner of the ESC meeting. APAF-CRT further solidifies electrophysiology as a major contributor to the care of patients with heart failure.
John Mandrola practices cardiac electrophysiology in Louisville, Kentucky, and is a writer and podcaster for Medscape. He espouses a conservative approach to medical practice. He participates in clinical research and writes often about the state of medical evidence.
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Cite this: John M. Mandrola. Ablate-and-Pace Delivers a Huge Win for Those Sick With AF - Medscape - Sep 02, 2021.