Results from the CASTLE AF study showing that catheter ablation improves outcomes for patients with left ventricular dysfunction and atrial fibrillation (AF) headlined results reported from AF trials at the European Society of Cardiology congress in Barcelona Aug 26-30.
Nassir Marrouche of the University of Utah in Salt Lake City presented the results from the Biotronik-sponsored trial during a Late-Breaking Clinical Trials session August 27. (Also see "ESC 2017: CASTLE AF, REVEAL AF Among Noteworthy Device Trials To Be Presented in Barcelona" - Medtech Insight, 24 Aug, 2017.) "AFib and heart failure are very intertwined and married together," Marrouche said in a webcast from the ESC meeting. About 30% of heart failure patients have AFib and these patients have a worse prognosis than heart failure patients without AF. "AFib still presents a major dilemma. Even the guidelines lack a straightforward suggestion or recommendation on how to treat these patients, so we have a variety of options, because there's no single study that shows one treatment is better than the other."
Marrouche's recommendation to electrophysiologists treating heart failure patients with AF is to "ablate them early on, very soon in the disease stage."
CASTLE AF randomized 397 patients with symptomatic paroxysmal or persistent AF and heart failure with a left-ventricular ejection fraction of less than 35% to radiofrequency catheter ablation or conventional medical therapy. All patients were implanted with a Biotronik implantable cardioverter defibrillator linked to the Home Monitoring network for continuous surveillance of AF. The ablation method was left up to the individual operators, but pulmonary vein isolation ablation was used in 98% of the patients.
During the median follow-up of 37.8 months, the primary endpoint – a composite of all-cause mortality and unplanned hospitalization for worsening heart failure – occurred at a significantly lower rate in the ablation group (28.5%) versus the control group (44.6%). The secondary endpoints of all-cause mortality (13.4% vs 25%) and heart-failure hospitalization (20.7% and 35.9%), measured separately, were also significantly lower in the ablation group than in the conventional treatment group. Overall, patients treated with ablation were 47% less likely to die, and 44% less likely to be hospitalized with worsening heart failure than patients treated with conventional therapy.
Commenting on the CASTLE-AF results at the congress, Carina Blomstrom-Lundqvist of Uppsala University in Sweden also pointed out that the trial showed that nearly 70% patients treated with ablation maintained sinus rhythm at least five years after the procedure, "which is not the pattern you usually see," she said.
Marrouche pointed out that the trial is the first randomized study of AF ablation to show a difference in universally accepted "hard endpoints" like death and heart-failure hospitalization, rather than quality of life measures or AF-burden, which are not always defined the same way. This was a major strength of the study and also why it took almost nine years to complete the trial, he said.
The ICDs implanted in every patient may have affected mortality in both groups, Marrouche said. And Blomstrom-Lundqvist pointed out that every patient's heart failure treatment was optimized before they were randomized, so "there could be some bias here – that you would optimize patients better with ablation better than those receiving antiarrhythmic drugs."
Marrouche's recommendation to electrophysiologists treating heart failure patients with AF is to "ablate them early on, very soon in the disease stage, before they get to a left-ventricular ejection fraction under 25% or New York Heart Association Class IV or advanced III." Blomstrom-Lundqvist agreed that "this is new information and I think we'll have to change our policy and be more deliberate and refer patients with atrial fibrillation and heart failure to catheter ablation." But, she cautioned, the trial only enrolled patients with symptomatic AF so the best approach for asymptomatic patients is still unclear.
CAPTAF Shows Ablation Improves Quality of Life
Atrial fibrillation improved quality of life better than antiarrhythmic drugs could on their own in 155 patients with symptomatic AF in the CAPTAF trial, but both therapies produced similar reductions in AF-burden.
Carina Blomstrom-Lundqvist of Uppsala University in Sweden presented the one-year results from the trial at the ESC conference on August 29. CAPTAF was sponsored by the Swedish Research Council, Swedish Heart-Lung Foundation, and Medtronic PLC .
"The primary endpoint [in previous AF trials] has been 30-second AF recurrence on Holter monitors. But we would like to use, as the primary endpoint, quality-of-life, because that is the [goal] for AF procedures, and that has not been done before," she said in a webcast from the meeting. "We also thought that rhythm-monitoring to assess AF burden was important and that has not been done before."
CAPTAF randomized 155 patients with symptomatic AF who had already failed to respond to one rate or rhythm control drug and had at least one symptomatic paroxysmal AF episode in the previous two months, or at least two symptomatic episodes of persistent AF in the previous year. All patients were implanted with a cardiac monitor. Following a two-month run-in, they were randomized to ablation with pulmonary vein isolation or antiarrhythmic drug therapy with adequate dosages as specified in the professional guidelines.
After one year the ablation group showed a greater improvement in average overall health, as measured by a standard survey, than the drug group –11.0 points versus 3.1 points. In addition, all quality-of-life subscales, except for bodily pain and social functioning, improved significantly more in the ablation group than in the drug group. European Heart Rhythm Association Symptom Classification also improved significantly in the ablation group than in the drug group
The reduction in AF burden, defined as the proportion of time the patient spent in in AF, was larger in the ablation than in the drug group, but the difference was not statistical significant. The complication rates in both groups were similar.
"The increase in AF diagnosis with patient ECG monitoring suggests that it has the potential to reduce stroke through earlier diagnosis and treatment with oral anticoagulation," says Julian Halcox, Swansea University Medical School, Wales.
"We have confirmed that quality-of-life is really improved [with ablation] and I think it's related to the side-effects of the antiarrhythmic drugs, although that has not yet been shown in this trial," Blomstrom-Lundqvist said.
Patients Find Their Own AF in REHEARSE-AF
Patients monitoring their hearts with AliveCor Inc.'s Kardia Mobile device identified more episodes of atrial fibrillation than routine care in the REHEARSE AF trial. Julian Halcox from Swansea University Medical School in Wales presented one-year data from the trial at the ESC congress on Aug 29.
The trial, co-sponsored by AliveCor and the Welsh Government, enrolled 1,003 patients 65-years or older with stroke risk-factors who were not taking anticoagulant drugs and did not have a prior diagnosis of AF. Patients randomized to the treatment group took two ECG recordings a week for a year with the Kardia Mobile device and sent them to their doctor for analysis. Patients randomized to the control group just made routine visits to local health-care providers.
During the year-long study period, 19 patients in the intervention group were diagnosed with AF compared to five in the control group even though they had similar number of risk factors. Just over 2% of the ECGs recorded and submitted were considered uninterpretable, usually due to electrical interference at the time of recording. Health economic modelling showed that each AF diagnosis in the intervention group cost around £8,255.
Most patients recording their ECGs with Kardia Mobile said they did not feel restricted or anxious about the process, while control patients reported being slightly more anxious about their risk of heart rhythm abnormalities and stroke, and frequently said they would have preferred to have been enrolled in the regular monitoring group.
"Our study was not designed to evaluate outcomes, but the increase in AF diagnosis with patient ECG monitoring suggests that it has the potential to reduce stroke through earlier diagnosis and treatment with oral anticoagulation," Halcox said. "A much larger outcome trial is needed to evaluate the clinical impact and cost-effectiveness of this approach.”
AFFIRM Shows Benefit Of BP Control In AF
A post-hoc analysis of the NIH-sponsored AFFIRM trial, presented Aug 28 by Marco Proietti from the University of Birmingham, England, shows that blood pressure control may reduce the risk of strokes and major bleeding events in patients with atrial fibrillation.
"Our findings suggest that consistency in blood pressure control, beyond the single measurement, is very important, and this appears to be the case across all types of AF patients, irrespective of age, blood pressure history, blood pressure level or clotting risk,” Proietti said.
AFFIRM compared pharmacologic ventricular rate control, rhythm control, and anticoagulation in 3,843 AF patients to measure the variability in systolic blood pressure. The patients systolic blood pressure was recorded four times in the year prior to the study and then every four months after enrollment.
Over a mean follow-up of 3.6 years, the patients in the trial suffered 149 strokes and 248 major bleeding events with a clear pattern of increasing risk linked to systolic blood pressure. After adjusting for variables, the analysis showed that patients whose systolic blood pressure varied by 13.86 mmHg or more were at significantly higher risk of stroke and major bleeding than those with lower blood-pressure variability.
"The main [objective] should be to understand why these patients have the highest variability and there are several [studies] in the literature that seem to suggest that one of the main relevant issues is [the patients'] adherence to medications," Proietti said. "So before prescribing we start prescribing more drugs, that in some ways may make things worse, we should be able to be sure that our patients are taking all the patients we prescribed and at the dose we prescribed."