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2018 AF Symposium: Findings from the CASTLE-AF Clinical Trial

by Steve S. Ryan, PhD.
FAQs Understanding Your A-Fib A-Fib.comPersonal note: Most people who’ve had a successful catheter ablation can tell you how wonderful it feels to have a heart that beats normally again. There are few other procedures that so improve one’s quality of life. (I had my procedure back in 1998 and still treasure being in normal sinus rhythm!)
One would think intuitively that having normal blood flow to the brain and body would improve overall health and lead to longer life. But there haven’t been many studies documenting this result…until now!
The findings of the CASTLE AF clinical trial are one of the most important studies for patients in the last decade!

Dr. Nassir Marrouche & the CASTLE-AF Clinical Trial

CASTLE-AF stands for Catheter Ablation versus Standard conventional Treatment in patients with LEft ventricular dysfunction and Atrial Fibrillation.

I reported briefly on the CASTLE AF clinical trial last October [see CASTLE AF Study: Live Longer―Have a Catheter Ablation]. At the time, it was a late-breaking study with few details.

Nassir Marrouche MD

N. Marrouche MD

At the January 2018 AF Symposium Dr. Nassir Marrouche presented results of the full CASTLE-AF study.

CASTLE-AF is a multicenter, randomized, controlled trial of A-Fib patients with managed heart failure. The trial was to determine if catheter ablation lowers morbidity and mortality as compared with drug therapy (rate or rhythm control).

The Case of the 50-Year-Old Man with an Ejection Fraction of 24%

Dr. Marrouche started his presentation by describing one of his patients, a 50-year-old man with A-Fib for 6 years who had progressed from paroxysmal to persistent. He’d taken various antiarrhythmic drugs (AADs) such as Sotalol and amiodarone.

Ejection Fraction is a measurement of the blood leaving your heart each time it contracts. Normal rate is 50%-75%.

He had failed Electrocardioversions. His Ejection Fraction (EF) was 24%―dangerously low and considered a stage of heart failure. [To learn more about EF, read my FAQ: Understanding A-Fib and Ejection Fraction.]

After a catheter ablation procedure, Dr. Marrouche’s patient’s Ejection Fraction improved from 24% to 44%. [This is a huge improvement! This man’s life was basically saved.]

Rate vs Rhythm Control & Amiodarone Toxicity

Dr. Marrouche discussed older studies such as AFFIRM comparing rate control drug therapy to rhythm control drug therapy using antiarrhythmic drugs (AADs).

Even though people on AADs were often in normal sinus rhythm and felt better, mortality in the rate control group and the AAD group was about the same. This somewhat surprising result may have occurred because one of the AADs used was amiodarone which is known for its toxic effects. [The toxicity of amiodarone may have offset the improved mortality of being in normal sinus rhythm.]

For more on amiodarone, see Amiodarone: Most Effective and Most Toxic)

Description of the CASTLE-AF Study

The 9-year, multicenter CASTLE-AF trial started in 2008 and focused on patients with A-Fib and systolic heart failure. The 398 participants were at 31 sites in 9 countries across Europe, Australia and the U.S.

Heart Failure occurs when it’s unable to pump enough blood to the other organs to satisfy their need for oxygen and nutrients (not that the heart has suddenly stopped).

All patients had sick hearts. Study participants had A-Fib, advanced heart failure (i.e., low ejection fraction less than 35%) and dual chamber Implantable Cardioverter Defibrillators (ICDs). Patients were randomized to receive either radiofrequency catheter ablation or conventional drug treatment.

Of the conventional drug therapy group, 30% were on antiarrhythmic drugs (AADs) and the rest were on rate control drugs.  (Note: amiodarone was used around 35% of the time as the AAD.)

EPs performing the RF catheter ablations could use whatever ablation techniques or systems deemed appropriate. 51% of ablation patients had additional isolation burns, mainly ablation lines and mapping/targeting complex fractionated atrial electrograms (CFAEs).

The median follow-up period was 37.8 months, which is longer than most other A-Fib ablation trials.

Results―Ablation Saves Lives―47% Reduction in Death Rate

Dr. Marrouche listed key results of the CASTLE-AF Clinical Trial:

Catheter ablation lowered the death rate by 47% vs conventional therapy;
In the catheter ablation group: 60% improved their ejection fraction by more than 35%;
After 5 years, 60% of the ablation group were in normal sinus rhythm compared to only 22% receiving conventional drug therapy;
There was a 51% reduction in cardiovascular mortality in the catheter group;
Even though 94% of the patients were taking Coumadin, the catheter ablation group’s stroke rate was ½ of the conventional drug treatment group;
There was a 38% reduction in all cause mortality and hospital admissions in the catheter group. A-Fib burden (percentage of time in A-Fib) also improved;
Heart failure hospital admissions improved immediately within 6 months of the ablation.

Dr. Marrouche stressed that catheter ablation for A-Fib patients should be performed early, the earlier the better. “…Ablate them early on, very soon in the disease stage.”

CASTLE-AF: Ablation Improves Quantity, Not Just Quality of Life

Catheter ablation was previously known to improve Quality of Life (QofL). But in the CASTLE-AF study, it also improved life outcomes (the quantity of life, how long one lives).

After catheter ablation, the death rate of trial patients was lowered by an amazing 47%! Catheter ablation improved lower-than-normal ejection fraction and consequently cured a major component of heart failure.

Presentation Q & A and Insightful Comments

Dr. Hugh Calkins, AF Symposium

Dr. Hugh Calkins

During the question and answer session after Dr. Marrouche’s presentation, Dr. Hugh Calkins of Johns Hopkins expressed the sentiments of not just the attendees but of all A-Fib patients and their doctors.

“This is such an unbelievably fantastic study. This is the first study to show that AF ablation improves mortality and heart failure. Hats off to you for getting this done. All of us believed in this procedure. But people kept asking us for hard end points (which you have provided).”
Dr. Douglas Packer

Dr. Douglas Packer

In a bit of hyperbole, Dr. Douglas Packer from the Mayo Clinic added,

“CABANA people everywhere were screaming with delight when they saw the results of your paper.”

Dr. Marrouche also talked about how difficult it was to get this study done, to get and keep funding, to motivate everyone involved to continue over the years. He especially thanked Medtronic Inc. for never wavering in their support of this study.

Editor’s Comments
My Anecdotal Evidence: I recently heard from a 73-year-old man I had advised who had persistent A-Fib. One month after an ablation by Dr. Andrea Natale, he is in normal sinus rhythm and his ejection fraction improved from a low 35% to a normal 55% (normal range is 50–75%)!
Even though he’s only a month into his blanking period, he reports he’s feeling terrific.
Today’s Ablation Treatments Strategies Much Improved: If the CASTLE-AF were started today rather than in 2008, we would expect to see even better results. There’s been a tremendous improvement in ablation treatment strategies over the years, such as contact force sensing catheters, balloon catheters, and advanced mapping systems.
Hard Data―Ablation Lowers Death Rate: Thanks to Dr. Marrouche and his colleagues, we now have hard data that a catheter ablation doesn’t just feel good but lets us live a healthier, longer life. It actually lowered the death rate of these very sick patients by 47% which is unheard of! (If the hard data weren’t there, no one would believe it.)
Dramatic Improvement in Heart Failure: People with congestive heart failure (low ejection fraction) say it sometimes feels like they are suffocating. (For those with advanced heart failure, nearly 90% die within one year.) Can you imagine what patients in the CASTLE-AF study experienced when their ejection fraction went from less than 35% to a 60% improvement? It’s like someone was giving them their life back again.
Personal note: When last measured, my EF was 65% ―pretty good for a 77-year-old.
Improvement of Ejection Fraction to 35% = No or Reduced Heart Failure: Over time A-Fib weakens the heart and reduces ejection fraction (leading to heart failure). Whereas patients in the ablation group reversed this remodeling effect. The most astounding statistic of CASTLE-AF is that 60% of patients improved their ejection fraction by 35% after their catheter ablation.
That kind of improvement means that many patients no longer suffered from heart failure. This is an amazing development in medicine. For people in this study, it’s like a miracle. They can now live more normal lives.
Less Hospital Admissions: A-Fib and heart failure are expensive diseases. A-Fib on average costs patients around $8,700/year. (See The Costs and Consequences of Living with Atrial Fibrillation.) It’s not inconsequential that successful catheter ablations reduce hospitalizations and trips to the ER.
Wider Adoption of Catheter Ablation: The CASTLE-AF study results could be a game changer for Atrial Fibrillation patients! Results could pave the way for wider adoption of catheter ablation and may prompt changes in current guidelines for treatment.
The Bottom Line: Becoming A-Fib free by a catheter ablation doesn’t just make you feel better and gets rid of your A-Fib symptoms. We now have hard data that an ablation lets you live a healthier and longer life.

Addition reference: Marrouche NF, et al. Catheter Ablation for Atrial Fibrillation with Heart Failure. N Engl J Med 2018; 378:417-427, Feb 01, 2018.

If you find any errors on this page, email us. Y Last updated: Thursday, March 14, 2024

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