A Selection of Notable Late-Breaking Clinical Trials Heart Rhythm Society (HRS) 39th Annual Meeting, May 8–11, 2018, Boston

The HRS annual meeting brings together healthcare providers and vendors focused on the diagnostic and therapeutic area of heart rhythm abnormalities and the impact on sudden cardiac death, heart failure, and stroke.

This review is only a subset of late-breaking clinical trials that were presented at this year’s HRS meeting.

Catheter Ablation vs. Antiarrhythmic Drug Therapy for Atrial Fibrillation. The Results of the CABANA Multi-Center International Randomized Clinical Trial.

Presenter: Douglas L. Packer, MD

This randomized trial enrolled 2,204 patients at 226 sites. Of these, 1,096 were randomized to drug therapy, and 1,108 were randomized to ablation therapy based on A-Fib that warranted treatment. Subjects were 65 years of age or older and had at least one risk factor for stroke.

“I’ve changed my approach to treating these patients,” Dr. Packer said. He believes the most common approach has been to start with medication management and “see what happens.” But now he believes that “ablation is reasonable with lower risks than we have previously thought. I believe you will see more ablations. Ablations eliminate the arrhythmia, whereas medications just manage.”

Packer does qualify that the underlying cause of symptoms needs careful evaluation: “You have to balance underlying heart disease and heart failure with risk,” he points out.

The study does not definitively show that ablation is superior to medication management, but it does show promise that it is not inferior to medication. It will likely lead to greater consideration of ablation as a first step rather than as a follow-up to medication management. However, most believe there needs to be more clinical evaluation with a larger cohort to truly determine whether it is superior to medication management along with a look at long-term results from each group.

In my opinion, this approach offers insight and clinically viable options pending further clinical validation. It does indicate that ablation is a safe and possibly permanent solution for the appropriate patient population. It can reduce the long-term medication management and issues with patient compliance and other challenges in dealing with A-Fib patients.

Prevention of Arrhythmia Device Infection Trial (PADIT).

Presenter: Andrew D. Krahn, MD

This study focuses on the pre-surgical antibiotic strategy for preventing infection during and after implantation of an arrhythmia device. Over two years, during four six-month periods, 28 centers used conventional, pre-surgical treatment with a cefazolin infusion, or vancomycin for penicillin-allergic patients. This was compared to a multi-level treatment using cefazolin and/or vancomycin with bacitracin pocket wash and two days of oral cephalexin post-implant.

The study enrolled 19,603 patients. According to Dr. Krahn, while the findings reflected improvement with the multi-level approach, it was not a statistically significant improvement. He concludes, “Current guidelines are okay, but for high-risk patients results of the PADIT trial may offer support for a clinical decision to move to the more aggressive pre-op/post-op approach using the four-step protocol.”

From my perspective, this does provide expanded parameters that suggest some reduction in the rate of infection when the multi-level treatment is used. The data suggesting the benefits of enhanced precautions in higher-risk patients is helpful in the decision process.

AV Synchronous Pacing with a Ventricular Leadless Pacemaker: Primary Results from the MARVEL Study (Micra Atrial Tracking Using Ventricular AccELerometer).

Presenter: Larry A. Chinitz, MD, FHRS

 This study is based on the Micra leadless VVI pacemaker, which is deployed in the right ventricle without surgery via a catheter. To maximize pacing it is ideal to have the ventricular activation synchronized to follow atrial activation, which is why traditional pacemakers have lead wires implanted in both the atria and ventricle. The Micra pacemaker has an integrated, rate response, 3-axis accelerometer (ACC). The MARVEL trial was established to evaluate the effectiveness of using the ACC coupled with custom software to detect the atrial contraction and allow the Micra to utilize synchronous pacing as a single-chamber ventricular leadless pacemaker.

The study was completed by 64 patients in 12 centers in 9 different countries. The patients had a median implant term of 6 months. AV synchrony (AVS) was achieved in 87% of patients with high-degree AV block and in 94.5% of patients with intact AV conduction. “The findings suggest that the Micra with the accelerometer provides both feasibility and significantly improves AV synchrony in patients with AV block and a single-chamber leadless pacemaker implanted in the RV,” said Dr. Chinitz.

I feel this is a valuable advancement based on the unique design of the Micra pacemaker. Physiologically and hemodynamically, synchronized pacing is more effective, producing a better cardiac output, which results in overall better perfusion to the patient. I see this as the first step toward considering a catheter-based leadless pacemaker as a less invasive alternative to the traditional surgically implanted pacemakers with lead wires connected and threaded through the vasculature into the atria and ventricle to provide direct AV pacing. While there remain many issues to be clinically evaluated regarding this device, this is a step in the right direction.

Atrial Fibrillation Burden and Impact on Mortality and Hospitalization: The CASTLE-AF Trial.

Presenter: Johannes Brachmann, MD, FHRS

 The study randomly assigned patients to catheter ablation (n=179) or pharmacological treatment (rate or rhythm control) (n=184) of atrial fibrillation. After a baseline was established, patients were followed for up to five years, median 37.8 months. The ablation group 28.5% vs. the medical therapy group 44.6% experienced the composite primary end point of worsening heart failure, re-hospitalization, or death from any cause.

The findings, said Dr. Brachmann, indicate that “catheter ablation for atrial fibrillation in patients with heart failure was associated with a significantly lower rate of composite end point of death from any cause or hospitalization for worsening heart failure compared with medical therapy.”

 I believe this shows that an approach of interventional treatment with catheter ablation for patients with heart failure who have atrial fibrillation provides findings that support ablation therapy for this patient population with both atrial fibrillation and heart failure.

Sources:

CABANA TrialAm Heart J. 2018 May;199:192-199. doi: 10.1016/j.ahj.2018.02.015. Epub 2018 Mar 7.

Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation (CABANA) Trial: Study Rationale and Design

Packer DL1, Mark DB2, Robb RA3, Monahan KH3, Bahnson TD2, Moretz K2, Poole JE4, Mascette A5, Rosenberg Y5, Jeffries N5, Al-Khalidi HR2, Lee KL2; CABANA Investigators

PADIT -TrialCan J Cardiol. 2013 Jun;29(6):652-8. doi: 10.1016/j.cjca.2013.01.020

Randomized cluster crossover trials for reliable, efficient, comparative effectiveness testing: design of the Prevention of Arrhythmia Device Infection Trial (PADIT)

Connolly SJ1, Philippon F, Longtin Y, Casanova A, Birnie DH, Exner DV, Dorian P, Prakash R, Alings M, Krahn AD

MARVEL TrialHeart Rhythm. 2018 May 8. pii: S1547-5271(18)30470-3. doi: 10.1016/j.hrthm.2018.05.004. [Epub ahead of print]

Accelerometer based AV synchronous pacing with a ventricular leadless pacemaker: Results from the Micra AV feasibility studies

Chinitz L1, Ritter P2, Khelae SK3, Iacopino S4, Garweg C5, Grazia-Bongiorni M6, Neuzil P7, Johansen JB8, Mont L9, Gonzalez E10, Sagi V11, Duray GZ12, Clementy N13, Sheldon T14, Splett V14, Stromberg K14, Wood N14, Steinwender C1

CASTLE-AF TrialN Engl J Med. 2018 Feb 1;378(5):417-427. doi: 10.1056/NEJMoa1707855

Catheter Ablation for Atrial Fibrillation with Heart Failure.

Marrouche NF1, Brachmann J1, Andresen D1, Siebels J1, Boersma L1, Jordaens L1, Merkely B1, Pokushalov E1, Sanders P1, Proff J1, Schunkert H1, Christ H1, Vogt J1, Bänsch D1; CASTLE-AF Investigators

Tom Watson, Senior Clinical Strategist

Tom Watson joined MD Buyline in 1986 and has over 40 years of experience in the field of cardiovascular medicine.