New Findings in the Management of AF in Pacemaker Patients

Results from the MINERVA Triala Medtronic sponsored trial

February 2014

Steven Zweibel, MD, FACC, FHRS, CCDS

Director of Electrophysiology

Hartford Hospital

Hartford, CT

2013 Late-Breaking Clinical

Trial Abstracts

Circulation. 2013;128:2704-2722

World Wide Web at:

http://circ.ahajournals.org/content/128/24/2704

Study Aim and DesignAim: to evaluate whether DDDRP + MVP or MVP reduces mortality, morbidity, or progression to permanent AF compared with standard dual chamber pacing.

Multicenter (63 centers), international, randomized, single blind study with 3 arms enrolling 1,166 patients with:

• Class I or class II indications for dual chamber pacing

• Previous atrial tachyarrhythmias

• No history of permanent AF or third degree AV block

Primary Objective

Compare the Control DDDR to DDDRP + MVP arms at 2 years using thecomposite clinical endpoint of:

• All-cause death

• CV hospitalizations

• Permanent AF

Patient Baseline Characteristics

* p < 0.05 DDDRP + MVP vs. the other two groups

Primary Outcome(All-Cause Death, CV Hospitalizations, or Permanent AF)Intention-to-treat survival analysis using time to first event

All-Cause DeathIntention-to-treat survival analysis using time to first event

CV HospitalizationsIntention-to-treat survival analysis using time to first event

Permanent AFIntention-to-treat survival analysis using time to first event

Permanent AFIntention-to-treat survival analysis using time to first event

• Cardioversion for atrial arrhythmias occurred less frequently in the DDDRP + MVP vs. Control DDDR (49% relative reduction, p = 0.001)

• AF-related hospitalizations and ER visits occurred less

frequently in the DDDRP + MVP vs. Control DDDR (52% relative reduction, p < 0.0001)

Incidence of AFIntention-to-treat survival analysis using time to first event

Potential Contribution of Reactive ATPRisk of AF > 7 days and aATP efficacy

Note:since ATP treated only episodes longer than 2 minutes, to compare the different groups in a correct and balanced way, this analysis considered only patients with at least 2 minutes of AF

Not conclusive results …Select Studies on Atrial Therapies

Evolution of Atrial ATPFirst Generation

Treated atrial arrhythmias as if they were ventricular arrhythmias All therapies exhausted within 10 minutes

• AT/AF detected

8 hours

• Rhythm changed

• No ATP available to potentially terminate

100 ms 350 ms

220 ms 320 ms

• All therapies delivered in 10 minutes

• ATP unsuccessful

Atrial Therapy Zone

Evolution of Atrial ATPSecond Generation

Reactive ATP

• AT/AF detected

8 hours

• Rhythm changed

• ATP Therapy available for possible termination

100 ms 350 ms

220 ms 320 ms

• All therapies delivered

• ATP Unsuccessful

150 ms 200 ms 250 ms 300 ms

Atrial Therapy Zone

Example of Legacy ATP

Successful Ramp Following the Rhythm Transition (11 hour episode)

Ramp ATP delivered

Successful termination

Example of Reactive ATP in a MINERVA Patient

Discussion Recap

• The MINERVA study demonstrates the potential ability of atrial pacing interventions and reactive ATP to slow the progression to permanent AF

• Reactive ATP was a key therapy component affecting the reduction in time to permanent AF

• Reactive ATP opportunistically treats episodes of AF when they spontaneously organize or slow down

Potential Practice Implications

• No reduction in mortality at 2 years

• No change in CV hospitalizations at 2 years

• 52% relative reduction in atrial cardioversion, 49% relative reduction in AF hospitalization and ER visits

• AFIB begets AFIB and NSR begets NSR

– Providing an extended opportunity for AF ablation

• Reasonable to consider Reactive ATP in any patient receiving a PM with history of AF or at risk

• Reasonable to consider Reactive ATP in ICD and/or CRT patients; however, they have not been studied

Thank You

Brief Statement

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UC201405311 ENFebruary 2014

Back Up

Intervention algorithms

• Atrial rate stabilization (ARS)

• Atrial pacing preference (APP)

• Post mode switch overdrive pacing (PMOP)

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Atrial Rate Stabilization (ARS)• Intrinsic premature beats not followed by a long

pause (“short-long”)

• Each atrial interval is measured. The next pacing escape is this interval + a percentage (12.5, 25 or 50%)

• The fastest pace allowed is set by the Minimum Interval (shared by APP)

• Marker Channel paces are marked “PP” if generated by ARS

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ARS - Atrial Rate Stabilization

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Atrial Pacing Preference (APP)

• Designed to maintain a high percentage of atrial pacing

• On every non-refractory atrial sense, pacing escape interval is shortened. Amount of decrease is programmable, nominally 50ms

• After consecutive atrial paces (nominally 10), the escape interval is lengthened by 20 ms

• APP cannot go faster than the Minimum Interval.• Marker Channel paces are marked “PP” if

generated by APP

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APP - Atrial Pacing Preference

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Post Mode Switch Overdrive

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paced beats

Atrial tachyarrhythmia

pacing rate(DDDR)

time

Atrial rate

Sinus RhythmOverdrive Rate

(DDIR)pacing rate (not slower than 70)

(DDIR)

Overdrive Period

Confirm sinus (about 15 beats)