Evidence Based Medicine

The Need to Avoid Unnecessary Ventricular Stimulation

for internal use only

ESC Guidelines

• Guidelines for cardiac pacing and CRT therapy • Published by task force for cardiac pacing and CRT of the ESC in collaboration with European Heart Rhythm Association • European Heart Journal (2007) 28, 2256-2295 for internal use only

ESC Guidelines

• For patients with Sinus Node Disease and AV block a DDDR pacemaker with options to minimize ventricular pacing is indicated • Class I, evidence level C indication • Class I: evidence and/or general agreement that a given treatment or procedure is beneficial, useful and effective • Level of evidence C: expert opinion and/or small studies, retrospective studies and registries • EVITA: Evaluation of VIp feaTure in pacemaker pAtients for internal use only

MO

de

S

election

T

rial

(MOST)

Adverse Effect of Ventricular Pacing On Heart Failure and Atrial Fibrillation Among Patients With Normal Baseline QRS Duration in a Clinical Trial of Pacemaker Therapy for Sinus Node Dysfunction

Sweeney et al. Circulation, 2003; vol 107: 2932 - 2937

for internal use only

MOST

Objectives Study the effect of Cumulative % of Ventricular Pacing in DDDR and VVIR mode on Heart Failure Hospitalization and AF in Sinus Node Disease Pts with QRS duration < 120 ms for internal use only

MOST

Randomization, Characteristics • Pts with SND • QRSd < 120 ms 1339 pts • Median EF 55% • Mild or no CHF DDDR 707 pts • > 50% history of A-tachycardia • PR interval < 200 ms or mildly prolonged VVIR 632 pts • DDDR and VVIR: lower rate  60, upper rate  110 bpm • DDDR: AV delay between 120 – 200 ms • 90% Ventricular Pacing in DDDR: due to AV < PR • 58% Ventricular Pacing in VVIR for internal use only

MOST

Results for internal use only

MOST

DDDR Heart Failure Hospitalization 

40% VP > 40% VP months

for internal use only

MOST

DDDR 1 st incidence of AF 

40% VP 40-70% VP 70-90% VP months

for internal use only

MOST DDDR Results • Risk of Heart Failure Hospitalization (HFH) for VP > 40% is 2.6 times risk compared with VP < 40% • Early, sustained and increasing incidence of HFH for VP > 40% compared with VP < 40% • The risk of AF increased by 1% for each % increase in percentage VP (up to 85%) • Early, sustained and increasing incidence of AF with increasing percentage of VP for internal use only

DAVID Trial Sponsor, Reference

Study Sponsor St. Jude Medical. The sponsor had no role in protocol, data collection/management, statistical analysis, manuscript (except review) Reference Wilkoff BL et al. JAMA, Dec 2002; vol 288: 3115 - 3123 for internal use only

David Trial Objectives, Hypothesis, End Points

Study Objectives Compare dual chamber with back-up single chamber pacing in pts with standard ICD indication (LVEF < 40%, no pacing indication) Hypothesis DDD(R) 70 bpm is superior to VVI 40 bpm End points 1. time to death 2. time to 1 st hospitalization for congestive heart failure for internal use only

David Trial Design, Randomization, Typical Result

design Single blinded, parallel-group, randomized clinical trial randomization typical result 506 pts VVI-40 256 pts DDDR-70 250 pts RV pacing 4 % RV pacing 70% (no AV delay recommendation) for internal use only

DAVID Trial

Endpoint: Death or 1st Hospitalization for New or Worsened CHF Relative Hazard (95% CI), 1.61 (1.06-2.44)

0.4

0.3

26.7%

0.2

16.1%

0.1

DDDR -70bpm VVI - 40bpm 0 0 6 Time, mo 12 18

No at Risk DDDR VVI 250 256 159 158 76 90 21 25 for internal use only

DAVID Trial Conclusion

In patients with: • standard ICD indication • • no pacing indication LVEF  40% DDDR-70 (no AV delay recommendation) versus VVI-40 offers: • no clinical advantage • may be detrimental by increasing the combined endpoint of death or hospitalization for heart failure for internal use only

DAVID Trial Clinical Implications

DDDR-70 may be detrimental compared to VVI-40 Is this rate related (70  40 bpm): no • • DAVID II (late braking trial HRS 2007) no difference in endpoint comparing AAI 70 with VVI 40 Is % RV pacing important: yes • • DAVID Sub-Analysis Sharma et al. Heart Rhythm 2005; 2: 830-834 for internal use only

David Sub-Analysis Objectives, Hypothesis, Remarks

Study Objectives • • Evaluate the effect of % RV apical pacing on endpoint Endpoint: death or CHF hospitalization Study design • • Pts: DAVID pts, with 3 months follow-up, that did not reach endpoint % RV pacing at 3 month follow-up was examined Remarks • There was a clear separation between DDDR pts with shipped settings of paced / sensed AV delay (180 – 150 ms) and an increased AV delay for internal use only

DAVID Sub-Analysis

Endpoint: Death or 1st Hospitalization for New or Worsened CHF 126 195 59 for internal use only 70 118 35 26 47 16 best separation for predicting endpoints was between DDDR > 40% and DDDR  40% pacing DDDR < 40% RV pacing patients were similar or better than VVI patients 3 5 4 No at Risk DDDR > 40% VVI unpaced DDDR  40%

Intrinsic RV Trial Sponsor, Reference

Study Sponsor Boston Scientific CRM Reference Olshansky B al. Circ, 2007; vol 115: 9-16 for internal use only

Intrinsic RV Trial Objectives, Hypothesis, End Points

Study Objectives Compare DDDR with algorithm to avoid ventricular pacing with back up single chamber pacing in pts with ICD indication Hypothesis DDD(R) + AV delay algorithm is not inferior to VVI-40 bpm End points 1. all-cause mortality 2. hospitalization for onset or worsening of CHF for internal use only

Intrinsic RV Trial Results

DDDR with AVSH trends towards superiority compared to VVI P=0.072

for internal use only

Intrinsic RV Trial Sub - Analysis

8% 3% Cumulative % RV pacing for internal use only 14%

How Can We Avoid Unnecessary Ventricular Stimulation

for internal use only

VIP

Ventricular Intrinsic Preference

VIP

Active Safety

for internal use only

VIP

Active Safety • Monitors the heart’s intrinsic conduction • Avoids unnecessary pacing • Provides pacing when needed • Activates and deactivates beat-by-beat • AV extension dynamically self-adjusts for internal use only

VIP

Advanced Programmability

for internal use only

VIP Advanced Programmability

VIP value  extension of paced / sensed AV-delay  Off - 200 ms, max paced / sensed AV delay 350 ms Search Interval  how often does the pm search for intrinsic rhythm  30 sec, 1, 3, 5, 10 or 30 min Search Cycles  the amount of cycles the AV-delay extension remains in effect while searching for intrinsic conduction  1, 2, 3 for internal use only

VIP To Activate VIP

for internal use only

VIP AV Extension

for internal use only

VIP Search Interval

for internal use only

VIP Search Cycles

for internal use only

VIP

Activation - Deactivation

for internal use only

VIP Activation Criteria

• One R-wave is sensed during the Search Interval • 3 consecutive R-waves occur within programmed AV delay but outside the Search Interval • 30 seconds after programming for internal use only

VIP Deactivation Criteria

VIP is deactivated when the consecutive number of VP events equals the number of programmed Search Cycles at the extended AV delay for internal use only

VIP

versus no VIP

for internal use only

Example: patient with intermittent complete AV block No VIP VIP long fixed AV delay (e.g. 320 ms) to prevent VP VIP induced AV delay extension to prevent VP AV conduction too long (e.g. 320 ms) fixed AV delay change to optimized AV delay (e.g. 195 ms) AV block for internal use only

VIP

Patient selection

for internal use only

VIP Patient Selection

• VIP most beneficial • • Intermittent AV block Mild prolongation of AV conduction • VIP not beneficial • • • Complete permanent AV block Marked 1st degree AV block If CRT therapy is indicated for internal use only

VIP

versus AAI



DDD algorithms

for internal use only

VIP Patient Type: 1

st

Degree AV block

• VIP provides immediate ventricular support at the appropriate AV delay, avoiding inappropriately long AV delay • AAI  DDD will continue in AAI mode with an inappropriately long AV delay until block occurs for internal use only

VIP

Patient Type: Intermittent 2 nd Degree AV block • VIP provides immediate ventricular support • VIP allows switch to extended AV delay (avoid VP) after 30 seconds ______________________________________________________ • AAI  DDD will continue in AAI mode with a (too) long AV delay until block occurs • AAI  DDD allows for repeated ventricular pauses (can cause pause dependent VTs 1,2 ) 1. Grey C, et al. Inappropriate application of “Managed Ventricular Pacing” in a patient with Brugada syndrome leading to polymorphic VT and ICD shocks. Heart Rhythm 2006; 3(5): S137 2. Van Mechelen R, et al. Risk of Managed Ventricular Pacing in a patient with heart block. Heart Rhythm 2006; 3(11): 1384-1385 for internal use only

VIP

Patient Type: High Grade 2 Intermittent 3 rd nd Degree, Degree AV Block • VIP provides immediate ventricular support at the first blocked ventricular event • AAI  DDD occurs only after block, creates long ventricular intervals (can cause pause dependent VTs 2 ) • AAI  DDD will not occur if ventricular escape rhythm during block is sufficiently fast: sustained AV dissociation 2. Van Mechelen R, et al. Risk of Managed Ventricular Pacing in a patient with heart block. Heart Rhythm 2006; 3(11): 1384-1385 for internal use only

VIP

clinical benefits

for internal use only

VIP Clinical Benefits

• Less risk of heart failure progression 3,4 • Less risk of developing AF 5 • Better QoL trough improved hemodynamics 6 3. Wilkoff BL, et al. DAVID investigators. Dual chamber pacing or ventricular back-up pacing in patients with an implantable ICD. JAMA 2002; 288(24): 3115 – 3123.

4. Olshansky B, et al. Is dual chamber programming inferior to single chamber programming in an ICD? Results of the INTRINSIC RV Study. Circulation 2007; 115: 9 – 16.

5. Sweeny MO , et al. Minimizing ventricular pacing to reduce AF in sinus node disease. N Engl J Med 2007; 357: 1000 - 1008 6. Ovsyshcher E. Toward physiological pacing: optimization of cardiac hemodynamics by AV delay adjustment. PACE 1997; 20: 861 - 865 for internal use only

VIP

additional information

for internal use only

VIP Additional Information

• PVCs have no effect on the timing of the VIP algorithm • If paced AV delay = 350ms: VIP is off • If rate responsive paced / sensed AV delay is enabled and active, the VIP AV delay extension will be added to the shortened paced / sensed AV delay for internal use only

VIP Disabled When:

• programmed base rate  110 bpm in DDD(R) or VDD(R) • paced / sensed atrial rate  110 bpm • Negative AV hysteresis / search is programmed On • Advanced Hysteresis Response is initiated • A magnet is applied for internal use only

VIP And AutoCapture

• When AutoCapture is On the VIP parameter needs to be  100 ms (VIP + paced AV delay  350 ms) • VIP is cancelled during AutoCapture Threshold Search and Loss of Capture recovery for internal use only

VIP Summary

• There is a need to avoid unnecessary ventricular pacing • VIP helps to avoid unnecessary ventricular pacing • Advanced programmability: VIP, Search Intervals, Search Cycles • Immediate ventricular support at the appropriate AV delay • Provide necessary pacing with optimized AV delay • To pace (with QuickOpt) or not to pace (with VIP) for internal use only

VIP

to avoid unnecessary ventricular stimulation for internal use only

for internal use only