Optimizing Ventricular Pacing in Sinus Node Disease Michael O. Sweeney, MD Brigham and Women’s Hospital Assistant Professor of Medicine Harvard Medical

Optimizing Ventricular Pacing Optimizing Ventricular Pacing in Sinus Node Diseasein Sinus Node Disease

Michael O. Sweeney, MDMichael O. Sweeney, MDBrigham and Women’s HospitalBrigham and Women’s Hospital

Assistant Professor of MedicineAssistant Professor of Medicine

Harvard Medical SchoolHarvard Medical School

Boston, MABoston, MA

Executive SummaryExecutive Summary

• Four major clinical trials have been unable to demonstrate a Four major clinical trials have been unable to demonstrate a clear benefit of DDDR pacing over VVIR for the clinical clear benefit of DDDR pacing over VVIR for the clinical endpoints of total mortality, cardiovascular mortality and endpoints of total mortality, cardiovascular mortality and stroke.stroke.

• It is possible that the higher level of ventricular pacing It is possible that the higher level of ventricular pacing associated with conventional DDDR pacing systems has associated with conventional DDDR pacing systems has adverse long-term effects on ventricular performance that adverse long-term effects on ventricular performance that mitigate the benefit of AV synchrony.mitigate the benefit of AV synchrony.

• Most patients with sinus node dysfunction (SND) have reliable Most patients with sinus node dysfunction (SND) have reliable AV conduction and normal ventricular activation. These AV conduction and normal ventricular activation. These patients would benefit from pacing systems that promote patients would benefit from pacing systems that promote intrinsic AV conduction.intrinsic AV conduction.

• The optimal pacing strategy to mitigate inappropriate The optimal pacing strategy to mitigate inappropriate ventricular pacing has not been identified.ventricular pacing has not been identified.

Presentation OverviewPresentation Overview• Background Background • Review of published clinical data on pacing mode in Review of published clinical data on pacing mode in

sinus node diseasesinus node disease– Danish– CTOPP– MOST– DAVID

• Why haven’t we been able to show a mortality and Why haven’t we been able to show a mortality and stroke benefit with DDDR pacing?stroke benefit with DDDR pacing?

• MOST Sub-Study: SND patients with QRS MOST Sub-Study: SND patients with QRS <<120 ms120 ms• Goals and strategies to reduce ventricular pacingGoals and strategies to reduce ventricular pacing• Identifying SND patients for minimal ventricular pacing Identifying SND patients for minimal ventricular pacing

strategiesstrategies• ConclusionsConclusions

BackgroundBackground

• Dual chamber pacing has long been considered Dual chamber pacing has long been considered “physiologic” due to maintenance of AV synchrony.“physiologic” due to maintenance of AV synchrony.

• Atrial pacing and dual-chamber pacing are similar Atrial pacing and dual-chamber pacing are similar only in that both maintain AV synchrony.only in that both maintain AV synchrony.

• Since most sinus node disease patients have intact or Since most sinus node disease patients have intact or intermittent conduction, the best pacing mode for intermittent conduction, the best pacing mode for these patients has often been debated. these patients has often been debated.

• Several large-scale clinical studies have attempted to Several large-scale clinical studies have attempted to identify the optimal pacing mode in patients with identify the optimal pacing mode in patients with sinus node disease.sinus node disease.

Clinical Data:Clinical Data: Pacing Mode and Sinus Node Pacing Mode and Sinus Node

DiseaseDiseaseDanish Study

CTOPPMOST DAVID

Danish StudyDanish Study

Danish StudyDanish Study OverviewOverview

• Hypothesis:Hypothesis:– In patients with SND, atrial pacing (AAI) will

result in less atrial fibrillation, thromboembolism, heart failure and overall mortality than ventricular pacing (VVI).

• Study Design:Study Design:– Single center, prospective, randomization of

patients referred for first pacemaker implant

• Primary:Primary:– Mortality– Cardiovascular death

• Secondary:Secondary:– Atrial fibrillation– Thromboembolic events– Heart failure– AV block

Danish Study Danish Study EndpointsEndpoints

• First pacemaker implantFirst pacemaker implant• Symptomatic bradycardia (<50 bpm or Symptomatic bradycardia (<50 bpm or

symptomatic QRS pauses >2 seconds)symptomatic QRS pauses >2 seconds)• >50 years of age>50 years of age• No history of:No history of:

– Chronic AF or AF >50% of time or AF with QRS rate <40 bpm

– Grade 1, 2, 3 AV block – Bundle branch block– Stroke within last 3 months– Hypertension (>250/120)

Danish Study Danish Study Inclusion CriteriaInclusion Criteria

Danish StudyDanish Study Patient CharacteristicsPatient Characteristics

AAl Group VVI Group

No. of PatientsNo. of Patients 110110 115115

Age, yAge, y 76 76 ++ 8 8 75 75 ++ 8 8

WomenWomen 7373 6969

MenMen 3737 4646

Sinus bradycardiaSinus bradycardia 1818 1818

Sino atrial blockSino atrial block 4949 4646

Brady-Tachy SyndromeBrady-Tachy Syndrome 4343 5151

Danish StudyDanish Study Patient CharacteristicsPatient Characteristics

AAl Group VVI Group

NYHA Class I 79 92

NYHA Class II 24 20

NYHA Class III 7 3

NYHA Class IV 0 0

Digoxin 22 11*

Beta Blocker 7 1

Calcium Blocker 13 11

Antiarrhythmic drugs 12 6

Furosemide, mg/d 32 + 51 23 + 39

Aspirin 48 46

Warfarin 6 1* P = 0.04, atrial versus ventricular group

Danish StudyDanish Study

Study Population (n=225)Study Population (n=225)

Randomised to AAI (n= 110)Randomised to AAI (n= 110) Randomised to VVI (n= 115)Randomised to VVI (n= 115)

VVIVVI AAIAAI DDDDDD AAIAAI VVIVVI DDDDDD IPG IPG removeremove

dd

ImplantationImplantation 66 104104 115115

Treatment at last Treatment at last FU or deathFU or death

1111 9494 55 11 109109 33 22

DeathsDeaths 33 3535 11 5656 11

Chronic AFChronic AF 33 66 2121

AF at one or AF at one or more abmulatory more abmulatory visitsvisits

99 1717 3737 22 11

ThromboembolisThromboembolismm

22 1111 2424 11 11

Danish Study Danish Study Overall survival by pacing modeOverall survival by pacing mode

Andersen H, et al. Lancet 1997; 350: 1210-16.

p = 0.045

Atrialpacing

Ventricularpacing

Time (years)

0 2 4 6 8 10

0

0-2

0-4

0-6

0-8

1-0

Number of patients at riskduring follow-up

Atrial

Ventricular

110

115

102

103

97

96

92

91

82

80

59

56

38

29

86

85

13

12

Danish Study Danish Study Cardiovascular death by pacing modeCardiovascular death by pacing mode


Time (years)

p = 0.0065

Atrial pacing

Ventricular pacing

0 2 4 6 8 10

0

0-2

0-4

0-6

0-8

1-0C

um

ula

tive

su

rviv

al


Atrial

Ventricular

110

115

102

103

97

96

92

91

82

80

59

56

38

29

86

85

13

12

Danish Study Danish Study Cumulative risk of PAF by pacing modeCumulative risk of PAF by pacing mode


0

0-2

0-4

0-6

0-8

1-0

p = 0.012

Atrialpacing

Ventricularpacing

Time (years)

0 2 4 6 8 10

Pro

port

ion

w

ith

ou

t A

F


Atrial

Ventricular

110 100 92 82 73 69 46 21 9

115 99 86 76 61 49 34 10 2

Danish Study Danish Study Cumulative risk of chronic AF by pacing Cumulative risk of chronic AF by pacing

modemode


p = 0.004

Atrialpacing

Ventricularpacing

Time (years)

0 2 4 6 8 10Pro

port

ion

wit

hou

t ch

ron

ic A

F

0

0-2

0-4

0-6

0-8

1-0


Atrial pacing

Ventricular pacing

110 102 96 91 80 74 49 26 10

115 102 92 84 75 65 41 18 5

Danish Study Danish Study Mortality as a result of CHFMortality as a result of CHF


1,00

,80

,600 2 4 6 8 10

Atrial pacing

Ventricular pacing

p = 0.18

Time (years)

Su

rviv

al w

ith

ou

t d

eath

fro

m C

HF

AAI: 110 102 97 92 86 82 59 38 13VVI: 115 103 96 91 85 80 56 29 12

Danish Study Danish Study CHF AnalysisCHF Analysis

• NYHA classification was higher in the ventricular NYHA classification was higher in the ventricular group vs. the atrial group (p=0.010) at long group vs. the atrial group (p=0.010) at long term follow up.term follow up.

• During follow up, NYHA class worsened in the During follow up, NYHA class worsened in the ventricular group vs. the atrial group (p<0.005)ventricular group vs. the atrial group (p<0.005)

• Mean dose of diuretics increased in the Mean dose of diuretics increased in the ventricular group vs. the atrial group (p=0.033)ventricular group vs. the atrial group (p=0.033)

Danish StudyDanish StudyConclusionsConclusions

In patients with SND, atrial pacing In patients with SND, atrial pacing is associated with a significantly is associated with a significantly higher survival, less atrial higher survival, less atrial fibrillation, fewer thromboembolic fibrillation, fewer thromboembolic complications, and less heart complications, and less heart failure compared to ventricular failure compared to ventricular pacing.pacing.

Danish Study Danish Study LimitationsLimitations

• Physical exam, NYHA classification and M-Physical exam, NYHA classification and M-mode echocardiography at follow-up were not mode echocardiography at follow-up were not done blinded with regard to randomization.done blinded with regard to randomization.– Possible impact: Observer bias in these parameters.

• NYHA class was difficult to define precisely, NYHA class was difficult to define precisely, but the higher use of diuretics in the but the higher use of diuretics in the ventricular group suggested a higher incidence ventricular group suggested a higher incidence of heart failure in this group.of heart failure in this group.

• Pacemaker event counters were not checked Pacemaker event counters were not checked regularly.regularly.– Possible impact: it was not possible to correlate

cumulative percent atrial or ventricular pacing to the changes in left atrial and left ventricular dimensions, LVFS, or occurrence of heart failure.

Danish Study Danish Study ReferencesReferences

• Andersen HR, Thuesen L, Bagger JP, et al. Prospective Andersen HR, Thuesen L, Bagger JP, et al. Prospective Trial of Atrial versus Ventricular Pacing in Sick Sinus Trial of Atrial versus Ventricular Pacing in Sick Sinus Syndrome. Syndrome. LancetLancet 1994; 344: 1523-28. 1994; 344: 1523-28.

• Andersen HR, Nielsen JC, Thomsen PE, et al. Long-Term Andersen HR, Nielsen JC, Thomsen PE, et al. Long-Term Follow-Up of Patients from a Randomised Trial of Atrial Follow-Up of Patients from a Randomised Trial of Atrial Versus Ventricular Pacing for Sick Sinus Syndrome. Versus Ventricular Pacing for Sick Sinus Syndrome. LancetLancet 1997; 350: 1210-16. 1997; 350: 1210-16.

• Nielsen JC, Andersen HR, Thomsen PE, et al. Heart Nielsen JC, Andersen HR, Thomsen PE, et al. Heart Failure and Echocardiographic Changes During Long-Failure and Echocardiographic Changes During Long-term Follow-up of Patients with Sick Sinus Syndrome term Follow-up of Patients with Sick Sinus Syndrome Randomized to Single-Chamber Atrial or Ventricular Randomized to Single-Chamber Atrial or Ventricular Pacing. Pacing. CirculationCirculation. 1998; 97: 987-995.. 1998; 97: 987-995.

CCanadian anadian TTrial rial oof f PPhysiologic hysiologic PPacingacing

CTOPPCTOPP

CTOPP Study OverviewCTOPP Study Overview

• Hypothesis:Hypothesis:– Physiologic (dual-chamber or atrial) pacing

is superior to single-chamber (ventricular) pacing because it is associated with lower risks of atrial fibrillation, stroke, and death.

• Study Design:Study Design:– 32 Canadian centers– Prospective, randomized

CTOPP Study EndpointsCTOPP Study Endpoints

• Primary:Primary:– Stroke or death due to cardiovascular

causes

• Secondary:Secondary:– Death from any cause– Atrial fibrillation– Hospitalization for heart failure

CTOPP Study Inclusion CriteriaCTOPP Study Inclusion Criteria

• All-cause bradycardiaAll-cause bradycardia• No chronic AFNo chronic AF• >18 years old>18 years old

CTOPP StudyCTOPP StudyBaseline Patient CharacteristicsBaseline Patient Characteristics

Physiologic Pacing Group

(n=1474)

Ventricular Pacing Group

(n=1094)

Mean age (yr) 73 + 10 73 + 10

Male sex (%) 60.2 57.0

NYHA Class > II (%) 37.2 41.5

Sinoatrial node disease 33.9 33.4

AV nodal disease 52.2 50.8

Both SA node and AV node disease

8.1 8.5

Intermittent atrial fibrillation

20.9 21.4

Anticoagulant drugs 10.4 11.9

Antiplatelet drugs 34.9 33.7

Antiarrhythmic drugs 11.5 12.6

CTOPP Study ProtocolCTOPP Study Protocol

Patients undergoing first IPG implant

n=2,568

Ventricular-Based Pacing

n = 1,474

Physiologic Pacing

n = 1,094

Follow for an average of 3 years and compare:

•Stroke or death due to cardiovascular causes

•Death from any cause

•Atrial fibrillation

•Hospitalization for HF

CTOPP CTOPP Cumulative Risk of Stroke or Cardiovascular Cumulative Risk of Stroke or Cardiovascular

Death Death C

um

ula

tive R

isk

Years after Randomization

0 1 2 3 4

0

0.1

0.2

0.3

0.4

P = 0.33

Ventricular pacing

Physiologic pacing

Connolly S et al. N Engl J Med 2000; 342: 1385-91.

No. at risk:Ventricular pacing 1474 1369 1259 847 366Physiologic pacing 1094 1005 954 637 287

CTOPP CTOPP Cumulative Risk of any AFCumulative Risk of any AF

Cu

mu

lati

ve R

isk

0

0.1

0.2

0.3

0.4

0 1 3 4

Years after Randomization

P = 0.05

Ventricular pacing

Physiologic pacing

Connolly S et al. N Engl J Med 2000; 342: 1385-91.

No. at risk:Ventricular pacing 1474 1276 1127 731 303Physiologic pacing 1094 936 857 559 250

2

CTOPP CTOPP Cumulative Risk of Chronic AFCumulative Risk of Chronic AF

Skanes A, et al. J Am Coll Cardiol 2001; 38: 167-72.

Cu

mu

lati

ve R

isk

Years Since Randomization

0 1 2 3 4

0.0

0.1

0.2

0.3

0.4

Number V 1474 1317 1180 779 331At Risk P 1094 975 906 601 269

P = 0.016

Ventricular pacing

Physiologic pacing

CTOPP CTOPP Subgroup AnalysesSubgroup Analyses

Skanes A, et al. J Am Coll Cardiol 2001; 38: 167-72.

Hazard Ratio

0.4 0.6 0.8 1.0 1.2 1.4 1.6

Physiologic Better Ventricular Better

Age: <74>=74

MICAD: NoYes

LVF: NormalAbnormal

SA Node: NoYes

AFib: NoYes

Hypten: NoYes

Diabetes: NoYes

P = 0.47

P = 0.09

P = 0.11

P = 0.65

P = 0.45

P = 0.80

P = 0.47

CTOPPCTOPPConclusionsConclusions

• Physiologic pacing (dual-chamber or Physiologic pacing (dual-chamber or atrial) provides little benefit over atrial) provides little benefit over ventricular pacing for the prevention of ventricular pacing for the prevention of stroke or death due to cardiovascular stroke or death due to cardiovascular causes.causes.

• Physiologic pacing does provide a Physiologic pacing does provide a reduction in the relative risk of atrial reduction in the relative risk of atrial fibrillation.fibrillation.

CTOPP CTOPP LimitationsLimitations

• Dual-chamber pacemakers used did not have Dual-chamber pacemakers used did not have algorithms designed to minimize ventricular algorithms designed to minimize ventricular pacingpacing– Possible result: High cumulative percentage of

ventricular pacing offset benefits of atrial-based pacing.

• Relatively short follow-up period (3 years) Relatively short follow-up period (3 years) – There may not have been enough time to detect a

true treatment effect if there is a delay before such an effect becomes evident.

CTOPP CTOPP ReferencesReferences

• Connolly SJ, Kerr CR, Gent M, et al. Effects of Connolly SJ, Kerr CR, Gent M, et al. Effects of Physiologic Pacing Versus Ventricular Pacing Physiologic Pacing Versus Ventricular Pacing on the Risk of Stroke and Death Due to on the Risk of Stroke and Death Due to Cardiovascular Causes. N Engl J Med 2000; Cardiovascular Causes. N Engl J Med 2000; 342: 1385-91.342: 1385-91.

• Skanes AC, Krahn AD, Yee R, et al. Skanes AC, Krahn AD, Yee R, et al. Progression to Chronic Atrial Fibrillation After Progression to Chronic Atrial Fibrillation After Pacing: The Canadian Trial of Physiologic Pacing: The Canadian Trial of Physiologic Pacing. J Am Coll Cardiol 2001; 38: 167-72.Pacing. J Am Coll Cardiol 2001; 38: 167-72.

MoMode de SSelection election TTrial rial in Sinus Node Dysfunctionin Sinus Node Dysfunction

MOSTMOST

MOST OverviewMOST Overview

• Hypothesis:Hypothesis:– Dual-chamber pacing improves survival and

quality versus single-chamber ventricular pacing in patients with SND.

• Study Design:Study Design:– 2,010 patients, randomized to DDDR vs.

VVIR– 91 clinical sites

MOST EndpointsMOST Endpoints• Primary:Primary:

– Death from any cause or nonfatal stroke

• Secondary:Secondary:– Composite of death from any cause, a first occurrence

of stroke or a first occurrence of hospitalization for heart failure

– Stroke– Death from any cause– Death from cardiovascular causes– Atrial fibrillation– The Minnesota Living with Heart Failure score– Pacemaker syndrome with a need for permanent

reprogramming to dual-chamber– Health-related quality of life

MOST Inclusion CriteriaMOST Inclusion Criteria

• Initial implant of a dual-chamber, rate Initial implant of a dual-chamber, rate modulated pacemaker for SNDmodulated pacemaker for SND

• >>21 years of age21 years of age• In sinus rhythm at implant In sinus rhythm at implant

randomizationrandomization• >> 17 or higher on the Mini-Mental State 17 or higher on the Mini-Mental State

ExaminationExamination

MOSTMOSTBaseline Patient CharacteristicsBaseline Patient Characteristics

CharacteristicCharacteristicVVIR

(n=996)DDDR

(n=1014) P-P-ValueValue

Median Age (yr)Median Age (yr) 7474 7474 0.580.58

Female sexFemale sex 477 (48)477 (48) 478 (47)478 (47) 0.740.74

Prior myocardial infarctionPrior myocardial infarction 243 (24)243 (24) 279 (28)279 (28) 0.110.11

Prior heart failurePrior heart failure 183 (18)183 (18) 221 (22)221 (22) 0.050.05

NYHA Class I or IINYHA Class I or II 841 (84)841 (84) 822 (81)822 (81) 0.050.05

Any supraventricular Any supraventricular tachycardiatachycardia

514 (52)514 (52) 545 (54)545 (54) 0.340.34

Arial fibrillationArial fibrillation 440 (44)440 (44) 477 (47)477 (47) 0.200.20

Any atrioventricular blockAny atrioventricular block 209 (21)209 (21) 204 (20)204 (20) 0.620.62

Complete heart blockComplete heart block 52 (5)52 (5) 39 (4)39 (4) 0.160.16

Second-degree HBSecond-degree HB 62 (6)62 (6) 72 (7)72 (7) 0.480.48

Prolonged AV intervalProlonged AV interval 102 (10)102 (10) 101 (10)101 (10) 0.830.83

Other heart blockOther heart block 23 (2)23 (2) 25 (2)25 (2) 0.880.88

VT or VFVT or VF 24 (2)24 (2) 42 (4)42 (4) 0.030.03

MOST ProtocolMOST Protocol

Patients Undergoing Initial IPG Implant for SND

n=2010

Dual-Chamber Pacing

n=1014

Ventricular Pacing

n=996

Follow for a median of 33 months and compare:•Death from any cause or non fatal stroke

•Composite of death, stroke, or hospitalization for HF

•Atrial fibrillation

•Heart Failure score

•Pacemaker syndrome

•Quality of Life

MOST MOST Total Mortality or StrokeTotal Mortality or Stroke

0 6 12 18 24 30 36 42 48 54 600.00

0.10

0.20

0.30

0.40

0.50

Months

Even

t R

ate

P = 0.48Adjusted P = 0.32

Ventricular pacing

Dual-chamber pacing

Lamas G, et al. N Engl J Med 2002; 346: 1854-62.

No. at risk:Ventricular pacing

Dual-chamber pacing 996 934 897 813 678 557 431 320 218 125 391014 963 930 833 693 555 431 328 214 120 28

MOST MOST CHF HospitalizationCHF Hospitalization


No at risk:Ventricular pacing


0 6 12 18 24 30 36 42 48 54 60

0.00

0.10

0.20

0.30

0.40

0.50

Months

Even

t R

ate

P = 0.13Adjusted P = 0.02

Ventricular pacing

Dual-chamber pacing

MOST MOST Heart Failure, Stroke, or DeathHeart Failure, Stroke, or Death


0.50



0 6 12 18 24 30 36 42 48 54 600.00

0.10

0.20

0.30

0.40

Months

Even

t R

ate

Ventricular pacing

Dual-chamber pacing

P= 0.23

Adjusted P = 0.05

MOST MOST Atrial FibrillationAtrial Fibrillation


0.50

0 6 12 18 24 30 36 42 48 54 60

0.00

0.10

0.20

0.30

0.40

Months

Even

t R

ate P = 0.008

Adjusted P = 0.004

Ventricular pacing

Dual-chamber pacing



MOST MOST Subgroup AnalysesSubgroup Analyses


0.5 1.0 2.0

Better Results withDual-Chamber

Pacing

Better ResultsWith Ventricular

Pacing

CHARACTERISTICNo. of

PATIENTS HAZARD RATIO (95% CI)

All patientsSex

FemaleMale

Age≥ 75 years≤ 75 years

RaceWhiteNonwhite

History of supra-ventriculartachycardia

YesNo

2010

9551055

9871023

1704306

1059951

0.90 (0.77-1.06)

0.89 (0.71-1.13)0.91 (0.73-1.15)

0.97 (0.79-1.21)0.83 (0.65-1.07)

0.88 (0.73-1.05)1.00 (0.68-1.46)

0.92 (0.74-1.14)0.88 (0.69-1.13)

MOST MOST ConclusionsConclusions

• In patients with SND, dual-chamber In patients with SND, dual-chamber pacing (versus single-chamber ventricular pacing (versus single-chamber ventricular pacing) reduces newly diagnosed and pacing) reduces newly diagnosed and chronic atrial fibrillation, reduces the chronic atrial fibrillation, reduces the signs and symptoms of heart failure, and signs and symptoms of heart failure, and slightly improves quality of life.slightly improves quality of life.

• Dual-chamber pacing did not improve the Dual-chamber pacing did not improve the rate of the primary endpoint of mortality rate of the primary endpoint of mortality or freedom from stroke.or freedom from stroke.

MOST MOST LimitationsLimitations

• Randomly assigned pacing mode but not the Randomly assigned pacing mode but not the type of pacemaker.type of pacemaker.– Possible result: ease of cross-over may have reduced

the number of clinical events in the ventricular arm

• Pacemakers used did not have algorithms Pacemakers used did not have algorithms designed to minimize ventricular pacing.designed to minimize ventricular pacing.– Possible result: High cumulative percent ventricular

pacing offset benefits of atrial-based pacing.

• Impossible to determine whether atrial-based Impossible to determine whether atrial-based pacing prevents AF or whether ventricular pacing prevents AF or whether ventricular pacing is arrhythmogenic, causing AF.pacing is arrhythmogenic, causing AF.

DDual-Chamber ual-Chamber aand nd VVVI VI IImplantable mplantable DDefibrillator Trialefibrillator Trial

DAVIDDAVID

DAVID Trial DAVID Trial OverviewOverview

• Hypothesis:Hypothesis:– Aggressive management of LV dysfunction with

optimized drug therapy and with dual chamber pacing could improve the combined endpoint of total mortality and hospitalization for heart failure, compared to similarly optimized drug therapy supported by ventricular backup pacing.

• Study design:Study design:– Single blind, multicenter, parallel group, randomized

trial comparing DDDR (70 bpm lower rate) vs. VVI (40 bpm lower rate) pacing modes

Wilkoff B, et al. JAMA. 2002; 288: 3115-3123.

DAVID Trial DAVID Trial EndpointsEndpoints

• Primary:Primary:– Freedom from death and heart failure

hospitalization


DAVID Trial DAVID Trial Inclusion CriteriaInclusion Criteria

• ICD indicated patientsICD indicated patients

• No indication for antibradycardia No indication for antibradycardia pacingpacing

• LVEF LVEF 40%40%• No persistent or frequent, No persistent or frequent,

uncontrolled AFuncontrolled AF


DAVID TrialDAVID Trial Baseline Patient CharacteristicsBaseline Patient Characteristics

VVI-40VVI-40 DDDR-70DDDR-70 p valuep value

Age, mean (SD), yAge, mean (SD), y 66(11)66(11) 64(11)64(11) 0.190.19

Male, %Male, % 8181 8686 0.150.15

LVEF, mean (SD), %LVEF, mean (SD), % 2828 2626 0.170.17

NYHA Class I, %NYHA Class I, % 5050 4747

NYHA Class II, %NYHA Class II, % 3939 4040 0.630.63

NYHA Class III/IV, %NYHA Class III/IV, % 1111 1313

History of MI, %History of MI, % 6767 7171 0.320.32

History of CHF, %History of CHF, % 5656 5858 0.660.66

History of CAD, %History of CAD, % 8484 8383 0.840.84


DAVID TrialDAVID Trial Baseline Patient CharacteristicsBaseline Patient Characteristics

Indications for ICD, %Indications for ICD, % VVI-40VVI-40 DDDR-70DDDR-70 P valueP value

VFVF 1919 1818

Syncopal VTSyncopal VT 77 66

Symptomatic sustained VTSymptomatic sustained VT 1616 2323

Symptomatic NSVT + EPS Symptomatic NSVT + EPS positivepositive

99 55

0.310.31

Asymptomatic NSVT + EPS Asymptomatic NSVT + EPS positivepositive

2525 2323

Unexplained syncope + EPS Unexplained syncope + EPS positivepositive

1515 1818

Hemodynamically stable VTHemodynamically stable VT 1010 88


DAVID Trial DAVID Trial ProtocolProtocol

760 assessed for eligibility250 excluded 149 Did not meet Rx criteria 55 refused 46 Other

510 eligible4 Not randomized 2 Required pacing 1 Inadequate defibrillation threshold 1 Decided not to implant

506 randomized

VVI-40 (n=256) DDDR-70 (n= 250)

• 1 had pacing mode set to DDD• 1 LTF• 10 Discontinued intervention• 5 Bradycardia• 1 CHF and AF• 1 Brady induced Torsade• 1 Heart Tx workup• 1 AF w rapid V response• 1 multiple shocks due to double counting

• 3 had pacing mode set to VVI• 2 LTF• 5 Discontinued intervention• 1 Angina• 1 CHF and Lead Failure• 1 CHF Hospitalization• 1 Exacerbation of VT• 1 Lead Migration


DAVID TrialDAVID Trial Drug Therapy 6 Months Post Drug Therapy 6 Months Post

RandomizationRandomizationDrug Therapy, %Drug Therapy, % VVI-40VVI-40

(n=156)(n=156)DDDR-70DDDR-70

(n=149)(n=149)p valuep value

ACE inhibitor or ARBACE inhibitor or ARB 8484 8787 0.420.42

ßß-Blocker-Blocker 8686 8585 0.740.74

ACE, ARB, ACE, ARB, ßßBB 9797 9999 0.440.44

DigoxinDigoxin 4141 4242 0.820.82

DiureticDiuretic 6464 6464 0.950.95

NitrateNitrate 2525 2222 0.560.56

SpironelactoneSpironelactone 1515 2222 0.130.13

AmiodaroneAmiodarone 2323 3232 0.100.10

SotololSotolol 77 22 0.040.04

Other ADDOther ADD 11 22 0.290.29


DAVIDDAVIDDeath or First Hospitalization for New or

Worsened CHF

Hazard ratio (95% CI), 1.61 (1.06-2.44)

0 6 12 18Months

Cu

mu

lati

ve P

rob

ab

ilit

y

0.4

0.3

0.2

0.1

0

250256

159158

7690

2125

No. at RiskDDDR

VVI


DDDR

VVI

DAVID Trial DAVID Trial ResultsResults

VVI-40 DDDR-70 HR (p-value, adj.)

CHF Hospitalization or Death

16.1% 26.7% 1.61(p = 0.03)

CHF Hospitalization

13.3% 22.6% 1.54(p=0.07)

Death 6.5% 10.1% 1.61(p=0.15)


DAVIDDAVIDFirst Hospitalization for New or Worsened

CHF

Hazard ratio (95% CI), 1.54 (0.97-2.46)

0 6 12 18Months

Cu

mu

lati

ve P

rob

ab

ilit

y

0.4

0.3

0.2

0.1

0

250256

155156

7489

2124

No. at RiskDDDR

VVI


DDDR

VVI

DAVIDDAVIDDeath From Any Cause


Hazard ratio (95% CI), 1.61 (0.84-3.09)

0 6 12 18Months

Cu

mu

lati

ve P

rob

ab

ilit

y

0.4

0.3

0.2

0.1

0

250256

173172

9596

3025

No. at RiskDDDR

VVI

DDDR

VVI

DAVIDDAVID


VVI-40VVI-40 DDDR-70DDDR-70 P-P-valuevalue

6-month EKG:

SinusSinus 97.1%97.1% 42.0%42.0% <0.001<0.001

V-pacedV-paced 2.9%2.9% 55.7%55.7% <0.001<0.001

QRSdQRSd 117 117 ++ 29 ms 29 ms 134 134 ++ 39 ms 39 ms <0.001<0.001

Cum % VP:

3 months3 months 1.5% 1.5% ++ 8.0% 8.0% 57.9% 57.9% + + 35.8% 35.8%

<0.001<0.001

6 months6 months 0.6% 0.6% ++ 1.7% 1.7% 59.6% 59.6% ++ 36.2%36.2%

<0.001<0.001

12 months12 months 3.5% 3.5% ++ 14.9%14.9%

58.9% 58.9% ++ 36.0%36.0%

<0.001<0.001

DAVIDDAVID

• Study results are consistent with the pacing Study results are consistent with the pacing literature.literature.– AAI was associated with slightly better survival and lower

rate of severe CHF compared to VVI pacing mode in patients with SSS1

– QOL was better in elderly patients with sinus node disease with VVI compared to DDD pacing.2

– More than 40% ventricular pacing was associated with increased CHF hospitalizations.3

– The benefit of DDDR pacing was most evident in patients who needed continuous pacing.4

3. Sweeney et al. Pacing Clin Electro. 2002;25:690.4. Kerr et al. Pacing Clin Electro. 2002;25:553.

1. Anderson et al. Lancet. 1997;350:1210-1216.2. Lamas et al. N Engl J Med. 1997;337:1576-1583.

DAVID DAVID ConclusionsConclusions

• Bradycardia pacing operation in dual-Bradycardia pacing operation in dual-chamber ICDs should be optimized for chamber ICDs should be optimized for individual patients.individual patients.– RV pacing in patients with LV dysfunction and

no bradycardia indication for pacing can be harmful.

– Programming of dual chamber devices to backup ventricular pacing is justified in this patient population.


DAVID DAVID LimitationsLimitations

• The specific programming choices made by The specific programming choices made by investigators and available pacemakers could have investigators and available pacemakers could have affected the results, e.g. affected the results, e.g. – Choice of DDDR pacing rate of 70 – Choice of AV interval– DDDR devices did not have algorithms to promote intrinsic

conduction (reduce ventricular pacing)

• Results may not apply to patients with a normal Results may not apply to patients with a normal ejection fraction or with standard pacing ejection fraction or with standard pacing indications. indications.


Summary of Clinical Trial Data:Summary of Clinical Trial Data: Atrial Based/Physiologic Pacing Benefits (vs. VVIR)Atrial Based/Physiologic Pacing Benefits (vs. VVIR)

MortaliMortalityty

HospitalizaHospitalization for tion for

CHFCHF

AtrialAtrial

FibrillationFibrillation StrokeStroke

DanishDanishAAIR vs. VVIR; All SND ptsAAIR vs. VVIR; All SND pts

But not But not until after 3 until after 3

years FUyears FU

Both acute Both acute and chronicand chronic

NSNS

CTOPP CTOPP Physiologic vs. ventricular Physiologic vs. ventricular pacing; ~40% of pts had pacing; ~40% of pts had SNDSND

But not until But not until 2 years FU2 years FU

MOSTMOSTDual-chamber vs. single Dual-chamber vs. single chamber; All SND ptschamber; All SND pts

But still But still 10% at 36 10% at 36

monthsmonths

But still 24-But still 24-25% at 36 25% at 36

monthsmonths

DAVIDDAVIDNo indication for No indication for pacingpacing

(Composite (Composite endpoint)endpoint)

NSNS NSNS

= No Difference ObservedNS = Not a studied endpoint

Summary of Major Clinical TrialsSummary of Major Clinical Trials

• Despite maintenance of AV synchrony, Despite maintenance of AV synchrony, DDDR did not improve survival or prevent DDDR did not improve survival or prevent stroke when compared with ventricular stroke when compared with ventricular pacing. pacing.

• DDDR pacing DDDR pacing doesdoes reduce the risk of reduce the risk of developing atrial fibrillation and may reduce developing atrial fibrillation and may reduce signs and symptoms of heart failure and signs and symptoms of heart failure and hospitalizations for heart failure in some, but hospitalizations for heart failure in some, but not all, patients.not all, patients.

• Normal ventricular activation requires the synchronized participation of the distal components of the specialized conduction system (the main bundle branches and their ramifications).

• Majority of patients (~80%) with SND, including those with CHF, have intact AV conduction and narrow QRS duration (normal ventricular activation).1

• Conventional RV apical pacing results in “forced” ventricular desynchronization, which mimics LBBB and has adverse effects on ventricular structure and function.

Why Haven’t We Been Able to Why Haven’t We Been Able to Prove A Mortality or Stroke Benefit Prove A Mortality or Stroke Benefit

with DDDR?with DDDR?

1 Medtronic device registration (1997-present).

• Conventional dual-chamber pacing systems* often result in a higher level of RV apical pacing due to:– AV delays that are programmed shorter than

the patient’s intrinsic AV conduction– Lower rate settings higher than

optimal/necessary– Rate-responsive algorithms which increase

ventricular pacing in response to stress

Why Haven’t We Been Able to Why Haven’t We Been Able to Prove A Mortality or Stroke Benefit Prove A Mortality or Stroke Benefit

with DDDR?with DDDR?

*without algorithms to minimize inappropriate V-pacing

Effect of Pacing Mode and Cumulative Effect of Pacing Mode and Cumulative Percent Time Ventricular Paced on Heart Percent Time Ventricular Paced on Heart Failure and Atrial Fibrillation in Patients Failure and Atrial Fibrillation in Patients

with Sinus Node Dysfunction and Baseline with Sinus Node Dysfunction and Baseline QRS Duration QRS Duration

<120 Milliseconds in MOST<120 Milliseconds in MOST

A MOST Sub-StudyA MOST Sub-Study

Michael O. Sweeney, Anne S. Hellkamp, Arnold J. Greenspon, Michael O. Sweeney, Anne S. Hellkamp, Arnold J. Greenspon, Robert Mittleman, John McAnulty, Kenneth Ellenbogen, Roger Robert Mittleman, John McAnulty, Kenneth Ellenbogen, Roger

Freedman, Kerry L. Lee, Gervasio A. Lamas, for the MOST Freedman, Kerry L. Lee, Gervasio A. Lamas, for the MOST InvestigatorsInvestigators

Circulation 2003, in pressCirculation 2003, in press

MOST Sub-StudyMOST Sub-Study

Background:Background:• DDDR pacing preserves AV synchrony and DDDR pacing preserves AV synchrony and

reduces CHF compared to VVIR pacing in SND.reduces CHF compared to VVIR pacing in SND.• DDDR pacing results in prolonged QRS durations DDDR pacing results in prolonged QRS durations

(QRSd) due to ventricular desynchronization.(QRSd) due to ventricular desynchronization.

Hypothesis:Hypothesis:• DDDR pacing often results in prolonged QRS DDDR pacing often results in prolonged QRS

duration (QRSd) due to ventricular duration (QRSd) due to ventricular desynchronization in patients with normal desynchronization in patients with normal baseline QRSd and may increase risk of heart baseline QRSd and may increase risk of heart failure and atrial fibrillationfailure and atrial fibrillation..

Sweeney MO, et al. Circulation 2003, in press

Methods:Methods:• Baseline QRSd obtained from 12-lead EKG prior to Baseline QRSd obtained from 12-lead EKG prior to

IPG implant in MOST (a 2,010 patient, 6-year IPG implant in MOST (a 2,010 patient, 6-year randomized trial of DDDR vs. VVIR pacing in SND).randomized trial of DDDR vs. VVIR pacing in SND).

• Cumulative % time ventricular paced was Cumulative % time ventricular paced was determined from stored pacemaker diagnostic determined from stored pacemaker diagnostic data.data.

• Baseline QRSd <120 ms was observed in 1332 Baseline QRSd <120 ms was observed in 1332 patients; 702 were randomized to DDDR; 640 to patients; 702 were randomized to DDDR; 640 to VVIR.VVIR.



0

2

4

6

8

10

12

14

16

Rate

of H

eart

Failure

H

osp

italiza

tion

< 10% Cum VP >90% Cum VP

DDDR VVIR

MOST Sub-Study: ResultsMOST Sub-Study: Results• Cum%VP was greater in DDDR (90%) vs. VVIR (51%). Cum%VP was greater in DDDR (90%) vs. VVIR (51%).

• The rates of CHF hospitalization increased with Cum%VP:The rates of CHF hospitalization increased with Cum%VP:


0

1

2

3

4

5

6

7

0 20 40 60 80 100

Cum% VP

Ris

k o

f H

FH

rela

tive t

oD

DD

R p

ati

ent

wit

h C

um

%VP=

0


MOST Sub-study:MOST Sub-study: Risk of HFH Relative to a DDDR Patient with Cum % Risk of HFH Relative to a DDDR Patient with Cum %

VP = 0VP = 0

•Risk of HFH increased between 0% and 40% Cum VP, but was level at Cum%VP above 40%.

•Risk can be reduced to about 2% if ventricular pacing is minimized.

0

1

2

3

4

5

6

7

0 20 40 60 80 100

Cum% VP

Ris

k o

f H

FH

rela

tiv

e t

o

VVIR

patie

nt w

ith C

um

%VP=

0


MOST Sub-Study: MOST Sub-Study: Risk of HFH Relative to a VVIR Patient with Cum % Risk of HFH Relative to a VVIR Patient with Cum %

VP = 0VP = 0

•Risk of CHF was constant between 0% and 80% Cum VP and increased by as much as 2.5-fold when Cum%VP exceeded 80%.

•Risk cannot be reduced regardless of minimization of ventricular pacing.

• DDDR: DDDR: – Cum%VP >40% was associated with 3 times

increased risk of CHF hospitalization (p=0.02). • The risk of CHF hospitalization increased by 54% for

each 10% increase in Cum%VP (Hazard ratio 1.54 [1.01, 2.36), p=0.05) between 0% and 40%.

• VVIR:VVIR:– Cum%VP > 80% was associated with 2.6 times

increased risk of CHF hospitalization (p=0.007).

• The risk of CHF hospitalization increased by 96% for each 10% increase in Cum%VP (Hazard ratio 1.96 [1.39, 2.77], p=0.0001) above 80%.


MOST Sub-Study: CHF RiskMOST Sub-Study: CHF Risk

Cum% Vp at 30 days and subsequent HFH eventsDDDR/ Normal QRS

0.8

0.825

0.85

0.875

0.9

0.925

0.95

0.975

1

0 12 24 36 48

Months

Pro

port

ion e

vent-

free

Cum% Vp <= 40

Cum% Vp > 40

P=0.047



Cum% Vp at 30 days and subsequent HFH eventsVVIR/ Normal QRS

0.8

0.825

0.85

0.875

0.9

0.925

0.95

0.975

1

0 12 24 36 48

Months

Pro

port

ion e

vent-

free

Cum% Vp <= 80

Cum% Vp > 80

P=0.0046



• Higher rates of CHF hospitalization were Higher rates of CHF hospitalization were associated with higher Cum% VP: associated with higher Cum% VP: – Cum % VP<10% was associated with the lowest rates of

CHF hospitalization (DDDR 2%, VVIR 7%).– Cum % VP >90% was associated with the highest rates

of CHF hospitalization (DDDR 12%, VVIR 16%).

• Ventricular pacing in the DDDR mode more than Ventricular pacing in the DDDR mode more than 40% confers a 3-fold increased risk of heart 40% confers a 3-fold increased risk of heart failure hospitalization failure hospitalization but can be reduced to about 2% if ventricular pacing is minimized.


MOST Sub-studyMOST Sub-studyConclusions: CHFConclusions: CHF

• In the VVIR mode, the risk of CHF hospitalization was level below Cum%VP 80% but cannot be reduced regardless of minimization of ventricular pacing. This risk is increased by as much as 2.5-fold when Cum%VP exceeds 80%.

MOST Sub-studyMOST Sub-studyConclusions: CHFConclusions: CHF

0

1

2

3

4

0 20 40 60 80 100

Cum% VP

Ris

k o

f A

F re

lati

ve t

oD

DD

R p

ati

ent

wit

h C

um

%VP=

0

0

1

2

3

4

0 20 40 60 80 100

Cum% VPR

isk o

f A

F re

lati

ve t

o

VVIR

pati

ent

wit

h C

um

%VP=

0


Risk of AF increases linearly with Cum%VP up to 80-85% in both DDDR and VVIR

MOST Sub-study: AF RiskMOST Sub-study: AF Risk

Cum% Vp in first 30 days and subsequent AF eventsDDDR/ Normal QRS

0.6

0.65

0.7

0.75

0.8

0.85

0.9

0.95

1

0 12 24 36 48

Months

Pro

port

ion e

vent-

free

%Vp <=40%%Vp 40-70%%Vp 70-90%



Cum% Vp in first 30 days and subsequent AF eventsVVIR/ Normal QRS

0.55

0.6

0.65

0.7

0.75

0.8

0.85

0.9

0.95

1

0 12 24 36 48

Months

Pro

port

ion e

vent-

free

%Vp <=40%%Vp 40-70%%Vp 70-90%



• Relationship between risk of AF and CumRelationship between risk of AF and Cum%VP was similar between pacing modes:%VP was similar between pacing modes:

– Risk of AF showed a linearly increasing relationship with increased Cum%VP from 0% pacing up to 80-85% pacing in both pacing modes.

– Within this range, the risk of AF increased by 1% for each 1% increase in Cum%VP (DDDR hazard ratio 1.01 [1.004, 1.022] p=0.012; VVIR 1.01 [1.001, 1.01], p=0.025).


MOST Sub-studyMOST Sub-studyConclusions: AFConclusions: AF

• The adverse effects of forced ventricular The adverse effects of forced ventricular desynchronization probably explain the desynchronization probably explain the difficulty in demonstrating a mortality and difficulty in demonstrating a mortality and stroke benefit with physiologic (DDDR) stroke benefit with physiologic (DDDR) compared to ventricular (VVIR) pacing in compared to ventricular (VVIR) pacing in randomized trials.randomized trials.

• Further research is necessary to clarify the Further research is necessary to clarify the role of “electrical unloading” of the left role of “electrical unloading” of the left ventricle using minimal ventricular pacing ventricle using minimal ventricular pacing strategies in SND and normal QRSd.strategies in SND and normal QRSd.


MOST Sub-Study:MOST Sub-Study:Overall ConclusionsOverall Conclusions

Goals and Strategies to Optimize Goals and Strategies to Optimize Ventricular PacingVentricular Pacing

The New Goals of Pacing The New Goals of Pacing Therapy Therapy

• Bradycardia-indicated patients (pacemaker and ICD Bradycardia-indicated patients (pacemaker and ICD patients)patients)– Prevent symptomatic bradycardia– Provide chronotropic competence when necessary– Maintain normal ventricular activation sequence whenever Maintain normal ventricular activation sequence whenever

possible using minimal ventricular pacing modespossible using minimal ventricular pacing modes

• Non-Bradycardia Patients (ICD patients with no Non-Bradycardia Patients (ICD patients with no brady indications)brady indications)– VT/VF detection– Maintain normal ventricular activation sequence whenever Maintain normal ventricular activation sequence whenever

possible using minimal ventricular pacing modespossible using minimal ventricular pacing modes

Strategies to Optimize RV PacingStrategies to Optimize RV Pacing

• Recognition of chronic adverse effects of RV Recognition of chronic adverse effects of RV pacing has stimulated interest in strategies pacing has stimulated interest in strategies to attenuate these effects.to attenuate these effects.

• Several approaches have been investigated:Several approaches have been investigated:– Optimal/novel RV pacing sites– Manipulation of DDDR timing cycles (AV delay) to

minimize unnecessary RV pacing– Use of AAI or DDI/R pacing modes– Novel pacing algorithms

Optimal RV Pacing SitesOptimal RV Pacing Sites

• RV apical pacing originated due to ease of placement, RV apical pacing originated due to ease of placement, stability of the electrode, and good pacing thresholds in stability of the electrode, and good pacing thresholds in this location—not for hemodynamic reasons.this location—not for hemodynamic reasons.

• With introduction of active fixation leads, alternative With introduction of active fixation leads, alternative pacing sites have been shown to be feasible with respect pacing sites have been shown to be feasible with respect to pacing thresholds, adequate sensing, and stability. to pacing thresholds, adequate sensing, and stability. 11

• RVOT and Right ventricular septum (RVS) are the most RVOT and Right ventricular septum (RVS) are the most frequently described alternate RV pacing sites.frequently described alternate RV pacing sites. 2 2

• Numerous acute and chronic studies have demonstrated Numerous acute and chronic studies have demonstrated mixed results—largely due to differences in study design mixed results—largely due to differences in study design ..3-173-17

Future Directions:Future Directions:• Large, long-term, randomized studies of Large, long-term, randomized studies of

alternative pacing sites vs. RV apex will alternative pacing sites vs. RV apex will be needed to change clinical practice. be needed to change clinical practice.

• Specifically-designed leads, delivery Specifically-designed leads, delivery systems, and pacing algorithms/modes to systems, and pacing algorithms/modes to facilitate alternative site placement facilitate alternative site placement and/or multisite stimulation will also be and/or multisite stimulation will also be needed for ease-of-use and broad needed for ease-of-use and broad acceptance.acceptance.

Optimal RV Pacing SitesOptimal RV Pacing Sites

Long AV Delays During Dual Long AV Delays During Dual Chamber Pacing: An Incomplete Chamber Pacing: An Incomplete

SolutionSolution

• Long AV delays may reduce unnecessary Long AV delays may reduce unnecessary ventricular pacing and maintain normal ventricular pacing and maintain normal ventricular activation sequence but require ventricular activation sequence but require reliable AV nodal conduction.reliable AV nodal conduction.

• Long AV delays may impose limitations on Long AV delays may impose limitations on optimal DDDR operation:optimal DDDR operation:– Reduced 2:1 block point due to increased TARP– Abandonment of mode-switching or significantly

delayed AF recognition– Susceptibility to endless loop tachycardias

Long AV delays do not Long AV delays do not sufficiently reduce ventricular sufficiently reduce ventricular

pacingpacing• Two approaches to programming long AV delays to Two approaches to programming long AV delays to

permit native ventricular activation:permit native ventricular activation:

1. AV delays > resting PR intervals1

• AV delays > resting PR intervals (22224 ms vs. 18423 ms)• Mean time Vp for all patients was 80%; > 50% for 88%

2. Long fixed AV delay (300 ms)2-3

• Mean time Vp 17.7% overall but 39% in nearly 50% of patients• Resting PQ interval (17728 vs. 20438), atrial stimulus-Q

interval at 100 bpm (21340 vs. 22049) or AV delay (2993.2 vs. 28821) did not predict Vp

• High incidence of endless loop tachycardia– Can be reduced if rate-adaptive AV delays are used

1 Sgarbossa E et al PACE 1993; ;16:872A. 2 Nielsen JC et al PACE 1997:20:1574A. 3 Nielsen JC et al Europace 1999;1:113-120

AAI Pacing: Too Risky?AAI Pacing: Too Risky?

• AAI pacing preserves a normal ventricular AAI pacing preserves a normal ventricular activation sequence but requires stable long-activation sequence but requires stable long-term AV conduction and sinus rhythmterm AV conduction and sinus rhythm

• SND is a spectrum of electrical disorders that SND is a spectrum of electrical disorders that includes AF and AV blockincludes AF and AV block

• AAI pacing is ineffectual for ventricular AAI pacing is ineffectual for ventricular bradycardia duringbradycardia during– Paroxysmal and permanent AF– AV block

Development of Persistent (Complete) AV Development of Persistent (Complete) AV Block in Studies of Pacemaker Therapy for Block in Studies of Pacemaker Therapy for

SNDSNDStudy Mean Follow-

Up TimeIncidence of

CHBAnnualized Incidence

Rosenqvist Rosenqvist 19891989(literature review)(literature review)

3 years3 years Median 2.1%Median 2.1%

Range: 0-Range: 0-11.9%11.9%

Median: 0.6%Median: 0.6%

Range: 0-4.5%Range: 0-4.5%

Andersen Andersen 19971997

8 years8 years 3.6%3.6% 0.6%0.6%

Brandt 1992Brandt 1992 5 years5 years 8.5%8.5% 1.8%1.8%

Sutton 1986Sutton 1986 3 years3 years 8.4%8.4% 2.8%2.8%

Rosenqvist Rosenqvist 19861986

2 years2 years 4.0%4.0% 2.0%2.0%

Rosenqvist Rosenqvist 19851985

5 years5 years 3.3%3.3% 0.7%0.7%

Hayes 1984Hayes 1984 3 years3 years 3.4%3.4% 1.1%1.1%

Development of Chronic AF in Studies of Development of Chronic AF in Studies of Pacemaker Therapy for SND and CHBPacemaker Therapy for SND and CHB

StudyPacing Mode

Mean Follow-Up

Time

Incidence of AF

Annualized

Incidence

Andersen Andersen 19971997

AAIAAI 5 years5 years 8.8%8.8% 1.8%1.8%

Sutton 1986Sutton 1986 AAIAAI 3 years3 years 4.5%4.5% 1.5%1.5%

Brandt 1992Brandt 1992 AAIAAI 5 years5 years 7.0%7.0% 1.4%1.4%

PASE 1998PASE 1998 DDDR DDDR onlyonly

18 months18 months 19.0%19.0% 12.7%12.7%

CTOPP 2000CTOPP 2000 DDDR/DDDR/

VVIRVVIR3 years3 years 16.6%16.6% 5.5% 5.5%

(DDDR)(DDDR)

DDIR Mode: A Limited SolutionDDIR Mode: A Limited Solution• Permits long AV delays without the possibility of upper Permits long AV delays without the possibility of upper

rate limit tracking during AF (unlike DDDR).rate limit tracking during AF (unlike DDDR).– However, limitations of long AV delays in reducing ventricular

pacing still persist.

• Unique limitations imposed by DDIR modeUnique limitations imposed by DDIR mode– Operationally VVIR during AV block if sinus rate exceeds lower

rate limit.– Competitive atrial pacing during sensor-modulation may

precipitate AF.• Can be mitigated with a non-competitive atrial pacing algorithm

• May be more applicable to the ICD populationMay be more applicable to the ICD population– Lower prevalence of AV block compared to conventional brady

pacing population.1-5

Novel Pacing Algorithms to Novel Pacing Algorithms to Optimize Ventricular Pacing Optimize Ventricular Pacing

• Current-generation devices have features Current-generation devices have features that work to minimize ventricular pacing in that work to minimize ventricular pacing in appropriate patient populations:appropriate patient populations:– Using Medtronic’s Search AV algorithm, 27%

and 47.2% reductions in ventricular pacing have been observed by Silverman and Ellenbogen, respectively, in patients with 1:1 conduction.1,2

Silverman et al, NASPE 2000

Novel Pacing Algorithms toNovel Pacing Algorithms toOptimize Ventricular Pacing Optimize Ventricular Pacing

• Minimal ventricular pacing modes can be used Minimal ventricular pacing modes can be used in all patients, but are most effective in SND in all patients, but are most effective in SND patients with reliable AV conduction and patients with reliable AV conduction and normal ventricular activation.normal ventricular activation.

• Development will continue on new pacing Development will continue on new pacing algorithms which have been identified as an algorithms which have been identified as an important means of minimizing ventricular important means of minimizing ventricular pacing.pacing.

Novel Pacing Algorithms to Novel Pacing Algorithms to Optimize Ventricular Pacing Optimize Ventricular Pacing

Identifying SND Patients for Identifying SND Patients for Optimize Ventricular Pacing Optimize Ventricular Pacing

• Suitable for all SND patients with reliable AV Suitable for all SND patients with reliable AV conduction and normal ventricular activation.conduction and normal ventricular activation.

• Factors that might constrain minimal ventricular Factors that might constrain minimal ventricular pacing modes in SND:pacing modes in SND:– incidence of AV block at time of pacemaker implantation,– incidence of abnormal ventricular activation at time of

pacemaker implantation– long-term stability of AV conduction– optimization of AV delay– development of chronic atrial fibrillation– rate-responsive atrial pacing with long AV delays

Overall ConclusionsOverall Conclusions

• Intact or intermittent 1:1 conduction is found Intact or intermittent 1:1 conduction is found in ~80+% of patients with sinus node in ~80+% of patients with sinus node dysfunction.dysfunction.

• In patients with SND and DDDR pacing In patients with SND and DDDR pacing systems, preserving 1:1 conduction:systems, preserving 1:1 conduction:– Reduces unnecessary ventricular pacing– Reduces the risk of CHF hospitalizations– Is associated with less AF– May increases device longevity

Overall ConclusionsOverall Conclusions• The long-term risks associated with chronic RV apical The long-term risks associated with chronic RV apical

pacing are now apparent.pacing are now apparent.

• Clinical attempts to preserve normal ventricular Clinical attempts to preserve normal ventricular activation sequence should be top priority.activation sequence should be top priority.

• AAI/DDI mode selections and long AV delays are AAI/DDI mode selections and long AV delays are limited solutions.limited solutions.

• Selective site pacing appears promising, but more Selective site pacing appears promising, but more studies are needed.studies are needed.

• Novel pacing algorithms have shown promise to Novel pacing algorithms have shown promise to date, and work will continue to improve these date, and work will continue to improve these algorithms to optimize the level of ventricular pacing.algorithms to optimize the level of ventricular pacing.

Documents

Optimizing Ventricular Pacing in Sinus Node Disease Michael O. Sweeney, MD Brigham and Women’s Hospital Assistant Professor of Medicine Harvard Medical