Optimizing Right Heart Pacing Site

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Optimizing Right Heart Pacing Site
2
What do we know about apical pacing?

• Altered left ventricular electrical and
  mechanical activation
• Altered ventricular function
• Less work produced for given LVEDV
• Delayed papillary muscle activation ? Valvular
  insufficiency
• Remodeling
• Modified regional blood flow patterns
• Increased oxygen consumption without increase in
  blood flow
• 60 change in blood flow between early and later
  activated regions
• Abnormal thickening of LV wall
• Cellular disarray
• Fibrosis (away from pacing lead location)
• Fat deposition
• Calcification
• Mitochondrial abnormalities

3
Altered LV Electrical Activation Pattern
Normal Sinus Rhythm
Right Ventricular Apical Pacing
Cassidy DM, et al. Circ 19847037-42
Vassallo JA, et al. JACC 198671228-33

• Two break-out locations on LV endocardium
• Inferior border of the mid-septum
• Superior basal aspect of free wall
• Latest activation
• Base of the inferior posterior wall
• Muscular conduction (less Purkinje fiber density)

• Single break-out location on LV endocardium
• Similar to left bundle branch block
• Latest activation
• Similar to intrinsic
• Inferioposterior base

4
Altered Left Ventricular Performance

• Wiggers (1925)
• The initial slower rise of intraventricular
  pressure is prolonged, isometric contraction
  phase is lengthened, the gradient is not so
  steep, the pressure maximum is lower, and the
  duration of systole is increased.
• Double contraction process
• Artificial stimuli induce local fractionate
  contractions ? Slow
• Impulse reaches the Purkinje system ? Rapid
• Lister (1964)
• Greater reduction in cardiac output when pacing
  from ventricular sites associated with longest
  total activation time ? muscle conduction
• Conduction velocity differences
• Purkinje 2-4 m/s
• Muscle 0.2-1 m/s

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Altered Left Ventricular Performance

• Boerth and Covell (1971)
• Reduced LV pressure, wall stress, and dP/dt
  despite normal perfusion
• Burkoff (1986)
• The more muscle mass activated by muscle
  conduction rather than Purkinje conduction, the
  weaker the beat ?? ineffective muscle mass
• Rosenqvist (1988)
• Increased incidence of congestive heart failure
  in ventricular paced patients

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Altered Myocardial Perfusion

• Heyndrickx (1985)
• Coronary blood flow was higher despite decreased
  cardiac output
• Prinzen (1990)
• Similarity in behavior of electrical activation,
  fiber strain and blood flow
• Redistribution of strain and blood flow with RV
  pacing
• Early activated regions 60 blood flow of late
  activated regions
• The regions of the heart activated via the
  Purkinje system (simultaneous activation) have
  greater fiber strain and blood flow

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Apical Pacing Histopathology

• Adomain (1986)
• Myofibril disarray was found in 75 of canine
  hearts after 3 months of pacing from RV apex
• Greatest at base of left ventricular free wall

• Karpawich (1990) Pediatric Canine Model
• LV myofibril disarray was found after 4 months
  of pacing from RV apex
• 90 degree misalignment of adjacent fibers
  (stress related?)
• Also noted appearance of prominent Purkinje cells
  in subendocardium, variable-sized mitochondria,
  and dystrophic calcification
• Karpawich (1999) Pediatric Patients
• Myofibril hypertrophy, intracellular vacuolation,
  degenerative fibrosis, and fatty deposits in the
  LV after more than 3 years RV apical pacing
• Independent of paced time, patient age, epi- or
  endocardial electrode placement, and mode

25X Karpawich PP, et al. Am Heart J
19901191077-83
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Human RV Apical Studies

• Impaired Diastolic Function
• Betocchi S, et al. JACC 1993211124-31
• Bedotto J, et al. JACC 199015658-64
• Stojnic B, et al. PACE 199619940-4
• Reduced Systolic Contraction
• Betocchi S, et al. JACC 1993211124-31
• Tse H and Lau C. JACC 199729744-9
• Altered Myocardial Perfusion
• Tse H and Lau C. JACC 199729744-9

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Pacing Mode Clinical Trials
DAVID Trial JAMA 20022883115-23 RV stimulation
may be more deleterious in patients with advanced
LV dysfunction (ICD candidates) DDDR-70 was
worse than VVI-40 more pacing (60) was seen in
DDDR-70 however, only 30.8 of the patients had
a QRSgt130ms
MOST Trial Sweeney M, et al. PACE
200225690 (mode selection trial in sinus-node
dysfunction) Hospitalization was not associated
with mode but with prevalence of more then 40 RV
pacing
Ventricular pacing, not a lack of AV synchrony,
is a more important predictor of LV dysfunction
Danish Pacemaker Study Andersen HR, et al. Lancet
19973501210-16 AAI vs. VVI for SSS Danish
pacemaker study AAI had slightly better survival
and was associated with lower occurrence of CHF
(native AV conduction is better)
Pacemaker Selection in the Elderly Lamas GA, et
al. NEJM 19983381097-1104 VVI vs. DDD for Sinus
Node Dysfunction or AV block no difference in
quality of life or outcome (CV or death)
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What are the Alternatives?

• Wiggers The shorter the distance for the impulse
  to travel to reach the Purkinje system, the more
  effective the contraction
• During direct ventricular stimulation, the
  contralateral ventricle contracts more
  effectively than the stimulated ventricle
• Contraction patterns can be normalized with
  pacing
• Despite increased dispersion of activation,
  duration of contraction is not affected with
  pacing (Boerth and Covell, 1971)
• Once the electrical activation reached the
  Purkinje system, the remaining fibers are
  activated quickly
• Different than left bundle branch block
• Electromechanical delay was longer but
  contraction time was shorter with pacing (Xiao,
  1993)

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Shortest Distance to Purkinje Fibers?
Right Ventricular Outflow Tract (RVOT) and/or
Right Ventricular Septum
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What Factors Need to be Considered?
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Are These Leads in the Same Location?
Tse HF, et al.JACC 2002401451-8
Bourke JP, et al. Europace 20024219-28
Victor F, et al. JACC 199933311-6
Conclusion No major differences but some
systolic improvement relative to RV apex after 6
months
Conclusion No hemodynamic benefit of RVOT pacing
relative to RV apex after 3 months
Conclusion RVOT pacing preserves LV systolic and
diastolic performance relative to RV apex after
6-18 months
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Definition of Sites

• Buckingham (1998)
• RVOT placed lead almost to the pulmonary
  valve, and then pulled back until the lead
  jumped and pointed in a lateral direction in
  the PA fluoroscopic view.
• High septal site in the trabeculated part of RV
• Giudici and Karpawich (1999)
• RV Inlet Septum Above, on, or beneath the
  annulus of the septal/anterior tricuspid valve
  leaflets. Relatively normal QRS morphology and
  axis.
• RV Infundibular Septum Proximal to the pulmonic
  valve distal to, or near, the crista
  supraventricularis. Left bundle branch, vertical
  axis.
• RV Outflow Septum Near the septal/moderator
  band insertion at the mid-position on the right
  ventricular septum. Left bundle branch, vertical
  axis.
• RV Apical Septum Proximal to the
  septal/moderator band continuity that does not
  typically produce a vertical QRS axis.

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Prevention of Remodeling with Septal Pacing

• Karpawich (1991)
• RV apical placement versus mid-septal placement
• Mid-septal lead position via appearance of normal
  paced QRS (no bundle branch block)
• Function
• Near normal ventricular conduction velocity
• Histology
• 4 month follow-up
• No calcification, degenerative changes, or
  altered mitochondrial morphology in the septal
  paced group

Karpawich PP, et al. Am Heart J 1991121827-33
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Mixed Results RVOT vs. RVA
?
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?
?
?
?
?
?
?
De Cock, CC, et al. Europace 20035275-8
Excluded 1) Indications other than symptomatic
brady (e.g., HOC) 2) Selective patient
populations (e.g., HF only) 3) Epicardial
placements
8 positive 1 negative 8 no difference
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Why are the Results Varied?

• Differences in historical studies
• Location in RVS and RVOT is unknown
• Non-physiological Pacing VVI not DDD
• Arbitrary AV delays in DDD similar for A-RVS and
  A-RVA?
• 30-50 msec delay in conduction between these
  sites
• Many studies Sites defined topographically
• Varied patient populations
• Co-morbidities?
• EF?
• QRS Duration?
• More chronic studies are needed

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Patient Populations More Benefit?

• Normal sinus rhythm no prior LV dysfunction
• Karpawich (1997)
• Pediatric patients with normal His-Purkinje
  conduction
• Acute septal pacing improves LV function relative
  to apical in the non-ischemic heart
• De Cock (1998)
• Acute RVOT pacing increased mean cardiac index
  relative to apical
• Wide variability
• Patients with CAD or EFlt50 showed decrease in
  function
• Kolettis (2000)
• Acute RVOT pacing improved LV diastolic
  relaxation relative to apical
• AV block mixed LV function
• Giudici (1997)
• Acute and chronic RVOT pacing improves LV
  function in AV block patients relative to apical
• Schwaab (1999)
• Acute septal pacing with decreased QRS increased
  ejection fraction relative to apical pacing
• Victor (1999)
• Chronic RVOT did not improve LV function relative
  to apical independent of baseline LVEF
• Safety of chronic RVOT was proven
• Bourke (2002)

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Patient Populations Less Benefit?

• Hypertrophic cardiomyopathy and outflow tract
  obstruction
• Fananapazir (1992, 1994)
• RVA pacing improves CO in hypertrophic
  obstructive cardiomyopathy
• Gadler (1996)
• RVA better than RVOT
• Dilated cardiomyopathy and symptomatic congestive
  heart failure
• Cowell (1994)
• EF lt 45 QRS gt 130 msec
• Cardiac output was higher in RVS relative to RVA
  with shorter AV delays
• Gold (1997)
• Class III or IV with SSS or AVB
• No improvement in function with VDD septal pacing
• Blanc (1997)
• Class III or IV with 1st degree AVB and/or BBB
• Inconclusive hemodynamic benefits of RVOT
• Some patients showed hemodynamic deterioration
• Gold (2000)
• Class II to IV with EF lt 35 QRS gt150 msec
• Acute RVOT high septum did not improve LV
  function relative to apical pacing

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The Debate on QRS Duration

• Shortest QRS duration has been used to identify
  optimal pacing site
• Harris (1999), Schwaab (1999)
• Critique Does QRS duration always reflect
  activation front?
• Foster (1995) Biventricular pacing improved
  function without shortening QRS duration
• Giudici (2003)
• RVOT Normalization of the axis of depolarization
• The wider the native QRS, the wider the RVOT
  paced QRS
• Involvement of the His-Purkinje system?
• CO is higher with RVOT vs. RVA in pts with narrow
  baseline QRS
• Going higher in the outflow tract did not result
  in narrower QRS or higher CO

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Optimal A-V Timing Site Specific

• Kosowsky (1968)
• Maintenance of AV contraction sequence is just as
  important as electrical activation
• Daggett (1970)
• Improvement of LV function with RV pacing site
  varies with different AV delays
• All Buckinghams studies used same AV delay (100
  msec)
• Studies have shown that short AV delays are
  optimal in most patients
• Rather than individual optimization, set to near
  normal value of 100ms
• No differences noted between RVOT and apical
  pacing
• Cowell (1994)
• Trend toward more improvement with shorter AV
  delays with septal versus apical pacing

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Where Does this Leave Us?

• More chronic studies with more selective patient
  criteria are needed
• Access and placement of leads in the RVOT/Septum
  is feasible
• Barin ES, et al. PACE 1991143-6
• Used RVOT because apex was inadequate (perf,
  thresh, diaphragmatic stim, sensing, etc.) No
  lead-related electrical difference from apical
  pacing
• Location of leads in alternate sites needs to be
  better documented
• AP and oblique images are needed to compare sites
  
• Role of paced QRS duration in hemodynamic
  function needs clarity
• More data is needed to confirm contribution of AV
  delay to hemodynamic function with alternate site
  pacing
• Individual optimization may be best alternative
• Patients with normal ventricular conduction
  distal to the AV node may show most benefit