cardiac resynchronization therapycardiac resynchronization therapy* in patients with severe systolic...
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Cardiac
Resynchronization
Therapy
Reda Deyab, MD.
Associate Professor of Cardiology
Cairo University
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Heart failure is a clinical syndrome resulting
from a structural or functional cardiac disorder
that impairs the ability of the ventricle to fill with
or eject blood commensurate with the needs of
the body, or that precludes it from doing so in
the absence of increased filling pressure.
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Heart failure affects approximately 4.9 million
persons in the USA, and more than 500 000 new
cases of heart failure are reported each year.
In the USA, approximately 300 000 persons die of
heart failure each year.
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Heart failure is a considerable economic
burden, and the costs of hospitalization represent
65–75% of the total cost of treating a patient.
In the USA, the annual expenditures for
hospitalization for heart failure exceed $40
billion.
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Heart failure is the end stage of all diseases of the
heart and is a major cause of morbidity and
mortality.
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Disorders of the conduction system are often
associated with myocardial dysfunction. Indeed,
prolongation of QRS (120 ms) occurs in 14–47%
of patients with heart failure and is generally
accepted as occurring in approximately 30% of
all patients with low-LVEF heart failure
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Left bundle branch block (LBBB) occurs more
commonly than right bundle branch block
(RBBB) (25–36% vs 4–6%, respectively).
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Prevalence of Inter- or
Intraventricular
Conduction Delay
1 Havranek E, Masoudi F, Westfall K, et al. Am Heart J 2002;143:412-417 2 Shenkman H, McKinnon J, Khandelwal A, et al. Circulation 2000;102(18 Suppl II): abstract 2293 3 Schoeller R, Andresen D, Buttner P, et al. Am J Cardiol. 1993;71:720-726 4 Aaronson K, Schwartz J, Chen T, et al. Circulation 1997;95:2660-2667 5 Farwell D, Patel N, Hall A, et al. Eur Heart J 2000;21:1246-1250
IVCD 15%
IVCD >30%
General HF Population1,2 Moderate to Severe HF Population3,4,5
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Increased Mortality Rate with
LBBB Increased 1-year mortality with
presence of complete LBBB
(QRS > 140 ms)
Risk remains significant even
after adjusting for age,
underlying cardiac disease,
indicators of
HF severity, and HF
medications
Baldasseroni S, Opasich C, Gorini M, et al. Am Heart J 2002;143:398-405
11.9
5.5
16.1
7.3
0
5
10
15
20
All Cause Sudden Cardiac
All patients N=5517
LBBB N=1391 HR* 1.70
(1.41-2.05)
HR * 1.58
(1.21-2.06)
Cause of Death
1-Y
ear
Mo
rtality
(%
)
* HR = Hazard Ratio
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Based on left ventricular (LV) ejection fraction
(LVEF), patients with heart failure can be
divided into those with primarily systolic
dysfunction and those with diastolic
dysfunction.
Patients with a low LVEF, usually <45%, are
considered to have systolic dysfunction.
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Proposed Mechanisms of
Cardiac Resynchronization
Cardiac Resynchronization
Improved Intraventricular
Synchrony
Improved Atrioventricular
Synchrony
Improved Interventricular
Synchrony
Yu C-M, Chau E, Sanderson J, et al. Circulation 2002;105:438-445
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Summary of Proposed
Mechanisms
Yu C-M, Chau E, Sanderson J, et al. Circulation 2002;105:438-445
Intraventricular
Synchrony
Atrioventricular
Synchrony
Interventricular
Synchrony
LA
Pressure
LV Diastolic
Filling
RV Stroke
Volume
LVESV LVEDV
Reverse Remodeling
Cardiac Resynchronization
MR
dP/dt, EF, CO
( Pulse Pressure)
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Proposed Mechanisms: Improved
Intraventricular Synchrony
dP/dt 1,3,4 EF1,5
Pulse Pressure 3,4 SV&CO1, 2
Improved Intraventricular
Synchrony1,2
MR1
LVESV1
LA
Pressure1
1 Yu C-M, Chau E, Sanderson J, et al. Circulation 2002;105:438-445 2 Søgaard P, Kim W, Jensen H, et al. Cardiology 2001;95:173-182 3 Kass D Chen-Huan C, Curry C, et al. Circulation 1999;99:1567-73 4 Auricchio A, Ding J, Spinelli J, et al. J Am Coll Cardiol 2002;39:1163-1169 5 Stellbrink C, Breithardt O, Franke A, et al. J Am Coll Cardiol 2001;38:1957- 65
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Clinical Consequences of
Ventricular Dysynchrony Abnormal interventricular septal wall motion1
Reduced dP/dt3,4
Reduced pulse pressure4
Reduced EF and CO4
Reduced diastolic filling time1,2,4
Prolonged MR duration1,2,4
1 Grines CL, Bashore TM, Boudoulas H, et al. Circulation 1989;79:845-853. 2 Xiao, HB, Lee CH, Gibson DG. Br Heart J 1991;66:443-447. 3 Xiao HB, Brecker SJD, Gibson DG. Br Heart J 1992;68:403-407. 4 Yu C-M, Chau E, Sanderson JE, et al. Circulation. 2002;105:438-445.
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Achieving Cardiac Resynchronization
Mechanical Goal: Atrial-synchronized bi-ventricular
pacing Transvenous Approach
Standard pacing lead in RA
Standard pacing or defibrillation lead in RV
Specially designed left heart lead placed in a left ventricular cardiac vein via the coronary sinus
Right Atrial
Lead
Right Ventricular
Lead
Left Ventricular
Lead
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Echocardiographic parameters of intraventricular dyssynchrony.
• M-mode: Septal to posterior wall motion delay (>130 ms)
• 2D echo:
a. Aortic Pre-ejection interval >140 ms
b. Wall motion phase analysis (lateral delay >25°)
c. Contrast enhanced systolic regional fractional area
• TDI:
a. Difference in time to peak systolic velocity (4 segment >65 ms)
b. 12 segment LV dyssynchrony index >31 ms
c. Tissue tracking, strain and strain-rate imaging
d. TSI
• 3D
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ACC/AHA/HRS 2008 Guidelines for Device-
Based Therapy of Cardiac Rhythm
Abnormalities
May 2008
Slide Set
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Cardiac Resynchronization
Therapy* in Patients With Severe
Systolic Heart Failure
For patients who have left ventricular ejection fraction (LVEF) less than or equal to 35%, a QRS duration greater than or equal to 0.12 seconds, and sinus rhythm, cardiac resynchronization therapy (CRT) with or without an ICD is indicated for the treatment of New York Heart Association (NYHA) functional Class III or ambulatory Class IV heart failure symptoms on optimal recommended medical therapy.
For patients who have LVEF less than or equal to 35%, a QRS duration greater than or equal to 0.12 seconds, and AF, CRT with or without an ICD is reasonable for the treatment of NYHA functional Class III or ambulatory Class IV heart failure symptoms on optimal recommended medical therapy.
For patients with LVEF less than or equal to 35% with NYHA functional Class III or ambulatory Class IV symptoms who are receiving optimal recommended medical therapy and who have frequent dependence on ventricular pacing, CRT is reasonable.
I IIa IIb III
I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III
I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III
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Cardiac Resynchronization Therapy*
in Patients With Severe Systolic
Heart Failure For patients with LVEF less than or equal to 35% with NYHA functional Class I or II symptoms who are receiving optimal recommended medical therapy and who are undergoing implantation of a permanent pacemaker and/or ICD with anticipated frequent ventricular pacing, CRT may be considered.
CRT is not indicated for asymptomatic patients with reduced LVEF in the absence of other indications for pacing.
CRT is not indicated for patients whose functional status and life expectancy are limited predominantly by chronic noncardiac conditions.
I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III
I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III
I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III
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2012 ACCF/AHA/HRS Focus
Updates of 2008 guidelines
For patients who have left ventricular ejection fraction (LVEF) less than or equal to 35%, a QRS duration greater than or equal to 150 ms, and sinus rhythm, cardiac resynchronization therapy (CRT) with or without an ICD is indicated for the treatment of New York Heart Association (NYHA) functional Class II, III or ambulatory Class IV on GDMT ( level of evidence A for NYHA III,IV and B for NYHA II).
I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III
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2012 ACCF/AHA/HRS Focused
Updates of 2008 guidelines
I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III
CRT can be useful for patients who have left
ventricular ejection fraction (LVEF) less than or
equal to 35%, sinus rhythm, LBBB and a QRS
duration 129-149 ms for the treatment of New
York Heart Association (NYHA) functional Class II,
III or ambulatory Class IV on GDMT ( level of
evidence B).
New recommendation
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2012 ACCF/AHA/HRS Focused
Updates of 2008 guidelines
I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III
CRT can be useful for patients who have left
ventricular ejection fraction (LVEF) less than or
equal to 35%, sinus rhythm, non LBBB and a QRS
duration greater than or equal to 150 ms for the
treatment of New York Heart Association (NYHA)
functional Class III or ambulatory Class IV on
GDMT ( level of evidence B).
New recommendation
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2012 ACCF/AHA/HRS Focused
Updates of 2008 guidelines
I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III
CRT can be useful for patients who have AF with
left ventricular ejection fraction (LVEF) less than or
equal to 35% on GDMT if (A ) AV nodal ablation
or pharmacologic rate control will allow 100 %
pacing with CRT.
(B) The patient requirees ventricular pacing or met
CRT criteria. ( level of evidence B).
New recommendation
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2012 ACCF/AHA/HRS Focused
Updates of 2008 guidelines
CRT can be useful for patients who on GDMT
with left ventricular ejection fraction (LVEF)
less than or equal to 35% and undergoing
pacement of new or replacement of device
with anticipated more than 40 % ventricular
pacing . ( level of evidence C ).
New recommendation
I IIa IIb III
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2012 ACCF/AHA/HRS Focused
Updates of 2008 guidelines
I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III
CRT may be considered For patients who have
left ventricular ejection fraction (LVEF) less
than or equal to 30%, ischemic HF with sinus
rhythm, LBBB and a QRS duration greater than
or equal to 150 ms NYHA Class I symptoms on
GDMT. ( level of evidence C).
New recommendation
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2012 ACCF/AHA/HRS Focused
Updates of 2008 guidelines
CRT may be considered For patients who have
left ventricular ejection fraction (LVEF) less than or equal to
35%, sinus rhythm, non LBBB and a QRS duration 120-149 ms
and NYHA Class III/ ambulatory class IV symptoms on
GDMT. ( level of evidence B).
New recommendation
I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III
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2012 ACCF/AHA/HRS Focused
Updates of 2008 guidelines
CRT may be considered For patients who have left ventricular ejection fraction (LVEF) less than or equal to 35%, sinus rhythm, non LBBB and a
QRS duration equal to or more than 150 ms and NYHA Class II symptoms on GDMT. ( level of
evidence B).
New recommendation
I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III
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2012 ACCF/AHA/HRS Focused
Updates of 2008 guidelines
CRT is not recommended for patients
with NYHA Class I , II and non LBBB with
QRS duration less than 150 ms. ( level of
evidence B).
New recommendation
I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III
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2012 ACCF/AHA/HRS Focused
Updates of 2008 guidelines
CRT is not indicated for patients whose
comorbidities and/or frailty limit survival with good
functional capacity to less than 1 year. ( level of
evidence C).
I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III
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CRT Implantation
General Health
Good Bad
No
CRT
Sinus
Rhythm
Non sinus
Rhythm
Basic Rhythm
QRS
Morphology
LBBB Non LBBB
QRS
Duration
ms 120 to 149
LVEF ≥ 35
%
150 ms≤ 150 ms≤
NYHA II, III,
ambulatory IV NYHA III,
ambulatory IV
Class I indication Class II a
indication
NYHA II, III,
ambulatory IV NYHA III,
ambulatory
IV
Class II a
indication
Class II b
indication
New or replacement of
device with ≤ 40%
ventricular pacing
AF
CRT indication
AV nodal
ablation or drug
guaranteed 100 %
CRT pacing
Class II b
indication
EF ≤ 30 %
IHD
NYHA I class
Class II a
indication
NYHA II
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MUSTIC (NEJM 2001) Crossover CRT vs no CRT in patients with
CHF NYHA III, EF < 35%, QRS >
150 ms, LVEDD > 60 mm, NSR
58 6
Improved 6MWT < 0.001
QOL < 0.001
Hospitalization < 0.05
Peak VO2 < 0.03
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MIRACLE (NEJM 2002) Parallel arms CRT vs no CRT in patients
with CHF NYHA III, EF < 35%, QRS >
130 ms, LVEDD > 55 mm, 6MWT
< 450 m, NSR
453 6 Improved 6MWT 0.005
NYHA class < 0.001
QOL = 0.001
LVEF < 0.001
Peak VO2
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PATH-CHF (JACC 2002) Crossover CRT (LV or BiV) vs no CRT in
patients with CHF NYHA III-IV, EF
< 35%, QRS > 120 ms, PR > 150 ms,
NSR
41 12
Improved 6MWT =0.03
Peak VO2 0.002
QOL 0.062
NYHA class < 0.001
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MIRACLE ICD (JAMA 2003) Parallel arms CRT + ICD vs CRT in patients
with CHF NYHA III, EF < 35%, QRS
> 130 ms, LVEDD > 55 mm, cardiac
arrest due to VT/VF, spontaneous VT or
inducible VT/VF, NSR
369 6 Improved NYHA class
QOL
No change
6MWT
=
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MIRACLE ICD (JAMA 2003) Parallel arms CRT + ICD vs CRT in patients
with CHF NYHA III, EF < 35%, QRS
> 130 ms, LVEDD > 55 mm, cardiac
arrest due to VT/VF, spontaneous VT or
inducible VT/VF, NSR
369 6
Improved NYHA class 0.007
QOL 0.02
6MWT 0.36
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CONTAK CD (JACC 2003) Crossover, parallel controlled CRT vs no
CRT in patients undergoing ICD
implantation with CHF NYHA II-IV,
EF < 35%, QRS > 120 ms, NSR,
indications for ICD implantation
490 6
Improved 6MWT = 0.043
Peak VO2 0.030
LVEF < 0.001
LV volumes 0.02
No significant change
NYHA class = 0.10
QOL = 0.40
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COMPANION (NEJM 2004) Parallel arms Optimal pharmacological
therapy (OPT) vs CRT vs CRT + ICD
(CRT-D) in patients with CHF NYHA
III-IV, EF 35%, QRS > 120 ms
1520 16 Death or hospitalization for
CHF reduced by 34% in CRT,
40% in CRT-D
As compared to OPT <0.002
All cause mortality reduced by
36% in CRT-D
24% in CRT <0.001
=
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PATH-CHF II (JACC 2003) Crossover CRT (LV only) vs no CRT in
patients with CHF NYHA II-IV, EF
< 30%, QRS > 120 ms, NSR, Peak
VO2 < 18 ml/min/kg
86 6
Improved 6MWT 0.021
QOL 0.015
Peak VO2 <0.001
No benefit in QRS 120–150 ms
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CARE-HF (NEJM 2005) Open label, randomized Medical therapy
vs Medical therapy + CRT in patients
with CHF NYHA III-IV, EF 35%,
QRS > 120 ms with dyssynchrony ( aortic
preejection > 140 ms, interventricular
mechanical delay > 40 ms, delayed
activation of postlateral LV) QRS
> 150 ms (no dyssynchrony evidence
needed)
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All cause mortality/
hospitalization reduction
by 37% in CRT < 0.001
All cause mortality reduced by
36% in CRT < 0.002
Improvement in QOL < 0.01
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REVERSE [54] 2008 610 Parallel arm 12 Clinical composite score
LVESVI (mL /m2)
Time to hospitalization
hazard ratio (HR)
16% worsened
(CRT) vs.
21% (CON),
P = 0.10
18.4 with
CRT (P < 0.001)
0.47, P = 0.03
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MADIT- CRT trial
Fig. 4 Improved heart failure-free survival with
cardiac
resynchronization therapy (CRT) in patients with
New
York Heart Association (NYHA) class II heart
failure (HF) in
the MADIT-CRT trial. Reprinted from the New
England
Journal of Medicine, Vol 361, Moss et al.,
Cardiac-Resynchronization
Therapy for the Prevention of Heart-Failure
Events, 1329-38, 2009, with permission [65].
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Reverse Trial
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RAFT Trial
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Non Responder
It has been reported that 10–30% of patients
undergoing CRT either do not experience an
improvement or in fact may worsen following
implantation of a biventricular (BiV) pacing
system and therefore have been termed
‘nonresponders’.
1–3
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Non Responder
Significant controversy persists, however,
regarding the definition of non-response, as
some experts would argue that evidence of
reverse remodeling (defined as a decrease in
end-systolic volume of >15%) is necessary
in order to categorize a patient as a
Responder.
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Non Responder
whereas others maintain that
parameters such as functional class (New York
Heart Association (NYHA) classification), global
quality-of life-scores, and hospitalizations should
be included in defining success or failure of the
therapy.
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Goals of AV Optimization
Allow adequate time for passive filling of the ventricles
Atrial diastole
Allow adequate time for a complete atrial contraction
Atrial kick a.k.a. atrial contribution to ventricular filling
Allow for ventricular contraction
Ventricular systole
When AV timing is not optimized and is too short
Ventricular filling time may be cut short
The atrial kick can be cut short
Hemodynamics can be impaired
If AV timing is too long, intrinsic and dyssynchronous ventricular activity can break through
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Echo Doppler Waveform
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Mitral Velocity Doppler Echo
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Echo for CRT Optimization
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Aortic Velocity Time Integral
(VTI) Echo Measure speed of blood flow past the aortic valve during
systole
Aortic VTI is proportional to cardiac output (CO)
Using Aortic VTI Echo, adjust the AV delay until you
find the greatest possible VTI value, which would
correspond to the greatest CO
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Aortic VTI
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Non-Echo Means of Timing
Optimization Impedance cardiography (IC)
Transthoracic impedance measurements calculate changes in
stroke volume
IC testing is fast (~ 15 minutes) but requires special equipment
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Pulse pressure
Difference between systolic and diastolic blood pressure
For example, a patient with 120/80 mmHG blood pressure has
a pulse pressure of 40 (120 minus 80)
Patients with LV dysfunction typically have very low pulse
pressures (i.e., systolic and diastolic BP are close to the same)
Clinician finds the AV delay that corresponds to the greatest
pulse pressure (which means greatest stroke volume)
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AV Delays with CRT Stimulation
If the patient has a good underlying atrial rhythm,
optimize the sensed AV delay
The patient will likely spend most time in atrial
tracking (atrial sensing with ventricular pacing)
If the patient requires a lot of atrial pacing,
optimize the paced AV delay
The patient will mostly be paced in the atrium
Most patients fall somewhere in-between
For these patients, optimize both sensed and paced
AV delays!
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VV Timing Optimization
VV timing refers to the synchronization of RV and
LV contractions
Controlled by the interventricular delay
Programmable interval
Allows for simultaneous pacing (RV and LV together)
Allows for an offset (one ventricle before the other)
The goal of VV timing optimization is to get the
ventricles to contract as a unified whole
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