Cardiac resynchronization therapy (CRT) involves using a special pacemaker to coordinate the contractions of the left and right ventricles in patients with heart failure. CRT works by using biventricular pacing to improve the heart's efficiency. Several landmark studies found that CRT improves symptoms, cardiac function, and reduces mortality in patients with heart failure, low ejection fraction, and prolonged QRS duration. Echocardiography is used to identify mechanical dyssynchrony before CRT, but trials found echocardiography has limited ability to predict patient response compared to electrocardiogram criteria.

1. Cardiac Resynchronization
Therapy

2. Cardiac resynchronization therapy (CRT)
• CRT, first proposed in ’90s, is a treatment
for congestive heart failure (CHF) caused by
uncoordinated contraction pattern of the
heart muscle.
• CRT is a special type of pacemaker that
works by biventricular pacing.
• CRT improves the heart’s efficiency and
increases blood flow by coordinating
electrical timing and contraction of the heart
muscle.

3. 4
HEART
FAILURE  Definiton:
 A clinical syndrome resulting from any structuralor
functional cardiac defect
 The heart is unable to pump sufficiently to maintain blood
flow to meet the body's needs

4. 9
Types of HF
 According to cardiac output:
a. Low-Output Heart Failure
b. High-Output Heart Failure
 According to anatomical side
a. Left side heart failure
b. Right side heart failure
 According to onset
a. Acute heart failure
b. Chronic heart failure

5. 28
Classification of HF
 American College of Cardiology and theAmerican
Heart Association(ACC/AHA) Guidelines
 Stage A : High risk of HF, without structural heart
disease or symptoms
 Stage B : Heart disease with asymptomatic left
ventricular dysfunction
 Stage C : Prior or current symptoms of
HF
 Stage D : Advanced heart disease and severely
symptomatic or refractory HF

6. Heart failure treatment and role of CRT
Jessup M, Brozena S. Medical Progress--Heart Failure. N Eng J Med 2003; 348: 2007-2018. Copyright2002 MassachusettsMedicalSociety.
Allrightsreserved.

7. Indications
• 2008 ACC/AHA/HRS guidelines for device-based
therapy of rhythm abnormalities, the 2005 ACC/AHA
HF guidelines with 2009 focused update patients
with LVEF ≤35 percent, a QRS duration ≥120 ms,
SR, NYHA functional class III or ambulatory class IV
symptoms with optimal medical therapy [1A]
• Patients with LVEF ≤35 percent, a QRS duration
≥120 ms, AF, NYHA functional class III or
ambulatory class IV symptoms with optimal medical
therapy [11a, B]

8. Ventricular Dysynchrony
• Ventricular Dysynchrony
– Electrical: Inter- or
Intraventricular conduction delays typically manifested
as left bundle branch block
– Structural: disruption of myocardial collagen matrix
impairing electrical conduction and mechanical
efficiency
– Mechanical: Regional wall motion abnormalities with
increased workload and stress—compromising
ventricular mechanics

9. Prevalence of Electrical Ventricular
Dyssynchrony in Heart Failure
Left Bundle Branch Block More Prevalent
with Impaired LV Systolic Function
38%
24%
8%
Moderate/Severe
HF (2)
Impaired LVSF
(1)
Preserved LVSF
(1)
1. Masoudi, et al. JACC 2003;41:217-23
2. Aaronson, et al. Circ 1997;95:2660-7

10. 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
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-YearMortality(%)

11. Clinical Consequences of
Ventricular Dysynchrony
• Abnormal
interventricular
septal wall motion
• Reduced dP/dt
• Reduced pulse
pressure
• Reduced EF and
CO
• Reduced diastolic
filling time
• MR

12. Proposed Mechanisms: Improved
Intraventricular Synchrony
 dP/dt, EF
 Pulse Pressure  SV & CO
Improved Intraventricular
Synchrony
 MR
 LVESV  LA
Pressure

13. Cardiac Resynchronization
– By atrial synchronized biventricular pacing
• Tries at modification of interventricular, intraventricular, and
atrial-ventricular activation sequences in patients with
ventricular dysynchrony
• Acts as complement to optimal medical therapy by improving
mechanics of heart

14. Before CRT
After CRT

15. LVDd-59.3
LVEF-31%
LVDd-61.3
LVEF-51.3%

17. Mechanism of resynchronization
1. Contractile function- greater coordination of global
contraction
- Myocardial contraction Improved
- Normal increase in dP/dt
at high heart rates
- Increase in LVEF
Trials Comments
CARE HF
Median LVEF ~25% baseline
LVEF in CRT vs. no CRT [3.7% in 3 m, 6.9% in 18 m]
increased dP/dt, SBP ; reduced BNP
MIRACLE 6m LVEF [increase by 3.6%]

18. Regional Wall Motion With CRT: Improved
LVEF
Septum
Lateral
Pacing Off
Pacing On
RegionalFractionalAreaChange
Seconds 0.40
Seconds 0.40
Adapted from Kass DA. Rev Cardiovasc Med. 2003;4(suppl 2):S3-S13.
Adapted from Kawaguchi M, et al. J Am Coll Cardiol. 2002;39:2052-2058.

19. Mechanism of resynchronization
2. Reverse LV remodeling
LV EDV
ESV
Mass
? Molecular changes- homogenous activation of stress kinases &
reduced apoptosis
CARE –HF,
MIRACLE,
CONTAK CD,
PATH-CHF,
VIGOR-CHF
Trials Comments
Circulation 2005;
112:1580
[n=141; f/up 2 yrs]
Responders [>10% decrease in LV ESV]
62 % responders  reduction in all cause mortality (7vs31);
reduction in CV mortality (2.3 vs. 24); reduction in HF events (12
vs. 33)
Cond

20. Ventricular Reverse Remodeling
With Resynchronization
Adapted from Abraham WT, et al. N Engl J Med. 2002;346:1845-1853.
End-DiastolicDimension(mm)
EjectionFraction(%)
6.0
6.5
7.5
10
20
P<0.001
Placebo
n=81
CRT
n=63
CRT
n=61
P<0.001
Placebo
n=63
30
CRT 6-monthControl 6-month CRT

21. CRT
•Acute dec MR [quantitatively related to an increase in LV + DP/dt
max and transmitral pressure]
• Chronic
• dec MR due to reduced LV dimensions from remodeling
•Ameliorates delayed sequential activation of papillary muscles due to
intraventricular delay.
Mechanism of resynchronization
3. Reduction in functional MR
Imbalance between the closing and tethering forces that act on mitral
leaflets
• Tethering force- V. dilatation and increased chamber sphericity increase the distance
b/w the papillary muscles to the enlarged mitral annulus as well as to each other,
restricting leaflet motion and increasing the force needed for effective mitral valve
closure.
• Closing force- determined by the systolic LV-LA pressure difference (transmitral
pressure gradient) MR orifice area will be largely determined by the phasic changes in
transmitral pressure. [Increasing the transmitral pressure can reduce the EROA]
cont

22. Mechanism of resynchronization
4. Other mechanisms
– Increase in cardiac index and reduced PCWP
– Tolerate more aggressive medical therapies [ beta blockers]
– Improved diastolic functions
– Improvement in heart rate variability

23. 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)

24. Landmark Studies on CRT
• MIRACLE (The Multicentre Insync Clinical
Evaluation) Trial
• Companion (The comparison of Medical therapy,
pacing and defibrillation in heart failure)
• Care-HF (The Cardiac Resynchronization – heart
failure) Trial

25. MIRACLE Trial (2002, NEJM)
• First large scale, prospective, randomised, double-
blind trial of CRT
• 453 patients of NYHA III & IV, with
- LVEF equal/less than 35%
- QRS equal/greater than 130ms
• Compared CRT turned ON vs OFF for 6 months
• Results : Improved QoL, 6-MWD (39m vs. 10m), EF
(+4.6% vs. – 0.2%), improved NYHA class &
treadmill time, fewer hospitalisations

26. COMPANION Trial (2004, NEJM)
• First large-scale, randomised trial to show mortality-
benefit
• 1520 patients of NYHA III & IV, with
- LVEF equal/less than 35%
- QRS equal/greater than 120ms
• Compared Optimal pharmacology therapy vs. CRT
vs. CRT+ICD for 16 months
• Results : Death or hospitalization for CHF reduced
by 34% in CRT arm, 40% in CRT+ICD arm as
compared to pharmacology thearapy

27. CARE-HF Trial (2005, NEJM)
• NYHA class III or IV,LVEF<35%,LVEDD>30 mm
(indexed to height),QRS≥150 ms/>120 ms +echo
evidence of dyssynchrony, SR, no indication for pacing
• Primary end point-composite of death from any cause or
an unplanned hospitalization for a major cardiovascular
event
• Secondary outcome - death from any cause, composite
of death from any cause and hospitalization with heart
failure , NYHA class and quality of life
• OMT-404 patients Vs OMT+CRT-409,mean follow-up
29.4 months

28. Other Trials
• MUSTIC (2001, NEJM)
• PATH-CHF (2002, JACC)
• MIRACLE (2003, JAMA)
• CONTAK CD (2003, JACC)
• PATH-CHF II (2003, JACC)

29. Summary of Major Trials
• Significant clinical benefit of CRT in patients with class III-IV HF,
low EF, and QRS > 120
– Improvement in symptoms
– Improvement in objective standards of HF
• Meta-analysis
– 29% decrease in HF hospitalization (13% vs. 17.4%)
– 51% decrease in deaths from HF (1.7% vs. 3.5%)
– Trend toward decrease in overall mortality (4.9% vs 6.3%)
• BUT: >30% non-responders consistent through most trials

30. Imaging Measures of Mechanical
Dyssynchrony:
• 20-30% of patients with evidence of electrical
dyssynchrony do not benefit from CRT regardless of
baseline QRS duration and QRS narrowing with
CRT
• Imaging allows direct visualization of mechanical
dyssynchrony

31. ECHO in INTRAventricular Dyssynchrony
Estimation
• M-Mode Echo
• Tissue Velocity
• Strain Imaging
• Three Dimensional Echo

32. M-Mode
• Septal to posterior wall delay
• Measures time between maximal displacement of
septum and posterior wall (SPWMD)
• ≥ 130 ms considered significant
• Easy to perform
• No specific equipment needed

33. Copyright ©2008 American Heart AssociationAnderson, L. J. et al. Circulation 2008;117:2009-2023
M-mode echocardiography with color-coded tissue velocity. a, Timing of ventricular
septal (VS) wall motion is difficult to define because of its severe hypokinesis and
the lack of distinct peaks. b, Color coding of tissue velocity helps to identify the
exact wall motion timing as transition point of blue to red color for septal wall
(arrows) and red to blue color for posterior wall (arrowheads) (right)

34. M-Mode- SPWMD Disadvantages
• Can only be quantified in regions perpendicular to
U/S beam
• Only feasible in half of patients studied
• In several reports, septal-posterior wall delay didn’t
predict outcome after CRT
• Only assesses motion of septal and posterior walls

35. Tissue Velocity/Tissue Doppler Imaging
• Measurement of either longitudinal tissue velocity or
deformation
- 4-segment Model: Opposing wall peak delay of >
65 ms defines dyssynchrony
- Yu index: (12 segment model) Asynchrony Index ≥
31 ms
• High temporal resolution
• Color-coded TDI- allows simultaneous processing of
multiple samples from the same image

36. Tissue velocity waveforms in a normal subject from 4-
chamber (left), apical long-axis (middle), and 2-chamber
views (right)

37. Color-coded tissue velocity recordings from 12 LV segments before and
after CRT in 65-year-old patient with nonischemic cardiomyopathy whose
LVEF improved by 17% at 6 months after CRT
Before CRT
After CRT
Apical 4 Ch Long axis 2 Chamber

38. TDI as Predictor of Response to CRT
• Sensitivity and specificity of 80% to predict CRT
response at a cut-off level of 65 ms of LV
dyssynchrony
• Response defined as improvement in NYHA
class and 6 min walk
• Sensitivity and specificity of 96% and 76% to
predict reverse LV remodeling using cutoff of
31ms
• Response is defined as improvement of LVESV
of ≥ 15%

39. TDI - Disadvantages
• Susceptible to translational motion or tethering effect
• Color coding can vary with time window setting
• Requires specific equipment
• High variability of sensitivity and specificity in
different studies

40. Strain Imaging
• TDI-derived and Speckle tracking
• Abnormal strain pattern- premature early systolic
shortening of septum accompanied by lateral
prestretch and followed by postsystolic lateral wall
shortening
• Less affected by tethering / translational motion

41. Copyright ©2008 American Heart Association
Anderson, L. J. et al. Circulation 2008;117:2009-2023
Radial strain curves from short-axis view of speckle tracking
Echocardiography: Significant timing difference was found
among time to peak radial strain before CRT (a),
and it was reduced after CRT (b).

42. Strain imaging
• Dependent on image quality; not feasible in all
patients
• Mixed results with respects to predicting success
after CRT

43. 3-D Echo
• Only one image allows entire assessment
• Short-term improvements in 3-D dyssynchrony index
noted after CRT

44. Three Dimensional
Echocardiography

45. 3-D Echo
• No study to date shows 3D Echo predicts response
to CRT
• Highly dependent on image quality
• Incomplete inclusion of the apex
• Can’t perform in a-fib or rhythm with several ectopic
beats

46. ECHO in INTERventricular Dyssynchrony
• Difference in preejection period between PW doppler
in Ao and PA
- Correlates with QRSd
- Exceeds 40s in patients with QRDs>150 ms
- Shown to be predictive of response post-CRT in
SCART and CARE-HF trials
• TV delay between RV and LV free wall not predictive
of effect of CRT

47. Evidence for echo in predicting
CRT outcomes
• Limited echo-CRT studies with hard endpoints
• Thus far, trials have enrolled 4000 patients based on
ECG versus ~500 by echocardiogram
• PROSPECT Study- largest study

48. PROSPECT Trial
• 498 patients with standard CRT indications
• Twelve echocardiographic parameters of
dyssynchrony
• Positive CRT response were improved clinical
composite score and 15% reduction in LVESV at 6
months
• Ability of the 12 echo parameters to predict clinical
composite score response-
– sensitivity ranging from 6% to 74%
– specificity ranging from 35% to 91%

49. PROSPECT Conclusions
• Echocardiographic measures of dyssynchrony aimed
at improving patient selection criteria for CRT did not
have a clinically relevant impact on improving
response rates
• Echocardiographic parameters assessing
dyssynchrony do not have enough predictive value
to be recommended as selection criteria for CRT
beyond current indications

50. Role of CMR in CRT
• Venous anatomy
– assessed noninvasively to determine whether a transvenous
approach is feasible or surgical approach should be used for
LV lead placement
• Assessment of dyssynchrony:
– 77 patients undergoing CRT, those with a CMR-TSI ≥ 110
ms were more likely to meet the endpoints of death or
adverse cardiac events
– Leyva F et al:JACC 2007

51. Role of CMR in CRT
• Internal flow fraction fraction (IFF) is defined as the
total internal flow as a percentage of stroke volume
• IFF of 10 ± 5% in typical CRT patients (NYHA class
III or IV,LVEF < 35%, QRS > 150 ms) and of 1 ± 1%
in the healthy controls (p < 0.001)
• IFF cut-off of 4% discriminated b/w patients and
controls with 90% sensitivity and 100% specificity.
• Fornwalt et al (JMRI,2008)

52. Role of CMR in CRT
• Assessment of scar
– White et al-scar burden < 15% as the best cut-off for
predicting a clinical response to CRT
• LV lead placement
– pacing outside the LV free wall scar is associated with a
better response than pacing over thescar (86% vs 33%, p =
0.004)

53. Complications
• Diaphragmatic stimulation due to proximity of phrenic nerve
• Coronary sinus dissection (0.3-4.0%)
• Coronary sinus perforation & tamponade (0.8-2.0%)
• Periprocedural death (0.4%)
• Dislodgement of LV lead (10%)
• Facilitation of VT in select patients
• Pneumothorax
• Complete Heart Block
• Asystole
• Pacemaker pocket infection and bleeding
• Incmptibilty to External electromagnetic field

54. Phrenic nerve stimulation
A: LV lead positioned in lateral marginal vein. This site was rejected
due to phrenic nerve stimulation.
B: Repositioning of a larger diameter LV lead more proximally in the
same vein eliminated phrenic nerve stimulation.

55. Limitations
• Unable to implant LV lead due to unfavourable
anatomy (3-10%)
• CRT loss
• Non-response

56. LOSS of CRT
• Atrial undersensing in situations like
- Sinus tachycardia with 1st degree block
- AF & other SVTs with rapid ventricular conduction
- Lead dislodgement
• Ventricular oversensing
• Frequent ventricular ectopics
• Loss of LV capture d/t increased LV pacing threshold
• Fusion or Pseudofusion

57. High LV stimulation threshold
• A good lead position does not guarantee a good
response
• Scar burden- presence, location and/or extent of left
ventricular scar may impact response to CRT
Articles Comments
Circulation
2006;
113:969.
[n= 40, Cardiac MRI] 14 had transmural posterolateral scar 
lower response rate to CRT
Am Heart J
2007; 153:105
[n=50, SPECT imaging] Global scar burden, number of
severely scarred segments and scar burden near the LV lead
were all inversely correlated with increase in LVEF after CRT

58. Optimal LV lead placement
• Varies b/w patients
– Venous anatomy
– Regional and global LV mechanical function
– Myocardial substrate
– Characterization of electrical activation
• Success depends on pacing from a site which causes a
change in activation sequence improvement in cardiac
function
• Systolic improvement and mechanical resynchronization
does not always require electrical synchronization

59. Responders vs. non-responders
• Non-responders not properly defined
• 18-30% pts fail to respond clinically
• Reasons
– Delayed ventricular activation may not produce mechanical
dysynchrony
– Technical limitation ( no good site for pacing) MIRACLE
study up to 57% patients had suboptimal lead positioning
• QRSd >150, LV +dP/dt <700 mmHg/sec greatest
predictor of acute hemodynamic response to CRT

60. Responders vs. non-responders
• Specificity curve indicates
that 80% of nonresponders
have QRSd< 150ms
• Sensitivity curve indicates
that 80% of responders
have QRSd>150 ms
• CRT response is defined as
greater than 5% acute
increase in LV + dP/dt
Drawbacks
•In some cases of LBBB, RV activation may be more
prolonged than LV
•LBBB with no mechanical dysynchrony

61. Responders vs. non-responders
• Delay between the max. posterior displacement of
septum and max. displacement of the LV posterior wall-
[mean 192 ms to 14ms after 1m of CRT; responder 15%
improvement in LV sys volume index]
• Tissue doppler imaging [currently the most widely
studied method for direct measurement of dysynchrony]
• Baseline contractile function indexed by LV +dP/dt max
inversely correlate with improvement after CRT
• Cardiac MRI (CMR)

62. Responders vs. non-responders
• Myocardial strain imaging
• Electrical activation patterns assessed by electrophysiological
mapping
• Multicenter, prospective, nonrandomized study (PROSPECT)
(n= 498) 12 echo dysynchrony measures (including 7 TDI
parameters) offered only modest sensitivity (9 to 77 percent)
and specificity (31 to 93 percent) to predict clinical composite
score response; large variability in the analysis of the
dysynchrony parameters.
• Therefore, no single echocardiographic measure of
dysynchrony can be recommended to improve patient
selection for CRT

63. Responders vs. non-responders
• Non- responders
– Ischemic vs. non ischemic
– Males vs. females
– RBBB vs. LBBB
• Avoid
– RA pacing with DDD
– Interruption of CRT- atrial arrhythmias( MC), loss of LV
capture

64. Reasons for NON-Response
• Suboptimal HF drug therapy
• Significant MR
• Endstage HF
• Other co-morbidities like obesity
• Scar burden- presence, location and/or extent of left
ventricular scar may impact response to CRT

65. Reasons for NON-Response
• Device related issues like
- Ineffective BiV pacing
- Suboptimal AV & VV timing
- Suboptimal Lead placement
- Absence of mechanical dyssynchrony

67. Emerging Indications for CRT
• HF with narrow QRS
• HF with Atrial fibrillation
• Minimally symptomatic heart failure
• Acute decompensated heart failure
• Pacemaker-dependent Patients

68. CRT in HF with narrow QRS
• Early non-randomised and meta-analysis of these
trials showed improvements in
- NYHA class
- LVEF
- 6 min walk test
• RethinQ Prospective Randomised study, compared
CRT+ICD Vs ICD alone, contradicted earlier results
• Technical flaws emerged in RethinQ, further studies
are underway to elucidate the contradictions and to
define role in Narrow QRS

69. HF with Atrial Fibrillation
• In those patients who have HF, AF and meet
standard criteria for CRT
• Many observational studies and one Randomised
trial have showen benefits
• Benefit seen only when
- ventricular rate was well contolled before CRT
- AV node ablation was done to make ventricles
independent
(because rapid ventricular rate inhibits/interferes in
BiV pacing)

70. Minimally symptomatic HF
• Ventricular remodeeling effect of CRT prompted
studies of CRT use in NYHA I & II patients with
- LVEF equal/less than 40%
- QRS duration equal/greaater than 120ms
(REVERSE Trial)
• REVERSE trail showed statistically significant
improvement in CRT patients
• MADIT-CRT (LVEF-30, QRS-130, NYHA I & II)
showed similar results
• FDA has approved CRT in NYHA I & II with rEF,
wQRS

71. Acute Decompensated HF
• aka Acute CRT implantation in patients admitted in
ICU with systolic HF
• In general, wait till stabilization of patient is preferred
approach
• But, many use CRT as an option for stabilzation
itself
• Also in patients who meet CRT criteria and who:
- can’t be weaned off from inotropes
- responding poorly to aggressive HF Mx

72. Pacemaker-dependent Patients
• RV Pacing in longrun is a/w hemodynamic
derangemant, promotion of dyssynchrony and
worsening of LV function in patients with pre-existing
LV dysfunction
• This lead to investigations for usefulness of CRT to
attenuate negative impact of RV pacing
• CRT has been shown superior
• PACE Trial – in normal EF, standard indications for
pacing, compared RV Pacing vs. BiV pacing
• CRT shown to be superior but conclusive results still
not there