This document summarizes information on device therapy for congestive heart failure, including cardiac resynchronization therapy (CRT). It discusses: 1) The prevalence and mortality rates of heart failure in the US. Up to 30% of CHF patients have intraventricular conduction delays which increase mortality. 2) NYHA heart failure classifications and guidelines for CRT approval for classes III and IV. 3) Clinical trials that demonstrated the benefits of CRT including increased exercise capacity, quality of life, and decreased hospitalizations and mortality. 4) Anatomical challenges of CRT implantation via the coronary sinus and risks of the procedure. Proper lead placement is important to reduce asynchrony.

1. Device Therapy in Congestive
Heart Failure
by
Dr. Chetan swaroop
interventional cardiologist
associate director cardiology
SSB Hospital , faridabad

2. Congestive Heart Failure
400,000 5.0 million 250,000
Annual
Incidence
Heart Failure
Prevalence
Annual
Mortality
U.S.
 Up to 30 % of CHF patients have an IVCD (80% with a LBBB) which
has been linked to increases in mortality and morbidity.
 1-2% of the population and 6% of the population >65
 Prevalence is on the rise.

3. Class I
Asymptomatic
heart failure
ejection fraction
(EF) <40%
Class II
Mild symptomatic
heart failure
with ordinary
exertion
Class IV
Symptomatic
heart failure
at rest
Class III
Moderate
symptomatic
heart failure
with less than
ordinary exertion
NYHA Class-evaluates the disability
imposed on the patient
 The FDA and the ACC/AHA Guidelines have
approved biventricular pacing for class 3 and 4.

4. 17
8
20
15
9
19
7
6
4
42 41 39.7 44
11
0
10
20
30
CHF-STAT GESICA SOLVD V-HeFT I MERIT-HF CIBIS-II CARVEDILOL-US
Control
Group
Mortality
Total Mortality
Sudden Death
Total Mortality ~15-40%; SCD accounts for ~50% of the total deaths.
12 months 16 months
41.4 months 27 months
13 months
45 months 6 months
SCD Rates in CHF Patients with LV
Dysfunction

5. 60%
70%
80%
90%
100%
0 60 120 180 240 300 360
Days
Cumulative
Survival
Duration
(msec)
<90
90 120
120 170
170 220
• QRS duration is an
independent predictor
of mortality (>140 ms)
• Other factors are:
age, creatinine, EF,
and HR
.
-
-
-
QRS
-
-
-
>220
SCD in Heart Failure

6.  Degree of SCD risk by class
 Mortality in NYHA class II is 5 to 15%
 50 to 80% of the deaths are Sudden
 Mortality in NYHA class III is 20 to 50%
 Up to 50% of the deaths are Sudden
 Mortality in NYHA class IV is 30 to 70%
 5 to 30% of deaths are Sudden
SCD in Heart Failure

7. Right Ventricular Pacing
 RV apex pacing is harmful in patients with
LV dysfunction
 “Paced” LBBB
 Abnormal LV activation
 Reduced stroke volume

8. RV pacing
 MADIT II (2002) had a survival benefit
with the ICD but in a subgroup analysis,
there was an increase in heart failure
morbidity (more hospitalizations) felt due to
forced RV pacing compared to controls in
which no pacing was present.

9. MADIT II: Complications
New or Worsening HF
14.9%
19.9%
0.00%
10.00%
20.00%
Conventional Therapy ICD Therapy
(p= 0.09)
N= 490 N= 742
•RV pacing causes ventricular
dysynchrony and may lead to
worsening HF.
• Intrinsic ventricular activation is
better for ICD patients with left
ventricular dysfunction who do not
“need” pacing.
•<10% of ICD patients have a Class
I pacing indication at the time of
implant.
•Physicians, when appropriate,
should consider programming of
ICDs to avoid frequent RV pacing.

10.  ICD indication but no
indication for a
pacemaker
 Ef < 40%
 DDDR @ 70BPM
versus VVI 40 BPM
DAVID — Dual Chamber and VVI
Implantable Defibrillator Trial

11. The Concept
 In most patients with an IVCD (QRS > 130 ms) ,
the presence of atrial-biventricular (RV + LV)
pacing will provide early stimulation to an
otherwise late segment of electrical activation in
the LV.
 This should translate into an increase in the EF,
decrease of the LV dimension, improvement in the
QOL and NYHA class.
 This may translate into an decrease in CHF
exacerbations , hospitalizations and a decrease in
mortality.

12. The Cardiac
Resynchronization
Clinical Trials
PATH-CHF, MUSTIC, MIRACLE,
COMPANION, and CARE-HF*
*This is not a complete list of all the CRT trials and the dates given are
when the trial results were published.

13. Cumulative Enrollment in Cardiac
Resynchronization Randomized
Trials
0
1000
2000
3000
4000
1999 2000 2001 2002 2003 2004 2005
Results Presented
Cumulative
Patients
PATHCHF
MUSTIC SR
MUSTIC AF
MIRACLE
CONTAKCD
MIRACLEICD
PATHCHFII
COMPANION
MIRACLEICD II
CAREHF

14.  This was the first multicenter trial and used
the standard endocardial RV lead and an
epicardial LV lead via thoracotomy or
thorascope
 Single blinded RCT
 53 centers in Europe
 41 patients
PATH-CHF: 1999
Pacing Therapy for Congestive Heart Failure

15. Acute hemodynamic testing
Randomization 1:1
Best single chamber CRT
Best mode
No CRT
4 weeks
8 weeks
One year
NYHA class III-IV
DCM
QRS > 120 ms
PR>150
No CRT
Implant
CRT Best single chamber
12 weeks
PATH-CHF

16. PATH-CHF
 Primary endpoints
 Peak VO2
 Six-minute walk distance
 Secondary endpoints
 Minnesota Living with Heart Failure score (QOL)
 NYHA class
 EF
 Trend towards decrease in Hospitalizations
 Acute hemodynamic testing revealed that the lateral and
posterolateral walls were the best target sites.
 The best responders were those with QRS>150 , long PR and
dP/dt < 700 mm Hg/s

17. MUSTIC: 2001
Multicenter Stimulation in CM
 European study with 67 patients
 QRS>150, CHF, EF <35%
 BiVP versus backup VVI pacing at 40 BPM
 Increase in 6 minute walk time , QOL and Peak VO2
with BiVP and persisted for up to 12 months
 60% decrease in CHF hospitalizations
 First to use endocardial LV leads via the CS
 No significant change in mortality, but a trend
towards an improvement.
 Acute hemodynamic studies showed the mid lateral
wall to be the best site

18. MIRACLE:2002
Multi-center In Sync Randomized Clinical
Evaluation Trial
 Double blinded RCT
 First US trial
 Class 3 or 4, on OPT, QRS >130 ms, EF<35%
 Enrollment of 453 patients

19. MIRACLE
NYHA class III-IV
LVEDD > 60 mm
QRS > 130 ms
Stable 3 month regimen of beta-blocker/ACE inhibitor
EF < 35%
Randomization
CRT on
CRT on
1- and 3-month follow-up
6-month follow-up
CRT off
1- and 3-month follow-up
6-month follow-up
Long-term follow-up

20. Nonresponders: older, ischemic CM, no MR, QRS<150
Responders: had shorter duration on CHF and longer QRS>155
MIRACLE
39%
34%
27%
67%
17% 16%
0%
20%
40%
60%
Improved No Change Worsened
Proportion
Control N=225 CRT N=228
P < 0.001

21. MIRACLE
 There was a decrease in hospitalizations of 50% at 6 months
and a trend towards a decrease in mortality.
 All other primary and secondary endpoints were met: 6 minute
walk time, peak Vo2, QOL, EF , NYHA class, LVEDD
Magnitude of improvement not influenced by degree of QRS
shortening with BiVP (average in all was –20msec)

22. FDA Approval
 The first CRT device was
approved by the FDA in
September 2001 .
 The first CRT with an ICD was
approved by the FDA in May
2002 .

23.  MADIT 1 1996 required a positive EP study
 MUSTT 1999 required a positive EP study
 Madit 2 2002 prior MI (ischemic cardiomyopathy) and
EF<30% (no EP study required) ;60% had CHF and 50%
had QRS > 120 ms; resulted in a 31% decrease risk of
death and halted prematurely due to the positive effect of
the ICD: resulted in the FDA approving the ICD for
primary prevention this patient population, but only those
with a QRS > 120 ms.
The primary ICD prevention trials

24. The primary ICD prevention trial
 SCD-Heft 2005 The SCD-Heft trial
resulted in FDA approval of the ICD
January 2005 in patients with CHF and
EF<35 % that included both ischemic and
nonischemic cardiomyopathy for primary
prevention without a positive EP study or
ventricular ectopy . No QRS cutoff was
required.

25. ACC/AHA/NASPE 2002 Indications for
Cardiac Resynchronization Therapy
 Class II a ( Level A) Indication for Biventricular Pacing in
Dilated Cardiomyopathy
 Biventricular pacing in medically refractory,
symptomatic NYHA Class III/IV patients with
idiopathic dilated or ischemic cardiomyopathy,
prolonged QRS interval (130 msec), LV end diastolic
diameter 55mm, and LVEF 35%

26. COMPANION:2004
• OPT
1
• OPT
• CRT
+
2
• OPT
• CRT-D
+
2
Randomization
Comparison of Medical Therapy, Pacing
and
Defibrillation in Heart Failure

27. COMPANION
 Enrolled 1520 patients class 3 and 4, QRS >120ms
 Primary endpoint: death or hospitalization for any cause
 CRT met the primary endpoints and the CRT +/- ICD
significantly reduces mortality
 This was the first to show mortality benefit from CRT
alone
 Showed that patients with CRT also benefit from ICD therapy
 OPT had SCD in 36%, 23% in CRT and 2.9% in CRT+ICD

28. • CRT arm had 20% reduction in mortality and
hospitalization over OPT arm but it was not statistically
significant
• Significant reduction in CRT-ICD arm of 40% for
mortality over OPT arm (19% in OPT and 11% in CRT-
ICD group)
• Study was halted prematurely due to its positive benefit.
• Mean follow up was 16 months
COMPANION

29. CARE-HF : March 2005
 The effect of cardiac resynchronization on morbidity and
mortality in heart failure in 813 patients in Europe (
prospective multicenter RCT) with completed enrollment
by 2002
 Large patient size and length of trial (average follow up of
29 months) allowed ability to asses effects of CRT
 Looked at CRT alone (no ICD)
 Patients with class 3 or 4, EF < 35%, QRS >120 ms
 There was a 37% reduced mortality or first hospitalization
for a cardiac cause compared to OPT

30. CARE-HF
 All endpoints were met : EF, NYHA, QOL, BNP, Echo and
hemodynamic parameters
 33% of the deaths in the CRT group were due to SCD
 For every 9 devices, one death and 3 hospitalizations were
prevented
 Echo criteria in patients with QRS 120-149ms to look for
asynchrony (had to have 2 of 3)
 Aortic pre-ejection delay of > 140 ms ( onset of QRS to Aortic
ejection)
 Interventricular mechanical delay of >40 ms ( RV-LV)
 Delayed activation of the postero-lateral LV wall (>50ms)

31. RA Anatomy

32. Anatomical Challenges
 Enlarged right atrium
 Abnormal CS location
 Presence of valves in CS
 Altered CS angulation
 Acute branch take offs
 Tortuous vessel anatomy

33. CRT Procedure and Device Related
Risks relative to CS placement
 CS lead dislogdement 8%
 CS dissection or perforation 5%
 Failure of lead placement 8%
 Phrenic nerve stimulation 2%
 ALL other risks associated with pacer or ICD implantation
and anesthesia in these patients.

34. CS Leads they now come in many shapes and sizes and the the
OTW system

35. Achieving Cardiac
Resynchronization
Goal:Atrialsynchronous
biventricularpacing
Transvenous approachfor left ventricular lead via
coronarysinus
Back-upepicardial approach
Right Atrial
Lead
Right Ventricular
Lead
Left Ventricular
Lead

36. RAO is best
to
distinguish
BASE
position
from
APEX
BASE
APEX
Posterior
Anterior

37. LAO is best
to
distinguish
LATERAL
position
from
SEPTAL
ANTERIOR
INFERIOR
L
A
T
E
R
A
L
S
E
P
T
A
L
Anterior
Posterior
Lateral

38. LAO

39. The implant
 3 separate sticks via Seldinger technique in the subclavian
vein -can be done from the right but it is more difficult.
 Use standard peel back sheaths for the RA and RV leads
 The RV lead is positioned first - could develop CHB or VT so
it is good to have this in (screw-in or tined)
 Advance the long guide sheath into the RA ( not to the CS)
 Advance a Coronary Sinus EP catheter via the long guide
sheath into the CS – the LAO is the best: point towards the
spine.
 Advance the sheath while pulling back on the CS catheter to
get the sheath into the CS
 Some would use dye at this point to look at the anatomy of the
CS and its branches

40. The implant
 Advance the CS lead with or without the OTW system and
make sure you place it in a mid/lateral or posterolateral
position. Never go where the LAD would be but where the
obtuse marginals would be.
 Test the CS lead including at 10 volts for phrenic nerve
stimulation
 Pull back on the sheath until it is out of the OS, then peel it
out with a retention guide wire in the CS-be careful about
dislodgement
 Position the atrial lead in the RAA (screw-in or tined)
 Test the ICD with induction of VF twice separated by 3-5
minutes: can do at a later time if the time is > 4 hours or the
patient has been unstable in any way. Always use a high
energy device in these patients.

41. The 3 levels of asynchrony
1. Intraventricular asynchrony is best treated by
placing the LV lead in the best anatomic
location-usually the lateral or posterolateral
(proven my multiple studies). Get the LV working.
2. Interventricular asynchrony is dealt with by
adjusting the V-V interval. Get the RV and the LV
to work together.
3. A-V asynchrony is dealt with by adjusting the A-V
interval. Get the atria and the ventricles working
together.

42. Change in LVEF [%]
2%
9%
0%
2%
4%
6%
8%
10%
P=0.04
-9.2
-28.4
-30
-25
-20
-15
-10
-5
0
P=0.04
Change in LV
End-systolic Volume [ml]
Improvement
Posterolateral or Lateral walls are the best with LBBB where
the septum contracts first and then the lateral wall last.
Paced at any
other LV site
Paced at most
mechanically
delayed LV site

43. CRT and Tissue Doppler Imaging -a measure of
intraventricular delay
• Measures
dyssynchronous (delayed)
contraction patterns @
different areas of the
ventricle
•Measure from the onset
of the QRS to the peak
systolic shortening of that
segment
•Defined as a segment
with > 50 ms delay: this
indicates intraventricular
delay or asynchrony by
ECHO criteria
•Colors: green-
yellow-red (the
longest delay of >300
ms)

44. AV Delay Optimization Methods
1. Electrocardiographic
 COMPANION trial method
2. Echocardiographic (combined)
 Aortic velocity time integral (VTI) methods
 Mitral velocity Doppler methods:E and A waves
 Ritter formula
3. Hemodynamic measurements
 Pulse pressure method
 dP/dtmax method

45. COMPANION Method:
QRS < 150
Sensed AV Delay:
Intracardiac AV interval:
AS to VS = 300 ms
Intrinsic QRS duration:
QRS = 140 ms

46. COMPANION Method:
QRS >150
Sensed AV Delay:
Intracardiac AV interval:
AS to VS = 240 ms
Intrinsic QRS duration:
QRS = 180 ms

47. Aortic VTI Method
 Objective:
 Identify the AV Delay that yields the maximum cardiac output
as determined by an aortic VTI measurement
 Procedure:
 Obtain continuous wave Doppler echo of aortic valve outflow
to obtain VTI measurement
 Record VTI values over a range of programmed AV Delays
 Program the AV Delay value that yields the maximum aortic
VTI

48. Mitral Velocity Doppler Echo
Method
 Objective:
 Identify the AV Delay that maximizes LV filling using mitral velocity
echocardiographic measurements1
 Procedure #1: “A-wave cutoff”
 Obtain transmitral Doppler echo at a “long” programmed AV Delay
during ventricular pacing
 Shorten the programmed AV Delay by 10-20 ms until the echo Doppler
A-wave becomes truncated (A wave is atrial contraction)
 Lengthen the programmed AV Delay back to the value where there is no
A-wave cutoff. This timing should enable ventricular contraction to occur
just at the end of atrial systole

49. V-V Timing: synchronize the RV
and the LV
 The best V-V setting by measuring the RVOT and LVOT via
PW Doppler
 V-V above > 40 ms is considered abnormal
 In normals, the RV will contract before the LV in the heart by
-20 ms
 LV and RV have different outputs in the newer devices that
allow sequential instead of simultaneous delivery of output
and thus allow for this to be programmable.

50. Therapy for Heart Failure
 EF <40%…then need to evaluate patient for etiology
of cardiomyopathy and begin to optimize medical
therapy.
 If the patient is Class 3 or 4 ,
has a QRS> 130 ms,
has had a documented EF<35% for >9 months…
then consider for CRT-ICD.

51. Stages of Heart Failure

52. Summary
 Large number of patients studied in multiple RCTs.
 CRT improves quality of life, exercise capacity,
functional capacity, EF, peak VO2.
 CRT reduces the risk of mortality, worsening HF, and
hospitalizations for CHF.
 CRT + ICD significantly reduces risk of mortality.

53. Thank you