Transcript CRT Overview - February 2004

Cardiac Resynchronization
Therapy for Heart Failure
Patient Selection
and Clinical Outcomes
Edited by A kharazi M.D
cardiac electrophysiologist
Heart Failure (HF) Definition
A complex clinical syndrome in which the heart
is incapable of maintaining a cardiac output
adequate to accommodate metabolic
requirements and the venous return.
Etiology of Heart Failure
What causes heart failure?
• The loss of a critical quantity of functioning
myocardial cells after injury to the heart due
to:
– Ischemic Heart Disease
– Hypertension
– Idiopathic Cardiomyopathy
– Infections (e.g., viral myocarditis, Chagas’ disease)
– Toxins (e.g., alcohol or cytotoxic drugs)
– Valvular Disease
– Prolonged Arrhythmias
Prevalence of HF by Age and Gender
United States: 1988-94
10
8
Percent of
Population
Males
Females
6
4
2
0
20-24 25-34 35-44 45-54 55-64 65-74
Source: NHANES III (1988-94), CDC/NCHS and the American Heart Association
75+
New York Heart Association
Functional Classification
Class I:
No symptoms with ordinary activity
Class II:
Slight limitation of physical activity. Rest comfortable
but ordinary physical activity results in fatigue,
palpitation, dyspnea, or angina
Class III:
Marked limitation of physical activity. Comfortable at
rest, but less than ordinary physical activity results in
fatigue, palpitation, dyspnea, or anginal pain
Class IV:
Unable to carry out any physical activity without
discomfort. Symptoms of cardiac insufficiency may be
present even at rest
Poor Quality of Life for HF patients
Overall perception of health
70
General population
58
Depression
Angina
56
52
AF symptomatic
Valve disease symptomatic
48
Chronic Bronchitis
48
55
Heart Failure NYHA Class II
45
Heart Failure NYHA Class III
Heart Failure NYHA Class IV
36
Adjusted SF 36 means
Hobbs FDR, et al. Eur Heart J 2002;23:1867-1876
Doug Smith:
Severity of Heart Failure
Modes of Death
NYHA II
NYHA III
CHF
CHF
12%
Other
26%
59%
Sudden
Death
24%
64%
Other
15%
n = 103
Sudden
Death
n = 103
NYHA IV
CHF
Other
33%
56%
11%
Sudden
Death
n = 27
MERIT-HF Study Group. Effect of Metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL randomized
intervention trial in congestive heart failure (MERIT-HF). LANCET. 1999;353:2001-07.
Left Ventricular Dysfunction
Volume
Overload
Pressure
Overload
Loss of
Myocardium
Impaired
Contractility
LV Dysfunction
EF < 40%
 End Systolic Volume
 Cardiac
Output
Hypoperfusion
 End Diastolic Volume
Pulmonary Congestion
Treatment Approach for the Patient
with Heart Failure
Stage A
Stage B
Stage C
Stage D
At high risk, no
structural disease
Structural heart
disease,
asymptomatic
Structural heart
disease with
prior/current
symptoms of HF
Refractory HF
requiring
specialized
interventions
Therapy
Therapy
Therapy
Therapy
• Treat Hypertension
• All measures under
stage A
• All measures under
stage A
• All measures under
stages A,B, and C
• ACE inhibitors in
appropriate
patients
Drugs:
• Mechanical assist
devices
• Treat lipid
disorders
• Encourage regular
exercise
• Discourage alcohol
intake
• ACE inhibition
• Beta-blockers in
appropriate
patients
• Diuretics
• ACE inhibitors
• Beta-blockers
• Digitalis
• Dietary salt
restriction
• Heart
transplantation
• Continuous (not
intermittent) IV
inotropic infusions
for palliation
• Hospice care
Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management of
Chronic Heart Failure in the Adult, 2001
Diuretics, ACE Inhibitors
Reduce the number of sacks on the wagon
ß-Blockers
Limit the donkey’s speed, thus saving energy
Digitalis Compounds
Like the carrot placed in front of the donkey
Ventricular Dysynchrony
• Abnormal ventricular conduction resulting in a
mechanical delay
– Wide QRS (IVCD); typically LBBB morphology
– Poor systolic function
– Impaired diastolic function
ECG depicting interventricular conduction delay
Prevalence of Ventricular Dyssynchrony in
Heart Failure
Left Bundle Branch Block More Prevalent
with Impaired LV Systolic Function
Preserved LVSF
(1)
8%
Impaired LVSF
(1)
Moderate/Severe
HF (2)
1. Masoudi, et al. JACC 2003;41:217-23
2. Aaronson, et al. Circ 1997;95:2660-7
24%
38%
Elements of Cardiac Dyssynchrony
Atrioventricular
Intraventricular
Interventricular
Cazeau, et al. PACE 2003; 26[Pt. II]: 137–143
Intra-ventricular Dyssynchrony
Septal-Posterior Wall Motion Delay
• Difference in times from
peak excursions of the
septum and of the
posterior wall at the
papillary muscle level
• SPWMD  130 ms
predicted response
(LVEDVi) to CRT in study
of 25 pts with QRS  140
ms1
 From parasternal short-axis
view at papillary muscle level
1. Pitzalis M, et al. JACC 2002;40:1615-1622
septum
Posterior
wall
Parasternal Long-axis View Shown
Animation – Ventricular Dysynchrony
Click to Start/Stop
Etiology of Ventricular Dysynchrony
• What Causes Ventricular Dysynchrony?1
– Inter- or intraventricular conduction delays usually
manifested as left bundle branch block
– Regional wall motion abnormalities with increased
workload and stress—compromising ventricular
mechanics
– Disruption of myocardial collagen matrix impairing
electrical conduction and mechanical efficiency
1
2
• Estimated that 15% of all HF patients have
dysynchrony2
Tavazziventricular
L. Eur Heart J 2000;21:1211-1214.
Shenkman et al. Circulation 2000; 102(18):Suppl II, abstract 2293.
Clinical Consequences of
Ventricular Dysynchrony
•
•
•
•
Abnormal interventricular
septal wall motion1
Reduced dP/dt3
Reduced diastolic filling
time1,2
Prolonged MR duration1,2
Click to Start/Stop
1
Grines CL, Bashore TM, Boudoulas H, et al. Circulation 1989;79:845-853.
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.
2 Xiao,
Deleterious Effects of Ventricular
Dyssynchrony on Cardiac Function
Reduced diastolic filling
time 1
+ Weakened contractility
2
+ Protracted mitral
regurgitation 2
+ Post systolic regional
contraction 3
= Diminished stroke
volume
Courtesy of Ole-A. Breithardt, MD
1. Grines CL, et al Circulation 1989;79: 845-853
2. Xiao HB, et al Br Heart J 1991;66: 443-447
3. Søgaard P, et al. J Am Coll Cardiol 2002;40:723–730
Cardiac Resynchronization Therapy
• The therapeutic intent of
atrial-synchronized, biventricular pacing
is to restore ventricular synchrony
• Complements drug therapy
Cardiac Resynchronization Therapy
Goals
• Improve hemodynamics
• Improve Quality of Life
Cardiac Resynchronization Therapy
• Cardiac resynchronization, in
association with an optimized
AV delay, improves
hemodynamic performance by
forcing the left ventricle to
complete contraction and
begin relaxation earlier,
allowing an increase in
ventricular filling time.
• Coordinate activation of the
ventricles and septum.
ECG depicting IVCD
ECG depicting cardiac resynchronization
Cardiac Resynchronization Therapy
Increase the donkey’s (heart) efficiency
Achieving Cardiac Resynchronization
Goal: Atrial synchronous
biventricular pacing
Transvenous approach for left ventricular lead via
coronary sinus
Right Atrial
Lead
Back-up epicardial approach
Left Ventricular
Lead
Right Ventricular
Lead
Doug Smith:
Achieving Cardiac Resynchronization
Mechanical Goal: Pace Right and Left Ventricles
• Transvenous Approach
– Standard pacing leads in RA and RV
– Specially designed left heart lead placed in a left ventricular cardiac
vein via the coronary sinus
Cardiac Resynchronization System
Proposed Mechanisms of
Cardiac Resynchronization
•
Improved Contraction Pattern
•
AV Interval Optimization
Click to Start/Stop
CRT Improves Cardiac Function at
Diminished Energy Cost
MVO2/HR (Relative Units)
0.24
p< 0.05
0.22
Dobutamine
0.20
0.18
LV Pacing
0.16
0.14
500
600
700
800
dP/dtmax (mmHg/s)
Nelson et al. Circulation 2000;102:3053-3059.
900
1000
CRT Improves Cardiac Function
at 6 Months in Moderate to Severe Heart Failure
P=0.029
6
LVEF
4
Avg. Change
(Absolute %) 2
P<0.001
P=0.12
0
0
MR Jet Area -1
Avg. Change
-2
(cm2)
-3
P=0.58
Not
Reported
P<0.001
MIRACLE
MIRACLE ICD
Contak CD
 Control  CRT
Data sources: MIRACLE: Circulation 2003;107:1985-1990
MIRACLE ICD:JAMA 2003;289:2685-2694
Contak CD: J Am Coll Cardiol 2003;2003;42:1454-1459
LV Reverse Remodeling after CRT
LV End Systolic and
Diastolic Volumes
MR area
40
Pacing
No pacing
†
*
200
*
175
Mitral regurgitation (%)
Left ventricular volume (mL)
225
*
*
150
125
†
*
*
100
†
35
*†
*
†
30
*
25
*
*
1mo
3mo
20
15
*
*
10
Baseline
1wk
1mo
3mo
off-immed off-1wk
off-4wk
Baseline
1wk
N = 25
Yu CM, et al, Circulation 2002;105:438-445
off-immed off-1wk
off-4wk
Mortality/Morbidity Comparison
Risk reduction with CRT or CRT + ICD
Study
(n random.)
Follow
-up
Treatment
MIRACLE1
(n=453)
6M
CRT
JAMA metaanalysis2 (n=1634)*
3-6M
CRT
Mortality
&
Hosp.
Mortal.
& HF
Hosp.
Mortality
39%
27%
23%
HF
Mort.
HF
Hosp.
50%
51%
29%
* Includes MIRACLE
Date Sources:
1. Abraham WT, et al. N Engl J Med 2002;346:1845-53
2. Bradley DJ, et al. JAMA 2003;289:730-740
P < 0.05
CRT Improves Submaximal Exercise
Distance Walked in 6 Minutes
Change from Baseline*
60
P=0.004
P=0.003
50
Meters
P=0.005
Baseline (meters)
291 ± 101
CRT
40
30
20
Control
10
305 ± 85
0
0
* Paired median change
Error bars are 95% CI.
1
3
Follow-up Period (Month)
Abraham WT, Fisher WG, Smith AL, et al. N Engl J Med 2002;346:1845-1853
6
CRT Improves Patients’ Quality of Life
Minnesota Living with Heart Failure Questionnaire
Baseline (score)
59 ± 21
59 ± 20
Score Improvement (points)
Change from Baseline*
25
P<0.001
P<0.001
20
CRT
15
Control
10
5
0
0
* Paired median change
Error bars are 95% CI.
P=0.001
1
3
Follow-up Period (Month)
Abraham WT, Fisher WG, Smith AL, et al. N Engl J Med 2002;346:1845-1853
6
CRT Improves NYHA Functional Class
P<0.001
Number of Patients
120
52%
100
59%
80
60
30%
32%
40
16%
20
0
4%
6%
Improved 2 or
more classes
Improved 1
class
No Change
Control
Abraham WT, Fisher WG, Smith AL, et al. N Engl J Med 2002;346:1845-1853
CRT
2%
Worsened
CRT Improves Exercise Capacity in
Moderate to Severe Heart Failure
P<0.001
60
6 Min Walk
40
Avg. Change
(m)
20
P=0.36
P=0.029
P<0.001
0
-20
3
Peak VO2 2
Avg. Change
1
(mL/kg/min)
P=0.029
P<0.001
P=0.003
P=0.04
0
0
0
MIRACLE
MUSTIC SR
Data sources:
MIRACLE: Circulation 2003;107:1985-90
MUSTIC SR: NEJM 2001;344:873-80
MIRACLE ICD:JAMA 2003;289:2685-94
Contak CD: J Am Coll Cardiol 2003;2003;42:1454-59
MIRACLE ICD
Contak CD
 Control  CRT
Optimizing VV Delay Based on Aortic VTI
• Obtain Pulsed Wave
Doppler of LVOT with
several different
sequential ventricular
paced intervals
• Select the setting
yielding the largest
VTI as the optimal
paced interval
• CSA is assumed constant,
therefore optimal delay is
based on VTI alone
LV first by 4 ms
LV first by 20 ms
RV first by 40 ms
Relative Cost of CRT
Cost per patient
Total Annual Expenditures
Dialysis
CABG
PTCA
Hip/knee replace
CRT
CRT+ICD
$60
$40
$20
$ thousands
Doug Smith:
$0
$0
$5
$10
$ Billions
$15
$20
CRT: Moderate to severe systolic heart
failure with wide QRS
Jessup M, Brozena S. Medical Progress--Heart Failure. N Eng J Med 2003; 348: 2007-2018. Copyright 2002 Massachusetts Medical Society. All
rights reserved.
Cardiac Resynchronization Therapy
Patient Indications
CRT device:
– Moderate to severe HF (NYHA Class III/IV) patients
– Symptomatic despite optimal, medical therapy
– QRS  130 msec
– LVEF  35%
CRT plus ICD:
– Same as above with ICD indication
Conclusions
In NYHA Class III and IV systolic heart failure
patients with intraventricular conduction delays,
cardiac resynchronization therapy:
– is safe and well tolerated
– improves quality of life, functional class,
and exercise capacity
– Improves cardiac function and structure
– improves heart failure composite response
– may have a favorable effect on combined
measures of morbidity and mortality
Abraham WT, Fisher WG, Smith AL, et al. N Engl J Med 2002;346:1845-1853
Summary
• Large number of patients studied in RCTs
• Concordant proof that CRT improves quality of
life, exercise capacity, functional capacity
– Improvements persist through 1 year
• CRT reduces the risk of mortality and heart
failure due to worsening HF
• CRT + ICD reduces risk of mortality
• CRT improves cardiac function and structure