Transcript Cardiac Resynchronisation Therapy

Cardiac
Resynchronisation
Therapy
September 2008
The Effect of Cardiac Resynchronization on
Morbidity and Mortality in Heart Failure (CARE-HF)
John G.F. Cleland, M.D., Jean-Claude Daubert, M.D., Erland Erdmann, M.D., Nick
Freemantle, Ph.D., Daniel Gras, M.D., Lukas Kappenberger, M.D. and Luigi Tavazzi,
M.D.
N Engl J Med
Volume 352;15:1539-1549
April 14, 2005
Background
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Despite pharmacological advances in treatment of HF, mortality & morbidity
remain high
Cardiac dyssynchrony (regions of delayed myocardial activation &
contraction) is common
Small studies (up to 6/12) cardiac resynchronisation therapy (CRT)
improved quality of life, exercise capacity & ventricular function
Trials with CRT +/- ICD (COMPANION) showed that with CRT alone the
decrease in risk of death was insignificant
Meta-analysis are inconclusive
This trial was designed to assess the effect of CRT on mortality in patients
with severe HF
Methods
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Multicenter, randomised, non blinded, international trial comparing
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“the risk of complications & death of standard pharmacological
therapy alone with that of combination of standard therapy and CRT
(without ICD) in patients with LV systolic dysfunction, cardiac dyssynchrony
and symptomatic heart failure”
82 European centers between Jan 2001 & March 2003
Inclusion Criteria:
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18yrs+
HF for at least 6 weeks
NYHA III/IV
LVEF < 35%
QRS of at least 120ms
Exclusion Criteria:
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Conventional indications for PPM/ICD
Major CV event in last 6/52
HF requiring IV therapy
Atrial arrhythymias
Methods
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End Points
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Primary: Composite of death from any cause or an unplanned hospitalisation
for major CV event (worsening HF, MI, USA, Stroke, Arrhythmia)
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Secondary: Death from any cause, Quality of life assessment
Statistical Analysis
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Intention to treat Principle
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Statistical power of 80% to identify a 14% relative reduction given an α value of
0.025 & predicted number of events as 300
Baseline Characteristics of the Patients
Cleland, J. et al. N Engl J Med 2005;352:1539-1549
Kaplan-Meier Estimates of the Time to the Primary End Point (Panel A) and the Principal
Secondary Outcome (Panel B)
Cleland, J. et al. N Engl J Med 2005;352:1539-1549
Study Outcomes in Analyses Stratified According to NYHA Class
Cleland, J. et al. N Engl J Med 2005;352:1539-1549
Hemodynamic, Echocardiographic, and Biochemical Assessments
Cleland, J. et al. N Engl J Med 2005;352:1539-1549
Discussion
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CRT substantially reduced risk of complications & death among patients
with moderate/severe heart failure
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Consistent with a reduction in cardiac dyssynchrony leading to improved
physiological parameters and clinical outcome:
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Quality of Life
Ventricular function
Blood pressure
Mortality
For every 9 devices implanted 1 death and 3 hospitalisations are prevented
Cardiac Resynchronisation Therapy
Background1
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Approx 25% of patients with CHF have intraventricular conduction delay;
commonly LBBB
Electrical activation of lateral aspect of LV can be delayed in relation to that
of RV and/or interventricular septum
This results in
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Dyssynchronous electrical activation & contraction
Unequal distribution of myocardial workload
Altered myocardial blood flow & metabolism
Patients with conducting disease have worse prognosis from CHF
Patients with a paced RV end up having an artificially induced
interventricular conducting delay and overall systolic function is poorer
Procedure2
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Simultaneous pacing of RV & LV =
Biventricular pacing
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RA, RV & LV
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LV paced via coronary sinus
Physiological Effects
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Doesn’t restore normal physiological conducting pattern
RA pacing with short AV delay ensures all beats are paced
RV & LV pacing reduces the delay in electrical activation of LV free wall
QRS duration tends to decrease
Haemodynamic response:
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Increase in rate of rise of LV pressure
Increases pulse pressure, LV stroke volume
Improves myocardial function without increasing myocardial energy
consumption
Evidence
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Early Trials: <500 patients, up to 1 year showed increases in functional
capacity & improvements in quality of life
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COMPANION3 (ICD): mortality from all causes was reduced with CRT &
ICD (p=0.003) but not from CRT alone (p=0.059)
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CARE-HF4: mortality from all causes was reduced (p<0.002)
Guidance for CRT5
NICE May 2007; must fulfil ALL the below
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NYHA III or IV
SR with QRS >150ms
SR with QRS 120-149ms & echo evidence of dyssynchrony
LVEF < 35%
Optimal pharmacological therapy
Cost: £3809
Number: 500/year
Guidance for CRT-D6
NICE May 2007 & January 2006
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Criteria as before plus:
Primary Prevention
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MI (>4/52) & either (LVEF <35% and NSVT on holter and inducible VT on EP
studies) OR (LVEF <30% and QRS >120ms)
Familial Tendency (longQT, Brugada, HOCM, ARVD)
Secondary Prevention (in absence of treatable cause)
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Post VT/VF arrest
Spontaneous sustained VT causing compromise
Sustained VT without compromise but LVEF >35%
Cost: £16000
Number: 500/year
Adverse Effects
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Unable to implant LV lead due to unfavourable anatomy (3-10%)
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%)
Pneumothorax
Complete Heart Block
Asystole
Pacemaker pocket infection
External electromagnetic field
Further Study
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? Benefit in NYHA I/II patients
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Approx. 20-30% of patients with CRT are non-responders
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REVERSE7: no significance at end point
MADIT-CRT: late 2009
Is the QRS duration a good predictor of CRT response?
Could echo evidence of ventricular dyssynchrony be more predictive?8
“Dyssynhcrony study”9
Application in patients with AF?
References
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Jarcho JA. Biventricular Pacing. N Engl J Med 2006;355:288-294
http://content.nejm.org/cgi/content/full/355/3/288
Jarcho JA. Resynchronising Ventricular Contraction in Heart Failure. N Engl J Med 2005;352:1594-1597
http://content.nejm.org/cgi/content/full/352/15/1594
Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable
defibrillator in advanced chronic heart failure. (COMPANION) N Engl J Med 2004;350:2140-2150
http://content.nejm.org/cgi/content/full/352/15/1539
Cleland JGF, Daubert J-C, Erdmann E, et al. The effect of cardiac resynchronization on morbidity and
mortality in heart failure (CARE-HF) N Engl J Med 2005;352:1539-1549
http://content.nejm.org/cgi/content/full/350/21/2140
NICE: Heart Failure – Cardiac Resynchronisation; May 2007 http://www.nice.org.uk/TA120
NICE: Arrhythmias – Implantable Cardioverter defibrillators: January 2006 http://www.nice.org.uk/TA95
Linde C, Abraham WT, Gold MR, Daubert J-C. Results of the REVERSE trial. Program and abstracts from
the American College of Cardiology 2008 Scientific Sessions, March 29-April 1, 2008, Chicago, Illinois
http://www.medscape.com/viewarticle/573311
Yu CM, Bax JJ, Monaghan M, Nihoyannopoulos. Echocardiographic evaluation of cardiac dyssynchrony for
predicting a favourable response to cardiac resynchronisation therapy. Heart 2004;90:vi17-vi22
http://heart.bmj.com/cgi/content/full/90/suppl_6/vi17
Bax JJ, Ansalone G, Breithardt et al. Echocardiographic evaluation of CRT: ready for routine clinical use? J
Am Coll Cardiol 2004;44:1-9 http://content.onlinejacc.org/cgi/content/full/44/1/1