Cardiac Resynchronisation Therapy

Cardiac Cardiac Resynchronisation Resynchronisation

TherapyTherapy

September 2008September 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 MedVolume 352;15:1539-1549

April 14, 2005

BackgroundBackground

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

MethodsMethods

Multicenter, randomised, non blinded, international trial comparing

“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: 18yrs+ HF for at least 6 weeks NYHA III/IV LVEF < 35% QRS of at least 120ms

Exclusion Criteria: Conventional indications for PPM/ICD Major CV event in last 6/52 HF requiring IV therapy Atrial arrhythymias

MethodsMethods

End Points

Primary: Composite of death from any cause or an unplanned hospitalisation for major CV event (worsening HF, MI, USA, Stroke, Arrhythmia)

Secondary: Death from any cause, Quality of life assessment

Statistical Analysis

Intention to treat Principle

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)


Study Outcomes in Analyses Stratified According to NYHA Class


Hemodynamic, Echocardiographic, and Biochemical Assessments


DiscussionDiscussion

CRT substantially reduced risk of complications & death among patients with moderate/severe heart failure

Consistent with a reduction in cardiac dyssynchrony leading to improved physiological parameters and clinical outcome:

Quality of Life Ventricular function Blood pressure Mortality

For every 9 devices implanted 1 death and 3 hospitalisations are prevented

Cardiac Resynchronisation Cardiac Resynchronisation TherapyTherapy

BackgroundBackground11

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 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

ProcedureProcedure22

Simultaneous pacing of RV & LV = Biventricular pacing

RA, RV & LV

LV paced via coronary sinus

Physiological EffectsPhysiological Effects

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:

Increase in rate of rise of LV pressure Increases pulse pressure, LV stroke volume Improves myocardial function without increasing myocardial energy

consumption

EvidenceEvidence

Early Trials: <500 patients, up to 1 year showed increases in functional capacity & improvements in quality of life

COMPANION3 (ICD): mortality from all causes was reduced with CRT & ICD (p=0.003) but not from CRT alone (p=0.059)

CARE-HF4: mortality from all causes was reduced (p<0.002)

Guidance for CRTGuidance for CRT55

NICE May 2007; must fulfil ALL the below

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-DGuidance for CRT-D66

NICE May 2007 & January 2006

Criteria as before plus: Primary Prevention

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)

Post VT/VF arrest Spontaneous sustained VT causing compromise Sustained VT without compromise but LVEF >35%

Cost: £16000

Number: 500/year

Adverse EffectsAdverse Effects

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 StudyFurther Study

? Benefit in NYHA I/II patients REVERSE7: no significance at end point MADIT-CRT: late 2009

Approx. 20-30% of patients with CRT are non-responders 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?

ReferencesReferences

1. Jarcho JA. Biventricular Pacing. N Engl J Med 2006;355:288-294 http://content.nejm.org/cgi/content/full/355/3/288

2. 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

3. 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

4. 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

5. NICE: Heart Failure – Cardiac Resynchronisation; May 2007 http://www.nice.org.uk/TA1206. NICE: Arrhythmias – Implantable Cardioverter defibrillators: January 2006 http://www.nice.org.uk/TA957. 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

8. 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

9. 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

Health & Medicine

Cardiac Resynchronisation Therapy