Cardiac Resynchronisation Therapy


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Cardiac Resynchronisation Therapy

  1. 1. Cardiac Resynchronisation Therapy September 2008
  2. 2. 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
  3. 3. Background <ul><li>Despite pharmacological advances in treatment of HF, mortality & morbidity remain high </li></ul><ul><li>Cardiac dyssynchrony (regions of delayed myocardial activation & contraction) is common </li></ul><ul><li>Small studies (up to 6/12) cardiac resynchronisation therapy (CRT) improved quality of life, exercise capacity & ventricular function </li></ul><ul><li>Trials with CRT +/- ICD (COMPANION) showed that with CRT alone the decrease in risk of death was insignificant </li></ul><ul><li>Meta-analysis are inconclusive </li></ul><ul><li>This trial was designed to assess the effect of CRT on mortality in patients with severe HF </li></ul>
  4. 4. Methods <ul><li>Multicenter, randomised, non blinded, international trial comparing </li></ul><ul><li>“ 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” </li></ul><ul><li>82 European centers between Jan 2001 & March 2003 </li></ul><ul><li>Inclusion Criteria: </li></ul><ul><ul><li>18yrs+ </li></ul></ul><ul><ul><li>HF for at least 6 weeks </li></ul></ul><ul><ul><li>NYHA III/IV </li></ul></ul><ul><ul><li>LVEF < 35% </li></ul></ul><ul><ul><li>QRS of at least 120ms </li></ul></ul><ul><li>Exclusion Criteria: </li></ul><ul><ul><li>Conventional indications for PPM/ICD </li></ul></ul><ul><ul><li>Major CV event in last 6/52 </li></ul></ul><ul><ul><li>HF requiring IV therapy </li></ul></ul><ul><ul><li>Atrial arrhythymias </li></ul></ul>
  5. 5. Methods <ul><li>End Points </li></ul><ul><ul><li>Primary: Composite of death from any cause or an unplanned hospitalisation for major CV event (worsening HF, MI, USA, Stroke, Arrhythmia) </li></ul></ul><ul><ul><li>Secondary: Death from any cause, Quality of life assessment </li></ul></ul><ul><li>Statistical Analysis </li></ul><ul><ul><li>Intention to treat Principle </li></ul></ul><ul><ul><li>Statistical power of 80% to identify a 14% relative reduction given an α value of 0.025 & predicted number of events as 300 </li></ul></ul>
  6. 6. Baseline Characteristics of the Patients Cleland, J. et al. N Engl J Med 2005;352:1539-1549
  7. 7. 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
  8. 8. Study Outcomes in Analyses Stratified According to NYHA Class Cleland, J. et al. N Engl J Med 2005;352:1539-1549
  9. 9. Hemodynamic, Echocardiographic, and Biochemical Assessments Cleland, J. et al. N Engl J Med 2005;352:1539-1549
  10. 10. Discussion <ul><li>CRT substantially reduced risk of complications & death among patients with moderate/severe heart failure </li></ul><ul><li>Consistent with a reduction in cardiac dyssynchrony leading to improved physiological parameters and clinical outcome: </li></ul><ul><ul><li>Quality of Life </li></ul></ul><ul><ul><li>Ventricular function </li></ul></ul><ul><ul><li>Blood pressure </li></ul></ul><ul><ul><li>Mortality </li></ul></ul><ul><li>For every 9 devices implanted 1 death and 3 hospitalisations are prevented </li></ul>
  11. 11. Cardiac Resynchronisation Therapy
  12. 12. Background 1 <ul><li>Approx 25% of patients with CHF have intraventricular conduction delay; commonly LBBB </li></ul><ul><li>Electrical activation of lateral aspect of LV can be delayed in relation to that of RV and/or interventricular septum </li></ul><ul><li>This results in </li></ul><ul><ul><li>Dyssynchronous electrical activation & contraction </li></ul></ul><ul><ul><li>Unequal distribution of myocardial workload </li></ul></ul><ul><ul><li>Altered myocardial blood flow & metabolism </li></ul></ul><ul><li>Patients with conducting disease have worse prognosis from CHF </li></ul><ul><li>Patients with a paced RV end up having an artificially induced interventricular conducting delay and overall systolic function is poorer </li></ul>
  13. 13. Procedure 2 <ul><li>Simultaneous pacing of RV & LV = Biventricular pacing </li></ul><ul><li>RA, RV & LV </li></ul><ul><li>LV paced via coronary sinus </li></ul>
  14. 14. Physiological Effects <ul><li>Doesn’t restore normal physiological conducting pattern </li></ul><ul><li>RA pacing with short AV delay ensures all beats are paced </li></ul><ul><li>RV & LV pacing reduces the delay in electrical activation of LV free wall </li></ul><ul><li>QRS duration tends to decrease </li></ul><ul><li>Haemodynamic response: </li></ul><ul><li>Increase in rate of rise of LV pressure </li></ul><ul><li>Increases pulse pressure, LV stroke volume </li></ul><ul><li>Improves myocardial function without increasing myocardial energy consumption </li></ul>
  15. 15. Evidence <ul><li>Early Trials : <500 patients, up to 1 year showed increases in functional capacity & improvements in quality of life </li></ul><ul><li>COMPANION 3 (ICD): mortality from all causes was reduced with CRT & ICD (p=0.003) but not from CRT alone (p=0.059) </li></ul><ul><li>CARE-HF 4 : mortality from all causes was reduced (p<0.002) </li></ul>
  16. 16. Guidance for CRT 5 <ul><li>NICE May 2007 ; must fulfil ALL the below </li></ul><ul><li>NYHA III or IV </li></ul><ul><li>SR with QRS >150ms </li></ul><ul><li>SR with QRS 120-149ms & echo evidence of dyssynchrony </li></ul><ul><li>LVEF < 35% </li></ul><ul><li>Optimal pharmacological therapy </li></ul><ul><li>Cost: £3809 </li></ul><ul><li>Number: 500/year </li></ul>
  17. 17. Guidance for CRT-D 6 <ul><li>NICE May 2007 & January 2006 </li></ul><ul><li>Criteria as before plus: </li></ul><ul><li>Primary Prevention </li></ul><ul><ul><li>MI (>4/52) & either (LVEF <35% and NSVT on holter and inducible VT on EP studies) OR (LVEF <30% and QRS >120ms) </li></ul></ul><ul><ul><li>Familial Tendency (longQT, Brugada, HOCM, ARVD) </li></ul></ul><ul><li>Secondary Prevention (in absence of treatable cause) </li></ul><ul><ul><li>Post VT/VF arrest </li></ul></ul><ul><ul><li>Spontaneous sustained VT causing compromise </li></ul></ul><ul><ul><li>Sustained VT without compromise but LVEF >35% </li></ul></ul><ul><li>Cost : £16000 </li></ul><ul><li>Number : 500/year </li></ul>
  18. 18. Adverse Effects <ul><li>Unable to implant LV lead due to unfavourable anatomy (3-10%) </li></ul><ul><li>Diaphragmatic stimulation due to proximity of phrenic nerve </li></ul><ul><li>Coronary sinus dissection (0.3-4.0%) </li></ul><ul><li>Coronary sinus perforation & tamponade (0.8-2.0%) </li></ul><ul><li>Periprocedural death (0.4%) </li></ul><ul><li>Dislodgement of LV lead (10%) </li></ul><ul><li>Pneumothorax </li></ul><ul><li>Complete Heart Block </li></ul><ul><li>Asystole </li></ul><ul><li>Pacemaker pocket infection </li></ul><ul><li>External electromagnetic field </li></ul>
  19. 19. Further Study <ul><li>? Benefit in NYHA I/II patients </li></ul><ul><ul><li>REVERSE 7 : no significance at end point </li></ul></ul><ul><ul><li>MADIT-CRT: late 2009 </li></ul></ul><ul><li>Approx. 20-30% of patients with CRT are non-responders </li></ul><ul><ul><li>Is the QRS duration a good predictor of CRT response? </li></ul></ul><ul><ul><li>Could echo evidence of ventricular dyssynchrony be more predictive? 8 </li></ul></ul><ul><ul><li>“ Dyssynhcrony study” 9 </li></ul></ul><ul><li>Application in patients with AF? </li></ul>
  20. 20. References <ul><li>Jarcho JA. Biventricular Pacing. N Engl J Med 2006;355:288-294 </li></ul><ul><li>Jarcho JA. Resynchronising Ventricular Contraction in Heart Failure. N Engl J Med 2005;352:1594-1597 </li></ul><ul><li>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 </li></ul><ul><li>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 </li></ul><ul><li>NICE: Heart Failure – Cardiac Resynchronisation; May 2007 </li></ul><ul><li>NICE: Arrhythmias – Implantable Cardioverter defibrillators: January 2006 </li></ul><ul><li>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 </li></ul><ul><li>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 </li></ul><ul><li>Bax JJ, Ansalone G, Breithardt et al. Echocardiographic evaluation of CRT: ready for routine clinical use? J Am Coll Cardiol 2004;44:1-9 </li></ul>