ΠΟΤΕ ΓΙΑΤΙ ΚΑΙ ΣΕ ΠΟΙΟΝ ΑΣΘΕΝΗ ΜΕ ΚΑΡΔΙΑΚΗ ΑΝΕΠΑΡΚΕΙΑ ΘΑ ΟΔΗΓΗΣΩ ΣΤΗΝ ΑΜΦΙΚΟΙΛΙΑΚΗ ΒΗΜΑΤΟΔΟΤΗΣΗ / ΑΠΙΝΙΔΩΣΗ

ΠΟΤΕ ΓΙΑΤΙ ΚΑΙ ΣΕ ΠΟΙΟΝ ΑΣΘΕΝΗ ΜΕ ΚΑΡΔΙΑΚΗ ΑΝΕΠΑΡΚΕΙΑ ΘΑ ΟΔΗΓΗΣΩ ΣΤΗΝ ΑΜΦΙΚΟΙΛΙΑΚΗ ΒΗΜΑΤΟΔΟΤΗΣΗ / ΑΠΙΝΙΔΩΣΗ ΕΦΡΑΙΜΙΔΗΣ ΜΙΧΑΛΗΣ MD Εργαστήριο Ηλεκτροφυσιολογίας Β Καρδιολογικής Κλινικής Νοσοκοµείο Ο ΕΥΑΓΓΕΛΙΣΜΟΣ

PATIENTS WITH NYHA ΙII-ΙV

All-Cause Mortality in CARE-HF 1.00 HR 0.64 (95% CI 0.48 to 0.85) Event-free Survival 0.75 0.50 0.25 CRT Medical Therapy P =.0019 Number at risk 0.00 0 500 1000 1500 Days CRT 409 376 351 213 89 8 Medical Therapy 404 365 321 192 71 5

NYHA III/IV Evidence is strongest for pts with typical LBBB Expectation of survival with good functional status for >1 year for CRT-D ESC Guidelines European Heart Journal 2010

CRT and RBBB

CRT and RBBB

CRT in IDC vs NIDC C. McLeod, Heart Rhythm 2011;8:377-382

Survival after CRT in IDC vs NIDC C. McLeod, Heart Rhythm 2011;8:377-382

Scar burden and CRT response E. Adelstein, European Heart Journal 2011; 32:93-103

Reverse Remodeling and Antiarrhythmic Effect

Antiarrhythmic Effect of Reverse Ventricular Remodeling Induced by Cardiac Resynchronization Therapy The InSync ICD (Implantable Cardioverter-Defibrillator) Italian Registry Biase L, J Am Coll Cardiol 2008;52:1442 9

Renal Function and CRT G. Lin European Heart Journal 2011;32:184-190

PATIENTS WITH NYHA I-II

NYHA II ESC Guidelines European Heart Journal 2010

REVERSE Study Determine if CRT ± ICD over 12 months can: Attenuate disease progression Reverse LV remodelling in patients with: NYHA Class I-II EF 40% QRS 120 ms

REVERSE: CRT reverses remodelling and improves LVESVi LVESVi (ml/mm 2 ) 115 110 105 100 95 90 85 80 75 0 Baseline P<0.0001 CRT off = -1.3 CRT on = -18.4 n=487 12 Months Linde et al. J Am Coll Cardiol 2008;52:1834-43

REVERSE: CRT delays time to first HF hospitalisation 15% P=0.03 Hazard Ratio=0.47 % of Patients Hospitalised for HF 10% 5% CRT OFF 53% reduction with CRT 0% CRT ON 0 3 6 9 12 Months Since Randomisation Number at Risk CRT OFF 191 187 181 176 119 CRT ON 419 415 411 409 251 Linde et al. J Am Coll Cardiol 2008;52:1834-43

REVERSE 24-months analysis: Time to First HF Hospitalisation or Death Percentage Hospitalised for HF or Died 30% 25% 20% 15% 10% 5% 0% Hazard Ratio: 0.38 95%CI: 0.20-0.73 P=0.003 CRT OFF CRT ON 0 6 12 18 24 Months Since Randomisation 24.0% 62% reduction with CRT 11.7% Number at Risk CRT OFF 82 79 76 70 39 CRT ON 180 176 173 168 77 Daubert C, J Am Coll Cardiol, 2009;54:1837-46

MADIT-CRT Design: ICD v CRT-D in mild Heart Failure Hypothesis: CRT-D will reduce the risk of mortality and HF events by ~25% Enrolment n=1820 Ischaemic (NYHA class I-II) Non-ischaemic (NYHA class II) EF 0.30% QRS duration 130 ms On optimal medical therapy Randomisation CRT-D therapy 3:2 CRT-D v ICD ICD therapy Follow up 1 month after randomisation Follow-up Event -driven 20-33 months Primary end point: Heart failure or death, whichever comes first Follow up visits every 3 months 38 Moss A, N Engl J Med 2009;361:1329-

MADIT-CRT CRT reduces Heart Failure events or Death Event rate HF and all-cause death 0.4 0.3 0.2 0.1 Primary endpoint (Heart Failure or death) p<0.001 ICD CRT-D 34% reduction with CRT-D 0.0 0 1 2 3 4 Years since randomisation Number at Risk ICD 731 621 379 173 43 CRT-D 1089 985 651 279 58 Moss A, N Engl J Med 2009;361:1329-38

MADIT-CRT Improvements in LV function with CRT-D Change from baseline in ml ICD Changes from baseline to 1-year follow-up LVEDV LVESV LVEF 11% -15 ml p<0.001 CRT-D -52 ml ICD -18 ml p<0.001 CRT-D -57 ml Change from baseline in % units 3% ICD CRT-D p<0.001 Moss A, N Engl J Med 2009;361:1329-38

MADIT-CRT in ischaemic and non-ischaemic patients A. Barsheshet, European Heart Journal 2011;32:1622-1630

RAFT Study

Patients with Atrial Fibrillation

Atrial Fibrillation ESC Guidelines European Heart Journal 2010

CRT and AF Gasparini M, J Am Coll Cardiol 2006;48:734-43

CRT and AF Gasparini M, Eur Heart J 2008;29:1644-52

CRT and the relationship of percent biventricular pacing D. Hayes, Heart Rhythm 2011; 8: 1469-75

HF and a concomitant Class I pacemaker indication ESC Guidelines European Heart Journal 2010

CRT Upgrade G. Frohlich European Heart Journal 2010;31:1477-1485

PATIENTS WITH NORMAL QRS

(RethinQ) Study Inclusion Criteria NYHA class III HF LVEF 35% Evidence of mechanical dyssynchrony QRS duration < 130ms Exclusion Criteria NYHA class I, II, or IV Permanent Atrial Fibrillation Recent MI, unstable angina or cardiac revascularization Prior cardiac resynchronization therapy

Results - Primary Endpoint Peak VO 2 (ml/kg/min) Median & 95% CI % Improved in Peak VO2 8 10 12 14 p = 0.75 0 20 40 60 80 100 41% Control n = 80 p = 0.63 46% CRT n = 76 Baseline 6-months Control (n = 80) CRT (n = 76) J. Beshai, N ENGL J MED 2007;357:2461-71

Peak VO 2 by sub-group Peak VO2 (% improved from baseline) Peak VO2 (% improved from baseline) 0 20 40 60 80 100 p = 0.02 CRT n = 17 Control n = 25 p = 0.45 Control CRT n = 55 n = 59 0 20 40 60 80 100 p = 0.82 Control CRT n = 41 n = 40 p = 0.25 CRT Control n = 36 n = 39 QRS 120 ms QRS < 120 ms Ischemic Non-ischemic J. Beshai, N ENGL J MED 2007;357:2461-71

Biventricular Pacing in Patients with Bradycardia and Normal Ejection Fraction

Biventricular Pacing in Patients with Bradycardia and Normal Ejection Fraction Yu C, N Engl J Med 2009;361:2123-34.

Biventricular Pacing in Patients with Bradycardia and Normal Ejection Fraction Yu C, N Engl J Med 2009;361:2123-34.

2-year results of the PACE trial J. Chan European Heart Journal 2011:1-8

Effectiveness of cardiac resynchronization therapy in heart failure patients with valvular heart disease

The InSync/InSync ICD Italian Registry *, Boriani G, European Heart Journal 2009; 30: 2275 2283

CRT in HOCM A. Berruezo, Heart Rhythm 2011;8:221-227

ΣΥΜΠΕΡΑΣΜΑΤΑ Η αµφικοιλιακή βηµατοδότηση µειώνει τη θνητότητα σε ασθενείς µε NYHA ΙII-ΙV Αναστρέφει την αρνητική αναδιαµόρφωση της αριστερής κοιλίας σε ασθενείς µε NYHA I-II. Υπόδιερεύνησηηεπίπτωσηστηνσυνολικήθνητότητασεασθενείςµε NYHA I-II. Οι ασθενείς µε στενό QRS δεν ωφελούνται. Στους ασθενείς µε κολπική µαρµαρυγή θα πρέπει να πράγµατοποιείται κατάλυση του κολποκοιλιακού κόµβου. Στους ασθενείς µε βαλβιδοπάθειες φαίνεται ότι το όφελος από τον αµφικοιλιακό βηµατοδότη-απινιδωτή να είναι το ίδιο µε τους ασθενείς µε ισχαιµική ή διατατική µυοκαρδιοπάθεια. Στους ασθενείς µε βραδυκαρδία και φυσιολογικό κλάσµα εξώθησης η αµφικοιλιακή βηµατοδότηση προλαµβάνει την αρνητική αναδιαµόρφωση της αριστερής κοιλίας αποτέλεσµα της δεξιάς κοιλιακής βηµατοδότησης.

Different ATP Sites in the termination of VT in CRT M. Haghjoo European Heart Journal 2011;13:509-513

RELEVANT Study FREEDOM FROM APPROPRIATE AND INAPPROPRIATE THERAPIES Gasparini M, European Heart Journal 2009; 30: 2758 2767

RELEVANT Study FREEDOM FROM HF HOSPITALIZATIONS European Heart Journal 2009; 30: 2758 2767

Impact of paced or intrinsic QRS morphology on outcomes and survival Wokhlu A, Heart Rhythm 2009;6:1439-1447

Impact of paced or intrinsic QRS morphology on outcomes and survival Wokhlu A, Heart Rhythm 2009;6:1439-1447

Cardiac resynchronization therapy utilization for heart failure: Findings from IMPROVE HF Curtis A, Am Heart J 2009;158:956-64.

Conclusions from RethinQ CRT did not improve Peak VO 2 during exercise in patients with NYHA Class III heart failure, QRS duration <130ms, EF 35% and mechanical dyssynchrony as specified in this trial. While there was a statistically significant improvement of NYHA class, a secondary endpoint, there was no improvement in quality-of-life, 6-minute walking test, or echocardiographic measures of reverse LV remodeling A subgroup of patients with QRS duration between 120 ms and 130 ms demonstrated an improvement from CRT, however patients with QRS duration < 120 ms did not demonstrate improvement The subgroup of patients stratified on the basis of cardiomyopathy etiology did not demonstrate an improvement in peak VO2.

Echocardiography and Noninvasive Imaging in Cardiac Resynchronization Therapy

Electrical or electromechanical dyssynchrony criteria to select pts for CRT? Electrical dyssynchrony does not always accompany mechanical dyssynchrony. Mechanical ventricular dyssynchrony is not always linked to electrical dyssynchrony.

Echocardiographic parameters for predicting CRT response PROSPECT Trial 498 pts EF 35% NYHA III-IV QRS 130ms Optimal pharmacologic therapy 12 echocardiographic parameters Clinical composite score 15% reduction in LVESV at 6 months Although several parameters predicted statistically significant improvement in clinical and reverse remodeling outcomes, sensitivity and specificity were modest Chung E, Circulation 2008;117:2608-2616

Echocardiographic parameters for predicting CRT response PROSPECT Trial Chung E, Circulation 2008;117:2608-2616

CRT-P or CRT-D?

CRT-P or CRT-D? COMPANION trial SCD-HeFT trial CARE-HF trial Class I: CRT-P to reduce morbidity and mortality Class I: CRT-D for pts who have expectancy of survival with good functional status for more than 1 year. The recommendation is based upon evaluation of the following 2 points: 1. The pt expectation of survival. ICD should exceed 1 year. 2. Cost considerations. ESC Guidelines. Europace 2007;9:959-998

SCD-HeFT Mortality Rate Non-Ischemic CHF Patients 0.5 Hazard Ratio (97.5% Cl) P-Value Amiodarone vs. Placebo 1.07 (0.76-1.51) 0.65 ICD vs. Placebo 0.73 (0.50-1.07) 0.06 Mortality Rate 0.4 0.3 0.2 Amiodarone Placebo ICD 0.1 0.0 0 12 24 36 48 60 No. at Risk Months of Follow-Up Amiodarone 419 388 369 257 150 51 Placebo 394 382 354 261 152 41 ICD 398 383 368 257 160 55 Bardy GH. N Engl J Med. 2005;352:225-237.

0.4 SCD-HeFT Mortality Rate Overall Results Hazard Ratio (97.5% Cl) P-Value Amiodarone vs. Placebo 1.06 (0.86-1.30) 0.53 ICD vs. Placebo 0.77 (0.62-0.96) 0.007 0.3 Mortality Rate 0.2 0.1 0.0 0 12 24 Months of Follow-Up No. at Risk Amiodarone 845 772 715 484 280 97 Placebo 847 797 724 505 304 89 ICD 829 778 733 501 304 103 36 Amiodarone Placebo ICD 48 60 Bardy GH. N Engl J Med. 2005;352:225-237.

APPROPRIATE AND INAPPROPRIATE THERAPIES IN PTS WITH ICD-CRT IMPALNTED FOR PRIMARY PREVENTION

MADIT-CRT: Similar benefits with CRT-D in ischaemic and non-ischaemic patients Variable Reduction p value Death or HF 34% 0.001 All patients Ischaemic patients Non-ischaemic patients Non-fatal HF 41% <0.001 All-cause death 0% 0.99 Death or HF 33% 0.003 Non-fatal HF 42% <0.001 All-cause death -6% 0.8 Death or HF 38% 0.01 Non-fatal HF 41% 0.01 All-cause death 13% 0.68 Moss A, N Engl J Med 2009;361:1329-38

MADIT-CRT in ischaemic and non-ischaemic patients A. Barsheshet, European Heart Journal 2011;32:1622-1630

Impact of CRT on symptoms and exercise tolerance Alleviation of symptoms Increase in exercise capacity NYHA Class decreases 6 min walk distance increases by a mean of 20%. Peak Oxygen consumption increases by 15%. Quality of life improves. Morbidity decreases Mortality decreases

Results - Secondary Endpoints Quality of Life Median & 95% CI NYHA Class 30 40 50 60 70 p = 0.91 0 20 40 60 80 100 p = 0.006 64% 54% 41% 29% 8%5% Baseline 6-months Improved No Change Worsened Control (n = 80) CRT (n = 76) Control (n = 80) CRT (n = 76) J. Beshai, N ENGL J MED 2007;357:2461-71

LV Volumes and Dimensions Change in LVEDV/ LVESV Median & 95% CI Change in LVEDD/ LVESD Median & 95% CI -40-20 0 10 p = 0.71 p = 0.81-4 -2 0 2 4 p = 0.49 p = 0.34 LVEDV LVESV LVEDD LVESD Control CRT J. Beshai, N ENGL J MED 2007;357:2461-71