2005 roma, convegno regionale, la terapia di resincronizzazione cardiaca nello scompenso cardiaco
•Download as PPT, PDF•
1 like•353 views
2005 roma, convegno regionale, la terapia di resincronizzazione cardiaca nello scompenso cardiaco
Recommended
Recommended
More Related Content
What's hot
What's hot (20)
Viewers also liked
Viewers also liked (16)
Similar to 2005 roma, convegno regionale, la terapia di resincronizzazione cardiaca nello scompenso cardiaco
Similar to 2005 roma, convegno regionale, la terapia di resincronizzazione cardiaca nello scompenso cardiaco (20)
More from Centro Diagnostico Nardi
More from Centro Diagnostico Nardi (20)
Recently uploaded
Recently uploaded (20)
2005 roma, convegno regionale, la terapia di resincronizzazione cardiaca nello scompenso cardiaco
- 1. ““ Cardiac Resynchronization Therapy ”Cardiac Resynchronization Therapy ” Stefano Nardi, MD AZIENDA OSPEDALIERA SANTA MARIA TERNIAZIENDA OSPEDALIERA SANTA MARIA TERNI DIPARTIMENTO CARDIOTORACOVASCOLAREDIPARTIMENTO CARDIOTORACOVASCOLARE STRUTTURA COMPLESSA DI CARDIOLOGIASTRUTTURA COMPLESSA DI CARDIOLOGIA UNITA’ OPERATIVA DI ARITMOLOGIA CARDIACAUNITA’ OPERATIVA DI ARITMOLOGIA CARDIACA LABORATORIO DI ELETTROFISIOLOGIA ED ELETTROSTIMOLAZIONELABORATORIO DI ELETTROFISIOLOGIA ED ELETTROSTIMOLAZIONE
- 2. NYHA CLASS Annualsurvival(%) Hospitalizations/year 100 75 50 25 0 I II III IV 1 10 Survival Hospitalization .1 Hospitalization / NYHA-class Cardiac Resynchronization TherapyCardiac Resynchronization Therapy
- 3. Quality of Life for HF patients Overall perception of health 36 45 55 48 48 52 56 58 70 Heart Failure NYHA Class IV Heart Failure NYHA Class III Heart Failure NYHA Class II Chronic Bronchitis Valve disease symptomatic AF symptomatic Angina Depression General population Hobbs FDR, et al. Eur Heart J 2002 Cardiac Resynchronization TherapyCardiac Resynchronization Therapy
- 4. Sinus node AV node Bundle branch or diffuse block Delayed conduction • Delayed AV sequence • Mitral regurgitation • Decreased filling time Delayed Ventricular ActivationDelayed Ventricular Activation What is abnormal in the HF pts?What is abnormal in the HF pts? Cardiac Resynchronization TherapyCardiac Resynchronization Therapy
- 5. SinusSinus nodenode AVAV nodenode BundleBundle branch orbranch or diffuse blockdiffuse block Delayed conductionDelayed conduction • Abnormal RV-LV sequence • Abnormal LV activation sequence • Segmentary dyskinesia • Aggravation of mitral regurgitation • Disynchrony of RV and LV filling flows Dyssynchrony Ventricular ContractionDyssynchrony Ventricular Contraction What is abnormal in the HF pts?What is abnormal in the HF pts? Cardiac Resynchronization TherapyCardiac Resynchronization Therapy
- 6. • Reduced LVEF remains the single most important risk factor for overall mortality and SCD.1 • Increased risk is measurable at EF above 30%, but an EF ≤30% is the single most powerful independent predictor for SCD.2 1 Prior SG, Aliot E, Blonstrom-Lundqvist C, et al. Task Force on Sudden Cardiac Death of the European Society of Cardiology. Eur Heart J, Vol. 22; 16; August 2001. 2 Myerburg RJ, Castellanos A. Cardiac Arrest and Sudden Cardiac Death, in Braunwald E, Zipes DP, Libby P, Heart Disease, A textbook of Cardiovascular Medicine. 6th ed. 2001. W.B. Saunders, Co., p. 895. Relationship of SCDRelationship of SCD and LV Dysfunctionand LV Dysfunction Cardiac Resynchronization TherapyCardiac Resynchronization Therapy
- 7. Which is the prognostic value of QRS width ? • VEST study analysis • NYHA Class II – IV pz • 3,654 ECGs digitally scanned • Age, creatinine, LVEF, heart rate, and QRS duration found to be independent predictors of mortality • Relative risk of widest QRS group 5x greater than narrowest 60% 70% 80% 90% 100% 0 60 120 180 240 300 360 Days in Trial CumulativeSurvival QRS Duration (msec) <90 90-120 120-170 170-220 >220 Adapted from Gottipaty et al. JACC 1999; 33(2):145A (abstract 847-4) Cardiac Resynchronization TherapyCardiac Resynchronization Therapy
- 8. CHF Population 6.5 Mio NYHA III + IV (30 - 35%) 1.95 Mio Wide QRS (10 - 30%) Resynchronization Rx Target Population: 195’000 650’000 Incidence = 580’000 (9.0%) Mortality = 300’000 (4.6%) CHF Population in EuropeCHF Population in Europe Cardiac Resynchronization TherapyCardiac Resynchronization Therapy
- 9. • WHO? Which criteria ? • WHEN? Which NYHA class ? • WHERE? RV+LV / LV ? • WHY? Symptoms / Mortality ? KEY QUESTIONSKEY QUESTIONS Cardiac Resynchronization TherapyCardiac Resynchronization Therapy
- 10. • Optimizes AV contraction sequence • Reduces pre-systolic mitral regurgitation • Improves atrial preloading of the ventricle • Increases filling time Mechanism IMechanism I Atrio-Ventricular SynchronyAtrio-Ventricular Synchrony Cardiac Resynchronization TherapyCardiac Resynchronization Therapy What does pacing changeWhat does pacing change??
- 11. OAVD Restores AV Synchrony PP RR INTRINSICINTRINSIC AorticAortic pressurepressure LVLV pressurepressure PPPP PeakPeak atrial systoleatrial systole Start ofStart of LV systoleLV systole Diastolic Mitral Regurgitation Maximum Effective Preload PP VV PACEDPACED PPPP SynchronizedSynchronized LV and atrialLV and atrial systolessystoles Auricchio et al, PACE 1998 Cardiac Resynchronization TherapyCardiac Resynchronization Therapy
- 12. • Optimizes ventricular activation • Increases pumping effectiveness • Reduces regional wall stress (WMSI) • Decreases mitral regurgitation • Resynchronizes ventricular filling flows • Decreases filling pressures Cardiac Resynchronization TherapyCardiac Resynchronization Therapy Mechanism IIMechanism II Ventricular CoordinationVentricular Coordination What does pacing changeWhat does pacing change??
- 13. LV Lead Implant Historical Evolution • Thoracic epicardial LV lead - 1994 1 • RV lead adapted for transvenous LV implant - 1996 2 • CS lead adapted for transvenous LV implant -1997 3 • Special designed transvenous LV lead - 1998 4 • Guiding catheter sheath for LV lead delivery -1998 5 1. Bakker et al. PACE 1994; 2. Cazeau et al. PACE 1996; 3.Daubert et al. PACE 1997; 4. Gras et al. PACE 1998 5. Lurie et al. Circulation 1998 Cardiac Resynchronization TherapyCardiac Resynchronization Therapy
- 14. Blanc et al., Circulation 199723 pts mean ± SD 90 100 110 120 130 140 150 SYSTOLICSYSTOLIC Blood PressureBlood Pressure RVARVA LV BVRVORVOBASBAS mmHgmmHg p<.01 p<.03 0 10 20 30 40 Pulmonary CapillaryPulmonary Capillary Wedge PressureWedge Pressure RVARVA LV BVBVRVORVOBASBAS p<.01 p<.01 Acute studies Cardiac Resynchronization TherapyCardiac Resynchronization Therapy
- 15. Kass et al,Kass et al, Circulation 99Circulation 99 IntrinsicIntrinsic PacedPaced 00 100100 200200 300300 00 4040 8080 120120 RV SeptumRV Septum 00 100100 200200 300300 00 4040 8080 120120 BiventricularBiventricular 00 100100 200200 300300 00 4040 8080 120120 RV ApexRV Apex 00 100100 200200 300300 00 4040 8080 120120 LV FreewallLV Freewall LV VolumeLV Volume (mL)(mL) LVPressureLVPressure (mmHg)(mmHg) LVPressureLVPressure (mmHg)(mmHg) LV VolumeLV Volume (mL)(mL) Acute studies Cardiac Resynchronization TherapyCardiac Resynchronization Therapy
- 16. Auricchio et al., NASPE ‘99 PATH-CHF: Inclusion Criteria (42 pts) • Dilated cardiomyopathy of any etiology • NYHA Class III (> 6 months) or NYHA IV • Optimal individual drug therapy • QRS duration >120 msec • PR Interval >150 msec • Sinus rate > 55 bpm • No conventional pacemaker indication PATHCHF Cardiac Resynchronization TherapyCardiac Resynchronization Therapy
- 17. 4 weeks 4 weeks One Year 4 weeks Acute Testing at Implant Randomization Prior to Discharge Pre-OP Evaluation Best Unichamber Biventricular No Pace No Pace Biventricular Best Unichamber Best Chronic Pacing Mode FlexStim PATH CHF: Study Design PATHCHF Cardiac Resynchronization TherapyCardiac Resynchronization Therapy
- 18. MUSTIC Inclusion Criteria (67 pts) • Dilated cardiomyopathy of any etiology • NYHA Class III • Optimal individual drug therapy • LBBB and QRS duration >150 msec • LVEF<35% and LVEDD>60mm • 6-MWT<450m • SR & no conventional pacemaker indication Cardiac Resynchronization TherapyCardiac Resynchronization Therapy
- 19. Results Active pacing Inactive pacing p 6-min w (m) 399 ± 100 326 ± 134 .0001 QOL score 29.6 ± 21.3 43.2 ± 22.8 .0002 VO2 (ml/min/Kg) 16.2 ± 4.7 15 ± 4.9 0.02 S.Cazeau et al NEJM 2001;344:873-80S.Cazeau et al NEJM 2001;344:873-80 Cardiac Resynchronization TherapyCardiac Resynchronization Therapy MUSTIC Results (67 pts)
- 20. Baseline 1wk 1mo 3mo off-immed off-1wk off-4wk 10 15 20 25 30 35 40 * * † * * * † † Mitralregurgitation(%) MR area Baseline 1wk 1mo 3mo off-immed off-1wk off-4wk 100 125 150 175 200 225 * * * * † * * * † Leftventricularvolume(mL) * LVESV and LVEDV LV Reverse Remodeling Pacing No pacing N = 25 Cardiac Resynchronization TherapyCardiac Resynchronization Therapy MUSTIC Results (67 pts)
- 21. MIRACLE Inclusion Criteria (571 pts) • Moderate or severe HF (NYHA III-IV) • Stable optimal HF medical therapy regimen for >1mo Diuretics (93-94%) ACE-I or ARB (90-93%) if tollerated β-blocker (55-62%) at stable regimen for>3 months • QRS duration ≥150 msec • LVEF ≤35% or LVEDD ≥55mm (echo measure) • Sinus rate > 55 bpm • 6 MWT <450m Cardiac Resynchronization TherapyCardiac Resynchronization Therapy Abraham WT, Fisher WG, Smith AL, et al. N Engl J Med 2002;346:1845-1853
- 22. Change in MR Jet AreaChange in MR Jet Area -4-4 -3-3 -2-2 -1-1 00 11 ControlControl (n=118)(n=118) CRTCRT (n=116)(n=116) cmcm22 P<0.001P<0.001 P=0.009P=0.009 Change in LVEDDChange in LVEDD -6-6 -4-4 -2-2 00 22 ControlControl (n=118)(n=118) CRTCRT (n=116)(n=116) mmmm P<0.001P<0.001 Absolute Change in LVEFAbsolute Change in LVEF -2-2 00 22 44 66 88 ControlControl (n=146)(n=146) CRTCRT (n=155)(n=155) %% Baseline (mm)Baseline (mm) 69 ± 10 70 ± 10 Baseline (cmBaseline (cm 2 ) 7.2 ± 4.9 7.6 ± 6.4 Baseline (%)Baseline (%) 22 ± 6 22 ± 6 Paired median change from baseline at 6 months Cardiac Function and Structure Cardiac Resynchronization TherapyCardiac Resynchronization Therapy MIRACLE
- 23. Improvement in Peak VOImprovement in Peak VO22 -0.5-0.5 0.00.0 0.50.5 1.01.0 1.51.5 2.02.0 ControlControl (n=145)(n=145) CRTCRT (n=158)(n=158) ml/kg/minml/kg/min P=0.009P=0.009 Improvement inImprovement in Total Exercise TimeTotal Exercise Time 00 3030 6060 9090 120120 ControlControl (n=146)(n=146) CRTCRT (n=159)(n=159)secondsseconds P=0.001P=0.001 BaselineBaseline (ml/kg/min)(ml/kg/min) 13.7 ± 3.8 14.0 ± 3.5 BaselineBaseline (secondsseconds) 462 ± 217 484 ± 209 Metabolic Exercise Cardiac Resynchronization TherapyCardiac Resynchronization Therapy MIRACLE Abraham WT, Fisher WG, Smith AL, et al. N Engl J Med 2002;346:1845-1853
- 24. VO2(ml/min/mVO2(ml/min/m22 )) DODO22 (ml/min/m(ml/min/m22 )) Cardiac Resynchronization TherapyCardiac Resynchronization Therapy OO22ERER Critical DOCritical DO22 DISOXIADISOXIA Critical VOCritical VO22 VOVO22 == DODO22 XX OO22ERER NormalNormal Myocardial Oxidative Metabolism
- 25. Control 225 214 204 197 191 179 70 CRT 228 218 213 209 204 201 99 Patients At RiskPatients At Risk 70%70% 75%75% 80%80% 85%85% 90%90% 95%95% 100%100% 00 11 22 33 44 55 66 Months After RandomizationMonths After Randomization EventFreeEventFreeSurvivalSurvival(%)(%) CRTCRT ControlControl P = 0.033P = 0.033 Relative risk = 0.60;Relative risk = 0.60; 95% CI (0.37, 0.96)95% CI (0.37, 0.96) Time to Death or Worsening HF requiring Hospitalization Cardiac Resynchronization TherapyCardiac Resynchronization Therapy MIRACLE
- 26. Survival 80% 85% 90% 95% 100% 0 1 2 3 4 5 6 Months Since Randomization %ofPatientsSurviving Control n=402 CRT n=415 P=0.42 W.T. Abraham for MIRACLE and MIRACLE ICD Investigators Cardiac Resynchronization TherapyCardiac Resynchronization Therapy MIRACLE and MIRACLE ICD Trials
- 27. QOL & Functional Capacity 6 Months in Moderate to Severe HF -20 -15 -10 -5 0 P<0.001 P=0.02 P=0.017P<0.001 QoL Score (MLWHF) Avg. Change 0% 20% 40% 60% 80% MIRACLE MUSTIC SR MIRACLE ICD Contak CD P<0.001 P=0.006P=0.007 Data sources: MIRACLE: Circulation 2003;107:1985-90 MUSTIC SR: NEJM 2001;344:873-80 MIRACLE ICD:JAMA 2003;289:2685-94 Contak CD: JACC 2003;2003;42:1454-59 Control CRT NYHA Class Proportion Changing 1 or more Classes Improve. ↓ Not Reported Cardiac Resynchronization TherapyCardiac Resynchronization Therapy
- 28. Exercise Capacity 6 Months in Moderate to Severe HF -20 0 20 40 60 P<0.001 P=0.36 P=0.029 P<0.001 6 Min Walk Avg. Change (m) 00 0 1 2 3 MIRACLE MUSTIC SR MIRACLE ICD Contak CD P<0.001 P=0.029 P=0.04 P=0.003 Data sources: MIRACLE: Circulation 2003;107:1985-90 MUSTIC SR: NEJM 2001;344:873-80 MIRACLE ICD:JAMA 2003;289:2685-94 Contak CD: JACC 2003;2003;42:1454-59 Control CRT Peak VO2 Avg. Change (mL/kg/min) Cardiac Resynchronization TherapyCardiac Resynchronization Therapy
- 29. Mortality/Morbidity from Published Randomized, Controlled Trials Risk reduction with CRT Study (n random.) FU Mor- tality & Hosp. Mortal. & HF Hosp. Mor- tality HF Mort. HF Hosp. MIRACLE (n=453) 6 Mo NR 39%* 27% NR 50%* MIRACLE ICD (n=369) 6 Mo 2% 0% 0% NR NR Contak CD (n=490) 3-6 Mo NR NR 30% NR 18% Meta-analysis (n=1634) 3-6 Mo NR NR 23% 51%* 29%* * P < 0.05 Cardiac Resynchronization TherapyCardiac Resynchronization Therapy
- 30. Effects on Cardiac Function and Oxidative Stress 0,14 0,16 0,18 0,20 0,22 0,24 500 600 700 800 900 dP/ dtmax (mm/ Hg/ s) MVO2/HR(RelativeUnits) Dobutamin LV Pacing P< 0.05 Nelson et al. Circulation 2000 Myocardial Oxidative Metabolism 0 0,02 0,04 0,06 LV RV kmono(min-1 ) p= 0.86 p= 0.62 n=8 Myocardial Efficiency Work Metabolic Index 0 2 4 6 8 10 12 mmHG·L·m-2 Baseline CRT p =0.024 Ukkonen et al. Circulation 2003 n=7 Cardiac Resynchronization TherapyCardiac Resynchronization Therapy
- 31. CRT Does Not Promote Ventricular Arrhythmias • Analyzed 1,044 patients with ICDs from 2 trials: – CONTAK CD – MIRACLE ICD • Odds ratio (CI): 0.92 (0.67 – 1.27) Patients with VT or VF during Follow-up 17,2% 18,4% No CRT CRT Proportion Bradley DJ, et al. JAMA 2003 Cardiac Resynchronization TherapyCardiac Resynchronization Therapy
- 32. Baseline ex CPX Implant Attempt Successful Implant Control ICD CRT CRT + ICD Pre-discharge Randomization 6 Month Follow-up 6 Month Follow-up CRT Double Blinded Stable Medical Therapy ≤ 1 week • Class NYHA II • Intent to treat analyses • Comparison between groups • Core labs: metabolic exercise, echocardiography, and neurohormone data CRT Long term follow up every 6 months CPX Cardiac Resynchronization TherapyCardiac Resynchronization Therapy MIRACLE ICD II
- 33. 210 Class II 429 Class III/IV 98 Completed 6M FU 82 Completed 6M FU 2 Death 2 1 Missed 6M FU 1 101 Control (ICD+OPT) 85 CRT (CRT+ICD+OPT) 639 Enrolled and Implant Attempted 19 Unsuccessful 191 (91%) Successful 186 Randomized 5 not randomized - 1 death - 4 LV lead dislodge. Cardiac Resynchronization TherapyCardiac Resynchronization Therapy MIRACLE ICD II
- 34. Left Ventricular End Systolic Diameter 200 250 300 350 400 cm3 Base 6 Mo P=0.01 Reverse Remodeling in Class II CHF Left Ventricular End Diastolic Diameter 200 250 300 350 400 cm3 Base 6 Mo P=0.04 Left Ventricular Ejection Fraction 20 22 24 26 28 30 % Base 6 Mo P=0.02 • Control (n=85) ♦ CRT (n=69) Cardiac Resynchronization TherapyCardiac Resynchronization Therapy MIRACLE ICD II
- 35. Cardiac Resynchronization TherapyCardiac Resynchronization Therapy Related Risks Com plicat ions ( 1) 4,8 3,7 1,5 1,0 1,8 0,3 10,6 10,0 2,3 2,4 1,7 0,3 0 5 10 15 Unsucess. Implant LV Lead Coronary Sinus Infection 30 day mortality Procedure death Percent of Pat ient s MIRACLE+CONTAK CD+MIRACLE ICD InSync III/Attain 4193 Reduced Procedure Time w it h I ncreased Experience (2) 60 120 180 240 300 Up t o first 5 Next 6 t o 10 Next 11 more Cent er-based experience ImplantTime(minutes) P < 0.001 Study Period Attempts Primary LV Lead MIRACLE 11/98 – 12/00 591 Attain 2187 Contak CD 2/98 – 12/00 517 EasyTrak MIRACLE ICD 10/99 – 8/01 636 Attain 4189 InSync III 11/00 – 6/02 334 Attain 4193 1. Greenberg, et al. PACE 2003;26(4p2): 952 (Abstract 93) 2. Unpublished data. Medtronic. Inc.
- 36. Cumulative Enrollment in C.R.T.Cumulative Enrollment in C.R.T. Randomized TrialsRandomized Trials 0 1000 2000 3000 4000 1999 2001 2003 2005 Results Presented CumulativePatients PATH CHF MUSTIC SR MUSTIC AF MIRACLE CONTAK CD MIRACLE ICD PATH CHF II COMPANION MIRACLE ICD II CARE HF •• Actual ProjectedActual ProjectedDOUG SMITHDOUG SMITH Cardiac Resynchronization TherapyCardiac Resynchronization Therapy
- 37. 0 5000 10000 15000 Baseline Post-implant Intensive care Cardiology Others Patient Cost Baseline: 12,784 Euro Patient Cost (Implant included): 12,362 Euro Patient Cost Post-implant: 1,680 Euro Hospital costs per patient Cost Effectiveness Analysis of Biventricular Pacing in HF Curnis A 2001 Cardiac Resynchronization TherapyCardiac Resynchronization Therapy
- 38. Relative Cost of CRT Cost per patient $0$20$40$60 CRT+ I CD CRT Hip/ knee replace PTCA CABG Dialysis $ t housands Total Annual Expenditures $0 $5 $10 $15 $20 $ Billions Doug Smith: Doug Smith: Cardiac Resynchronization TherapyCardiac Resynchronization Therapy
- 39. Weight of Evidence: CRT • More than 4000 patients evaluated in randomized controlled trials • Consistent improvement in QOL, functional status, and exercise capacity • Strong evidence for reverse remodeling – ↓ LV volumes and dimensions ↑ LV ejection fraction – ↓ Mitral regurgitation Courtesy of Dr. Bill Abraham Cardiac Resynchronization TherapyCardiac Resynchronization Therapy
- 40. Reduced Mortality in Heart Failure ACE-I & Beta Blockade Reduce Mortality 11,5% 15,6% 12,4% 7,8% 0% 4% 8% 12% 16% SOLVD-T MERIT-HF + CIBIS II 1YearMortality Placebo Treatment Further Reduction with CRT + ICD for Higher Risk Patients CHF Mortality Sudden Cardiac Death CRT ICD Cardiac Resynchronization TherapyCardiac Resynchronization Therapy
- 41. Cardiac Resynchronization TherapyCardiac Resynchronization Therapy • CRT in NYHA class II ? • Which implication in pts with unstable Haemodinamic profile ? • CRT in chronic Atrial Fibrillation ? • CRT in Right Bundle Branch Block ? • QRS<120ms or QTc dispersion ? • “Up-grading” in RVA pacing ? Actual Key QuestionsActual Key Questions
- 42. Creating Realistic patients expectations Cardiac Resynchronization TherapyCardiac Resynchronization Therapy • Approximately two-third of patients should experience improvement (responders vs. non-responders)1 • Some patients may not experience immediate improvement
- 43. • Have patients set their own goals of what they would like to do following CRT: Grocery shopping, Decreasing Lasix dose Walking to the mailbox without stopping, Lying flat to sleep • Encourage them to be part of the group that responds to their therapy Cardiac Resynchronization TherapyCardiac Resynchronization Therapy Creating Realistic patients expectations
Editor's Notes
- &lt;number&gt; HF is a progressive disease with no therapeutic option to cure the illness. This graph shows the correlation between the severity of HF expressed by the 4 NYHA functional classes and survival as well as hospitalization. You can see a very clear decrease of survival (or in other words: an tremendous increase of mortality) and an increase in the frequency of hospital admissions with increasing NYHA function class.
- &lt;number&gt; Main purpose: Remind all of the poor quality of life that burdens heart failure patients Key messages: Patients with heart failure have statistically significant impairment of all aspects of their quality of life when compared with other chronic disorders. Additional information: From a community screening study involving over 4,000 people in Birmingham, UK. The SF 36 is a standard quality of life instrument that should be familiar to most clinicians. The lower the score, the more significant is the perceived impairment.
- &lt;number&gt;
- &lt;number&gt;
- &lt;number&gt;
- &lt;number&gt;
- &lt;number&gt; Bakker P, Meijburg H, de Jonge N, van Mechelen R, Wittkampf F, Mower M, Thomas A. Beneficial effects of biventricular pacing in congestive heart failure. PACE 1994;17:820 (abstract 318). CPI study of 5 NYHA Class III/IV pts with DCM, complete LBBB and prolonged PR interval. DDD pacemaker implanted with endocardial RV lead and epicardial LV lead. LV capture lost in 1 pt at 3 months, who had improved initially. 4 pts improved at least 1 NYHA Class at 3 months. Cazeau S, Ritter Ph, Lazarus A, Gras D, Backdach H, Mundler O, Mugica J. Multisite pacing for end-stage heart failure: early experience. PACE 1996;19[II]:1748-1757. Initial experience on 8 pts with wide QRS (mean 200 35 ms) and end-stage HF (NYHA Class IV) with biventricular pacing including 5 pts with transvenous LV system. Daubert JC, Ritter Ph, Gras D, Pavin D, Cazeau S, Mabo Ph. Use of specifically designed coronary sinus leads for permanent left ventricular pacing: preliminary experience. PACE 1997; 20[II]:? (NASPE abstract 17). 15 pts, mean follow-up 6 months (2-10) with either model 2188 or custom 2879 (2188 with different bend) implanted in the LV. Successful implant in 11 pts (73%). 1.3±0.7 V pacing threshold acutely vs. 1.9±1.0 V threshold chronically. No lead dislodgment or other lead-related complication was observed. “In conclusion, this preliminary experience is encouraging in terms of feasibility, safety and long term results. Further improvement in lead configuration is needed to increase implantation success rate.” Gras D, Mabo Ph, Tscheliessnigg KH, Pedersen AK, Tang T. Early results regarding implant procedures of a new biventricular atrial synchronized pacing system. PACE 1998; 21[II]:824 (NASPE Abstract). 18 DCM pts. 16 successful implants (89%), 14 in lateral vein, 2 in GCV. Total procedure duration: 101 35 min. Fluoroscopic time: 24 12 min. Lurie K, , Benditt D, Samiah N, Blanc JJ. A transvenous “Long Guiding Sheath” technique for permanent left ventricular pacing lead implantation in patients with heart failure. Circulation 1998; 98[17]: I-841 (abstract 4414). Report on use of a 45 cm radiopaque peel away introducer sheath by Daig for LV lead placement. The steps: 1) sheath is placed in SVC as introducer; 2) EP catheter (Daig CSL) is put through the sheath and introduced into the CS; 3) A venogram is obtained using the EP catheter; 4) sheath is advanced over the EP catheter into the CS; 5) EP catheter is removed; 6) LV lead (std RV leads used) is placed through the sheath into the CS. 80% success rate with no complications in 20 pts.
- &lt;number&gt;
- &lt;number&gt;
- &lt;number&gt;
- &lt;number&gt;
- &lt;number&gt;
- &lt;number&gt; Main purpose: Demonstrate evidence of left ventricular reverse remodeling. Key messages: Following 3 months of chronic cardiac resynchronization, LV volumes return slowly to baseline, pre-implant levels after the device is turned off indicating reverse remodeling. On the other hand, mitral regurgitation increases acutely, a finding corroborated by Breithardt and colleagues (J Am Coll Cardiol 2003;41:765–70).
- &lt;number&gt;
- &lt;number&gt; Key Points: (Note – a subset of the 453 patients provide the paired data) Measures of both cardiac function and cardiac structure showed improvement with cardiac resynchronization. A 4.6 percentage point improvement in LVEF within the CRT group of patients contrasted significantly with a reduction of 0.2 percentage points in the Control group. Likewise, patients receiving CRT showed a reduction in mitral regurgitation (-2.7 cm2)that was statistically significantly greater than the modest improvement (-0.5 cm2) observed within the Control group of patients. The reduction in left ventricular end diastolic diameter of 3.5 mm for CRT patients was significant compared with no change on average for Control group patients. Other Information: Echocardiographic results are from a single observer at a core laboratory (University of Pennsylvania). All data are paired; data for the same patients are shown for each time point. While ventricular pacing spikes were often observed on the simultaneously recorded ECG, each echo study was blinded with regard to identity and analyzed individually and without reference to echocardiographic images or knowledge of measurements from other studies of the same patient.
- &lt;number&gt; Key Points: (Note – a subset of the 453 patients provide the paired data) Peak VO2 had virtually no change in the Control group of patients compared with a 1.1 ml/kg/min improvement for CRT group patients. The treatment effect was statistically significant. Total exercise time during the cardiopulmonary exercise test showed similar results. A modest average improvement by Control group patients was overshadowed by an increase of over 1 minute by the patients receiving CRT. Other Information: Cardiopulmonary exercise results were assessed by a core laboratory (University of Cincinnati). All data are paired; data for the same patients are shown for each time point.
- &lt;number&gt;
- &lt;number&gt; The MIRACLE study was not powered to study mortality. However, you can conclude from the results here that cardiac resynchronization does not worsen survival.
- &lt;number&gt; Combined Results: These studies were NOT powered for survival, therefore we will not make mortality claims for the InSync and InSync ICD devices. Medtronic is conducting a European study in Europe with the primary end points of Mortality and Morbidity, called CARE-HF. It will enroll 800 patients and is randomized 1:1 to optimal drug therapy only, or optimal drug therapy + biventricular pacing. The conclusion one can deduce from this graph is that CRT does not appear to worsen survival.
- &lt;number&gt; Main purpose: Show concordance of proof from randomized controlled trials that CRT improves quality of life and functional status. Key messages: Results from blinded studies that randomized 1,000 NYHA Class III/IV heart failure patients with a wide QRS show that CRT dramatically improves patients’ perceived quality of life and the clinicians’ assessment of functional status. The so-called placebo effect was expected. These studies were designed to assess whether there was a treatment effect, and all consistently demonstrated a positive effect.
- &lt;number&gt; Main purpose: Show concordance of proof from randomized controlled trials that CRT improves exercise capacity. Key messages: From the graph on top, 3 of the 4 randomized trials showed that CRT improves this measure of sub-maximal exercise capacity. All studies showed that CRT improves peak VO2, regarded as a more objective measure of exercise and functional capacity, compared to control. Additional information: The authors of the MIRACLE ICD paper make the following comment on the discrepancy in the 6 minute walk test: “However, the absence of a positive treatment effect on the 6-MW contrasts with these earlier trials, and with the improvements observed in this study with the more objective measurements of peak oxygen consumption and treadmill exercise duration. Whether these discrepancies are due to differences between patient populations, or to the different timing of the 6-MW test (performed before instead of after CRT system implantation) remains uncertain.”
- &lt;number&gt; Main purpose: Illustrate improvements in mortality and hospitalization with CRT and CRT + ICD on top of optimal medical therapy Key messages: Neither MIRACLE, nor MIRACLE ICD, nor Contak CD were powered to detect differences in mortality or hospitalizations. Additional information: Reprints of MIRACLE: UC200200338EN Reprints of JAMA meta-analysis: UC200303498 EN
- &lt;number&gt; Main purpose: Respond to safety concern that CRT may be an “electronic positive inotrope.” Key messages: CRT improves cardiac function and efficiency without increased myocardial oxygen consumption. Additional information: Graph at left: Comparison of mechanoenergetic responses to LV free wall electrical stimulation vs intravenous dobutamine. Absolute values are shown for dP/dtmax (abscissa) and for heart rate (HR)-adjusted MVO2 index (ordinate). Both sets of studies had similar dP/dtmax baseline and increase because of intervention. However, dobutamine significantly raised MOV2, whereas pacing/stimulation reduced it (P&lt;0.05). Conclusion: unlike inotropes, CRT does not increase myocardial oxygen consumption with improved systolic performance. EF is improved by a more efficient, rather than stronger, contraction. Graph at right: Acute positron emission tomography study in 8 HF pts with wide QRS. Compared atrial pacing to atrial synchronized biventricular pacing (CRT). Stroke volume index increased without increasing LV oxidative metabolism with CRT.
- &lt;number&gt; Main purpose: Address safety concern that CRT is pro-arrhythmic Key messages: No difference between CRT and no CRT in the number of patients with VT/VF events Additional information: These data come from a meta-analysis of CRT. The two studies combined assessed CRT in patients with a pre-existing indication fro an ICD. VT/VF events are collected in the devices’ (InSync ICD, Contak CD) diagnostics.
- &lt;number&gt;
- &lt;number&gt; Backup Only: 7 pts did not maintain treatment assignment 4 due to brady indication, 3 due to worsening HF, data included based on intention to treat principle There were 9 pts who did not have their 6 mo follow up data in the database as of the the database closure date : 5 of 9 Medtronic received follow up form after PMA update data cutoff 1 of 9 died but from had not yet been received 3 of 9 status unknown at time of PMA Update Overall study visit compliance is 98% (2247 due, 2203 completed) 27 of 579 enrolled met inclusion/exclusion criteria (97%)
- &lt;number&gt; Main purpose: Explain the risks of a CRT system implant to referral clinicians. Based on Medtronic’s MIRACLE study program and on Guidant’s Contak CD trial. Source of complications is abstract presented at NASPE 2003. Key messages: Each clinical trial utilized a clinical events review committee to evaluate complications, including defined procedure-related mortality. Chiefly due to challenging venous anatomy, implants have been unsuccessful in approximately 10% of patients attempted. Complication rates by category appeared to be reduced with the Medtronic Attain 4193, with an over-the-wire delivery system, used in the InSync III trial. Coronary sinus dissection or perforation generally were resolved without further complication. For comparison, the 30-day mortality in the CABG-PATCH and the AVID trials were 5.4% and 2.4% respectively. Left ventricular lead complications, primarily dislodgements, occurred in 9% of all cases (4% in the InSync II study). There is a learning curve. Implant times came down with increased center-based experience.
- &lt;number&gt; Main purpose: Show that a large number of patients have been studied in completed and ongoing randomized controlled studies of CRT. Use in conjunction with previous slide. Key messages: Over 3000 patients have been enrolled in randomized controlled clinical trials presented to date. When CARE-HF, another landmark trial assessing mortality and hospitalization, is reported, close to 4,000 patients will have been studied.
- &lt;number&gt; Main purpose: Respond to concern that CRT/CRT + ICD is too expensive. Key messages: Like cardiac resynchronization therapy, a variety of medical procedures exist to help improve patients’ quality of life, clinical status, and survival. Many of these procedures –and their associated costs – are accepted as standard of care. Total annual expenditures for CRT and CRT+ICD remain relatively minor when compared with other standards of care. CRT and CRT+ICD devices last 4 to 6 years Additional information: US data only. Data sources: All except dialysis: Weighted DRG payment for 2003 using the number of discharges in 2000: HCUPnet, Healthcare Cost and Utilization Project. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/data/hcup/hcupnet.htm. Dialysis: Medicare 2000 payment per patient: The United States Renal Data System (USRDS), 2002. www.usrds.org +This cost comparison is meant for illustrative purposes only; it is not intended as a therapeutic comparison.
- &lt;number&gt; Main purpose: Set up discussion for next slide. Key messages: Despite the significant contributions of ACE inhibitors and beta blockers to help heart failure patients live longer, the annual mortality of heart failure patients remains high. As previously shown, moderate to severe heart failure patients with a wide QRS are at higher risk. Cardiac resynchronization and ICD therapies can help this higher risk group live longer Additional information: SOLVD-T was a landmark trial reported in 1991 that showed ACE inhibitors reduced mortality in symptomatic heart failure patients. The MERIT-HF (metroprolol study in Europe and North America) and the CIBIS II (bucindilol in Europe) studies reported in 1999, demonstrated that the addition of beta blockade to conventional treatment, including ACE-inhibitors, further improved survival. The results from these trials are consistent with those reported from the US cardvedilol trial. As reported in the same review paper, if one extracts NYHA III/IV patients from the combined CIBIS II, MERIT-HF and US carvedilol trials, 1- year mortality in the control and treatment groups are 15.15 and 9.5% respectively.
- &lt;number&gt; It is very important that a patient set his/her own goals to therapy that are realistic.
- &lt;number&gt; It is very important that a patient set his/her own goals to therapy that are realistic.