1. Implantable Electronic Cardiac Devices for Prevention of Sudden Cardiac Death and Treatment of Cardiac Arrhythmias. What are the Limits to Use It? Limits and Interfaces in Science São Paulo, November 28-30, 2009. Roberto Costa rcosta@incor.usp.br

2. Implantable Cardiac Devices Sudden Cardiac Death Current Statistics National Vital Statistics Report. 2001;49;11. MMWR. 2002;51:123-126. Sudden Cardiac Arrest (SCA) 0%5%10%15%20%25% Septicemia Nephritis Alzheimer’s Disease Influenza/Pneumonia Diabetes Accidents/Injuries Chronic Lower Respiratory Diseases Cerebrovascular Disease Other Cardiac Causes All Cancers SCD is a leading cause of death in the U.S., second to all cancers combined.

3. Implantable Cardiac Devices Sudden Cardiac Death Current Statistics Incidence (cases/year) Survival Worldwide3,000,000<1% U.S.450,0005% W. Europe400,0005% Brazil250,000 NA American Heart Association. Heart Disease and Stroke Statistics – 2009 Update DATASUS - 2008; Sociedade Brasileira de Cardiologia - 2008

4. Implantable Cardiac Devices Causes of Sudden Cardiac Death Albert CM. Circulation. 2003;107:2096-2101. 12% Other Cardiac Cause 88% Arrhythmic Cause

5. Implantable Cardiac Devices Mechanisms of Sudden Arrhythmic Death Bayés de Luna A. Am Heart J. 1989;117:151-159. Bradycardia 17% VT 62% Primary VF 8% Torsades de Pointes 13%

6. Implantable Cardiac Devices 1958 First Antiarrhythmic Devices

7. Implantable Cardiac Devices Antibradycardia Devices Conventional Pacemakers

8. Implantable Cardiac Devices Rassi A. Not published data Survival (Years) % Survival p < 0,01 Treatment of Atrioventricular Block Conventional Pacemakers

9. Implantable Cardiac Devices Implantable Electronic Cardiac Devices Historical Aspects 1932195819641970 1980’s 1994 Hyman Senning and Elmquist 1st implant of an electronic PM Mirowski Development of the 1st ICD – implant in dogs 1st report of CRT RECENTLY Furman 1st endocardiac PM Heart Failure control Home Monitoring

10. Implantable Cardiac Devices Antitachycardia Devices Implantable Cardioverter Defibrillator

11. Implantable Cardiac Devices Antitachycardia Devices Implantable Cardioverter Defibrillator

12. Implantable Cardiac Devices NEJM 1997;337;1576-83 Secondary Prevention of Sudden Arrhythmic Death AVID Study

13. Implantable Cardiac Devices N of Patients at Risk ICD 742502 (0.91)274 (0.84) 110 (0.78) 9 Conventional 490329 (0.90)170 (0.78) 65 (0.69) 3 Moss AJ. N Engl J Med 2002;346:877-883 ICD Conventional P = 0.007 1.0 0.9 0.8 0.7 0.6 0.0 Survival Probability 01234 Years 0.78 0.69 -31% Primary Prevention of Sudden Arrhythmic Death MADIT II Study

14. Implantable Cardiac Devices Longer Shorter Relaxed Courtesy of Dr Kass, MD, Johns Hopkins University, Maryland. SEPTUM BASE APEX SEPTUM BASE Normal Dilated Cardiomyopathy APEX Left Ventricular Dysfunction Electromechanical Dyssynchrony

15. Implantable Cardiac Devices Cortesia de D. Kass, MD, Johns Hopkins University, Maryland. SEPTUM BASE APEX SEPTUM BASE APEX Longer Shorter Relaxed Normal Activation Electromechanical Delay Left Ventricular Dysfunction Electromechanical Dyssynchrony

16. Implantable Cardiac Devices Cardiac Resynchronization Atrio-biventricular Pacing LVRV

17. Implantable Cardiac Devices Cleland et al, Eur Heart J 2006;27(16):1928-32 050010001500 0 25 50 75 Days P<0.0001 Event-free Survival 571192321365404 889213351376409 Control CRT N of Patients at Risk Medical Therapy CRT 100 HF CF III/IV EF<0.35 QRS>130ms Cardiac Resynchronization CARE-HF Study: Overall Mortality

18. Implantable Cardiac Devices Cardiac Resynchronization CARE-HF Study: Sudden Mortality Cleland et al, Eur Heart J 2006;27(16):1928-32 CRT Medical Therapy Survival Time (days) Hazard ratio 0.54 (95% CI 0.35-0.84. P = 0.006) CRT = 32 sudden deaths (7.8%) Medical therapy = 54 sudden deaths (13.4%) 1.00 0.75 0.50 0.25 0.00 0 400 800 1200 1600

19. Implantable Cardiac Devices Cardiac Resynchronization + ICD COMPANION Study: Overall Mortality N Engl J Med 2005 CRT-D CRT TMO Sobrevida livre de eventos (%) 19% 12% 15% N:1520

20. Implantable Cardiac Devices Implantable Electronic Cardiac Devices Historical Aspects 1932195819641970 1980’s 1994 Hyman Senning e Elmquist 1st implant of an electronic PM Mirowski Development of the 1st ICD – implant in dogs 1st report of CRT RECENTLY Furman 1st endocardiac PM Heart Failure control Home Monitoring

21. Implantable Cardiac Devices Remote Transmission of Arrhythmias Therapies Applied by the Device

22. Implantable Cardiac Devices HIGH intrathoracic impedance indicates dry lungs Better Worse Clinical and Hemodynamical Diagnosis Analysis of the Thoracic Impedance LOW intrathoracic impedance indicates pulmonary congestion

23. Implantable Cardiac Devices Pressure Change (9 of 12) Hospitalization Days Relative to Event Baseline -7 -6 -5 -4 -3 -2 -1 Recovery Baseline -7 -6 -5 -4 -3 -2 -1 Recovery Percent Change Percent Change -10 0 10 20 30 40 RV Sistolic Pressure Estimated Pulmonary Artery Diastolic Pressure Heart Rate Continuous Volemia Evaluation Possibility of a Precocious Intervention Adamson PB et al. J Am Coll Cardiol. 2003; 41: 565

24. Implantable Cardiac Devices PatientTransmitterWireless transmission* Service centerData sent to the physician Remote Monitoring System * By landline phone or GSM network

25. Implantable Cardiac Devices  Device Complications  Clinical Complications In-clinic Follow-up Next evaluation (90-180 days) Remote Monitoring System

26. Implantable Cardiac Devices 24% of all stroke events Remote Transmission of Arrhythmias Atrial Fibrillation

27. Implantable Cardiac Devices Atrial Fibrillation Incidence

28. Implantable Cardiac Devices May 2009 Last statistical analysis N = 260 patients Loss to follow-up: 3 Without 1st consultation: 31 Remote Monitoring 116 Control Group 110 226 patients Atrial Fibrillation in the Elderly with Pacemaker Inclusion and Randomization

29. Implantable Cardiac Devices Inclusion Age ≥ 60 years Classic indication for AVPM implant or replacement Surgical procedure Randomization 1:1 0-7 days after surgery Intervention group Remote monitoring MAS ≥ 10% - extra consultation Control group Booked for ambulatory consultation 131812624 months Atrial Fibrillation in the Elderly with Pacemaker Study Design

30. Implantable Cardiac Devices Event-free Survival GI = 22 (19%) GII = 23 (20.9%) p=0.52 Intervention Control Total=45 episódios (19,91%) Total=45 episodes (19.91%) Atrial Fibrillation in the Elderly with Pacemaker Episodes Incidence (months)

31. Implantable Cardiac Devices Atrial Fibrillation in the Elderly with Pacemaker Incidence of new AF episodes after follow-up p=0,08 Median (days) Average (days) 3856 39,9679,9 RemotoControle P = 0,045 Time to diagnosys of AF (months)

32. Implantable Cardiac Devices Conducts in Extra Consultations (23) Atrial Fibrillation in the Elderly with Pacemaker Conducts Established in Extra Consultations

33. Implantable Cardiac Devices (5 Yr) (2.4 Yr) (3 Yr) (3 Yr) (3.5 Yr) (1 Yr) (6 Yr) (2 Yr) (5 Yr) (2.4 Yr) (3 Yr) (3 Yr) (3.5 Yr) (1 Yr) (6 Yr) (2 Yr) NNT x years = 100 / (% Mortality in Control Group – % Mortality in Treatment Group) ICD Therapy simvastatin captopril Metoprolol succinate amiodarone Drug Therapy Cardioverter Defibrillator Number Needed to Treat

34. Implantable Cardiac Devices $0.6$0.6 $2.0 $2.8 $4.6 $6.8 $8.5 $14.9 Weighted DRG payment 2003 with discharges from 2000. HCUPnet. www.ahrq.gov/data/hcupnet.htm Medicare 2000 Dialysis payment per patient: The United States Renal Data System (USRDS), 2002.. www.usrds.org Weighted DRG payment for 2003 using weighted 2002 industry implants (CRT, CRT+ICD), including replacements DialysisCABGStent Hip / Knee ReplacementHeartValves ICD AorticAneurysmCRT 0 2 4 6 8 10 12 14 $16 Procedure $ Billion Yearly Expenditures for Medical Procedures DRG Payment by Procedure Dialysis $ 54,262 Heart Valves33,525 ICD 30,394 CRT 25,112 CABG 24,272 Aortic Aneurysm17,655 Stent11,646 Hip / Knee Replacement10,365 Total Comparative Expenses Influence of the Prevalence

35. Implantable Electronic Cardiac Devices for Prevention of Sudden Cardiac Death and Treatment of Cardiac Arrhythmias. What are the Limits to Use It? Limits and Interfaces in Science São Paulo, November 28-30, 2009. Roberto Costa rcosta@incor.usp.br