1. 1 New Approaches to Monitoring Heart Failure Before Symptoms Appear William T. Abraham, MD, FACP, FACC Professor of Medicine Chief, Division of Cardiovascular Medicine Associate Director, Davis Heart & Lung Research Institute The Ohio State University Columbus, Ohio

2. 2 Asymptomatic fluid retention Change in impedance or pressure Worsening heart failure Can Implantable Monitors Predict Worsening Heart Failure? Can this prevent hospitalization for worsening heart failure?

3. 3 Intrathoracic Impedance as a Measure of Heart Failure Clinical Status

4. 4 Impedance “Wetter” Lungs Impedance Decreases With Increasing Lung Wetness

5. 5 Impedance Prior to CHF Admission More Fluid Less -28-21-14-70 60 70 80 90 Impedance (  ) Days Before Hospitalization Impedance Reduction Duration of Impedance Reduction Reference Baseline CHF, congestive heart failure.

6. 6 Evidence Supporting the Use of Intrathoracic Impedance  Animal studies  Completed MID-HeFT study: Medtronic Impedance Diagnostics in Heart Failure Trial  Ongoing FAST study: Fluid Accumulation Status Trial

7. 7 MID-HeFT Study  MIDHeFT study –33 patients, 628 months of follow-up (as of 9/1/03) –25 hospitalizations for fluid overload from 10 patients –Demonstrated an inverse correlation between impedance and both PCWP and net fluid I/O in patients hospitalized for fluid overload –Demonstrated consistent decreases in impedance in the days preceding hospitalization (ie, predicted hospitalization!) PCWP, pulmonary capillary wedge pressure; I/O, in/out. Yu C-M, et al. Circulation. 2005;112:841-848.

8. 8 MID-HeFT Study Results  Intrathoracic impedance decline preceded the onset of symptoms by mean lead time of 10.3 days (P<0.0001)  Retrospective analysis of the clinical data showed that intrathoracic impedances gradually decreased over approximately 2 weeks prior to HF hospitalization (14 days, P<0.0001) with a total reduction of 11.3%  Using a single detection threshold for all patients, the OptiVol algorithm would have detected 76% of admissions for fluid overload, with an average of only one false warning for every 322 days of patient monitoring HF, heart failure Yu C-M, et al. Circulation. 2005;112:841-848.

9. 9 01234 Days In Hospital 10 20 30 PCWP (mm Hg) -6 -4 -2 0 Fluid I/O (liters) 55 60 65 70 Impedance (  ) Example: Fluid Status During Diuresis

10. 10 50 60 70 80 90 Impedance (  ) Reference BaselineOne Day Prior to Admission -12.3 +/- 5.3% (P<0.001) 18.3 +/- 10.1 Days Impedance Leading Up To Admission (n=24)

11. 11 Days Prior to Admission Symptom OnsetImpedance Decline 0 10 20 30 40 Impedance Decline Precedes Symptoms (n=20)

12. 12 Automated Detection of Decreases in Intrathoracic Impedance That Precede Hospitalization for CHF

13. 13 OptiVol Feature Physician- programmed threshold Reference impedance slowly adapts to daily impedance Daily impedance is the average of one day’s measurements Accumulation of the difference between the daily and reference impedance Jun 98Aug 98 Oct 98 0 40 80 120 160 200 60 70 80 90 100 >120 110 Jun 98Aug 98 Oct 98 Thoracic Impedance (ohms) Daily Reference OptiVol Fluid Index OptiVol Threshold Fluid P P, program.

14. 14 4080120160200 0 20 60 100 Days Fluid Index (  days) 0 4080120160200 70 80 90 Days Impedance (  ) 0 0 Overview of Detection Algorithm

15. 15 FAST Study  FAST study –44 patients enrolled/downloaded –47 months of total follow-up –32 patients to 1 month –7 patients with an HF event; 25 were event-free 3 clinically relevant HF hospitalizations (in 2 patients)* 11 clinically relevant HF medication changes (in 5 patients)* 4 adverse events from HF medication changes (in 4 patients)* –Study corroborated impedance performance from the MID- HeFT study in both event-free and HF event occurrences *Patients with events are not mutually exclusive.

16. 16 FAST Case Study 2 – HF Event H, hospitalization; O, outpatient visit; M, medication change; F, protocol scheduled follow-up. Threshold crossed 19 days prior to hospitalization. Discharged after 1.5 lbs of diuresis Discharged after 10.8 lbs of diuresis Days Impedance Patient 110270001 0102030405060708090100 30 40 50 60 70 HHHHHHH F F MMMMMM Days Cumulative Diff 0102030405060708090100 0 30 60 90 120 HHHHHHH F F MMMMMM Days Weight (lbs) 0102030405060708090100 260 270 280 290 300 FF

17. 17 Nov. 5: Lead replacement. Impedance stabilizes several days after procedure. Oct. 28: Hospitalization for decompensation: orthopnea, peripheral edema, and crackles in lower lungs. Sept. 29: Crossed OptiVol fluid threshold. Oct. 7: LV lead dislodgement observed. Decided to reposition lead in November. Sep 04Nov 04 0 40 80 120 160 >200 40 50 60 70 80 >100 90 Sep 04Nov 04 Thoracic Impedance (ohms) Daily Reference OptiVol Fluid Index OptiVol Threshold Fluid InSync Sentry ™ Case: Loss of CRT CRT, cardiac resynchronization therapy.

18. 18 Aug 04Oct 04 0 40 80 120 160 >200 40 50 60 70 80 >100 90 Aug 04Oct 04 Thoracic Impedance (ohms) Daily Reference OptiVol Fluid Index OptiVol Threshold Fluid Dec 04 InSync Sentry Case: Precipitous Drop in Impedance

19. 19 Aug 04Oct 04 40 60 70 80 90 >100 0 150 >200 4 8 24 20 Thoracic Impedance (ohms) Daily Reference Dec 04 50 16 12 100 <50 AT/AF Total hours/day V. rate during AT/AF (bpm) Max/day Avg/day AT, atrial tachycardia; AF, atrial fibrillation; V. rate, ventricular rate. InSync Sentry Case: Precipitous Drop in Impedance

20. 20 Implantable Hemodynamic Monitoring Systems

21. 21 Implantable Hemodynamic Monitor

22. 22 IHMHome MonitorClinician Access Secure Network  RV systolic pressure  RV diastolic pressure  Estimated PA diastolic pressure  Other parameters IHM System and Information Flow IHM, implantable hemodynamic monitor; RV, right ventricular; PA, pulmonary artery.

23. 23 IHM-Guided Care Reduces Worsening HF in NYHA Class III Patients Cumulative Events 0 20 40 60 80 100 120 Events TCA (n=112) BCA (n=122) Patients With Events (#) 3348 Total HF-Related Events 4989 Hospitalizations 4176 Emergency Department Visits 611 Urgent Clinic Visits 22 Event Rate/ 6 Months 0. 530.90 Reduction in Event Rate (%) 41% (P=0.03) TCA BCA 6 4 2 Months NYHA, New York Heart Association; BCA, blocked clinician access; TCA, total clinician access. Bourge RC, et al. ACC 2005.

24. 24 IHM Case Study  59-year-old white female with ICM –S/P AWMI 2001; CABG 4 SVG 2001  Participant in COMPASS-HF Trial (BCA)  Called 5 days after Valentine’s Day 2005 due to bloating and increased shortness of breath  Weight “stable”  Asked to transmit data ICM, ischemic cardiomyopathy; AWMI, anterior wall myocardial infarction; CABG, coronary artery bypass graft; SVG, saphenous vein graft; BCA, blocked clinician access.

25. RV Diastolic Pressure (mm Hg) RV Systolic Pressure (mm Hg) ePAD (mm Hg) ePAD, estimated pulmonary artery diastolic pressure.

26. 26 IHM Case Study  Had celebrated Valentine’s Day by going out to eat –At an Indian restaurant! –Very thirsty – increased fluids  Diuretics increased

27. 27 Summary  Long-term trends in intrathoracic impedance may provide an early warning of impending episodes of decompensation in outpatients  Implantable hemodynamic monitoring (IHM) enables the day-to-day management of ventricular filling pressures in CHF patients  Intrathoracic impedance and IHM represent complimentary and promising new technologies for the management of HF