This document discusses new approaches to monitoring heart failure patients using implantable sensors to continuously measure pulmonary artery or left atrial pressures. It describes a clinical trial that found implanting a pulmonary artery pressure sensor and using the pressure readings to guide medication adjustments significantly reduced heart failure hospitalizations compared to usual care. A separate study implanted a left atrial pressure sensor and developed an algorithm to guide diuretic dosing based on pressure levels. Initial results found the sensor remained calibrated over time and the system was able to control left atrial pressures.

1. New Physician/Patient Paradigms in Heart Failure ManagementWilliam T. Abraham, MD

2. BackgroundDespite current therapies and disease management approaches, the rate of heart failure hospitalization remains unacceptably high> 1.1 million heart failure hospitalizations annually> 25% readmission rate at 1 month; 50% at 6 months> $18 billion in annual direct costsCurrent methods for monitoring heart failure patients have not adequately addressed this issue

3. Key Therapeutic Goal in Heart Failure:Maintain Optimal Volume/Pressure StatusHypervolemia/Elevated Intra-cardiac and Pulmonary Artery Pressures:Increased symptoms, increased risk of hospitalization, increased risk of arrhythmias, increased mortalityEuvolemia/Normal Intra-cardiac and Pulmonary Artery Pressures:Low riskHypovolemia/Low Intra-cardiac and Pulmonary Artery Pressures:Symptomatic hypotension, syncope, pre-renal azotemia

4. What Do We Really Need To Monitor?What do we really want to know?Pulmonary congestion / left ventricular filling pressure (LVFP)How do we currently assess these in patients with chronic heart failure?SymptomsDaily weightsPhysical examinationBiomarkersHow well do these assessments perform?Not very well

5. Limitations of Available Monitoring SystemsWeight and Symptoms – Recent large, landmark clinical studies (Tele-HF, TIM-HF) investigating the effectiveness of telemonitoring demonstrated no benefit in reducing HF hospitalizationsBNP - PRIMA and other studies guided identification of patients at risk for HF events, but showed no significant reduction in HF-related admissionsDevice-Based Diagnostics - May be useful for identifying patients that may be at higher risk for a HF hospitalization(PARTNERS-HF Study), but have not demonstrated a reduction in HF-related hospitalizationsTele-HF: Yale Heart Failure Telemonitoring Study; NEJM, 2010TIM-HF: Telemonitoring Intervention in Heart Failure, Eur J. Heart Failure, 2010PRIMA: Can Pro-BNP guided heart failure therapy improve morbidity and mortality? J Am Coll Card, 2010PARTNERS-HF: Combined Heart Failure Device Diagnostics Identify Patients at Higher Risk of Subsequent Heart Failure Hospitalizations. J Am Coll Card, 2010

6. Premise of Physiological Heart Failure Monitoring (1)Heart Failure EventSymptomsHemodynamicChangesDays-21-14- 7 0 ProactiveReactive

7. Premise of Physiological Heart Failure Monitoring (2)AvertedHeart Failure EventMedical InterventionHemodynamicChangesDays-21-14- 7 0 Proactive

8. LV Pressure SensorRV Pressure SensorsPA Pressure SensorsLA Pressure SensorImplantable Hemodynamic Monitors

9. MEMS-based pressure sensorHome electronicsPA Measurement databaseThe Pulmonary Artery Pressure Measurement System*Catheter-based delivery system*CardioMEMS Inc., Atlanta, Georgia, USA

10. Primary Results of the CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients (CHAMPION) Trial

11. CHAMPION Study DesignProspective, multi-center, randomized (1:1), controlled single-blind clinical trialTreatment group received traditional HF management guided by hemodynamic information from the sensorControl group received traditional HF disease management550 subjects enrolled at 63 sites in the U.S. between October 2007 and September 2009All subjects followed in their randomized single-blind study assignment until the last patient reached 6 months of follow-up

12. Cumulative HF Hospitalizations Over Entire Randomized Follow-Up Period p < 0.001, based on Negative Binomial RegressionCumulative Number of HF HospitalizationsDays from Implant

13. Secondary Efficacy Results

14. CHAMPION: Putting It AltogetherPulmonary Artery PressureMedication Changes On Basis of Pulmonary Artery PressureP<0.0001Pulmonary Artery Pressure ReductionP=0.008Heart Failure Related Hospitalization ReductionP<0.0001Quality of Life ImprovementP=0.024P values for Treatment Vs Control Group

15. Proximal anchor7 mmDistal anchorTi diaphragm 3 mmLeft Atrial Pressure Monitor*Implantable Sensor Lead(ISL)Sensor moduleImplantable Communications module (ICM)Sensor module featuresHermetic Ti housing /sensing diaphragmCustom ASIC measures LAP, IEGM,TempFolding nitinol septal fixation anchorsFull digital waveform telemetryRF power, no implanted battery*St. Jude Medical, Sylmar, CA

16. Physician-Directed, Patient-Self ManagementLAP ≥28 …Very High… furosemide 80mg, call MDLAP 19-27 …High………. 40mgLAP 10-18 …Optimal…… 20mgLAP 6-9 …Low…………10mgLAP ≤ 5 …Very Low…. hold, increase fluid intakeOptimal LAP makes it easier to up-titrate β-Blockers and ACE-I/ARBsDirect USB (in-clinic)RF TelemetryRemote(patient’s home)Patient Advisory ModuleApplication SoftwareTrends, Waveforms, PrescriptionsPC or Web Based

17. (s) carvedilol(25mg),1 tab(s) lisinopril(20mg), 1 tab*(d) furosemide(40mg),1 tabHandheldPatient Advisor ModulePAMPowers implant by RF

18. Atmospheric reference

19. Stores telemetry

20. Alerts patient to monitor

21. DynamicRX™

22. Meds, activity, MD contactCirculation 2010; 121:1086-1095

23. Inclusion /Exclusionn=40Implantn=40Observation PeriodStandard therapy without LAP-guidance for 3 monthsRHC at 3 months 1º Safety EndpointMACNE at 6 weeksn=40Titration PeriodLAP-guided therapy rapid drug titration for 3 monthsStability PeriodLAP-guided therapy for ≥ 6 monthsRHC at 12 months12 month follow-upn=35, 4 deaths, 1 withdrawalLonger term follow-upmedian 25 monthsn= 30, 9 deaths, 1 withdrawalHOMEOSTASIS I & IIEndpoints, Design, Subject AccountingOpen-label, registry1º Endpoint (safety)Freedom from Major Adverse Cardiac and Neurological Events (MACNE) at 6 weeks2º Endpoints (functionality)CalibrationLAP vs. PCWP3º Endpoints (Effectiveness surrogates)Control of LAPHospitalizationClinical parameters

24. HF Event Rates(ADHF and All-Cause Death)Comparison of Periods with and without LAP-Guidance