Philip B. Adamson, MD, FACC

Transcription

1 Sensed Hemodynamics Coupled to Remote Patient Monitoring in Heart Failure: Has the Search for the Holy Grail Ended? Philip B. Adamson, MD, FACC Director, Heart Failure Institute at Oklahoma Heart Hospital Director, Oklahoma Foundation for Cardiovascular Research Adjunct Associate Professor of Physiology, University of Oklahoma Health Sciences Center

2 Philip B. Adamson, MD, FACC Disclosure Information I will discuss off label use or investigational use in my presentation. I have financial relationships to disclose: Employee of: N/A Consultant for: Medtronic, Inc; St. Jude Medical; CardioMEMS, RespiCardia, Inc, Mitralign Stockholder in: N/A Research support from: N/A Honoraria from: Medtronic, Inc; St. Jude Medical; CardioMEMS; Boston Scientific

3 Cardiovascular Disease Mortality PTCA STENT

4 Interventional Technology and CV Mortality Death LHC PCI

5 EP Technology HRS National ICD Registry report for ,284 procedures were performed in 259,395 patients Kremers MS, et al Heart Rhythm 2013 Josephson ME et al. Annals of Internal Med 2000;133:901

6 Pharmacologic and Device Technologies and Mortality in Heart Failure Neurohormonal Era Device Era NHLBI Statistics

7 Altering Mortality or Hospitalizations? Same survival, but very different outcomes!

8 Shift from Acute to Chronic Disease Management 400 Coronary Deaths 1,200 Heart Failure Hospitalizations 350 1, Coronary deaths are down by half 400 But heart failure has almost tripled Source: National Hospital Discharge Survey, CDC/NCHS and NHLBI.

9 All-Cause 30 Day Readmission Rates After HF Hospitalization

10 Major Problem: Most Days of Heart Failure Management Are Not Clinic Days What is the right signal at home? Shah M, et al Am Heart J 2005;149:

11 Weights are Not Sensitive at Predicting Heart Failure Hospitalization Weight Changes Before HF Hospitalization Chaudhry et al, NEJM 2007

12 More Intense Daily Monitoring of Weights and Symptoms Does NOT Improve Outcomes Tele-HF (NEJM 2010) 1653 patients randomized to telemonitoring or standard of care Daily weights, BP, and symptoms 29,163 physician calls to patients during 6 months End Point Telemonitoring (N = 826) Usual Care (N = 827) Death or Hospitalization # (%) 432 (52.3) 426 (51.5) Heart Failure Hospitalization # (%) 227 (27.5) 223 (27.0)

13 More Intense Daily Monitoring of Weights and Symptoms Does NOT Improve Outcomes TIM-HF (Circulation 2011) 710 patients randomized to telemonitoring or standard of care Daily weights, BP, and symptoms End Point Telemonitoring n=354 (%) Usual Care n=356 (%) All-cause readmission/death All-cause readmission All-cause mortality

14 Even The Experts Cannot Stop The Tides of Congestion With Current Heart Failure Management After 60 days out of hospital Post hoc analysis of 463 ADHF patients from DOSE-HF and CARRESS-HF trials Of patients decongested at discharge, 2/3 had clinical re-congestion by 60 days Lala, et al. for H-FAN HFSA 2013

15 Prevention vs. Crisis Management Role of Device Monitoring Right Signal Rapid Re-evaluation Right Response Actionable Adapted from LW Stevenson et al

16 Pathogenesis of Worsening Heart Failure Fluid retention Fluid redistribution Increased pulmonary artery pressures Worsening dyspnea leading to hospitalization The Dawn of the HEMODYNAMIC ERA

17 Studies in Hemodynamic Monitoring Preceding CHAMPION CH-17 Managing to pressures helps maintain stable pressures High pressures increase risk of hospitalization Management of pressures minimizes congestion, maintains health and reduces HF hospitalizations Steimle, 1997 COMPASS-HF, 2008 REDUCE-HF, 2011 CHAMPION, 2011 Managing to pressures Chronicle, 2003 HOMEOSTASIS, 2010 CardioMEMS Feasibility, 2006 Evolution of Managing Pressures Steimle AE, et al. Circulation, 1997 Chronicle: Adamson, et al JACC, 2003 Zile MR, et al. Circulation, 2008 COMPASS-HF: Bourge RC, et al. JACC, 2008 CHAMPION Feasibility: Abraham WT, et al. Am Heart J, 2011 CHAMPION Design: Adamson PB, et al. J Card Fail CHAMPION: Abraham WT, et al. Lancet, 2011 HOMEOSTASIS: Ritzema J, et al. Circulation, 2010 REDUCE-HF: Adamson PB, et al: Congestive Heart Failure 2011

18 Approaches to Implantable Hemodynamic Monitoring an Evolution of Thought Hemodynamic monitoring- Right Ventricular Outflow Tract COMPASS-HF Hemodynamic monitoring- Left Atrial Pressure LAPTOP HF Hemodynamic monitoring- Pulmonary Artery Pressure CHAMPION Trial

19 Right Ventricular Implantable Hemodynamic Monitor (IHM) Pressures Right Ventricular (RV) Systolic and Diastolic Pressures Estimated Pulmonary Artery Diastolic Pressure (epad) Heart Rate, Temperature, Activity

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21 1 Efficacy Objective # of Pts with Events Total HF Related Events IHM (n =134) Control (n = 140) Hospitalizations Emergency Department Visits Urgent Clinic Visits 2 3 Event Rate / 6months* % Reduction in Event Rate % (p= ; p= ) Events Cumulative Events IHM Control 2 Months 1. Poisson model - Scaled Deviance = Negative Binomial model - Scaled Deviance = Bourge RC, Abraham WT, Adamson PB, et al: J Am Coll Cardiol 2008;51:

22 Acute Decompensated Heart Failure Event epad (mmhg) Systolic Heart Failure Diastolic Heart Failure Time (days) Heart Failure Related Event Zile MR, Bennett TD, St. John Sutton M, et al: Circulation 2008;118:

23 Stevenson LW, et al Circ Heart Fail 2010;3:580

24 Approaches to Implantable Hemodynamic Monitoring an Evolution of Thought Hemodynamic monitoring- Right Ventricular Pressure COMPASS-HF Hemodynamic monitoring- Left Atrial Pressure LAPTOP HF Hemodynamic monitoring- Pulmonary Artery Pressure CHAMPION Trial

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26 LAP Monitoring

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30 Approaches to Implantable Hemodynamic Monitoring an Evolution of Thought Hemodynamic monitoring- Right Ventricular Pressure COMPASS-HF Hemodynamic monitoring- Left Atrial Pressure LAPTOP HF Hemodynamic monitoring- Pulmonary Artery pressure CHAMPION Trial

31 Champion HF Monitoring System PA Pressure Sensor on Catheter Delivery System 4.5c m 120cm Patient Home Electronics Unit PA Pressure Database Physician Access Via Secure Website

32 Sensor Physics

33 Wireless Power and Communication Press ure Radiofrequency powered No battery No leads High fidelity PA Pressure waveform

34 Sensor Delivery System Over-the-wire Implant Tether release system Hydrophilic coating Radiopaque shaft Guidewire: Introducer sheath: 11Fr Terumo

35 PA Pressure Sensor Implant

36 Caution: Investigational Device Not Approved by the USFDA

37 Primary Results of the CHAMPION Trial Presented at European Society of Cardiology HF Congress May 31, 2010 Published February 2011: Abraham WT, Adamson PB, Bourge RC, et al. Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: a randomised controlled trial. Lancet. 2011; 377: Caution: Investigational Device Not Approved by the USFDA

38 Adamson PB, Abraham WT, Aaron M, et al J Card Fail 2011;17:3-10 Pressure-Based Medical Management Workflow Patient Treatment decisions Care Team Takes pressure readings Website Reviews readings on Web site

39 CHAMPION Study Design: Prospective, Randomized, Single-blind Trial Hemodynamic data Treatment Group Implant + PAP readings + Pressure management + Standard of care Successful Implantation n = 550 Hemodynamic data Randomized 1:1 Patients remain in study group, blinded, until last patient finishes 6 month follow-up Control Group Implant + PAP readings, No pressure management + Standard of care mpap= 26 mmhg PCWP= 15 mmhg Adamson PB, Abraham WT, Aaron M, et al J Card Fail 2011;17: months 17.2 months

40 Primary Safety Endpoints Met 100% 95% Freedom from Device/System Related Complication (%) 90% 85% 80% 75% 70% 65% 60% (Objective (Objective Performance Criteria) 1167 patient-years of follow-up 8 device system-related complications (DSRC) DSRC per patient-year All DSRC occurred within 30 days of implant No sensor failures Days from Implant Procedure No. At Risk

41 CHAMPION Trial The Effect of Fancy Tools 2.0 Nelson-Aalen Cumulative Hazard Rate Month Primary Endpoint, 28% reduction, P= Entire Randomized Access Phase, 33% reduction, P < Treatment Control No. At Risk Days from Implant Treatment Control Abraham WT, Adamson PB, Bourge RC, et al: Lancet 2012 Not approved by USFDA

42 BD Pg 61 All Secondary Efficacy Endpoints Met Tested in Hierarchical Fashion CR-42 Change from Baseline in Mean Pulmonary Artery Pressure, mean AUC (mmhg-days) Proportion of Patients Hospitalized for HF Days Alive Outside the Hospital for HF, mean Quality of Life (Minnesota Living with HF Questionnaire), mean Treatment (n=270) Control (n=280) p-value (20%) 80 (29%) p value from two-group t-test

43 Supplementary Analysis Over Study Duration Rate of HF Hospitalizations by Baseline Ejection Fraction EF p= RRR=33% Treatment Control p= RRR=52% HF Hospitalization Rate N=208 N=222 N=62 N=57 Reduced (EF<40%) Preserved (EF 40%)

44 All-Cause 30 Day Readmission Rates After HF Hospitalization - CHAMPION CHAMPION Control 23 % CHAMPION Treatment 14 %* *FDA Panel Proceedings October 2013

45 Heart Failure Medication Changes PA Pressure versus Non-Pressure Based CR-45 Average medication changes/patient month p value from Wilcoxon rank sum test BD Pg p< NA Total Pressure Based Non-pressure Based Up to 6 Month Follow-up Period Treatment ~1 more pressure based medication change per patient per month in treatment group Control

46 BD Pg 113 Baseline to 6 Months HF Medications Change in Dose CR-46 Total daily Dose Mean Change from baseline (mg) Treatment Control Beta-blocker ACE/ARB Aldosterone OPT at baseline Antagonists Nitrates Hydralazine Loop Diuretic Beta-blocker -Carvedilol equivalent, ACE/ARB- Enalapril equivalent, Diuretic -Furosemide equivalent

47 Clinical Significance of CHAMPION Results Intervention Trial Mean Duration of Randomized Follow-Up Annualized Reduction in HF Hospitalization Rates Number Needed to Treat (NNT) per year to Prevent 1 HF Hospitalization Beta-blocker COPERNICUS 10 months 33% 7 Aldosterone antagonist RALES 24 months 36% 7 Cardiac resynchronization CARE-HF 29 months 52% 7 Beta-blocker MERIT-HF 12 months 29% 15 ACE inhibitor SOLVD 41 months 30% 15 Aldosterone antagonist EMPHASIS-HF 21 months 38% 16 Digoxin DIG 37 months 24% 17 Angiotensin receptor blocker Val-HeFT 23 months 23% 18 Angiotensin receptor blocker CHARM 40 months 27% 19 Pulmonary artery pressure monitoring at home CHAMPION 17 months 33% 4 Abraham WT, Adamson PB, Bourge RC, et al Lancet 2012 USFDA Panel proceedings October 2013

48 We NEED New Technology to Modify OUTCOMES!! Filling pressures Increase Intrathoracic Impedance Changes Hospitalization Symptoms Days Autonomic Adaptation Weights Change Adamson PB Curr Heart Fail Reports 2009;6:287

49 Implantable Device Monitoring Hypothesis Avoiding Clinical Events Medical Intervention Averted Heart Failure Event Monitoring to Promote Stability Days Proactive Adamson PB Curr Heart Fail Reports 2009;6:287 49

50 Application of New Technology Prevention vs. Crisis Management Maintaining Stability Right Signal Rapid Re-evaluation Right Response Actionable Adapted from LW Stevenson et al