Congestive Heart Failure: Turning Failure Into Success. Wednesday, Feb 21, 2018

Transcription

1 Congestive Heart Failure: Turning Failure Into Success Wednesday, Feb 21, 2018

2 Welcome & Opening Remarks Robert T. Smith, MD, FACP

3 Introduction of Conference Theme & Speaker Brian Schwartz, MD, FACP, FACC, FSCAI Kettering Heart and Vascular Medical Director

4 Keynote Speaker Javed Butler, MD, PhD Heart Failure 2018: Where Are We and Where Are We Going! Evolution to HFpEF

5 Q&A With Dr. Butler Robert T. Smith, MD, FACP

6 Break, Vendor Fair, and Refreshments

7 Understanding HFrEF/Advanced HF Deepthi Mosali, MD, FACC

8 Mechanisms of HFrEF

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13 Effects of persistent SNS activation

14 RAAS System activation

15 Natriuretic Peptides

16 Beta-Adrenergic signaling

17 Excitation-Contraction coupling

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19 Changes in the biology of the failing heart

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26 Is that it? Lot of patients with so called stable chronic ds are indeed not stable with most patients exhibiting elevated cardiac biomarkers such as troponin reflective of continued cardiomyocyte necrosis or loss. This is reflective of a underlying dynamic process contributing to ds progression

27 Mechanisms that drive LV Dysfunction: Intrinsic 1. Cardiac Apoptosis cardiomyocyte loss is the hallmark of HFrEF. Limited capacity for self renewal so gradual loss f functional units through cell death leads to ds progression 2. Mitochondrial abnormalities: abnormalities of ATP synthesis and excess production of ROS. 3. Impaired intracellular calcium cycling (calcium signalling plays an important role in modulating systolic and diastolic function and in regulating excitation-contraction coupling. Abnormalities of intracellular calcium handling such a reduced SERCA activity, impaired phosphorylation of phospholamban and ryanodine channel leading to calcium leaks. This ca cause calcium overload, arrhythmias, cardiomyocyte dysfunction and death 4. Wall stress (Laplace s law, increased MVO2) 5. Fibrosis and cardiomyocyte hypertrophy (reactive interstitial fibrosis, reduced capillary density, increased oxygen diffusion all causing hypoxia and increasing LV stiffness and contributing to LV dysfunction

28 Physiology Hemodynamics and PV loops

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38 Therapeutics Targeting the Neuroharmonal pathways Treating at the periphery Despite blockade of the maladaptive processes there is still progression of disease

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41 Mechanism of ARNI

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44 Biomarkers

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46 Progression to Stage D or Advanced HF

47 Advanced HF is the presence of progressive and/or persistent severe symptoms of heart failure despite optimized medical, surgical and device therapy

48 HFrEF now becomes a systemic ds Passive liver congestion, ascites Bone marrow dysfunction and anemia Endothelial dysfunction Sleep disordered breathing Renal dysfunction Skeletal muscle abnormalities Persistent venous congestion causes inflammation with elevated biomarkers and systemic inflammation

49 Who Has Advanced Heart Failure? Definition and Epidemiology Congestive Heart Failure Volume 17, Issue 4, pages , 21 JUL 2011 DOI: /j x

50 A depiction of the clinical course of heart failure with associated types and intensities of available therapies. Larry A. Allen et al. Circulation. 2012;125: Copyright American Heart Association, Inc. All rights reserved.

51 ACC/AHA/HFSA focused updated guidelines for HF

52 Impact of recurrent heart failure hospitalization on mortality. Median survival (50% mortality) with 95% confidence limits in patients with heart failure after each heart failure hospitalization. (From Setoguchi S, Stevenson LW, Schneeweiss S. Repeated hospitalizations predict mortality in the community population with heart failure. Am Heart J 2007;154(2):262;)

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54 Who Has Advanced Heart Failure? Definition and Epidemiology Congestive Heart Failure Volume 17, Issue 4, pages , 21 JUL 2011 DOI: /j x

55 END OF PRESENTATION

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62 Clinical Assessment

63 Who Has Advanced Heart Failure? Definition and Epidemiology Congestive Heart Failure Volume 17, Issue 4, pages , 21 JUL 2011 DOI: /j x

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65 Virtual Heart Failure Clinic Smart HF management Sateesh Kesari MD FACC

66 Disclosures I have no current or past relationships with commercial entities Speaking fees for current program: I have received no speaker s fee for this learning activity Acknowledgements: Slides courtesy of Abbott/ST Jude Medtronic Boston Scientific

67 Scope of the presentation Financial and clinical burden of heart failure Tele monitoring Device monitoring Hemodynamic monitoring

68 Scope of the presentation Financial and clinical burden of heart failure Tele monitoring Device monitoring Hemodynamic monitoring

69 Heart Failure is a Growing Economic Burden UNITED STATES HOSPITALIZATIONS AND READMISSIONS > 1,100,000 hospitalizations > 3,000,000 hospitalizations for HF 1 include HF as ~5 days average length of hospital a contributor. 2 ~25% all-cause readmission stay 3 within 30 days; ~50% within 6 months. 4,5 Total medical costs for HF are projected to increase to $70B by 2030, a 2x increase from 2013.* COSTS 50% of the costs are attributed to hospitalization. 6 Despite advances in medical therapies to treat heart failure, the hospitalization rate has not changed significantly from As a result, heart failure continues to be a MAJOR DRIVER OF OVERALL HEALTH CARE COSTS. *Study projections assumes HF prevalence remains constant and continuation of current hospitalization practices 1. CDC NCHS National Hospital Discharge Survey, Blekcer et al. J Am Coll Cardiol, Yancy et al. J Am Coll Cardiol, Wxler DJ, et al. Am Heart J, Krumholz HM, et al. Circ Cardiovas Qual Outcomes, Yancy CW, et al. Circulation, SJM-MEM (1)a(9) Item approved for global use. 69

70 Heart Failure is a Growing Global Clinical Burden UNITED STATES PREVALENCE 2.2% Prevalence 1 5.7m HF patients 1 Projected to increase to > 8M people 18 years of age with HF by INCIDENCE 915,000 people 45 years of age are newly diagnosed each year with HF. 1 MORBIDITY AND MORTALITY For AHA/ACC stage C/D patients diagnosed with HF: 50% 50% 6 months. 2 5 years. 3 Readmitted within Will die within HIGH INCIDENCE, HIGH PREVALENCE, AND POOR PROGNOSIS despite advances in the treatment of heart failure over the past few decades. 1. AHA 2016 Statistics at a Glance, Krumholz HM, et al. Circ Cardiovas Qual Outcomes, Heidenreich PA, et al. Circ Heart Failure, SJM-MEM (1)a(9) Item approved for global use. 70

71 Long-term Mortality Risk Increases with Multiple Hospitalizations Mortality Survival Setoguchi S, Stevenson LW, Schneeweiss S, Am Heart J, 2007;154:

72 MYOCARDIAL FUNCTION Goal of Heart Failure Management: SLOW DISEASE PROGRESSION BY PREVENTING DECOMPENSATION EACH EVENT ACCELERATES DOWNWARD SPIRAL OF MYOCARDIAL FUNCTION With each subsequent HF-related admission, the patient leaves the hospital with a further decrease in cardiac function. Acute Event THE GOAL: Maintain fluid volume to avoid acute decompensation and hospitalization TIME Gheorghiade MD, et al. Am J. Cardiol, HF HOSPITALIZATION is a valid endpoint for measuring decompensation SJM-MEM (1)a(9) Item approved for global use. 72

73 Scope of the presentation Financial and clinical burden of heart failure Tele monitoring Device monitoring Hemodynamic monitoring

74 Monitored days of a HF patient. Lynn Stevenson et al

75 Parameters Daily Impedence Ventricular pacing (ICD) Heart rate variability Night time HR Patient Activity Atrial fibrillation/at/afl Biventricular pacing < 90% Ventricular tachycardia/icd shocks

76 Remote monitoring HF trials TRIAL N PARAMETER MONITORED IMPACT ON HF HOSPITALIZATION TELE-HF 1 1,653 Signs/symptoms, daily weights None JOURNAL The New England Journal of Medicine, 2010 TIM-HF Signs/symptoms, daily weights None Circulation, 2011 TEN- HMS BEAT-HF 4 1,437 INH DOT-HF Signs/symptoms, daily weights, BP, nurse telephone support None Journal of the American College of Cardiology, 2005 Signs/symptoms, daily weights, nurse communications None American Heart Association, 2016 Signs/symptoms, telemonitoring, nurse coordinated DM None Circulation Heart Failure, 2012 Intrathoracic impedance with patient alert Increased Circulation, 2011 Optilink 7 1,002 Intrathoracic impedance None REM-HF 8 1,650 MORE CARE Total 8,793 Remote monitoring via ICD, CRT-D or CRT-P Remote monitoring of advanced diagnostics via CRT-D None None MULTIPLE TRIALS, > 8,500 PATIENTS: No reduction in HF hospitalization European Journal of Heart Failure, 2011 European Society of Cardiology, 2017 European Journal of Heart Failure, Chaudhry SI, et al. N Engl J Med, Ong MK, et al. JAMA Intern Med, van Veldhuisen DJ, et al. Circulation, Cowie MR, ESC, Koehler F, et al. Circulation, Angermann DE, et al. Circ Heart Fail, Brachmann J, et al. Eur J Heart Fail, Boriani G, et al. Eur J Heart Fail, Cleland JG, et al. J Am Coll Cardiol, SJM-MEM (1)a(9) Item approved for global use. 76

77 Impedence

78 Impedence

79 Example # 1 Impedence cases Example # 2 -Drop in Impedence -Preceded by AT/AF -High Ventricular rates -Loss of CRT pacing -Drop in impedence -followed by VT storm

80 Device monitoring with multiple paramaters Heart Logic Multisense trial Manage HF trial Beacon HF system Partners HF trial

81 Multisense trial for HeartLogic JACC: Heart Failure vol 5. no. march 2017;216-25

82 HeartLogic index trend in pts with and without HFE JACC: Heart Failure vol 5. no. march 2017;216-25

83 Disclosures

84 PARTNERS-HF: COMBINED DIAGNOSTICS Partners HF study showed monthly review of HF diagnostic data could have identified patients at higher risk of HF hospitalizations within the subsequent month. OptiVol/HFMR identified patients were 5.5 times as likely to be hospitalized within 30 days + Diagnostic TWO diagnostic criteria met Whellan DJ, et al. J Am Coll Cardiol. 2010;55: Fluid Index 100 Fluid Index 60 Avg. Activity < 1 hr over 1 week Avg night HR > 85 bpm for 7 consecutive days HRV < 60 ms for 7 consecutive days % V pacing < 90% for 5 of 7 days One or more shocks AF > 6 hrs on at least one day in pts without persistent AF AF > 24 hrs & VR-AF > 90 bpm N = 694 patients Monthly Evaluations = 5693 HF Events = Beacon Heart Failure Management Service Division of Medtronic Care Management Services Confidential Information

85 LONGITUDINAL PATIENT DATA TRIAGE COMBINING DEVICE DIAGNOSTICS & EXTERNAL BIOMETRICS BROAD CLINICAL INPUTS ROBUST RISK ANALYSIS EXPERT CHFN* ASSESSMENT ACTIONABLE REPORTING DEVICE DIAGNOSTICS OptiVol + Parameters Symptom Acuity Multiple High Risk Markers Identified, Follow up 24 hours! Care Plan Adherence BIOMETRICS SYMPTOMS Clinical Intervention Ongoing Education BEACON HF MGMT REPORT High Risk Markers Identified, Follow up 72 hours Limited High Risk Markers Identified, Follow Up 1 week RISK STRATIFICATION IP/ER EVENT STATUS CHFN Analysis Low Risk, Routine Clinical Follow Up *Certified Heart Failure Nurse, certified by the American Association of Heart Failure Nurses Beacon Heart Failure Management Service Division of Medtronic Care Management Services Confidential Information 85

86 Device Diagnostics COMBINING DYNAMIC DATA TO PROVIDE ADVANCED INSIGHTS % monthly evaluations with HF hospitalizations in next 30 days Diagnostic Parameters Dynamic Algorithm 1 Bayesian Combination 10x Greater Risk Probability / Likelihood Off.. Days after diagnostic evaluation Patients with a high risk score were 10 times more likely to have a heart failure event in the next 30 days than those with a low risk score 1 1 Cowie MR, Sarkar S, Koehler J, et al. Eur Heart J Aug;34(31): Beacon Heart Failure Management Service Division of Medtronic Care Management Services Confidential Information

87 Scope of the presentation Burden of heart failure with financial and clinical impact Tele monitoring Device monitoring Hemodynamic monitoring

88 Current Parameters for Managing HF are Reactive and Inexact HOSPITALIZATION Reactive and Inexact Weight Change Symptoms Autonomic Adaptation Transthoracic Impedance CHANGE Filling Pressure INCREASE Hemodynamically Stable Presymptomatic Congestion Decompensation Time Preceding Hospitalization (Days) Adamson PB, et al. Curr Heart Fail Reports, SJM-MEM (1)a(9) Item approved for global use. 88

89 Monitoring for Increased Filling Pressures is Proactive and Actionable, and Predictive of Acute Decompensation Reactive and Inexact Weight Change Symptoms HOSPITALIZATION Proactive and Actionable Autonomic Adaptation Transthoracic Impedance CHANGE Filling Pressure INCREASE Hemodynamically Stable Presymptomatic Congestion Decompensation Time Preceding Hospitalization (Days) Adamson PB, et al. Curr Heart Fail Reports, SJM-MEM (1)a(9) Item approved for global use. 89

90 Monitoring Pulmonary Artery Pressures, Proactive and Actionable GAIN IN TIME Clinical Congestion HOSPITALIZATION Hemodynamic Congestion Reactive and Inexact Weight Change Symptoms Proactive and Actionable Autonomic Adaptation Transthoracic Impedance CHANGE Filling Pressure INCREASE Hemodynamically Stable Presymptomatic Congestion Decompensation Time Preceding Hospitalization (Days) Adamson PB, et al. Curr Heart Fail Reports, SJM-MEM (1)a(9) Item approved for global use. 90

91 Monitoring Pulmonary Artery Pressures, Proactive and Actionable GAIN IN TIME Clinical Congestion HOSPITALIZATION Hemodynamic Congestion Reactive and Inexact Weight Change Symptoms Proactive and Actionable Autonomic Adaptation Transthoracic Impedance CHANGE Filling Pressure INCREASE Physical exam Tele monitoring Hemodynamically Stable Presymptomatic Congestion Decompensation Time Preceding Hospitalization (Days) Adamson PB, et al. Curr Heart Fail Reports, SJM-MEM (1)a(9) Item approved for global use. 91

92 Monitoring Pulmonary Artery Pressures, Proactive and Actionable GAIN IN TIME Clinical Congestion HOSPITALIZATION Hemodynamic Congestion Reactive and Inexact Weight Change Symptoms Proactive and Actionable Autonomic Adaptation Transthoracic Impedance CHANGE Filling Pressure INCREASE Device monitoring Physical exam Tele monitoring Hemodynamically Stable Presymptomatic Congestion Decompensation Time Preceding Hospitalization (Days) Adamson PB, et al. Curr Heart Fail Reports, SJM-MEM (1)a(9) Item approved for global use. 92

93 Monitoring Pulmonary Artery Pressures, Proactive and Actionable Clinical Congestion GAIN IN TIME HOSPITALIZATION Hemodynamic Congestion Reactive and Inexact Weight Change Symptoms Proactive and Actionable Autonomic Adaptation Transthoracic Impedance CHANGE Filling Pressure INCREASE Hemodynamic monitoring Device monitoring Physical exam Tele monitoring Hemodynamically Stable Presymptomatic Congestion Decompensation Time Preceding Hospitalization (Days) Adamson PB, et al. Curr Heart Fail Reports, SJM-MEM (1)a(9) Item approved for global use. 93

94 Intracardiac hemodynamics Chronicle device Zile et al, Circulation. 2008;118:

95 CardioMEMS HF System for the Management of HF Delivers insight into the early onset of worsening HF to more proactively manage HF patients and improve outcomes PULMONARY ARTERY PRESSURE SENSOR TARGET LOCATION FOR PA PRESSURE SENSOR PATIENT ELECTRONICS SYSTEM MERLIN.NET PCN Abraham WT, Lancet, SJM-MEM (1)a(9) Item approved for 9 global use. 5

96 Microelectrical Mechanical System (MEMS) No lead or battery, no need for replacement SJM-MEM (1)a(9) Item approved for global use. 96

97 The CardioMEMS HF System Implant Procedure PA PRESSURE SENSOR IS INSERTED DURING A RIGHT HEART CATHETERIZATION PROCEDURE VIA FEMORAL VEIN APPROACH SJM-MEM (1)a(9) Item approved for global use. 97

98 Summary of CHAMPION Randomized Clinical Trial: 550 PREVIOUSLY HOSPITALIZED NYHA CLASS III PATIENTS Pulmonary Artery Pressure Medication Changes Based on Pulmonary Artery Pressure (p < ) Pulmonary Artery Pressure Reduction (p = 0.008) MANAGING PRESSURES TO TARGET GOAL RANGES: PA pressure systolic mmhg PA pressure diastolic 8 20 mmhg PA pressure mean mmhg Reduction in Heart Failure Hospitalizations (p < ) Quality of Life Improvement (p = 0.024) Using diuretics and vasodilators, in addition to guideline-directed medical therapies 1. Abraham WT, et al. Lancet, Abraham WT, et al. Lancet, Adamson PB, et al. J Card Fail, 2010.

99 Cumulative Hazard Rate Primary Efficacy Endpoint Met with Significantly Reduced Heart Failure Hospitalization PART 1: RANDOMIZED ACCESS 33% RELATIVE RISK REDUCTION IN HF HOSPITALIZATIONS: TREATMENT GROUP VS. CONTROL GROUP CONTROL TREATMENT p < No. at Risk Days From Implant CONTROL TREATMENT Abraham W, et al. Lancet, SJM-MEM (1)a(9) Item approved for global use. 99

100 Freedom from Device/System Related Complications (%) Both Primary Safety Endpoints Met 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 SJM-MEM (1)a(9) Item approved for global use. 100

101 All Secondary Endpoints Met PART 1: RANDOMIZED ACCESS PART 2: OPEN ACCESS PART 1: RANDOMIZED ACCESS TREATMENT (N = 270) CONTROL (N = 280) P-VALUE Change from baseline in PA mean pressure (mean AUC [mmhg x days]) SECONDARY ENDPOINTS Number and proportion of patients hospitalized for HF (%) 55 (20%) 80 (29%) 0.03 Days alive and out of hospital for HF (mean ± SD) ± ± Quality of life (Minnesota Living with Heart Failure Questionnaire, mean ± SD) 45 ± ± *Total of 8 DSRCs including 2 events in Consented not implanted patients (n = 25) Abraham WT, et al. Lancet, SJM-MEM (1)a(9) Item approved for global use. 101

102 Real-world Use of the CardioMEMS HF System: ASSOCIATED HF HOSPITALIZATION COSTS $80K $70K $60K -$13,190 $50K $40K $30K $20K $10K -$10,510 $28,870 $18,360 $47,690 $34,500 $0K 6-MONTH COHORT Pre-Implant 12-MONTH COHORT Post-Implant Large (N = 1114) retrospective cohort study using the CardioMEMS HF System patients from CMS database Desai, AS, et al. J Am Coll Cardiol, 2017;69(19): SJM-MEM (1)a(9) Item approved for global use

103 Monitoring Pulmonary Artery Pressures, Proactive and Actionable GAIN IN TIME Clinical Congestion HOSPITALIZATION Hemodynamic Congestion Reactive and Inexact Weight Change Symptoms Proactive and Actionable Autonomic Adaptation Transthoracic Impedance CHANGE Filling Pressure INCREASE Physical exam Tele monitoring Hemodynamically Stable Presymptomatic Congestion Decompensation Time Preceding Hospitalization (Days) Adamson PB, et al. Curr Heart Fail Reports, SJM-MEM (1)a(9) Item approved for global use. 103

104 Monitoring Pulmonary Artery Pressures, Proactive and Actionable GAIN IN TIME Clinical Congestion HOSPITALIZATION Hemodynamic Congestion Reactive and Inexact Weight Change Symptoms Proactive and Actionable Autonomic Adaptation Transthoracic Impedance CHANGE Filling Pressure INCREASE Device monitoring Physical exam Tele monitoring Hemodynamically Stable Presymptomatic Congestion Decompensation Time Preceding Hospitalization (Days) Adamson PB, et al. Curr Heart Fail Reports, SJM-MEM (1)a(9) Item approved for global use. 104

105 Monitoring Pulmonary Artery Pressures, Proactive and Actionable Clinical Congestion GAIN IN TIME HOSPITALIZATION Hemodynamic Congestion Reactive and Inexact Weight Change Symptoms Proactive and Actionable Autonomic Adaptation Transthoracic Impedance CHANGE Filling Pressure INCREASE Hemodynamic monitoring Device monitoring Physical exam Tele monitoring Hemodynamically Stable Presymptomatic Congestion Decompensation Time Preceding Hospitalization (Days) Adamson PB, et al. Curr Heart Fail Reports, SJM-MEM (1)a(9) Item approved for global use. 105

106 Information Overload MA/Nurse APP/Physician

107 Workflow HF NP Reviews and adjusts treatment plan HF physician Patient transmits daily MA/Nurse reviews twice weekly initially and then prn for alerts EP njurse reviews and adjusts treatment EP Physician

108 Virtual HF clinic-key elements Identify key team members Alerts Patient selection Policies and procedures for monitoring Establish workflows/orders Staffing Keep medication changes on website Education Providers Patients Staff Buy in from other providers Network support for resources and staffing

109 The End

110 The CHAMPION Trial Subgroup Analyses PROSPECTIVE ANALYSES: Effects of PAP pressure monitoring on: HFpEF subgroup HFrEF subgroup, HFrEF subgroup already on GDMT RETROSPECTIVE SUBGROUP ANALYSES: T h e r a p y g u i d e d by PA P a l o n e v s. s i g n s a n d sympto m s M e d i c a r e - e l i g i b l e p o p u l a t i o n s PA-guided m e d i c a l m a n a g e m e n t H F p a t i e nts w i t h c o m m o n c o m o r b i d i t i e s SJM-MEM (1)a(9) Item approved for global use. 110

111 Prospective Subgroup Analysis: HFpEF PATIENTS MANAGED WITH THE CardioMEMS HF SYSTEM SHOW SIGNIFICANT REDUCTION IN HF Hospitalization Control Group, HFpEF Treatment Group, HFpEF 50 % reduction in HF Hospitalization Avg. 18 months follow-up 50% RRR, p < Adamson PB, Abraham WT, Bourge RC, et al. Circ Heart Fail, 2014 Nov;7(6): SJM-MEM (1)a(9) Item approved for global use. 111

112 Rates Events/Patient-yr Survival Probability (%) Prospective Subgroup Analysis: HFrEF PATIENTS SHOWS SIGNIFICANT REDUCTION IN HF Hospitalization AND STRONG TREND TOWARDS IMPROVED SURVIVAL * Clinical Outcomes Survival Probability p = % reduction 0.49 p = % reduction Control Treatment 0 HF Hospitalization Rate Control Mortality Rate Treatment No. at Risk CONTROL TREATMENT Kaplan-Meier Survival Analysis *The CardioMEMS HF System is not labeled for a reduction in mortality Givertz M, et al. J Am Coll Cardiol, SJM-MEM (1)a(9) Item approved for global use.112

113 HF Hospitalization/Patient-yr Deaths/Patient-yr HF Hospitalization/Patient-yr Deaths/Patient-yr Retrospective Subgroup Analysis: HFrEF PATIENTS SHOW SYNERGY BETWEEN OPTIMAL GDMT AND HEMODYNAMIC CARE Partial GDMT Optimal GDMT p = p = p = p = % reduction 37 % reduction 43 % reduction 57 % reduction HF Hospitalization Mortality HF Hospitalization Mortality Control Treatment Control Treatment *The CardioMEMS HF System is not labeled for a reduction in mortality Givertz M, et al. J Am Coll Cardiol, SJM-MEM (1)a(9) Item approved for global use.113

114 Managing GDMT Based on PA Pressures Alone Led to Significant Reduction in HF Hospitalization Clinical Only Triggered Rx Clinical Only Triggered Rx HF Hospitalization Rate (Events/year) p < 0.05 vs. Control Patients Clinical and PAP Triggered Rx 67 % RRR of HF Hospitalizations p = vs. Control Patients 0.39 Control Group PAP Management Group PAP Only Triggered Rx Managing medical therapy based on PA pressures, along with follow-up lab and patient assessment led to SIGNIFICANTLY BETTER OUTCOMES THAN MANAGING BASED ON CLINICAL SIGNS AND SYMPTOMS Goldberg, et al. HRS SJM-MEM (1)a(9) Item approved for global use.114

115 Number of Hospitalizations Events/Patient Year Subgroup Analysis: MEDICARE-ELIGIBLE POPULATION SHOWS SIGNIFICANT REDUCTION IN 30-DAY READMISSIONS % reduction p < p = p = HF Hospitalizations All Cause 30 Day Readmissions HF 30 Day Readmissions 13 Control (Standard of Care) Treatment (PA Pressure Monitoring) 58 % reduction 78 % 18 reduction 4 STATISTICALLY SIGNIFICANT REDUCTIONS in 30-day readmission and HF Hospitalization in Medicare-eligible patients 65 years or older (n = 245), when PA pressures are monitored using the CardioMEMS HF System. Adamson, et al. Circ Heart Fail, SJM-MEM (1)a(9) Item approved for global use.115

116 Subgroup Analysis: HFrEF PATIENTS WITH CRT-D FOLLOWING GDMT 64% reduction (p = 0.028) Abraham, et al. HRS SJM-MEM (1)a(9) Item approved for global use.116

117 Medication Changes Subgroup Analysis: PA-GUIDED MEDICAL MANAGEMENT Frequency of Medication Changes by Drug Class PA Pressure Guided HF Management (Treatment Group) Standard of Care HF Management Only (Control Group) All Medication Changes Diuretic (Loop or Thiazide) Vasodilator (Nitrate and Hydralazine) ACEI/ARB Beta Blocker Aldosterone Antagonist Medication changes based on PA pressure information were MORE EFFECTIVE IN REDUCING HF HOSPITALIZATIONS than using signs and symptoms alone. Costanzo, et al. J Am Coll Cardiol Heart Failure, SJM-MEM (1)a(9) Item approved for global use.117

118 Medication Dose Increases/Decreases from Baseline to 6 Months Medication Increases and Decreases in Response to PAP 1500 ALL MEDICATION CHANGES DIURETIC (LOOP AND THIAZIDE) VASODILATOR (NITRATE AND HYDRALAZINE) ACE/ARB BETA BLOCKER ALDOSTERONE ANTAGONIST PA Pressure Guided HF Management (Treatment Group) Standard of Care HF Management Only (Control Group) p < 0.05 PA Pressure Guided HF Management vs. Standard of Care HF Management No Change represents where a medication was changed (ie., dose frequency, route, etc.) which resulted in no net dose equivalent change Costanzo MR, et al. J Am Coll Cardiol HF, SJM-MEM (1)a(9) Item approved for global use.118

119 The CHAMPION Trial Subgroup Analyses: REDUCTION OF HF HOSPITALIZATION IN PATIENT GROUPS WITH COMMON COMORBIDITIES Sub-Group or Comorbidity n (control) n (treatment) Follow-up Period (months) Reduction of HF Hospitalization Rate in Treatment Group vs. control Medicare population %, p < HFpEF %, p < HFrEF following GDMT %, p < CRT-D or ICD following GDMT %, p < History of myocardial infarction %, p < COPD 6, %, p = Pulmonary hypertension %, p = AF %, p < Chronic kidney disease %, p = Patients with common HF comorbidities and patients in important subgroups HAVE CONSISTENT REDUCTION IN HF HOSPITALIZATIONS with PA pressure-guided therapy. 1. Adamson, et al. Circ Heart Fail, Adamson, et al. Circ Heart Fail, Abraham, et al. ACC, Abraham, et al. HRS Strickland WL, et al. J Am Coll Cardiol, Criner G, et al. Eur Respir J, Martinez F, et al. Eur Respir J, Benza R, et al. J Card Fail, Miller AB, et al. J Am Coll Cardiol, Abraham, et al. J Card Fail, SJM-MEM (1)a(9) Item approved for global use.119

120 Cumulative HF Hospitalizations Reduction of HF Hospitalization in the CardioMEMS HF System Post-Approval Study Days from Implant CHAMPION Control CHAMPION Treatment Post-Approval Study In the post-approval study, there were 56 HF Hospitalizations (0.20 events/pt-6m) in 43 pts Raval, et al. Presented at HFSA SJM-MEM (1)a(9) Item approved for global use.120

121 Number of Medication Changes Medication Changes Significantly Reduced in First 90 Days vs. Second 90 Days in the PAS Medication Changes First 90 days vs. second 90 days % reduction % reduction 341 Total Up Titrations Down Titrations New First 90 Days Second 90 Days 31% reduction 74% p < p < p = p < reduction 45 65% of the overall HF medication changes were made in the first 90 days, with trends of stabilization and significantly fewer medication changes during the second 90 days. Raval, et al. Presented at HFSA SJM-MEM (1)a(9) Item approved for global use.121

122 p = p < The CardioMEMS HF System PAS Short-term Results REDUCED HF Hospitalization AND MEAN PAP AUC (mmhg day) 1 Month 3 Months 6 Months CHAMPION Control (275 pts) 3.1 ± 6.7 (270 pts) -5.5 ± 24.7 (251 pts) 42.0 ± 65.0 (228 pts) Short-term Cohort (n = 300) CHAMPION Treatment (270 pts) -7.0 ± 7.7 (266 pts) ± 27.6 (257 pts) ± 71.0 (236 pts) CHAMPION Control CHAMPION Treatment Post Approval Study PAS (300 pts) ± 7.0 (291 pts) ± 26.0 (275 pts) ± 63.5 (262 pts) SIGNIFICANTLY GREATER REDUCTIONS IN MEAN PAP for the PAS cohort relative to the CHAMPION control group after 6 months, and QUALITATIVELY GREATER REDUCTIONS compared to the CHAMPION treatment group. Raval, et al. Presented at HFSA SJM-MEM (1)a(9) Item approved for global use. 122

123 Pressures are Reduced Equally Well in HFrEF and HFpEF, as well as Male and Female AUC Mean PAP Stratified by Ejection Fraction AUC Mean PAP Stratified by Gender EF 40 EF < 40 Female Male Heywood JT, Jermyn R, Shavelle D, et al. Circulation 2017;135: SJM-MEM (1)a(9) Item approved for global use.123

124 Pressure Changes Stratified by Baseline PA Pressure Baseline meanpap < 25 mmhg 35 > Baseline meanpap 25 mmhg Baseline meanpap 35 mmhg Greatest reduction in mean PAP observed for the CardioMEMS HF System patients with higher baseline PAP. Patients in the treatment group with baseline PAP at goal, remained at goal over time.. Heywood JT, Jermyn R, Shavelle D, et al. Circulation 2017;135: SJM-MEM (1)a(9) Item approved for global use.124

125 Real-world Use of the CardioMEMS HF System: REDUCED HF HOSPITALIZATIONS Cumulative HF Hospitalization During Period Before and After CardioMEMS HF System Implant 45% reduction at 6 months (p < 0.001) Pre-implant Post-implant PRE-IMPLANT POST-IMPLANT Time (months) Large (N = 1114) retrospective cohort study using the CardioMEMS HF System patients from CMS database Desai, AS, et al. J Am Coll Cardiol, 2017;69(19): SJM-MEM (1)a(9) Item approved for global use

126 Real-world Use of the CardioMEMS HF System: ASSOCIATED HF HOSPITALIZATION COSTS $80K $70K $60K -$13,190 $50K $40K $30K $20K $10K -$10,510 $28,870 $18,360 $47,690 $34,500 $0K 6-MONTH COHORT Pre-Implant 12-MONTH COHORT Post-Implant Large (N = 1114) retrospective cohort study using the CardioMEMS HF System patients from CMS database Desai, AS, et al. J Am Coll Cardiol, 2017;69(19): SJM-MEM (1)a(9) Item approved for global use

127 Distance (m) Score Northwell Health: SIGNIFICANT IMPROVEMENT IN FC AND QoL IN PATIENTS IMPLANTED WITH THE CardioMEMS HF SYSTEM KCCQ: 3-fold greater improvement in scores p < p = CardioMEMS (n = 34) Control (n = 32) Baseline 90 days 6-minute walk: Avg. increase of 96 meters at 90 days versus no increase in the SoC group 400 p < compared to baseline Baseline 30 days 90 days Alam A, et al. Abstract presented at ACC, CardioMEMS PA Sensor (n = 34) Control (n = 32) SJM-MEM (1)a(9) Item approved for global use.127

128 CONCLUDING SUMMARY The CardioMEMS HF System is safe, reliable and clinically proven in clinical trials and real-world settings. It provides a proactive, personalized approach to prevent acute decompensation in both HFrEF and HFpEF patients SJM-MEM (1)a(9) Item approved for global use. 128

129 Panel Discussion: Clinical Care Management Studies Acute Heart Failure, Cardiorenal Syndrome, Evolution to HFpEF

130 Closing Remarks Jayne Testa, CMPE Kettering Heart & Vascular Executive Director