New Hemodynamic Technologies in Heart Failure Management

Robert A. Watson III, MD, FACCCo-Director of Comprehensive Heart

Failure ProgramAbington- Jefferson Health

Disclosures

• None.

Prevalence, Incidence, Mortality and Hospitalization Rates

Economic Burden of HF and Medicare Reform Initiatives

HEART FAILURE

• In 2010, there were 1 million hospitalizations in the US with HF as the principal diagnosis1

– Hospitalization rate did not change significantly from 20001

• Average length of hospital stay

– Approximately 5 days (US)2

– 11 days (Europe)3

• HF is also associated with high readmission rates:

– ~25% all-cause readmission within 30 days and ~50% within 6 months4,5

Heart Failure Is Associated with High Hospitalization and Readmissions

Graph from www.health.org.uk. Bridging the gap: Heart Failure, 2010.

Data from Organization for Economic Cooperation and Development, 2009.

1. CDC NCHS National Hospital Discharge Survey, 2000-2010

2. Yancy et al. JACC, 2006.

3. Cleland et al. EuroHeart, 2003.

4. Krumholz HM, et al. Circ Cardiovas Qual Outcomes 2009.

5. Wexler DJ, et al. Am Heart J 2001.

Data from the EFFECT study, n = 9138 patients1

Among 1 year survivors after index EFFECT-HF discharge, the number of heart failure hospitalizations in the preceding year stratified the risk of death in crude analysis.1

Heart Failure Readmissions are Strong Predictors

Data from Setoguchi et al., n = 14,374 patients2

KP cumulative mortality curve for all-cause mortality after each subsequent hospitalization for HF.2

Studies show each admission decreases a patient’s chance of survival.

1. Lee DS, et al. Am J of Med, 2009.

2. Setoguchi S, et al. Am Heart J, 2007.

Medicare’s Hospital Readmissions Reduction program penalizes hospitals that have above average all-cause readmissions within 30 days following HFdischarge.

Percent withholding of all inpatient Medicare payments will increase to up to 3% by 2015 and beyond.3

Economic Risks of HF Readmissions in the US

22.7%national average 30-day

readmissions rate1,2

Fiscal Year 2013 2014 2015+

% payment withholding up to 1% up to 2% up to 3%1. Dharmarajan K, et al. JAMA. 2013;309(4):355-363.

2. Linden A, Adler-Milstein J. Health Care Finance Rev. 2008;29(3):1-11.

3. CMS Hospitals Readmissions Reductions Program of the Patient Protection and Affordable Care Act (PPACA), 2010.

Worsening Heart Failure/Physiologic Markers of Decompensation

Weight, Blood Pressure, Symptoms

Impedance

Clinical Evaluations

PHYSIOLOGIC MONITORING

Physiologic Markers of Acute Decompensation

Graph adapted from Adamson PB, et al. Curr Heart Fail Reports, 2009.

• 90% of HF hospitalizations present with symptoms of pulmonary congestion.1,2

• Post-hoc analysis of 463 acute decompensated HF patients from DOSE-HF and CARRESS-HFtrials showed:

– 40% of patients are discharged with moderate to severe congestion.3

– Of patients decongested at discharge, 41% had severe or partial re-congestion by 60 days.3

59%24%

17%

Congestion state of patients discharged without congestion at 60-day follow-up3

Maintained decongestion

Partial recongestion

Relapse to severe congestion

Current HF Management Is Inadequate For Identifying and Managing Congestion Leading

to DecompensationIdentifying congestion early will lead to early treatment,

prevent hospitalizations and slow the progression of HF.

60%40%

Congestion state at discharge

Absent or mild congestion

Moderate to severe congestion

1. Adams KF, et al. Am Heart J. 2005

2. Krum H and Abraham WT. Lancet 2009

3. Lala A, et al. JCF 2013

• Randomized study of 1653 patients

• Primary endpoint: Readmission for any reason or death from any cause within 180 daysafter enrollment

• Control group = Standard-of-care (no telemonitoring)

• Treatment group = telemonitoring of symptoms and weight

• Results: No difference in number of deaths, readmissions or days in hospital

TELE-HF Trial: Telemonitoring of Weight and Symptoms Do Not Reduce Readmission or Death

0

10

20

30

40

50

60

Re-hospitalization Death

% o

f P

atie

nts Telemonitoring of Symptoms

and Weight group

Standard-of-care Group

p =

0.39

p = 0.86

Chaudhry SI, et al. N Engl J Med, 2010.

Monitoring intrathoracic impedance (OptiVol™ algorithm, Medtronic) with an audible alert did not improve mortality and increased HF hospitalizations

DOT-HF Trial: Monitoring Impedance With Audible Alert Increased HF

Hospitalizations

van Veldhuisen DJ, et al. Circulation, 2011.

• Intra-thoracic impedance has been shown to be more sensitive than weight changes.1

• Impedance still has a high false-positive rate1-3 when used to predict acute events.

Note:

• Results from FAST1 and MID-HeFT3 are not included in the table above as these studies used a broader definition of True Positive and therefore cannot be compared to the results from SENSE-HF.

• Definition for True Positive was comparable but not the same in the calculations for Sensitivity, FP/pt/yr, and PPV% between SENSE-HF and DEFEAT-PE; therefore, these numbers should not be directly compared.

Sensitivity of Impedance

Study FP/pt/yr PPV % Sensitivity %

SENSE-HF2 1 4.7 20.7-42.1

DEFEAT-PE4 0.96 16.07 26.6%

1. Abraham WT, et al. Congest Heart Fail, 2011.

2. Conraads VM, et al. EHJ, 2011.

3. Yu CM, et al. Circulation, 2005.

4. St. Jude Medical. Bradycardia and Tachycardia Devices Merlin® Patient Care System Help Manual, 2012.

Data from clinical evaluations has poor sensitivity and predictive value in determining hemodynamic profile

Clinical Examination has Limited Reliability in Assessing Filling

PressuresCapomolla, 2005. N = 366

VariableEstimate

ofSensitivity (%) Specificity (%)

PPV

(%)

NPV

(%)

JVP

Edema

RAP 48

10

78

94

60

55

69

60

Pulse Press Cardiac Index 27 69 52 44

S3

Dyspnea

Rales

PCWP 36

50

13

81

73

90

69

67

60

54

57

48

Table adapted from Capomolla S, et al. Eur J Heart Failure, 2005.

Managing Pressures in the Heart Failure Patient

CardioMEMS™ HF System

CHAMPION Clinical Trial

HEMODYNAMIC MONITORING FOR HEART FAILURE MANAGEMENT

Managing Pressures in the Heart Failure Patient

Pressures Patient

When patients are stable Their pressures remain very stable over time.

When patients decompensate Pressures increase, leading to exacerbation.

The pressures return to baseline when

the exacerbation is treated and volume

returns to normal

Pressures reflect the underlying volume state

in HF patients.

Strongly supports the hypothesis that measuring

those pressures frequently or continuously using

implantable devices and managing those pressures

may be a superior management strategy.

Managing to targeted pressure ranges Can reduce overall pressures and ultimately

lead to a reduction in HF events.

Adamson PB, et al. Curr Heart Fail Reports, 2009

• Prospective, multicenter randomized, single-blind trial of 274 class III/IV HF patients

• Increases in PA Pressures – Not Body Weight – Precede HF Hospitalization

COMPASS Trial: Monitoring of Hemodynamic Data

Data based on Zile MR, et al. Circulation, 2008. Presented at FDA Advisory Panel, October 9, 2013

Pulmonary Artery Pressure Sensor

Patient Electronics System

CardioMEMS™ HF System Website

CardioMEMS™ HF System

The pulmonary artery pressure sensor is implanted via a right heart catheterization procedure via femoral vein approach.

CardioMEMS™ HF SystemTarget location for pulmonary artery pressure sensor

Patients with moderate NYHA class III HF for at least 3 months, irrespective of LVEFand a HF hospitalization within the past 12 months were included in the study.

CHAMPION Clinical Trial: The Effect of Pulmonary Artery Pressure-Guided Therapy on HF Hospitalizations vs. Standard of Care

550 Pts with CardioMEMS™ HF System Implants

All Pts Take Daily readings

Treatment

270 Pts

Management Based on

PA Pressure +Traditional Info

Control

280 Pts

Management Based on

Traditional Info

26 (9.6%) Exited

< 6 Months

15 (5.6%) Death

11 (4.0%) Other

Primary Endpoint: Rate of HF Hospitalization26 (9.6%) Exited

< 6 Months

20 (7.1%) Death

6 (2.2%) Other

Secondary Endpoints:

Change in PA Pressure at 6 months

No. of patients admitted to hospital for HF

Days alive outside of hospital

QOLAbraham WT, et al. Lancet, 2011.

e

CHAMPION Clinical Trial: Managing Target PA Pressures

550 Pts with CardioMEMS™ HF System Implants

All Pts Take Daily readings

Treatment

270 Pts

Management Based on

PA Pressure +Traditional Info

Control

280 Pts

Management Based on

Traditional Info

26 (9.6%) Exited

< 6 Months

15 (5.6%) Death

11 (4.0%) Other

Primary Endpoint: rate of HF Hospitalization26 (9.6%) Exited

< 6 Months

20 (7.1%) Death

6 (2.2%) Other

Secondary Endpoints included:

Change in PA Pressure at 6 months

No. of patients admitted to hospital for HF

Days alive outside of hospital

QOL

PA pressures were managed to target goal

pressures by physicians with appropriate

titration of HF medications.

Target Goal PA Pressures:

PA Pressure Systolic 15 – 35 mmHg

PA Pressure diastolic 8 – 20 mmHg

PA Pressure mean 10 – 25 mmHg

Abraham WT, et al. Lancet, 2011.

CHAMPION Clinical Trial: PA Pressure-guided Therapy Reduces HF

Hospitalizations

Patients managed with PA pressure data had significantly fewer

HF hospitalizations as compared to the control group.Abraham WT, et al. Lancet, 2011.

Treatment

(n = 270)

Control

(n = 280)P-value

Primary Safety

Endpoints

Device-related or system-related complications3 (1%) 3 (1%)

Total 8 (1%)* < 0.0001

Pressure-sensor failures 0 0 < 0.0001

Secondary

Endpoints

Change from baseline in PA mean pressure

(mean AUC [mm Hg x days])-156 33 0.008

Number and proportion of patients hospitalized

for HF (%)55 (20%) 80 (29%) 0.03

Days alive and out of hospital for HF (mean ±

SD)

174.4 ±

31.1172.1 ± 37.8 0.02

Quality of life (Minnesota Living with Heart

Failure Questionnaire, mean ± SD)45 ± 26 51±25 0.02

CHAMPION CLINICAL Trial: Both Primary Safety Endpoints and All Secondary Endpoints Were Met at 6 months

* Total of 8 DSRCs including 2 events in Consented not implanted patients (n = 25)

Abraham WT, et al. Lancet, 2011.

CHAMPION Clinical Trial: Reasons for Medication Changes

~1 per patient month

2517

1113

1404

1061 1061

0

500

1000

1500

2000

2500

3000

Total Based on signs& symptoms

Based on knowledgeof PA pressures

Nu

mb

er o

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edic

atio

n c

han

ges

du

rin

g P

rim

ary

En

dp

oin

t P

erio

d

Treatment Control

CHAMPION Clinical Trial: PA Pressure Mean Change from Baseline

PA

Me

an

Pre

as

ure

AU

C (

mm

Hg

-Da

ys

)

-220

-200

-180

-160

-140

-120

-100

-80

-60

-40

-20

0

20

40

60

80

100

Days from Implant

0 30 60 90 120 150 180

p = 0.0077

Treatment (-155.7 mmHg-Days)Control (33.1 mmHg-Days)

CHAMPION Clinical Trial: By Targeting Pressure Ranges and Titrating Medications, Overall PA

Pressures Can Be Reduced

Monitoring of PA pressure with the CardioMEMS™ HF System allows managing the pressure

spikes that lead directly to exacerbation, as well as the long-term trends.

Compared to the control group,

patients managed with PA pressure

had persistently lower mean PA

pressures over the treatment period.

Abraham WT, et al. Lancet, 2011.

Intervention Trial

Mean Duration

of Randomized

Follow-Up

Annualized Reduction

in HF Hospitalization

Rates

NNT per year to

Prevent 1 HF

Hospitalization

Beta-blocker COPERNICUS 10 months 33% 7

Aldosterone antagonist RALES 24 months 36% 7

CRT 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 blockerVal-HeFT 23 months 23% 18

Angiotensin

receptor blockerCHARM 40 months 27% 19

PA pressure monitoring CHAMPION 17 months 33% 4

CHAMPION Clinical Trial: The Number Needed to Treat (NNT) to Prevent One HF-related Hospitalization is Lower vs. Other Therapies

Cost reduction is attributable to1:

Economic Analysis shows that PA pressure Monitoring is Cost Effective

Reduction in hospitalization

Reduction in mortality

Improvement in quality of life

$30,167 ICER

BELOW THE US ACCEPTED ICER

THRESHOLD OF $50,000 PER QALY2

Well under the World Health Organization

threshold of approximately $160,000

for the US3

1. Adamson et al HRS 2015

2. Weinstein MC Med Care 2008

3. Neumann et al NEJM 2014

Pulmonary Artery Pressure

Medication Changes based on Pulmonary Artery Pressure (p < 0.0001)

Pulmonary Artery Pressure Reduction (p = 0.008)

Reduction in Heart Failure Hospitalizations (p < 0.0001)

Quality of Life Improvement (p = 0.024)

Managing pressures to target goal ranges:

PA Pressure systolic 15–35 mmHg

PA Pressure diastolic 8–20 mmHg

PA Pressure mean 10–25 mmHg

Summary: CHAMPION Clinical Trial

Abraham WT, et al. Lancet, 2011.

• Preserved Ejection Fraction Heart Failure (HFpEF) or diastolic HF patients represent ~50% of all HF patients

• Pulmonary artery pressure-guided therapy significantly reduced HF hospitalizations in HFpEF patients in the treatment group by 46% at 6 months (p<0.0001) and by 50% at 18 months (p<0.0001)

• The effect in HFpEF patients is even more dramatic than HFrEF or systolic patients with an estimated NNT = 2

CHAMPION Clinical Trial: PA Pressure-Guided Therapy Improves Outcomes in Patients with Preserved Ejection Fraction

Adamson PB,, et al.. Circ Heart Fail. 2014.

0%

10%

20%

30%

40%

50%

60%

HFrEF HFpEF

Rel

ativ

e R

isk

Red

uct

ion

HF Hospitalization Reduction (18 mo follow-up)

P<0.0001 vs. control

preserved EF (≥ 40%)

p<0.0001 vs. control

reduced EF (< 40%)

• Study Compared Class III HF patients with Chronic Kidney Disease (CKD) managed with PA pressure (n = 150) to those managed with Standard of Care (SOC) (n = 147).

• For HF patients with CKD PA pressure monitoring reduced heart failure hospitalizations by 42% compared to SOC.

– (0.48 vs. 83, HR 0.58, p,0.001)

• Changes in CKD indicators (creatinine and GFR) were not adversely affected in the PA pressure monitored group.

– Intensified HF medical therapy due to PA pressure monitoring was safe and did not adversely affect renal function.

Champion Clinical Trial: Sub-Analysis Shows Reduced HF Hospitalizations in Chronic Kidney Disease Patients

42%reduction

Abraham, et al. HFSA 2014

117

31

18

60

134

0

20

40

60

80

100

120

HF Hospitalizations All Cause 30 Day Readmissions HF 30 Day Readmissions

Nu

mb

er o

f H

osp

ital

izat

ion

sE

ven

ts/p

atie

nt

year

Control (Standard of Care) Treatment (PA pressure monitoring)

• Retrospective analysis of patients 65 years or older (n = 245)

• Compared 30-day readmissions and HF hospitalizations between patients managed with PA pressure vs. Standard of Care

• Results showed statistically significant reductions in readmissions and HFhospitalizations in treatment group

Champion Clinical Trial: Substantial reduction in 30-day readmissions in Medicare-eligible patients

58% reduction

p = 0.0062

78% reduction

p = 0.0027

In Medicare-eligible patients 65 years or older PA pressure monitoring with

the CardioMEMS™ HF System significantly reduced 30-day readmissions

49% reduction

p < 0.0001

Adamson, et al. AHA 2014.

Champion Clinical Trial: Substantial reduction in Hospitalizations and Mortality in patients on GDMT

Abraham, et al. ACC 2015

*

*

Reduction in HF Hospitalizations

43%

Champion Clinical Trial: Substantial reduction in Hospitalizations and Mortality in patients on GDMT

Abraham, et al. ACC 2015

*

*

Reduction in Mortality

57%

Pulmonary Artery Pressure Database

seconds

Trend Data

Discrete data Reading

Systolic: 24

Mean: 19

Diastolic: 16

Heart Rate: 81

Elevated PA Mean Pressure Treatment Strategies

Re-evaluate PA pressures2-3 days per week until PA pressures stabilize

Add or increase diuretic- increase/add loop diuretic

- change loop diuretic

- add thiazide diuretic

- IV loop diuretic

Add or increase vasodilators- add or increase nitrate

Elevated PA Pressure (Hyper-volemic)PA Pressure trending above the normal hemodynamic range

Evaluate other etiologies if PA pressures remain elevated i.e. dietary indiscretion, sleep apnea, etc.