Upload
others
View
2
Download
0
Embed Size (px)
Citation preview
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
f m
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.