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Advanced Heart Failure Improving Outcomes with Current Therapies
Ravinder Kumar, MD, FACC
Feb 10, 2018
Disclosure
• Employee-Iowa Heart Center/Mercy-Des Moines
Learning Objectives
• Burden of Heart Failure
• Staging of HF
• Overview of therapies available for various stages of HF
• Advances in Heart Failure therapy
• Advanced Heart Failure – Definition
– Risk stratification
– Therapies
Burden of HF
• 5.7 million Americans ≥20 years of age have HF • Projected prevalence of HF will increase 46% from
2012 to 2030 • Lifetime risk of developing HF is 20% for Americans ≥40
years of age • 870,000 new HF cases annually • In 2013, HF costs in the United States exceeded $30
billion • Most common cause of hospitalization
– Primary diagnosis in >1 million hospital discharges – Readmission rates 20-25%
Clyde W. Yancy et al. Circulation. 2013;128:e240-e327
Definition of HF
• HF is a complex clinical syndrome that results from any structural or functional impairment of ventricular filling or ejection of blood
• The cardinal manifestations of HF
– dyspnea and fatigue leading to limited exercise tolerance
– fluid retention leading to pulmonary and/or splanchnic congestion and/or peripheral edema
Classification of HF
Clyde W. Yancy et al. Circulation. 2013;128:e240-e327
Stages of HF and NYHA functional class
Clyde W. Yancy et al. Circulation. 2013;128:e240-e327
Stages in the development of HF and recommended therapy by stage.
Clyde W. Yancy et al. Circulation. 2013;128:e240-e327
Clyde W. Yancy et al. JACC 2017;70:776-803
Heart Failure Pathway Writing Committee et al. JACC
Trial Evidence for Mortality Benefit of Drugs in HF
Beta blocker
Mineralocorticoid receptor
antagonist ACE
inhibitor
Angiotensin receptor blocker
Drugs that inhibit the renin-angiotensin system have modest effects on
survival
Based on results of SOLVD-Treatment, CHARM-Alternative,
COPERNICUS, MERIT-HF, CIBIS II, RALES and EMPHASIS-HF
10%
20%
30%
40%
0%
% D
ec
rea
se
in
Mo
rta
lity
Drugs That Reduce Mortality in Heart
Failure With Reduced Ejection Fraction
PARADIGM-HF
RAAS and Natriuretic peptide system
RAAS and Natriuretic peptide system
Angiotensin receptor Neprilysin Inhibitor
2 weeks 1-2 weeks 2-4 weeks
Single-blind run-in period Double-blind period
(1:1 randomization)
Enalapril
10 mg BID
100 mg BID
200 mg BID
Enalapril 10 mg BID
LCZ696 200 mg BID
Randomization
LCZ696
PARADIGM-HF Study Design
McMurray JJV et al. N Engl J Med 2014;371:993-1004
PARADIGM-HF
McMurray et al. NEJM 2014
10%
20%
30%
40%
ACE inhibitor
Angiotensin receptor blocker
0%
% D
ec
rea
se
in
Mo
rta
lity
18%
20%
Effect of ARB vs placebo derived from CHARM-Alternative trial
Effect of ACE inhibitor vs placebo derived from SOLVD-Treatment trial
Effect of LCZ696 vs ACE inhibitor derived from PARADIGM-HF trial
Angiotensin neprilysin inhibition
15%
LCZ696 Doubles Effect on CV Mortality
10%
20%
30%
40%
ACE inhibitor
Angiotensin receptor blocker
0%
% D
ec
rea
se
in
Mo
rta
lity
18%
20%
Effect of ARB vs placebo derived from CHARM-Alternative trial
Effect of ACE inhibitor vs placebo derived from SOLVD-Treatment trial
Effect of LCZ696 vs ACE inhibitor derived from PARADIGM-HF trial
Angiotensin neprilysin inhibition
15%
LCZ696 Doubles Effect on CV Mortality
NNT to Reduce any cause Mortality
Jessup M. N Engl J Med 2014;371:1062-1064.
Lancet 2010; 376: 875–85
SHIFT Trial
Lancet 2010; 376: 875–85
2017 ACC/AHA/HFSA update
Lancet 2011; 377: 658–66
Device Therapy - ICD & CRT
Clyde W. Yancy et al. Circulation. 2013;128:e240-e327
Advanced HF/Stage D HF
ESC Definition of Advanced HF
Identifying Patients With Advanced HF
INTERMACS Profiles
Modifiers: Frequent flyer: for Profile 3-6 Arrhythmia TCS(temporary circulatory support) for profile 1-3
Tools for Prognostication
When “optimal medical therapy” fails, what are the options?
• Inotropes
• Mechanical circulatory support
• Heart Transplant
• Clinical Trials
• Palliative Care
D Refractory
Heart
Failure
ACT - Advanced Cardiac Therapies
Yancy C, et. al. Circ. 2013;128:e240-e327
Milrinone: Bridge to Transplant
• 60 milrinone-dependent patients, listed for transplant • 76% successfully bridged with milrinone (waited 59 days for txp) • 24% required LVAD (waited 93 days for txp) • 5 died (waited 130 days for txp)
J. Cardiac Failure 2008; 14(10): 839-843
Continuous Outpatient Support with Inotropes: Palliation
• 36 patients – Inotrope-dependent
– Refused/ineligible for transplant
• Rehospitalizations infrequent
• Infection/sepsis common
• Survival 3.4 months – Most died at home
J. Cardiac Failure 2003; 9(3): 180-187
Chronic inotrope infusion associated with high mortality
• OPTIME-CHF and PROMISE
• Randomized, double blinded
• 1000 patients/ea randomized to milrinone or placebo
• High rates of hypotension, arrhythmia, syncope
• 53% increase in mortality – Pts not “wet and cold”
– Inotropic therapy was not considered essential for management
JAMA 2002; 287(12): 1541-1547
NEJM 1991; 325: 1468-1475
Heart Transplant COR I
• Cardiac transplantation is considered the gold standard for the treatment of refractory end-stage HF.
• First successful cardiac transplantation in 1967
• Over last 50 years post transplant survival has improved
• Post transplant survival at 1-, 3-, and 5-year is 87.8%, 78.5%, and 71.7% in adults, respectively
Heart Transplant
Status at time of transplant impacts post-transplant survival
Barge-Caballero Circ Heart Failure. 2013
Heart Transplant Trends
JHLT 2011 Oct; 30(10): 1071-1132
Unmet Need in Advanced HF
• 150,000-300,000 patients 2000 heart transplants
+ 1500 VAD implants
• --------------------------------
= more pts need referrals!
HM III LVAD
Heartmate II (axial flow) HVAD
Syncardia TAH
MCS • BTT • Bridge to recovery • Destination therapy
Improvement in Survival with LVADs
N Engl J Med 2009;361:2241-51
N Engl J Med 2001;345:1435-43
REMATCH
2001
HVAD ADVANCE BTT Trial
Keith D. Aaronson et al. Circulation. 2012;125:3191-3200
Quality of Life
Rogers JG, Aaronson KD, Boyle AJ et al, JACC, 2010;55:1826-34.
Change in NYHA Class After HMII
Six Month
Follow-up for
BTT Patients
Two Year
Follow-up for
DT Patients
Change in Quality of Life
After HeartMate II:
MLWHF*
Survival Post LVAD implant
2017 INTERMACS Report. J HeartLungTransplant2017;36:1080–1086
J HeartLungTransplant2015;34:1495–1504
Optimal timing of ACT referral
J Am Coll Cardiol 2015;66:1747–61
INTERMACS Profiles
ROADMAP study
1 2 3 4 5 6 7 INTERMACS Profiles
CMS Coverage: Class IV
FDA Approval: Class IIIB/IV
Currently Not Approved Limited Adoption Acceptance
NYHA Class III Class
IIIB
Class IV
(Ambulatory)
Class IV
(On Inotropes)
1.0% 1.4% 3.0% 14.6% 29.9% 36.4% 14.3% Percent of current
implants in INTERMACS
ROADMAP Study
Jerry D. Estep et al. JACC 2015;66:1747-1761
Jerry D. Estep et al. JACC 2015;66:1747-1761
Common VAD complications
Events/100 pt months • Bleeding (17-24) • Thromboembolism
(1.5-2.5) • Neurologic events (2-
4) • Infection (11-28) • Mechanical failure
(0.8-3) • Right heart failure
(2.2-3.1)
Kirklin et. al. Second INTERMACs annual report. JHLT 29 (1), 2009
N Engl J Med 2014;370:33-40
LVAD Thrombosis
N Engl J Med 2014;370:33-40
HeartMate III LVAD
N Engl J Med 2017;376:440-50.
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Contraindications to Advanced Heart Failure Therapies
• Irreversible kidney, liver, neurologic dz
• Uncorrectable, severe PVD
• Active infection
• Severe psychosocial concerns
– Inadequate social support system
– Ongoing alcohol or substance abuse
• Medical nonadherence
• Other life-limiting disease
Contraindications to Heart Transplant (but not DT VAD)
• Advanced age (> 70-75)
• Morbid obesity (BMI > 40)
• Substance abuse
• PVR > 5
Goals of an assessment of candidacy for ACT
• Identify medical appropriateness (is the pt sick enough?)
• Identify social appropriateness
• Identify contraindications, opportunities for management
• Estimate prognosis
• Risk stratify
– Intermacs profile, DT risk score, MELD
• Determine which therapy is right for the individual patient
– Inotropes, VAD, heart transplant, palliative care, something else
• Educate
• Informed consent – shared decision making
Eur Heart J. 2015;36(48):3467-3470
Eur Heart J. 2015;36(48):3467-3470.
Summary
• Heart failure prevalence/incidence is increasing
• Post transplant survival has improved over last 50 years
• Scarcity of donors led to development of durable MCS devices
• Durable MCS devices have improved survival and quality of life in patients with advanced heart failure
Thank you