Download New Options in Heart Failure for the Primary Care

Treatment Options in
Advanced Heart Failure
December 7, 2016
Hansie M. Mathelier MD, FACC
Clinical Assistant Professor of Medicine
Penn Presbyterian Medical Center
The Impact of Heart Failure
• Most common cause of hospitalization
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Primary diagnosis in > 1million discharges per year
Affects 10% of men, 8% women over 60
30-Day readmission rate 20-25%
Of incident hospitalized HF events, 53% had HFrEF and
47% had HFpEF
• Overall cost: $39.2 billion/year
– $131 for every man, woman and child
– By 2030, 69.7 billion.. $244 for every US adult
JACC HF 2013, 1: 2-20
ACEInhibitor
ARB
Beta
Blockers
Diuretics
LVAD
ISDN
Hydralazine
Digoxin
Transplant
Aldosterone
Blockers
Ivabradine
(Corlanor)
ARNI
Angiotensin
receptor
/neprilysin
inhibitor
Heart Failure
Heart Failure with
preserved EF
Heart Failure with
reduced EF
HF-REF: Building Blocks of Therapy
Mineralocorticoid
receptor antagonist
Traditional Therapies
• Beta Blockers
– Reduce catecholamine effects
– Decrease myocardial O2
demand
– Antiarrhythmic
• ACE/ARBs
– Reduce afterload
– Prevent remodeling
– Reduce RAAS impact on heart
and vascular
• Aldosterone Inhibitors
(MRA)
– Prevent myocardial
hypertrophy
– Reduce fibrosis
– Decrease arrhythmia
potential
• Diuretics
– Decrease after/preload
– Reduce dyspnea
– Decongest splanchnic
circulation
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HF Mortality Reduction with Medical Therapy
1991-2005
1991
1995
1999
28%
Add’l
+34%
Add’l+
15%
Mentz, Felker, Mann. Heart Failure: A
companion to Braunwald’s Heart Fisease, 2014
Heart Rate:
A prognostic Risk Factor in HF
Fox, K et al
Lancet 2008
HR Reduction and Mortality in HF
Major criticism of COMET (Carvedilol vs metoprolol)
Kjekshus J. Eur
Heart J 1999.
Ivabradine - Corlanor
• Ivabradine selectively
inhibits the “funny”
current in the sinus
node
• Slows HR independent
of BB effect “Less
negative inotropy”
• Implications for
patients with impaired
stroke volume
6558 patients were randomized to Ivabradine vs placebo
They were followed for 22.9 months, maximum 41.7 months.
SHIFT STUDY
• Randomized, double-blind, placebo-controlled,
parallel group study
• 6558 patients with systolic HF followed for 23
months
– NYHA class II, III, IV symptoms
– In stable condition for >4 weeks
– On guideline-based HF medication regimen
without changes in meds or doses for >4 weeks
• HF exacerbation admission within 12 months
Swedberg K, et al. SHIFT Study. Lancet 2010;376:875-85.
ARR- Absolute Risk Reduction
NNT - # needed to Treat
Months
Ivabradine vs. Placebo
• Reduced primary events (24% vs. 29%, 95% CI 0.750.90; p<0.0001; NNT=20)
• Decreased HF deaths (3% vs. 5%; p=0.014)
• Decreased HF admissions (16% vs. 21%; p<0.0001)
• Did not significantly reduce cardiovascular/all-cause
deaths (p=0.128)
Swedberg K, et al. SHIFT Study. Lancet 2010;376:875-85.
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Ivabradine indicated for
sinus rhythm and
HR >= 70 bpm
McMurray JJV.
EHJ 2012
Entresto (Sacubitril/Valsartan)
PARADIGM -HF
• 8399 were randomized with median follow of 27
months
• NYHA Class II-IV
• EF < 35-40%
• Any use of ACE-I/ARB
– Able to tolerate stable dose equivalent to enalapril
10mg daily > 4 weeks
– GDMT for beta blockers and MRAs
• Systolic Blood Pressure> 95, eGFR >30, and K <5.4
McMurray NEJM 2014 9:11; 371 [11] 993-1004
Current Estimate of the Number of Advanced HF
Patients
JACC 2013, 61: 1209–21
What’s Advanced Heart Failure
Median Survival Decreases Progressively
After Each HF Hospitalization
Average age of HF
hospitalized in the
community 74-77 years
Hospital admissions not only decrease QOL,
but they are also associated with shorter longevity
JACC 2013;61:1209-1221
Which patients should worry you?
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Inability to walk a block without shortness of breath
Intolerant or refractory to ACE inhibitors, ARBs, B-blockers
1 HF–related admission in the past 6 months
CRT nonresponder
High diuretic dose (e.g., 120 mg/d furosemide)
Serum sodium < 136 mmol/L
BUN > 40 mg/dL
Hematocrit < 35%
Ventricular Assist Devices
I
LVADs
VENTRICULAR ASSIST DEVICES
• Initially developed to address short term
needs in patients who struggled coming off
pump during cardiac surgery
• With new technology, subsequently used
when needed to provide hemodynamic
support for those patients who were clinically
declining while awaiting transplant
VENTRICULAR ASSIST DEVICES
• Bridge to recovery
– explant once clinically stabilized with expectation of
acceptable native cardiac function (post MI)
• Bridge to transplant
– unable to wait until an organ is available
• Bridge to decision
– options unclear
• Destination Therapy
– non-transplant candidate
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What is Destination Therapy?
• Refers to VAD implantation for long-term use,
rather than as a bridge to transplantation or
recovery
• Evolving technologies increase the horizon of
time support can be sustained
• These are not artificial hearts
REMATCH: A New Era
• “The use of a left ventricular assist device in patients
with advanced heart failure resulted in a clinically
meaningful survival benefit and an improved quality
of life.
• A left ventricular assist device is an acceptable
alternative therapy in selected patients who are not
candidates for cardiac transplantation.”
• One-year survival: 52% vs. 25% (p=0.002)
• Two-year survival: 23% vs. 8% (p=0.09)
N ENGL J MED 2001; 345:1435-1443
REMATCH Criteria
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Chronic end-stage heart failure
Ejection fraction < 25%
NYHA class IV for 90 days
Peak exercise oxygen consumption study < 12
mL/kg/min
Broadened criteria
• NYHA class III or IV for 28 days with intra-aortic
balloon pump or inotrope dependence (not
weanable)
25% vs. 8% at 2 Years
J Thor CV Surg 2006, 129: 6 1464
HeartMate XVE
Continuous vs Pulsatile Flow vs OMM
NEJM 2009, 361:2282
HeartMate II Key Design Features
 Valveless
– Only one moving part, the rotor
– Blood immersed bearings designed
for minimization of blood damage
– All motor drive and control
electronics are outside of the
implanted blood pump
 Weight: 10 oz.
 Speed: 6,000-15,000 rpm
 Flow range: 3 – 10 L/min
VADs Improve Functional Status
• > 80% of patients tested improved to NYHA class I/II
from NYHA class IIIB/IV by 6 months
– Sustained through 24 months
• Six-minute walk distance improved to 340 m by 6
months from 181+/-138 and 225 +/- 142 m
– Sustained through 24 months
Circ Heart Fail 2012;5;241-248
VADs Improve Quality of Life
• When surveyed about lifestyle changes, VAD
patients highlight the ability to drive, exercise,
travel, return to work or school, and engage in
hobbies and sexual activity as major
contributors to improved QOL
J Thorac Cardiovasc Surg 2004;127:1432–5
J Thorac Cardiovasc Surg 2000;119:251–9
HeartWare HVAD
HeartWare HVAD
• Pericardial placement – no pump pocket
– Eliminates the need for abdominal surgery and device pockets
• Provides up to 10 l/min of flow
• Centrifugal design, continuous flow
– Hybrid magnetic / hydrodynamic impeller suspension
– Optimizes flow, pump surface washing, and hemocompatibility
• Displaced volume = 50cc, Weight = 160g
• Thin (4.2 mm), flexible driveline with fatigue-resistant cables
ENDURANCE Trial
• Prospective, randomized, un-blinded, multi-center, non-inferiority
clinical trial to evaluate HVAD for destination therapy
• Study population:
– End-stage HF patients ineligible for cardiac transplantation
• Primary endpoint: stroke-free survival at two years
• Secondary endpoints: incidence of bleeding, major infection, device
failure, health and functional status improvement.
• Largest trial to date for long-term LVAD use
HEARTMATE 3
HEARTMATE 3
• Fully Magnetically Levitated
– No bearings
• Large pump gaps reduce blood trauma
• Artificial pulse
– Reduces risk of bleeding, AI, thrombosis, stroke
• Textured blood contacting surfaces allow endothelialization
• Output 2 – 10 L/min
The Evolution of Mechanical Support
Who is a VAD Candidate?
Selection Criteria
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Inability to walk a block without shortness of breath
Intolerant or refractory to ACE inhibitors, ARBs, B-blockers
1 HF–related admission in the past 6 months
CRT nonresponder
High diuretic dose (e.g., 120 mg/d furosemide)
Serum sodium < 136 mmol/L
BUN > 40 mg/dL
Hematocrit < 35%
Issues to Assess Pre-operatively
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RV function – there is no DT RVAD
Aortic insufficiency – may require AVR
Anticoagulation - contraindications
Insight/compliance – not a “quick fix”
Family/social support – a total buy-in
Financial – will insurance cover it?
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When Should You Refer?
• Medication intolerance
• Repeat hospitalizations
• Can’t “bounce back”
• Failure to thrive
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Before they get too sick
A VAD is NOT a “Hail Mary Pass”
HFpEF
Heart Failure with
Preserved EF