Download J Thorac Cardiovasc Surg

THE TREATMENT OF
ADVANCED HEART FAILURE
ROSS ZIMMER MD, FACC
DIRECTOR, HEART FAILURE PROGRAM
CLINICAL ASSOCIATE PROFESSOR OF MEDICINE
PENN PRESBYTERIAN MEDICAL CENTER
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Traditional Therapies

Beta Blockers




Reduce catecholamine
effects
Decrease myocardial O2
demand
Antiarrhythmic
ACE/ARBs




Reduce afteroad
Prevent remodeling
Reduce RAAS impact on
heart and vascular
Aldosterone Inhibitors




Prevent myocardial
hypertrophy
Reduce fibrosis
Decrease arrhythmia
potential
Diuretics



Decrease after/preload
Reduce dyspnea
Decongest splanchnic
circulation
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Ivabradine

First-in-class to selectively inhibit
hyperpolarization-activated cyclic nucleotide
(HCN) gated (If current) channel within the SA
node that lowers heart rate

Dose-dependent reduction in heart rate

Degree of effect is dependent on the baseline
heart rate
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The SHIFT (Systolic Heart Failure Treatment
with the If Inhibitor Ivabradine) trial
Chronic stable HF with LVEF ≤35 percent
 In sinus resting heart rate ≥70 bpm
 On max dose (or maximally tolerated dose)
Beta-blocker
 Primary end point: composite of cardiovascular
death or hospital admission for worsening HF

Swedberg K, et al. SHIFT Study. Lancet 2010;376:875-85.
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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
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Swedberg K, et al. SHIFT Study. Lancet 2010;376:875-85.
Ivabradine vs. Placebo

Reduced primary events (24% vs. 29%, 95% CI
0.75-0.90; 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/allcause deaths (p=0.128)
Swedberg K, et al. SHIFT Study. Lancet 2010;376:875-85.
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(all comparisons are versus
enalapril 20 mg daily, not versus placebo)
Neprilysin Inhibition Promotes Action of
Endogenous Vasoactive Peptides
that Benefit the Failing Heart
Endogenous
vasoactive peptides
(natriuretic peptides,
adrenomedullin,
bradykinin, substance P,
calcitonin gene-related peptide)
Neprilysin
Inactive metabolites
Neurohormonal
activation
Vascular tone
Cardiac fibrosis,
hypertrophy
Sodium retention
Neprilysin
inhibition
PARADIGM-HF
 Randomized

double-blind trial
sacubitril-valsartan vs. enalapril
 8442
patients
 LVEF ≤40 percent
 NYHA functional class II, III, or IV
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PARADIGM-HF: Cardiovascular Death or Heart Failure
Hospitalization (Primary Endpoint)
Kaplan-Meier Estimate of
Cumulative Rates (%)
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0
Enalapril
3
2
(n=4212)
914
2
4
LCZ696
(n=4187)
1
6
HR = 0.80 (0.73-0.87)
P = 0.0000002
Number needed to treat = 21
8
0
0
180
360
540
720
900
1080
1260
896
853
249
236
Days After Randomization
Patients at Risk
LCZ696
Enalapril
1117
4187
4212
3922
3883
3663
3579
3018
2922
2257
2123
1544
1488
PARADIGM-HF
Sacubitril-valsartan reduced risk of:




Primary outcome of death from cardiovascular
causes or HF hospitalization
(21.8 vs 26.5%; HR 0.80; 95% CI 0.73-0.87)
All-cause mortality
(17.0 vs 19.8%; HR 0.84; 95% CI 0.76-0.93)
Death from cardiovascular causes
(13.3 vs 16.5%; HR 0.80; 95% CI 0.71-0.89)
HF hospitalization
(12.8 vs 15.6%; HR 0.79; 95% CI 0.71-0.89).
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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
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
HMII 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
Length: 3 in.
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
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
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
Who is a VAD Candidate?
Selection Criteria

Inability to walk a block without shortness of breath
 Intolerant or refractory to ACE inhibitors, ARBs, Bblockers
 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%
Thoratec
Issues to Assess Pre-operatively
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

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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
 Repeat
 Can’t
intolerance
hospitalizations
“bounce back”
 Failure
to thrive
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Before they get too sick
A VAD is NOT a “Hail Mary Pass”
Survival after LVAD implantation by the candidate’s
operative risk
Lietz K et al. Circulation 2007;116:497-505
Copyright © American Heart Association
MERIT-HF