Support Devices for Acute CHFDestination LVADs to exclude Transplant

Expectations, Indications, Benefits ,Risks

Donna Mancini, MDMt Sinai School of Medicine

Conflict of Interest

• None

Refractory cardiogenic Shock

• 1. Use of temporary percutaneous devices in AHF/cardiogenic shock

• 2. Durable devices for Destination therapy

Cardiogenic Shock Definition (SHOCK Trial)

• Hypotension systolic BP < 90 mm Hg for > 30 min or mean BP 30 mm Hg lower than baseline

• Need for pharmacologic or IABP support to maintain SBP > 90

• End organ hypoperfusion• Cool extremities• Urine output < 30 cc/hr• Altered mental status• Lactate > 2 mmol/l• Pulmonary congestion

• Hemodynamic criteria• CI < 2.2 l/min/m2 and PCW >15 mm Hg

Etiology of Cardiogenic Shock

• Acute Myocardial Infarction• Large infarct• Moderate or small infarct w pre existing LV dysfn• Mechanical complication of MI- acute MR, VSD, LV rupture• RV infarct

• End Stage Cardiomyopathy

• Myocarditis

• Valvular Heart Disease

• Stress induced cadiomyopathy

• Cardiac Tamponade

Cardiogenic Shock

• AMI occurs in 1 million patients in US and 8 million patients annually worldwide

• Cardiogenic Shock occurs in 4-12% of AMI patients

• 1 yr Mortality rate is about 65%

• IABP-SHOCK II trial failed to show 30 day survival benefit in AMI patients w cardiogenic shock supported by IABP

• Shift now is to examine use of other percutaneous devices in these patients

The downward spiral of refractory cardiogenic shock

SIRS

Shock Trial

Hochman JAMA 2001;285:190

SHOCK II Trial 2012

Thiele NEJM 2012;367:1287

Non Selective NOS inhibitor

Cardiogenic Shock

IABP

ECMO

LV to Aorta LA-Aorta V-A

Short Term Mechanical Circulatory Support Devices

IABP ECMO TandemHeart Impella

Afterload Reduced Increased Increased Neutral

LV stroke volume Slight increase Reduced Reduced Reduced

Coronary

perfusion

Slight increase Unknown Unknown Unknown

LV pre-load Slightly reduced Reduced Reduced Slightly reduced

PCW pressure Slightly reduced Reduced Reduced Slightly reduced

Peripheral tissue

perfusion

No significant

increase

Improved Improved Improved

VA ECMO

J Am Coll Cardiol. 2015;66(23):2663-2674.

EDP and arterial elastase as ECMO flow

TPR

ECMO + IABPEcpella

Elastase EDV to ESP

KVAD = ECMO+ mini LVAD

Centrimag pump

Oxygenator LV apical cannula through mini-thoracotomy

Axillary outflow

Femoral v. drainage LV unloading

RV unloading

Pulmonary unloading

Koji Takeda Md, Phd

J Am Coll Cardiol. 2015;66(23):2663-2674.

.

LA to Ao

Tandem Heart

Effect of LV to arterial MCS

J Am Coll Cardiol. 2015;66(23):2663-2674.

Impella; durable VADs

Reyentovich, A. et al. (2016)

Nat. Rev. Cardiol.

Tandem Heart n=33

Impella 2.5 n=26

Tandem Heart n=41

Randomized trials of Percutaneous MCS vs IABP in AMI

3 trials totaling 100 patients

Reyentovich, A. et al. (2016)

Nat. Rev. Cardiol.

Randomized trials of Percutaneous MCS vs IABP in AMI

Guideline Recommendations of Short Term MechanicalAssist Devices in Cardiogenic shock

ACC/AHA/SCAI ESC/EACTS

IABP Class IIA Hemodynamic instability after AMI

IIb Hemodynamic instability after AMI

ECMO none none none ECMO implantation should be considered for temporary support in patients with acute heart failure with potential for functional recovery following revascularization.

Tandem Heart IIB Same as IABP IIb Routine use of percutaneous centrifugal pumps is not recommended.

Impella IIB Same as IABP none none

NYHA I II IIINYHA

IV

NYHA Symptom Class:Back and forth

ARisk

BAsx

Structural dx

CSx ever

ACC/AHA Stages: One-way progression

D= IV sxRefractory to

Optimal Med Rx

INTERMACSProfiles

e.g. Tx, VAD,Continuous Inotropes onlyindicated for Stage D

Evolution of Heart Failure Classification

INTERMACS: Interagency Registry for Mechanically

Assisted Circulatory Support

Green Bars DT

LVAD vs TxLVAD Tx

Body Size Still w limits

BSA<1.3 ??

All sizes

Age No age limit 70

RV failure RVSWI PVR< 6 Wood U

Restrictive CM Inadequate Yes

Urgent

Situations

Yes No

Assess Neuro

Status

Yes No

Patient Selection for VADs

• Severity of CHF• INTERMACS; HFSS; Seattle HFM

• Exclude significant co-morbidity:

if unclear support with short term device

• Assess need for biventricular support

• Assess need for short vs long term support

• Assess peri-operative risk

No severe end-organ dysfunction/failure

Ability to tolerate anticoagulant or antiplatelet therapieswithout plans for correction

ADULT PROFILES IV Ino IABP/V

ent

Official Shorthand NYHA

CLASS

INTERMACS

LEVEL 1

X X “Crash and burn” IV

INTERMACS

LEVEL 2

X X “Sliding fast” on inotropes IV

INTERMACS

LEVEL 3

X “Stable” Continuous Ino-”Dependent” * IV

INTERMACS

LEVEL 4

Resting symptoms on oral therapy at

home.

ambul

IV

INTERMACS

LEVEL 5

“Housebound”,

Comfortable at rest, symptoms with

minimum activity ADL

ambuI

IV

INTERMACS

LEVEL 6

“Walking wounded”-ADL possible but

meaningful activity limited

IIIB

INTERMACS

LEVEL 7

Advanced Class III III

HeartMate IITM LVAS

The HeartMate II LVAS (St. Jude Medical, Inc.) is a mechanical

bearing axial continuous-flow blood pump;

only device in the US approved for both Bridge-To-Transplant

(BTT) and Destination Therapy (DT) patients

Mehra MR, Naka Y, et al. Published Nov 16, 2016 at

NEJM.org

Estep J JACC 2015;66:1748

Estep J JACC 2015;66:1748

Adverse Events OMM (n = 103) LVAD (n = 94) DT Trial§(EPPY)

Bleeding 1 (1) [0.02] 44 (47) [1.22]‡ 1.13

GI bleeding 1 (1) [0.02] 29 (31) [0.76]‡‖ —

Driveline infection — 9 (9.6) [0.14]‡ 0.22

Pump thrombus — 6 (6.4) [0.08]† 0.07¶

Pump exchange yr 1 — 4 (4.3) 2.10%

Stroke 2 (2) [0.02] 8 (8.5) [0.09]∗ 0.08

Arrhythmias VT/VF 6 (5.8) [0.12] 17 (18.1) [0.23]∗ 0.46

Worsening HF# 36 (35) [0.68] 10 (10.6) [0.12]‡ —

Rehospitalizations 64 (62) [1.43] 75 (79.8) [2.49]‡ 2.64∗∗

Composite event rate†† 39 (38) [0.83] 62 (66) [1.89]‡ 2.09

Relative Risk (95% CI):OMM/LVAD: 0.44 (0.35-).56)

Adverse Events in ROADMAP

HeartMate II LVASHeartMate 3TM LVAS Magnetic Levitation Technology

The HeartMate 3 LVAS (St. Jude Medical, Inc.) is a

centrifugal-flow, fully magnetically levitated blood pump

engineered to minimize destruction of red blood cells and

thrombosis

• Wide blood-flow passages to reduce shear stress

• Frictionless with absence of mechanical bearings

• Intrinsic Pulse designed to reduce stasis and avert thrombosis

Mehra MR, Naka Y, et al. Published Nov 16, 2016 at

NEJM.org

• Patients with advanced heart failure and severe limitations (NYHA IIIB or IV), refractory to standard medical therapy and deemed as necessary candidates for left ventricular assist device implantation, irrespective of the intended goal of pump support (BTT or DT)

• Key exclusion criteria included planned biventricular support, irreversible end-organ dysfunction, or active infection

Target Population

Patient meets

MOMENTUM 3

eligibility

criteria?

Short Term (ST) Cohort

N=294

6-month follow-up

Randomization

1:1

Study Design

HeartMate II

HeartMate 3

Long Term (LT) Cohort

N=366

24-month follow-up

Full Study Cohort

N=1028

24-month follow-up for

powered secondary endpointHeartMate 3

N=152

HeartMate II

N=142

Treatment failures(not treated with study device)

N=4

No LVAD implant: 1Withdrawal of consent: 1

Transplant: 1Implanted with non-study LVAD:

1

Treatment failures(not treated with study device)

N=1

Death: 1

Implanted with

HeartMate 3

N=151

Implanted with

HeartMate II

N=138

Intent-to-Treat (ITT) Population

N=294

As Treated Population

N=289

• Primary Endpoint (composite, by ITT):

• Survival at 6 months free of disabling stroke (modified Rankin score >3) or reoperation to replace or remove the pump (other than for recovery)

• Demonstration of non-inferiority of HeartMate3™ LVAS to HeartMate II™ LVAD

Study Endpoint

Caution – HeartMate 3 LVAS is an investigational device. Limited by Federal (United States) law to investigational use

SJM-HM3-1116-0003 | Item approved for global use.

Baseline Characteristics

Characteristic

HeartMate 3

(n=152)

HeartMate II

(n=142)Age - years

Mean 60 ± 12 59 ± 12

Left ventricular ejection fraction - % 17.1 ± 5.0 17.3 ± 4.9

Male sex - no. (%) 121 (80) 114 (80)

Race – no. (%)

White 104 (68) 107 (75)

Black or African American 37 (24) 24 (17)

Other* 11 (8) 11 (8)

Body surface area - m2 2.1 ± 0.3 2.1 ± 0.3

Ischemic cause of heart failure - no. (%) 68 (45) 72 (51)

History of stroke - no. (%) 12 (8) 14 (10)

Concomitant medication or intervention - no (%)

Intravenous inotropic agents 132 (87) 121 (85)

IABP 18 (12) 21 (15)

INTERMACS 2 50 (33) 44 (31)

INTERMACS 3 76 (50) 69 (49)

Bridge to Transplant (BTT) 41 (27) 37 (26)

Bridge to Candidacy 27 (18) 27 (18)

Destination Therapy (DT) 84 (55) 78 (55)

Primary End Point Analysis (ITT)

0.00

0.20

0.40

0.60

0.80

1.00

0 1 2 3 4 5 6

Pro

bab

ility

of

Even

t Fr

ee

Surv

ival

Months no. at risk

HeartMate 3 152 146 138 135 130 128 127

HeartMate II 142 125 119 116 110 106 103

HeartMate II

HeartMate 3

77%

86%

Survival at 6 months free of disabling stroke or

reoperation to replace or remove the pump

Non-inferiority Analysis

Absolute difference +9.4% (95% LCB -2.1%), P<0.0001

Superiority Analysis

HR 0.55, (95% CI 0.32-0.95), P=0.037

Primary Endpoint (ITT)

HeartMate 3

(n=152)

n (% [95%CI])

HeartMate II

(n=142)

n (% [95%CI])

Superiority Analysis Hazard Ratio† P

value

Survival free from disabling stroke and

reoperation to repair or replace the LVAD at 6

months

131 (86.2 [80 - 91]) 109 (76.8 [69 - 83]) 0.55 (0.32 - 0.95) 0.037

First event that prevented patient from

reaching the primary endpoint

Did not receive assigned pump 1(1[0-4]) 4 (3 [1 - 7]) 0.23 (0.03 – 2.09) 0.15

Disabling stroke (Rankin Score > 3) 6 (4 [1 - 8]) 4 (3 [1 - 7]) 1.31 (0.37 - 4.64) 0.59

Reoperation to repair or replace pump* 1 (1 [0 - 4]) 11 (8 [4 - 13]) 0.08 (0.01 - 0.60) 0.002

Death within 180 days after implant 13 (9 [5 - 14]) 14 (10 [6 - 16]) 0.82 (0.38 - 1.73) 0.70

†Hazard ratios were calculated with the use of Cox regression.

* includes two cases of urgent heart transplant due to device malfunction in the axial-flow pump group

CI denotes confidence interval and LVAD left ventricular assist deviceCaution – HeartMate 3 LVAS is an investigational device. Limited by Federal (United States) law to investigational use

SJM-HM3-1116-0003 | Item approved for global use.

*

Conclusions

• Short and long term mechanical support devices are being used for the treatment of cardiogenic shock and Stage D Heart Failure

• There are continued improvements in pump design

• Short term devices have not yet been shown to improve survival in cardiogenic shock but clearly provide greater hemodynamic support

• Adverse events remain common in the use of durable device support