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Are LVADs Ready To Be Mainstream?
Joseph G. Rogers, MD
Associate Professor of Medicine
Duke University Medical Center
J105-0311
Mainstream Therapies
 Address a large patient population
 Established safety and efficacy
 Have a proven track record of clinical success
 Have an acceptable risk / reward tradeoff
Addressing An Unmet Need
The VAD patient population is approaching 100,000
in the United States alone.
US population1
301,000,000
Target population (35-74 age cohort)1
139,100,000
Diagnosed CHF population2
 All ages
5,520,000
 35-74
3,744,000
NYHA Class IIIB and IV3 in 35-74 age cohort
374,400
Comorbidities estimated in this cohort
(280,800)
Target VAD patient population (35-74 years)
93,600
1
US Census Bureau Statistics (2007)
Heart and Stroke Statistics, American Heart Association
3 Cardiovascular Round Table research and analysis, The Advisory Board company (2009)
2
Heart Failure Has A High Mortality Rate Similar To
Aggressive Malignancies
Medical therapy alone can be a
poor long-term treatment option for
many in the more advanced stages
of heart failure.
Four major publications show the
mortality risk associated with
NYHA Class IV heart failure is
high, with a 1-year mortality
between 60 and 94 percent.1-4
Class IV heart failure patients treated with
medical therapy alone have mortality rates similar
to or greater than aggressive forms of cancer.5
1
2
Rose, Gelijns, Moskowitz, et al. NEJM. 345:1435-43, 2001.
Rogers, Butler, Lansman, et al. J Am Coll Cardiol. 50:741-47, 2007.
3 Hershberger, Nauman, Walker, et al. J Card Fail. 22:616-24, 2003.
4 Gorodeski, Chu, Reese, et al. Circ Heart Fail. 2:320-24, 2009.
5 Data on file. Pleasanton, Calif: Thoratec Corp.
HeartMate II®—A Proven Adjuvant Therapy For
Advanced-Stage Heart Failure
HeartMate II is the first and only FDA-approved continuous flow device
for both Bridge-to-Transplantation (BTT) and Destination Therapy (DT).
Bridge-to-Transplantation
 Non-reversible left heart failure
 Imminent risk of death
 Candidate for cardiac transplantation
Destination Therapy
 NYHA Class IIIB or IV heart failure
 Optimal medical therapy 45 of last 60 days
 Not a candidate for cardiac transplantation
For inpatient and outpatient use
HeartMate II—Design Features
 Optimized blood flow
 Low thrombosis risk
 Low anticoagulation
requirements
 Reliability
-
HeartMate II—Widespread Approval And Adoption
 Received European CE Mark
in November 2005
 Received FDA approval for
BTT in April 2008
 Received Health Canada
approval in May 2009
 Received FDA approval for DT
in January 2010
 Distributed throughout Asia
and Australia
European CE Mark
November 2005
FDA approval for BTT
April 2008
FDA approval for DT
January 2010
HeartMate II—Most Widely Used, Proven Efficacious, and
Durable in Broad Patient Population
More than 6,000 patients, spanning
over 6,000 patient years across 254
centers worldwide, have now been
implanted with the HeartMate II LVAD*
 Patients supported  2 years: 700
 Over 60 patients supported 4 or more
years
 Longest support duration: 6 years
 Smallest patient: 1.1 BSA
 Largest patient: 3.2 BSA
 Age range: 11–87
*As of January 13, 2011
HeartMate II—Peer-Reviewed Publications
HeartMate II has an unparalleled number of peerreviewed published studies in highly regarded
publications including NEJM and JACC.
Data featuring HeartMate II has been published in
more than 120* peer-reviewed articles including:
 3 New England Journal of Medicine
 6 Journal of American College of Cardiology
 5 Circulation
 35 Journal of Heart and Lung Transplantation
 11 Annals of Thoracic Surgery
 10 Journal of Thoracic Cardiovascular Surgery
*As of January 2011
Improvements With BTT Results Over Time
n = 133
n = 281
n = 169
Miller, Pagani, Russell, et al. NEJM. 357:885-96, 2007.
Pagani, Miller, Russell, et al. JACC. 54:312-21, 2009.
Starling, Naka, Boyle, et al. JACC, in press 2010.
HeartMate II—Contemporary BTT Outcomes
The HeartMate II BTT post-approval study was initiated to assess
outcomes in a broader patient care environment outside of a clinical
setting, representing real life situations.
HeartMate II Group
 First 169 consecutive HeartMate II patients enrolled in INTERMACS listed, or
likely to be listed, for transplant
 77 centers enrolled patients from April to August 2008, and were followed for
at least 1 year post-implant
Endpoints
 The primary endpoint was survival, and secondary endpoints included
adverse events reported upon occurrence and functional status using the
6-minute walk test and EuroQoL scale—determined at baseline and 3, 6,
and 12 months post-implant
Kirklin JK, Naftel DC, Kormos RL, et al. Second INTERMACS annual report: more than
1,000 primary left ventricular assist device implants. J Heart Lung Transplant. 2010;29:1-10.
HeartMate II Post-Approval Study Patient Demographics
The majority of enrolled patients were
noted to be INTERMACS 1 or 2.
HeartMate II Post-Approval Study Actuarial Survival
Operative 30-day survival was 96%
and patients achieved 90%
successful outcomes at 6 months and
85% at 1 year.
Starling, Naka, Boyle, et al. JACC, in press 2010.
HeartMate II Post-Approval Study Quality Of Life
As demonstrated by the EuroQoL
instrument, HeartMate II patients
experienced early and sustained
improvement in quality of life over
the course of follow-up, with scores
doubling at 12 months post-implant.
Starling, Naka, Boyle, et al. JACC, in press 2010.
HeartMate II Adverse Event Rates From The BTT PostApproval Study
The HeartMate II postapproval study
demonstrated low
adverse event rates for
stroke and RV failure.
Stroke and RV failure
rates have improved
from the HeartMate II
pivotal clinical trial.
Events per patient year.
Pagani FD, Miller LW, Russell SD. Extended mechanical circulatory support with a continuous-flow
rotary left ventricular assist device. J Am Coll Cardiol. 2009;54:312-21.
Starling, Naka, Boyle, et al. JACC, in press 2010.
.
Destination Therapy Pivotal Trial
Slaughter MS, Rogers JG, Milano CA, et al. Advanced heart failure treated with
continuous-flow left ventricular assist device. N Engl J Med. 2009;361(23):2241-51.
Survival In The Destination Therapy Pivotal Trial
The pivotal HeartMate II
Destination Therapy trial
demonstrated significant
improvements in outcomes
compared to randomized
patients with pulsatile LVADs
 68% survival at 1 year
 58% survival at 2 years
Slaughter MS, Rogers JG, Milano CA, et al. Advanced heart failure treated with continuousflow left ventricular assist device. N Engl J Med. 2009;361(23):2241-51.
Fang JC. Rise of the machines–left ventricular assist devices as permanent therapy for
advanced heart failure. N Engl J Med. 2009;361(23):2282-84.
Destination Therapy Trial CAP: Overview And Baseline
More than 500 additional DT patients have been enrolled under a
continued access protocol (CAP).
Trial Overview and Baseline Characteristics
DT Trial Experience
Cohort description:
HeartMate II patients:
Enrollment period:
Early Trial
Mid-Trial
Primary data cohort
Portion of DT CAP
N = 133
N = 281
March 2005 –
May 2007
May 2007 –
March 2009
 Mid-trial patients did not vary in baseline characteristics
Park SJ. AHA Scientific Sessions, November 2010.
Improvements In DT Survival
Patients enrolled in the mid-trial experienced better survival.
* P value adjusted for body surface area
Park SJ. AHA Scientific Sessions, November 2010.
DT CAP Trial Shows Significant Reductions
In Adverse Events
 Hemorrhagic stroke > 50%
reduction
 0.03 events per patient year
* p < 0.05
** p < 0.01
 Device-related infections > 35%
reduction
 0.27 events per patient year
 Sepsis > 25% reduction
 0.27 events per patient year
Park SJ. AHA Scientific Sessions, November 2010.
Stroke Rates Similar To Other Cardiac Surgical Procedures
HeartMate II therapy stroke rates are similar to other commonly accepted
cardiac surgical procedures such as CABG and valve procedures.
Incidence of stroke by cardiac surgical procedure
(data collected at Johns Hopkins from 2001 – 2004)
McKhann GM, Grega MA, Borowicz LM, et al. Stroke and encephalopathy after cardiac surgery - an update. Stroke. 2006;37:562-71.
Boyle AJ, Russell SD, Teuteberg JJ, et al. Low thromboembolism and pump thrombosis with the HeartMate II left ventricular assist device:
analysis of outpatient anti-coagulation. J Heart Lung Transplant. 2009;28:881-87.
DT CAP Trial Functional Class Improvements
All patients were Class IIIB or IV at baseline.
n = 266
n = 191
n = 158
n = 125
n = 67
Park SJ. AHA Scientific Sessions, November 2010.
DT CAP Trial Quality Of Life Improvements
343 m
74
225 m
30
Park SJ. AHA Scientific Sessions, November 2010.
LVAD Survival Compared To OMM Therapy
Park SJ. AHA Scientific Sessions, November 2010.
Improved Timing Of Patient Referral For Evaluation
A range of referral criteria
assessments and scoring systems
can be utilized to define the right
moment to screen a patient for a
HeartMate II implant.1
Appropriate timing for referral is
when a patient presents in Class
IIIB or IV heart failure and has more
than one of the functional or
laboratory risk factors.
1 Russell SD, Miller LW, Pagani FD. Advanced heart failure: a call to action.
Congest Heart Fail. 2008;14:316-21.
2 Teuteberg J, Lewis E, Nohria A, et al. Characteristics of patients who die
with heart failure and low ejection fraction in the new millennium. J Card Fail.
2006;12(1):47-53.
Functional Assessment
 Inability to walk one block without
shortness of breath
 Intolerant or refractory to ACE inhibitor,
angiotensin receptor blockers, or betablockers
 One heart failure-related hospital
admission in the past 6 months2
 CRT nonresponder
 High diuretic dose (e.g., 120 mg/d
Furosemide)
Lab Assessment
 Serum sodium < 136 mmol/L
 BUN > 40 mg/dL or Serum Creatinine >
1.8 mg/dL
 Hemotocrit < 35%
In Summary
HeartMate II:
 Compelling data from large clinical trials
demonstrates efficacy
 Achieved very high survival rates
 BTT – 90% 6 months, 85% 1 year
 DT – 74% 1 year, 64% 2 years
 Superior to what is anticipated with optimal medical
management
 Substantial and sustained quality of life
improvements
 Acceptable adverse event profile
Case Study
 67 y/o referred for advanced heart failure therapy
 Ischemic cardiomyopathy
 EF < 20% with LVEDD = 7.3 cm
 Cath 1 month prior: 20% pLM, 100% pLAD, stent in pLCX, 50% stenosis pOM1,
60% pRCA with diffuse 50% stenosis throughout. Patent LIMA to LAD, patent SVG
to PDA with 50% proximal stenosis
 Thallium: anterior infarct, no ischemia
 ICD
 Co-morbidities: HTN, DM, hyperlipidemia
Case Study
 Hospitalized once in past 6 months
 Progressive exertional dyspnea and fatigue (e.g., unable to climb 1
flight of stairs without dyspnea or unhappy with current level of
functionality)
 Occasional nocturnal dyspnea
 No edema
 Appetite adequate and no weight change
 No ICD shocks
 Meds: ASA 81 mg daily, Clopidogrel 75 mg daily, Furosemide 40 mg
daily, Lisinopril 10 mg daily, Metoprolol Tartrate 25 mg twice daily,
Simvastatin 20 mg daily, Spironolactone 25 mg daily
Case Study
 Examination

HR=92, BP=96/78

Clear lungs

Depressed carotid upstrokes, JVP=12, RRR, No S3 or murmur

Trace LE edema
 Labs: Sodium=134mmol/L, BUN=12 mg/dl, Cr=0.8 mg/dl,
BNP=436pg/ml, Albumin=3.5 g/dl
Case Study
Case Study
 Level 1 CPX Results
 2 minutes and 37 seconds, Ekelund protocol
 Peak HR=148, Peak BP=102/71
 RER=1.16
 Peak VO2=11.6 ml/kg/min (49% predicted)
 VE-VCO2 Slope=49.8
Case Study
 Questions:
 Should this patient receive an ICD upgrade to BiV-ICD?
 Are there opportunities for revascularization?
 Are the medications optimized?
 Is this patient an appropriate VAD patient?