Are LVADs Ready To Be Mainstream? Joseph G. Rogers, MD Associate Professor of Medicine Duke...

Are LVADs Ready To Be Mainstream?Joseph G. Rogers, MDAssociate Professor of MedicineDuke University Medical Center

J105-0311

Address a large patient population

Established safety and efficacy

Have a proven track record of clinical success

Have an acceptable risk / reward tradeoff

Mainstream Therapies

Addressing An Unmet Need

The VAD patient population is approaching 100,000 in the United States alone.

US population1

Target population (35-74 age cohort)1

Diagnosed CHF population2

All ages

35-74

NYHA Class IIIB and IV3 in 35-74 age cohort

Comorbidities estimated in this cohort

Target VAD patient population (35-74 years)

301,000,000

139,100,000

5,520,000

3,744,000

374,400

(280,800)

93,600

1 US Census Bureau Statistics (2007)2 Heart and Stroke Statistics, American Heart Association

3 Cardiovascular Round Table research and analysis, The Advisory Board company (2009)

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

Heart Failure Has A High Mortality Rate Similar To Aggressive Malignancies

Class IV heart failure patients treated with medical therapy alone have mortality rates similar to or greater than aggressive forms of cancer.5

1 Rose, Gelijns, Moskowitz, et al. NEJM. 345:1435-43, 2001. 2 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 is the first and only FDA-approved continuous flow device for both Bridge-to-Transplantation (BTT) and Destination Therapy (DT).

HeartMate II®—A Proven Adjuvant Therapy For Advanced-Stage Heart Failure

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

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

HeartMate II—Widespread Approval And Adoption

FDA approval for BTTApril 2008

European CE MarkNovember 2005

FDA approval for DTJanuary 2010

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

HeartMate II—Most Widely Used, Proven Efficacious, and Durable in Broad Patient Population

*As of January 13, 2011

HeartMate II has an unparalleled number of peer-reviewed 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

HeartMate II—Peer-Reviewed Publications

*As of January 2011

Improvements With BTT Results Over Time

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.

n = 133 n = 281 n = 169

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.

The majority of enrolled patients were noted to be INTERMACS 1 or 2.

HeartMate II Post-Approval Study Patient Demographics

Operative 30-day survival was 96% and patients achieved 90% successful outcomes at 6 months and 85% at 1 year.

HeartMate II Post-Approval Study Actuarial Survival


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.

HeartMate II Post-Approval Study Quality Of Life


HeartMate II Adverse Event Rates From The BTT Post-Approval Study

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..

The HeartMate II post-approval 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.

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.

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

Survival In The 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.

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

Park SJ. AHA Scientific Sessions, November 2010.

More than 500 additional DT patients have been enrolled under a continued access protocol (CAP).

Mid-trial patients did not vary in baseline characteristics

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.


Hemorrhagic stroke > 50% reduction

0.03 events per patient year

Device-related infections > 35%

reduction


Sepsis > 25% reduction


DT CAP Trial Shows Significant ReductionsIn Adverse Events

* p < 0.05** p < 0.01

HeartMate II therapy stroke rates are similar to other commonly accepted cardiac surgical procedures such as CABG and valve procedures.

Stroke Rates Similar To Other Cardiac Surgical Procedures

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.

Incidence of stroke by cardiac surgical procedure(data collected at Johns Hopkins from 2001 – 2004)

DT CAP Trial Functional Class Improvements


n = 266 n = 191 n = 158 n = 125 n = 67

All patients were Class IIIB or IV at baseline.

DT CAP Trial Quality Of Life Improvements

74

30

225 m

343 m


LVAD Survival Compared To OMM Therapy


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.

Improved Timing Of Patient Referral For Evaluation

Functional AssessmentInability to walk one block without shortness

of breathIntolerant or refractory to ACE inhibitor,

angiotensin receptor blockers, or beta-

blockersOne heart failure-related hospital admission

in the past 6 months2

CRT nonresponderHigh diuretic dose (e.g., 120 mg/d

Furosemide)

Lab AssessmentSerum sodium < 136 mmol/LBUN > 40 mg/dL or Serum Creatinine > 1.8

mg/dLHemotocrit < 35%

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.

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

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?

Case Study

Are LVADs Ready To Be Mainstream? Joseph G. Rogers, MD Associate Professor of Medicine Duke...

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