Hemolysis in Patients Supported with Durable, Long-Term Left

Ventricular Assist Device Therapy

Jason N. Katz, MD,MHS; Brian C. Jensen, MD; Patricia P. Chang, MD, MHS; Susan L. Myers, BBA; Francis D. Pagani, MD, PhD; James K.

Kirklin, MD

DISCLOSURES

• None

BACKGROUND

• Despite the beneficial effects of LVAD therapy, most patients will suffer an adverse event after device implantation

• Hemolysis is a known complication of MCS

– 1 out of 10 in patients with short-term support1

– Rare early after durable LVAD placement?2

1Bennett M, et al. Perfusion 2004. 2Genovese EA, et al. Ann Thorac Surg 2009.

BACKGROUND

• HeartMate II Destination Trial1

– Hemolysis incidence 4% (0.02 events/pt-yr)

• HeartMate II Bridge-to-Transplant Trial2

– Hemolysis incidence 4% (0.06 events/pt-yr)

1Slaughter MS, et al. NEJM 2009. 2Pagani FD, et al. JACC 2009.

BACKGROUND

• Hemocompatibility with LVAD impacted by: – Blood-surface interactions – Alterations in flow-dynamics – Changes in coagulation – Abnormalities of host immunity

• Not only is epidemiology of hemolysis in contemporary LVAD populations unclear, but so too are the clinical consequences

METHODS

• Data obtained from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) – represents 117 centers

• All adult patients with a primary, intracorporeal, CF-LVAD between Jun 2006-Mar 2012

• Descriptive statistics, χ2, Fisher’s exact test, t-test, and Wilcoxon rank-sum test

METHODS

• Hemolysis Event

Plasma-free hemoglobin >40 mg/dL, in association with clinical signs of hemolysis, when occurring at least 72 hours following

LVAD implantation

METHODS

• Survival analysis performed using Kaplan-Meier method, with censoring for heart transplantation or cardiac recovery

• Stratified time-to-event curves compared

using the log-rank test

DERIVATION OF STUDY POPULATION

BASELINE CHARACTERISTICS VARIABLE NO HEMOLYSIS HEMOLYSIS P-VALUE

Age (yrs) 56.3 52.7 <0.0001

Male sex 79.4% 72.3% 0.01

White race 70.2% 67.7% 0.39

BMI (kg/m2) 28.6 29.9 0.003

INTERMACS 1 14.3% 14.2% 0.99

INTERMACS 2 40.3% 44.2% 0.21

INTERMACS 3 26.0% 22.3% 0.18

INTERMACS 4 13.3% 13.1% 0.91

INTERMACS 5 3.3% 3.1% 0.84

INTERMACS 6 1.9% 1.2% 0.39

INTERMACS 7 0.9% 1.9% 0.11

BASELINE CHARACTERISTICS VARIABLE NO HEMOLYSIS HEMOLYSIS P-VALUE

Destination Therapy 29.0% 28.5% 0.85

Diabetes 39.2% 41.5% 0.46

CVD 7.9% 8.7% 0.68

Prior CABG 22.9% 17.7% 0.05

Prior Valve Surgery 7.3% 5.4% 0.24

Concomitant Rx

Inotrope 80.2% 82.7% 0.32

IABP 31.6% 33.1% 0.62

ECMO 2.0% 2.7% 0.20

No differences in baseline lab values, baseline hemodynamics, or other evaluable

characteristics prior to implant

Younger age (<60yrs) independently associated with hemolysis, p=0.01

CAUSE OF DEATH PRIMARY CAUSE OF DEATH NO HEMOLYSIS (N=863) HEMOLYSIS (N=80)

CVA 10.2% 16.3%

Infection 10.3% 3.8%

Right Ventricular Failure 4.6%% 7.5%

Hepatic Failure 1.0% 6.3%

Renal Failure 2.0% 2.5%

Device Malfunction 1.6% 3.8%

Hemorrhage 9.4% 5.0%

Unknown/Undocumented 12.2% 22.5%

Other 22.9% 21.3%

Device Malfunction Due to Suspected or Confirmed Thrombosis

Patients, N=260 Device malfunction due to thrombus, N=27

Need for Device Exchange

≈20% chance of needing device exchange early

after event

Events Stratified by Year

Adult Primary Continuous Flow LVADs, n=4850 Time to 1st Hemolysis Event by Implant Year

Months post implant

Free

dom

from

Hem

olys

is

% freedom post Implant Year n events implant at 3 months 2008 442 30 97% 2009 825 44 98% 2010 1515 82 98% 2011 1671 93 96% 2012 (March) 397 11 95%

P(overall) = .005

STUDY LIMITATIONS

• Retrospective study design • Candidate variables limited to those collected

routinely in INTERMACS – no reliable data on pump speed, cannula position

• Limited data on concomitant meds (esp. antiplatelet & antithrombotic therapies)

• More contemporary INTERMACS hemolysis definition (employing LDH & risk stratifying “minor and major” events) not used

CONCLUSIONS

• Hemolysis is relatively common in “real-world” CF-LVAD populations

• Survival is significantly reduced following a hemolytic event and device exchange is common

• Need to develop consistent definitions for hemolysis, particularly ones that are reliable despite evolving technologies, patient characteristics, and indications

CONCLUSIONS

• These findings should not temper our enthusiasm for VAD therapy, but rather should compel us to focus on key care processes and best practice principles which will allow our patients to reap greater benefits from the technology

• Future evaluation should focus on device and implant characteristics leading to hemolysis, as well as appropriate strategies for optimally defining, detecting and managing these events

THANK YOU.