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
None DISCLOSURES
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 support 1 Rare early after durable LVAD placement? 2 1 Bennett M, et al. Perfusion 2004. 2 Genovese EA, et al. Ann Thorac Surg 2009.
BACKGROUND HeartMate II Destination Trial 1 Hemolysis incidence 4% (0.02 events/pt-yr) HeartMate II Bridge-to-Transplant Trial 2 Hemolysis incidence 4% (0.06 events/pt-yr) 1 Slaughter MS, et al. NEJM 2009. 2 Pagani 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, χ 2, 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 1 st Hemolysis Event by Implant Year Freedom from Hemolysis P(overall) =.005 % 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% Months post implant
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 realworld 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.