title: Hemolysis: a harbinger of adverse outcome after left ventricular assist device implant.
abstract: BACKGROUND
  The clinical relevance of elevated serum markers of hemolysis during left ventricular assist device (LVAD) support has not been fully ascertained.
  
  
  METHODS
  Lactate dehydrogenase (LDH) and serum free hemoglobin (sfHg) values were tallied monthly in 182 patients on HeartMate II (Thoratec, Pleasanton, CA) LVAD support. Peak values for each marker were identified, and 2 hemolysis definitions were applied to the cohort: Hemolysis according to Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) criteria (sfHg > 40 mg/dl with signs/symptoms) and/or hemolysis defined by an LDH ≥ 600 IU/liter (2.5-times the upper limit of laboratory normal). Kaplan-Meier survival free from death, urgent United Network of Organ Sharing 1A transplant for thrombosis, device exchange for thrombosis, and stroke/peripheral embolism was estimated, and Cox hazard ratios (HR) with the 95% confidence interval (95% CI) were calculated. Areas under the receiver-operating characteristic curves (AUCs) for predicting 1-year event-free survival were calculated.
  
  
  RESULTS
  Hemolysis occurred in 32 patients (18%) by INTERMACS criteria and in 68 (37%) patients by LDH criteria. Over a median (25(th), 75(th)) support of 427 days (245, 793 days), there were 78 events. One year event-free survival after the onset of INTERMACS-defined hemolysis was 16% ± 8.3% compared with 85% ± 3.2% in non-hemolyzers (HR, 14.7; 95% CI, 7.9-27; AUC 0.70 ± 0.05; p < 0.001; ). One year event-free survival after the onset of LDH-defined hemolysis was 32% ± 7.2% compared with 89% ± 3.2% in those with persistent LDH values < 600 IU/liter (HR, 8.0; 95% CI, 4.4-14; AUC 0.87 ± 0.04; p < 0.001). Patients who met the LDH hemolysis definition had longer times from hemolysis onset to clinical events and larger magnitudes of risk for embolism and device exchange for thrombosis than those with INTERMACS hemolysis.
  
  
  CONCLUSIONS
  Serum hemolysis marker elevations are associated with increased events in LVAD patients. LDH monitoring provides an earlier diagnosis of adverse events than sfHg, supporting need for a new INTERMACS definition of VAD-associated hemolysis.
authors.affiliation: Division of Cardiovascular Medicine, University of Michigan Health System, Ann Arbor, Michigan. Electronic address: jennifercowger@gmail.com.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Cowger
authors.affiliation: Department of Cardiac Surgery, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Romano
authors.affiliation: Division of Cardiovascular Medicine, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Palak
authors.initials: P
authors.lastname: Shah
authors.affiliation: Division of Cardiovascular Medicine, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Neha
authors.initials: N
authors.lastname: Shah
authors.affiliation: Department of Cardiac Surgery, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Vivek
authors.initials: V
authors.lastname: Mehta
authors.affiliation: Department of Cardiac Surgery, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Haft
authors.affiliation: Division of Cardiovascular Medicine, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Keith D
authors.initials: KD
authors.lastname: Aaronson
authors.affiliation: Department of Cardiac Surgery, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Francis D
authors.initials: FD
authors.lastname: Pagani
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy*; D006353:Heart-Assist Devices / Q000009:adverse effects*; D006454:Hemoglobins / Q000378:metabolism; D006461:Hemolysis / Q000502:physiology*; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008875:Middle Aged; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D013927:Thrombosis / Q000453:epidemiology* / Q000401:mortality; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology / Q000628:therapy*
chemical_list: D015415:Biomarkers; D006454:Hemoglobins; D007770:L-Lactate Dehydrogenase
keywords: hemolysis; lactate dehydrogenase; left ventricular assist device; serum free hemoglobin