title: Left ventricular global longitudinal strain predicts major adverse cardiac events and all-cause mortality in heart transplant patients.
abstract: BACKGROUND
  Left ventricular global longitudinal strain (LVGLS) is a robust longitudinal myocardial deformation marker that is strongly affected by cardiac allograft vasculopathy (CAV), microvascular dysfunction, and acute cellular rejection (ACR). We evaluated graft deformation for risk stratification in long-term heart transplant (HTx) patients.
  
  
  METHODS
  The study included 196 patients who underwent HTx between 2011 and 2013. Patients underwent comprehensive echocardiography and coronary angiography. Previous rejection burden was assessed, and ACR grades were calculated. Patients were prospectively followed until February 24, 2016. Major adverse cardiac events (MACE), including coronary event, heart failure, treated rejection, and cardiovascular death, and all-cause mortality were recorded.
  
  
  RESULTS
  During follow-up, 57 patients experienced MACE. Median follow-up was 1,035 (interquartile range [IQR] 856-1,124) days. Median time to first event was 534 (IQR 276-763) days. LVGLS was a strong predictor of MACE (hazard ratio [HR] 4.9, 95% confidence interval [CI] 2.7-8.9, p < 0.0001) in patients with and without CAV. LVGLS was a strong predictor of all-cause mortality (HR 4.9, 95% CI 2.2-10.8, p < 0.0001). Left ventricular ejection fraction (LVEF) also predicted MACE, but only in patients with CAV. No relationship between LVEF and all-cause mortality was seen. We obtained a strong MACE (HR 6.3, 95% CI 2.8-14.1, p < 0.0001) and all-cause mortality (HR 6.6, 95% CI 2.3-19.2, p < 0.0001) predictive model by combining LVGLS and restrictive left ventricular filling pattern (LVFP), which remained strong after adjustment for CAV, ACR score, hemoglobin, creatinine, and time since transplantation.
  
  
  CONCLUSIONS
  Measurement of LVGLS strongly predicts MACE and mortality in long-term HTx patients. Predictive ability was seen in patients with and without CAV. A combined model of left ventricular systolic deformation by LVGLS and diastolic graft performance by LVFP was a stronger model for prediction of MACE and all-cause mortality.
authors.affiliation: Departments of Cardiology, Aarhus University Hospital, Aarhus, Denmark. Electronic address: torclemm@rm.dk.
authors.forename: Tor Skibsted
authors.initials: TS
authors.lastname: Clemmensen
authors.affiliation: Departments of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Hans
authors.initials: H
authors.lastname: Eiskjær
authors.affiliation: Departments of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Brian Bridal
authors.initials: BB
authors.lastname: Løgstrup
authors.affiliation: Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Lars Bo
authors.initials: LB
authors.lastname: Ilkjær
authors.affiliation: Departments of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Steen Hvitfeldt
authors.initials: SH
authors.lastname: Poulsen
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D000704:Analysis of Variance; D002423:Cause of Death; D015331:Cohort Studies; D017023:Coronary Angiography / Q000379:methods; D003718:Denmark; D004452:Echocardiography / Q000379:methods; D005260:Female; D006084:Graft Rejection / Q000401:mortality*; D006333:Heart Failure / Q000401:mortality / Q000601:surgery; D016027:Heart Transplantation / Q000009:adverse effects* / Q000379:methods / Q000401:mortality; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D013318:Stroke Volume / Q000502:physiology*; D016019:Survival Analysis; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000209:etiology / Q000401:mortality*
keywords: cardiac allograft vasculopathy; global longitudinal systolic function; heart transplantation; prognosis; time-to-event analysis