Natural history of left ventricular mechanics in transplanted hearts: relationships with clinical variables and genetic expression profiles of allograft rejection.
OBJECTIVE
The aim of this study was to explore the temporal evolution of left ventricular (LV) mechanics in relation to clinical variables and genetic expression profiles implicated in cardiac allograft function.


BACKGROUND
Considerable uncertainty exists regarding the range and determinants of variability in LV systolic performance in transplanted hearts (TXH).


METHODS
Fifty-one patients (mean age 53 ± 12 years; 37 men) underwent serial assessment of echocardiograms, cardiac catheterization, gene expression profiles, and endomyocardial biopsy data within 2 weeks and at 3, 6, 12, and 24 months after transplantation. Two-dimensional speckle-tracking data were compared between patients with TXH and 37 controls (including 12 post-coronary artery bypass patients). Post-transplantation mortality and hospitalizations were recorded with a median follow-up period of 944 days.


RESULTS
Global longitudinal strain (LS) and radial strain remained attenuated in patients with TXH at all time points (p < 0.001 and p = 0.005), independent of clinical rejection episodes. Failure to improve global LS at 3 months (≥ 1 SD) was associated with higher incidence of death and cardiac events (hazard ratio: 5.92; 95% confidence interval: 1.96 to 17.91; p = 0.049). Multivariate analysis revealed gene expression score as the only independent predictor of global LS (R(2) = 0.53, p = 0.005), with SEMA7A gene expression having the highest correlation with global LS (r = -0.84, p < 0.001).


CONCLUSIONS
Speckle tracking-derived LV strains are helpful in estimating the burden of LV dysfunction in patients with TXH that evolves independent of biopsy-detected cellular rejection. Failure to improve global LS at 3 months after transplantation is associated with a higher incidence of death and cardiac events. Serial changes in LV mechanics correlate with peripheral blood gene expression profiles and may affect the clinical assessment of long-term prognosis in patients with TXH.
Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic College of Medicine, Scottsdale, Arizona, USA.
Mackram F
MF
Eleid
Giuseppe
G
Caracciolo
Eun Joo
EJ
Cho
Robert L
RL
Scott
D Eric
DE
Steidley
Susan
S
Wilansky
Francisco A
FA
Arabia
Bijoy K
BK
Khandheria
Partho P
PP
Sengupta
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics; D001706:Biopsy; D006328:Cardiac Catheterization; D016022:Case-Control Studies; D004452:Echocardiography; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006084:Graft Rejection / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics / Q000401:mortality / Q000503:physiopathology; D016027:Heart Transplantation / Q000009:adverse effects* / Q000401:mortality; D006760:Hospitalization; D006801:Humans; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D039961:Semaphorins / Q000235:genetics; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics / Q000401:mortality / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000235:genetics
D015703:Antigens, CD; D058851:GPI-Linked Proteins; C118753:SEMA7A protein, human; D039961:Semaphorins