AimTo identify predictors of 3-month mortality after heart transplantation in a Croatian academic center.MethodsA retrospective review of institutional database identified 117 heart transplantations from January 2008 to July 2014. Two children <14 years were excluded from the study. The remaining 115 patients were dichotomized into survivors and non-survivors adjudicated at 3-months postoperatively, and their demographic, clinical, and longitudinal hemodynamic data were analyzed.Results3-month survival after heart transplantation was 86%. Non-survivors were older (59 ± 8 vs 50 ± 14 years, P = 0.009), more likely to have previous cardiac surgery (44% vs 19%; odds ratio [OR] 3.28, 95% confidence interval [CI] 1.08-9.90; P = 0.029), lower body mass index (BMI) (25 ± 4 vs 28 ± 2 kg/m2, P = 0.001), and be diabetics (44% vs 23%; OR 2.57, 95% CI 0.86-7.66; P = 0.083). Creatinine clearance was marginally superior among survivors (59 ± 19 vs 48 ± 20 mL/min, P = 0.059). Donor age and sex did not affect outcomes. Non-survivors were more likely to have had ischemic cardiomyopathy (69% vs 32%, P = 0.010). Postoperative utilization of epinephrine as a second line inotropic agent was a strong predictor of mortality (63% vs 7%; OR 21.91; 95% CI 6.15-78.06; P < 0.001). Serum lactate concentrations were consistently higher among non-survivors, with the difference being most pronounced 2 hours after cardiopulmonary bypass (9.8 ± 3.5 vs 5.2 ± 3.2 mmol/L, P < 0.001). The donor hearts exhibited inferior early hemodynamics in non-survivors (cardiac index 3.0 ± 1.0 vs 4.0 ± 1.1 L/min/m2, P = 0.001), stroke volume (49 ± 24 vs 59 ± 19 mL, P = 0.063), and left and right ventricular stroke work indices (18 ± 8 vs 30 ± 11 g/beat/m2, P < 0.001 and 5 ± 3 vs 7 ± 4 g/beat/m2, P = 0.060, respectively). Non-survivors were more likely to require postoperative re-sternotomy (50% vs 12%; OR 7.25, 95% CI 2.29-22.92; P < 0.001), renal replacement therapy (RRT) (69% vs 9%; OR 22.00, 95% CI 6.24-77.54; P < 0.001), and mechanical circulatory assistance (MCS) (44% vs 5%; OR 14.62, 95% CI 3.84-55.62; P < 0.001). Binary logistic regression revealed recipient age (P = 0.024), serum lactates 2 hours after CPB (P = 0.007), and epinephrine use on postoperative day 1 (P = 0.007) to be independently associated with 3-month mortality.ConclusionPretransplant predictors of adverse outcome after heart transplantation were recipient age, lower BMI, ischemic cardiomyopathy, reoperation and diabetes. Postoperative predictors of mortality were inferior donor heart hemodynamics, epinephrine use, and serum lactate concentrations. Non-survivors were more likely to require re-sternotomy, MCS, and RRT.

BackgroundMitochondrial dysfunction is one of key factors causing heart failure. We performed a comprehensive analysis of expression of mitochondrial quality control (MQC) genes in heart failure.MethodsMyocardial samples were obtained from patients with ischemic and dilated cardiomyopathy in a terminal stage of heart failure and donors without heart disease. Using quantitative real‐time PCR, we analysed a total of 45 MQC genes belonging to mitochondrial biogenesis, fusion‐fission balance, mitochondrial unfolded protein response (UPRmt), translocase of the inner membrane (TIM) and mitophagy. Protein expression was analysed by ELISA and immunohistochemistry.ResultsThe following genes were downregulated in ischemic and dilated cardiomyopathy: COX1, NRF1, TFAM, SIRT1, MTOR, MFF, DNM1L, DDIT3, UBL5, HSPA9, HSPE1, YME1L, LONP1, SPG7, HTRA2, OMA1, TIMM23, TIMM17A, TIMM17B, TIMM44, PAM16, TIMM22, TIMM9, TIMM10, PINK1, PARK2, ROTH1, PARL, FUNDC1, BNIP3, BNIP3L, TPCN2, LAMP2, MAP1LC3A and BECN1. Moreover, MT‐ATP8, MFN2, EIF2AK4 and ULK1 were downregulated in heart failure from dilated, but not ischemic cardiomyopathy. VDAC1 and JUN were only genes that exhibited significantly different expression between ischemic and dilated cardiomyopathy. Expression of PPARGC1, OPA1, JUN, CEBPB, EIF2A, HSPD1, TIMM50 and TPCN1 was not significantly different between control and any form of heart failure. TOMM20 and COX proteins were downregulated in ICM and DCM.ConclusionsHeart failure in patients with ischemic and dilated cardiomyopathy is associated with downregulation of large number of UPRmt, mitophagy, TIM and fusion‐fission balance genes. This indicates multiple defects in MQC and represents one of potential mechanisms underlying mitochondrial dysfunction in patients with heart failure.

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