Primary graft dysfunction (PGD) remains the leading cause of early mortality post-heart transplantation. Despite improvements in mechanical circulatory support and critical care measures, the rate of PGD remains significant. A recent consensus statement by the International Society of Heart and Lung Transplantation (ISHLT) has formulated a definition for PGD. Five years on, we look at current concepts and future directions of PGD in the current era of transplantation.

Aims: In recent years there has been an increase in the number of biomarkers in heart failure(HF). The clinical role for these novel biomarkers in combination is not clear. Methods:The following novel biomarkers were measured from 628 patients recently hospitalised with decompensated HF; mid regional pro-adrenomedullin(MR-proADM), mid regional pro-atrial natriuretic peptide(MR-proANP), copeptin, high sensitivity cardiac troponin T(hs-cTnT), ST2, galectin-3, cystatin C, combined free light chains(cFLC) and high sensitivity C-reactive protein(hsCRP). The incremental prognostic value of these novel biomarkers was evaluated within an extensive model containing established predictors of mortality.Results: During a mean(SD) follow-up of 3.2(1.5) years, 290(46%) patients died.Elevated concentrations of all of the novel biomarkers were associated with an increased unadjusted risk of mortality but only two-thirds were independent predictors following multivariable analysis. Using dichotomized cut-points from ROC analysis, MR-proADM, hs-cTnT, cFLC, hsCRP and ST2 remained independent predictors of mortality. Further dichotomization into low(0-2 elevated biomarkers) or high(at least 3 of the 5 biomarkers elevated) risk groups provided greatest incremental prognostic value(HR 2.20; 95%CI, 1.37 to 3.54; p=0.001) and improved the predictive power of the model(C-statistic 0.730 from 0.721, NRI 32.5%). Conclusion:The novel biomarkers included in this study added little, if any, incremental prognostic value on their own to an extensive model containing established predictors of 3 mortality. However, following dichotomization, 5 of the novel biomarkers provided incremental prognostic value. There was a clear gradient in the risk of death with increasing numbers of elevated novel biomarkers; the presence of at least 3 identifying patients at greatest mortality risk.

AimsApelin, a novel peptide with a putative role in cardiovascular homeostasis, has gained interest as an endogenous inotrope, but has yet to be described following acute myocardial infarction (AMI) in man. We aimed to characterize plasma apelin concentrations following AMI and to examine its relationship with clinical and prognostic biomarkers. Methods and resultsPlasma concentrations of apelin, N-terminal probrain natriuretic peptide (NT-proBNP), norepinephrine, and arginine vasopressin were measured in 100 patients [mean age 58.9 + 12 (SD) years, 77% male] admitted with AMI, with echocardiographic left ventricular (LV) ejection fraction ,40%, at mean 46 h after admission and at 24 weeks. Cardiac magnetic resonance imaging was performed pre-discharge and at 24 weeks. Thirty-eight subjects with no cardiac history acted as controls. Apelin concentration was reduced early after AMI (0.54 + 0.25 vs. 3.22 + 3.01 ng/mL, P ,0.001) and remained low at 24 weeks, although it did increase significantly from baseline to 0.62 + 0.36 ng/mL, P ¼ 0.030. Apelin had no relationship with any parameter of LV function over time. A relationship was found between baseline apelin and norepinephrine (r ¼ 0.26, P ¼ 0.008). Both NT-proBNP and norepinephrine correlated with adverse ventricular function after AMI. ConclusionPlasma apelin concentration is reduced early after AMI, increases significantly over time, but remains depressed at 24 weeks.--

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