PurposeCare bundles are recommended in patients at high risk for acute kidney injury (AKI), although they have not been proven to improve outcomes. We sought to establish the efficacy of an implementation of the Kidney Disease Improving Global Outcomes (KDIGO) guidelines to prevent cardiac surgery-associated AKI in high risk patients defined by renal biomarkers.MethodsIn this single-center trial, we examined the effect of a “KDIGO bundle” consisting of optimization of volume status and hemodynamics, avoidance of nephrotoxic drugs, and preventing hyperglycemia in high risk patients defined as urinary [TIMP-2]·[IGFBP7] > 0.3 undergoing cardiac surgery. The primary endpoint was the rate of AKI defined by KDIGO criteria within the first 72 h after surgery. Secondary endpoints included AKI severity, need for dialysis, length of stay, and major adverse kidney events (MAKE) at days 30, 60, and 90.ResultsAKI was significantly reduced with the intervention compared to controls [55.1 vs. 71.7%; ARR 16.6% (95 CI 5.5–27.9%); p = 0.004]. The implementation of the bundle resulted in significantly improved hemodynamic parameters at different time points (p < 0.05), less hyperglycemia (p < 0.001) and use of ACEi/ARBs (p < 0.001) compared to controls. Rates of moderate to severe AKI were also significantly reduced by the intervention compared to controls. There were no significant effects on other secondary outcomes.ConclusionAn implementation of the KDIGO guidelines compared with standard care reduced the frequency and severity of AKI after cardiac surgery in high risk patients. Adequately powered multicenter trials are warranted to examine mortality and long-term renal outcomes.Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-016-4670-3) contains supplementary material, which is available to authorized users.

Patients with cardiac tumors should undergo surgery in a timely fashion in a specialized center. This holds for both malignant and benign tumors, particularly for atrial myxoma, which can cause serious secondary complications by embolization.

In the diagnostic algorithm of cardiac tumors, the noninvasive determination of malignancy and metastatic spread is of major interest to stratify patients and to select and monitor therapies. In the diagnostic work-up, morphologic imaging modalities such as echocardiography or magnetic resonance tomography offer information on, for example, size, invasiveness, and vascularization. However, preoperative assessment of malignancy may be unsatisfactory. The aim of this study was to evaluate the diagnostic value of 18 F-FDG PET and the incremental diagnostic value of an optimized CT score in this clinical scenario. Methods: 18 F-FDG PET/CT scans (wholebody imaging with low-dose CT) of 24 consecutive patients with newly diagnosed cardiac tumors were analyzed (11 men, 13 women; mean age 6 SD, 59 6 13 y). The maximum standardized uptake values (SUV max ) of the tumors were measured. Patients were divided into 2 groups: benign cardiac tumors (n 5 7) and malignant cardiac tumors (n 5 17) (cardiac primaries [n 5 8] and metastases [n 5 9]). SUV max was compared between the 2 groups. Results were compared with contrast-enhanced CT, using standardized criteria of malignancy. Histology served as ground truth. Results: Mean SUV max was 2.8 6 0.6 in benign cardiac tumors and significantly higher both in malignant primary and in secondary cardiac tumors (8.0 6 2.1 and 10.8 6 4.9, P , 0.01). Malignancy was determined with a sensitivity of 100% and specificity of 86% (accuracy, 96%), after a cutoff with high sensitivity (SUV max of 3.5) was chosen to avoid false-negatives. Morphologic imaging reached a sensitivity of 82% and a specificity of 86% (accuracy, 83%). Both false-positive and false-negative decisions in morphology could be corrected in all but 1 case using a metabolic threshold with an SUV max of 3.5. In addition, extracardiac tumor manifestations were detected in 4 patients by whole-body 18 F-FDG PET/CT. Conclusion: 18 F-FDG PET/ CT can aid the noninvasive preoperative determination of malignancy and may be helpful in detecting metastases of malignant cardiac tumors.

In this preliminary study, we demonstrate the potential utility of CE-IR MRI for selective plaque visualization and differentiation of plaque types. The observed contrast uptake may be associated with endothelial dysfunction, neovascularization, inflammation, and/or fibrosis.

BackgroundNormal development of the atria requires left-right differentiation during embryonic development. Reduced expression of Pitx2c (paired-like homeodomain transcription factor 2, isoform c), a key regulator of left-right asymmetry, has recently been linked to atrial fibrillation. We therefore systematically studied the molecular composition of left and right atrial tissue in adult murine and human atria.MethodsWe compared left and right atrial gene expression in healthy, adult mice of different strains and ages by employing whole genome array analyses on freshly frozen atrial tissue. Selected genes with enriched expression in either atrium were validated by RT-qPCR and Western blot in further animals and in shock-frozen left and right atrial appendages of patients undergoing open heart surgery.ResultsWe identified 77 genes with preferential expression in one atrium that were common in all strains and age groups analysed. Independent of strain and age, Pitx2c was the gene with the highest enrichment in left atrium, while Bmp10, a member of the TGFβ family, showed highest enrichment in right atrium. These differences were validated by RT-qPCR in murine and human tissue. Western blot showed a 2-fold left-right concentration gradient in PITX2 protein in adult human atria. Several of the genes and gene groups enriched in left atria have a known biological role for maintenance of healthy physiology, specifically the prevention of atrial pathologies involved in atrial fibrillation, including membrane electrophysiology, metabolic cellular function, and regulation of inflammatory processes. Comparison of the array datasets with published array analyses in heterozygous Pitx2c+/− atria suggested that approximately half of the genes with left-sided enrichment are regulated by Pitx2c.ConclusionsOur study reveals systematic differences between left and right atrial gene expression and supports the hypothesis that Pitx2c has a functional role in maintaining “leftness” in the atrium in adult murine and human hearts.

The agreement between EV-CO and TOE-CO is clinically acceptable, and these two techniques can be used interchangeably.

Primary cardiac angiosarcomas are rare tumors with unfavorable prognosis. Pathogenic driver mutations are largely unknown. We therefore analyzed a collection of cases for genomic aberrations using SNP arrays and targeted next-generation sequencing (tNGS) of oncogenes and tumor-suppressor genes. Recurrent gains of chromosome 1q and a small region of chromosome 4 encompassing KDR and KIT were identified by SNP array analysis. Repeatedly mutated genes identified by tNGS were KDR with different nonsynonymous mutations, MLL2 with different nonsense mutations, and PLCG1 with a recurrent nonsynonymous mutation (R707Q) in the highly conserved autoinhibitory SH2 domain in three of 10 cases. PLCg1 is usually activated by Y783 phosphorylation and activates protein kinase C and Ca 2þ -dependent second messengers, with effects on cellular proliferation, migration, and invasiveness. Ectopic expression of the PLCg1-R707Q mutant in endothelial cells revealed reduced PLCg1-Y783 phosphorylation with concomitant increased c-RAF/MEK/ ERK1/2 phosphorylation, increased IP3 amounts, and increased Ca 2þ -dependent calcineurin activation compared with ectopic expressed PLCg1-wild-type. Furthermore, cofilin, whose activation is associated with actin skeleton reorganization, showed decreased phosphorylation, and thus activation after expression of PLCg1-R707Q compared with PLCg1-wild-type. At the cellular level, expression of PLCg1-R707Q in endothelial cells had no influence on proliferation rate, but increased apoptosis resistance and migration and invasiveness in in vitro assays. Together, these findings indicate that the PLCg1-R707Q mutation causes constitutive activation of PLCg1 and may represent an alternative way of activation of KDR/PLCg1 signaling besides KDR activation in angiosarcomas, with implications for VEGF/KDR targeted therapies. Cancer Res; 74(21); 6173-83. Ó2014 AACR.

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