Low D-dimer in acute coronary syndrome and heart failure: Screening for large vessel diseases in patients with chest symptoms.

Background: Distinguishing between large-vessel diseases such as acute aortic syndrome (AAS) and pulmonary embolism (PE), and non-large-vessel diseases, such as acute coronary syndrome (ACS), heart failure (HF), and neurogenic diseases, in patients presenting with chest symptoms remains a challenge, which can result in a significant number of misdiagnoses. Simultaneously distinguishing both AAS and PE is essential because large-vessel diseases require angio-computed tomography (CT) during initial presentation whereas, non-large-vessel diseases do not. This study aimed to determine the optimal method for differentiating between large-vessel and non-large-vessel diseases using D-dimer, troponin I, and pretest probability scores. Methods: From the 11683 patients who presented with chest symptoms including chest pain, discomfort, or dyspnea, this retrospective observational study included 1817 patients who had complete data for essential biomarkers; 105 with AAS, 139 with PE, 1093 with ACS, 451 with HF, and 83 with neurogenic diseases. Results: D-dimer, D-dimer/troponin I ratio (DT ratio), and troponin I results distinguished the 2 groups: D-dimer (>2.38 µg/mL), AUC 0.935; DT ratio, AUC 0.827; and troponin I, AUC 0.653. For predicting AAS, the performances of D-dimer level and aortic dissection detection risk score (ADD-RS) were AUCs of 0.915 (p < 0.0001) and 0.67 (p = 0.0004), respectively; for predicting PE, the AUCs of D-dimer level and modified Wells score were 0.95 (p = 0.0001) and 0.857 (p < 0.0001), respectively. Conclusions: The D-dimer levels proved to be a crucial discriminator for identifying AAS and PE, even when compared with the ADD-RS and modified Wells scores. Moderately elevated D-dimer levels suggest the need to consider AAS and PE diagnoses via angio-CT for patients with chest symptoms.

A Novel Tool for Distinguishing Type A Acute Aortic Syndrome from Heart Failure and Acute Coronary Syndrome.

Type A acute aortic syndrome (urgent AAS, UAAS) has a low incidence and high mortality rate; however, it is often missed or diagnosed late. Our aim was to create a new tool for distinguishing UAAS by using multiple modalities to select patients for CT aortography. This study included 75 patients with UAAS, 77 with acute coronary syndrome (ACS), and 81 with heart failure (HF) who received urgent treatment after propensity matching. Specific symptoms, past medical history, mediastinal width, region of interest (ROI) ratio in the lung base/apex, D-dimers, and troponin I were investigated to differentiate UAAS from ACS and HF. The most significant variables were selected to create a new scoring system. The UAAS score exhibited a performance AUC of 0.982. A simple UAAS score >1, excluding ROI ratios in lung base/apex, showed an AUC of 0.977, a sensitivity of 96%, and specificity of 92.41%. The results were validated using an external data set of 292 patients (simple UAAS score > 1: AUC of 0.966, sensitivity 93.33%, and specificity 95.36%). The simple UAAS score may be a valuable tool for suspecting UAAS and may reduce the likelihood of misdiagnosis or performing unnecessary CT aortography.

Loss of Aquaporin-3 in Placenta and Fetal Membranes Induces Growth Restriction in Mice.

Aquaporin (AQP) 3, a facilitated transporter of water and glycerol, expresses in placenta and fetal membranes, but the detailed localization and function of AQP3 in placenta remain unclear. To elucidate a role of AQP3 in placenta, we defined the expression and cellular localization of AQP3 in placenta and fetal membranes, and investigated the structural and functional differences between wild-type and AQP3 null mice. Gestational sacs were removed during mid-gestational period and amniotic fluid was aspirated for measurements of volume and composition. Fetuses with attached placenta and fetal membranes were weighed and processed for histological assessment. AQP3 strongly expressed in basolateral membrane of visceral yolk sac cells of fetal membrane, the syncytiotrophoblasts of the labyrinthine placenta and fetal nucleated red blood cell membrane. Mice lacking AQP3 did not exhibit a significant defect in differentiation of trophoblast stem cells and normal placentation. However, AQP3 null fetuses were smaller than their control litter mates in spite of a decrease in litter size. The total amniotic fluid volume per gestational sac was reduced, but the amniotic fluid-to-fetal weight ratio was increased in AQP3 null mice compared with wild-type mice. Glycerol, free fatty acid and triglyceride levels in amniotic fluid of AQP3 null mice were significantly reduced, whereas lactate level increased when compared to those of wild-type mice. These results suggest a role for AQP3 in supplying nutrients from yolk sac and maternal blood to developing fetus by facilitating transport of glycerol in addition to water, and its implication for the fetal growth in utero.