For cardiac defibrillator testing and design purposes, the range and limits of the human TTI is of high interest. Potential influencing factors regarding the electronic configurations, the electrode/tissue interface and patient characteristics were identified and analyzed. A literature survey based on 71 selected articles was used to review and assess human TTI and the influencing factors found. The human TTI extended from 12 to 212 $\Omega$ in the literature selected. Excluding outliers and pediatric measurements, the mean TTI recordings ranged from 51 to 112 $\Omega$ with an average TTI of 76.7 $\Omega$ under normal distribution. The wide range of human impedance can be attributed to 12 different influencing factors, including shock waveforms and protocols, coupling devices, electrode size and pressure, electrode position, patient age, gender, body dimensions, respiration and lung volume, blood hemoglobin saturation and different pathologies. The coupling device, electrode size and electrode pressure have the greatest influence on TTI.

Registration of dynamic CT image sequences is a crucial preprocessing step for clinical evaluation of multiple physiological determinants in the heart such as global and regional myocardial perfusion. In this work, we present a deformable deep learning-based image registration method for quantitative myocardial perfusion CT examinations, which in contrast to previous approaches, takes into account some unique challenges such as low image quality with less accurate anatomical landmarks, dynamic changes of contrast agent concentration in the heart chambers and tissue, and misalignment caused by cardiac stress, respiration, and patient motion. The introduced method uses a recursive cascade network with a ventricle segmentation module, and a novel loss function that accounts for local contrast changes over time. It was trained and validated on a dataset of n = 118 patients with known or suspected coronary artery disease and/or aortic valve insufficiency. Our results demonstrate that the proposed method is capable of registering dynamic cardiac perfusion sequences by reducing local tissue displacements of the left ventricle (LV), whereas contrast changes do not affect the registration and image quality, in particular the absolute CT (HU) values of the entire CT sequence. In addition, the deep learning-based approach presented reveals a short processing time of a few seconds compared to conventional image registration methods, demonstrating its application potential for quantitative CT myocardial perfusion measurements in daily clinical routine.

We improved, evaluated, and used Sanger sequencing for quantification of single nucleotide polymorphism (SNP) variants in transcripts and gDNA samples. This improved assay resulted in highly reproducible relative allele frequencies (e.g., for a heterozygous gDNA 50.0±1.4%, and for a missense mutation‐bearing transcript 46.9±3.7%) with a lower detection limit of 3–9%. It provided excellent accuracy and linear correlation between expected and observed relative allele frequencies. This sequencing assay, which can also be used for the quantification of copy number variations (CNVs), methylations, mosaicisms, and DNA pools, enabled us to analyze transcripts of the FBN1 gene in fibroblasts and blood samples of patients with suspected Marfan syndrome not only qualitatively but also quantitatively. We report a total of 18 novel and 19 known FBN1 sequence variants leading to a premature termination codon (PTC), 26 of which we analyzed by quantitative sequencing both at gDNA and cDNA levels. The relative amounts of PTC‐containing FBN1 transcripts in fresh and PAXgene‐stabilized blood samples were significantly higher (33.0±3.9% to 80.0±7.2%) than those detected in affected fibroblasts with inhibition of nonsense‐mediated mRNA decay (NMD) (11.0±2.1% to 25.0±1.8%), whereas in fibroblasts without NMD inhibition no mutant alleles could be detected. These results provide evidence for incomplete NMD in leukocytes and have particular importance for RNA‐based analyses not only in FBN1 but also in other genes. Hum Mutat 30:1–10, 2009.

Patients with Marfan syndrome (MFS) have an increased risk of aortic aneurysm formation, dissection and development of a subtle cardiomyopathy. We analyzed amino acid and lipid metabolic pathways in MFS patients, seeking biomarker patterns as potential monitoring tools of cardiovascular risk with deterioration of myocardial function. We assessed myocardial function in 24 adult MFS patients and compared traditional laboratory values and mass spectrometry-based amino acid, phospholipid and acylcarnitine metabolomes in patients with those in healthy controls. Analytes for which values differed between patients and controls were subjected to regression analysis. A high proportion of patients had signs of impaired diastolic function and elevated serum levels of NT-proBNP. Patients had lower serum levels of taurine, histidine and PCaeC42:3 than controls. The evidence of diastolic dysfunction, aortic root dimensions and history of aortic root surgery correlated with NT-proBNP and taurine levels. Alterations in serum levels of metabolism derived analytes link MFS pathophysiology with inflammation, oxidative stress and incipient cardiomyopathy.

Background: Hemodynamic alterations in Fontan patients (FP) are associated with hemostatic dysbalance and Fontan-associated liver disease. Studies of other hepatopathologies indicate an interplay between cholestasis, tissue factor (TF), and von Willebrand factor (VWF). Hence, we hypothesized a relationship between the accumulation of bile acids (BA) and these hemostatic factors in FP. Methods: We included 34 FP (Phenprocoumon n = 15, acetylsalicylic acid (ASA) n = 16). BA were assessed by mass spectrometry. TF activity and VWF antigen (VWF:Ag) were determined by chromogenic assays. VWF collagen-binding activity (VWF:CB) was assessed via ELISA. Results: Cholestasis was observed in 6/34 FP (total BA ≥ 10 µM). BA levels and TF activity did not correlate (p = 0.724). Cholestatic FP had lower platelet counts (p = 0.013) from which 5/6 FP were not treated with ASA. VWF:Ag levels were increased in 9/34 FP and significantly lower in FP receiving ASA (p = 0.044). Acquired von Willebrand syndrome (AVWS) was observed in 10/34-FP, with a higher incidence in cholestatic FP (4/6) (p = 0.048). Conclusions: Cholestasis is unexpectedly infrequent in FP and seems to be less frequent under ASA therapy. Therefore, ASA may reduce the risk of advanced liver fibrosis. FP should be screened for AVWS to avoid bleeding events, especially in cholestatic states.