No abstract

Right heart thrombus in transit is an increasingly recognized medical emergency with very high mortality rate. Echocardiography helps to establish the diagnosis and can differentiate between right heart thrombi that result from atrial fibrillation and those originating from deep venous thrombosis. We present two cases of right heart thrombus in transit diagnosed with echocardiography that were managed with different approaches.Electronic supplementary materialThe online version of this article (doi:10.1186/s13089-017-0069-9) contains supplementary material, which is available to authorized users.

LIG4/Dnl4 is the DNA ligase that (re)joins DNA double-strand breaks (DSBs) via nonhomologous end joining (NHEJ), an activity supported by binding of its tandem BRCT domains to the ligase accessory protein XRCC4/Lif1. We screened a panel of 88 distinct ligase mutants to explore the structure-function relationships of the yeast Dnl4 BRCT domains and inter-BRCT linker in NHEJ. Screen results suggested two distinct classes of BRCT mutations with differential effects on Lif1 interaction as compared to NHEJ completion. Validated constructs confirmed that D800K and GG(868:869)AA mutations, which target the Lif1 binding interface, showed a severely defective Dnl4-Lif1 interaction but a less consistent and often small decrease in NHEJ activity in some assays, as well as nearly normal levels of Dnl4 accumulation at DSBs. In contrast, mutants K742A and KTT(742:744)ATA, which target the β3-α2 region of the first BRCT domain, substantially decreased NHEJ function commensurate with a large defect in Dnl4 recruitment to DSBs, despite a comparatively greater preservation of the Lif1 interaction. Together, these separation-of-function mutants indicate that Dnl4 BRCT1 supports DSB recruitment and NHEJ in a manner distinct from Lif1 binding and reveal a complexity of Dnl4 BRCT domain functions in support of stable DSB association.

Bioprosthetic aortic valve degeneration may present as acute, severe aortic regurgitation and cardiogenic shock. Such patients may be unsuitable for emergency valve replacement surgery due to excessive risk of operative mortality but could be treatable with transfemoral valve-in-valve transcatheter aortic valve implantation (TAVI). There is a paucity of data regarding the feasibility of valve-in-valve TAVI in patients presenting with cardiogenic shock due to acute aortic insufficiency from stentless bioprosthetic valve degeneration. We present one such case, highlighting the unique aspects of valve-in-valve TAVI for this challenging patient subset.

Background: Invasive fractional flow reserve (FFR INV ) is the standard technique for assessing myocardial ischemia. Pressure distortions and measurement location may influence FFR INV interpretation. We report a technique for performing invasive fractional flow reserve (FFR INV ) by minimizing pressure distortions and identifying the proper location to measure FFR INV . Methods: FFR INV recordings were obtained prospectively during manual hyperemic pullback in 100 normal and diseased coronary arteries with single stenosis, using 4 measurements from the terminal vessel, distal-to-the-lesion, proximal vessel, and guiding catheter. FFR INV profiles were developed by plotting FFR INV values ( y -axis) and site of measurement ( x -axis), stratified by stenosis severity. FFR INV ≤0.8 was considered positive for lesion-specific ischemia. Results: Erroneous FFR INV values were observed in 10% of vessels because of aortic pressure distortion and in 21% because of distal pressure drift; these were corrected by disengagement of the guiding catheter and re-equalization of distal pressure/aortic pressure, respectively. There were significant declines in FFR INV from the proximal to the terminal vessel in normal and stenotic coronary arteries ( P <0.001). The rate of positive FFR INV was 41% when measured from the terminal vessel and 20% when measured distal-to-the-lesion ( P <0.001); 41.5% of positive terminal measurements were reclassified to negative when measured distal-to-the-lesion. Measuring FFR INV 20 to 30 mm distal-to-the-lesion (rather than from the terminal vessel) can reduce errors in measurement and optimize the assessment of lesion-specific ischemia. Conclusions: Meticulous technique (disengagement of the guiding catheter, FFR INV pullback) is required to avoid erroneous FFR INV , which occur in 31% of vessels. Even with optimal technique, FFR INV values are influenced by stenosis severity and the site of pressure measurement. FFR INV values from the terminal vessel may overestimate lesion-specific ischemia, leading to unnecessary revascularization.