Incidental findings on routine preoperative noncontrast chest computed tomography and chest radiography prior to cardiac surgery in the multicenter randomized controlled CRICKET study.

OBJECTIVE: To describe the prevalence and consequences of incidental findings when implementing routine noncontrast CT prior to cardiac surgery. METHODS: In the multicenter randomized controlled CRICKET study, 862 adult patients scheduled for cardiac surgery were randomized 1:1 to undergo standard of care (SoC), which included a chest-radiograph, or an additional preoperative noncontrast chest CT-scan (SoC+CT). In this subanalysis, all incidental findings detected on the chest radiograph and CT-scan were analyzed. The influence of smoking status on incidental findings was also evaluated, adjusting for sex, age, and group allocation. RESULTS: Incidental findings were observed in 11.4% (n = 49) of patients in the SoC+CT group and in 3.7% (n = 16) of patients in the SoC-group (p < 0.001). The largest difference was observed in findings requiring follow-up (SoC+CT 7.7% (n = 33) vs SoC 2.3% (n = 10), p < 0.001). Clinically relevant findings changing the surgical approach or requiring specific treatment were observed in 10 patients (1.2%, SoC+CT: 1.6% SoC: 0.7%), including lung cancer in 0.5% of patients (n = 4) and aortic dilatation requiring replacement in 0.2% of patients (n = 2). Incidental findings were more frequent in patients who stopped smoking (OR 1.91, 1.03-3.63) or who actively smoked (OR 3.91, 1.85-8.23). CONCLUSIONS: Routine CT-screening increases the rate of incidental findings, mainly by identifying more pulmonary findings requiring follow-up. Incidental findings are more prevalent in patients with a history of smoking, and preoperative CT might increase the yield of identifying lung cancer in these patients. Incidental findings, but not specifically the use of routine CT, are associated with delay of surgery. KEY POINTS: • Clinically relevant incidental findings are identified more often after a routine preoperative CT-scan, when compared to a standard of care workup, with some findings changing patient management. • Patients with a history of smoking have a higher rate of incidental findings and a lung cancer rate comparable to that of lung cancer screening trials. • We observed no clear delay in the time to surgery when adding routine CT screening.

Relapsing low-flow alarms due to suboptimal alignment of the left ventricular assist device inflow cannula.

OBJECTIVES: This retrospective study investigated the correlation between the angular position of the left ventricular assist device (LVAD) inflow cannula and relapsing low-flow alarms. METHODS: Medical charts were reviewed of all patients with HeartMate 3 LVAD support for relapsing low-flow alarms. A standardized protocol was created to measure the angular position with a contrast-enhanced computed tomography scan. Statistics were done using a gamma frailty model with a constant rate function. RESULTS: For this analysis, 48 LVAD-supported patients were included. The majority of the patients were male (79%) with a median age of 57 years and a median follow-up of 30 months (interquartile range: 19-41). Low-flow alarm(s) were experienced in 30 (63%) patients. Angulation towards the septal-lateral plane showed a significant increase in low-flow alarms over time with a constant rate function of 0.031 increase in low-flow alarms per month of follow-up per increasing degree of angulation (P = 0.048). When dividing this group using an optimal cut-off point, a significant increase in low-flow alarms was observed when the septal-lateral angulation was 28° or more (P = 0.001). Anterior-posterior and maximal inflow cannula angulation did not show a significant difference. CONCLUSIONS: This study showed an increasing number of low-flow alarms when the degrees of LVAD inflow cannula expand towards the septal-lateral plane. This emphasizes the importance of the LVAD inflow cannula angular position to prevent relapsing low-flow alarms with the risk of diminished quality of life and morbidity.

Relapsing low-flow alarms due to suboptimal alignment of the left ventricular assist device inflow cannula.

OBJECTIVES: This retrospective study investigated the correlation between the angular position of the left ventricular assist device (LVAD) inflow cannula and relapsing low-flow alarms. METHODS: Medical charts were reviewed of all patients with HeartMate 3 LVAD support for relapsing low-flow alarms. A standardized protocol was created to measure the angular position with a contrast-enhanced computed tomography scan. Statistics were done using a gamma frailty model with a constant rate function. RESULTS: For this analysis, 48 LVAD-supported patients were included. The majority of the patients were male (79%) with a median age of 57 years and a median follow-up of 30 months (interquartile range: 19-41). Low-flow alarm(s) were experienced in 30 (63%) patients. Angulation towards the septal-lateral plane showed a significant increase in low-flow alarms over time with a constant rate function of 0.031 increase in low-flow alarms per month of follow-up per increasing degree of angulation (P = 0.048). When dividing this group using an optimal cut-off point, a significant increase in low-flow alarms was observed when the septal-lateral angulation was 28° or more (P = 0.001). Anterior-posterior and maximal inflow cannula angulation did not show a significant difference. CONCLUSIONS: This study showed an increasing number of low-flow alarms when the degrees of LVAD inflow cannula expand towards the septal-lateral plane. This emphasizes the importance of the LVAD inflow cannula angular position to prevent relapsing low-flow alarms with the risk of diminished quality of life and morbidity.

Leaflet Thickening and Motion After Transcatheter Aortic Valve Replacement: Design and Rationale of the Rotterdam Edoxaban Trial.

BACKGROUND: Multislice computed tomography (MSCT) may reveal hypo-attenuated leaflet thickening (HALT) and/or reduced leaflet motion (RELM) in approximately 15 % of patients after transcatheter aortic valve replacement (TAVR). These supposedly thrombogenic phenomena may be associated with neurological events and increased transprosthetic gradients. It is unclear whether oral anticoagulant therapy -specifically a factor Xa inhibitor- could affect the incidence of HALT/RELM. STUDY DESIGN: The Rotterdam EDOXaban (REDOX) trial is an investigator-initiated, single-center, prospective registry in which 100 patients with no formal indication for oral anticoagulant drugs or dual antiplatelet therapy, will receive a 3-month treatment with edoxaban, followed by a MSCT to detect HALT/RELM. The primary endpoint is the incidence of HALT at 3-months follow-up. Secondary endpoints include the incidence of RELM at 3 months; change in transprosthetic gradients at 1 year and the clinical composite endpoint of all-cause death, myocardial infarction (MI), ischemic stroke, systemic thromboembolism, valve thrombosis and major bleeding (International Society on Thrombosis and Hemostasis [ISTH] definition) at 1 year follow up. The study is powered to demonstrate with 90 % statistical power and a 0.025 alpha a 4 % incidence of HALT with edoxaban as compared to the expected 15 % rate with an antiplatelet regimen and will enroll 100 patients to account for loss of follow-up or CT-drop out. CONCLUSION: The REDOX trial will investigate the short-term effect of an Xa-inhibitor on the incidence of HALT after TAVR. (ClinicalTrials.gov Identifier: NCT04171726).

Effect of routine preoperative screening for aortic calcifications using noncontrast computed tomography on stroke rate in cardiac surgery: the randomized controlled CRICKET study.

OBJECTIVES: To evaluate if routine screening for aortic calcification using unenhanced CT lowers the risk of stroke and alters the surgical approach in patients undergoing general cardiac surgery compared with standard of care (SoC). METHODS: In this prospective, multicenter, randomized controlled trial, adult patients scheduled for cardiac surgery from September 2014 to October 2019 were randomized 1:1 into two groups: SoC alone, including chest radiography, vs. SoC plus preoperative noncontrast CT. The primary endpoint was in-hospital perioperative stroke. Secondary endpoints were preoperative change of the surgical approach, in-hospital mortality, and postoperative delirium. The trial was halted halfway for expected futility, as the conditional power analysis showed a chance < 1% of finding the hypothesized effect. RESULTS: A total of 862 patients were evaluated (SoC-group: 433 patients (66 ± 11 years; 74.1% male) vs. SoC + CT-group: 429 patients (66 ± 10 years; 69.9% male)). The perioperative stroke rate (SoC + CT: 2.1%, 9/429 vs. SoC: 1.2%, 5/433, p = 0.27) and rate of changed surgical approach (SoC + CT: 4.0% (17/429) vs. SoC: 2.8% (12/433, p = 0.35) did not differ between groups. In-hospital mortality and postoperative delirium were comparable between groups. In the SoC + CT group, aortic calcification was observed on CT in the ascending aorta in 28% (108/380) and in the aortic arch in 70% (265/379). CONCLUSIONS: Preoperative noncontrast CT in cardiac surgery candidates did not influence the surgical approach nor the incidence of perioperative stroke compared with standard of care. Aortic calcification is a frequent finding on the CT scan in these patients but results in major surgical alterations to prevent stroke in only few patients. KEY POINTS: • Aortic calcification is a frequent finding on noncontrast computed tomography prior to cardiac surgery. • Routine use of noncontrast computed tomography does not often lead to a change of the surgical approach, when compared to standard of care. • No effect was observed on perioperative stroke after cardiac surgery when using routine noncontrast computed tomography screening on top of standard of care.

A case report of an interrupted inferior vena cava and azygos continuation: implications for preoperative screening in minimally invasive cardiac surgery.

BACKGROUND: Femoral cannulation is commonly used in minimally invasive cardiac surgery to establish extracorporeal circulation. We present a case with a finding that should be evaluated when screening candidates for minimally invasive cardiac surgery. CASE SUMMARY: A 57-year-old male patient was scheduled for minimally invasive repair of the mitral and tricuspid valve and a MAZE procedure. During surgery there was difficulty advancing the venous cannula inserted in the right femoral vein. On transoesophageal echocardiography a guidewire advanced from the femoral vein was observed entering the right atrium from the superior vena cava. Despite inserting a second venous cannula in the jugular vein, venous drainage was insufficient for minimal invasive surgery. The approach was converted to a median sternotomy with bicaval cannulation. Re-examination of the preoperative computed tomography (CT) scan showed an interrupted inferior vena cava (IVC) with azygos continuation. DISCUSSION: In patients with major venous malformations such as the interrupted IVC with azygos continuation a full sternotomy is the preferred approach. The venous system should be evaluated when screening candidates for minimally invasive mitral valve surgery with preoperative CT. Additional cues to suspect interruption of the IVC are polysplenia and a broad superior mediastinal projection on the chest radiograph, mimicking a right paratracheal mass.

Intimal aortic atherosclerosis in cardiac surgery: surgical strategies to prevent embolic stroke.

OBJECTIVES: Although the incidence of perioperative stroke after cardiac surgery gradually decreased over the last decades, there is much variation between centres. This review aimed to create a concise overview of the evidence on possible surgical strategies to prevent embolic stroke in patients with intimal aortic atherosclerosis. METHODS: The PubMed and EMBASE databases were searched for studies on surgical management of aortic atherosclerosis and the association with perioperative stroke in cardiac surgery, including specific searches on the most common types of surgery. Articles were screened with emphasis on studies comparing multiple strategies and studies reporting on the patients' severity of aortic atherosclerosis. The main findings were summarized in a figure, with a grade of the corresponding level of evidence. RESULTS: Regarding embolic stroke risk, aortic atherosclerosis of the tunica intima is most relevant. Although several strategies in general cardiac surgery seem to be beneficial in severe disease, none have conclusively been proven most effective. Off-pump surgery in coronary artery bypass grafting should be preferred with severe atherosclerosis, if the required expertise is present. Although transcatheter aortic valve replacement is used as an alternative to surgery in patients with a porcelain aorta, the risk profile concerning intimal atherosclerosis remains poorly defined. CONCLUSIONS: A tailored approach that uses the discussed alternative strategies in carefully selected patients is best suited to reduce the risk of perioperative stroke without compromising other outcomes. More research is needed, especially on the perioperative stroke risk in patients with moderate aortic atherosclerosis.

Screening for coronary artery disease in early surgical treatment of acute aortic valve infective endocarditis.

OBJECTIVES: In patients with unknown coronary status undergoing surgery for acute infective endocarditis (IE), the need to screen for coronary artery disease (CAD) and the risk of embolization during invasive coronary angiography (ICA) are debated. Coronary computed tomography angiography (CCTA) is a non-invasive alternative in these patients. We aimed to evaluate the safety and feasibility of ICA and CCTA to diagnose CAD, and the necessity to treat CAD to prevent CAD-related postoperative complications. METHODS: In this single-centre retrospective cohort study, all patients with acute aortic IE between 2009 and 2019 undergoing surgery were selected. Outcomes were any clinically evident embolization after preoperative ICA, in-hospital mortality, perioperative myocardial infarction or unplanned revascularization and postoperative renal function. RESULTS: Of the 159 included patients, CAD status was already known in 14. No preoperative diagnostics for CAD was done in 46/145, a CCTA was performed in 54/145 patients and an ICA in 52/145 patients. Significant CAD was found after CCTA in 22% and after ICA in 21% of patients. In 1 of the 52 (2%) patients undergoing preoperative ICA, a cerebral embolism occurred. The rate of perioperative myocardial infarction or unplanned revascularization in patients not screened for CAD was 2% (1 out of 46 patients). CONCLUSIONS: Although the risk of embolism after preoperative ICA is low, it should be carefully weighed against the estimated risk of CAD-related perioperative complications. CCTA can serve as a gatekeeper for ICA in most patients with acute aortic IE.

Preoperative Chest Computed Tomography Screening for Coronavirus Disease 2019 in Asymptomatic Patients Undergoing Cardiac Surgery.

Due to the outbreak of Severe Acute Respiratory Syndrome coronavirus (SARS-Cov-2), an efficient COVID-19 screening strategy is required for patients undergoing cardiac surgery. The objective of this prospective observational study was to evaluate the role of preoperative computed tomography (CT) screening for COVID-19 in a population of COVID-19 asymptomatic patients scheduled for cardiac surgery. Between the 29th of March and the 26th of May 2020, patients asymptomatic for COVID-19 underwent a CT-scan the day before surgery, with reverse-transcriptase polymerase-chain reaction (RT-PCR) reserved for abnormal scan results. The primary endpoint was the prevalence of abnormal scans, which was evaluated using the CO-RADS score, a COVID-19 specific grading system. In a secondary analysis, the rate of abnormal scans was compared between the screening cohort and matched historical controls who underwent routine preoperative CT-screening prior to the SARS-Cov-2 outbreak. Of the 109 patients that underwent CT-screening, an abnormal scan result was observed in 7.3% (95% confidence interval: 3.2-14.0%). One patient, with a normal screening CT, was tested positive for COVID-19, with the first positive RT-PCR on the ninth day after surgery. A rate of preoperative CT-scan abnormalities of 8% (n = 8) was found in the unexposed historical controls (P > 0.999). In asymptomatic patients undergoing cardiac surgery, preoperative screening for COVID-19 using computed tomography will identify pulmonary abnormalities in a small percentage of patients that do not seem to have COVID-19. Depending on the prevalence of COVID-19, this results in an unfavorable positive predictive value of CT screening. Care should be taken when considering CT as a screening tool prior to cardiac surgery.

Aortic calcifications on routine preoperative chest X-ray and perioperative stroke during cardiac surgery: a nested matched case-control study.

OBJECTIVES: Perioperative stroke in cardiac surgery is most often embolic in origin. Preoperative chest X-ray (CXR) is routinely used amongst others to screen for relevant aortic calcification, a potential source of embolic stroke. We performed a nested matched case-control study to examine the relationship between aortic calcifications on CXR and the occurrence of embolic stroke. METHODS: Among all consecutive patients undergoing cardiac surgery in our hospital between January 2014 and July 2017, we selected all patients with perioperative embolic stroke (cases). Controls, all patients without perioperative stroke, were matched on age, sex and type of surgery. All preoperative CXRs were scored for aortic calcifications (none, mild, severe) in the ascending aorta, arch, aortic knob and descending aorta. RESULTS: Out of the 3038 eligible patients, 27 cases were detected and 78 controls were selected. In the stroke group, mild-to-severe calcifications were found least often in the ascending aorta [9% of patients, 95% confidence interval (CI) 1-29%] and most frequently in the aortic knob (63% of patients, 95% CI 44-78%). The distribution of aortic calcification was comparable in cases versus controls. CONCLUSIONS: Calcification burden was comparable between the cases and their matched controls. In our study population, CXR findings on aortic calcification were not related to the risk of embolic stroke. In these patients, the correlation between findings on the preoperative CXR and the risk of stroke might, therefore, be too weak to use the CXR directly for the assessment of the safety of manipulating the ascending aorta during surgery.

The Bachmann bundle and interatrial conduction: comparing atrial morphology to electrical activity.

BACKGROUND: The Bachmann bundle (BB) is one of the major interatrial muscular connections. Macroscopic anatomy and electrophysiological properties of BB have so far not been linked, and differences in activation patterns are most likely due to anatomical variations. OBJECTIVES: The goals of this study were to analyze different activation patterns and couple those wavefronts to epicardial morphological structures on cadaveric hearts. METHODS: High-resolution epicardial mapping over BB during sinus rhythm was performed in 185 patients undergoing coronary artery bypass graft surgery. The epicardial atrial musculature was macroscopically examined in 19 postmortem dissected human hearts, which are different from those examined in the mapping study. The morphology of BB and surrounding interatrial connections were evaluated. Activation patterns were subsequently linked to morphological variance found in the dissected hearts. RESULTS: Epicardial mapping showed that BB is activated in a right-to-left direction in the majority of patients. In almost one-third of patients, a wavefront emerging or entering in the middle of BB was also observed. In some patients, left-to-right activation of BB was observed. BB was macroscopically present in all postmortem hearts. In addition, a newly found posterosuperior bundle was consistently seen, joining BB from the posterior border over the interatrial groove. Other connections identified were the septopulmonary bundle and posterior interatrial connections. CONCLUSION: The morphological interatrial connections correspond to the interatrial pathways observed with high-resolution epicardial mapping of BB. Of these connections, BB and the posterosuperior bundle seem to be most consistent, both morphologically and electrophysiologically.

A multicharge ion source (Supernanogan) for the OLIS facility at ISAC/TRIUMF.

The Off-Line Ion Source (OLIS) [K. Jayamanna, D. Yuan, T. Kuo, M. MacDonald, P. Schmor, and G. Dutto, Rev. Sci. Instrum. 67, 1061 (1996); K. Jayamanna, Rev. Sci. Instrum. 79, 02711 (2008)] facility consists of a high voltage terminal containing a microwave cusp ion source, either a surface ion source or a hybrid surface-arc discharge ion source [K. Jayamanna and C. Vockenhuber, Rev. Sci. Instrum. 79, 02C712 (2008)], and an electrostatic switch that allows the selection of any one of the sources without mechanical intervention. These sources provide a variety of +1 beams up to mass 30 for Isotope Separator and ACcelerator (ISAC) [R. E. Laxdal, Nucl. Instrum. Methods Phys. Res. B 204, 400 (2003)] experiments, commissioning the accelerators, setting up the radioactive experiments, and for tuning the beam lines. The radio frequency quadrupole (RFQ) [M. Marchetto, Z. T. Ang, K. Jayamanna, R. E. Laxdal, A. Mitra, and V. Zvyagintsev, Eur. Phys. J. Spec. Top. 150, 241 (2005)] injector accelerator is a constant velocity machine designed to accept only 2 keV/u and the source extraction energy is limited to 60 kV. Further stripping is then needed downstream of the RFQ to inject the beam into the drift tube linac [M. Marchetto, Z. T. Ang, K. Jayamanna, R. E. Laxdal, A. Mitra, and V. Zvyagintsev, Eur. Phys. J. Spec. Top. 150, 241 (2005)] accelerator that requires A/q up to 6. Base on this constraints a multicharge ion source capable to deliver beams above mass 30 with A/q up to 6 was needed in order to reach full capability of the ISAC facility. A Supernanogan [C. Bieth et al., Nucleonika 48, S93 (2003)] multicharge ion source was then purchased from Pantechnik and was installed in the OLIS terminal. Commissioning and performance of the Supernanogan with some results such as emittance dependence of the charge states as well as charge state efficiencies are presented.

A twenty strain survey and backcross localization of the erythrocytic GTP concentration determining locus Gtpc on mouse chromosome 9.

Erythrocyte nucleotide concentrations were surveyed among 20 inbred strains of mice in order to further assess the variability in GTP concentration. There was no significant difference in erythrocytic ATP concentration (Scheffé's test at P = 0.01), 678-1154 nmol/mL packed cells, among the strains surveyed. Two groups were distinguishable with respect to erythrocytic GTP concentration, 8 strains having high GTP, 215 +/- 44 nmole/mL packed cells, and 12 strains having low GTP, 34 +/- 12 nmole/mL packed cells. The erythrocytic GTP concentration determining trait Gtpc was previously shown to be linked to transferrin, Trf, on chromosome 9. Analysis of 232 [(B6 x WB) F1 x B6] backcross individuals for Gtpc and 8 microsatellite markers restricted the localization of Gtpc to a 5.6 +/- 2.1 cM region. The gene order and genetic distances in cM +/- SE are: (D9Mit14) 0.4 +/- 0.4 (D9Mit24) 1.7 +/- 0.8 (Gtpc, D9Mit51, D9Mit116, D9Mit212) 3.9 +/- 1.3 (D9Mit200) 3.0 +/- 1.1 (D9Mit20) 7.8 +/- 1.8 (D9Mit18). The GTP concentration determining trait appears to be a property of erythrocytes as no differences were observed for GTP/ATP ratios of brain, kidney, liver, and tongue from a low GTP strain, C3H/HeHa x Pgk-la and a high GTP strain, C57BL/6J.

Detection of new metabolites of trifluridine (F3TdR) using 19F NMR spectroscopy.

The metabolism of 5-trifluoromethyl-2'-deoxyuridine (trifluridine, F3TdR) in male BALB/C mice has been studied by 19F NMR spectroscopy. Contrary to previous reports, a number of fluorinated metabolites were observed in urine, whole livers and blood samples taken from mice after i.p. injection of F3TdR. The present study describes the identification of two new metabolites in mouse urine using the 19F NMR technique. The NMR of crude urine showed the presence of F3TdR 5-trifluorothymine (F3T), the newly-identified metabolites, 5-trifluoromethyl-5,6-dihydrouracil (DHF3T) and 5-trifluoromethyl-5,6-dihydroxyracil (DOHF3T), and several new, as yet unidentified fluorinate metabolites. These two new metabolites were characterized by comparison to authentic compounds prepared synthetically from F3T.