IL-17 and IFN-γ-producing respiratory tissue resident memory CD4†T cells persist for decades in adults immunized as children with whole cell pertussis vaccines.

The objective was to determine if antigen-specific tissue resident memory T (TRM) cells persist in respiratory tissues of adults immunized as children with whole cell pertussis (wP) or acellular pertussis (aP) vaccines. Mononuclear cells from tonsil or nasal tissue cells were cultured with Bordetella pertussis antigens and TRM cells quantified by flow cytometry. Adults immunized with wP vaccines as children had significantly more IL-17A and IFN-y-producing TRM cells that respond to B. pertussis antigens in respiratory tissues when compared with aP-primed donors. Our findings demonstrate that wP vaccines induce CD4 TRM cells that can persist in respiratory tissues for decades.

Improving Neuromuscular Monitoring Through Education-Based Interventions and Studying Its Association With Adverse Postoperative Outcomes: A Retrospective Observational Study.

BACKGROUND: We assessed the association between education-based interventions, the frequency of train-of-four (TOF) monitoring, and postoperative outcomes. METHODS: We studied adults undergoing noncardiac surgery from February 1, 2020 through October 31, 2021. Our education-based interventions consisted of 3 phases. An interrupted time-series analysis, adjusting for patient- and procedure-related characteristics and secular trends over time, was used to assess the associations between education-based interventions and the frequency of TOF monitoring, postoperative pulmonary complications (PPCs), 90-day mortality, and sugammadex dosage. For each outcome and intervention phase, we tested whether the intervention at that phase was associated with an immediate change in the outcome or its trend (weekly rate of change) over time. In a sensitivity analysis, the association between education-based interventions and postoperative outcomes was adjusted for TOF monitoring. RESULTS: Of 19,422 cases, 11,636 (59.9%) had documented TOF monitoring. Monitoring frequency increased from 44.2% in the first week of preintervention stage to 83.4% in the final week of the postintervention phase. During the preintervention phase, the odds of TOF monitoring trended upward by 0.5% per week (odds ratio [OR], 1.005; 95% confidence interval [CI], 1.002-1.007). Phase 1 saw an immediate 54% increase (OR, 1.54; 95% CI, 1.33-1.79) in the odds, and the trend OR increased by 3% (OR, 1.03; 95% CI, 1.01-1.05) to 1.035, or 3.5% per week (joint Wald test, P < .001). Phase 2 was associated with a further immediate 29% increase (OR, 1.29; 95% CI, 1.02-1.64) but no significant association with trend (OR, 0.96; 95% CI, 0.93-1.01) of TOF monitoring (joint test, P = .04). Phase 3 and postintervention phase were not significantly associated with the frequency of TOF monitoring (joint test, P = .16 and P = .61). The study phases were not significantly associated with PPCs or sugammadex administration. The trend OR for 90-day mortality was larger by 24% (OR, 1.24; 95% CI, 1.06-1.45; joint test, P = .03) in phase 2 versus phase 1, from a weekly decrease of 8% to a weekly increase of 14%. However, this trend reversed again at the transition from phase 3 to the postintervention phase (OR, 0.82; 95% CI, 0.68-0.99; joint test, P = .05), from a 14% weekly increase to a 6.2% weekly decrease in the odds of 90-day mortality. In sensitivity analyses, adjusting for TOF monitoring, we found similar associations between study initiatives and postoperative outcomes. TOF monitoring was associated with lower odds of PPCs (OR, 0.69; 95% CI, 0.55-0.86) and 90-day mortality (OR, 0.79; 95% CI, 0.63-0.98), but not sugammadex dosing (mean difference, -0.02; 95% CI, -0.04 to 0.01). CONCLUSIONS: Our education-based interventions were associated with both TOF utilization and 90-day mortality but were not associated with either the odds of PPCs or sugammadex dosing. TOF monitoring was associated with reduced odds of PPCs and 90-day mortality.

Anatomic, histologic, and mechanical features of the right atrium: implications for leadless atrial pacemaker implantation.

BACKGROUND: Leadless pacemakers (LPs) may mitigate the risk of lead failure and pocket infection related to conventional transvenous pacemakers. Atrial LPs are currently being investigated. However, the optimal and safest implant site is not known. OBJECTIVES: We aimed to evaluate the right atrial (RA) anatomy and the adjacent structures using complementary analytic models [gross anatomy, cardiac magnetic resonance imaging (MRI), and computer simulation], to identify the optimal safest location to implant an atrial LP human. METHODS AND RESULTS: Wall thickness and anatomic relationships of the RA were studied in 45 formalin-preserved human hearts. In vivo RA anatomy was assessed in 100 cardiac MRI scans. Finally, 3D collision modelling was undertaken assessing for mechanical device interaction. Three potential locations for an atrial LP were identified; the right atrial appendage (RAA) base, apex, and RA lateral wall. The RAA base had a wall thickness of 2.7 ± 1.6 mm, with a low incidence of collision in virtual implants. The anteromedial recess of the RAA apex had a wall thickness of only 1.3 ± 0.4 mm and minimal interaction in the collision modelling. The RA lateral wall thickness was 2.6 ± 0.9 mm but is in close proximity to the phrenic nerve and sinoatrial artery. CONCLUSIONS: Based on anatomical review and 3D modelling, the best compromise for an atrial LP implantation may be the RAA base (low incidence of collision, relatively thick myocardial tissue, and without proximity to relevant epicardial structures); the anteromedial recess of the RAA apex and lateral wall are alternate sites. The mid-RAA, RA/superior vena cava junction, and septum appear to be sub-optimal fixation locations.

Development of a cardiovascular magnetic resonance-compatible large animal isolated heart model for direct comparison of beating and arrested hearts.

Cardiac motion results in image artefacts and quantification errors in many cardiovascular magnetic resonance (CMR) techniques, including microstructural assessment using diffusion tensor cardiovascular magnetic resonance (DT-CMR). Here, we develop a CMR-compatible isolated perfused porcine heart model that allows comparison of data obtained in beating and arrested states. Ten porcine hearts (8/10 for protocol optimisation) were harvested using a donor heart retrieval protocol and transported to the remote CMR facility. Langendorff perfusion in a 3D-printed chamber and perfusion circuit re-established contraction. Hearts were imaged using cine, parametric mapping and STEAM DT-CMR at cardiac phases with the minimum and maximum wall thickness. High potassium and lithium perfusates were then used to arrest the heart in a slack and contracted state, respectively. Imaging was repeated in both arrested states. After imaging, tissue was removed for subsequent histology in a location matched to the DT-CMR data using fiducial markers. Regular sustained contraction was successfully established in six out of 10 hearts, including the final five hearts. Imaging was performed in four hearts and one underwent the full protocol, including colocalised histology. The image quality was good and there was good agreement between DT-CMR data in equivalent beating and arrested states. Despite the use of autologous blood and dextran within the perfusate, T2 mapping results, DT-CMR measures and an increase in mass were consistent with development of myocardial oedema, resulting in failure to achieve a true diastolic-like state. A contiguous stack of 313 5-µm histological sections at and a 100-µm thick section showing cell morphology on 3D fluorescent confocal microscopy colocalised to DT-CMR data were obtained. A CMR-compatible isolated perfused beating heart setup for large animal hearts allows direct comparisons of beating and arrested heart data with subsequent colocalised histology, without the need for onsite preclinical facilities.

Validation of an Intensive Care Unit Data Mart for Research and Quality Improvement.

Data derived from the electronic health record (EHR) is frequently extracted using undefined approaches that may affect the accuracy of collected variables. Further, efforts to assess data accuracy often suffer from limited collaboration between clinicians and data analysts who perform the extraction. In this manuscript, we describe the methodology behind creation of a structured, rigorously derived intensive care unit (ICU) data mart based on data automatically and routinely derived from the EHR. This ICU data mart includes high-quality data elements commonly used for quality improvement and research purposes. These data elements were identified by physicians working closely with data analysts to iteratively develop and refine algorithmic definitions for complex outcomes and risk factors. We contend that this methodology can be reproduced and applied across other institution or to other clinical domains to create high quality data marts, inclusive of complex outcomes data.

Immediate and Midterm Cardiac Remodeling After Surgical Pulmonary Valve Replacement in Adults With Repaired Tetralogy of Fallot: A Prospective Cardiovascular Magnetic Resonance and Clinical Study.

BACKGROUND: Pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot provides symptomatic benefit and right ventricular (RV) volume reduction. However, data on the rate of ventricular structural and functional adaptation are scarce. We aimed to assess immediate and midterm post-PVR changes and predictors of reverse remoeling. METHODS: Fifty-seven patients with repaired tetralogy of Fallot (age ≥16 y; mean age, 35.8±10.1 y; 38 male) undergoing PVR were prospectively recruited for cardiovascular magnetic resonance performed before PVR (pPVR), immediately after PVR (median, 6 d), and midterm after PVR (mPVR; median, 3 y). RESULTS: There were immediate and midterm reductions in indexed RV end-diastolic volumes and RV end-systolic volumes (RVESVi) (indexed RV end-diastolic volume pPVR versus immediately after PVR versus mPVR, 156.1±41.9 versus 104.9±28.4 versus 104.2±34.4 mL/m2; RVESVi pPVR versus immediately after PVR versus mPVR, 74.9±26.2 versus 57.4±22.7 versus 50.5±21.7 mL/m2; P<0.01). Normal postoperative diastolic and systolic RV volumes (the primary end point) achieved in 70% of patients were predicted by a preoperative indexed RV end-diastolic volume ≤158 mL/m2 and RVESVi ≤82 mL/m2. RVESVi showed a progressive decrease from baseline to immediate to midterm follow-up, indicating ongoing intrinsic RV functional improvement after PVR. Left ventricular ejection fraction improved (pPVR versus mPVR, 59.4±7.6% versus 61.9±6.8%; P<0.01), and right atrial reverse remodeling occurred (pPVR versus mPVR, 15.2±3.4 versus 13.8±3.6 cm2/m2; P<0.01). Larger preoperative RV outflow tract scar was associated with a smaller improvement in post-PVR RV/left ventricular ejection fraction. RV ejection fraction and peak oxygen uptake predicted mortality (P=0.03) over a median of 9.5 years of follow-up. CONCLUSIONS: Significant right heart structural reverse remodeling takes place immediately after PVR, followed by a continuing process of further biological remodeling manifested by further reduction in RVESVi. PVR before RVESVi reaches 82 mL/m2 confers optimal chances of normalization of RV function.

In vivo cardiovascular magnetic resonance diffusion tensor imaging shows evidence of abnormal myocardial laminar orientations and mobility in hypertrophic cardiomyopathy.

BACKGROUND: Cardiac diffusion tensor imaging (cDTI) measures the magnitudes and directions of intramyocardial water diffusion. Assuming the cross-myocyte components to be constrained by the laminar microstructures of myocardium, we hypothesized that cDTI at two cardiac phases might identify any abnormalities of laminar orientation and mobility in hypertrophic cardiomyopathy (HCM). METHODS: We performed cDTI in vivo at 3 Tesla at end-systole and late diastole in 11 healthy controls and 11 patients with HCM, as well as late gadolinium enhancement (LGE) for detection of regional fibrosis. RESULTS: Voxel-wise analysis of diffusion tensors relative to left ventricular coordinates showed expected transmural changes of myocardial helix-angle, with no significant differences between phases or between HCM and control groups. In controls, the angle of the second eigenvector of diffusion (E2A) relative to the local wall tangent plane was larger in systole than diastole, in accord with previously reported changes of laminar orientation. HCM hearts showed higher than normal global E2A in systole (63.9° vs 56.4° controls, p=0.026) and markedly raised E2A in diastole (46.8° vs 24.0° controls, p<0.001). In hypertrophic regions, E2A retained a high, systole-like angulation even in diastole, independent of LGE, while regions of normal wall thickness did not (LGE present 57.8°, p=0.0028, LGE absent 54.8°, p=0.0022 vs normal thickness 38.1°). CONCLUSIONS: In healthy controls, the angles of cross-myocyte components of diffusion were consistent with previously reported transmural orientations of laminar microstructures and their changes with contraction. In HCM, especially in hypertrophic regions, they were consistent with hypercontraction in systole and failure of relaxation in diastole. Further investigation of this finding is required as previously postulated effects of strain might be a confounding factor.

Machine learning predicts cerebral vasospasm in patients with subarachnoid haemorrhage.

BACKGROUND: Cerebral vasospasm (CV) is a feared complication which occurs after 20-40% of subarachnoid haemorrhage (SAH). It is standard practice to admit patients with SAH to intensive care for an extended period of resource-intensive monitoring. We used machine learning to predict CV requiring verapamil (CVRV) in the largest and only multi-center study to date. METHODS: Patients with SAH admitted to UCLA from 2013 to 2022 and a validation cohort from VUMC from 2018 to 2023 were included. For each patient, 172 unique intensive care unit (ICU) variables were extracted through the primary endpoint, namely first verapamil administration or no verapamil. At each institution, a light gradient boosting machine (LightGBM) was trained using five-fold cross validation to predict the primary endpoint at various hospitalization timepoints. FINDINGS: A total of 1750 patients were included from UCLA, 125 receiving verapamil. LightGBM achieved an area under the ROC (AUC) of 0.88 > 1 week in advance and ruled out 8% of non-verapamil patients with zero false negatives. Our models predicted "no CVRV" vs "CVRV within three days" vs "CVRV after three days" with AUCs = 0.88, 0.83, and 0.88, respectively. From VUMC, 1654 patients were included, 75 receiving verapamil. VUMC predictions averaged within 0.01 AUC points of UCLA predictions. INTERPRETATION: We present an accurate and early predictor of CVRV using machine learning with multi-center validation. This represents a significant step towards optimized clinical management and resource allocation in patients with SAH. FUNDING: Robert E. Freundlich is supported by National Center for Advancing Translational Sciences federal grant UL1TR002243 and National Heart, Lung, and Blood Institute federal grant K23HL148640; these funders did not play any role in this study. The National Institutes of Health supports Vanderbilt University Medical Center which indirectly supported these research efforts. Neither this study nor any other authors personally received financial support for the research presented in this manuscript. No support from pharmaceutical companies was received.

Machine Learning Predicts Cerebral Vasospasm in Subarachnoid Hemorrhage Patients.

Background: Cerebral vasospasm (CV) is a feared complication occurring in 20-40% of patients following subarachnoid hemorrhage (SAH) and is known to contribute to delayed cerebral ischemia. It is standard practice to admit SAH patients to intensive care for an extended period of vigilant, resource-intensive, clinical monitoring. We used machine learning to predict CV requiring verapamil (CVRV) in the largest and only multi-center study to date. Methods: SAH patients admitted to UCLA from 2013-2022 and a validation cohort from VUMC from 2018-2023 were included. For each patient, 172 unique intensive care unit (ICU) variables were extracted through the primary endpoint, namely first verapamil administration or ICU downgrade. At each institution, a light gradient boosting machine (LightGBM) was trained using five- fold cross validation to predict the primary endpoint at various timepoints during hospital admission. Receiver-operator curves (ROC) and precision-recall (PR) curves were generated. Results: A total of 1,750 patients were included from UCLA, 125 receiving verapamil. LightGBM achieved an area under the ROC (AUC) of 0.88 an average of over one week in advance, and successfully ruled out 8% of non-verapamil patients with zero false negatives. Minimum leukocyte count, maximum platelet count, and maximum intracranial pressure were the variables with highest predictive accuracy. Our models predicted "no CVRV" vs "CVRV within three days" vs "CVRV after three days" with AUCs=0.88, 0.83, and 0.88, respectively. For external validation at VUMC, 1,654 patients were included, 75 receiving verapamil. Predictive models at VUMC performed very similarly to those at UCLA, averaging 0.01 AUC points lower. Conclusions: We present an accurate (AUC=0.88) and early (>1 week prior) predictor of CVRV using machine learning over two large cohorts of subarachnoid hemorrhage patients at separate institutions. This represents a significant step towards optimized clinical management and improved resource allocation in the intensive care setting of subarachnoid hemorrhage patients.

IL-10 inhibition during immunization improves vaccine-induced protection against Staphylococcus aureus infection.

Staphylococcus aureus is a major human pathogen. An effective anti-S. aureus vaccine remains elusive as the correlates of protection are ill-defined. Targeting specific T cell populations is an important strategy for improving anti-S. aureus vaccine efficacy. Potential bottlenecks that remain are S. aureus-induced immunosuppression and the impact this might have on vaccine-induced immunity. S. aureus induces IL-10, which impedes effector T cell responses, facilitating persistence during both colonization and infection. Thus, it was hypothesized that transient targeting of IL-10 might represent an innovative way to improve vaccine efficacy. In this study, IL-10 expression was elevated in the nares of persistent carriers of S. aureus, and this was associated with reduced systemic S. aureus-specific Th1 responses. This suggests that systemic responses are remodeled because of commensal exposure to S. aureus, which negatively implicates vaccine function. To provide proof of concept that targeting immunosuppressive responses during immunization may be a useful approach to improve vaccine efficacy, we immunized mice with T cell-activating vaccines in combination with IL-10-neutralizing antibodies. Blocking IL-10 during vaccination enhanced effector T cell responses and improved bacterial clearance during subsequent systemic and subcutaneous infection. Taken together, these results reveal a potentially novel strategy for improving anti-S. aureus vaccine efficacy.

Right atrial appendage and vestibule: further anatomical insights with implications for invasive electrophysiology.

AIMS: Despite recognition that understanding gross anatomy of the right atrium is important in the era of invasive electrophysiology, areas such as the right atrial appendage (RAA) wall or the vestibule are not fully appreciated. The aim of this study was to conduct an anatomical assessment focusing on these structures to gain further insights into electrophysiological procedures. METHODS: Forty-four normal human hearts were examined macro- and microscopically. RESULTS: Inside the RAA, two prominent muscle bundles; the crista terminalis (CT) and the sagittal bundle (SB) were identified. The medial wall at which the CT originated from and its surrounding area was the thickest part adjacent anteriorly to the thin aortic mound, suggesting non-uniform wall thickness of this area. Histological sections revealed that myocardial strands of the SB connected the CT and RAA tip, implying preferential anterior conduction of the sinus impulse. The vestibule had a thin myocardium with extensive fat covering along the epicardial side of the tricuspid annulus. The proximal portion of the right coronary artery (RCA) was relatively distant from the annulus, followed by gradual shortening of the distance from the endocardium to the RCA, which led to a very close relationship (<3.0 mm) at the inferior annulus. CONCLUSION: Non-uniform wall thickness and muscle fibre orientation in the RAA should be taken into consideration during lead/catheter positioning. The RCA proximity in the inferior portion of the vestibule and the deeper fatty plane of the anterior atrioventricular groove are important anatomical features relevant to accessory pathway ablation.

Double outlet ventricles: review of anatomic and imaging characteristics.

Hearts with double outlet ventricles and concordant atrioventricular connections account for about 1%-3% of all cases of congenital heart disease. We review hearts with two ventricles and concordant atrioventricular connections with double outlet right ventricle (DORV), double outlet left ventricle (DOLV) and double outlet both ventricles (DOBV) from the morphological and clinical imaging perspectives. These hearts are a heterogeneous group of congenital cardiac malformations with a wide range of pathophysiologies that require an individualised surgical approach based on a precise understanding of the complex cardiovascular anatomy. Owing to their differing temporal, spatial and contrast resolutions, we propose that multimodality imaging provides optimal characterisation of various intracardiac morphological features of double outlet hearts. This approach aids clinical diagnosis for optimising treatment options across these malformations.

Nasal vaccines for pertussis.

Whooping cough, caused by Bordetella pertussis, is still a major cause of morbidity and mortality worldwide. Current acellular pertussis (aP) vaccines induce potent circulating IgG and prevent severe disease in children/adults and in infants born to vaccinated mothers. However, they do not prevent nasal infection, allowing asymptomatic transmission of B. pertussis. Studies in animal models have demonstrated that, unlike natural infection, immunization with aP vaccines fails to induce secretory immunoglobulin A (IgA) or interleukin-17 (IL-17)-secreting tissue-resident memory CD4 T (TRM) cells, required for sustained sterilizing immunity in the nasal mucosa. Live-attenuated vaccines or aP vaccines formulated with novel adjuvants that induce respiratory IgA and TRM cells, especially when delivered by the nasal route, are in development and have considerable promise as next-generation vaccines against pertussis.

Improving Compliance With Institutional Performance on Train of Four Monitoring.

Background: We performed a multistep quality improvement project related to neuromuscular blockade and monitoring to evaluate the effectiveness of a comprehensive quality improvement program based upon the Multi-institutional Perioperative Outcomes Group (MPOG) Anesthesiology Performance Improvement and Reporting Exchange (ASPIRE) metrics targeted specifically at improving train of four (TOF) monitoring rates. Methods: We adapted the plan-do-study-act (PDSA) framework and implemented 2 PDSA cycles between January 2021 and December 2021. PDSA Cycle 1 (Phase I) and PDSA Cycle 2 (Phase II) included a multipart program consisting of (1) a departmental survey assessing attitudes toward intended results, outcomes, and barriers for TOF monitoring, (2) personalized MPOG ASPIRE quality performance reports displaying provider performance, (3) a dashboard access to help providers complete a case-by-case review, and (4) a web-based app spaced education module concerning TOF monitoring and residual neuromuscular blockade. Our primary outcome was to identify the facilitators and barriers to implementation of our intervention aimed at increasing TOF monitoring. Results: In Phase I, 25 anesthesia providers participated in the preintervention and postintervention needs assessment survey and received personalized quality metric reports. In Phase II, 222 providers participated in the preintervention needs assessment survey and 201 participated in the postintervention survey. Thematic analysis of Phase I survey data aimed at identifying the facilitators and barriers to implementation of a program aimed at increasing TOF monitoring revealed the following: intended results were centered on quality of patient care, barriers to implementation largely encompassed issues with technology/equipment and the increased burden placed on providers, and important outcomes were focused on patient outcomes and improving provider knowledge. Results of Phase II survey data was similar to that of Phase I. Notably in Phase II a few additional barriers to implementation were mentioned including a fear of loss of individualization due to standardization of patient care plan, differences between the attending overseeing the case and the in-room provider who is making decisions/completing documentation, and the frequency of intraoperative handovers. Compared to preintervention, postintervention compliance with TOF monitoring increased from 42% to 70% (28% absolute difference across N = 10 169 cases; P < .001). Conclusions: Implementation of a structured quality improvement program using a novel educational intervention showed improvements in process metrics regarding neuromuscular monitoring, while giving us a better understanding of how best to implement improvements in this metric at this magnitude.

PeRiOperative Glucose PRAgMatic (PROGRAM) trial protocol and statistical analysis plan for comparing automated intraoperative reminders to standardise insulin administration in surgical patients at high risk of hyperglycaemia.

INTRODUCTION: Studies finding perioperative hyperglycaemia is associated with adverse patient outcomes in surgical procedures spurred the development of blood glucose guidelines at many institutions. In this trial, we will assess the implementation of a clinical decision support tool that is integrated into the intraoperative portion of our electronic health record and provides real-time best practice recommendations for intraoperative insulin dosing in surgical patients at high risk for hyperglycaemia. METHODS AND DESIGN: We will assess this intervention using a sequential and repeated cross-over design at the institutional level with periods of time for wash-out, control and study intervention. The unit of analysis will be the surgical case. The primary outcome will be the frequency of hyperglycaemia (>180 mg/dL (10 mmol/L)) at first postoperative anaesthesia care unit measurement. There are several prespecified secondary analyses focused on perioperative glycaemic control. DISCUSSION: This protocol and statistical analysis plan describes the methodology, primary and secondary analyses. The PeRiOperative Glucose PRAgMatic (PROGRAM) trial was approved by the Vanderbilt University Institutional Review Board (IRB), Vanderbilt University Medical Center, Nashville, Tennessee, USA (IRB, 220991). The study results will be disseminated via publication in a peer-reviewed journal and presented at national scientific conferences. The results of PROGRAM trial will inform best practice for perioperative standardised insulin administration in surgical patients at high risk of hyperglycaemia. TRIAL REGISTRATION NUMBER: NCT05426096.

Anatomic assessment of variations in myocardial approaches to the atrioventricular node.

INTRODUCTION: The tissues in the posteroinferior atrioventricular (AV) junction around the AV node are important in procedures for ablating and manipulation of catheters in and around the coronary sinus (CS). However, information with regard to the histological arrangement of perinodal myocardium relative to the CS is lacking. METHODS AND RESULTS: We examined 21 postmortem human hearts without any abnormalities (9 women; mean age 68.8 ± 14.3 years). After making measurements, the posteroinferior AV junction was removed and processed for histology. Sections were cut parallel to the septum. We assessed the myocardial arrangements from the atrial septum and the CS toward the AV nodal tissue, including the transitional cell zone, and measured the dimensions between the compact AV node and the CS, and the circumference of the CS. We observed 3 patterns of myocardial approaches to the AV node: extension of myocardium from the atrial septum (Group A; n = 6); extension of CS musculature (Group B; n = 6); and both septal and CS musculature (Group C; n = 9). The distance between the AV node and the CS in Group A was significantly longer than in the other groups (mean 11.5 ± 3.1 mm, 1.7 ± 0.6 mm, 3.8 ± 1.5 mm, respectively; P < 0.0001), and the circumference of the CS in Group B was longer than in Group A (mean 31.1 ± 7.9 mm*, 44.4 ± 8.4 mm*, 33.7 ± 6.9 mm, respectively; P < 0.05). CONCLUSION: The myocardial approaches including the transitional cell zone toward the AV node are variable in normal hearts. The location and size of the CS can affect the myocardial arrangements and the area of transitional cells around the AV node.

Reproducibility of in-vivo diffusion tensor cardiovascular magnetic resonance in hypertrophic cardiomyopathy.

BACKGROUND: Myocardial disarray is an important histological feature of hypertrophic cardiomyopathy (HCM) which has been studied post-mortem, but its in-vivo prevalence and extent is unknown. Cardiac Diffusion Tensor Imaging (cDTI) provides information on mean intravoxel myocyte orientation and potentially myocardial disarray. Recent technical advances have improved in-vivo cDTI, and the aim of this study was to assess the interstudy reproducibility of quantitative in-vivo cDTI in patients with HCM. METHODS AND RESULTS: A stimulated-echo single-shot-EPI sequence with zonal excitation and parallel imaging was implemented. Ten patients with HCM were each scanned on 2 different days. For each scan 3 short axis mid-ventricular slices were acquired with cDTI at end systole. Fractional anisotropy (FA), mean diffusivity (MD), and helix angle (HA) maps were created using a cDTI post-processing platform developed in-house. The mean ± SD global FA was 0.613 ± 0.044, MD was 0.750 ± 0.154 × 10-3 mm2/s and HA was epicardium -34.3 ± 7.6°, mesocardium 3.5 ± 6.9° and endocardium 38.9 ± 8.1°. Comparison of initial and repeat studies showed global interstudy reproducibility for FA (SD = ± 0.045, Coefficient of Variation (CoV) = 7.2%), MD (SD = ± 0.135 × 10-3 mm2/s, CoV = 18.6%) and HA (epicardium SD = ± 4.8°; mesocardium SD = ± 3.4°; endocardium SD = ± 2.9°). Reproducibility of FA was superior to MD (p = 0.003). MD was significantly higher in the septum than the reference lateral wall (0.784 ±0.188 vs 0.714 ±0.155 ×10-3 mm2/s, p <0.001) [corrected]. Septal HA was significantly lower than the reference lateral wall in all 3 transmural layers (from -8.3° to -10.4°, all p < 0.001). CONCLUSIONS: To the best of our knowledge, this is the first study to assess the interstudy reproducibility of DTI in the human HCM heart in-vivo and the largest cDTI study in HCM to date. Our results show good reproducibility of FA, MD and HA which indicates that current technology yields robust in-vivo measurements that have potential clinical value. The interpretation of regional differences in the septum requires further investigation.

Association of Time to Surgery After COVID-19 Infection With Risk of Postoperative Cardiovascular Morbidity.

Importance: The time interval between COVID-19 infection and surgery is a potentially modifiable but understudied risk factor for postoperative complications. Objective: To examine the association between time to surgery after COVID-19 diagnosis and the risk of a composite of major postoperative cardiovascular morbidity events within 30 days of surgery. Design, Setting, and Participants: This single-center, retrospective cohort study was conducted among 3997 adult patients (aged ≥18 years) with a previous diagnosis of COVID-19, as documented by a positive polymerase chain reaction test result, who were undergoing surgery from January 1, 2020, to December 6, 2021. Data were obtained through Structured Query Language access of an existing perioperative data warehouse. Statistical analysis was performed March 29, 2022. Exposure: The time interval between COVID-19 diagnosis and surgery. Main Outcomes and Measures: The primary outcome was the composite occurrence of major cardiovascular comorbidity, defined as deep vein thrombosis, pulmonary embolism, cerebrovascular accident, myocardial injury, acute kidney injury, and death within 30 days after surgery, using multivariable logistic regression. Results: A total of 3997 patients (2223 [55.6%]; median age, 51.3 years [IQR, 35.1-64.4 years]; 667 [16.7%] African American or Black; 2990 [74.8%] White; and 340 [8.5%] other race) were included in the study. The median time from COVID-19 diagnosis to surgery was 98 days (IQR, 30-225 days). Major postoperative adverse cardiovascular events were identified in 485 patients (12.1%). Increased time from COVID-19 diagnosis to surgery was associated with a decreased rate of the composite outcome (adjusted odds ratio, 0.99 [per 10 days]; 95% CI, 0.98-1.00; P = .006). This trend persisted for the 1552 patients who had received at least 1 dose of COVID-19 vaccine (adjusted odds ratio, 0.98 [per 10 days]; 95% CI, 0.97-1.00; P = .04). Conclusions and Relevance: This study suggests that increased time from COVID-19 diagnosis to surgery was associated with a decreased odds of experiencing major postoperative cardiovascular morbidity. This information should be used to better inform risk-benefit discussions concerning optimal surgical timing and perioperative outcomes for patients with a history of COVID-19 infection.

Predicting Survival in Repaired Tetralogy of Fallot: A Lesion-Specific and Personalized Approach.

OBJECTIVES: This study sought to identify patients with repaired tetralogy of Fallot (rTOF) at high risk of death and malignant ventricular arrhythmia (VA). BACKGROUND: To date there is no robust risk stratification scheme to predict outcomes in adults with rTOF. METHODS: Consecutive patients were prospectively recruited for late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) to define right and left ventricular (RV, LV) fibrosis in addition to proven risk markers. RESULTS: The primary endpoint was all-cause mortality. Of the 550 patients (median age 32 years, 56% male), 27 died (mean follow-up 6.4 ± 5.8; total 3,512 years). Mortality was independently predicted by RVLGE extent, presence of LVLGE, RV ejection fraction ≤47%, LV ejection fraction ≤55%, B-type natriuretic peptide ≥127 ng/L, peak exercise oxygen uptake (V02) ≤17 mL/kg/min, prior sustained atrial arrhythmia, and age ≥50 years. The weighted scores for each of the preceding independent predictors differentiated a high-risk subgroup of patients with a 4.4%, annual risk of mortality (area under the curve [AUC]: 0.87; P < 0.001). The secondary endpoint (VA), a composite of life-threatening sustained ventricular tachycardia/resuscitated ventricular fibrillation/sudden cardiac death occurred in 29. Weighted scores that included several predictors of mortality and RV outflow tract akinetic length ≥55 mm and RV systolic pressure ≥47 mm Hg identified high-risk patients with a 3.7% annual risk of VA (AUC: 0.79; P < 0.001) RVLGE was heavily weighted in both risk scores caused by its strong relative prognostic value. CONCLUSIONS: We present a score integrating multiple appropriately weighted risk factors to identify the subgroup of patients with rTOF who are at high annual risk of death who may benefit from targeted therapy.

Total anomalous pulmonary venous connection: morphology and outcome from an international population-based study.

BACKGROUND: late mortality after repair of total anomalous pulmonary venous connection is frequently associated with pulmonary venous obstruction (PVO). We aimed to describe the morphological spectrum of total anomalous pulmonary venous connection and identify risk factors for death and postoperative PVO. METHODS AND RESULTS: we conducted a retrospective, international, collaborative, population-based study involving all 19 pediatric cardiac centers in the United Kingdom, Ireland, and Sweden. All infants with total anomalous pulmonary venous connection born between 1998 and 2004 were identified. Cases with functionally univentricular circulations or atrial isomerism were excluded. All available data and imaging were reviewed. Of 422 live-born cases, 205 (48.6%) had supracardiac, 110 (26.1%) had infracardiac, 67 (15.9%) had cardiac, and 37 (8.8%) had mixed connections. There were 2 cases (0.5%) of common pulmonary vein atresia. Some patients had extremely hypoplastic veins or, rarely, discrete stenosis of the individual veins. Sixty (14.2%) had associated cardiac anomalies. Sixteen died before intervention. Three-year survival for surgically treated patients was 85.2% (95% confidence interval 81.3% to 88.4%). Risk factors for death in multivariable analysis comprised earlier age at surgery, hypoplastic/stenotic pulmonary veins, associated complex cardiac lesions, postoperative pulmonary hypertension, and postoperative PVO. Sixty (14.8%) of the 406 patients undergoing total anomalous pulmonary venous connection repair had postoperative PVO that required reintervention. Three-year survival after initial surgery for patients with postoperative PVO was 58.7% (95% confidence interval 46.2% to 69.2%). Risk factors for postoperative PVO comprised preoperative hypoplastic/stenotic pulmonary veins and absence of a common confluence. CONCLUSIONS: preoperative clinical and morphological features are important risk factors for postoperative PVO and survival.