Search

Abstract Background Pericardial adipose tissue (PAT) has been shown to be an independent predictor of coronary artery disease. To date its assessment has been restricted to the use of surrogate echocardiographic indices such as measurement of epicardial fat thickness over the right ventricular free wall, which have limitations. Cardiovascular magnetic resonance (CMR) offers the potential to non-invasively assess total PAT, however like other imaging modalities, CMR has not yet been validated for this purpose. Thus, we sought to describe a novel technique for assessing total PAT with validation in an ovine model. Methods 11 merino sheep were studied. A standard clinical series of ventricular short axis CMR images (1.5T Siemens Sonata) were obtained during mechanical ventilation breath-holds. Beginning at the mitral annulus, consecutive end-diastolic ventricular images were used to determine the area and volume of epicardial, paracardial and pericardial adipose tissue. In addition adipose thickness was measured at the right ventricular free wall. Following euthanasia, the paracardial adipose tissue was removed from the ventricle and weighed to allow comparison with corresponding CMR measurements. Results There was a strong correlation between CMR-derived paracardial adipose tissue volume and ex vivo paracardial mass (R2 = 0.89, p < 0.001). In contrast, CMR measurements of corresponding RV free wall paracardial adipose thickness did not correlate with ex vivo paracardial mass (R2 = 0.003, p = 0.878). Conclusion In this ovine model, CMR-derived paracardial adipose tissue volume, but not the corresponding and conventional measure of paracardial adipose thickness over the RV free wall, accurately reflected paracardial adipose tissue mass. This study validates for the first time, the use of clinically utilised CMR sequences for the accurate and reproducible assessment of pericardial adiposity. Furthermore this non-invasive modality does not use ionising radiation and therefore is ideally suited for future studies of PAT and its role in cardiovascular risk prediction and disease in clinical practice.

Reactivation or primary infection with double-stranded DNA viruses is common in recipients of solid organ transplants (SOTs) and is associated with significant morbidity and mortality. Treatment with conventional antiviral medications is limited by toxicities, resistance, and a lack of effective options for adenovirus (ADV) and BK polyomavirus (BKPyV). Virus-specific T cells (VSTs) have been shown to be an effective treatment for infections with ADV, BKPyV, cytomegalovirus (CMV), and Epstein-Barr virus (EBV). Most of these studies have been conducted in stem cell recipients, and no large studies have been published in the SOT population to date. In this study, we report on the outcome of quadrivalent third-party VST infusions in 98 recipients of SOTs in the context of an open-label phase 2 trial. The 98 patients received a total of 181 infusions, with a median of 2 infusions per patient. The overall response rate was 45% for BKPyV, 65% for cytomegalovirus, 68% for ADV, and 61% for Epstein-Barr virus. Twenty percent of patients with posttransplant lymphoproliferative disorder had a complete response and 40% of patients had a partial response. All the VST infusions were well tolerated. We conclude that VSTs are safe and effective in the treatment of viral infections in SOT recipients., (Copyright © 2024. Published by Elsevier Inc.)

Background: Cardiac computed tomography quantification of extracellular volume fraction (CT-ECV) is an emerging biomarker of myocardial fibrosis which has demonstrated high reproducibility, diagnostic and prognostic utility. However, there has been wide variation in the CT-ECV protocol in the literature and useful disease cut-offs are yet to be established. The objectives of this meta-analysis were to describe mean CT-ECV estimates and to estimate the effect of CT-ECV protocol parameters on between-study variation., Methods: We conducted a meta-analysis of studies assessing CT-ECV in healthy and diseased participants. We used meta-analytic methods to pool estimates of CT-ECV and performed meta-regression to identify the contribution of protocol parameters to CT-ECV heterogeneity., Results: Thirteen studies had a total of 248 healthy participants who underwent CT-ECV assessment. Studies of healthy participants had high variation in CT-ECV protocol parameters. The pooled estimate of CT-ECV in healthy participants was 27.6% (95%CI 25.7%-29.4%) with significant heterogeneity (I 2  ​= ​93%) compared to 50.2% (95%CI 46.2%-54.2%) in amyloidosis, 31.2% (28.5%-33.8%) in severe aortic stenosis and 36.9% (31.6%-42.3%) in non-ischaemic dilated cardiomyopathies. Meta-regression revealed that CT protocol parameters account for approximately 25% of the heterogeneity in CT-ECV estimates., Conclusion: CT-ECV estimates for healthy individuals vary widely in the literature and there is significant overlap with estimates in cardiac disease. One quarter of this heterogeneity is explained by differences in CT-ECV protocol parameters. Standardization of CT-ECV protocols is necessary for widespread implementation of CT-ECV assessment for diagnosis and prognosis., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Angiographic assessment of left main coronary artery (LMCA) stenosis severity can be unreliable. In cases of ambiguity, intravascular ultrasound (IVUS) can be utilised with a minimal lumen area (MLA) of ≥6 ​mm 2 an accepted threshold for safe deferral of revascularization. We sought to assess whether quantitative computer tomography coronary angiography (CTCA) measures could assist clinicians making LMCA revascularization decisions when compared with IVUS as gold standard., Methods: Consecutive patients undergoing IVUS assessment of angiographically intermediate LMCA stenosis were included. All patients had undergone 320-slice CTCA <90 days prior to IVUS imaging. Offline quantitative assessment of IVUS- and CT-derived measures were undertaken with the cohort divided into those with significant (s-LMCA) versus non-significant (ns-LMCA) disease using the accepted IVUS threshold., Results: Fifty-eight patients were included, with no difference in mean age (61.5 ​± ​12.2 vs. 59.7 ​± ​11.9 years, p ​= ​0.57), diabetic status (24.2% vs 16.0%, p ​= ​0.44) or other baseline demographics between groups. Patients with ns-LMCA had larger CT luminal area (8.64 ​± ​3.91 vs. 5.41 ​± ​1.54 ​mm 2 , p ​< ​0.001), larger minimal lumen diameter (MLD) (3.25 ​± ​0.74 vs. 2.56 ​± ​0.38 ​mm, p ​< ​0.001) and lower area stenosis (45.74 ​± ​18.10 vs. 60.93 ​± ​14.68%, p ​= ​0.001). There was a significant positive correlation between CTCA and IVUS MLA (r ​= ​0.68, p ​< ​0.001) and MLD (r ​= ​0.67, p ​< ​0.001). ROC analysis demonstrated CTCA MLA cut-off <8.29 ​mm 2 provides the greatest negative predictive value and sensitivity in predicting the presence of significant LMCA disease., Conclusion: CTCA derived MLA and MLD have a strong correlation with IVUS. A CTCA derived MLA cut-off <8.29 ​mm 2 showed greatest clinical utility for predicting the need for further assessment, based on IVUS gold standard., Competing Interests: Declaration of competing interest The authors have no specific conflict of interests to declare with respect to this work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

A 4-year-old boy with Nuclear factor-kappa B Essential Modulator deficiency syndrome presented with encephalopathy post haematopoietic stem cell transplantation. MRI demonstrated T2/FLAIR-hyperintensities in the posterior cerebral cortex concerning for posterior reversible encephalopathy syndrome. Clinical improvement was appreciated following withdrawal of the suspected offending pharmacological agent (Cyclosporine). An 18 F-FDG PET/CT performed 2 months later to screen for post-transplant lymphoproliferative disease demonstrated markedly reduced FDG uptake in the posterior cerebral cortex, involving the parietal and occipital lobes. We describe, to the best of our knowledge, the first case of profound cerebral hypometabolism in a child with clinically resolved posterior reversible encephalopathy syndrome., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Objective: To explore the effect of SMS nudge messages amongst people with varying health literacy on their intention to get a Heart Health Check., Methods: A 3 (Initial SMS: scarcity, regret, or control nudge) x 2 (Reminder SMS: social norm or control nudge) factorial design was used in a hypothetical online experiment. 705 participants eligible for Heart Health Checks were recruited. Outcomes included intention to attend a Heart Health Check and psychological responses., Results: In the control condition, people with lower health literacy had lower behavioural intentions compared to those with higher health literacy (p = .011). Scarcity and regret nudges closed this gap, resulting in similar intention levels for lower and higher health literacy. There was no interactive effect of the reminder nudge and health literacy (p = .724)., Conclusion: Scarcity and regret nudge messages closed the health literacy gap in behavioural intentions compared to a control message, while a reminder nudge had limited additional benefit. Health literacy should be considered in behavioural intervention evaluations to ensure health equity is addressed., Practice Implications: Results informed a national screening program using a universal precautions approach, where messages with higher engagement for lower health literacy groups were used in clinical practice., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Cardiovascular disease (CVD) is the leading cause of disease burden worldwide, with a significant proportion of cases and deaths attributable to modifiable risk factors. Recent interest has emerged in using cardiac computed tomography (CT) imaging as a tool to enhance motivation and drive positive behavioural changes. However, the impact of providing visual feedback of plaque from CT on risk factor control and individual health behaviours remains understudied. This study aimed to assess the effects of visual feedback from cardiac CT imaging on health-related behaviours and risk factor control. A systematic search of electronic databases was conducted, yielding nine studies (five randomised controlled trials and four observational studies) for analysis. The results varied, but based on the limited low-quality data, CT imaging appears to have short-term favourable effects on cholesterol levels and systolic blood pressure reductions, and positive dietary behavioural changes. Further research is warranted to better understand the long-term impact of cardiac CT imaging on health behaviours and risk factor modification., (Copyright © 2024 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: Seasonal influenza immunisation reduces cardiovascular events in high-risk patients, but 50% do not receive routine immunisation. The perceptions and current role of cardiologists in recommending and prescribing influenza immunisation has not been well described., Methods: We used an exploratory sequential mixed methods design. Semi-structured interviews of 10 cardiologists were performed to identify themes for quantitative evaluation. 63 cardiologists undertook quantitative evaluation in an online survey. The interviews and surveys addressed (a) attitudes and behaviours regarding influenza immunisation and (b) preventative care in cardiology., Results: One quarter (25.4%, n = 16) of cardiologists recommended influenza immunisation to all patients. Less than half (49.2%, n = 31) recommended influenza immunisation to secondary prevention patients. Almost 1/3 of respondents (31.7%, n = 20) were uncertain or unaware of the guidelines regarding influenza immunisation and patients with cardiac disease. Most cardiologists believed that general practitioners were responsible for ensuring patients received influenza immunisation (76.2%, n = 48)., Conclusions: Despite reducing cardiovascular events in high-risk patients, influenza immunisation is not widely recommended by cardiologists. Further clinician education is needed to address the knowledge gaps which prevent recommendation and uptake of this guideline directed treatment., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Adequate pain control is a critical component of rib fracture management. Our study aimed to evaluate the in-hospital and post-discharge outcomes of geriatric rib fracture patients who received paravertebral nerve block (PVNB) versus epidural analgesia (EA) on a national level., Methods: We performed a 5-year (2011-15) retrospective analysis of the Nationwide Readmission database. We included all the geriatric (≥65 years) blunt trauma patients with rib fractures who received a paravertebral nerve block (PVNB) or Epidural analgesia (EA) for chest injuries. We excluded patients who were dead on arrival, those with head AIS≥3, spine AIS >0, and those with cognitive impairment. Patients were stratified into two groups (PVNB and EA). A propensity score matching (1:2) was performed, and the two groups were compared. Our outcomes included delirium, hospital length of stay (LOS), 90-day readmissions, 90-day mechanical ventilation, and initial and 90-day mortality., Results: A total of 2,855 geriatric rib fracture patients were identified, out of which 352 (12 %) received PVNB and 2,503 (87 %) received EA. The mean (SD) age was 78 (8) years and 53 % were female. A total of 1,041 patients were matched (PVNB=347, EA=694 patients). The median [IQR] Injury severity score was 9 [3-15], median chest AIS was 3 [2-4], and 70 % had ≥3 rib fractures. The total mortality during index admission was 6 %, 13 % experienced delirium, and the median hospital LOS was 6 [4-10] days. There was no difference in the primary outcomes of the two groups including rates of index admission mortality (PVNB: 5.2% vs. EA:6.3 %, p = 0.548) and delirium (PVNB: 12.4% vs. EA:12.9 %, p = 0.862). We also found no statistically significant difference between these groups in terms of 90-day respiratory complications (p = 1.000), 90-day readmission (p = 0.111), 90-day mortality (p = 0.718), and 90-day need for mechanical ventilation (p = 1.000)., Conclusion: The use of PVNB in geriatric trauma patients with multiple rib fractures is associated with comparable in-hospital and post-discharge outcomes relative to EA. PVNB is relatively easy to perform and has a better side effect profile. The use of PVNB as part of rib fracture management protocols warrants further consideration., Level of Evidence: III STUDY TYPE: Therapeutic/Care Management., Competing Interests: Declaration of Competing Interest There are no identifiable conflicts of interest to report., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: It remains unclear whether geriatrics benefit from care at higher-level trauma centers (TCs). We aimed to assess the impact of the TC verification level on frail geriatric trauma patients' outcomes. We hypothesized that frail patients cared for at higher-level TCs would have improved outcomes., Study Design: Patients ≥65 years were identified from the Trauma Quality Improvement Program (TQIP) database (2017-2019). Patients transferred, discharged from emergency department (ED), and those with head abbreviated injury scale >3 were excluded. 11-factor modified frailty index was utilized. Propensity score matching (1:1) was performed. Outcomes included discharge to skilled nursing facility or rehab (SNF/rehab), withdrawal of life-supporting treatment (WLST), mortality, complications, failure-to-rescue, intensive care unit (ICU) admission, hospital length of stay (LOS), and ventilator days., Results: 110,680 patients were matched (Frail:55,340, Non-Frail:55,340). Mean age was 79 (7), 90% presented following falls, and median ISS was 5 [2-9]. Level-I/II TCs had lower rates of discharge to SNF/rehab (52.6% vs. 55.8% vs. 60.9%; p < 0.001), failure-to-rescue (0.5% vs. 0.4% vs. 0.6%;p = 0.005), and higher rates of WLST (2.4% vs. 2.1% vs. 0.3%; p < 0.001) compared to level-III regardless of injury severity and frailty. Compared to Level-III centers, Level-I/II centers had higher complications among moderate-to-severely injured patients (4.1% vs. 3.3% vs. 2.7%; p < 0.001), and lower mortality only among frail patients regardless of injury severity (1.8% vs. 1.5% vs. 2.6%; p < 0.001). Patients at Level-I TCs were more likely to be admitted to ICU, and had longer hospital LOS and ventilator days compared to Level-II and III TCs (p < 0.05)., Conclusion: Frailty may play an important role when triaging geriatric trauma patients. In fact, the benefit of care at higher-level TCs is particularly evident for patients who are frail. Level III centers may be underperforming in providing access to palliative and end-of-life care., Competing Interests: Declaration of Competing Interest There are no identifiable conflicts of interest to report., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Up to a quarter of all traumatic deaths are due to thoracic injuries. Current guidelines recommend consideration of evacuation of all hemothoraces with tube thoracostomy. The aim of our study was to determine the impact of pre-injury anticoagulation on outcomes of traumatic hemothorax patients., Materials and Methods: We performed a 4-year (2017 - 2020) analysis of the ACS-TQIP database. We included all adult trauma patients (age ≥18 years) presenting with hemothorax and no other severe injuries (other body regions <3). Patients with a history of bleeding disorders, chronic liver disease, or cancer were excluded from this study. Patients were stratified into two groups based on the history of preinjury anticoagulant use (AC, preinjury anticoagulant use: No-AC, no preinjury anticoagulant use). Propensity score matching (1:1) was done by adjusting for demographics, ED vitals, injury parameters, comorbidities, thromboprophylaxis type, and trauma center verification level. Outcome measures were interventions for hemothorax (chest tube, video-assisted thoracoscopic surgery [VATS]), reinterventions (chest tube > once), overall complications, hospital length of stay (LOS), and mortality., Results: A matched cohort of 6,962 patients (AC, 3,481; No-AC, 3,481) was analyzed. The median age was 75 years, and the median ISS was 10. The AC and No-AC groups were similar in terms of baseline characteristics. Compared to the No-AC group, AC group had higher rates of chest tube placement (46% vs 43%, p = 0.018), overall complications (8% vs 7%, p = 0.046), and longer hospital LOS (7[4-12] vs 6[3-10] days, p ≤ 0.001). Reintervention and mortality rates were similar between the groups (p>0.05)., Conclusion: The use of preinjury anticoagulants in hemothorax patients negatively impacts patient outcomes. Increased surveillance is required while dealing with hemothorax patients on pre-injury anticoagulants, and consideration should be given to earlier interventions for such patients., Competing Interests: Declaration of Competing Interest There are no identifiable conflicts of interest to report., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Obicetrapib, a selective cholesteryl ester transfer protein (CETP) inhibitor, reduces low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), lipoprotein particles, and apolipoproteins, when added to high-intensity statin in patients with dyslipidemia., Objective: To evaluate the safety and lipid-altering efficacy of obicetrapib plus ezetimibe combination therapy as an adjunct to high-intensity statin therapy., Methods: This double-blind, randomized, phase 2 trial administered 10 mg obicetrapib plus 10 mg ezetimibe (n = 40), 10 mg obicetrapib (n = 39), or placebo (n = 40) for 12 weeks to patients with LDL-C >70 mg/dL and triglycerides (TG) <400 mg/dL, on stable high-intensity statin. Endpoints included concentrations of lipids, apolipoproteins, lipoprotein particles, and proprotein convertase subtilisin kexin type 9 (PCSK9), safety, and tolerability., Results: Ninety-seven patients were included in the primary analysis (mean age 62.6 years, 63.9% male, 84.5% white, average body mass index of 30.9 kg/m 2 ). LDL-C decreased from baseline to week 12 by 63.4%, 43.5%, and 6.35% in combination, monotherapy, and placebo groups, respectively (p<0.0001 vs. placebo). LDL-C levels of <100, <70, and <55 mg/dL were achieved by 100%, 93.5%, and 87.1%, respectively, of patients taking the combination. Both active treatments also significantly reduced concentrations of non-HDL-C, apolipoprotein B, and total and small LDL particles. Obicetrapib was well tolerated and no safety issues were identified., Conclusion: The combination of obicetrapib plus ezetimibe significantly lowered atherogenic lipid and lipoprotein parameters, and was safe and well tolerated when administered on top of high-intensity statin to patients with elevated LDL-C., (Copyright © 2023. Published by Elsevier Inc.)

Background: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of numerous cancers but are associated with increased risk of myocardial infarction. The prevalence of traditional cardiovascular risk factors (CVRF) in patients treated with ICIs is unknown. This study sought to describe the frequency of reporting of CVRFs among landmark ICI trials., Methods: A systematic review of all phase 2 or 3 cancer trials employing ICIs that led to United States Food and Drug Administration approval was conducted., Results: Of the 69 identified trials, only one study reported baseline rates of hypertension, diabetes mellitus, and dyslipidemia. Smoking history was reported in 27 studies (39 %) and three (4 %) reported body mass index. No study reported history of previous cardiovascular disease, although 17 (25 %), six (9 %), and 21 (30 %) studies excluded patients with recent myocardial infarction, revascularization and heart failure respectively. Similarly low rates of cardiovascular risk factor reporting were observed in studies employing concurrent vascular endothelial growth factor inhibitors and recruiting (neo)adjuvant cohorts., Conclusion: The prevalence of CVRFs is poorly described in ICI trials despite increasingly reported risks of myocardial infarction. A systematic approach to collecting and reporting CVRFs should be considered in future trials and real world populations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Randomized clinical trials have demonstrated that increasingly intensive lowering of low-density lipoprotein cholesterol (LDL-C) reduces the rate of cardiovascular events in the primary and secondary prevention setting. Integration of serial coronary imaging within clinical trials has enabled evaluation of medical therapies on the natural history of coronary disease. These studies have extended from early investigation of coronary obstruction with angiography to more contemporary evaluation of plaque burden and composition with imaging modalities that directly visualize the artery wall. The findings of these trials have demonstrated that intensive lipid lowering promotes plaque regression and stabilization. The lessons of this body of research provide a biological rationale underscoring the ability of intensive lipid lowering to reduce cardiovascular risk and have the potential to promote greater uptake in clinical practice., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Y.K. has received research support from Kowa, and speaker honoraria from Abbott Vascular, Amgen, CSL Behring, Daiichi Sankyo, Kowa, Nipro, and Takeda. S.J.N. has received research support from AstraZeneca, Amgen, Anthera, CSL Behring, Cerenis, Eli Lilly, Esperion, Resverlogix, Novartis, InfraReDx and Sanofi-Regeneron and is a consultant for Amgen, Akcea, AstraZeneca, Boehringer Ingelheim, CSL Behring, Eli Lilly, Esperion, Kowa, Merck, Takeda, Pfizer, Sanofi-Regeneron and Novo Nordisk. All other authors have no relationships to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Ground-level falls (GLFs) in older adults are increasing as life expectancy increases, and more patients are being discharged to skilled nursing facilities (SNFs) for continuity of care. However, GLF patients are not a homogenous cohort, and the role of frailty remains to be assessed. Thus, the aim of this study is to examine the impact of frailty on the in-hospital and 30-day outcomes of GLF patients., Materials and Methods: This is a cohort analysis from the Nationwide Readmissions Database 2017. Geriatric (age ≥65 years) trauma patients presenting following GLFs were identified and grouped based on their frailty status. The associations between frailty and 30-day mortality and emergency readmission were examined by multivariate regression analyses adjusting for patient demographics and injury characteristics., Results: A total of 100,850 geriatric GLF patients were identified (frail: 41% vs. non-frail: 59%). Frail GLF patients were younger (81[74-87] vs. 83[76-89] years; p<0.001) and less severely injured-Injury Severity Score [ISS] (4[1-9] vs. 5[2-9]; p<0.001). Frail patients had a higher index mortality (2.9% vs. 1.9%; p<0.001) and higher 30-day readmissions (14.0% vs. 9.8%; p<0.001). Readmission mortality was also higher in the frail group (15.2% vs. 10.9%; p<0.001), with 75.2% of those patients readmitted from an SNF. On multivariate analysis, frailty was associated with 30-day mortality (OR 1.75; p<0.001) and 30-day readmission (OR 1.49; p<0.001)., Conclusion: Frail geriatric patients are at 75% higher odds of mortality and 49% higher odds of readmission following GLFs. Of those readmitted on an emergency basis, more than one in seven patients died, 75% of whom were readmitted from an SNF. This underscores the need for optimization plans that extend to the post-discharge period to reduce readmissions and subsequent high-impact consequences., Competing Interests: Declaration of Competing Interest There are no identifiable conflicts of interest to report., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Acute myocardial infarction with non-obstructive coronary artery disease (MINOCA) is frequent in patients experiencing an early-onset MI, but data concerning its long-term prognosis are limited and conflicting., Methods: The Italian Genetic Study on Early-onset MI enrolled 2000 patients experiencing a first MI before the age of 45 years, and had a median follow-up of 19.9 years. The composite primary endpoint was cardiovascular (CV) death, non-fatal MI, and non-fatal stroke (MACE); the secondary endpoint was rehospitalisation for coronary revascularisation., Results: MINOCA occurred in 317 patients (15.9%) and, during the follow-up, there was no significant difference in MACE rates between them and the patients with obstructive coronary artery disease (MICAD: 27.8% vs 37.5%; adjusted hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.57-1.09;p = 0.15). The CV death rate was lower in the MINOCA group (4.2% vs 8.4%, HR 0.26, 95%CI 0.08-0.86;p = 0.03), whereas the rates of non-fatal reinfarction (17.3% vs 25.4%; HR 0.76, 95%CI 0.52-1.13;p = 0.18), non-fatal ischemic stroke (9.5% vs 3.7%; HR 1.79, 95%CI 0.87-3.70;p = 0.12), and all-cause mortality (14.1% vs 20.7%, HR 0.73, 95%CI 0.43-1.25;p = 0.26) were not significantly different in the two groups. The rate of rehospitalisation for coronary revascularisation was lower among the MINOCA patients (6.7% vs 27.7%; HR 0.27, 95% CI 0.15-0.47;p < 0.001)., Conclusions: MINOCA is frequent and not benign in patients with early-onset MI. Although there is a lower likelihood of CV death,the long-term risk of MACE and overall mortality is not significantly different from that of MICAD patients., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Aims: Identifying patient subgroups with cardiovascular disease (CVD) at highest risk for recurrent events remains challenging. Angiographic features may provide incremental value in risk prediction beyond clinical characteristics., Methods: We included all cardiac catheterization patients from the Duke Databank for Cardiovascular Disease with significant coronary artery disease (CAD; 07/01/2007-12/31/2012) and an outpatient follow-up visit with a primary care physician or cardiologist in the same health system within 3 months post-catheterization. Follow-up occurred for 3 years for the primary major adverse cardiovascular event endpoint (time to all-cause death, myocardial infarction [MI], or stroke). A multivariable model to predict recurrent events was developed based on clinical variables only, then adding angiographic variables from the catheterization. Next, we compared discrimination of clinical vs. clinical plus angiographic risk prediction models., Results: Among 3366 patients with angiographically-defined CAD, 633 (19.2%) experienced cardiovascular events (death, MI, or stroke) within 3 years. A multivariable model including 18 baseline clinical factors and initial revascularization had modest ability to predict future atherosclerotic cardiovascular disease events (c-statistic = 0.716). Among angiographic predictors, number of diseased vessels, left main stenosis, left anterior descending stenosis, and the Duke CAD Index had the highest value for secondary risk prediction; however, the clinical plus angiographic model only slightly improved discrimination (c-statistic = 0.724; delta 0.008). The net benefit for angiographic features was also small, with a relative integrated discrimination improvement of 0.05 (95% confidence interval: 0.03-0.08)., Conclusions: The inclusion of coronary angiographic features added little incremental value in secondary risk prediction beyond clinical characteristics., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Rib fractures are one of the most frequent causes of morbidity following blunt injury to the chest. Many of these patients require ICU care and often develop pulmonary complications. Prior studies have attempted to identify changes in predicted lung volumes or utilized the number of rib fractures to guide clinical decisions. A rib fracture triage pathway was developed to identify which patients will benefit from ICU level of care and shorten hospital length of stay for patients that do not require ICU care., Methods: The triage pathway utilized patient's age, number of rib fractures, significant cardiopulmonary co-morbidities, and incentive spirometry volumes to determine admission disposition. The triage pathway was implemented on November 2016. All patients with rib fractures from November 2015 to 2017 were identified in the trauma registry. Data was collected on patients age, gender, Glasgow Coma Scale on arrival (GCS), injury severity score (ISS), number of rib fractures, incentive spirometry volumes, days in intensive care (ICU), ventilator days, length of stay (LOS), complications, and mortality. Patients with severe TBI, those arriving intubated, or died within 48 h were excluded. The patients remaining were 278 patients in the pre triage pathway group and 370 in the post triage pathway., Results: There was no difference in age, gender, GCS, ISS, predicted incentive spirometry or number of rib fractures. The post treatment patients required significantly lower ICU admissions (64% vs 75%, p = 0.003), significantly lower pulmonary complication (5.1% vs 10.4%, p = 0.01), and significantly shorter hospital length of stay (6.8 d vs 7.5, p = 0.001) with no difference in mortality (1.6% vs 2.5%, p = 0.42) or readmission (0.3% vs. 0.7%, p = 0.4). Patient post triage protocol were also more likely to be discharge home (81% vs 70%, p = 0.0009) with less patients going to a skilled nursing facility (13% vs 21%, p = 0.01)., Conclusions: Developing a rib fracture treatment and triage pathway can decrease ICU and hospital resource utilization and decrease pulmonary complications without increase in readmissions or mortality. Patients are more likely to be discharge home over a skilled nursing facility further decreasing health care cost. Level of Evidence IV Retrospective Study, Prognostic., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Overactivated complement is a high-risk feature in hematopoietic stem cell transplant (HSCT) recipients with transplant-associated thrombotic microangiopathy (TA-TMA), and untreated patients have dismal outcomes. We present our experience with 64 pediatric HSCT recipients who had high-risk TA-TMA (hrTA-TMA) and multiorgan injury treated with the complement blocker eculizumab. We demonstrate significant improvement to 66% in 1-year post-HSCT survival in treated patients from our previously reported untreated cohort with same hrTA-TMA features that had 1-year post-HSCT survival of 16.7%. Responding patients benefited from a brief but intensive course of eculizumab using pharmacokinetic/pharmacodynamic-guided dosing, requiring a median of 11 doses of eculizumab (interquartile range [IQR] 7-20). Treatment was discontinued because TA-TMA resolved at a median of 66 days (IQR 41-110). Subjects with higher complement activation measured by elevated blood sC5b-9 at the start of treatment were less likely to respond (odds ratio, 0.15; P = .0014) and required more doses of eculizumab (r = 0.43; P = .0004). Patients with intestinal bleeding had the fastest eculizumab clearance, required the highest number of eculizumab doses (20 vs 9; P = .0015), and had lower 1-year survival (44% vs 78%; P = .01). Over 70% of survivors had proteinuria on long-term follow-up. The best glomerular filtration rate (GFR) recovery in survivors was a median 20% lower (IQR, 7.3%-40.3%) than their pre-HSCT GFR. In summary, complement blockade with eculizumab is an effective therapeutic strategy for hrTA-TMA, but some patients with severe disease lacked a complete response, prompting us to propose early intervention and search for additional targetable endothelial injury pathways., (© 2020 by The American Society of Hematology.)

Despite improvements, mortality after allogeneic hematopoietic cell transplantation (HCT) for nonmalignant diseases remains a significant problem. We evaluated whether pre-HCT conditions defined by the HCT Comorbidity Index (HCT-CI) predict probability of posttransplant survival. Using the Center for International Blood and Marrow Transplant Research database, we identified 4083 patients with nonmalignant diseases transplanted between 2007 and 2014. Primary outcome was overall survival (OS) using the Kaplan-Meier method. Hazard ratios (HRs) were estimated by multivariable Cox regression models. Increasing HCT-CI scores translated to decreased 2-year OS of 82.7%, 80.3%, 74%, and 55.8% for patients with HCT-CI scores of 0, 1 to 2, 3 to 4, and ≥5, respectively, regardless of conditioning intensity. HCT-CI scores of 1 to 2 did not differ relative to scores of 0 (HR, 1.12 [95% CI, 0.93-1.34]), but HCT-CI of 3 to 4 and ≥5 posed significantly greater risks of mortality (HR, 1.33 [95% CI, 1.09-1.63]; and HR, 2.31 [95% CI, 1.79-2.96], respectively). The effect of HCT-CI differed by disease indication. Patients with acquired aplastic anemia, primary immune deficiencies, and congenital bone marrow failure syndromes with scores ≥3 had increased risk of death after HCT. However, higher HCT-CI scores among hemoglobinopathy patients did not increase mortality risk. In conclusion, this is the largest study to date reporting on patients with nonmalignant diseases demonstrating HCT-CI scores ≥3 that had inferior survival after HCT, except for patients with hemoglobinopathies. Our findings suggest that using the HCT-CI score, in addition to disease-specific factors, could be useful when developing treatment plans for nonmalignant diseases., (© 2019 by The American Society of Hematology.)

Type 2 diabetes is associated with elevated levels of triglycerides and small, dense low-density lipoprotein particles, in addition to low levels of high-density lipoprotein cholesterol. Clinical trials have demonstrated the clear cardiovascular benefit of use of statin therapy in patients with diabetes. Additional lipid-modifying agents are typically guided by the presence of additional lipid abnormalities. The optimal use of existing lipid agents and the potential for novel therapies in patients with diabetes is reviewed., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background and Aims: Echocardiographic studies have shown improvements in cardiac indices associated with renal sympathetic denervation (RDN), however, the benefits on myocardial perfusion have never been assessed. This trial was designed to study the effects of RDN on myocardial perfusion using cardiac magnetic resonance (CMR) imaging., Methods: A total of 14 patients with resistant hypertension were recruited for RDN and myocardial perfusion, alongside other CMR indices, was assessed at baseline and at 6 months., Results: RDN showed significant reduction of mean office blood pressures from 181/100 ± 19/16 mmHg to 147/85 ± 19/17 mmHg, 6 months after the procedure (p < 0.0001). This was combined with significant improvement in regional aortic distensibility (p < 0.02) and associated with trends of improved myocardial perfusion reserve index (baseline = 2.2 ± 1; 6 months = 2.9 ± 1 units) (p = 0.08). Left ventricular end systolic volume index decreased from baseline to 6 months post procedure, 27 ± 13 ml/m 2 vs. 22 ± 10 ml/m 2 (p = 0.03), but there was no significant change in left ventricular end diastolic volume index (p = 0.09). There was significant improvement in mean left ventricular ejection fraction from 68 ± 10% to 72 + 9%, 6 months post procedure (p = 0.04). T1 mapping failed to detect fibrosis in these patients at baseline and therefore no change was noted, however, extracellular volume percent improved from 46 ± 4% at baseline to 41 ± 8% at 6 months (p = 0.002)., Conclusions: This study demonstrates that renal sympathetic denervation increased myocardial perfusion by 32% as assessed by CMR, and, this was associated with improvements in cardiac volumes and function. Larger well controlled and randomized studies are required to assess the clinical significance of these findings., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Cardiovascular disease is the most frequent cause of morbidity and mortality among individuals with diabetes and although there has been significant reduction in excess risk, these individuals remain at least twice as likely to sustain atherosclerotic events. Aggressive management of traditional factors, such as dyslipidemia, remains the cornerstone of risk mitigation. Diabetes and its associated insulin resistance generate qualitative and quantitative changes in lipid profile, which complicate effective treatment. This review summaries the background to diabetic dyslipidemia and provides a précis of the available management options., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Proteasome inhibitors, such as bortezomib and carfilzomib, are FDA approved for the treatment of hemopoietic cancers, but recent studies have shown their great potential for treatment of solid tumors. BaxΔ2, a unique proapoptotic Bax isoform, promotes non-mitochondrial cell death and sensitizes cancer cells to chemotherapy. However, endogenous BaxΔ2 proteins are unstable and susceptible to proteasomal degradation. Here, we screened a panel of proteasome inhibitors in colorectal cancer cells with different Bax statuses. We found that all proteasome inhibitors tested were able to block BaxΔ2 degradation without affecting the level of Baxα or Bcl-2 proteins. Among the inhibitors tested, only bortezomib and carfilzomib were able to induce differential cell death corresponding to the distinct Bax statuses. BaxΔ2-positive cells had a significantly higher level of cell death at low nanomolar concentrations than Baxα-positive or Bax-negative cells. Furthermore, bortezomib-induced cell death in BaxΔ2-positive cells was predominantly dependent on the caspase 8/3 pathway, consistent with our previous studies. These results imply that BaxΔ2 can selectively sensitize cancer cells to proteasome inhibitors, enhancing their potential to treat colon cancer and other solid tumors., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

The introduction of fluorine has been widely exploited to tune the biological functions of small molecules. Indeed, around 20% of leading drugs contain at least one fluorine atom. Yet, despite profound effects of fluorination on conformation, there is only a limited toolkit of reactions that enable stereoselective synthesis of fluorinated compounds. Aldolases are useful catalysts for the stereoselective synthesis of bioactive small molecules; however, despite fluoropyruvate being a viable nucleophile for some aldolases, the potential of aldolases to control the formation of fluorine-bearing stereocentres has largely been untapped. Very recently, it has been shown that aldolase-catalysed stereoselective carboncarbon bond formation with fluoropyruvate as nucleophile enable the synthesis of many α-fluoro β-hydroxy carboxyl derivatives. Furthermore, an understanding of the structural basis for the stereocontrol observed in these reactions is beginning to emerge. Here, we review the application of aldolase catalysis in the stereocontrolled synthesis of chiral fluorinated small molecules, and highlight likely areas for future developments., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background Aims: Traditionally, stem cell therapy for myocardial infarction (MI) has been administered as a single treatment in the acute or subacute period after MI. These time intervals coincide with marked differences in the post-infarct myocardial environment, raising the prospect that repeat cell dosing could provide incremental benefit beyond a solitary intervention. This prospect was evaluated with the use of mesenchymal stromal cells (MSCs)., Methods: Three groups of rats were studied. Single-therapy and dual-therapy groups received allogeneic, prospectively isolated MSCs (1 × 10(6) cells) by trans-epicardial injection immediately after MI, with additional dosing 1 week later in the dual-therapy cohort. Control animals received cryopreservant solution only. Left ventricular (LV) dimensions and ejection fraction (EF) were assessed by cardiac magnetic resonance immediately before MI and at 1, 2 and 4 weeks after MI., Results: Immediate MSC treatment attenuated early myocardial damage with EF of 35.3 ± 3.1% (dual group, n = 12) and 35.2 ± 2.2% (single group, n = 15) at 1 week after MI compared with 22.1 ± 1.9% in controls (n = 17, P < 0.01). In animals receiving a second dose of MSCs, EF increased to 40.7 ± 3.1% by week 4, which was significantly higher than in the single-therapy group (EF 35.9 ± 1.8%, P < 0.05). Dual MSC treatment was also associated with greater myocardial mass and arteriolar density, with trends toward reduced myocardial fibrosis. These incremental benefits were especially observed in remote (non-infarct) segments of LV myocardium., Conclusions: Repeated stem cell intervention in both the acute and the sub-acute period after MI provides additional improvement in ventricular function beyond solitary cell dosing, largely owing to beneficial changes remote to the area of infarction., (Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Aldolases are seen as an attractive route to the production of biologically important compounds due to their ability to form carbon-carbon bonds. However, for many industrial reactions there are no naturally occurring enzymes, and so many different engineering approaches have been used to address this problem. Engineering methods have been used to alter the stability, substrate specificity and stereospecificity of aldolases to produce excellent enzymes for biocatalytic processes. Recently greater understanding of the aldolase mechanism has allowed many successes with both rational engineering approaches and computational design of aldolases. Rational engineering approaches have produced desired enzymes quickly and efficiently while combination of computational design with laboratory methods has created enzymes with activity approaching that of natural enzymes., (Copyright © 2013 Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The high diagnostic accuracy of adenosine stress cardiac magnetic resonance (AS-CMR) for detecting coronary artery stenoses, with high sensitivity and specificity, is well documented. Prognostic data, particularly in non-low risk study populations and for greater than 12 months of follow up, is however lacking or variable in its findings. We present prognostic data, in an intermediate cardiovascular risk cohort undergoing adenosine stress perfusion CMR, over approximately 2 years of follow up., Methods: The study population comprised 362 patients referred for a clinically indicated stress CMR and included patients with proven coronary artery disease (CAD; n=157) or unknown CAD status, yet an intermediate cardiovascular risk profile (n=205). Perfusion imaging was performed at stress (adenosine 140 μg/kg/min) and rest on a 1.5 T system. Patient records and state-wide hospital databases were reviewed. Major adverse cardiac events--death, myocardial infarction, revascularisation or ischaemic hospitalisation--were evaluated over a median follow up of 22 months., Results: Of the 362 cases, 90 had a stress perfusion CMR positive for ischaemia and experienced a MACE rate of 24%. Of the 272 negative CMR scans, 225 were also negative for late gadolinium enhancement, and in this group MACE was encountered in only 6 (2.7%) patients. Accordingly a negative stress CMR afforded a freedom from MACE of 97.3%. Freedom from death/myocardial infarction was 99.6%., Conclusions: In patients with confirmed coronary artery disease or at intermediate risk for cardiovascular events, a negative stress perfusion CMR is associated with an excellent prognosis over nearly 2 years of follow up., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Obesity is associated with atrial fibrillation (AF); however, the mechanisms by which it induces AF are unknown., Objective: To examine the effect of progressive weight gain on the substrate for AF., Methods: Thirty sheep were studied at baseline, 4 months, and 8 months, following a high-calorie diet. Ten sheep were sampled at each time point for cardiac magnetic resonance imaging and hemodynamic studies. High-density multisite biatrial epicardial mapping was used to quantify effective refractory period, conduction velocity, and conduction heterogeneity index at 4 pacing cycle lengths and AF inducibility. Histology was performed for atrial fibrosis, inflammation, and intramyocardial lipidosis, and molecular analysis was performed for endothelin-A and -B receptors, endothelin-1 peptide, platelet-derived growth factor, transforming growth factor β1, and connective tissue growth factor., Results: Increasing weight was associated with increasing left atrial volume (P = .01), fibrosis (P = .02), inflammatory infiltrates (P = .01), and lipidosis (P = .02). While there was no change in the effective refractory period (P = .2), there was a decrease in conduction velocity (P<.001), increase in conduction heterogeneity index (P<.001), and increase in inducible (P = .001) and spontaneous (P = .001) AF. There was an increase in atrial cardiomyocyte endothelin-A and -B receptors (P = .001) and endothelin-1 (P = .03) with an increase in adiposity. In association, there was a significant increase in atrial interstitial and cytoplasmic transforming growth factor β1 (P = .02) and platelet-derived growth factor (P = .02) levels., Conclusions: Obesity is associated with atrial electrostructural remodeling. With progressive obesity, there were changes in atrial size, conduction, histology, and expression of profibrotic mediators. These changes were associated with spontaneous and more persistent AF., (Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.)

Gastrointestinal mucormycosis is an uncommon, life-threatening, angioinvasive infection with only one previous report of disease involving the jejunum. We present a case of invasive jejunal mucormycosis and review the literature, highlighting the rare clinical presentation and the value of molecular diagnostic methods. Given the global increase in patient populations at risk of mucormycosis, clinicians need to maintain a high index of suspicion and perform timely and appropriate evaluation to improve patient outcome.

Background: It has been suggested that omega-3 polyunsaturated fatty acids (n-3 PUFAs) may prevent the development of atrial fibrillation (AF)., Objective: The purpose of this study was to evaluate the impact of these agents on development of the AF substrate in heart failure (HF)., Methods: In this study, HF was induced by intracoronary doxorubicin infusions. Twenty-one sheep [7 with n-3 PUFAs treated HF (HF-PUFA), 7 with olive oil-treated HF controls (HF-CTL), 7 controls (CTL)] were studied. Open chest electrophysiologic study was performed with assessment of biatrial effective refractory period (ERP) and conduction. Cardiac function was monitored by magnetic resonance imaging. Atrial n-3 PUFAs levels were quantified using chromatography. Structural analysis was also performed., Results: Atrial n-3 PUFAs levels were twofold to threefold higher in the HF-PUFA group. n-3 PUFAs prevented the development of HF-related left atrial enlargement (P = .001) but not left ventricular/atrial dysfunction. Atrial ERP was significantly lower in the HF-PUFA group (P <.001), but ERP heterogeneity was unchanged. In addition, n-3 PUFAs suppressed atrial conduction abnormalities seen in HF of prolonged P-wave duration (P = .01) and slowed (P <.001) and heterogeneous (P <.05) conduction. The duration of induced AF episodes in HF-PUFA was shorter (P = .02), although AF inducibility was unaltered (P = NS). A 20% reduction of atrial interstitial fibrosis was seen in the HF-PUFA group (P <.05)., Conclusion: In this ovine HF study, chronic n-3 PUFAs use protected against adverse atrial remodeling by preventing atrial enlargement, fibrosis, and conduction abnormalities leading to shorter AF episodes despite lower ERP., (Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.)

The substrate specificity of Escherichia coli N-acetylneuraminic acid lyase was previously switched from the natural condensation of pyruvate with N-acetylmannosamine, yielding N-acetylneuraminic acid, to the aldol condensation generating N-alkylcarboxamide analogues of N-acetylneuraminic acid. This was achieved by a single mutation of Glu192 to Asn. In order to analyze the structural changes involved and to more fully understand the basis of this switch in specificity, we have isolated all 20 variants of the enzyme at position 192 and determined the activities with a range of substrates. We have also determined five high-resolution crystal structures: the structures of wild-type E. coli N-acetylneuraminic acid lyase in the presence and in the absence of pyruvate, the structures of the E192N variant in the presence and in the absence of pyruvate, and the structure of the E192N variant in the presence of pyruvate and a competitive inhibitor (2R,3R)-2,3,4-trihydroxy-N,N-dipropylbutanamide. All structures were solved in space group P2(1) at resolutions ranging from 1.65 Å to 2.2 Å. A comparison of these structures, in combination with the specificity profiles of the variants, reveals subtle differences that explain the details of the specificity changes. This work demonstrates the subtleties of enzyme-substrate interactions and the importance of determining the structures of enzymes produced by directed evolution, where the specificity determinants may change from one substrate to another., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: Hypertension accounts for more atrial fibrillation (AF) than any other predisposing factor., Objective: The purpose of this study was to characterize the time course, extent, and electrostructural correlation of atrial remodeling in chronic hypertension., Methods: Thirty-two sheep were studied: 21 with induced "one-kidney, one-clip" hypertension and 11 controls. Sequential closed-chest electrophysiologic studies were performed in 12 conscious animals (6 hypertensive, 6 controls) to evaluate progressive remodeling over 15 weeks. Additional atrial structural/functional analyses were performed in 5 controls and at 5, 10, and 15 weeks of hypertension (five per time point) via histology/cardiac magnetic resonance imaging to correlate with open-chest electrophysiologic parameters., Results: The hypertensive group developed a progressive increase in mean arterial pressure (P <.001). Mean effective refractory periods were uniformly higher at all time points (P <.001). Progressive biatrial hypertrophy (P = .003), left atrial dysfunction (P <.05) and greater AF inducibility were seen early with increased inflammation from 5 weeks of hypertension. In contrast, significant conduction slowing (P <.001) with increased heterogeneity (P <.001) along with increased interstitial fibrosis resulted in longer and more fractionated AF episodes only from 10 weeks of hypertension. Significant electrostructural correlation was seen in conduction abnormalities and AF inducibility with both atrial inflammation and fibrosis., Conclusion: Hypertension is associated with early and progressive changes in atrial remodeling. Atrial remodeling occurs at different time domains in chronic hypertension with significant electrostructural correlation of the remodeling cascade. Early institution of antihypertensive treatment may prevent formation of substrate capable of maintaining AF., (Copyright 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: This study set out to evaluate the safety and efficacy of allogeneic bone marrow mesenchymal precursor cells (MPC) delivered by multisegmental, transendocardial implantation in the setting of nonischemic cardiomyopathy (NICM)., Background: Prospectively isolated MPC have shown capacity to mediate cardiovascular repair in myocardial ischemia. However, their efficacy in NICM remains undetermined., Methods: Mesenchymal precursor cells were prepared from ovine bone marrow by immunoselection using the tissue nonspecific alkaline phosphatase, or STRO-3, monoclonal antibody. Fifteen sheep with anthracycline-induced NICM were assigned to catheter-based, transendocardial injections of allogeneic MPC (n = 7) or placebo (n = 8), under electromechanical mapping guidance. Follow-up was for 8 weeks, with end points assessed by cardiac magnetic resonance, echocardiography, and histology., Results: Intramyocardial injections were distributed similarly throughout the left ventricle in both groups. Cell transplantation was associated with 1 death late in follow-up, compared with 3 early deaths among placebo animals. Left ventricular end-diastolic size increased in both cohorts, but MPC therapy attenuated end-systolic dilation and stabilized ejection fraction, with a nonsignificant increase (37.3 ± 2.8% before, 39.2 ± 1.4% after) compared with progressive deterioration after placebo (38.8 ± 4.4% before, 32.5 ± 4.9% after, p < 0.05). Histological outcomes of cell therapy included less fibrosis burden than in the placebo group and an increased density of karyokinetic cardiomyocytes and myocardial arterioles (p < 0.05 for each). These changes occurred in the presence of modest cellular engraftment after transplantation., Conclusions: Multisegmental, transendocardial delivery of cell therapy can be achieved effectively in NICM using electromechanical navigation. The pleiotropic properties of immunoselected MPC confer benefit to nonischemic cardiac disease, extending their therapeutic potential beyond the setting of myocardial ischemia., (Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Hypertension is frequently complicated by the development of atrial fibrillation (AF). However, the mechanisms of this link remain poorly understood. In addition, whether short-term hypertension can result in a substrate for AF is not known., Objective: The purpose of this study was to characterize the atrial substrate predisposing to AF due to short-duration hypertension., Methods: Sixteen sheep were studied: 10 had induced hypertension for 7 +/- 4 weeks via the "one-kidney, one-clip" model, and six were controls. Cardiac magnetic resonance imaging was used to assess functional changes. Open-chest electrophysiological study was performed using a custom-made 128-electrode epicardial plaque applied to both right (RA) and left atria (LA), including the Bachmann's bundle, to determine effective refractory periods (ERPs) and conduction velocity at four pacing cycle lengths from six sites. Tissue specimens were harvested for structural analysis., Results: The hypertensive group demonstrated the following compared with controls: higher blood pressure (P <.0001), enlarged LA (P <.05), reduced LA ejection fraction (P <.05), uniformly higher mean ERP (P <.001), slower mean conduction velocity (P <.001), higher conduction heterogeneity index (P <.0001), greater AF inducibility (P = .03), and increased AF durations (P = .04). Picrosirius red staining of atrial tissues revealed increased interstitial fibrosis (P <.0001). There was also evidence of increased inflammatory cell infiltrates (P <.0001)., Conclusion: Short-duration hypertension is associated with significant atrial remodeling characterized by atrial enlargement/dysfunction, interstitial fibrosis, inflammation, slowed/heterogeneous conduction, increased ERP, and greater propensity for AF., (Copyright 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)