Restrictive or Liberal Transfusion Strategy in Myocardial Infarction and Anemia.

BACKGROUND: A strategy of administering a transfusion only when the hemoglobin level falls below 7 or 8 g per deciliter has been widely adopted. However, patients with acute myocardial infarction may benefit from a higher hemoglobin level. METHODS: In this phase 3, interventional trial, we randomly assigned patients with myocardial infarction and a hemoglobin level of less than 10 g per deciliter to a restrictive transfusion strategy (hemoglobin cutoff for transfusion, 7 or 8 g per deciliter) or a liberal transfusion strategy (hemoglobin cutoff, <10 g per deciliter). The primary outcome was a composite of myocardial infarction or death at 30 days. RESULTS: A total of 3504 patients were included in the primary analysis. The mean (±SD) number of red-cell units that were transfused was 0.7±1.6 in the restrictive-strategy group and 2.5±2.3 in the liberal-strategy group. The mean hemoglobin level was 1.3 to 1.6 g per deciliter lower in the restrictive-strategy group than in the liberal-strategy group on days 1 to 3 after randomization. A primary-outcome event occurred in 295 of 1749 patients (16.9%) in the restrictive-strategy group and in 255 of 1755 patients (14.5%) in the liberal-strategy group (risk ratio modeled with multiple imputation for incomplete follow-up, 1.15; 95% confidence interval [CI], 0.99 to 1.34; P = 0.07). Death occurred in 9.9% of the patients with the restrictive strategy and in 8.3% of the patients with the liberal strategy (risk ratio, 1.19; 95% CI, 0.96 to 1.47); myocardial infarction occurred in 8.5% and 7.2% of the patients, respectively (risk ratio, 1.19; 95% CI, 0.94 to 1.49). CONCLUSIONS: In patients with acute myocardial infarction and anemia, a liberal transfusion strategy did not significantly reduce the risk of recurrent myocardial infarction or death at 30 days. However, potential harms of a restrictive transfusion strategy cannot be excluded. (Funded by the National Heart, Lung, and Blood Institute and others; MINT ClinicalTrials.gov number, NCT02981407.).

Placental Abruption and Cardiovascular Event Risk (PACER): Design, data linkage, and preliminary findings.

BACKGROUND: Obstetrical complications impact the health of mothers and offspring along the life course, resulting in an increased burden of chronic diseases. One specific complication is abruption, a life-threatening condition with consequences for cardiovascular health that remains poorly studied. OBJECTIVES: To describe the design and data linkage algorithms for the Placental Abruption and Cardiovascular Event Risk (PACER) cohort. POPULATION: All subjects who delivered in New Jersey, USA, between 1993 and 2020. DESIGN: Retrospective, population-based, birth cohort study. METHODS: We linked the vital records data of foetal deaths and live births to delivery and all subsequent hospitalisations along the life course for birthing persons and newborns. The linkage was based on a probabilistic record-matching algorithm. PRELIMINARY RESULTS: Over the 28 years of follow-up, we identified 1,877,824 birthing persons with 3,093,241 deliveries (1.1%, n = 33,058 abruption prevalence). The linkage rates for live births-hospitalisations and foetal deaths-hospitalisations were 92.4% (n = 2,842,012) and 70.7% (n = 13,796), respectively, for the maternal cohort. The corresponding linkage rate for the live births-hospitalisations for the offspring cohort was 70.3% (n = 2,160,736). The median (interquartile range) follow-up for the maternal and offspring cohorts was 15.4 (8.1, 22.4) and 14.4 (7.4, 21.0) years, respectively. We will undertake multiple imputations for missing data and develop inverse probability weights to account for selection bias owing to unlinked records. CONCLUSIONS: Pregnancy offers a unique window to study chronic diseases along the life course and efforts to identify the aetiology of abruption may provide important insights into the causes of future CVD. This project presents an unprecedented opportunity to understand how abruption may predispose women and their offspring to develop CVD complications and chronic conditions later in life.

Factors influencing the indication of coronary angiography in patients presenting with chest pain unspecified: an analysis of two decades (1994-2014).

Guidelines for cardiac catheterization in patients with non-specific chest pain (NSCP) provide significant room for provider discretion, which has resulted in variability in the utilization of invasive coronary angiograms (CAs) and a high rate of normal angiograms. The overutilization of CAs in patients with NSCP and discharged without a diagnosis of coronary artery disease is an important issue in medical care quality. As a result, we sought to identify patient demographic, socioeconomic, and geographic factors that influenced the performance of a CA in patients with NSCP who were discharged without a diagnosis of coronary artery disease. We intended to establish reference data points for gauging the success of new initiatives for the evaluation of this patient population. In this 20-year retrospective cohort study (1994-2014), we examined 107 796 patients with NSCP from the Myocardial Infarction Data Acquisition System, a large statewide validated database that contains discharge data for all patients with cardiovascular disease admitted to every non-federal hospital in NJ. Patients were partitioned into two groups: those offered a CA (CA group; n = 12 541) and those that were not (No-CA group; n = 95 255). Geographic, demographic, and socioeconomic variables were compared between the two groups using multivariable logistic regression, which determined the predictive value of each categorical variable on the odds of receiving a CA. Whites were more likely than Blacks and other racial counterparts (19.7% vs. 5.6% and 16.5%, respectively; P < .001) to receive a CA. Geographically, patients who received a CA were more likely admitted to a large hospital compared to small- or medium-sized ones (12.5% vs. 8.9% and 9.7%, respectively; P < .05), a primary teaching institution rather than a teaching affiliate or community center (16.1 % vs. 14.3% and 9.1%, respectively; P < .001), and at a non-rural facility compared to a rural one (12.1% vs. 6.5%; P < .001). Lastly from a socioeconomic standpoint, patients with commercial insurance more often received a CA compared to those having Medicare or Medicaid/self-pay (13.7% vs. 9.5% and 6.0%, respectively; P < .001). The utilization of CA in patients with NSCP discharged without a diagnosis of coronary artery disease in NJ during the study period may be explained by differences in geographic, demographic, and socioeconomic factors. Patients with NSCP should be well scrutinized for CA eligibility, and reliable strategies are needed to reduce discretionary medical decisions and improve quality of care.

Epidemiologic trends and risk factors associated with the decline in mortality from coronary heart disease in the United States, 1990-2019.

BACKGROUND: Despite the decline in the rate of coronary heart disease (CHD) mortality, it is unknown how the 3 strong and modifiable risk factors - alcohol, smoking, and obesity -have impacted these trends. We examine changes in CHD mortality rates in the United States and estimate the preventable fraction of CHD deaths by eliminating CHD risk factors. METHODS: We performed a sequential time-series analysis to examine mortality trends among females and males aged 25 to 84 years in the United States, 1990-2019, with CHD recorded as the underlying cause of death. We also examined mortality rates from chronic ischemic heart disease (IHD), acute myocardial infarction (AMI), and atherosclerotic heart disease (AHD). All underlying causes of CHD deaths were classified based on the International Classification of Disease 9th and 10th revisions. We estimated the preventable fraction of CHD deaths attributable to alcohol, smoking, and high body-mass index (BMI) through the Global Burden of Disease. RESULTS: Among females (3,452,043 CHD deaths; mean [standard deviation, SD] age 49.3 [15.7] years), the age-standardized CHD mortality rate declined from 210.5 in 1990 to 66.8 per 100,000 in 2019 (annual change -4.04%, 95% CI -4.05, -4.03; incidence rate ratio [IRR] 0.32, 95% CI, 0.41, 0.43). Among males (5,572,629 CHD deaths; mean [SD] age 47.9 [15.1] years), the age-standardized CHD mortality rate declined from 442.4 to 156.7 per 100,000 (annual change -3.74%, 95% CI, -3.75, -3.74; IRR 0.36, 95% CI, 0.35, 0.37). A slowing of the decline in CHD mortality rates among younger cohorts was evident. Correction for unmeasured confounders through a quantitative bias analysis slightly attenuated the decline. Half of all CHD deaths could have been prevented with the elimination of smoking, alcohol, and obesity, including 1,726,022 female and 2,897,767 male CHD deaths between 1990 and 2019. CONCLUSIONS: The decline in CHD mortality is slowing among younger cohorts. The complex dynamics of risk factors appear to shape mortality rates, underscoring the importance of targeted strategies to reduce modifiable risk factors that contribute to CHD mortality.

Rationale and design for the myocardial ischemia and transfusion (MINT) randomized clinical trial.

BACKGROUND: Accumulating evidence from clinical trials suggests that a lower (restrictive) hemoglobin threshold (<8 g/dL) for red blood cell (RBC) transfusion, compared with a higher (liberal) threshold (≥10 g/dL) is safe. However, in anemic patients with acute myocardial infarction (MI), maintaining a higher hemoglobin level may increase oxygen delivery to vulnerable myocardium resulting in improved clinical outcomes. Conversely, RBC transfusion may result in increased blood viscosity, vascular inflammation, and reduction in available nitric oxide resulting in worse clinical outcomes. We hypothesize that a liberal transfusion strategy would improve clinical outcomes as compared to a more restrictive strategy. METHODS: We will enroll 3500 patients with acute MI (type 1, 2, 4b or 4c) as defined by the Third Universal Definition of MI and a hemoglobin <10 g/dL at 144 centers in the United States, Canada, France, Brazil, New Zealand, and Australia. We randomly assign trial participants to a liberal or restrictive transfusion strategy. Participants assigned to the liberal strategy receive transfusion of RBCs sufficient to raise their hemoglobin to at least 10 g/dL. Participants assigned to the restrictive strategy are permitted to receive transfusion of RBCs if the hemoglobin falls below 8 g/dL or for persistent angina despite medical therapy. We will contact each participant at 30 days to assess clinical outcomes and at 180 days to ascertain vital status. The primary end point is a composite of all-cause death or recurrent MI through 30 days following randomization. Secondary end points include all-cause mortality at 30 days, recurrent adjudicated MI, and the composite outcome of all-cause mortality, nonfatal recurrent MI, ischemia driven unscheduled coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting), or readmission to the hospital for ischemic cardiac diagnosis within 30 days. The trial will assess multiple tertiary end points. CONCLUSIONS: The MINT trial will inform RBC transfusion practice in patients with acute MI.

Post-COVID-19 Cardiovascular Evaluation in National Collegiate Athletic Association Division I Athletes.

OBJECTIVE: To evaluate the necessity of cardiac testing after a COVID-19 diagnosis as it relates to myocarditis in collegiate athletes. DESIGN: Cross-sectional retrospective case series. SETTING: National Collegiate Athletic Association Division I University. PATIENTS: One hundred sixty-five collegiate athletes diagnosed with COVID-19 by reverse transcriptase-polymerase chain reaction or immunoglobulin G antibody between August and December 2020 without exclusion. INTERVENTIONS: All participants underwent cardiac workup consisting of serum troponin, electrocardiogram, transthoracic echocardiogram, and cardiac magnetic resonance (CMR). All results were reviewed by team physicians and sports cardiologists. MAIN OUTCOME MEASURES: Prevalence of myocarditis and abnormality on cardiac testing after COVID-19 infection at a single institution. RESULTS: One (0.61% [95% CI, 0.02%-3.3%] asymptomatic athlete had CMR findings of an age-indeterminate myocardial injury with further cardiac testing being otherwise normal. No athlete had CMR abnormalities consistent with acute myocarditis by the modified Lake Louise Criteria. CONCLUSIONS: Occurrence of myocarditis was lower in this population compared with other studies. No student athlete was permanently disqualified from participation because of testing. A stratified, risk-based testing strategy with CMR may be more appropriate than a universal screening strategy.

Stroke Recovery Program with Modified Cardiac Rehabilitation Improves Mortality, Functional & Cardiovascular Performance.

BACKGROUND: Physical activity and exercise after stroke is strongly recommended, providing many positive influences on function and secondary stroke prevention. The purpose of this study was to investigate the effect of a stroke recovery program (SRP) integrating modified cardiac rehabilitation on mortality and functional outcomes for stroke survivors. METHODS: This study used a retrospective analysis of data from a prospectively collected stroke rehabilitation database which followed 449 acute stroke survivors discharged from an inpatient rehabilitation facility between 2015 and 2020. For 1-year post-stroke, 246 SRP-participants and 203 nonparticipants were compared. The association of the SRP including modified cardiac rehabilitation with all-cause mortality and functional performance was assessed using the following statistical techniques: log rank test, Cox proportional hazard model and linear mixed effect models. Cardiovascular performance over 36 sessions of modified cardiac rehabilitation was assessed using linear effect model with Tukey procedure. The primary outcome measure was 1-year all-cause mortality rate. Secondary outcomes were functional performance measured in Activity Measure of Post-Acute Care scores and cardiovascular performance measured in metabolic equivalent of tasks times minutes. RESULTS: The SRP-participants had: (1) a significantly reduced 1-year post-stroke mortality rate from hospital admission corresponding to a four-fold reduction in mortality (P = 0.005, CI for risk ratio = [0.08, 0.71]), (2) statistically and clinically significant improvement of function in all Activity Measure of Post-Acute Care domains (P < 0.001 for all, 95% CI for differences in Basic Mobility [5.9, 10.1], Daily Activity [6.2, 11.8], and Applied Cognitive [3.0, 6.8]) compared to the matched cohort and (3) an improvement in cardiovascular performance over 36 sessions with an increase of 78% metabolic equivalent of tasks times minutes (P < 0.001, 95% CI [70.6, 85.9%]) compared to baseline. CONCLUSIONS: Stroke survivors who participated in a comprehensive stroke recovery program incorporating modified cardiac rehabilitation had decreased all-cause mortality, improved overall function, and improved cardiovascular performance.

Maternal Cardiovascular and Cerebrovascular Health After Placental Abruption: A Systematic Review and Meta-Analysis (CHAP-SR).

Placental abruption and cardiovascular disease (CVD) have common etiological underpinnings, and there is accumulating evidence that abruption may be associated with future CVD. We estimated associations between abruption and coronary heart disease (CHD) and stroke. The meta-analysis was based on the random-effects risk ratio (RR) and 95% confidence interval (CI) as the effect measure. We conducted a bias analysis to account for abruption misclassification, selection bias, and unmeasured confounding. We included 11 cohort studies comprising 6,325,152 pregnancies, 69,759 abruptions, and 49,265 CHD and stroke cases (1967-2016). Risks of combined CVD morbidity-mortality among abruption and nonabruption groups were 16.7 and 9.3 per 1,000 births, respectively (RR = 1.76, 95% CI: 1.24, 2.50; I2 = 94%; τ2 = 0.22). Women who suffered abruption were at 2.65-fold (95% CI: 1.55, 4.54; I2 = 85%; τ2 = 0.36) higher risk of death related to CHD/stroke than nonfatal CHD/stroke complications (RR = 1.32, 95% CI: 0.91, 1.92; I2 = 93%; τ2 = 0.15). Abruption was associated with higher mortality from CHD (RR = 2.64, 95% CI: 1.57, 4.44; I2 = 76%; τ2 = 0.31) than stroke (RR = 1.70, 95% CI: 1.19, 2.42; I2 = 40%; τ2 = 0.05). Corrections for the aforementioned biases increased these estimates. Women with pregnancies complicated by placental abruption may benefit from postpartum screening or therapeutic interventions to help mitigate CVD risks.

A Simple Scoring Tool to Predict Medical Intensive Care Unit Readmissions Based on Both Patient and Process Factors.

BACKGROUND: Although many predictive models have been developed to risk assess medical intensive care unit (MICU) readmissions, they tend to be cumbersome with complex calculations that are not efficient for a clinician planning a MICU discharge. OBJECTIVE: To develop a simple scoring tool that comprehensively takes into account not only patient factors but also system and process factors in a single model to predict MICU readmissions. DESIGN: Retrospective chart review. PARTICIPANTS: We included all patients admitted to the MICU of Robert Wood Johnson University Hospital, a tertiary care center, between June 2016 and May 2017 except those who were < 18 years of age, pregnant, or planned for hospice care at discharge. MAIN MEASURES: Logistic regression models and a scoring tool for MICU readmissions were developed on a training set of 409 patients, and validated in an independent set of 474 patients. KEY RESULTS: Readmission rate in the training and validation sets were 8.8% and 9.1% respectively. The scoring tool derived from the training dataset included the following variables: MICU admission diagnosis of sepsis, intubation during MICU stay, duration of mechanical ventilation, tracheostomy during MICU stay, non-emergency department admission source to MICU, weekend MICU discharge, and length of stay in the MICU. The area under the curve of the scoring tool on the validation dataset was 0.76 (95% CI, 0.68-0.84), and the model fit the data well (Hosmer-Lemeshow p = 0.644). Readmission rate was 3.95% among cases in the lowest scoring range and 50% in the highest scoring range. CONCLUSION: We developed a simple seven-variable scoring tool that can be used by clinicians at MICU discharge to efficiently assess a patient's risk of MICU readmission. Additionally, this is one of the first studies to show an association between MICU admission diagnosis of sepsis and MICU readmissions.

Pulmonary vein antral isolation causes depolarization of vein sleeves: Implications for the assessment of isolation.

PURPOSE: Pulmonary vein isolation (PVI) for atrial fibrillation has been shown to result in inexcitability of a large fraction of pulmonary veins (PVs), but the mechanism is unknown. We investigated the mechanism of PV inexcitability by assessing the effects of PVI on the electrophysiology of PV sleeves. METHODS: Patients undergoing first-time radiofrequency PVI were studied. Capture threshold, effective refractory period (ERP), and excitability were measured in PVs and the left atrial appendage (LAA) before and after ablation. Adenosine was used to assess both transient reconnection and transient venous re-excitability. RESULTS: We assessed 248 veins among 67 patients. Mean PV ERP (249.7 ± 54.0 ms) and capture threshold (1.4 ± 1.6 mA) increased to 300.5 ± 67.1 and 5.7 ± 5.6 mA, respectively (P < .0001 for both) in the 26.9% PVs that remained excitable, but no change was noted in either measure in the LAA. In 16.3% of the 73.1% inexcitable veins, transient PV re-excitability (as opposed to reconnection) was seen with adenosine administration. CONCLUSIONS: Antral PVI causes inexcitability in a majority of the PVs, which can transiently be restored in some with adenosine. Among PVs that remain excitable, ERP and capture threshold increase significantly. These data imply resting membrane potential depolarization of the of PV myocardial sleeves. As PV inexcitability hampers the assessment of entrance and exit block, demonstrating transient PV re-excitability during adenosine administration helps ensure true isolation.

Surgical and endoscopic management of a pericardioesophageal fistula after radiofrequency pulmonary vein isolation.

INTRODUCTION: The most feared complication of pulmonary vein isolation (PVI) is an atrioesophageal fistula (AEF). While rare (0.1-0.25%), primary surgical closure (as opposed to esophageal stenting) is associated with lower mortality. Pericardioesophageal fistula (PEF) may present prior to fistulization into the atrium. Unfortunately, data on the optimal management of PEFs are lacking. CASE REPORT: Seventy-one-year-old male with AF presented with chest pain 3 weeks after radiofrequency PVI. Computed tomography angiography (CTA) chest and echocardiogram showed pneumopericardium. Barium esophagram showed extravasation from esophagus into the pericardium without connection to the left atrium. Sternotomy with mediastinal exploration exposed the pericardial defect, over which a CorMatrix patch was placed. The fistula was then stented endoscopically with endosuture fixation. Poststent esophagram did not show barium leak, and the patient was discharged home. One week later, the patient returned with enterococcal and candida bacteremia and an acute right parietal/occipital lobe infarct. Barium esophagram showed contrast extravasation into the pericardium. The patient rapidly succumbed to his illness and died. Autopsy revealed pericardial abscess posterior to the LA in communication with the esophagus. Extension to the LA was not seen. CONCLUSION: While the surgical treatment of AEF is relatively well established, there is no consensus in the management of PEF. While prior small series have suggested PEF may be managed with esophageal stenting, our case illustrates the limitations of this approach.

ACE Inhibitor-Induced Angioedema: a Review.

PURPOSE OF REVIEW: This study aims to examine current knowledge on the occurrence, pathophysiology, and treatment of angioedema among patients who receive angiotensin-converting enzyme inhibitors. RECENT FINDINGS: Angiotensin-converting enzyme inhibitors (ACE-I), a medication class used by an estimated 40 million people worldwide, are associated with angioedema that occurs with incidence ranging from 0.1 to 0.7%. The widespread use of ACE-I resulted in one third of all emergency department visits for angioedema. Angioedema occurs more frequently in African Americans, smokers, women, older individuals, and those with a history of drug rash, seasonal allergies, and use of immunosuppressive therapy. The pathophysiology of ACE-I-induced angioedema involves inhibition of bradykinin and substance P degradation by ACE (kininase II) leading to vasodilator and plasma extravasation. Treatment modalities include antihistamines, steroids, and epinephrine, as well as endotracheal intubation in cases of airway compromise. Patients with a history of ACE-I-induced angioedema should not be re-challenged with this class of agents, as there is a relatively high risk of recurrence. CONCLUSION: ACE-I are frequently used therapeutic agents that are associated with angioedema. Their use should be avoided in high-risk individuals and early diagnosis, tracheal intubation in cases of airway compromise, and absolute avoidance of re-challenge are important.

Quality of Meta-Analyses for Randomized Trials in the Field of Hypertension: an Updated and Improved Systematic Review.

Publications of hypertension-related meta-analyses (MAs) have increased exponentially in the past 25 years and now average 8/month. Theoretically, this is facilitating evidence-based management of patients. However, some practitioners and authors of guidelines have questioned the quality of published MAs. By extending a prior review, we have assessed the quality of 212 hypertension-related meta-analyses over 5 years based on systematically searching three computerized libraries. Seventeen criteria grouped into four domains of quality yielded the following results: (1) Assessment of trial quality was accomplished in 89% of MAs, and 38% analyzed trials in subgroups of trial quality where appropriate. (2) All three measures of heterogeneity (I 2, tau, and P for heterogeneity) were reported in 36%, reflecting the failure to report tau, the standard deviation of the main effect. (3) Publication bias was assessed in 75%, and 43% of MAs used a statistical test for publication bias. (4) Regarding transparency, 9 to 31% of MAs reported problems in the previous three domains in the article's abstract. Journal impact factor reporting the MAs declined significantly over 5 years. The percent with criteria of quality in a MA was modestly correlated with journal impact factor (R 2 = 0.05, P = 0.001). False-positive results from inappropriate application of the DerSimonian-Laird model affected 25% of articles, which reported these false positives in the article's abstract in 72%. No more than 25% of MAs had 67% or more of the criteria of quality. In conclusion, skepticism of hypertension-related MAs is justified, but their quality can be readily corrected.

A Novel Annotation Technique During Mapping to Facilitate the Termination of Atrial Tachycardia Following Ablation for Atrial Fibrillation.

INTRODUCTION: The treatment of atrial tachycardia (AT) occurring after ablation for atrial fibrillation (AF) is challenging. The most common ablation strategy relies on entrainment, and electroanatomic activation mapping (EAM) using a conventional window of interest (WOI), centered on the easily detectable atrial signal on the coronary sinus catheter. We describe a novel EAM annotation technique that uses a WOI starting 40 milliseconds prior to the P wave in order to detect the reentrant AT exit site. This WOI timing is based on the similarity between scar-related reentrant AT and scar-related ventricular tachycardia. METHODS: Patients with AT after prior ablation for AF were included. The EAM of the AT was performed using the novel mapping annotation technique. The ablation was considered successful if the AT terminated during ablation at the site identified by this strategy. RESULTS: Twenty-eight patients with 36 ATs were included. The ATs were classified as follows: mitral annulus (13/36), roof (11/36), anterior/posterior/lateral left atrial wall (10/36), and RA (2/36). A complete EAM using the novel annotation technique was achieved in 34 of 36 AT's, encompassing 94 ± 6.5% of the cycle length. Low amplitude pre-P fractionated electrograms were found in 34 of 36 (94%) ATs and these occurred at a mean distance of 1.8 ± 1.2 mm from the "early-meets-late" line. Ablation at these areas resulted in termination of 34 of 36 ATs (94%). CONCLUSION: The novel EAM annotation allows the accurate detection of the critical isthmus of post-AF ablation AT. Ablation of these isthmuses results in termination of the AT in the vast majority of patients.

Polarization sensitive optical coherence microscopy for brain imaging.

Optical coherence tomography (OCT) and optical coherence microscopy (OCM) have demonstrated the ability to investigate cyto- and myelo-architecture in the brain. Polarization-sensitive OCT provides sensitivity to additional contrast mechanisms, specifically the birefringence of myelination and, therefore, is advantageous for investigating white matter fiber tracts. In this Letter, we developed a polarization-sensitive optical coherence microscope (PS-OCM) with a 3.5 µm axial and 1.3 µm transverse resolution to investigate fiber organization and orientation at a finer scale than previously demonstrated with PS-OCT. In a reconstructed mouse brain section, we showed that at the focal depths of 20-70 µm, the PS-OCM reliably identifies the neuronal fibers and quantifies the in-plane orientation.

Diffusion tensor imaging in patients with obstetric antiphospholipid syndrome without neuropsychiatric symptoms.

OBJECTIVES: To evaluate white matter (WM) integrity in neurologically asymptomatic antiphospholipid syndrome (APS) using diffusion tensor imaging (DTI) in women with no thrombotic history but with pregnancy loss. METHODS: Imaging was performed with a 3 T scanner using structural MRI (T1-weighted, fluid attenuation inversion recovery [FLAIR]) and DTI sequences in 66 women with APS and a control group of 17 women. Women with APS were further categorized as positive for lupus anticoagulant (LA) and/or aß2GPI-G antibodies (LA/aß2GPI-G-positive, N = 29) or negative (LA/aß2GPI-G-negative, N = 37) for both. Tract-based spatial statistics of standard DTI-based indices were compared among groups. RESULTS: Women with APS had significantly lower fractional anisotropy (p < 0.05) associated with higher mean diffusivity and radial diffusivity compared to the control group. There was a stronger association of abnormal DTI features among women positive for LA and/or aß2GPI-IgG antibodies than those who were negative. CONCLUSIONS: DTI appears sensitive to subtle WM changes in women with APS with no thrombotic history but with pregnancy loss, compatible with alterations in axonal structure and in the myelin sheath. The preferential association of abnormal DTI features with the two most pathogenic aPLAbs reinforces the pathophysiological relevance of our findings. KEY POINTS: • APS women exhibited lower FA and higher MD and RD than controls. • WM impairments are more severe in patients with positive LA or aß2GPI-IgG. • An association exists between abnormal DTI features and LA or aß2GPI-IgG positivity. • Diffusion tensor imaging detects microstructural white matter abnormalities in APS women.

Microstructural impact of ischemia and bone marrow-derived cell therapy revealed with diffusion tensor magnetic resonance imaging tractography of the heart in vivo.

BACKGROUND: The arrangement of myofibers in the heart is highly complex and must be replicated by injected cells to produce functional myocardium. A novel approach to characterize the microstructural response of the myocardium to ischemia and cell therapy, with the use of serial diffusion tensor magnetic resonance imaging tractography of the heart in vivo, is presented. METHODS AND RESULTS: Validation of the approach was performed in normal (n=6) and infarcted mice (n=6) as well as healthy human volunteers. Mice (n=12) were then injected with bone marrow mononuclear cells 3 weeks after coronary ligation. In half of the mice the donor and recipient strains were identical, and in half the strains were different. A positive response to cell injection was defined by a decrease in mean diffusivity, an increase in fractional anisotropy, and the appearance of new myofiber tracts with the correct orientation. A positive response to bone marrow mononuclear cell injection was seen in 1 mouse. The response of the majority of mice to bone marrow mononuclear cell injection was neutral (9/12) or negative (2/12). The in vivo tractography findings were confirmed with histology. CONCLUSIONS: Diffusion tensor magnetic resonance imaging tractography was able to directly resolve the ability of injected cells to generate new myofiber tracts and provided a fundamental readout of their regenerative capacity. A highly novel and translatable approach to assess the efficacy of cell therapy in the heart is thus presented.

How low an LDL-C should we go with statin therapy?

There is evidence from epidemiology, pathophysiology, and clinical trials that high LDL cholesterol levels cause atherosclerotic heart disease. Current guidelines recommend an LDL cholesterol target of 70 mg/dL for patients at high or very high risk. The risk imposed by LDL cholesterol is modulated by the presence of additional risk factors such as age, smoking, and indices of inflammation. Epidemiologic studies as well as rare congenital conditions (e.g., hypobetalipoproteinemia) have shown that very low LDL cholesterol (lower than 70 mg/dL) levels are associated with a very low risk of cardiovascular disease. Analyses of randomized clinical trials have shown a greater benefit in reducing the risk of cardiovascular disease (without an increase in adverse events) among those with very low achieved LDL (below 40 mg/dL). In one study of patients with achieved LDL cholesterol below 30 mg/dL, there was no increase in the usual adverse events compared to patients with LDL cholesterol levels above 30 mg/dL. High-intensity statin therapy is associated with a higher rate of transaminase elevations, but no hepatic failure, a very small risk of myopathy, and an increased risk of developing diabetes. However, the small increase in the risk of developing diabetes is much smaller than the marked lowering of cardiovascular risk. The duration of statin therapy may be important in studies of primary prevention and early, probably low-dose statin therapy, may achieve primordial prevention of atherosclerotic disease.