Characterizing regional and global effects of epicardial adipose tissue on cardiac systolic and diastolic function.

OBJECTIVE: The aim of this retrospective study was to determine whether regional epicardial adipose tissue (EAT) exerts localized effects on adjacent myocardial left ventricular (LV) function. METHODS: Cardiac magnetic resonance imaging (MRI), echocardiography, dual-energy x-ray absorptiometry, and exercise testing were performed in 71 patients with obesity with elevated cardiac biomarkers and visceral fat. Total and regional (anterior, inferior, lateral, right ventricular) EAT was quantified by MRI. Diastolic function was quantified by echocardiography. MRI was used to quantify regional longitudinal LV strain. RESULTS: EAT was associated with visceral adiposity (r = 0.47, p < 0.0001) but not total fat mass. Total EAT was associated with markers of diastolic function (early tissue Doppler relaxation velocity [e'], mitral inflow velocity ratio [E/A], early mitral inflow/e' ratio [E/e']), but only E/A remained significant after adjustment for visceral adiposity (r = -0.30, p = 0.015). Right ventricular and LV EAT had similar associations with diastolic function. There was no evidence for localized effects of regional EAT deposition on adjacent regional longitudinal strain. CONCLUSIONS: There was no association between regional EAT deposition and corresponding regional LV segment function. Furthermore, the association between total EAT and diastolic function was attenuated after adjustment for visceral fat, indicating that systemic metabolic impairments contribute to diastolic dysfunction in high-risk middle-aged adults.

A Triple Threat: Takayasu Arteritis, Bicuspid Aortic Valve, and Triplets.

Takayasu arteritis is a vasculitis affecting women of reproductive age. Appropriate care of these patients requires a multidisciplinary approach and close monitoring. We present the case of a woman with a triplet gestation and Takayasu arteritis complicated by an ascending aortic aneurysm, aortic regurgitation, and bicuspid aortic valve.

A Clinical Update on Vasoactive Medication in the Management of Cardiogenic Shock.

This is a focused review looking at the pharmacological support in cardiogenic shock. There are a plethora of data evaluating vasopressors and inotropes in septic shock, but the data are limited for cardiogenic shock. This review article describes in detail the pathophysiology of cardiogenic shock, the mechanism of action of different vasopressors and inotropes emphasizing their indications and potential side effects. This review article incorporates the currently used specific risk-prediction models in cardiogenic shock as well as integrates data from many trials on the use of vasopressors and inotropes. Lastly, this review seeks to discuss the future direction for vasoactive medications in cardiogenic shock.

Racial and ethnic disparities in the management and outcomes of cardiogenic shock complicating acute myocardial infarction.

BACKGROUND: It remains unclear if there remain racial/ethnic differences in the management and in-hospital outcomes of acute myocardial infarction-cardiogenic shock (AMI-CS) in contemporary practice. METHODS: We used the National inpatient Sample (2012-2017) to identify a cohort of adult AMI-CS hospitalizations. Race was classified as White, Black and Others (Hispanic, Asian/Pacific Islander, Native Americans). Primary outcome of interest was in-hospital mortality, and secondary outcomes included use of invasive cardiac procedures, length of hospital stay and discharge disposition. RESULTS: Among 203,905 AMI-CS admissions, 70.4% were White, 8.1% were Black and 15.7% belonged to Other races. Black AMI-CS admissions were more often female, with lower socio-economic status, greater comorbidity, and higher rates of non-ST-segment-elevation AMI-CS, cardiac arrest, and multi-organ failure. Compared to White AMI-CS admissions, Black and Other races had lower rates of coronary angiography (75.3% vs 69.3% vs 73.6%), percutaneous coronary intervention (52.7% vs 48.6% vs 54.8%), and mechanical circulatory devices (48.3% vs 42.8% vs 43.7%) (all p < 0.001). Unadjusted in-hospital mortality was comparable between White (33.3%) and Black (33.8%) admissions, but lower for other races (32.1%). Adjusted analysis with White race as the reference identified lower in-hospital mortality for Black (odds ratio [OR] 0.85 [95% confidence interval {CI} 0.82-0.88]; p < 0.001) and Other races (OR 0.97 [95% CI 0.94-1.00]; p = 0.02). Admissions of Black race had longer hospital stay, and less frequent discharges to home. CONCLUSIONS: Contrary to previous studies, we identified Black and Other race AMI-CS admissions had lower in-hospital mortality despite lower rates of cardiac procedures when compared to White admissions.

Coronary Embolism despite CHA2DS2-VASc Score of Zero: Should We Reconsider Anticoagulation?

Coronary embolism (CE) is a rare but important cause of acute coronary syndrome. The most common source of emboli is considered to be infective endocarditis and atrial fibrillation. Various studies have estimated the prevalence of coronary embolism; however, diagnosis is challenging. Often, it is difficult to differentiate. Nonetheless, this is an important step as treating the underlying cause of an embolism is essential to limit recurrence. However, while this condition may have fatal consequences, due to its uncommon occurrence, there is no consensus on diagnosis and management. We present a case of a 53-year-old obese male, with a history of paroxysmal atrial fibrillation not on anticoagulation due to a low CHA2DS2-VASc score, who presented with chest pain associated with lightheadedness. ECG on admission revealed coarse atrial fibrillation, and troponin was gradually elevating on serial lab workup. Coronary angiography revealed a distal left anterior descending artery occlusion with apical wall akinesis without any evidence of atherosclerotic coronary artery disease. A presumptive diagnosis of coronary embolism secondary to paroxysmal atrial fibrillation was made, and the patient was started on anticoagulation despite a low CHA2DS2-VASc score. This case not only highlights coronary embolism but also illustrates that a low CHA2DS2-VASc score does not mean there is no risk of emboli. For such patients, it is important to take clinical reasoning into account along with the CHA2DS2-VASc score to determine the benefit of anticoagulation.

Impact of Right Ventricular Dysfunction on Short-term and Long-term Mortality in Sepsis: A Meta-analysis of 1,373 Patients.

BACKGROUND: Right ventricular (RV) dysfunction in sepsis and septic shock has been infrequently studied and has uncertain prognostic significance. RESEARCH QUESTION: Does RV function impact mortality in sepsis and septic shock? STUDY DESIGN AND METHODS: We reviewed the published literature from January 1999 to April 2020 for studies evaluating adult patients with sepsis and septic shock. Study definition of RV dysfunction was used to classify patients. The primary outcome was all-cause mortality divided into short-term mortality (ICU stay, hospital stay, or mortality ≤30 days) and long-term mortality (>30 days). Effect estimates from the individual studies were extracted and combined, using the random-effects, generic inverse variance method of DerSimonian and Laird. RESULTS: Ten studies, 1,373 patients, were included; RV dysfunction was noted in 477 (34.7%). RV dysfunction was variably classified as decreased RV systolic motion, high RV/left ventricular ratio and decreased RV ejection fraction. Septic shock, ARDS, and mechanical ventilation were noted in 82.0%, 27.5%, and 78.4% of the population, respectively. Patients with RV dysfunction had lower rates of mechanical ventilation (71.9% vs 81.9%; P < .001), higher rates of acute hemodialysis (38.1% vs 22.4%; P = .04), but comparable rates of septic shock and ARDS. Studies showed moderate (I2 = 58%) and low (I2 = 49%) heterogeneity for short-term and long-term mortality, respectively. RV dysfunction was associated with higher short-term (pooled OR, 2.42; 95%CI, 1.52-3.85; P = .0002) (10 studies) and long-term (pooled OR, 2.26; 95%CI, 1.29-3.95; P = .004) (4 studies) mortality. INTERPRETATION: In this meta-analysis of observational studies, RV dysfunction was associated with higher short-term and long-term mortality in sepsis and septic shock.

Pulmonary artery catheter use in acute myocardial infarction-cardiogenic shock.

AIMS: The aim of this study is to evaluate the contemporary use of a pulmonary artery catheter (PAC) in acute myocardial infarction-cardiogenic shock (AMI-CS). METHODS AND RESULTS: A retrospective cohort of AMI-CS admissions using the National Inpatient Sample (2000-2014) was identified. Admissions with concomitant cardiac surgery or non-AMI aetiology for cardiogenic shock were excluded. The outcomes of interest were in-hospital mortality, resource utilization, and temporal trends in cohorts with and without PAC use. In the non-PAC cohort, the use and outcomes of right heart catheterization was evaluated. Multivariable regression and propensity matching was used to adjust for confounding. During 2000-2014, 364 001 admissions with AMI-CS were included. PAC was used in 8.1% with a 75% decrease during over the study period (13.9% to 5.4%). Greater proportion of admissions to urban teaching hospitals received PACs (9.5%) compared with urban non-teaching (7.1%) and rural hospitals (5.4%); P < 0.001. Younger age, male sex, white race, higher comorbidity, noncardiac organ failure, use of mechanical circulatory support, and noncardiac support were independent predictors of PAC use. The PAC cohort had higher in-hospital mortality (adjusted odds ratio 1.07 [95% confidence interval 1.04-1.10]), longer length of stay (10.9 ± 10.9 vs. 8.2 ± 9.3 days), higher hospitalization costs ($128 247 ± 138 181 vs. $96 509 ± 116 060), and lesser discharges to home (36.3% vs. 46.4%) (all P < 0.001). In 6200 propensity-matched pairs, in-hospital mortality was comparable between the two cohorts (odds ratio 1.01 [95% confidence interval 0.94-1.08]). Right heart catheterization was used in 12.5% of non-PAC admissions and was a marker of greater severity but did not indicate worse outcomes. CONCLUSIONS: In AMI-CS, there was a 75% decrease in PAC use between 2000 and 2014. Admissions receiving a PAC were a higher risk cohort with worse clinical outcomes.

Impaired myogenic development, differentiation and function in hESC-derived SMA myoblasts and myotubes.

Spinal muscular atrophy (SMA) is a severe genetic disorder that manifests in progressive neuromuscular degeneration. SMA originates from loss-of-function mutations of the SMN1 (Survival of Motor Neuron 1) gene. Recent evidence has implicated peripheral deficits, especially in skeletal muscle, as key contributors to disease progression in SMA. In this study we generated myogenic cells from two SMA-affected human embryonic stem cell (hESC) lines with deletion of SMN1 bearing two copies of the SMN2 gene and recapitulating the molecular phenotype of Type 1 SMA. We characterized myoblasts and myotubes by comparing them to two unaffected, control hESC lines and demonstrate that SMA myoblasts and myotubes showed altered expression of various myogenic markers, which translated into an impaired in vitro myogenic maturation and development process. Additionally, we provide evidence that these SMN1 deficient cells display functional deficits in cholinergic calcium signaling response, glycolysis and oxidative phosphorylation. Our data describe a novel human myogenic SMA model that might be used for interrogating the effect of SMN depletion during skeletal muscle development, and as model to investigate biological mechanisms targeting myogenic differentiation, mitochondrial respiration and calcium signaling processes in SMA muscle cells.

My46: a Web-based tool for self-guided management of genomic test results in research and clinical settings.

A major challenge to implementing precision medicine is the need for an efficient and cost-effective strategy for returning individual genomic test results that is easily scalable and can be incorporated into multiple models of clinical practice. My46 is a Web-based tool for managing the return of genetic results that was designed and developed to support a wide range of approaches to disclosing results, ranging from traditional face-to-face disclosure to self-guided models. My46 has five key functions: set and modify results-return preferences, return results, educate, manage the return of results, and assess the return of results. These key functions are supported by six distinct modules and a suite of features that enhance the user experience, ease site navigation, facilitate knowledge sharing, and enable results-return tracking. My46 is a potentially effective solution for returning results and supports current trends toward shared decision making between patients and providers and patient-driven health management.Genet Med 19 4, 467-475.

"We don't know her history, her background": adoptive parents' perspectives on whole genome sequencing results.

Exome sequencing and whole genome sequencing (ES/WGS) can provide parents with a wide range of genetic information about their children, and adoptive parents may have unique issues to consider regarding possible access to this information. The few papers published on adoption and genetics have focused on targeted genetic testing of children in the pre-adoption context. There are no data on adoptive parents' perspectives about pediatric ES/WGS, including their preferences about different kinds of results, and the potential benefits and risks of receiving results. To explore these issues, we conducted four exploratory focus groups with adoptive parents (N = 26). The majority lacked information about their children's biological family health history and ancestry, and many viewed WGS results as a way to fill in these gaps in knowledge. Some expressed concerns about protecting their children's future privacy and autonomy, but at the same time stated that WGS results could possibly help them be proactive about their children's health. A few parents expressed concerns about the risks of WGS in a pre-adoption context, specifically about decreasing a child's chance of adoption. These results suggest that issues surrounding genetic information in the post-adoption and ES/WGS contexts need to be considered, as well as concerns about risks in the pre-adoption context. A critical challenge for ES/WGS in the context of adoption will be balancing the right to know different kinds of genetic information with the right not to know. Specific guidance for geneticists and genetic counselors may be needed to maximize benefits of WGS while minimizing harms and prohibiting misuse of the information in the adoption process.