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Supplemental Digital Content is available in the text., Myocarditis has been recognized as a rare complication of coronavirus disease 2019 (COVID-19) mRNA vaccinations, especially in young adult and adolescent males. According to the US Centers for Disease Control and Prevention, myocarditis/pericarditis rates are ≈12.6 cases per million doses of second-dose mRNA vaccine among individuals 12 to 39 years of age. In reported cases, patients with myocarditis invariably presented with chest pain, usually 2 to 3 days after a second dose of mRNA vaccination, and had elevated cardiac troponin levels. ECG was abnormal with ST elevations in most, and cardiac MRI was suggestive of myocarditis in all tested patients. There was no evidence of acute COVID-19 or other viral infections. In 1 case, a cardiomyopathy gene panel was negative, but autoantibody levels against certain self-antigens and frequency of natural killer cells were increased. Although the mechanisms for development of myocarditis are not clear, molecular mimicry between the spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and self-antigens, trigger of preexisting dysregulated immune pathways in certain individuals, immune response to mRNA, and activation of immunologic pathways, and dysregulated cytokine expression have been proposed. The reasons for male predominance in myocarditis cases are unknown, but possible explanations relate to sex hormone differences in immune response and myocarditis, and also underdiagnosis of cardiac disease in women. Almost all patients had resolution of symptoms and signs and improvement in diagnostic markers and imaging with or without treatment. Despite rare cases of myocarditis, the benefit-risk assessment for COVID-19 vaccination shows a favorable balance for all age and sex groups; therefore, COVID-19 vaccination is recommended for everyone ≥12 years of age.

Device therapy for severe heart failure (HF) has shown efficacy both in the acute and chronic settings. Recent percutaneous device innovations have pioneered a field known as interventional HF, providing clinicians with a variety of options for acute decompensated HF that are centered on non-surgical mechanical circulatory support. Other structural-based therapies are aimed at the pathophysiology of chronic HF and target the underlying etiologies such as functional mitral regurgitation, ischemic cardiomyopathy, and increased neurohumoral activity. Remote hemodynamic monitoring devices have also been shown to be efficacious for the for ambulatory management of HF. We review the current data on devices and investigational therapies for HF management where pharmacotherapy falls short.

Background As more left ventricular-assist devices (LVADs) are implanted, multidrug-resistant LVAD infections are becoming increasingly common, partly due to bacterial biofilm production. To aid in developing bacteriophage therapy for LVAD infections, we have identified the most common bacterial pathogens that cause LVAD driveline infections (DLIs) in our heart transplant referral center. Materials and methods We studied a retrospective cohort of patients who received LVADs from November 2003 to August 2017 to identify the common causative organisms of LVAD infection. We also studied a prospective cohort of patients diagnosed with DLIs from October 2018 to May 2019 to collect bacterial strains from DLIs for developing bacteriophages to lyse causative pathogens. LVAD infections were classified as DLI, bacteremia, and pump/device infections in the retrospective cohort. Results In the retrospective cohort of 582 patients, 186 (32.0%) developed an LVAD infection, with 372 microbial isolates identified. In the prospective cohort, 96 bacterial strains were isolated from 54 DLIs. The microorganisms causing DLIs were similar in the two cohorts; the most common isolate was Staphylococcus aureus. We identified 6 prospective S. aureus strains capable of biofilm formation. We developed 3 bacteriophages that were able to lyse 5 of 6 of the biofilm-forming S. aureus strains. Conclusions Similar pathogens caused LVAD DLIs in our retrospective and prospective cohorts, indicating our bacterial strain bank will be representative of future DLIs. Our banked bacterial strains will be useful in developing phage cocktails that can lyse ≥80% of the bacteria causing LVAD infections at our institution.

Because of the diverse etiologies of community-acquired pneumonia (CAP) and the limitations of current diagnostic modalities, serum procalcitonin levels have been proposed as a novel tool to guide antibiotic therapy. Outcome data from procalcitonin-guided therapy trials have shown similar mortality, but the essential question is whether the sensitivity and specificity of procalcitonin levels enable the practitioner to distinguish bacterial pneumonia, which requires antibiotic therapy, from viral pneumonia, which does not. In this meta-analysis of 12 studies in 2408 patients with CAP that included etiologic diagnoses and sufficient data to enable analysis, the sensitivity and specificity of serum procalcitonin were 0.55 (95% confidence interval [CI], .37–.71; I2 = 95.5%) and 0.76 (95% CI, .62–.86; I2 = 94.1%), respectively. Thus, a procalcitonin level is unlikely to provide reliable evidence either to mandate administration of antibiotics or to enable withholding such treatment in patients with CAP.

Introduction A shortage of medical devices designed for children persists due to the smaller pediatric population and market factors. Furthermore, pediatric device development is challenging due to the limited available funding sources. We describe our experience with pediatric device projects that successfully received federal grant support towards commercializing the devices that can serve as a guide for future innovators. Methods The developmental pathways of pediatric device projects at a tertiary-care children's hospital that received NIH SBIR/STTR funding between 2016–2019 were reviewed. The clinical problems, designs, specific aims, and development phase were delineated. Results Pediatric faculty successfully secured NIH SBIR/STTR funding for five pediatric devices via qualified small business concerns (SBC's). Three projects were initiated in the capstone engineering design programs and developed further at two affiliated engineering schools, while the other two projects were developed in the faculty members’ labs. Four projects received funding via established SBC's, while one was awarded funding via a newly established SBC. Conclusion NIH SBIR/STTR grants are an essential source of external non-dilutive funding for pediatric device innovation and especially for academic-initiated projects. This funding can provide needed early-stage support to facilitate commercialization. In addition, these grants can serve as achievable accomplishments for pediatric faculty portfolios toward academic promotion. Our experience shows that it is possible to build a robust innovation ecosystem comprised of academic faculty (clinical/engineering) collaborating with local device development companies while jointly implementing a product development strategy leveraging NIH SBIR/STTR funding for critical translational research phases of pediatric device development.

As procedures such as epicardial ventricular ablation and left atrial appendage occlusion become more commonplace, the need grows for safer techniques to access the physiologic pericardial space. Because this space contains minimal fluid for lubrication, prevailing methods of pericardial access pose considerable periprocedural risk to cardiac structures. Therefore, we devised a novel method of pericardial access in which carbon dioxide (CO2) is insufflated through a right atrial puncture under fluoroscopic guidance, enabling clear visualization of the cardiac silhouette separating from the chest wall. We performed the procedure in 8 Landrace pigs, after which transthoracic percutaneous pericardial access was obtained by conventional means. All of the animals remained hemodynamically stable during the procedure, and none showed evidence of epicardial or coronary injury. The protective layer of CO2 in the pericardial space anterior to the heart facilitated percutaneous access in our porcine model, and the absence of complications supports the potential safety of this method.

Heart failure decompensations accounts for over one million hospitalizations annually and are the most common cause of US hospital admission in patients over 65. While this results in a reduced quality of life for patients, hospital admissions within 30 days of discharge for heart failure are not reimbursed, making this patient population incredibly expensive for hospitals to treat. US expenditure on heart failure exceeds $30 billion annually and is projected to rise by 127% to nearly $70 billion by 2030 as the population ages. Scheduling a follow up appointment within one week of discharge has been shown to reduce rates of readmission. This quality improvement initiative is aimed at improving post-discharge follow up rates in a tertiary referral hospital. The affiliated follow up clinic uses a different electronic medical record (EMR) system, so a system of cross-communication is key. The initial intervention introduced an EMR order that, once placed in the inpatient setting, created an appointment request in the follow up clinic. The cardiology consult nurse practitioner was assigned and educated about the task of entering this follow up order. With this intervention, an increase the number of confirmed follow up appointments scheduled by discharge for patients admitted with acute decompensated heart failure was expected. The initial intervention of introducing an EMR order resulted in a median of 18 patient referrals per month over a period of 5 months. The intervention of introducing a dedicated nurse practitioner the task of placing the order resulted in an increase to 25 orders in the next month. Similarly, the percentage of completed referrals increased from 29% over 5 months to 44% in the last month when a dedicated nurse practitioner was tasked with placing the order for follow up. In recognizing the delicate process of discharging patients with heart failure decompensations, a unified process to organize follow up in a tertiary referral hospital was necessary to communicate with the affiliated clinic. This initial intervention shows promise that continuity of care can be established in an intricate medical system. Further interventions include better equipping the cardiology clinic with personnel to accommodate for the bolus of new post-discharge follow up appointments.

Medication nonadherence is highly prevalent among patients with chronic cardiovascular disease. Poor adherence has been associated with increased morbidity and mortality. Medication cost is a major driver for medication nonadherence. Utilizing data from the 2016 to 2018 Behavioral Risk Factor Surveillance System (BRFSS) survey, we estimated the prevalence of cost-related medication nonadherence (CRMNA) among the overall population and among individuals who reported a history of diabetes, atherosclerotic cardiovascular disease (ASCVD), or hypertension. We then performed multivariable logistic regression to analyze sociodemographic factors associated with CRMNA. Our study population consisted of 142,577 individuals of whom 24% were older than 65 years, 47% were men, 66% were White, 17% Black, 35% had hypertension, 13% had diabetes mellitus, and 10% had ASCVD. CRMNA was reported in 10% of the overall population, 12% among those with hypertension, 17% among those with diabetes, and 17% among those with ASCVD. Age below 65 years, female gender, unemployment, lower income, lower educational attainment, having at least 1 comorbidity, and living in a state that did not expand Medicaid were independently associated with CRMNA. The prevalence of CRMNA increased with greater number of these high-risk sociodemographic factors. We conclude that the prevalence of CRMNA is 10% among U.S. adults overall and is higher among those with common chronic diseases. Risk factors associated with CRMNA should be addressed in order to improve adherence rates and health outcomes among high-risk individuals.

BACKGROUND: Type 2 myocardial infarction (MI) is increasingly diagnosed in patients with heart failure (HF). A paucity of data exists pertinent to the contemporary prevalence and impact of type 2 MI in patients with HF. We studied the patient profiles and the prognostic impact of type 2 MI on outcomes of HF hospitalizations. METHODS: The Nationwide Readmission Database 2018 was queried for patients with HF hospitalizations with and without type 2 MI. Baseline characteristics, inpatient outcomes, and 30-day all-cause readmissions between both cohorts were compared. RESULTS: Of 1,072,674 primary HF hospitalizations included in the study, 28,813 (2.7%) had type 2 MI. Patients with type 2 MI were more likely to be males (56.5% vs 51.6%; P < .001) and had a higher prevalence of hypertension (94% vs 92.2%; P < .001), prior myocardial infarction (17.1% vs 14.9%; P < .001), anemia (9.1% vs 8.1%; P < .001), chronic kidney disease (55.7% vs 49.4%; P < .001), neurological disorders (9.4% vs 7.3%; P < .001), and weight loss (7.3% vs 5.6%; P < .001). Compared with their counterparts without type 2 MI, patients with HF with type 2 MI had significantly higher in-hospital mortality (adjusted odds ratio [aOR], 1.53; 95% confidence interval [CI], 1.37–1.72), hospital costs (adjusted parameter estimate, $1785; 95% CI, 1388–2182), discharge to nursing facility (aOR, 1.22; 95% CI, 1.15–1.29), longer length of stay (adjusted parameter estimate, 0.53; 95% CI, 0.42–0.64), and rate of 30-day all-cause readmissions (aOR, 1.06; 95% CI, 1.01–1.12). CONCLUSION: Type 2 MI in patients hospitalized with HF is associated with higher mortality and resource utilization in the United States.

To assess the contemporary use of adenosine diphosphate (ADP) receptor inhibitors in acute coronary syndrome at a large, quaternary academic medical center.A retrospective observational study was conducted using health records to compare patients who were treated with ticagrelor (Brilinta, AstraZeneca), prasugrel, or clopidogrel for a primary diagnosis of new-onset acute coronary syndrome between January 2014 and December 2014.A total of 275 patients were identified. Clopidogrel was the most commonly prescribed ADP receptor antagonist (52%), followed by ticagrelor (26%) and prasugrel (22%). Patients who were prescribed clopidogrel were more likely female (Clopidogrel continues to be the most commonly prescribed antiplatelet agent, particularly in older patients with more comorbidities.

Myxedema coma can mask cardiac causes of hypotension. Careful assessment is needed once initial therapy fails. A 43-year-old woman with untreated hypothyroidism presented with hypotension, respiratory distress, and somnolence after 6 months of progressive dyspnea and weight gain. She was

Several 7-peptide-substituted pterins were synthesized and tested as competitive active-site inhibitors of ricin toxin A (RTA). Focus began on dipeptide conjugates, and these results further guided the construction of several tripeptide conjugates. The binding of these compounds to RTA was studied via a luminescence-based kinetic assay, as well as through X-ray crystallography. Despite the relatively polar, solvent exposed active site, several hydrophobic interactions, most commonly π-interactions not predicted by modeling programs, were identified in all of the best-performing inhibitors. Nearly all of these compounds provide IC₅₀ values in the low micromolar range.

The optimization of a series of pterin amides for use as Ricin Toxin A (RTA) inhibitors is reported. On the basis of crystallographic data of a previous furan-linked pterin, various expanded furans were synthesized, linked to the pterin, and tested for inhibition. Concurrently, heteroanalogues of furan were explored, leading to the discovery of more potent triazole-linked pterins. Additionally, we discuss a dramatic improvement in the synthesis of these pterin amides via a dual role by diazabicycloundecene (DBU). This synthetic enhancement facilitates rapid diversification of the previously challenging pterin heterocycle, potentially aiding future medicinal research involving this structure.