Myocarditis With COVID-19 mRNA Vaccines.

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.

Identifying Causative Microorganisms in Left Ventricular Assist Device Infections as a Guide for Developing Bacteriophage Therapy.

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.

Prevalence and predictors of cost-related medication nonadherence in individuals with cardiovascular disease: Results from the Behavioral Risk Factor Surveillance System (BRFSS) survey.

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.

Procalcitonin to Distinguish Viral From Bacterial Pneumonia: A Systematic Review and Meta-analysis.

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.

WORSENING RENAL FUNCTION IN ACUTE DECOMPENSATED HEART FAILURE: A BAD SIGN, OR MAYBE NOT?

Introduction: Prognostic role of worsening renal function (WRF) during hospitalization for acute decompensated heart failure remains controversial. Methods: We reviewed the medical literature on the association of WRF during acute decompensated heart failure with clinical outcomes. Results: WRF is reported in approximately 25% to 40% of acute decompensated heart failure patients. WRF is usually, but not always associated with worse outcomes in patients with heart failure. Transient WRF accompanied with hemoconcentration, effective decongestion strategies, and initiation of appropriate medical treatment for heart failure with angiotensin-converting enzyme inhibitors or mineralocorticoid receptor antagonists is not associated with worse outcomes. Conclusions: Multiple mechanisms may contribute to WRF in acute decompensated heart failure, and prognosis will differ according to etiology, patient features, and treatment strategies. During hospitalization, treatment should focus on the patient's clinical status, resolution of symptoms and signs of congestion rather than temporary changes in renal function.

Contemporary Prescription Patterns of Adenosine Diphosphate Receptor Inhibitors in Acute Coronary Syndrome.

PURPOSE: To assess the contemporary use of adenosine diphosphate (ADP) receptor inhibitors in acute coronary syndrome at a large, quaternary academic medical center. METHODS: 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. RESULTS: 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 (P < 0.01), 75 years of age or older (P < 0.01), and 60 kg or less in weight (P = 0.02), and they had more comorbidities. Of the patients on clopidogrel prior to admission, 21% were switched to prasugrel or ticagrelor for inadequate platelet inhibition, restenosis, or new stent placement. Of the patients on ticagrelor or prasugrel prior to admission, 17% were switched to clopidogrel for concerns about bleeding or cost. Clopidogrel was prescribed 13% of the time, prasugrel 13% of the time, and ticagrelor 4% of the time (P = 0.13) outside the recommended use per Food and Drug Administration-approved prescribing information based on relative or absolute contraindications. CONCLUSION: Clopidogrel continues to be the most commonly prescribed antiplatelet agent, particularly in older patients with more comorbidities.

Impact of Elevated Gradients After Transcatheter Aortic Valve Implantation for Degenerated Surgical Aortic Valve Bioprostheses.

BACKGROUND: Elevated aortic valve gradients are common after transcatheter aortic valve implantation for degenerated surgical aortic valve replacement bioprostheses, but their clinical impact is uncertain. METHODS: A total of 12 122 patients who underwent transcatheter aortic valve implantation-in-surgical aortic valve replacement from November 2011 to December 2019 in the Society of Thoracic Surgery/American College of Cardiology Transvalvular Therapeutics Registry were included. The primary outcome was a composite of 1-year all-cause mortality, stroke, myocardial infarction, or valve reintervention. Secondary outcomes included 1-year all-cause mortality, readmission, and change from baseline 12-question self-administered Kansas City Cardiomyopathy Questionnaire-Overall Summary Score. Due to nonlinearity observed with restricted cubic splines analysis, a Cox regression analysis with aortic valve mean gradient modeled as a spline-continuous variable (with 20 mm Hg as a cutoff) was used to study the 1-year composite outcome and mortality. RESULTS: The composite outcome occurred most frequently in patients with aortic valve mean gradient ≥30 and <10 mm Hg, as compared with those with 10 to 20 and 20 to 30 mm Hg ranges (unadjusted rates, 13.9%, 12.1%, 7.5%, and 6.5%, respectively; P=0.002). When the mean aortic valve gradient was ≥20 mm Hg, higher gradients were associated with greater risk of the 1-year composite outcome (adjusted hazard ratio, 1.02 [1.02-1.03] per mm Hg; P<0.001) and 1-year mortality (adjusted hazard ratio, 1.02 [1.00-1.03] per mm Hg; P=0.007). Whereas when the mean aortic valve gradient was <20 mm Hg, higher gradients were not significantly associated with the composite outcome (adjusted hazard ratio, 0.99 [0.98-1.003] per mm Hg; P=0.12) but were associated with lower 1-year mortality (adjusted hazard ratio, 0.98 [0.97-0.99] per mm Hg; P=0.007). CONCLUSIONS: The relationship between postprocedural aortic valve mean gradient after transcatheter aortic valve implantation-in-surgical aortic valve replacement and clinical outcomes is complex and nonlinear, with relatively greater adverse events occurring at low and high gradient extremes. Further study of factors mediating the relationship between postprocedural gradients and clinical outcomes, including low-flow states, is necessary.

Innovations in atrial fibrillation ablation.

BACKGROUND: Catheter-based ablation to perform pulmonary vein isolation (PVI) has established itself as a mainstay in the rhythm control strategy of atrial fibrillation. This review article aims to provide an overview of recent advances in atrial fibrillation ablation technology. METHODS: We reviewed the available literature and clinical trials of innovations in atrial fibrillation ablation technologies including ablation catheter designs, alternative energy sources, esophageal protection methods, electroanatomical mapping, and novel ablation targets. RESULTS: Innovative radiofrequency (RF) catheter designs maximize energy delivery while avoiding overheating associated with conventional catheters. Single-shot balloon catheters in the form of cryoballoons, radiofrequency, and laser balloons have proven effective at producing pulmonary vein isolation and improving procedural efficiency and reproducibility. Pulsed field ablation (PFA) is a highly anticipated novel nonthermal energy source under development, which demonstrates selective ablation of the myocardium, producing durable lesions while also minimizing collateral damage. Innovative devices for esophageal protection including esophageal deviation and cooling devices have been developed to reduce esophageal complications. Improved electroanatomical mapping systems are being developed to help identify additional non-pulmonary triggers, which may benefit from ablation, especially with persistent atrial fibrillation. Lastly, the vein of Marshall alcohol ablation has been recently studied as an adjunct therapy for improving outcomes with catheter ablation for persistent atrial fibrillation. CONCLUSIONS: Numerous advances have been made in the field of atrial fibrillation ablation in the past decade. While further long-term data is still needed for these novel technologies, they show potential to improve procedural efficacy and safety.

Catheter-Based Management of Heart Failure: Pathophysiology and Contemporary Data.

Device therapy for severe heart failure (HF) has shown efficacy both in 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 nonsurgical 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 ambulatory management of HF. We review the current data on devices and investigational therapies for HF management whereby pharmacotherapy falls short.

Outcomes of Hospitalizations With Septic Shock Complicated by Types 1 and 2 Myocardial Infarction.

Septic shock is a life-threatening host response to infection and a significant contributor to cost burden in the United States. Furthermore, sepsis-related inflammation has been linked to myocardial infarction (MI). We sought to examine the association of type 1 and type 2 MI with outcomes in hospitalizations admitted with septic shock. The National Readmission Database 2018 was queried to identify hospitalizations with hospital discharge diagnoses of septic shock without MI, septic shock with type 1 MI, or septic shock with type 2 MI. Complex-sample multivariable logistic and linear regression models were used to determine the association of these conditions with clinical outcomes. Of 354,528 hospitalizations with septic shock, 11,519 had type 1 MI (3.2%) and 13,970 had type 2 MI (3.9%). Compared with septic shock without MI, type 1 MI was associated with higher mortality (adjusted odds ratio [OR] 1.67, 95% confidence interval [CI] 1.57 to 1.77), costs (adjusted parameter estimate $4,571, 95% CI 3,020 to 6,122), and discharge to facility (adjusted OR 1.09, 95% CI 1.01 to 1.17). In contrast, septic shock with type 2 MI was associated with similar mortality and discharge to nursing facility and higher costs (adjusted parameter estimate 1,798, 95% CI 549 to 3,047). Septic shock hospitalizations with type 1 MI had higher in-hospital mortality (adjusted OR 1.74, 95% CI 1.60 to 1.90, p <0.001) compared with type 2 MI. In conclusion, type 1 MI is associated with higher mortality and resource utilization among septic shock hospitalizations. Furthermore, type 2 MI was associated with higher resource utilization.

Outcomes and Resource Utilization in Patients Hospitalized with Gastrointestinal Bleeding Complicated by Types 1 and 2 Myocardial Infarction.

BACKGROUND: Types 1 and 2 myocardial infarction (MI) may occur in the setting of gastrointestinal bleeding (GIB). There is a paucity of data pertinent to the contemporary prevalence and impact of types 1 and 2 MI following GIB. We examined clinical profiles and the prognostic impact of both MI types on outcomes of patients hospitalized with GIB. METHODS: The 2018 Nationwide Readmission Database was queried for patients hospitalized for the primary diagnosis of GIB and had concomitant diagnoses of type 1 or type 2 MI. Baseline characteristics, in-hospital mortality, resource utilization, and 30-day all-cause readmissions were compared among groups. RESULTS: Of 381,867 primary GIB hospitalizations, 2902 (0.75%) had type 1 MI and 3963 (1.0%) had type 2 MI. GIB patients with type 1 and type 2 MI had significantly higher in-hospital mortality compared to their counterparts without MI (adjusted odds ratios [aOR]: 4.72, 95% confidence interval [CI] 3.43-6.48; and aOR: 2.17, 95% CI 1.48-3.16, respectively). Both types 1 and 2 MI were associated with higher rates of discharge to a nursing facility (aOR of type 1 vs. no MI: 1.65, 95% CI 1.45-1.89, and aOR of type 2 vs no MI: 1.37, 95% CI 1.22-1.54), longer length of stay, higher hospital costs, and more 30-day all-cause readmissions (aOR of type 1 vs no MI: 1.22, 95% CI 1.08-1.38; aOR of type 2 vs no MI: 1.17, 95% CI 1.05-1.30). CONCLUSION: Types 1 and 2 MI are associated with higher in-hospital mortality and resource utilization among patients hospitalized with GIB in the United States.

Pericardial Access Through the Right Atrium in a Porcine Model.

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.

Advancing pediatric medical device development via non-dilutive NIH SBIR/STTR grant funding.

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.

Patient Characteristics and Outcomes of Type 2 Myocardial Infarction During Heart Failure Hospitalizations in the United States.

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.

Peptide-conjugated pterins as inhibitors of ricin toxin A.

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.

Optimized 5-membered heterocycle-linked pterins for the inhibition of Ricin Toxin A.

The optimization of a series of pterin amides for use as Ricin Toxin A (RTA) inhibitors is reported. Based upon crystallographic data of a previous furan-linked pterin, various expanded furans were synthesized, linked to the pterin and tested for inhibition. Concurrently, hetero-analogs of furan were explored, leading to the discovery of more potent triazol-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.