Disparity in the Under-Utilization of Novel P2Y12 Inhibitors in ST-Elevation Myocardial Infarction Following Percutaneous Coronary Intervention.

Background: The most recent guidelines (European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association (ACC/AHA)) all favor prasugrel/ticagrelor over clopidogrel in the setting of acute coronary syndrome (ACS). We therefore sought to investigate which P2Y12 inhibitors were being prescribed in our community hospital setting upon discharge among patients undergoing percutaneous coronary intervention (PCI) in the setting of ST-elevation myocardial infarction (STEMI). Methods: We identified patients presenting to two Metro Detroit Michigan hospitals with STEMI between January 1, 2018, to December 31, 2021 using the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2) PCI registry. The primary outcome was the choice of P2Y12 inhibitor prescribed on day of discharge following hospitalization for STEMI, and baseline characteristics were compared including race, sex and type of insurance. Results: A total of 366 patients presented to these two Metro Detroit hospitals from January 1, 2018, to December 31, 2021. Female and non-White patients were more likely to be discharged on clopidogrel than ticagrelor or prasugrel (odds ratio (OR): 1.56, confidence interval (CI): 0.99 - 2.45, and OR: 1.43, CI: 0.91 - 2.25, respectively), however, did not reach statistical significance. Patients without private insurance presenting with STEMI were more likely to be discharged on clopidogrel (OR: 1.83, CI: 1.22 - 2.74), which did reach statistical significance in our cohort. Conclusions: In this retrospective single-center study evaluating BMC2 registry, we demonstrate a clinically significant disparity in prescribing patterns based on insurance, with trends for disparity based on gender and ethnicity.

Renovascular Hypertension with Progressive Atherosclerotic Renal Artery Stenosis in an Elderly Patient with Known Fibromuscular Dysplasia: A Case Report.

BACKGROUND Atherosclerotic renal artery stenosis (ARAS) and renovascular fibromuscular dysplasia (FMD) are 2 of the most common etiologies of renovascular hypertension. They have different pathophysiologies, risk factors, presentations, and treatment options. However, as our population ages, it can become increasingly common to see patients who previously had FMD who develop ARAS at an advanced age, indicated by recurrent renovascular hypertension. CASE REPORT We present a case of a 66-year-old female patient who, in 2007, had presented with uncontrolled hypertension. She underwent magnetic resonance angiography and was found to have bilateral FMD, for which she received balloon angioplasty to a severe lesion on the mid-right renal artery and subsequently had normalization of blood pressures and resolution of symptoms. In 2021 she returned with uncontrolled hypertension while being treated with 3 antihypertensives. Bilateral renal arteriography revealed new severe ostial stenosis of the left renal artery and a patent right renal artery in which balloon angioplasty was performed 14 years ago. Based on the angiographic pattern of this new left RAS, we concluded this lesion was caused by atherosclerosis. The left ostial lesion was treated with a bare-metal stent and the patient was continued on antihypertensive medication and statin; at follow-up 4 months later, her blood pressures had normalized. CONCLUSIONS This case features a patient who developed severe ARAS with underlying history of bilateral renal artery FMD. Clinicians need to be aware that in patients with FMD, worsening renovascular hypertension at an advanced age could indicate the development of new hemodynamically significant ARAS. These patients need repeat diagnostic testing and treatment with medial optimization with or without endovascular revascularization in the appropriate clinical setting.

Burnout of Support Personnel in the Cardiac Catheterization Laboratory.

Background: Healthcare professionals experience stressors in the workplace, putting them at elevated risk for burnout. The cardiac catheterization lab is a dynamic environment with high-acuity patients; however, little has been published investigating burnout syndrome among healthcare workers. The aim of the study was to identify the prevalence, demographic, and workload factors, which contribute to burnout syndrome among this population. Methods: This is a multicenter cross-sectional study assessing burnout with the Maslach Burnout Inventory (MBI) among registered nurses and registered cardiac invasive specialists working in the catheterization/electrophysiology lab and cardiac observation unit at four hospital centers in the metro Detroit area. Results: Of the 48 participants, 69% (n = 33) were female. The overall prevalence of burnout syndrome was 33% (n = 16). Significantly more males experienced burnout than females (P < 0.05). Of the participants experiencing burnout, a greater proportion worked in the catheterization lab compared to the cardiac observation unit (93.8% vs. 6.3%). Burned-out participants worked on average more day shifts, ST-segment elevation myocardial infarction (STEMI) call shifts, and extended day shifts per month compared to those not experiencing burnout. The rate of burnout was significantly higher for individuals reporting increased stress during the pandemic (69% vs. 18%, P < 0.05). Conclusions: Registered nurses and registered cardiac invasive specialists working in the cardiac catheterization or electrophysiology lab experience elevated levels of burnout. Greater attention should be placed in identifying and optimizing workplace variables which contribute to burnout among this population.

The Relationship Between Coronary Dominance and Positive Results in Myocardial Perfusion Imaging.

Objective Our study aims to evaluate the possible relationship between coronary artery dominance and its effect on accurately identifying reversible ischemia of inferior/inferior-lateral wall on cardiac perfusion imaging. Background Coronary artery dominance is conventionally defined by the vessel which gives the rise to the AV nodal artery/posterior descending artery (PDA). Previous studies have explored the potential effect of coronary dominance on the accuracy of single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) tests in detecting inferior/inferior-lateral wall ischemia; further evidence is necessary to study that potential effect. Methods We conducted a single-center retrospective analysis to explore the potential relationship between coronary artery dominance and inferior/inferior-lateral wall ischemia on SPECT imaging. We identified a cohort of patients with a reversible defect(s) in the inferior and/or inferolateral walls on SPECT MPI who had subsequently undergone invasive coronary angiography. Coronary angiography was used to determine coronary dominance and to confirm the presence/absence of obstructive coronary artery disease in the distribution of the inferior and/or inferolateral wall(s). We correlated the findings on SPECT MPI to coronary angiography to identify true positives and false positive MPIs. Results A cohort of 200 patients was identified, patients in the cohort had undergone stress MPI with reversible defects with subsequent invasive coronary angiography. Baseline characteristics including age, BMI and sex were fairly well-balanced between the groups. The mean age was 68 +/- 11 in the right dominant group and 70 +/- 9 in the non right dominant group. One hundred and sixty-one patients (81%) were found to have right dominant circulation and 39 patients (19%) were found to have left or codominant circulation. Of the 161 patients in the right dominant group, 58 patients (36%) were found to have false positive stress MPI. Of the 39 patients in the left or codominant group, 23 patients (59%) were found to have false positive stress MPI. The incidence of false positive stress MPI in the inferior and inferolateral distribution is significantly higher in patients with non-right dominant coronary anatomy (p-value: 0.01). Conclusion Non-right coronary dominant anatomy could have high false positive MPI results in the inferior and inferolateral distribution. Therefore, the interpreting clinicians should exercise caution during the clinical evaluation of these patients.

Extraordinary Creatine Phosphokinase Levels in Coxsackie B Necrotizing Myopathy Complicated by Rhabdomyolysis.

Coxsackie B infections can have varying clinical presentations. Necrotizing myopathy and rhabdomyolysis with remarkably high creatine phosphokinase levels is a rare complication associated with high morbidity and mortality. A 28-year-old male presented with complaints of weakness, body aches, and decreased urine output. Initial lab work showed a creatine phosphokinase level estimated at 5,366,100 U/l. Initial Coxsackie B4 titers were at 1:160. Muscle biopsy of the right calf revealed necrotizing myopathy consistent with viral myopathy. This case highlights Coxsackie B4 as a potential pathogen that can cause extensive muscle necrosis producing extreme creatine phosphokinase levels leading to rhabdomyolysis. Taking a comprehensive history is essential to identify viral prodromal symptoms to guide broader serological testing for uncommon viral species.

Isolated Sub-Pulmonic Valve Endocarditis in a Patient With a History of Konno Procedure and Mechanical Aortic Valve.

Pulmonic and sub-pulmonic valve endocarditis are rarely encountered in clinical practice. We present the first case of isolated sub-pulmonic endocarditis. A 30-year-old man with a history of mechanical aortic valve presented to the emergency department with multiple complaints including nausea, vomiting, body aches, and fevers. The patient underwent surgical resection for sub-aortic stenosis followed by a modified Konno procedure later in life. A modified basal short-axis view on the trans-thoracic echocardiogram revealed a sub-pulmonic mobile structure highly suggestive of infective endocarditis. Blood cultures grew methicillin-sensitive Staphylococcus aureus within 24 hours. Higher oxygen demand prompted chest imaging, chest CT showed the development of bilateral airspace consolidation, suggestive of pneumonia. After treatment with extended intravenous antibiotics, follow-up echocardiogram four months later showed no identifiable sub-pulmonic vegetation. This case describes a situation where clinicians may suspect infective endocarditis in a typical location such as a mechanical aortic valve. However, in patients who develop pneumonia, infective endocarditis of the right heart should be suspected. The pulmonic valve and sub-pulmonic ridge are often difficult to image given their anatomical location, a modified basal short-axis view on trans-thoracic echocardiogram can better image these structures.

Protein production is an early biomarker for RNA-targeted therapies.

OBJECTIVES: Clinical trials for progressive neurodegenerative disorders such as Alzheimer's Disease and Amyotrophic Lateral Sclerosis have been hindered due to the absence of effective pharmacodynamics markers to assay target engagement. We tested whether measurements of new protein production would be a viable pharmacodynamics tool for RNA-targeted therapies. METHODS: Transgenic animal models expressing human proteins implicated in neurodegenerative disorders - microtubule-associated protein tau (hTau) or superoxide dismutase-1 (hSOD1) - were treated with antisense oligonucleotides (ASOs) delivered to the central nervous system to target these human mRNA transcripts. Simultaneously, animals were administered 13C6-leucine via drinking water to measure new protein synthesis after ASO treatment. Measures of new protein synthesis and protein concentration were assayed at designated time points after ASO treatment using targeted proteomics. RESULTS: ASO treatment lowered hTau mRNA and protein production (measured by 13C6-leucine-labeled hTau protein) earlier than total hTau protein concentration in transgenic mouse cortex. In the CSF of hSOD1 transgenic rats, ASO treatment lowered newly generated hSOD1 protein driven by decreases in newly synthesized hSOD1 protein, not overall protein concentration, 30 days after treatment. At later time points, decreases in newly generated protein were still observed after mRNA lowering reached a steady state after ASO treatment. INTERPRETATION: Measures of newly generated protein show earlier pharmacodynamics changes for RNA-lowering therapeutics compared with total protein concentration. Early in ASO treatment, decreases in newly generated protein are driven by changes in newly synthesized protein. Measuring new protein production in CSF may be a promising early pharmacodynamics marker for RNA-targeted therapeutics.

Trimerization Dictates Solution Opalescence of a Monoclonal Antibody.

Opalescence, sometimes observed in antibody solutions, is thought to be mediated by light scattering of soluble oligomers or insoluble particulates. However, mechanistic features, such as stoichiometry and self-association affinity of oligomeric species related to opalescence, are poorly understood. Here, opalescence behavior of a monoclonal antibody (mAb-1) solution was studied over a wide range of solution conditions including different protein concentrations, pH, and in the presence or absence of salt. Hydrodynamic and thermodynamic properties of mAb-1 solutions were studied by analytical ultracentrifugation and dynamic light scattering. Opalescence in mAb-1 solutions is pH and concentration dependent. The degree of opalescence correlates with reversible monomer-trimer equilibrium detected by analytical ultracentrifugation. Increased trimer formation corresponds to increased opalescence in mAb-1 solutions at higher pH and protein concentrations. Addition of NaCl shifts this equilibrium toward monomer and reduces solution opalescence. This study demonstrates that opalescence in mAb-1 solutions does not arise from the light scattering of monomer or random molecular self-associations but is strongly correlated with a specific self-association stoichiometry and affinity. Importantly, at pH 5.5 (far below isoelectric point of mAb-1), the solution is not opalescent and with nonideal behavior. This study also dissects several parameters to describe the hydrodynamic and thermodynamic nonideality.