Post hoc assessment of the relationship among coronary stenosis, electrocardiography, and ventricular function in patients with heart disease.

Cardiovascular diseases including cardiac arrhythmias lead to fatal events in patients with coronary artery disease; however, clinical associations from echocardiography, electrocardiography (ECG), and biomarkers remain unknown. We sought to identify the factors that may be related to elevated QRS intervals in patients with risk for coronary artery disease. In this study, we performed analysis of clinical data from 503 patients divided into two groups, i.e., patients with either <50% coronary artery stenosis or >50% coronary artery stenosis. We further examined patients with elevated ECG parameters such as QRS > 100 ms and QTc > 440 ms. Patients with >50% coronary artery stenosis exhibited significant increases in age, triglycerides, and troponin levels. Further, ECG parameters demonstrated increased QRS and QTc durations, while echocardiographic parameters highlighted a decrease in ejection fraction (EF) and fractional shortening (FS). Patients with QTc > 440 ms exhibited increased brain natriuretic peptide and creatinine levels with a decrease in estimated glomerular filtration rate clearance rates. Patients with QRS > 100 ms had greater left ventricular (LV) mass and LV internal diameter in systole and diastole. Multimodal logistic regression showed significant relation between QTc, age, and creatinine. These findings suggest that patients with significant coronary stenosis may have lower EF and FS with prolonged QRS intervals, demonstrating greater risk for arrhythmic events.

Improving Access to Cardiovascular Care Through Telehealth: A Single-Center Experience.

Background: Historically, access to healthcare has been a serious shortcoming of our healthcare system. Approximately 14.5% of US adults lack readily available access to health care and this has been worsened by the coronavirus disease 2019 (COVID-19) pandemic. There are limited data on the use of telehealth in cardiology. We share our single-center experience in improving access to care via telehealth at the University of Florida, Jacksonville cardiology fellows' clinic. Methods: Demographic and social variables were collected 6 months before and 6 months after the initiation of telehealth services. The effect of telehealth was determined via Chi-square and multiple logistic regression while controlling for demographic covariates. Results: We analyzed 3,316 cardiac clinic appointments over 1 year. Of these, 1,569 and 1,747 were before and after the start of telehealth, respectively. Fifteen percent (272 clinical encounters) out of the 1,747 clinic visits during the post-telehealth era were through telehealth, completed via audio or video consultation. Overall, there was a 7.2 % increase in attendance after the implementation of telehealth (P value < 0.001). Patients who attended their scheduled follow-up had significantly greater odds of being in the post-telehealth group while controlling for marital status and insurance type (odds ratio (OR): 1.31, 95% confidence interval (CI): 1.07 - 1.62). Patients who attended had higher odds of having City-Contract insurance - an institution-specific indigenous care plan (OR: 3.51, 95% CI: 1.79 - 6.87) compared to private insurance. Patients who attended also had higher odds of being previously married (OR: 1.34, 95% CI: 1.05 - 1.70) or married/dating (OR: 1.39, 95% CI: 1.05 - 1.82) compared to patients who were single. Surprisingly, telehealth did not lead to an increase in the use of Mychart, our electronic patient portal (P value = 0.55). Conclusions: Telehealth enhanced patients' access to care by improving appointment show-rate in a cardiology fellows' clinic during the COVID-19 pandemic. Telehealth as a resource adjunct to traditional care in cardiology fellows' clinic should be further explored.

Cardiac Amyloidosis Presenting as Biventricular Systolic Heart Failure.

A previously healthy octogenarian presented with new onset heart failure symptoms. Comprehensive multimodality imaging including complete echocardiography with longitudinal strain analysis, cardiac magnetic resonance imaging (cMRI), nuclear medicine pyrophosphate (99-mcTcPYP) scan along with biomarker, monoclonal protein analysis, and fat pad biopsy confirmed diagnosis of transthyretin cardiac amyloidosis.

Myocardial Bridging Unmasks as an Acute Coronary Syndrome from Dehydration.

A 50-year-old male presented for loss of consciousness. He was initially treated with intravenous epinephrine and fluids, and an electrocardiogram (ECG) displayed an ST-segment elevation in lead aVR with global ST-segment depressions. A subsequent left heart catheterization revealed that the middle segment of the left anterior descending artery (LAD) demonstrated severe stenosis during systole but would become patent during diastole, which was suggestive of myocardial bridging. After stopping the epinephrine and increasing the fluid infusion, the ECG changes rapidly resolved. The patient had later admitted to significant dehydration all day. Myocardial bridging is a congenital anomaly in which a coronary artery segment courses through the myocardium instead of the usual epicardial surface. Occasionally, myocardial bridging may present similarly to acute coronary syndrome in severe dehydration or hyperadrenergic states. The diagnosis can be made through coronary angiography, which reveals a dynamic vessel obstruction pattern corresponding with the cardiac cycle. Long-term effects may also include accelerated atherosclerosis. Treatment consists of reversing precipitating causes during acute presentations and decreasing the risk of coronary artery disease on a chronic basis.

Cardiac papillary fibroelastoma.

Papillary fibroelastoma (PFE) is a primary, histologically benign endocardial neoplasm. Though PFE has long been reported as the second most common primary cardiac neoplasm, it has since pulled ahead of cardiac myxomas, largely due to evolving cardiac imaging modalities. While PFEs are benign histologically, they have the potential for devastating clinical consequences, transient ischemic attack, stroke, myocardial infarction, syncope, pulmonary, and peripheral embolism. Despite increased detection rate, there remains uncertainty regarding etiology, exact prevalence, and clinical management of PFEs. This paucity of information is reflected by the lack of official guidelines on this matter. In this article, we aim to summarize the current state of understanding regarding PFE and discuss areas of ongoing controversy.

Efavirenz promotes ß-secretase expression and increased Aß1-40,42 via oxidative stress and reduced microglial phagocytosis: implications for HIV associated neurocognitive disorders (HAND).

Efavirenz (EFV) is among the most commonly used antiretroviral drugs globally, causes neurological symptoms that interfere with adherence and reduce tolerability, and may have central nervous system (CNS) effects that contribute in part to HIV associated neurocognitive disorders (HAND) in patients on combination antiretroviral therapy (cART). Thus we evaluated a commonly used EFV containing regimen: EFV/zidovudine (AZT)/lamivudine (3TC) in murine N2a cells transfected with the human "Swedish" mutant form of amyloid precursor protein (SweAPP N2a cells) to assess for promotion of amyloid-beta (Aß) production. Treatment with EFV or the EFV containing regimen generated significantly increased soluble amyloid beta (Aß), and promoted increased ß-secretase-1 (BACE-1) expression while 3TC, AZT, or, vehicle control did not significantly alter these endpoints. Further, EFV or the EFV containing regimen promoted significantly more mitochondrial stress in SweAPP N2a cells as compared to 3TC, AZT, or vehicle control. We next tested the EFV containing regimen in Aß - producing Tg2576 mice combined or singly using clinically relevant doses. EFV or the EFV containing regimen promoted significantly more BACE-1 expression and soluble Aß generation while 3TC, AZT, or vehicle control did not. Finally, microglial Aß phagocytosis was significantly reduced by EFV or the EFV containing regimen but not by AZT, 3TC, or vehicle control alone. These data suggest the majority of Aß promoting effects of this cART regimen are dependent upon EFV as it promotes both increased production, and decreased clearance of Aß peptide.

HIV-1 Tat-induced microglial activation and neuronal damage is inhibited via CD45 modulation: A potential new treatment target for HAND.

Microglia become activated in humans subsequent to infection with HIV, and uncontrolled brain inflammation plays a key role in neuronal injury and and cognitive dysfunction during HIV infection. Various studies have shown a deleterious role for the HIV regulatory protein Tat in the development and maintenance of HIV-associated neurocognitive disorders (HAND). One cell surface receptor implicated in inhibiting microglial activation is the protein-tyrosine phosphatase (PTP), CD45. It is especially effective at inhibiting microglial activation because its action takes place far upstream from proinflammatory intracellular signaling mediators. To investigate the possible role of CD45 in microglial responsiveness to HIV-1 Tat protein, we treated BV-2 microglia with a tyrosine phosphatase inhibitor [potassium bisperoxo (1, 10-phenanthroline) oxovanadate (phen), 5 µM] and HIV-1 Tat protein (700ng/ml). We found a synergistic pro-inflammatory microglial activation as supported by tumor necrosis factor-alpha (TNF-α) and interleukin 1-beta (IL-1ß) release, both of which were dependent on p44/42 mitogen-activated protein kinase (MAPK) activation. Stimulation of microglial CD45 by anti-CD45 antibody markedly inhibited these Tat or Tat/Phen effects via attenuation of p44/42 MAPK, suggesting CD45 negatively regulates microglial activation. As a validation of these findings in vivo, brains from transgenic mice deficient for CD45 through complete genetic ablation, or by CNS delivery of CD45shRNA, demonstrate markedly increased production of TNF-α 24 hours after intracerebroventricular injection of HIV-Tat protein (5µg/mouse) compared to control mice. This increased microglial activation was accompanied by astrogliosis and a significant loss of cortical neurons due to apoptosis in CD45 deficient animals. These results suggest therapeutic agents that activate CD45 PTP signaling may be effective in suppressing microglial activation associated with HAND.

EVALUATION OF HOW CIGARETTE SMOKE IS A DIRECT RISK FACTOR FOR ALZHEIMER'S DISEASE.

Cigarette smoking is a risk for Alzheimer's disease (AD), the pathological hallmark of which is amyloid-ß (Aß) brain deposits. We found the adjusted risk of AD was significantly increased among medium level smokers (RR = 2.56; 95% CI = 1.65-5.52), with an even higher risk in the heavy smoking group (RR = 3.03; 95% CI = 1.25-4.02). This systematic review and original data further support this association. We searched Pubmed, Google scholar, and PsyINFO for original population study articles, meta-analyses, and reviews published between 1987 and 2011. Some studies were excluded due to design flaws including survivor bias. We performed analyses of: 1) amyloid precursor protein (APP) processing in N2a cells overexpressing Swedish mutant APP (SweAPP N2a) exposed to cigarette smoke condensate (CSC), 2) microglial inflammatory response to CSC, and 3) CSC exposed microglial phagocytosis of Aß(1-42). CSC significantly promotes neuronal Aß generation, increases microglial IL-1ß and TNF-α production, and decreases microglial Aß(1-42) phagocytosis. The mechanism underlying the epidemiological association of cigarette smoking with AD might involve the effect of cigarette smoke on APP processing, a reduction of Aß clearance by microglia, and/or an increased microglial proinflammatory response. In vivo studies are required to fully elucidate how cigarette smoke promotes AD.

Flipping the switches: CD40 and CD45 modulation of microglial activation states in HIV associated dementia (HAD).

Microglial dysfunction is associated with the pathogenesis and progression of a number of neurodegenerative disorders including HIV associated dementia (HAD). HIV promotion of an M1 antigen presenting cell (APC) - like microglial phenotype, through the promotion of CD40 activity, may impair endogenous mechanisms important for amyloid- beta (Aß) protein clearance. Further, a chronic pro-inflammatory cycle is established in this manner. CD45 is a protein tyrosine phosphatase receptor which negatively regulates CD40L-CD40-induced microglial M1 activation; an effect leading to the promotion of an M2 phenotype better suited to phagocytose and clear Aß. Moreover, this CD45 mediated activation state appears to dampen harmful cytokine production. As such, this property of microglial CD45 as a regulatory "off switch" for a CD40-promoted M1, APC-type microglia activation phenotype may represent a critical therapeutic target for the prevention and treatment of neurodegeneration, as well as microglial dysfunction, found in patients with HAD.