Approach to Imaging Ischemia in Women.

Approach to imaging ischemia in women Coronary artery disease in women tends to have a worse short- and long-term prognosis relative to men and remains the leading cause of mortality worldwide. Both clinical symptoms and diagnostic approach remain challenging in women due to lesser likelihood of women presenting with classic anginal symptoms on one hand and underperformance of conventional exercise treadmill testing in women on the other. Moreover, a higher proportion of women with signs and symptoms suggestive of ischemia are more likely to have nonobstructive coronary artery disease (CAD) that requires additional imaging and therapeutic considerations. New imaging techniques such as coronary computed tomography (CT) angiography, CT myocardial perfusion imaging, CT functional flow reserve assessment, and cardiac magnetic resonance imaging carry substantially better sensitivity and specificity for the detection of ischemia and coronary artery disease in women. Familiarity with various clinical subtypes of ischemic heart disease in women and with the major advantages and disadvantages of advanced imaging tests to ensure the decision to select one modality over another is one of the keys to successful diagnosis of CAD in women. This review compares the 2 major types of ischemic heart disease in women - obstructive and nonobstructive, while focusing on sex-specific elements of its pathophysiology.

Uhl's Anomaly With Left Ventricular Noncompaction: Role of Multimodality Imaging in a Rare Association.

Uhl's anomaly is a rare congenital heart disease characterized by partial or complete absence of the right ventricle myocardium. We report the first case, in a 21-year-old man, of Uhl's anomaly-associated left ventricular noncompaction. This association represents a unique clinical entity and has important implications for management strategies. (Level of Difficulty: Intermediate.).

Torsades de Pointes due to Excessive Marijuana Use in a Susceptible Patient.

There are several recent reports of tetrahydrocannabinol vaping-related sudden cardiac arrest, and the mechanisms are unclear. We report a unique case of a 19-year-old female who suffered documented prolonged QTc leading to Torsades de pointes and cardiac arrest in the setting of frequent marijuana wax vaping. While she demonstrated normal baseline QTc measurements years earlier, she was found to have a genetic predisposition to QTc prolongation (genetic mutation, family history of prolonged QTc), suggesting that specific patient populations are at higher risk of these adverse events. The patient was acutely managed with isoproterenol to increase the heart rate and was discharged on nadolol after placement of an implantable cardioverter-defibrillator. Marijuana wax vaping and dabbing may cause fatal Torsades de pointes in susceptible patients, and further research is required to identify these patients a priori.

Trial of Oral Diuretics Prior to Discharge Is Not Associated With Improved Outcomes in Decompensated Heart Failure.

BACKGROUND: Current heart failure guidelines recommend transition of intravenous (IV) diuretics to oral > 24 h prior to hospital discharge. The aim of this study was to determine whether transition to oral diuretics prior to discharge in patients hospitalized with decompensated systolic heart failure (SHF) was associated with improved 30-day events. METHODS: This was a retrospective cohort study, in which adults admitted to the Loma Linda Medical Center for 3 - 14 days with a primary discharge diagnosis of acute on chronic SHF were included. Mortality data were obtained from the National Death Index, while readmission only to our facility was included. The t-test and Chi-square test were used for analyses. RESULTS: A total of 314 patients were studied. Patients who were managed with guideline-recommended trial of oral diuretics, and patients who continued to receive IV diuretics on the last full hospital day were overall similar in baseline characteristics. Patients who received oral diuretics on the day prior to discharge had longer length of stay, less weight loss, were discharged on lower diuretic doses (all P < 0.05), and had similar outcomes of 30-day readmission and 30-day hospitalization-free survival. CONCLUSIONS: The transition to oral diuretics prior to discharge in patients with decompensated SHF was not associated with improved 30-day outcomes. These results require validation in prospective trials but suggest that guideline recommendations regarding transitioning to oral diuretics prior to discharge may deserve re-evaluation.

A Review of Inotropes and Inopressors for Effective Utilization in Patients With Acute Decompensated Heart Failure.

ABSTRACT: Inotropes and inopressors are often first-line treatment in patients with cardiogenic shock. We summarize the pharmacology, indications, and contraindications of dobutamine, milrinone, dopamine, norepinephrine, epinephrine, and levosimendan. We also review the data on the use of these medications for acute decompensated heart failure and cardiogenic shock in this article.

Diffuse coronary artery vasospasm in a patient with subarachnoid hemorrhage: A case report.

BACKGROUND: Coronary artery vasospasm (CAV) is a reversible, transient form of vasoconstriction with clinical manifestations ranging from stable angina to acute coronary syndromes (ACS). Vasospasm of epicardial coronary arteries or associated micro-vasculature can lead to total or subtotal occlusion and has been demonstrated in nearly 50% of patients undergoing angiography for suspected ACS. The mechanism for CAV has been described in literature, but in a subgroup of patients presenting with intracranial hemorrhage, it appears to be multifactorial. These patients tend to have electrocardiographic changes, elevation of cardiac biomarkers of injury and neurogenic stress cardiomyopathy. CASE SUMMARY: A 44-year-old woman presented with severe headaches and tonic-clonic seizures. She was found to have diffuse subarachnoid hemorrhage (SAH) requiring ventricular drain placement, coil embolization and induced hypertension. She subsequently developed chest pain with ST elevations in anterior precordial leads, elevated cardiac enzymes and apical ballooning with left ventricular ejection fraction of 35% on transthoracic echocardiogram. Coronary angiogram revealed severe diffuse triple vessel stenoses secondary to CAV seen distally. Subsequent cardiac MRI notable for apical non-viability and scar formation. CONCLUSION: This case highlights a unique etiology of acute myocardial infarction in a patient with SAH leading to ST elevations, diffuse triple vessel CAV and apical scar.

Protection of the Queuosine Biosynthesis Enzyme QueF from Irreversible Oxidation by a Conserved Intramolecular Disulfide.

QueF enzymes catalyze the nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of the nitrile group of 7-cyano-7-deazaguanine (preQ0) to 7-aminomethyl-7-deazaguanine (preQ1) in the biosynthetic pathway to the tRNA modified nucleoside queuosine. The QueF-catalyzed reaction includes formation of a covalent thioimide intermediate with a conserved active site cysteine that is prone to oxidation in vivo. Here, we report the crystal structure of a mutant of Bacillus subtilis QueF, which reveals an unanticipated intramolecular disulfide formed between the catalytic Cys55 and a conserved Cys99 located near the active site. This structure is more symmetric than the substrate-bound structure and exhibits major rearrangement of the loops responsible for substrate binding. Mutation of Cys99 to Ala/Ser does not compromise enzyme activity, indicating that the disulfide does not play a catalytic role. Peroxide-induced inactivation of the wild-type enzyme is reversible with thioredoxin, while such inactivation of the Cys99Ala/Ser mutants is irreversible, consistent with protection of Cys55 from irreversible oxidation by disulfide formation with Cys99. Conservation of the cysteine pair, and the reported in vivo interaction of QueF with the thioredoxin-like hydroperoxide reductase AhpC in Escherichia coli suggest that regulation by the thioredoxin disulfide-thiol exchange system may constitute a general mechanism for protection of QueF from oxidative stress in vivo.

Influenza polymerase encoding mRNAs utilize atypical mRNA nuclear export.

BACKGROUND: Influenza is a segmented negative strand RNA virus. Each RNA segment is encapsulated by influenza nucleoprotein and bound by the viral RNA dependent RNA polymerase (RdRP) to form viral ribonucleoproteins responsible for RNA synthesis in the nucleus of the host cell. Influenza transcription results in spliced mRNAs (M2 and NS2), intron-containing mRNAs (M1 and NS1), and intron-less mRNAs (HA, NA, NP, PB1, PB2, and PA), all of which undergo nuclear export into the cytoplasm for translation. Most cellular mRNA nuclear export is Nxf1-mediated, while select mRNAs utilize Crm1. METHODS: Here we inhibited Nxf1 and Crm1 nuclear export prior to infection with influenza A/Udorn/307/1972(H3N2) virus and analyzed influenza intron-less mRNAs using cellular fractionation and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We examined direct interaction between Nxf1 and influenza intron-less mRNAs using immuno purification of Nxf1 and RT-PCR of associated RNA. RESULTS: Inhibition of Nxf1 resulted in less influenza intron-less mRNA export into the cytoplasm for HA and NA influenza mRNAs in both human embryonic kidney cell line (293 T) and human lung adenocarcinoma epithelial cell line (A549). However, in 293 T cells no change was observed for mRNAs encoding the components of the viral ribonucleoproteins; NP, PA, PB1, and PB2, while in A549 cells, only PA, PB1, and PB2 mRNAs, encoding the RdRP, remained unaffected; NP mRNA was reduced in the cytoplasm. In A549 cells NP, NA, HA, mRNAs were found associated with Nxf1 but PA, PB1, and PB2 mRNAs were not. Crm1 inhibition also resulted in no significant difference in PA, PB1, and PB2 mRNA nuclear export. CONCLUSIONS: These results further confirm Nxf1-mediated nuclear export is functional during the influenza life cycle and hijacked for select influenza mRNA nuclear export. We reveal a cell type difference for Nxf1-mediated nuclear export of influenza NP mRNA, a reminder that cell type can influence molecular mechanisms. Importantly, we conclude that in both A549 and 293 T cells, PA, PB1, and PB2 mRNA nuclear export is Nxf1 and Crm1 independent. Our data support the hypothesis that PA, PB1, and PB2 mRNAs, encoding the influenza RdRP, utilize atypical mRNA nuclear export.