Depressed Ejection Fraction Does Not Affect Perioperative Mortality After Thoracic Endovascular Aortic Repair for Type B Aortic Dissection.

BACKGROUND: Despite the expanded application of thoracic endovascular aortic repair (TEVAR) in patients with significant cardiac comorbidities, the effect of decreased left ventricular ejection fraction (EF) on outcomes remains unknown. The aim of this study was to compare outcomes in patients with normal and abnormal EFs undergoing TEVAR for type-B aortic dissection (TBAD). METHODS: The Vascular Quality Initiative database was reviewed from 2012 to 2020. Patients were categorized into severely reduced (EF ≤ 30%), reduced (EF 30-50%) and normal EF (EF>50%). Baseline characteristics, procedural details and 18-month outcomes were compared. Multivariable logistic regression identified factors associated with mortality, major adverse cardiac events (MACEs), and aortic-related reintervention. RESULTS: Of 1,993 patients, 38 (2%) and 208 (10%) patients had severely reduced ejection fraction (SREF) and reduced ejection fraction (REF). Patients with abnormal EF were more likely to have cardiac comorbidities and be prescribed angiotensin-converting enzyme inhibitors and anticoagulants. Perioperatively, patients with SREF were more likely to experience mortality (13.2% vs. 6.7% vs. 4.4%, P = 0.018), MACE (26.3% vs. 11.5% vs. 8%, P < 0.001), hemodialysis (13.5% vs. 5% vs. 2.9%, P = 0.001) and aortic related reintervention (21.1% vs. 13% vs. 10%, P = 0.041), compared to REF and normal ejection fraction (NEF) patients. However, these associations were not present on multivariable analysis. At 18 months, mortality was significantly higher in patients with SREF, which was confirmed on multivariable analysis, but depressed EF was not associated with increased aortic reintervention compared to NEF. CONCLUSIONS: SREF was not independently associated with perioperative mortality or MACE compared to NEF. REF had similar risk of morbidity and mortality compared to NEF in both the perioperative and early postoperative periods. TEVAR-related complications were similar among the cohorts. As such, TEVAR may be offered to appropriately selected patients regardless of EF.

Impact of a Persistent Pelvic Pain Clinic: Emergency attendances following multidisciplinary management of persistent pelvic pain.

Persistent pelvic pain (PPP) is an important cause of psychological distress and productivity loss in women. In 2017, a multidisciplinary clinic was established to care for Queensland women with PPP. By analysing clinic and emergency department data, we found 19% fewer patients required any presentation to the emergency department for exacerbations of pelvic pain (P = 0.003) within 12 months of clinic attendance. There was also a reduction in number of presentations, short stay admissions and daily opiate use in regular users. The Persistent Pelvic Pain Clinic (PPPC) made a difference to these women and reduced resource burden on a busy emergency department.

A case of nonvalvular endocarditis with biventricular apical infected thrombi.

We report what appears to be the first case of biopsy-proven nonvalvular endocarditis with biventricular apical infected thrombi. A 47-year-old man presented with hypoxic respiratory failure from a multilobar pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA). Transthoracic echocardiography and cardiac magnetic resonance imaging revealed biventricular apical masses suggestive of nonvalvular endocarditis with infected thrombi. Given concern for ongoing septic embolization to the lungs and brain despite appropriate antimicrobial therapy, the masses were surgically resected. Culture and histopathology confirmed MRSA-positive infected thrombi. In this case report, we highlight the differential diagnosis of apical masses and the role of multimodality imaging.

Predicting the duration of induction of labour in nulliparous women.

This study examined if the modified Bishops score (MBS) at the start of an induction of labour (IOL) (VE-1) or if the MBS after pharmacological/mechanical ripening (VE-2) was the better predictor of the duration of induced labour and whether there was one component of the score that was most predictive of time to delivery.The measures at VE-2 were correlated more strongly with the time to birth, than VE-1 measures. At both VE-1 and VE-2, component measures (especially position of the cervix) showed weak correlation compared to composite measures. Omitting position from the composite score resulted in a simplified modified Bishops score (sMBS) that had the highest correlation coefficients. A model comprising sMBS and 5 clinical variables explained ∼73% of the variance.The vaginal examination findings prior to an IOL do not impact how long the labour may take. A more favourable cervix ∼12 h later (measured using a 4-item composite of dilatation, length, consistency and station) predicts a quicker induced labour.Impact statementWhat is already known? Induction of labour (IOL) is a common obstetric intervention in Australia. The IOL process can be a protracted and sometimes frustrating experience for women, and it may not result in a vaginal birth. A 'failed induction' or 'failure to progress' are relatively common indications for caesarean section (CS) in this setting where, despite many hours of an oxytocin infusion, the woman does not establish or progress in the active phase of labour.What does this study add? The measures at VE-2 were correlated more strongly with the time to birth, than VE-1 measures. At both VE-1 and VE-2, component measures (especially position of the cervix) showed weak correlation compared to composite measures. Omitting position from the composite score resulted in a simplified modified Bishops score (sMBS) that had the highest correlation coefficients. A model comprising sMBS and 5 clinical variables explained ∼73% of the variance.What are the implications of these findings? It is not the initial VE that is most predictive of the duration of labour but rather the VE after cervical ripening (mechanical or pharmacological). Simplified MBS (without the component of position of cervix) is most predictive of labour duration.

Sex differences in the prognostic value of troponin and D-dimer in COVID-19 illness.

BACKGROUND: Male sex, elevated troponin levels, and elevated D-dimer levels are associated with more complicated COVID-19 illness and greater mortality; however, while there are known sex differences in the prognostic value of troponin and D-dimer in other disease states, it is unknown whether they exist in the setting of COVID-19. OBJECTIVE: We assessed whether sex modified the relationship between troponin, D-dimer, and severe COVID-19 illness (defined as mechanical ventilation, ICU admission or transfer, discharge to hospice, or death). METHODS: We conducted a retrospective cohort study of patients hospitalized with COVID-19 at a large, academic health system. We used multivariable regression to assess associations between sex, troponin, D-dimer, and severe COVID-19 illness, adjusting for demographic, clinical, and laboratory covariates. To test whether sex modified the relationship between severe COVID-19 illness and troponin or D-dimer, models with interaction terms were utilized. RESULTS: Among 4,574 patients hospitalized with COVID-19, male sex was associated with higher levels of troponin and greater odds of severe COVID-19 illness, but lower levels of initial D-dimer when compared with female sex. While sex did not modify the relationship between troponin level and severe COVID-19 illness, peak D-dimer level was more strongly associated with severe COVID-19 illness in male patients compared to female patients (males: OR=2.91, 95%CI=2.63-2.34, p<0.001; females: OR=2.31, 95%CI=2.04-2.63, p<0.001; p-interaction=0.005). CONCLUSION: Sex did not modify the association between troponin level and severe COVID-19 illness, but did modify the association between peak D-dimer and severe COVID-19 illness, suggesting greater prognostic value for D-dimer in males with COVID-19.

Radiation-Induced Left Main Coronary Artery Stenosis in a Patient with Atretic Internal Mammary Arteries.

Coronary artery disease (CAD) is a known potential complication of thoracic radiation treatment that typically affects the proximal segments of the coronary arteries, requiring coronary artery bypass grafting (CABG). We present a case of acute coronary syndrome occurring in a 57-year-old man with prior thoracic radiation therapy following resection of a chest wall chondrosarcoma. Coronary angiogram demonstrated significant areas of stenosis in the left main coronary artery (LMCA) and ostial left anterior descending (LAD) coronary artery. The patient was also found to have atretic bilateral internal mammary arteries as a consequence of his radiation therapy, rendering them unsuitable as grafts. Percutaneous coronary intervention (PCI) was thus performed with a successful outcome. To our knowledge, this is the first case of radiation-induced CAD of the LMCA with atretic internal mammary arteries treated successfully with PCI.

A novel hybrid multichannel biphasic calcium phosphate granule-based composite scaffold for cartilage tissue regeneration.

The objective of the present study was to develop a novel hybrid multichannel biphasic calcium phosphate granule (MCG)-based composite system for cartilage regeneration. First, hyaluronic acid-gelatin (HG) hydrogel was coated onto MCG matrix (MCG-HG). Poly(lactic-co-glycolic acid) (PLGA) microspheres was separately prepared and modified with polydopamine subsequent to BMP-7 loading (B). The surface-modified microspheres were finally embedded into MCG-HG scaffold to develop the novel hybrid (MCG-HG-PLGA-PD-B) composite system. The newly developed MCG-HG-PLGA-PD-B composite was then subjected to scanning electron microscopy, energy dispersive X-ray spectroscopy, Fourier Transform infrared spectroscopy, porosity, compressive strength, swelling, BMP-7 release and in-vitro biocompatibility studies. Results showed that 60% of BMP-7 retained on the granular surface after 28 days. A hybrid MCG-HG-PLGA-PD-B composite scaffold exhibited higher swelling and compressive strength compared to MCG-HG or MCG. In-vitro studies showed that MCG-HG-PLGA-PD-B had improved cell viability and cell proliferation for both MC3T3-E1 pre-osteoblasts and ATDC5 pre-chondrocytes cell line with respect to MCG-HG or MCG scaffold. Our results suggest that a hybrid MCG-HG-PLGA-PD-B composite scaffold can be a promising candidate for cartilage regeneration applications.

Complete Resolution of Tumor Burden of Primary Cardiac Non-Hodgkin's Lymphoma.

Primary cardiac tumors are a rare set of benign and malignant neoplasms found in the heart or pericardium. We describe a patient presenting with nonspecific symptoms and ultimately diagnosed with primary cardiac non-Hodgkin's lymphoma (PCL). Our patient had extensive tumor in the right ventricle, which extended into the right atrium and right ventricular outflow tract. The tumor also encased the right coronary artery, which manifested as ischemic changes on EKG and cardiac MRI. The patient was treated with chemotherapy and achieved complete remission, with dramatic and full resolution of the mass on repeat echocardiography in nine weeks. More studies are needed to understand the optimal management and prognosis of patients with PCL.

Mast cells: a pivotal role in pulmonary fibrosis.

Pulmonary fibrosis is characterized by an inflammatory response that includes macrophages, neutrophils, lymphocytes, and mast cells. The purpose of this study was to evaluate whether mast cells play a role in initiating pulmonary fibrosis. Pulmonary fibrosis was induced with bleomycin in mast-cell-deficient WBB6F1-W/W(v) (MCD) mice and their congenic controls (WBB6F1-(+)/(+)). Mast cell deficiency protected against bleomycin-induced pulmonary fibrosis, but protection was reversed with the re-introduction of mast cells to the lungs of MCD mice. Two mast cell mediators were identified as fibrogenic: histamine and renin, via angiotensin (ANG II). Both human and rat lung fibroblasts express the histamine H1 and ANG II AT1 receptor subtypes and when activated, they promote proliferation, transforming growth factor ß1 secretion, and collagen synthesis. Mast cells appear to be critical to pulmonary fibrosis. Therapeutic blockade of mast cell degranulation and/or histamine and ANG II receptors should attenuate pulmonary fibrosis.

Modulation of contractility by myocyte-derived arginase in normal and hypertrophied feline myocardium.

L-Arginine, the sole substrate for the nitric oxide (NO) synthase (NOS) enzyme in producing NO, is also a substrate for arginase. We examined normal feline hearts and hearts with compensated left ventricular (LV) hypertrophy (LVH) produced by ascending aorta banding. Using Western blot analysis, we examined the abundance of arginase isozymes in crude homogenates and isolated cardiac myocytes obtained from the LVs of normal and LVH hearts. We examined the functional significance of myocyte arginase via measurement of shortening and intracellular calcium in isolated myocytes in the presence and absence of boronoethyl chloride (BEC), a specific pharmacological inhibitor of arginase. Both arginase I and II were detected in crude myocardial homogenates, but only arginase I was present in isolated cardiac myocytes. Arginase I was downregulated in LVH compared with normal. Inhibition of arginase with BEC reduced fractional shortening, maximal rate of shortening (+dL/dt) and relengthening (-dL/dt), and the peak of the free cytosolic calcium transient in normal myocytes but did not affect these parameters in LVH myocytes. These negative inotropic actions of arginase inhibition were associated with increases in cGMP generation. These studies indicate that only arginase I is present in cardiac myocytes where it tends to limit NO and cGMP production with the effect of supporting basal contractility. In experimental LVH induced by pressure overload, our studies demonstrate reduced arginase I expression and reduced functional significance, allowing greater arginine substrate availability for NO/cGMP signaling.

Pharmacological effects of ATI22-107 [2-(2-{2-[2-chloro-4-(6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl)-phenoxy]-acetylamino}-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid dimethyl ester)], a novel dual pharmacophore, on myocyte calcium cycling and contractility.

Historically, inhibitors of type III phosphodiesterases (PDE-III) have been effective inotropes in mammalian myocardium, but their clinical utility has been limited by adverse events, including arrhythmias that are considered to be due to Ca(2+) overload. ATI22-107 [2-(2-{2-[2-chloro-4-(6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl)-phenoxy]-acetylamino}-ethoxymethyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid dimethyl ester)], a novel, dual pharmacophore compound, was designed to simultaneously inhibit the cardiac phosphodiesterase (PDE-III) and produce inotropic effects, whereas inhibiting the L-type calcium channel (LTCC) was designed to minimize increases in diastolic Ca(2+). We compared the effects of ATI22-107 and enoximone, a pure PDE-III inhibitor, on the Fluo-3 calcium transient in normal feline ventricular myocytes and trabeculae. Enoximone-induced dose-dependent increases in peak [Ca(2+)](i), diastolic [Ca(2+)](i), T50, and T75. ATI22-107 demonstrated similar dose-dependent increases in peak [Ca(2+)](i) at 300 nM and 1.0 microM doses, with no further increases at higher doses. Throughout the dosing range, ATI22-107 induced much smaller, if any, increases in diastolic [Ca(2+)](i), T(25), and T(75). Current measurement of LTCC via patch-clamp techniques revealed dose-dependent decreases in LTCC current with an increasing dose of ATI22-107, thereby validating the dual functionality of the drug that has been proposed in this study. Studies in isolated trabeculae demonstrated that enoximone-induced a dose-dependent augmentation of the entire force-frequency relation in normal myocardium, whereas augmentation of contractility was only observed at lower stimulation frequencies with ATI22-107. These results demonstrate the effects of the LTCC-antagonizing moiety of ATI22-107 and suggest that the novel simultaneous combination of PDE-III and LTCC inhibition by one molecule may produce a favorable profile of limited inotropy without detrimental effects of increased diastolic [Ca(2+)](i).

Simulated microgravity produces attenuated baroreflex-mediated pressor, chronotropic, and inotropic responses in mice.

Whether myocardial contractile impairment contributes to orthostatic intolerance (OI) is controversial. Accordingly, we used transient bilateral carotid occlusion (TBCO) to compare the in vivo pressor, chronotropic, and inotropic responses (parts 1 and 2) to open-loop selective carotid baroreceptor unloading in anesthetized mice. In part 3, in vitro myocyte responses to isoproterenol in mice exposed to hindlimb unweighting (HLU) for approximately 2 wk were determined. Heart rate (HR) and mean arterial pressure (MAP) responses to TBCO were measured. In control mice, TBCO increased HR (15 +/- 2 beats/min, P < 0.05) and MAP (17 +/- 2 mmHg, P < 0.05). These responses were markedly potentiated in denervated control (DC) mice, in which the aortic depressor nerve and sympathetic trunk were sectioned before measurement. Baroreflex responses to TBCO were eliminated by blockade with hexamethonium bromide (10 microg/kg). In HLU (denervated) mice, HR and MAP responses were reduced approximately 70% compared with DC mice. In part 2, myocardial contractile responses to TBCO were measured with a left ventricular micromanometer-conductance catheter. TBCO in DC mice increased the slope of the end-systolic pressure-volume relation (end-systolic elastance) by 86 +/- 13%. This inotropic response was attenuated (14 +/- 10%, P < 0.005) after HLU. In part 3, contractile responses to isoproterenol were impaired in myocytes isolated from HLU mice. In conclusion, selective carotid baroreceptor unloading stimulates HR, blood pressure, and myocardial contractility, and HLU attenuates each response. These findings have important implications for the management of OI in astronauts, the elderly, and individuals subjected to prolonged bed rest.

Critical role for the alpha-1B adrenergic receptor at the sympathetic neuroeffector junction.

The alpha-1 adrenergic receptors (alpha(1)ARs) are critical in sympathetically mediated vasoconstriction. The specific role of each alpha(1)AR subtype in regulating vasoconstriction remains highly controversial. Limited pharmacological studies suggest that differential alpha(1)AR responses may be the result of differential activation of junctional versus extrajunctional receptors. We tested the hypothesis that the alpha(1B)AR subtype is critical in mediating sympathetic junctional neurotransmission. We measured in vivo integrated cardiovascular responses to a hypotensive stimulus (induced via transient bilateral carotid occlusion [TBCO]) in alpha(1B)AR knockout (KO) mice and their wild-type (WT) littermates. In WT mice, after dissection of the carotid arteries and denervation of aortic baroreceptor buffering nerves, TBCO produced significant pressor and positive inotropic effects. Both responses were markedly attenuated in alpha(1B)AR KO mice (change systolic blood pressure 46+/-8 versus 11+/-2 mm Hg; percentage change in the end-systolic pressure-volume relationship [ESPVR] 36+/-7% versus 12+/-2%; WT versus KO; P<0.003). In vitro alpha(1)AR mesenteric microvascular contractile responses to endogenous norepinephrine (NE; elicited by electrical field stimulation 10 Hz) was markedly depressed in alpha(1B)AR KO mice compared with WT (12.4+/-1.7% versus 21.5+/-1.2%; P<0.001). In contrast, responses to exogenous NE were similar in alpha(1B)AR KO and WT mice (22.4+/-7.3% versus 33.4+/-4.3%; NS). Collectively, these results demonstrate a critical role for the alpha(1B)AR in baroreceptor-mediated adrenergic signaling at the vascular neuroeffector junction. Moreover, alpha(1B)ARs modulate inotropic responses to baroreceptor activation. The critical role for alpha(1B)AR in neuroeffector regulation of vascular tone and myocardial contractility has profound clinical implications for designing therapies for orthostatic intolerance.