The prevalence and prognostic implications of pre-procedural hyperbilirubinemia in patients undergoing transcatheter aortic valve replacement.

Preoperative hyperbilirubinemia is associated with increased mortality and morbidity after cardiac surgery. However, this clinical significance is unclear with transcatheter aortic valve replacement (TAVR) procedures. The aims of this study were to determine the prevalence and prognostic implications of preoperative elevations of serum total bilirubin on TAVR outcomes. In 611 consecutive patients who underwent an elective TAVR procedure, 576 patients had recorded serum total bilirubin levels. Hyperbilirubinemia was defined as any value of serum total bilirubin ≥ 1.2 mg/dL obtained within 30-days prior to the TAVR procedure. The primary composite endpoint was post-TAVR all-cause in-hospital mortality or stroke. The overall prevalence of hyperbilirubinemia was 10% (n = 58). There were no patients with a prespecified diagnosis of liver cirrhosis. Pre-TAVR hyperbilirubinemia compared to normal bilirubin level was more common in younger (78 ± 10 vs. 82 ± 8 years old, p < 0.001) males (15 vs. 6%, p < 0.001), with history of pacemaker or ICD (33 vs. 18%, p = 0.005), congestive heart failure New York Heart Association class IV within 2 weeks from TAVR (35 vs. 14%, p < 0.001), severe tricuspid regurgitation (14 vs. 4%, p < 0.001), and atrial fibrillation or flutter (60 vs. 40%, p = 0.004, respectively). Pre-TAVR hyperbilirubinemia was independently associated with an increased post-TAVR in-hospital mortality (7 vs. 2% in normal bilirubin, p = 0.03), stroke (5 vs. 1%, p = 0.019, respectively), and a composite endpoint of death or stroke (12 vs. 3%, p < 0.001). Preoperative hyperbilirubinemia in patients undergoing TAVR is more prevalent than previously considered with multifactorial causes. Hyperbilirubinemia is independently associated with an increased post-TAVR in-hospital mortality and stroke.

Renal artery stenosis: to intervene, or not to intervene, "that is the question".

Renal artery stenosis (RAS) due to atherosclerosis continues to be a major cause of secondary hypertension. It can also lead to renal dysfunction due to ischemic nephropathy. While major clinical trials have emphasized that medical management should be preferred over angioplasty and stenting for the treatment of renal artery stenosis, clinical scenarios continue to raise doubts about the optimal management strategy. Herein, we present two cases that were admitted with hypertensive emergency and renal function deterioration. Medical therapy failed to control the blood pressure and in one patient, renal failure progressed to a point where renal replacement therapy was required. Both patients underwent angioplasty (for >90% stenosis) and stent insertion with successful resolution of stenosis by interventional radiology. Postoperatively, blood pressure gradually decreased with improvement in serum creatinine. Dialysis therapy was discontinued. At 4- and 8-month follow-up, both patients continue to do well with blood pressure readings in the 132-145/70-90 mmHg range. This article highlights the importance of percutaneous interventions in the management of atherosclerotic RAS and calls for heightened awareness and careful identification of candidates who would benefit from angioplasty and stent insertion.

Association of Lipoprotein Subfractions With Presence and Severity of Coronary Artery Disease in Patients Referred for Coronary Angiography.

Lipoprotein subfractions (LS) can be used for better risk stratification in subjects deemed not at high risk for coronary artery disease (CAD). In this study, we evaluated the correlation between LS with CAD presence and severity. This is a prospective case-control study of 157 patients referred for coronary angiography who were not on lipid-lowering therapy and had LS measured by nuclear magnetic resonance spectroscopy. Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) scores were calculated to estimate CAD severity. Univariate and multivariable regression analysis was performed to determine correlation of LS with CAD presence and severity and acute coronary syndrome (ACS). There was significant association of certain LS (positive for total low-density lipoprotein particle [LDL-P], small LDL-P and apolipoprotein B, negative for large high-density lipoprotein particle [HDL-P] and apolipoprotein A1 [ApoA1]) with the presence of obstructive CAD and CAD severity. Small LDL-P and HDL-P were still predictive for obstructive CAD after adjusting for traditional risk factors, 10-year atherosclerotic cardiovascular disease risk score and in those with low-density lipoprotein cholesterol <100 mg/100 ml. Total LDL-P and ApoA1 were predictive of CAD severity on multivariable analysis. Higher small LDL-P and lower large HDL-P were associated with ACS presence, although only large HDL-P had a significant inverse correlation with ACS on adjusted analysis (odds ratio 0.74 95% confidence interval 0.58, 0.95) In conclusion, in our cohort of patients referred for coronary angiography, total LDL-P, small LDL-P, and apolipoprotein B had significant direct correlation, and large HDL-P and ApoA1 had significant inverse correlation with obstructive CAD and CAD severity.

Transient sinus arrest due to sinus node artery thrombus after revascularisation of the left circumflex artery.

We present a case of sinus arrest and junctional escape rhythm from sinus node artery (SNA) thrombus in a 55-year-old man after revascularisation of right coronary and proximal circumflex arteries for infero-posterior wall ST-segement elevation myocardial infarction (STEMI). Sinus arrest from occlusion of the SNA is uncommon. The ensuing bradycardia may have haemodynamic consequences requiring temporary pacing but is almost always self-limited.

Worsening Mitral Stenosis Due to Post-transcatheter Aortic Valve Replacement Improvement of Concomitant Aortic Insufficiency.

Transcatheter aortic valve replacement (TAVR) has become an alternative to surgical treatment in severe aortic valve stenosis, with expanding indications and rapidly growing number of performed procedures. Poor opposition of TAVR prosthesis to the aortic root causes paravalvular leak, while mitral regurgitation and stenosis have been associated with valve implantation low in the left ventricular outflow tract (LVOT). We report an unusual case of a patient with combined severe aortic stenosis and moderate aortic insufficiency who underwent elective TAVR, which resulted in significant increase of a pre-existing mitral valve gradient. Rapid post-TAVR increase in mitral valve gradient was likely due to improvement in aortic regurgitation and decreased left ventricular end-diastolic pressure (LVEDP).

Differential modulation of Rhodnius prolixus nitric oxide activities following challenge with Trypanosoma rangeli, T. cruzi and bacterial cell wall components.

Nitric oxide (NO) is a key immune effector and signaling molecule in many organisms. However, the contribution NO makes towards insect immunity has received little attention, particularly in non-dipteran species. In this study, tissue- and time-specific alterations in NO synthase (NOS) gene expression and NO production were documented in the hemipteran vector of Chagas' disease, Rhodnius prolixus, following in vivo immune challenge by Trypanosoma cruzi, T. rangeli and crude bacterial lipopolysaccharide (LPS). The most pronounced reactions to crude LPS occurred in major immune tissues (fat body and blood cells), while tissues of the digestive tract were most responsive to infections by T. cruzi and T. rangeli. The data suggest the NO-mediated immune responses of R. prolixus are pathogen-specific and independently modified both at the transcriptional and enzyme levels.

Melanization immune responses in mosquito vectors.

The production and deposition of melanin pigments on invading pathogens and parasites represents a unique, innate immune response in the phylum Arthropoda. This immune response has started to receive considerable attention because of the potential to exploit this mechanism to control mosquito-borne diseases. In this article, we summarize knowledge about this complex biochemistry, the use of melanin biosynthesis in diverse physiological processes and the gaps in knowledge that must be addressed if this immune process is to be manipulated in genetic-based control strategies.

Production and utilization of hydrogen peroxide associated with melanogenesis and tyrosinase-mediated oxidations of DOPA and dopamine.

The synthesis and involvement of H(2)O(2) during the early stages of melanogenesis involving the oxidations of DOPA and dopamine (diphenolase activity) were established by two sensitive and specific electrochemical detection systems. Catalase-treated reaction mixtures showed diminished rates of H(2)O(2) production during the autoxidation and tyrosinase-mediated oxidation of both diphenols. Inhibition studies with the radical scavenger resveratrol revealed the involvement in these reactions of additional reactive intermediate of oxygen (ROI), one of which appears to be superoxide anion. There was no evidence to suggest that H(2)O(2) or any other ROI was produced during the tyrosinase-mediated conversion of tyrosine to DOPA (monophenolase activity). Establishing by electrochemical methods the endogenous production H(2)O(2) in real time confirms recent reports, based in large part on the use of exogenous H(2)O(2), that tyrosinase can manifest both catalase and peroxidase activities. The detection of ROI in tyrosinase-mediated in vitro reactions provides evidence for sequential univalent reductions of O(2), most likely occurring at the enzyme active site copper. Collectively, these observations focus attention on the possible involvement of peroxidase-H(2)O(2) systems and related ROI-mediated reactions in promoting melanocytotoxic and melanoprotective processes.

Dexamethasone inhibition of the cellular immune response of Drosophila melanogaster against a parasitoid.

Host larvae of Drosophila melanogaster injected with the eicosanoid biosynthesis inhibitor, dexamethasone, prior to parasitization by the wasp Leptopilina boulardi, exhibited significantly reduced rates of melanotic encapsulation in comparison with control and saline-injected larvae. The results of this investigation suggest that prostaglandins and other eicosanoids are involved as cell-signaling molecules in the hemocytic encapsulation reaction of D. melanogaster larvae.

Takotsubo Cardiomyopathy: Typical and Atypical Variants, A Two-Year Retrospective Cohort Study.

BACKGROUND: Typical or classical takotsubo cardiomyopathy (TCM) is associated with the characteristic abnormality of a ballooned left ventricular apex with basal segmental hyperkinesis. TCM may not present with the "classical" wall motion abnormalities but can have a variety of segmental wall motion abnormalities. The aim of our work was to assess for any unique identifying factors that can help distinguish typical and atypical variants of TCM. METHODS: We studied 11 consecutive patients between 2010 and 2012 admitted with chest pain, electrocardiographic and cardiac biomarker changes consistent with acute coronary syndrome (ACS) who underwent left heart angiography and were clinically diagnosed to have TCM. RESULTS: Our study found no specific features distinguishing typical and atypical variants of TCM. In our study, all patients were female and all had excellent outcome. One patient was in fourth decade of life, three patients in fifth and sixth decade of life, while remaining were older. One patient had diabetes mellitus, five had hypertension, four had concurrent coronary artery disease, but no patient had any family history of TCM. Nine of 11 patients had immediate clear-cut stressors. Three patients had normal ECG, two with ST segment elevation, with nine patients having only modest troponin elevations. One patient had an anomalous RCA take-off from the right coronary cusp, otherwise remaining patients had normal anatomy. One patient had only apical involvement, remaining had multiple wall motion abnormalities, and all patients had involvement of the anterior wall. Four patients had apical sparing. No inverted TCM pattern with basal akinesis with normal wall motion in the midventricular and apical regions was found among our patients. CONCLUSIONS: We report that the classification of TCM as typical versus atypical is probably not clinically meaningful. The regional wall motion abnormalities are related to catecholamine excess and to the susceptibility of that particular region to excess catecholamine. We do not know why such differences in regional susceptibility exist, and agree with the other authors that sub-classification would only add to confusion, and a delay in understanding of the disease process.

Tumor blush: left ventricular cardiac hemangioma with supply from both the left anterior descending and circumflex arteries.

A fifty-year-old male had an echocardiogram for an abnormal electrocardiogram; it revealed a left ventricular mass. A cardiac catheterization revealed normal coronary arteries and a fine tumor blush of the cardiac tumor with feeding arteries from the circumflex as well as the second diagonal coronary vessels. Due to increased risk of embolization, he underwent surgery via a transatrial approach and a 1.5 cm cavernous-capillary hemangioma was removed from the base of the posteromedial papillary muscle. Primary tumors of the heart are rare, and the symptoms and signs depend on the location and size of the tumor. Coronary angiography remains an integral part in the evaluation of cardiac tumors and often can reveal a characteristic 'tumor blush.' The natural history of the tumor is unpredictable and excision of the tumor remains the treatment of choice. We present a rare case of characteristic angiographic tumor blush of a left ventricular cardiac hemangioma with feeding arteries from both the left anterior descending as well as the circumflex arteries. This rare two-system supply was due to the intracavitary location of the hemangioma, and fortunately did not pose any excessive difficulty in mobilization and excision during surgery.

Conversion of infarction-associated atrial fibrillation by restoration of atrial perfusion.

We report a patient who presented with new onset atrial fibrillation in the setting of inferior ST-segment elevation myocardial infarction (STEMI). Cardiac catheterization revealed proximal occlusion of the left circumflex artery. Balloon angioplasty and stenting restored flow to a large left atrial branch, with prompt conversion of the rhythm to atrial flutter, and then to sinus rhythm. To our knowledge this represents the first demonstration of restoration of sinus rhythm by reversing left atrial ischemia in the setting of STEMI.

A pathogenic parasite interferes with phagocytosis of insect immunocompetent cells.

Phagocytosis activity of hemocytes of the host Galleria mellonella (Lepidoptera) was modulated by the infection of the entomopathogenic nematode Steinernema feltiae (Rahbditida) and was found to be correlated with the opsonization of bacteria by hemolymph factors. The presence of nematodes resulted in a significative decrease in phagocytosis of bacteria by host hemocytes, both in in vivo and in in vitro assays. Host interacting proteins (HIPs), which appear to function as opsonic factors and are essential to perform immune responses, were removed by S. feltiae from host hemolymph, by means of its epicuticle binding properties. Host humoral factors sequestered by the parasite have been identified by monodimensional and 2D electrophoretic analysis. The data suggest that S. feltiae, living in association with symbiontic bacteria (Xenorhabdus nematophilus), develop an immune suppressive strategy to support its bacteria, which diminished the effectiveness of immunological surveillance by the host.

Parasite suppression of the oxidations of eumelanin precursors in Drosophila melanogaster.

In insects, eukaryotic endoparasites encounter a series of innate immune effector responses mediated in large part by circulating blood cells (hemocytes) that rapidly form multilayer capsules around foreign organisms. Critical components of the encapsulation response are chemical and enzyme-catalyzed oxidations involving phenolic and catecholic substrates that lead to synthesis of eumelanin. These responses are initiated immediately upon infection and are very site-specific, provoking no undesirable systemic responses in the host. In this study, we were interested to learn if the principal oxidation pathways leading to the synthesis of eumelanin in larvae of Drosophila melanogaster were targets for inhibition by immune suppressive factors (ISF) derived from a virulent strain of the endoparasitic wasp Leptopilina boulardi. Comparative in vitro assays monitored by sensitive electrochemical detection methods showed that ISF derived from female reproductive tissues significantly diminished the oxidations of the two diphenol eumelanin precursors, dopamine and 5,6-dihydroxyindole (DHI). The oxidations of the monophenol tyrosine, and two other related diphenols, dopa and 5,6-dihydroxyindole-2-carboxylic acid (DHICA), were not significantly inhibited by ISF. The data suggest that melanogenesis represents at least one of the host responses suppressed by L. boulardi ISF, and that the oxidation pathways selectively targeted for inhibition are those synthesizing decarboxylated pigment precursors derived from DHI. These observations, together with previous reports of adverse effects of ISF on the ability of hemocytes to adhere to foreign surfaces, suggest a multifaceted approach by the parasitoid to circumvent the innate immune response of D. melanogaster.

Interactions of iron with reactive intermediates of oxygen and nitrogen.

Iron not only functions as a cofactor for various enzymes, but it is also a source of potentially cytotoxic molecules produced through interactions with certain reactive intermediates of oxygen (ROI) and nitrogen (RNI). Protection from such iron-mediated damage results in large part from homeostatic mechanisms that regulate the sequestration of iron. Perturbations in iron homeostasis can result in an array of adverse cellular manifestations including oxidative and nitrosative stress, enhanced production of free radicals, macromolecular damage, and cell death. This brief review focuses on some of the potentially adverse reactions of iron with ROI and RNI.