Mycotic Intracranial Aneurysm Secondary to Left Ventricular Assist Device Infection.

BACKGROUND: Mycotic aneurysms are a complication of infective endocarditis. Infection of left ventricular assist devices (LVADs) may lead to bacteremia and fever causing complications similar to those seen in patients with prosthetic valve endocarditis. Intracranial mycotic aneurysms are rare, and their presence is signaled by the development of subarachnoid hemorrhage in the setting of bacteremia and aneurysms located distal to the circle of Willis. CASE PRESENTATION: We present the case of a patient with a LVAD presenting with headache who is found to have an intracranial mycotic aneurysm through computed tomography angiography of the head. The patient was successfully treated with endovascular intervention. CONCLUSION: In patients with LVADs, mycotic aneurysms have been reported, however not intracranially. To the best of our knowledge, this is the first intracranial mycotic aneurysm secondary to LVAD infection that was successfully treated with endovascular repair. Intracranial mycotic aneurysms associated with LVADs are a rare phenomenon. The diagnosis of mycotic aneurysms requires a high index of suspicion in patients who present with bacteremia with or without headache and other neurological symptoms. DISCLOSURE: None.

A variant of Brugada syndrome.

Brugada syndrome is an inherited disorder that can present with syncope, cardiac arrest, or sudden cardiac death. Multiple genetic mutations have been described that cause this disease. We present a 56-year-old man who sustained an out-of-hospital cardiac arrest, was resuscitated, and was found to have typical features of the Brugada criteria on the electrocardiogram. Genetic testing was positive for a heterozygous mutation in the sodium voltage-gated channel alpha subunit 5 (SCN5A) gene with a p. Leu227Pro (L227P) variant located on exon 6. To our knowledge, this is the first described case with this variant causing malignant arrhythmia with a cardiac arrest.

Use of non-selective ß-blockers is associated with decreased tumor proliferative indices in early stage breast cancer.

Previous studies suggest beta-adrenergic receptor (ß-AR) antagonists (ß-blockers) decrease breast cancer progression, tumor metastasis, and patient mortality; however the mechanism for this is unknown. Immunohistochemical analysis of normal and malignant breast tissue revealed overexpression of ß1-AR and ß3-AR in breast cancer. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of ß-blocker usage on tumor proliferation. Our analysis revealed that non-selective ß-blockers, but not selective ß-blockers, reduced tumor proliferation by 66% (p < 0.0001) in early stage breast cancer compared to non-users. We tested the efficacy of propranolol on an early stage breast cancer patient, and quantified the tumor proliferative index before and after treatment, revealing a propranolol-mediated 23% reduction (p = 0.02) in Ki67 positive tumor cells over a three-week period. The anti-proliferative effects of ß-blockers were measured in a panel of breast cancer lines, demonstrating that mammary epithelial cells were resistant to propranolol, and that most breast cancer cell lines displayed dose dependent viability decreases following treatment. Selective ß-blockers alone or in combination were not as effective as propranolol at reducing breast cancer cell proliferation. Molecular analysis revealed that propranolol treatment of the SK-BR-3 breast cancer line, which showed high sensitivity to beta blockade, led to a reduction in Ki67 protein expression, decreased phosphorylation of the mitogenic signaling regulators p44/42 MAPK, p38 MAPK, JNK, and CREB, increased phosphorylation of the cell survival/apoptosis regulators AKT, p53, and GSK3ß. In conclusion, use of non-selective ß-blockers in patients with early stage breast cancer may lead to decreased tumor proliferation.

Myxomatous Mitral Valve with Prolapse and Flail Scallop.

BACKGROUND: Myxomatous mitral valve with prolapse are classically seen with abnormal leaflet apposition during contraction of the heart. Hemodynamic disorders can result from eccentric mitral regurgitation usually caused by chordae tendinae rupture or papillary muscle dysfunction. Echocardiography is the gold standard for evaluation of leaflet flail and prolapse due to high sensitivity and specificity. Though most mitral valve prolapse are asymptomatic those that cause severe regurgitation need emergent surgical intervention to prevent disease progression. CASE REPORT: We report a 54 year old Hispanic male who presented with progressively worsening dyspnea and palpitations. Initial evaluation was significant for atrial fibrillation on electrocardiogram with subsequent echocardiography revealing myxomatous mitral valve with prolapse. Following surgical repair of the mitral valve, the dyspnea and palpitations resolved. CONCLUSIONS: Mitral valve prolapse is a common valvular abnormality but the pathogenic cause of myxomatous valves has not been elucidated. Several theories describe multiple superfamilies of proteins to be involved in the process. Proper identification of these severe mitral regurgitation due to these disease valves will help relieve symptomatic mitral valve prolapse patients.

Rumpel-Leede phenomenon presenting as a hypertensive urgency.

Rumpel-Leede (R-L) phenomenon is the rare event in which the small dermal capillaries of an extremity rupture in response to application of a compressive device to that extremity, such as when inflating a cuff during noninvasive blood pressure monitoring or when applying a tourniquet to draw blood. This capillary rupture results in formation of a petechial rash distal to the compressive device. R-L phenomenon is believed to occur most often in patients with underlying vascular disease, such as diabetes mellitus or thrombocytopenia. R-L phenomenon is most often benign, though it may rarely be associated with pain and discomfort. There is no treatment for this condition apart from treatment of the underlying vascular disease or thrombocytopenia. We report a 57-year-old woman who presented with hypertensive urgency and experienced R-L phenomenon during blood pressure cuff inflation.

Current Role of Ivabradine in Stable Coronary Artery Disease Without Heart Failure.

Increase in heart rate represents a significant contribution in the pathophysiology of coronary artery disease and heart failure, by promoting atherosclerotic process and endothelial dysfunction. Thus, it negatively influences cardiovascular risk in the general population. The aim of this review is to analyze the current, controversial, and future role of ivabradine as an anti-anginal agent in the setting of coronary artery disease without heart failure. Ivabradine represents a selective heart rate-lowering agent that increased diastolic perfusion time and improving energetics in the ischemic myocardium.

Congenital Absence of Left Circumflex Presenting After an Emotional Stressor.

BACKGROUND: Absence of the left circumflex artery (LCX) is an extremely rare congenital anomaly of the coronary circulation. While some coronary circulation anomalies are associated with significant complications, including sudden cardiac death and premature atherosclerosis, absence of the LCX is largely considered benign, though it has been associated with exertional chest pain, which may mimic acute coronary syndrome. Diagnosis is made when heart catheterization is performed in the work up for acute coronary syndrome or when computed tomography coronary angiography is performed during evaluation of coronary artery disease. CASE REPORT: We report a 55 year old female who presented with non-exertional chest pain in the setting of an emotional stressor. The initial work up was only significant for elevated troponins, and subsequent left heart catheterization revealed findings consistent with congenital absence of the LCX. No significant stenosis was appreciated, and no intervention was performed. Following catheterization, the patient's troponins began to trend down, and her chest pain resolved. CONCLUSIONS: Congenitally absent LCX is a rare entity detected when work up is performed to rule out acute coronary syndrome in patients presenting with exertional chest pain. This is the first reported case of chest pain unrelated to physical activity reported in a patient with an absent LCX. There is no specific treatment for an absent LCX; however, proper identification of this anomaly and differentiation from complete occlusion of the LCX is important in making an accurate diagnosis of myocardial ischemia and for choosing the best intervention when ischemia is present.

A Review of Sodium Glucose Co-transporter 2 Inhibitors Canagliflozin, Dapagliflozin and Empagliflozin.

Sodium glucose co-transporter 2 (SGLT2) inhibitors are a new class of anti-diabetic medications. Canagliflozin was the first drug approved in this group in 2013 and subsequently dapagliflozin was approved in January 2014 and empagliflozin was approved in August 2014. Preclinical studies have demonstrated safety, tolerability, and efficacy in terms of glycemic control and HbA1c level in type 2 diabetes mellitus (T2DM) patients in comparison to other anti-diabetic drugs. The U.S. Food and Drug Administration (FDA) recently released a warning that some of the patients who used SGLT2 inhibitors developed diabetic ketoacidosis (DKA). Empagliflozin has showed safety in type 2 diabetics with renal impairment. Each of these medications can be used as a single treatment or in combination with other anti-diabetic medications.

Pulmonary veno-occlusive disease as a cause of pulmonary arterial hypertension.

Pulmonary veno-occlusive disease (PVOD) represents a rare form of precapillary pulmonary arterial hypertension. We present a young patient hospitalized with progressive dyspnea, with initial workup suggestive of pulmonary hypertension and unexplained noncardiogenic pulmonary edema. His subsequent clinical course was consistent with the diagnosis of PVOD.

Finger necrosis due to cryoglobulinemic vasculitis in association with membranous nephropathy.

Cryoglobulinemic vasculitis is a small vessel vasculitis that has been associated with chronic infections and autoimmune, lymphoproliferative, and neoplastic disorders. When no significant etiological factors are identified, it is called essential mixed cryoglobulinemia. A detailed and thorough laboratory investigation is required to exclude all possible causes of cryoglobulin formation. Although cryoglobulin testing is simple, careful temperature regulation is needed to avoid false-negative results. Consensus diagnosis should be developed and implemented for appropriate cryoglobulin detection and accurate clinical diagnosis for cryoglobulinemic vasculitis. Here we present an interesting, first-ever case report of a 54-year-old Hispanic-American woman with essential mixed cryoglobulinemia presenting with significant digital necrosis in association with membranous nephropathy.

Reverse takotsubo cardiomyopathy with use of male enhancers.

Reverse takotsubo cardiomyopathy is a rare heart failure condition characterized by systolic dysfunction of the basal segments of the left ventricle in the absence of obstructive coronary artery disease. We present a case of a 54-year-old man with an overdose of Extenze (a male enhancer pill containing yohimbine) who was hospitalized with heart failure due to reverse takotsubo cardiomyopathy.

Myopericarditis as a complication of nonspecific colitis.

PATIENT: Male, 31 FINAL DIAGNOSIS: Myopericarditis Symptoms: Abdominal pain • diarrhea MEDICATION: - Clinical Procedure: - Specialty: Cardiology. OBJECTIVE: Unusual setting of medical care. BACKGROUND: Myopericarditis is a condition involving inflammation of the pericardium and myocardium. It has been reported in conjunction with inflammatory bowel disease as well as infectious colitis caused by a cardiotropic organism. The etiology of myopericarditis includes a long list of infectious causes (especially viral), toxic causes, autoimmune disorders, and vasculitides. CASE REPORT: A 31-year-old previously healthy Hispanic man complained of sudden onset of watery, non-bloody diarrhea associated with mucus and crampy abdominal pain. ECG showed ST-segment elevation in the infero-lateral leads, with elevated troponin I level. Urgent cardiac catheterization revealed normal coronary arteries and the patient was diagnosed with myopericarditis. The echocardiogram results were within normal limits, with 65% ejection fraction and no evidence of wall motion abnormalities. Colonoscopy showed macroscopically congested mucosa in the descending colon, sigmoid colon, and rectum, with scattered petechiae indicative of nonspecific colitis. Microscopic examination of obtained biopsies revealed evidence of acute mucosal inflammation without ulceration, granulomas or ischemia. The patient was started on Naproxen 250 mg twice daily and chest pain started to improve gradually. The patient was discharged on Naproxen and was followed up in clinic 2 weeks after discharge, where he was found to be completely asymptomatic, with troponin level <0.015 ng/ml. CONCLUSIONS: Myopericarditis is a challenging diagnosis that has been reported in association with colitis, either as an extraintestinal manifestation of IBD or due to infectious colitis with a cardiotropic organism.

Recurrent myopericarditis as a complication of Marijuana use.

PATIENT: Male, 29 FINAL DIAGNOSIS: Myopericarditis Symptoms: Chest pain Medication: Ibuprofen Clinical Procedure: - Specialty: Cardiology. OBJECTIVE: Unusual clinical course. BACKGROUND: Cannabis is the most commonly used illegal substance worldwide and its consumption portends significant side effects. Nowadays, in order to increase its psychotropic effect, various substances are being added constantly to it to promote its potency that might hold toxic effects to different organs including the heart and might lead to other unreported complications such as myopericarditis. Herein, we are presenting a unique case of recurrent myopericarditis after the consumption of contaminated marijuana, an association that has not been reported in literature before. CASE REPORT: A 29-year-old man presented to our institution with pressure-like left-sided chest pain that is aggravated by cough and deep inspiration and relieved by sitting and leaning forward. Examination revealed pericardial rub and workup showed elevated white blood cell count, C-reactive protein and troponin I level of 2.99 ng/ml. ECG upon admission showed ST-segment elevation in the inferior leads with PR-segment depression. Echocardiogram revealed only concentric hypertrophy. PATIENT was admitted to another institution with similar symptoms 2 months earlier. PATIENT admitted to using adulterated Marijuana on both occasions prior to hospitalization. Review of medical records from the outside hospital revealed similar ECG and laboratory findings. Treatment with Ibuprofen resulted in resolution of patient's symptoms and ECG abnormalities. CONCLUSIONS: Recurrent myopericarditis in our patient is likely the result of consumption of contaminated Marijuana. Careful history taking in patients presenting with myopericarditis is crucial as it might be the causal link.

Chemical images of marine bio-active compounds by surface enhanced Raman spectroscopy and transposed orthogonal partial least squares (T-OPLS).

Surface enhanced Raman spectroscopy combined with transposed Orthogonal Partial Least Squares (T-OPLS) was shown to produce chemical images of the natural antibacterial surface-active compound 1,1,3,3-tetrabromo-2-heptanone (TBH) on Bonnemaisonia hamifera. The use of gold colloids functionalised with the internal standard 4-mercapto-benzonitrile (MBN) made it possible to create images of the relative concentration of TBH over the surfaces. A gradient of TBH could be mapped over and in the close vicinity of the B. hamifera algal vesicles at the attomol/pixel level. T-OPLS produced a measure of the spectral correlation for each pixel of the hyperspectral images whilst not including spectral variation that was linearly independent of the target spectrum. In this paper we show the possibility to retrieve specific spectral information with a low magnitude in a complex matrix.

PPAR- γ agonist in treatment of diabetes: cardiovascular safety considerations.

The peroxisome proliferator-activated receptors (PPARs) are nuclear fatty acid receptors, which contain a type II zinc finger DNA binding motif and a hydrophobic ligand binding pocket. These receptors are thought to play an important role in metabolic diseases such as obesity, insulin resistance, and coronary artery disease. Three subtypes of PPAR receptors have been described: PPARα, PPARδ/ß, and PPARγ. PPARα is found in the liver, muscle, kidney, and heart. In the liver, its role is to up-regulate genes involved in fatty acid uptake, binding, ß-oxidation and electron transport, and oxidative phosphorylation in subcutaneous fat but not in skeletal muscle. PPARδ/ß is expressed in many tissues but markedly in brain, adipose tissue, and skin. PPARγ has high expression in fat, low expression in the liver, and very low expression in the muscle. The thiazolidinediones (TZD) are synthetic ligands of PPARγ. By activating a number of genes in tissues, PPARγ increases glucose and lipid uptake, increases glucose oxidation, decreases free fatty acid concentration, and decreases insulin resistance. Although, there is a rationale for the use of TZDs in patients with type 2 diabetes mellitus, clinical studies have produced conflicting data. While currently used TZDs are clearly associated with heart failure (HF) worsening; with regards to cardiovascular outcomes, pioglitazone seems to be related to a trend toward reduction in cardiovascular morbidity and mortality, whereas rosiglitazone may actually increase risk of cardiovascular events. We review the existing literature on TZDs and discuss role and cardiovascular safety of these agents for the contemporary treatment of diabetes. Other side effects of these agents i.e. increase in osteoporosis and possible risk of bladder cancer is also discussed.

Adiposity-independent sympathetic activity in black men.

Obesity is thought to lead to sympathetic overactivity as a compensatory adjustment to weight gain. However, most of the experimental support for the hypothesis has been derived from white cohorts. Our previous study in blacks indicated that sympathetic nerve activity (SNA) is closely correlated with body mass index only in women, whereas, in black men, SNA is elevated and dissociated from adiposity (Abate et al., Hypertension 38: 379-383, 2001). To further determine whether total and regional adiposity are determinants of SNA in blacks, we performed a prospective weight loss study in 12 normotensive obese black men and 9 obese black women. SNA, body mass index, and abdominal fat mass were measured before and 16 wk after hypocaloric diet. The major new findings are that, in obese black men, the dietary-induced weight loss of 11.3+/-0.8 kg resulted in reduction in plasma leptin, insulin, and visceral abdominal fat but had no effect on SNA (from baseline of 26+/-4 to 28+/-3 bursts/min, P=not significant). In contrast, in black women, weight loss of 8.0+/-0.9 kg caused similar reductions in plasma leptin, insulin, and visceral abdominal fat and led to a reduction in SNA by 40% (from baseline of 22+/-2 to 13+/-3 bursts/min, P<0.05). In conclusion, these new data from this prospective study provide strong support for a major adiposity-independent sympathetic activity in black men and adiposity-related sympathetic activity in black women.

Contrasting effects of oral versus transdermal estrogen on serum amyloid A (SAA) and high-density lipoprotein-SAA in postmenopausal women.

OBJECTIVES: Previous studies indicated that oral estrogen increased C-reactive protein by a first-pass hepatic effect. In this study, we determine whether the route of estrogen administration influences serum amyloid A (SAA), another acute-phase protein produced by the liver, and the SAA content of the high-density lipoprotein (HDL-SAA) in postmenopausal women. METHODS AND RESULTS: In 29 postmenopausal women without coronary heart disease, we conducted a randomized crossover placebo-controlled study to compare effects of transdermal versus oral estrogen on SAA and HDL-SAA. SAA, apolipoprotein A-I, HDL, and HDL-SAA were measured before and after 8 weeks of transdermal estradiol (100 microg per day), oral-conjugated estrogens (0.625 mg per day), or placebo. We found that oral estrogen significantly increased levels of SAA, HDL, and HDL-SAA, whereas transdermal estrogen reduced both SAA and HDL-SAA but had no effect on HDL in the same women. CONCLUSIONS: Oral estrogen increased SAA and altered HDL composition to contain a higher level of SAA by a first-pass hepatic mechanism. Because elevated SAA levels predict adverse prognosis in healthy postmenopausal women, and elevated HDL-SAA levels have been shown to interfere with HDL function, the route of administration may be an important consideration in minimizing side effects of estrogen replacement therapy on cardiovascular outcomes.

Reflex sympathetic activation during static exercise is severely impaired in patients with myophosphorylase deficiency.

During static exercise, metabolites accumulate in the muscle interstitium where they stimulate chemosensitive afferent nerves that reflexly increase efferent muscle sympathetic nerve activity (MSNA) and blood pressure. In experimental animals, lactic acid potently stimulates the muscle metaboreflex, but its role in humans is more controversial. To determine if lactic acid is a critical mediator of metaboreflex activation in humans, we performed microelectrode recordings of MSNA in eight patients with myophosphorylase deficiency (McArdle's disease) who cannot metabolize intramuscular glycogen and do not generate lactic acid in exercising muscles. Each patient was matched with three healthy control subjects to maximize statistical power. In controls, 2 min of static handgrip performed at 33 % or 45 % of maximal voluntary contraction (MVC) produced intensity-dependent increases in MSNA (171 +/- 22 % and 379 +/- 95 %, respectively). In the patients, MSNA responses to static handgrip were markedly attenuated (33 +/- 14 % at 33 % MVC; 32 +/- 19 % at 45 % MVC; P < 0.05 vs. controls). Likewise, when static handgrip (30 % MVC) was performed to fatigue, MSNA increased by 366 +/- 73 % in controls but only by 51 +/- 14 % in patients (P < 0.05). Pressor responses to static handgrip were also attenuated in patients compared to controls, whereas heart rate responses were identical. In contrast to exercise, the MSNA responses to other reflex stimuli (the cold pressor test or Valsalva's manoeuvre) were similar in patients and controls. Together these data indicate that appropriate activation of glycogenolytic pathways is obligatory for normal metaboreflex-mediated sympathoexcitation during static exercise in humans.