Circulating microRNAs predispose to takotsubo syndrome following high-dose adrenaline exposure.

AIMS: Takotsubo syndrome (TTS) is an acute heart failure, typically triggered by high adrenaline during physical or emotional stress. It is distinguished from myocardial infarction (MI) by a characteristic pattern of ventricular basal hypercontractility with hypokinesis of apical segments, and in the absence of culprit coronary occlusion. We aimed to understand whether recently discovered circulating biomarkers miR-16 and miR-26a, which differentiate TTS from MI at presentation, were mechanistically involved in the pathophysiology of TTS. METHODS AND RESULTS: miR-16 and miR-26a were co-overexpressed in rats with AAV and TTS induced with an adrenaline bolus. Untreated isolated rat cardiomyocytes were transfected with pre-/anti-miRs and functionally assessed. Ventricular basal hypercontraction and apical depression were accentuated in miR-transfected animals after induction of TTS. In vitro miR-16 and/or miR-26a overexpression in isolated apical (but not basal), cardiomyocytes produced strong depression of contraction, with loss of adrenaline sensitivity. They also enhanced the initial positive inotropic effect of adrenaline in basal cells. Decreased contractility after TTS-miRs was reproduced in non-failing human apical cardiomyocytes. Bioinformatic profiling of miR targets, followed by expression assays and functional experiments, identified reductions of CACNB1 (L-type calcium channel Cavß subunit), RGS4 (regulator of G-protein signalling 4), and G-protein subunit Gß (GNB1) as underlying these effects. CONCLUSION: miR-16 and miR-26a sensitize the heart to TTS-like changes produced by adrenaline. Since these miRs have been associated with anxiety and depression, they could provide a mechanism whereby priming of the heart by previous stress causes an increased likelihood of TTS in the future.

A Case of Wernicke Encephalopathy Secondary to Anorexia Nervosa Complicated by Refeeding Syndrome and Takotsubo Cardiomyopathy.

BACKGROUND Wernicke encephalopathy (WE) is a neurological condition commonly associated with sustained alcohol abuse. However, it should be noted that disorders resulting in severe malnutrition, such as anorexia nervosa (AN), can precipitate nonalcoholic WE. AN is a life threatening psychological and eating disorder defined by inappropriate weight loss from food restriction due to the fear of gaining weight and immoderate desire to be thin. Treatment of those suffering with AN can often be complicated by severe electrolyte derangements after caloric intake termed refeeding syndrome. Although extremely rare, severe cardiomyopathy and ultimately death may occur in patients from AN. CASE REPORT Herein describes the case of a 20-year-old female with AN induced WE complicated by refeeding syndrome and hemodynamic compromise in the setting of findings consistent with takotsubo cardiomyopathy. She required ventilatory and hemodynamic support with aggressive intravenous thiamine and phosphorus repletion. Nutritional supplementation was imperative and carefully administered throughout her hospitalization. Her symptoms improved over the course of a few weeks with an ultimate reversal of her cardiomyopathy. CONCLUSIONS Given the morbidity surrounding AN, practitioners should exhibit caution when caring for those with severe nutritional deficiencies. Clinicians must monitor for severe electrolyte abnormalities and offer aggressive repletion. In addition to electrolyte derangements, severe cardiomyopathy may result as a rare sequela of the aforementioned complications associated with AN. Moreover, it is imperative to understand that patients with AN have the highest mortality of any psychiatric disorder and early intervention is necessary for survival in this vulnerable patient population.

Takotsubo cardiomyopathy complicated with apical thrombus formation on first day of the illness: a case report and literature review.

BACKGROUND: Takotsubo cardiomyopathy is characterized by transient systolic dysfunction of the apical and mid segments of the left ventricle in the absence of obstructive coronary artery disease. Intraventricular thrombus formation is a rare complication of Takotsubo cardiomyopathy and current data almost exclusively consists of isolated case reports and a few case series. Here we describe a case of Takotsubo cardiomyopathy with formation of an apical thrombus within 24 h of symptom onset, which has been reported in the literature only once previously, to the best of our knowledge. We have reviewed the available literature that may aid clinicians in their approach to the condition, since no published guidelines are available. CASE PRESENTATION: A 68-year-old Sri Lankan female presented to a local hospital with chest pain. Electrocardiogram (ECG) showed ST elevation, and antiplatelets, intravenous streptokinase and a high dose statin were administered. Despite this ST elevation persisted; however the coronary angiogram was negative for obstructive coronary artery disease. Echocardiogram revealed hypokinesia of the mid and apical segments of the left ventricle with typical apical ballooning and a sizable apical thrombus. She had recently had a viral infection and was also emotionally distressed as her sister was recently diagnosed with a terminal cancer. A diagnosis of Takotsubo cardiomyopathy was made and anticoagulation was started with heparin and warfarin. The follow up echocardiogram performed 1 week later revealed a small persistent thrombus, which had completely resolved at 3 weeks. CONCLUSION: Though severe systolic dysfunction is observed in almost all the patients with Takotsubo cardiomyopathy, intraventricular thrombus formation on the first day of the illness is rare. The possibility of underdiagnosis of thrombus can be prevented by early echocardiogram in Takotsubo cardiomyopathy. The majority of reports found in the literature review were of cases that had formed an intraventriclar thrombus within the first 2 weeks, emphasizing the importance of follow up echocardiography at least 2 weeks later. The management of a left ventricular thrombus in Takotsubo cardiomyopathy is controversial and in most cases warfarin and heparin were used for a short duration.

Use of an argatroban-based purge solution in a percutaneous ventricular assist device.

PURPOSE: The use of an argatroban-based percutaneous ventricular assist device (pVAD) purge solution in a patient with suspected heparin-induced thrombocytopenia (HIT) is described. SUMMARY: A 70-year-old woman in cardiogenic shock was admitted to a coronary care unit after being discovered unresponsive at home. A transthoracic echocardiogram revealed a low ejection fraction and findings consistent with takotsubo cardiomyopathy. Administration of multiple inotropes and vasopressors was initially required for hemodynamic support. The patient was implanted with an Impella pVAD (Abiomed, Inc., Danvers, MA) using a heparin-based purge solution; an i.v. heparin infusion was initiated for supplemental systemic anticoagulation. Over the next 24 hours, the patient's platelet count decreased from 168,000 to 37,000 cells/µL. Given a differential diagnosis that included HIT, the patient was transitioned to an argatroban-based purge solution. Due to prolonged activated partial thromboplastin times, a systemic argatroban infusion was not initiated, and the patient remained fully anticoagulated throughout pVAD support with only the argatroban-based purge solution. An HIT antibody test was negative. On hospitalization day 9 (day 6 of pVAD support with argatroban use), the patient became hemodynamically stable and was weaned off pVAD support. Three days later, the platelet count had recovered to 117,000 cells/µL (from a nadir of 21,000 cells/µL). During pVAD support, the patient developed hemolytic anemia with minimal bleeding complications. CONCLUSION: Argatroban was used as a purge solution anticoagulant in a patient with an Impella pVAD and found to be a safe and effective alternative to heparin.

Transient reverse takotsubo cardiomyopathy following a spider bite in Greece: a case report.

Black widow spider is endemic in the Mediterranean area and although envenomations are rare, may occasionally lead to death. We present a case of a 64-year-old female developing a rare variant of takotsubo, stress-induced, cardiomyopathy after a spider bite. This resulted in acute heart failure within 24  hours of the bite. With medical treatment and supportive care, the patient's clinical condition improved. Reverse takotsubo cardiomyopathy was diagnosed by echocardiography, which was transient. Clinical and echocardiographic findings have been completely resolved on follow-up 46 days later. Reverse takotsubo cardiomyopathy has not been yet described following a spider bite. Doctors in the emergency department of endemic countries should be familiar with this potential complication.