Coagulative Disorders in Critically Ill COVID-19 Patients with Acute Distress Respiratory Syndrome: A Critical Review.

In critically ill patients with acute respiratory distress syndrome (ARDS) coronavirus disease 2019 (COVID-19), a high incidence of thromboembolic and hemorrhagic events is reported. COVID-19 may lead to impairment of the coagulation cascade, with an imbalance in platelet function and the regulatory mechanisms of coagulation and fibrinolysis. Clinical manifestations vary from a rise in laboratory markers and subclinical microthrombi to thromboembolic events, bleeding, and disseminated intravascular coagulation. After an inflammatory trigger, the mechanism for activation of the coagulation cascade in COVID-19 is the tissue factor pathway, which causes endotoxin and tumor necrosis factor-mediated production of interleukins and platelet activation. The consequent massive infiltration of activated platelets may be responsible for inflammatory infiltrates in the endothelial space, as well as thrombocytopenia. The variety of clinical presentations of the coagulopathy confronts the clinician with the difficult questions of whether and how to provide optimal supportive care. In addition to coagulation tests, advanced laboratory tests such as protein C, protein S, antithrombin, tissue factor pathway inhibitors, D-dimers, activated factor Xa, and quantification of specific coagulation factors can be useful, as can thromboelastography or thromboelastometry. Treatment should be tailored, focusing on the estimated risk of bleeding and thrombosis. The aim of this review is to explore the pathophysiology and clinical evidence of coagulation disorders in severe ARDS-related COVID-19 patients.

Pharmacokinetics and pharmacodynamics of ticagrelor in the treatment of cardiac ischemia.

INTRODUCTION: After acute coronary syndromes (ACS), the so-called dual antiplatelet therapy (DAPT), which usually consists of low-dose of aspirin in combination with a thienopyridine (clopidogrel, prasugrel) or with a cyclopentyltriazolopyrimidine (ticagrelor), reduces the risk of ischemic events. Ticagrelor, un particular, is an effective drug as it isn' a prodrug, doesn't require metabolic activation and demonstrates a rapid onset and faster offset of action. Areas covered: This article evaluates the pharmacokinetics, efficacy, safety and tolerability of ticagrelor during DAPT after ACS and its potential use beyond the canonical twelve months after PCI. The review discusses studies comparing: ticagrelor and clopidogrel (DISPERSE, DISPERSE-2, PLATO, RESPOND Trial, ONSET/OFFSET Trials), ticagrelor and placebo (PEGASUS TIMI 54 Trial). Expert opinion: For ACS patients, the PLATO trial showed that ticagrelor was superior to clopidogrel in the reduction of cardiovascular death, myocardial infarction and stroke. PEGASUS TIMI 54 showed that patients in whom ischemic events and cardiovascular death outweigh the risk of life-threatening bleeding, may benefit from prolonged ticagrelor-based dual antiplatelet therapy, over 12 months. This strategy has been recently approved by the ACC/AHA guidelines. Further studies are needed to evaluate and eventually validate the role of the prolonged DAPT in patients treated with new generation stents.

Mutation Analysis of PRKAR1A Gene in a Patient with Atrial Myxoma.

BACKGROUND: Intracardiac myxomas are frequent benign tumors of the heart and typically localize in the left atri- um and interatrial septum. When myxomas generate at other sites, they are designated as atypical. Mutations in the PRKAR1A gene (a tumor suppressor gene that encodes a protein kinase A [PKA] regulatory 1-alpha subunit) have been identified in both syndromic and non-syndromic cardiac atypical myxomas. METHODS: We report the case of a 33-year old woman suffering from night fever, weight loss, asthenia, and progressive dyspnea. RESULTS: The blood laboratory tests revealed microcytic anemia, leukocytosis, thrombocytosis, increased serum levels of C-reactive protein level, and negative blood cultures. Physical examination also demonstrated a 2/6 systolic murmur. Transthoracic and trans-esophageal echocardiography showed a voluminous, mobile mass in the left atrium with a secondary dynamic obstruction of the left cardiac chamber and a significant functional mitral stenosis. A myxoma was supposed and the patient underwent surgery. Histologically, the lesion was identified as myxomatous tumor with gelatinous pattern. No germline mutations of the PRKAR1A gene were detected. The postoperative course did not present any complications, and the patient was discharged on the sixth postoperative day in good clinical condition. Accordingly, there was an improvement in the laboratory tests' results and a resolution of symptoms. CONCLUSIONS: The patient presented an atrial giant gelatinous myxoma with peculiarity of fever of unknown origin, without PRKAR1A gene germline mutations.

Stress Computed Tomography Myocardial Perfusion Imaging: A New Topic in Cardiology.

Since its introduction about 15 years ago, coronary computed tomography angiography has become today the most accurate clinical instrument for noninvasive assessment of coronary atherosclerosis. Important technical developments have led to a continuous stream of new clinical applications together with a significant reduction in radiation dose exposure. Latest generation computed tomography scanners (≥ 64 slices) allow the possibility of performing static or dynamic perfusion imaging during stress by using coronary vasodilator agents (adenosine, dipyridamole, or regadenoson), combining both functional and anatomical information in the same examination. In this article, the emerging role and state-of-the-art of myocardial computed tomography perfusion imaging are reviewed and are illustrated by clinical cases from our experience with a second-generation dual-source 128-slice scanner (Somatom Definition Flash, Siemens; Erlangen, Germany). Technical aspects, data analysis, diagnostic accuracy, radiation dose and future prospects are reviewed.

Comorbidities frequency in Takotsubo syndrome: an international collaborative systematic review including 1109 patients.

BACKGROUND: To identify predisposing factors that can result in the onset of takotsubo syndrome, we performed an international, collaborative systematic review focusing on clinical characteristics and comorbidities of patients with takotsubo syndrome. METHODS: We searched and reviewed cited references up to August 2013 to identify relevant studies. Corresponding authors of selected studies were contacted and asked to provide additional quantitative details. Data from each study were extracted by 2 independent reviewers. The cumulative prevalence of presenting features and comorbidities was assessed. Nineteen studies whose authors sent the requested information were included in the systematic review, with a total of 1109 patients (951 women; mean age, 59-76 years). Evaluation of risk factors showed that obesity was present in 17% of patients (range, 2%-48%), hypertension in 54% (range, 27%-83%), dyslipidemia in 32% (range, 7%-59%), diabetes in 17% (range, 4%-34%), and smoking in 22% (range, 6%-49%). Emotional stressors preceded takotsubo syndrome in 39% of patients and physical stressors in 35%. The most common comorbidities were psychological disorders (24%; range, 0-49%), pulmonary diseases (15%; range, 0-22%), and malignancies (10%; range, 4%-29%). Other common associated disorders were neurologic diseases (7%; range, 0-22%), chronic kidney disease (7%; range, 2%-27%), and thyroid diseases (6%; range, 0-37%). CONCLUSIONS: Patients with takotsubo syndrome have a relevant prevalence of cardiovascular risk factors and associated comorbidities. Such of associations needs to be evaluated in further studies.

Secondary prevention after acute myocardial infarction: drug adherence, treatment goals, and predictors of health lifestyle habits. The BLITZ-4 Registry.

BACKGROUND: To describe drug adherence and treatment goals, and to identify the independent predictors of smoking persistence and unsatisfactory lifestyle habits six months after an acute myocardial infarction (AMI). METHODS AND RESULTS: 11,706 patients with AMI (30% female, mean age 68 years) were enrolled in 163 large-volume coronary care units (CCUs). At six months, drug adherence was ≥90%, while blood pressure (BP) <140/90 mmHg, low density lipoprotein (LDL) <100 mg/dl (in patients on statins), HbA1c <7% (in treated diabetics), and smoking persistence were observed in 74%, 76%, 45%, and 27% of patients, respectively. Inadequate fish intake decreased from 73% to 55%, inadequate intake of fruit and vegetables from 32% to 23%, and insufficient exercise in eligible patients from 74% to 59% (p < 0.0001). At multivariable analysis, a post-discharge cardiac visit and referral to cardiac rehabilitation at follow-up were independently associated with a lower risk of insufficient physical exercise (odds ratio (OR) 0.71 and 0.70, respectively) and persistent smoking (OR 0.68 and 0.60), whereas only referral to cardiac rehabilitation was associated with a lower risk of inadequate fish and fruit/vegetable intake (OR 0.70 and 0.65). CONCLUSIONS: Six months after an AMI, despite a high adherence to drug treatments, BP, LDL, and diabetic goals are inadequately achieved. Subjects with healthy lifestyles improved after discharge, but the rate of those with regular exercise habits and adequate fish intake could be further improved. Access to post-discharge cardiac visit and referral to cardiac rehabilitation were associated with better adherence to healthy lifestyles. Knowledge of the variables associated with specific lifestyle changes may help in tailoring secondary prevention programmes.