Empagliflozin in acute myocardial infarction: the EMMY trial.

AIMS: Sodium-glucose co-transporter 2 inhibition reduces the risk of hospitalization for heart failure and for death in patients with symptomatic heart failure. However, trials investigating the effects of this drug class in patients following acute myocardial infarction are lacking. METHODS AND RESULTS: In this academic, multicentre, double-blind trial, patients (n = 476) with acute myocardial infarction accompanied by a large creatine kinase elevation (>800 IU/L) were randomly assigned to empagliflozin 10 mg or matching placebo once daily within 72 h of percutaneous coronary intervention. The primary outcome was the N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP) change over 26 weeks. Secondary outcomes included changes in echocardiographic parameters. Baseline median (interquartile range) NT-proBNP was 1294 (757-2246) pg/mL. NT-proBNP reduction was significantly greater in the empagliflozin group, compared with placebo, being 15% lower [95% confidence interval (CI) -4.4% to -23.6%] after adjusting for baseline NT-proBNP, sex, and diabetes status (P = 0.026). Absolute left-ventricular ejection fraction improvement was significantly greater (1.5%, 95% CI 0.2-2.9%, P = 0.029), mean E/e' reduction was 6.8% (95% CI 1.3-11.3%, P = 0.015) greater, and left-ventricular end-systolic and end-diastolic volumes were lower by 7.5 mL (95% CI 3.4-11.5 mL, P = 0.0003) and 9.7 mL (95% CI 3.7-15.7 mL, P = 0.0015), respectively, in the empagliflozin group, compared with placebo. Seven patients were hospitalized for heart failure (three in the empagliflozin group). Other predefined serious adverse events were rare and did not differ significantly between groups. CONCLUSION: In patients with a recent myocardial infarction, empagliflozin was associated with a significantly greater NT-proBNP reduction over 26 weeks, accompanied by a significant improvement in echocardiographic functional and structural parameters. CLINICALTRIALS.GOV REGISTRATION: NCT03087773.

[Systemic consequences and clinical aspects of SARS-CoV-2 infection]. / Systemische Auswirkungen und klinische Aspekte der SARS-CoV-2-Infektion.

BACKGROUND: COVID-19 is considered a systemic disease. A severe course with fatal outcome is possible and unpredictable. OBJECTIVES: Which organ systems are predominantly involved? Which diseases are predisposed for a fatal course? Which organ changes are found with lethal outcome? MATERIALS AND METHODS: Data from published autopsy studies (28 cases by our group) with respect to organ changes and possible cause of death. RESULTS: The most severe alterations are found in the lungs by diffuse alveolar damage as a symptom of an acute respiratory distress syndrome (ARDS), in part with fibrosis. Thrombosis of small- to mid-sized pulmonary arteries is associated with hemorrhagic lung infarction. Frequent complications are bacterial pneumonias and less frequently fungal pneumonias by aspergillus. Pulmonary thromboembolism is found in 20-30% of lethal courses, also in the absence of deep venous thrombosis. Intestinal involvement of COVID-19 can be associated with intestinal ischemia, caused by shock or local thrombosis. In most cases, the kidneys display acute tubular injury reflecting acute renal failure, depletion of lymphocytes in the lymph nodes and spleen, and hyperplastic adrenal glands. The liver frequently reveals steatosis, liver cell necrosis, portal inflammation, and proliferation of Kupffer cells. Important preexisting diseases in autopsy studies are arterial hypertension with hypertensive and ischemic cardiomyopathy and diabetes mellitus but large population-based studies reveal increased risk of mortality only for diabetes mellitus not for arterial hypertension. CONCLUSIONS: Alterations of the pulmonary circulation with pulmonary arterial thrombosis, infarction, and bacterial pneumonia are important and often lethal complications of COVID-19-associated ARDS. Findings from autopsy studies have influenced therapy and prophylaxis.

Pulmonary Arterial Thrombosis in COVID-19 With Fatal Outcome : Results From a Prospective, Single-Center, Clinicopathologic Case Series.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become pandemic, with substantial mortality. OBJECTIVE: To evaluate the pathologic changes of organ systems and the clinicopathologic basis for severe and fatal outcomes. DESIGN: Prospective autopsy study. SETTING: Single pathology department. PARTICIPANTS: 11 deceased patients with COVID-19 (10 of whom were selected at random for autopsy). MEASUREMENTS: Systematic macroscopic, histopathologic, and viral analysis (SARS-CoV-2 on real-time polymerase chain reaction assay), with correlation of pathologic and clinical features, including comorbidities, comedication, and laboratory values. RESULTS: Patients' age ranged from 66 to 91 years (mean, 80.5 years; 8 men, 3 women). Ten of the 11 patients received prophylactic anticoagulant therapy; venous thromboembolism was not clinically suspected antemortem in any of the patients. Both lungs showed various stages of diffuse alveolar damage (DAD), including edema, hyaline membranes, and proliferation of pneumocytes and fibroblasts. Thrombosis of small and mid-sized pulmonary arteries was found in various degrees in all 11 patients and was associated with infarction in 8 patients and bronchopneumonia in 6 patients. Kupffer cell proliferation was seen in all patients, and chronic hepatic congestion in 8 patients. Other changes in the liver included hepatic steatosis, portal fibrosis, lymphocytic infiltrates and ductular proliferation, lobular cholestasis, and acute liver cell necrosis, together with central vein thrombosis. Additional frequent findings included renal proximal tubular injury, focal pancreatitis, adrenocortical hyperplasia, and lymphocyte depletion of spleen and lymph nodes. Viral RNA was detectable in pharyngeal, bronchial, and colonic mucosa but not bile. LIMITATION: The sample was small. CONCLUSION: COVID-19 predominantly involves the lungs, causing DAD and leading to acute respiratory insufficiency. Death may be caused by the thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite the use of prophylactic anticoagulation. Studies are needed to further understand the thrombotic complications of COVID-19, together with the roles for strict thrombosis prophylaxis, laboratory and imaging studies, and early anticoagulant therapy for suspected pulmonary arterial thrombosis or thromboembolism. PRIMARY FUNDING SOURCE: None.

B-Lines for the assessment of extravascular lung water: Just focused or semi-quantitative?

BACKGROUND: B-lines as typical artefacts of lung ultrasound are considered as surrogate measurement for extravascular lung water. However, B-lines develop in the sub-pleural space and do not allow assessment of the whole lung. Here, we present data from the first observational multi-centre study focusing on the correlation between a B-lines score and extravascular lung water in critically ill patients suffering from a variety of diseases. PATIENTS AND METHODS: In 184 adult patients, 443 measurements were obtained. B-lines were counted and expressed in a score which was compared to extravascular lung water, measured by single-indicator transpulmonary thermodilution. Appropriate correlation coefficients were calculated and receiver operating characteristics (ROC-) curves were plotted. RESULTS: Overall, B-lines score was correlated with body weight-indexed extravascular lung water characterized by r = .59. The subgroup analysis revealed a correlation coefficient in patients without an infection of r = .44, in those with a pulmonary infection of r = .75 and in those with an abdominal infection of r = .23, respectively. Using ROC-analysis the sensitivity and specificity of B-lines for detecting an increased extravascular lung water (>10 mL/kg) was 63% and 79%, respectively. In patients with a P/F ratio <200 mm Hg, sensitivity and specificity to predict an increased extravascular lung water was 71% and 93%, respectively. CONCLUSIONS: Assessment of B-lines does not accurately reflect actual extravascular lung water. In presence of an impaired oxygenation, B-lines may reliably indicate increased extravascular lung water as cause of the oxygenation disorders.

Impact of EMpagliflozin on cardiac function and biomarkers of heart failure in patients with acute MYocardial infarction-The EMMY trial.

BACKGROUND: Sodium glucose cotransporter 2 (SGLT2) inhibitors are established antidiabetic drugs with proven cardiovascular benefit. Although growing evidence suggests beneficial effects on myocardial remodeling, fluid balance and cardiac function, the impact of empagliflozin initiated early after acute myocardial infarction (AMI) has not been investigated yet. Therefore, the impact of EMpagliflozin on cardiac function and biomarkers of heart failure in patients with acute MYocardial infarction (EMMY) trial was designed to investigate the efficacy and safety of empagliflozin in diabetic and non-diabetic patients after severe AMI. METHODS: Within a multicenter, randomized, double-blind, placebo-controlled, phase 3b trial we will enroll patients with AMI and characteristics suggestive of severe myocardial necrosis are randomized in a 1:1 ratio to empagliflozin (10 mg once daily) or matching placebo. The primary endpoint is the impact of empagliflozin on changes in NT-proBNP within 6 months after AMI. Secondary endpoints include changes in echocardiographic parameters, levels of ketone body concentrations, HbA1c levels and body weight, respectively. Hospitalization rate due to heart failure or other causes, the duration of hospital stay and all-cause mortality will be assessed as exploratory secondary endpoints. DISCUSSION: The EMMY trial will test empagliflozin in patients with AMI regardless of their diabetic status. The EMMY trial may therefore underpin the concept of SGLT2 inhibition to improve cardiac remodeling, pre-and afterload reduction and cardiac metabolism regardless of its antidiabetic effects. Results will provide the rationale for the conduct of a cardiovascular outcome trial to test the effect of empagliflozin in patients with AMI.

Does the integration of personalized ultrasound change patient management in critical care medicine? Observational trials.

Objective. To test the influence of personalized ultrasound (PersUS) on patient management in critical care. Design of the Study. Prospective, observational, and critical care setting. Four substudies compared PersUS and mobile ultrasound, work distribution, and diagnostic and procedural quality. Patients and Interventions. 640 patient ultrasound exams including 548 focused diagnostic exams and 92 interventional procedures. Main Outcome Measures. Number of studies, physician's judgement of feasibility, time of usage per patient, and referrals to echo lab. Results. Randomized availability of PersUS increased its application in ICU work shifts more than twofold from 33 to 68 exams mainly for detection and therapy of effusions. Diagnostic and procedural quality was rated as excellent/very good in PersUS-guided puncture in 95% of cases. Integrating PersUS within an initial physical examination of 48 randomized cases in an emergency department, PersUS extended the examination time by 100 seconds. Interestingly, PersUS integration into 53 randomized regular ward rounds of 1007 patients significantly reduced average contact time per patient by 103 seconds from 8.9 to 7.2 minutes. Moreover, it lowered the patient referral rate to an echo lab from 20% to 2% within the study population. Conclusions. We propose the development of novel ultrasound-based clinical pathways by integration of PersUS.

Lung ultrasound in the diagnosis and follow-up of community-acquired pneumonia: a prospective, multicenter, diagnostic accuracy study.

BACKGROUND: The aim of this prospective, multicenter study was to define the accuracy of lung ultrasound (LUS) in the diagnosis of community-acquired pneumonia (CAP). METHODS: Three hundred sixty-two patients with suspected CAP were enrolled in 14 European centers. At baseline, history, clinical examination, laboratory testing, and LUS were performed as well as the reference test, which was a radiograph in two planes or a low-dose CT scan in case of inconclusive or negative radiographic but positive LUS findings. In patients with CAP, follow-up between days 5 and 8 and 13 and 16 was scheduled. RESULTS: CAP was confirmed in 229 patients (63.3%). LUS revealed a sensitivity of 93.4% (95% CI, 89.2%-96.3%), specificity of 97.7% (95% CI, 93.4%-99.6%), and likelihood ratios (LRs) of 40.5 (95% CI, 13.2-123.9) for positive and 0.07 (95% CI, 0.04-0.11) for negative results. A combination of auscultation and LUS increased the positive LR to 42.9 (95% CI, 10.8-170.0) and decreased the negative LR to 0.04 (95% CI, 0.02-0.09). We found 97.6% (205 of 211) of patients with CAP showed breath-dependent motion of infiltrates, 86.7% (183 of 211) an air bronchogram, 76.5% (156 of 204) blurred margins, and 54.4% (105 of 193) a basal pleural effusion. During follow-up, median C-reactive protein levels decreased from 137 mg/dL to 6.3 mg/dL at days 13 to 16 as did signs of CAP; median area of lesions decreased from 15.3 cm2 to 0.2 cm2 and pleural effusion from 50 mL to 0 mL. CONCLUSIONS: LUS is a noninvasive, usually available tool used for high-accuracy diagnosis of CAP. This is especially important if radiography is not available or applicable. About 8% of pneumonic lesions are not detectable by LUS; therefore, an inconspicuous LUS does not exclude pneumonia.

Cardiac movement identified on prehospital echocardiography predicts outcome in cardiac arrest patients.

INTRODUCTION: The prognostic value of emergency echocardiography (EE) in the management of cardiac arrest patients has previously been studied in an in-hospital setting. These studies mainly included patients who underwent cardiopulmonary resuscitation (CPR) by emergency medicine technicians at the scene and who arrived at the emergency department (ED) still in a state of cardiac arrest. In most European countries, cardiac arrest patients are normally treated by physician-staffed emergency medical services (EMS) teams on scene. Transportation to the ED while undergoing CPR is uncommon. OBJECTIVE: To evaluate the ability of EE to predict outcome in cardiac arrest patients when it is performed by ultrasound-inexperienced emergency physicians on scene. METHODS: We performed a prospective, observational study of nonconsecutive, nontrauma, adult cardiac arrest patients who were treated by physician-staffed urban EMS teams on scene. Participating emergency physicians (EPs) received a two-hour course in EE during CPR. After initial procedures were accomplished, EE was performed during a rhythm and pulse check. A single subxiphoid, four-chamber view was required for study enrollment. We defined sonographic evidence of cardiac kinetic activity as any detected motion of the myocardium, ranging from visible ventricular fibrillation to coordinated ventricular contractions. The CPR had to be continued for at least 15 minutes after the initial echocardiography. No clinical decisions were made based on the results of EE. RESULTS: Forty-two patients were enrolled in the study. The heart could be visualized successfully in all patients. Five (11.9%) patients survived to hospital admission. Of the 32 patients who had cardiac standstill on initial EE, only one (3.1%) survived to hospital admission, whereas four out of 10 (40%) patients with cardiac movement on initial EE survived to hospital admission (p = 0.008). Neither asystole on initial electrocardiogram nor peak capnography value, age, bystander CPR, or downtime was a significant predictor of survival. Only cardiac movement was associated with survival, and cardiac standstill at any time during CPR resulted in a positive predictive value of 97.1% for death at the scene. CONCLUSION: Our results support the idea of focused echocardiography as an additional criterion in the evaluation of outcome in CPR patients and demonstrate its feasibility in the prehospital setting.

Contrast-enhanced ultrasound detects gallbladder perforation in a patient with acute abdominal pain.

We present the case of a patient with abdominal pain, in which gallbladder perforation was detected by contrast-enhanced ultrasound. A 90-year-old patient presented to the emergency department with a complaint of acute abdominal pain and vomiting. An abdominal ultrasound revealed a thickened gallbladder wall and small amounts of perihepatic fluid. Because these findings were suspicious for gallbladder perforation and contrast-enhanced computed tomography could not be performed because of a history of monoclonal gammopathy, a contrast-enhanced ultrasound scan was performed. After the administration of 2.5 mL of SonoVue (Bracco, Milan, Italy), a defect of the gallbladder wall was detected. The patient underwent laparotomy, on which the diagnosis of gallbladder perforation was confirmed.

[Thoracoabdominal sonography (E-FAST plus) -AI training module 5 in anaesthesiologist: performed focussed sonography]. / DGAI-zertifizierte Seminarreihe Anästhesie Fokussierte Sonografie - Modul 5: Thorakoabdominelle Sonografie (E-FAST plus).

Anesthesiologists and Critical Care Physicians are confronted with the differential diagnoses of dyspnea, complications of mechanical ventilation or rapid assessment of trauma patients on a nearly daily basis. This requires the timely diagnosis or exclusion of a wide variety of disease processes including pleura effusion, pneumonia, pneumothorax as well as thoracical or abdominal bleeding. Furthermore, the anaesthesiologist or intensivist often makes decisions leading to invasive procedures like thoracentesis or percutaneous dilatational tracheostomy. Bedside ultrasound as the "visual stethoscope" of the acute care physician offers an alternative to other imaging modalities like X-ray and CAT scan and can reduce associated high-risk transportation of mechanically ventilated patients. In this article, we introduce a new training module based on the DGAI curriculum.

Prehospital lung ultrasound in the distinction between pulmonary edema and exacerbation of chronic obstructive pulmonary disease.

We present 2 cases of dyspneic patients, where prehospital lung ultrasound helped to distinguish between pulmonary edema and acute exacerbation of chronic obstructive pulmonary disease.