Trimethylamine-N-oxide is associated with cardiovascular mortality and vascular brain lesions in patients with atrial fibrillation.

OBJECTIVE: Trimethylamine-N-oxide (TMAO) is a metabolite derived from the microbial processing of dietary phosphatidylcholine and carnitine and the subsequent hepatic oxidation. Due to its prothrombotic and inflammatory mechanisms, we aimed to assess its role in the prediction of adverse events in a susceptible population, namely patients with atrial fibrillation. METHODS: Baseline TMAO plasma levels were measured by liquid chromatography-tandem mass spectrometry in 2379 subjects from the ongoing Swiss Atrial Fibrillation cohort. 1722 underwent brain MRI at baseline. Participants were prospectively followed for 4 years (Q1-Q3: 3.0-5.0) and stratified into baseline TMAO tertiles. Cox proportional hazards and linear and logistic mixed effect models were employed adjusting for risk factors. RESULTS: Subjects in the highest TMAO tertile were older (75.4±8.1 vs 70.6±8.5 years, p<0.01), had poorer renal function (median glomerular filtration rate: 49.0 mL/min/1.73 m2 (35.6-62.5) vs 67.3 mL/min/1.73 m2 (57.8-78.9), p<0.01), were more likely to have diabetes (26.9% vs 9.1%, p<0.01) and had a higher prevalence of heart failure (37.9% vs 15.8%, p<0.01) compared with patients in the lowest tertile. Oral anticoagulants were taken by 89.1%, 94.0% and 88.2% of participants, respectively (from high to low tertiles). Cox models, adjusting for baseline covariates, showed increased total mortality (HR 1.65, 95% CI 1.17 to 2.32, p<0.01) as well as cardiovascular mortality (HR 1.86, 95% CI 1.21 to 2.88, p<0.01) in the highest compared with the lowest tertile. When present, subjects in the highest tertile had more voluminous, large, non-cortical and cortical infarcts on MRI (log-transformed volumes; exponentiated estimate 1.89, 95% CI 1.11 to 3.21, p=0.02) and a higher chance of small non-cortical infarcts (OR 1.61, 95% CI 1.16 to 2.22, p<0.01). CONCLUSIONS: High levels of TMAO are associated with increased risk of cardiovascular mortality and cerebral infarction in patients with atrial fibrillation. TRIAL REGISTRATION NUMBER: NCT02105844.

Analysis of Diagnostic Modalities in Hospital-admitted Patients Evaluated for COVID-19.

BACKGROUND/AIM: To assess the diagnostic performance of reverse transcriptase polymerase chain reaction (RT-PCR), low-dose chest computed tomography (CT), and serological testing, alone and in combinations, as well as routine inflammatory markers in patients evaluated for COVID-19 during the first wave in early 2020. PATIENTS AND METHODS: We retrospectively analyzed data of all patients who were admitted to the emergency department due to fever and/or respiratory symptoms. CT scans were rated using the COVID-19 Reporting and Data System (CO-RADS) suspicion score. True disease status (COVID-19 - positive vs. negative) was adjudicated by two independent clinicians. Receiver-operating characteristic curves and areas under the curves were calculated for inflammatory markers. Sensitivities and specificities were calculated for RT-PCR, CT, and serology alone, as well as the combinations of RT-PCR+CT, RT-PCR+serology, CT+serology, and all three modalities. RESULTS: Of 221 patients with a median age of 72 years, 113 were classified as COVID-19 positive. Among 180 patients from which data on CT and RT-PCR were available, RT-PCR had the highest sensitivity to detect COVID-19 (0.87; 95%CI=0.78-0.93). Notably, the addition of CT in the analysis increased sensitivity to 0.89 (95%CI=0.8-0.94), but lowered specificity from 1 (95%CI=0.96-1) to 0.9 (95%CI=0.83-0.95). The combination of RT-PCR, CT and serology (n=60 patients with complete dataset) yielded a sensitivity of 0.83 (95%CI=0.61-0.94) and specificity of 0.86 (95%CI=0.72-0.93). CONCLUSION: RT-PCR was the best single test in patients evaluated for COVID-19. Conversely, the routine performance of chest CT adds little sensitivity and decreases specificity.

Out-of-hospital cardiac arrests and mortality in Swiss Cantons with high and low COVID-19 incidence: A nationwide analysis.

AIMS: Many countries reported an increase of out-of-hospital cardiac arrests (OHCAs) and mortality during the COVID-19 pandemic. However, all these data refer to regional settings and national data are still missing. We aimed to assess the OHCA incidence and population mortality during COVID-19 pandemic in whole Switzerland and in the different regions (Cantons) according to the infection rate. METHODS: We considered OHCAs and deaths which occurred in Switzerland after the first diagnosed case of COVID-19 (February 25th) and for the subsequent 65 days and in the same period in 2019. We also compared Cantons with high versus low COVID-19 incidence. RESULTS: A 2.4% reduction in OHCA cases was observed in Switzerland. The reduction was particularly high (-21.4%) in high-incidence COVID-19 cantons, whilst OHCAs increased by 7.7% in low-incidence COVID-19 cantons. Mortality increased by 8.6% in the entire nation: a 27.8% increase in high-incidence cantons and a slight decrease (-0.7%) in low-incidence cantons was observed. The OHCA occurred more frequently at home, CPR and AED use by bystander were less frequent during the pandemic. Conversely, the OHCAs percentage in which a first responder was present, initiated the CPR and used an AED, increased. The outcome of patients in COVID-19 high-incidence cantons was worse compared to low-incidence cantons. CONCLUSIONS: During the COVID-19 pandemic in Switzerland mortality increased in Cantons with high-incidence of infection, whilst not in the low-incidence ones. OHCA occurrence followed an opposite trend showing how variables related to the health-system and EMS organization deeply influence OHCA occurrence during a pandemic.

Patient voluntarily delays call to emergency medical system for ST-elevation myocardial infarction during COVID-19 pandemic.

BACKGROUND: An increase in the time from the symptoms onset to first medical contact and to primary percutaneous coronary intervention (pPCI) has been observed in countries with high-incidence of COVID-19 cases. We aimed to verify if there was any change in the patient delay and in the EMS response times up to the pPCI for STEMI patients in Swiss Ticino Canton. METHODS: We assessed STEMI management including time from symptoms onset to EMS call, time of EMS response, time to pPCI in Swiss Canton Ticino. Data were retrieved from the Acute-Coronary-Syndrome-Ticino-Registry. We considered the patients included in the registry from March to May 2020 (pandemic period) and then from June to August 2020 (post-pandemic period) in whom a pPCI was performed. We compared these patients to those undergoing a pPCI in the same months in the year 2016-2019. RESULTS: During the pandemic period, the time from symptoms onset to pPCI significantly increased compared to non-pandemic periods. This was due to a significant prolongation of the time from symptoms onset to EMS call, that nearly tripled. In contrast, after the pandemic period, there was a significantly shorter time from symptom onset to EMS call compared to non-pandemic years, whereas all other times remained unchanged. CONCLUSION: Patients delay the call to EMS despite symptoms of myocardial infarction during the COVID-19 pandemic also in a region with a relatively low incidence of COVID-19.

Serum lactate at 24 hours is associated with outcome in children requiring extracorporeal membrane oxygenation for pulmonary causes - a retrospective, observational study.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) has become an essential life-saving tool. Being resource-intensive, judicious use and optimising the outcomes of this precious resource is important. This retrospective, explanatory, observational study aimed to quantify associations between factors and outcome after pulmonary ECMO in children. METHODS: This study included 39 consecutive ECMO runs in 38 children performed for pulmonary indications at our hospital from 2008 to 2018. Indications included acute respiratory distress syndrome, infection, drowning, meconium aspiration and pulmonary hypertension, among others. Depending on the need for haemodynamic support, 21 patients (53.8%) received veno-venous ECMO, while 18 (46.2%) received veno-arterial ECMO. We sought to compare the 11 non-survivors with the 27 survivors with respect to time-independent and time-dependent variables. Logistic regression models and Cox proportional hazards models were used. Threshold analysis was done using the “minimum p-value approach”. RESULTS: 27/39 (69%) ECMO runs could be weaned; 27/38 (71%) patients were discharged. 20/27 (74%) survivors had unremarkable neurological status, six (22%) had mild findings (convulsions, muscular hypotony, neuropathy) and one (4%) had a hemi-syndrome at discharge. Univariate analyses showed a hazard ratio (HR) of 0.48 for log(pH) (95% confidence interval [CI] 0.22 to 1.02, p = 0.055) and an HR of 4.48 for log(lactate) (95% CI 1.92 to 10.48, p = 0.0005). Multivariate models showed an HR of 0.99 for log(pH) (95% CI 0.43 to 2.26, p = 0.98) and an HR of 4.44 for log(lactate) (95% CI 1.65 to 11.95, p = 0.003). Threshold analysis showed lactate >4.1 to be associated with mortality, with an HR of 32.7 (95% CI 4.8 to 221.7, p = 0.0002). This threshold should, however, be interpreted very cautiously. Evidence of an association between serum lactate at 24 hours and mortality was found (difference between survivors and non-survivors: −2.78, 95% CI −5.36 to −0.20, p = 0.037). CONCLUSIONS: The results of ECMO for pulmonary indications are very good. Serum lactate may be an early prognostic indicator.