Proteomic Profiling of Dilated Cardiomyopathy Plasma Samples ─ Searching for Biomarkers with Potential to Predict the Outcome of Therapy.

Determination of the prognosis and treatment outcomes of dilated cardiomyopathy is a serious problem due to the lack of valid specific protein markers. Using in-depth proteome discovery analysis, we compared 49 plasma samples from patients suffering from dilated cardiomyopathy with plasma samples from their healthy counterparts. In total, we identified 97 proteins exhibiting statistically significant dysregulation in diseased plasma samples. The functional enrichment analysis of differentially expressed proteins uncovered dysregulation in biological processes like inflammatory response, wound healing, complement cascade, blood coagulation, and lipid metabolism in dilated cardiomyopathy patients. The same proteome approach was employed in order to find protein markers whose expression differs between the patients well-responding to therapy and nonresponders. In this case, 45 plasma proteins revealed statistically significant different expression between these two groups. Of them, fructose-1,6-bisphosphate aldolase seems to be a promising biomarker candidate because it accumulates in plasma samples obtained from patients with insufficient treatment response and with worse or fatal outcome. Data are available via ProteomeXchange with the identifier PXD046288.

Effects of Hypothermia vs Normothermia on Societal Participation and Cognitive Function at 6 Months in Survivors After Out-of-Hospital Cardiac Arrest: A Predefined Analysis of the TTM2 Randomized Clinical Trial.

Importance: The Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial reported no difference in mortality or poor functional outcome at 6 months after out-of-hospital cardiac arrest (OHCA). This predefined exploratory analysis provides more detailed estimation of brain dysfunction for the comparison of the 2 intervention regimens. Objectives: To investigate the effects of targeted hypothermia vs targeted normothermia on functional outcome with focus on societal participation and cognitive function in survivors 6 months after OHCA. Design, Setting, and Participants: This study is a predefined analysis of an international multicenter, randomized clinical trial that took place from November 2017 to January 2020 and included participants at 61 hospitals in 14 countries. A structured follow-up for survivors performed at 6 months was by masked outcome assessors. The last follow-up took place in October 2020. Participants included 1861 adult (older than 18 years) patients with OHCA who were comatose at hospital admission. At 6 months, 939 of 1861 were alive and invited to a follow-up, of which 103 of 939 declined or were missing. Interventions: Randomization 1:1 to temperature control with targeted hypothermia at 33 °C or targeted normothermia and early treatment of fever (37.8 °C or higher). Main outcomes and measures: Functional outcome focusing on societal participation assessed by the Glasgow Outcome Scale Extended ([GOSE] 1 to 8) and cognitive function assessed by the Montreal Cognitive Assessment ([MoCA] 0 to 30) and the Symbol Digit Modalities Test ([SDMT] z scores). Higher scores represent better outcomes. Results: At 6 months, 836 of 939 survivors with a mean age of 60 (SD, 13) (range, 18 to 88) years (700 of 836 male [84%]) participated in the follow-up. There were no differences between the 2 intervention groups in functional outcome focusing on societal participation (GOSE score, odds ratio, 0.91; 95% CI, 0.71-1.17; P = .46) or in cognitive function by MoCA (mean difference, 0.36; 95% CI,-0.33 to 1.05; P = .37) and SDMT (mean difference, 0.06; 95% CI,-0.16 to 0.27; P = .62). Limitations in societal participation (GOSE score less than 7) were common regardless of intervention (hypothermia, 178 of 415 [43%]; normothermia, 168 of 419 [40%]). Cognitive impairment was identified in 353 of 599 survivors (59%). Conclusions: In this predefined analysis of comatose patients after OHCA, hypothermia did not lead to better functional outcome assessed with a focus on societal participation and cognitive function than management with normothermia. At 6 months, many survivors had not regained their pre-arrest activities and roles, and mild cognitive dysfunction was common. Trial Registration: ClinicalTrials.gov Identifier: NCT02908308.

Characteristics and outcomes of patients admitted for acute heart failure in a single-centre study.

AIMS: Acute heart failure represents a medical condition with very high mortality. Accurate risk stratification can help physicians to improve the health care about these patients. The aim of our study was to characterize real-life patients admitted for acute heart failure in a specific region with one tertiary medical centre and to describe risk factors of short-term and long-term mortality. METHODS AND RESULTS: We performed a retrospective analysis of patients admitted from January 2017 to December 2017 to Department of cardiology of the tertiary medical centre University Hospital in Hradec Kralove. We identified 385 patients admitted for acute heart failure to the standard care and intensive care unit. The median of age was 74 years (IQR 67.5-80) and 34% of patients were female. Hospital admission was due to de novo heart failure in 222 (57.7%) patients. The most common comorbidities were arterial hypertension (77.7%), dyslipidaemia (67.3%) and coronary artery disease (63.1%). Coronary artery disease (52.7% of cases) and valve disease (28.1% of cases) were the most common aetiologies of heart failure. The all-cause in-hospital mortality was 12.7%, 30-day mortality was 14.6% and 1 year mortality was 34%. Among risk factors of in-hospital mortality, the most significant factors were haemodialysis during the hospitalization [odds ratio (OR) 15.82, 95% confidence interval (CI) 2.96-84.57, P = 0.0008], chronic heart failure (OR 4.27, 95% CI 1.66-11.03, P = 0.001) and STEMI as a precipitating factor of heart failure (OR 4.19, 95% CI 1.23-14.25, P = 0.023). Haemodialysis during the hospitalization (OR 4.28, 95% CI 1.17-15.61, P = 0.025) and the comorbidity depression and anxiety (OR 3.49, 95% CI 1.45-8.39, P = 0.005) were the most significant risk factors of long-term mortality. CONCLUSIONS: Our study confirms very high mortality rates among patients with acute heart failure underlying poor prognosis of these patients. Comorbidities (peripheral artery disease, atrial fibrillation, chronic heart failure and depression and anxiety), precipitating factors of heart failure (myocardial infarction with ST segment elevation), complications occurring during the hospitalization (acute kidney injury, pulmonary ventilation for respiratory failure and haemodialysis) and the age of patients should be included in the risk stratification of in-hospital, 30 day and 1 year mortality.

Comparison of six decision aid rules for diagnosis of acute myocardial infarction in elderly patients presenting to the emergency department with acute chest pain.

OBJECTIVE: This study aimed to evaluate the accuracy and effectiveness of different strategies for the diagnosis of acute myocardial infarction (AMI) in the elderly in real-life clinical practice. METHODS: Patients older than 70 years presenting to the emergency department with chest pain were included. The performance of six decision aid rules (T-MACS, HEART, EDACS, TIMI, GRACE, and ADAPT) and solo troponin T strategy for diagnosing AMI was evaluated by calculating sensitivity, specificity, odds ratios, negative and positive predictive values. RESULTS: A total of 250 patients, with a mean age of 78.5 years, were enrolled. Forty-eight patients (19.2 %) had an acute myocardial infarction in a 30 day follow-up period. The sensitivity for ruling-out AMI was 100 % for T-MACS, HEART, and ADAPT; 97.9 % for EDACS, 93.8 % for TIMI, and 81.3 % for GRACE and solo TnT strategy. For ruling-in AMI, the specificity was 97.5 % for T-MACS, 95 % for TIMI, 83.2 % for HEART, 81.7 % for GRACE, and 46 % for ADAPT. CONCLUSION: T-MACS decision aid had the best performance for rule-out and rule-in diagnostics of AMI. Risk stratification of patients with suspected acute coronary syndrome based on decision aid rules can be used in real-life practice, even in the population of the elderly (Tab. 6, Fig. 1, Ref. 17).