Effect of COMBinAtion therapy with remote ischemic conditioning and exenatide on the Myocardial Infarct size: a two-by-two factorial randomized trial (COMBAT-MI).

Remote ischemic conditioning (RIC) and the GLP-1 analog exenatide activate different cardioprotective pathways and may have additive effects on infarct size (IS). Here, we aimed to assess the efficacy of RIC as compared with sham procedure, and of exenatide, as compared with placebo, and the interaction between both, to reduce IS in humans. We designed a two-by-two factorial, randomized controlled, blinded, multicenter, clinical trial. Patients with ST-segment elevation myocardial infarction receiving primary percutaneous coronary intervention (PPCI) within 6 h of symptoms were randomized to RIC or sham procedure and exenatide or matching placebo. The primary outcome was IS measured by late gadolinium enhancement in cardiac magnetic resonance performed 3-7 days after PPCI. The secondary outcomes were myocardial salvage index, transmurality index, left ventricular ejection fraction and relative microvascular obstruction volume. A total of 378 patients were randomly allocated, and after applying exclusion criteria, 222 patients were available for analysis. There were no significant interactions between the two randomization factors on the primary or secondary outcomes. IS was similar between groups for the RIC (24 ± 11.8% in the RIC group vs 23.7 ± 10.9% in the sham group, P = 0.827) and the exenatide hypotheses (25.1 ± 11.5% in the exenatide group vs 22.5 ± 10.9% in the placebo group, P = 0.092). There were no effects with either RIC or exenatide on the secondary outcomes. Unexpected adverse events or side effects of RIC and exenatide were not observed. In conclusion, neither RIC nor exenatide, or its combination, were able to reduce IS in STEMI patients when administered as an adjunct to PPCI.

A simple combination of biomarkers for risk stratification in octogenarians with acute myocardial infarction.

The aim of this observational study was to assess long-term prognosis of a contemporary octogenarian population admitted to an Intensive Cardiac Care Unit with acute myocardial infarction (MI), and the prognostic value of two simple biomarkers obtained at admission: glucose blood level (ABG) and estimated glomerular filtration rate (eGFR). A total of 293 consecutive patients were included (202 with ST elevation MI and 91 with non-ST elevation MI) with median age 83.9 years, 172 (58.7%) male. The optimal cut-off points for all-cause death defined by ROC curves were ABG >186 mg/dL and eGFR <50 mL/min/1.73 m2. The cohort was segregated into 3 groups according to these values: no biomarker present (group 1), either of the two biomarkers present (group 2) or both biomarkers present (group 3). Patients in group 3 were more frequently female, with worse Charlson index, Killip class and ventricular function, and higher GRACE scores. PCI was performed in 248 patients (84.6%). The highest in-hospital and long-term mortality, and composite MACE was observed in groups 2 and 3. All-cause mortality (median follow-up 2.2 years) was 44%. In multivariate analysis, ABG >186 mg/dL and eGFR <50 mL/min/1.73 m2 were associated with a 4.2 odds ratio (OR) (Model 1: medical history variables) and 2.6 OR (Model 2: admission event variables) of mortality. The addition of these variables to ROC curves improved long-term risk prediction for Model 1 (C-statistics 0.718 versus 0.780, p = 0.006) and reclassification and discrimination in both models.

Biomarkers and short-term prognosis in COVID-19.

PURPOSE: The aim of our study was to analyse the short-term prognostic value of different biomarkers in patients with COVID-19. METHODS: We included patients admitted to emergency department with COVID-19 and available concentrations of cardiac troponin I (cTnI), D-dimer, C-reactive protein (CRP) and lactate dehydrogenase (LDH). Patients were classified for each biomarker into two groups (low vs. high concentrations) according to their best cut-off point, and 30-day all-cause death was evaluated. RESULTS: After multivariate adjustment, cTnI ≥21 ng/L, D-dimer ≥1112 ng/mL, CRP ≥10 mg/dL and LDH ≥334 U/L at admission were associated with an increased risk of 30-day all-cause death (hazard ratio (HR) 4.30; 95% CI 1.74-10.58; p = 0.002; HR 3.35; 95% CI 1.58-7.13; p = 0.002; HR 2.25; 95% CI 1.13-4.50; p = 0.021; HR 2.00; 95% CI 1.04-3.84; p = 0.039, respectively). The area under the curve for cTnI was 0.825 (95% CI 0.759-0.892) and, in comparison, was significantly better than CRP (0.685; 95% CI 0.600-0.770; p = 0.009) and LDH (0.643; 95% CI 0.534-0.753; p = 0.006) but non-significantly better than D-dimer (0.756; 95% CI 0.674-0.837; p = 0.115). CONCLUSIONS: In patients with COVID-19, increased concentrations of cTnI, D-dimer, CRP and LDH are associated with short-term mortality. Of these, cTnI provides better mortality risk prediction. However, differences with D-dimer were non-significant.

Clinical outcomes and safety of passive leg raising in out-of-hospital cardiac arrest: a randomized controlled trial.

BACKGROUND: There are data suggesting that passive leg raising (PLR) improves hemodynamics during cardiopulmonary resuscitation (CPR). This trial aimed to determine the effectiveness and safety of PLR during CPR in out-of-hospital cardiac arrest (OHCA). METHODS: We conducted a randomized controlled trial with blinded assessment of the outcomes that assigned adults OHCA to be treated with PLR or in the flat position. The trial was conducted in the Camp de Tarragona region. The main end point was survival to hospital discharge with good neurological outcome defined as cerebral performance category (CPC 1-2). To study possible adverse effects, we assessed the presence of pulmonary complications on the first chest X-rays, brain edema on the computerized tomography (CT) in survivors and brain and lungs weights from autopsies in non-survivors. RESULTS: In total, 588 randomized cases were included, 301 were treated with PLR and 287 were controls. Overall, 67.8% were men and the median age was 72 (IQR 60-82) years. At hospital discharge, 3.3% in the PLR group and 3.5% in the control group were alive with CPC 1-2 (OR 0.9; 95% CI 0.4-2.3, p = 0.91). No significant differences in survival at hospital admission were found in all patients (OR 1.0; 95% CI 0.7-1.6, p = 0.95) and among patients with an initial shockable rhythm (OR 1.7; 95% CI 0.8-3.4, p = 0.15). There were no differences in pulmonary complication rates in chest X-rays [7 (25.9%) vs 5 (17.9%), p = 0.47] and brain edema on CT [5 (29.4%) vs 10 (32.6%), p = 0.84]. There were no differences in lung weight [1223 mg (IQR 909-1500) vs 1239 mg (IQR 900-1507), p = 0.82] or brain weight [1352 mg (IQR 1227-1457) vs 1380 mg (IQR 1255-1470), p = 0.43] among the 106 autopsies performed. CONCLUSION: In this trial, PLR during CPR did not improve survival to hospital discharge with CPC 1-2. No evidence of adverse effects has been found. Clinical trial registration ClinicalTrials.gov: NCT01952197, registration date: September 27, 2013, https://clinicaltrials.gov/ct2/show/NCT01952197 .

Clinical characteristics and prognostic implications of diabetes and myocardial injury in patients admitted to the emergency room.

BACKGROUND: This study aimed to investigate the clinical features and prognosis of diabetes and myocardial injury in patients admitted to the emergency department. METHODS: We analyzed the clinical data of all consecutive patients admitted to the emergency department during the years 2012 and 2013 with at least 1 cardiac Troponin I (cTnI Ultra Siemens, Advia Centaur) determination, and were classified according to the status of diabetes mellitus (DM) and myocardial injury (MI). Clinical events were evaluated in a 4-year follow-up. RESULTS: A total of 3622 patients were classified according to the presence of DM (n = 924 (25.55%)) and MI (n = 1049 (28.96%)). The proportion of MI in patients with DM was 40% and 25% in patients without DM. Mortality during follow-up was 10.9% in non-DM patients without MI, 21.3% in DM patients without MI, 40.1% in non-DM patients with MI, and 52.8% in DM patients with MI. A competitive risk model was used to obtain the Hazard Ratio (HR) for readmission for myocardial infarction or heart failure. There was a similar proportion of readmission for myocardial infarction and heart failure at a four-year follow-up in patients with DM or MI, which was much higher when DM was associated with MI, with respect to patients without DM or MI. The HR (95% Coefficient Interval) for myocardial infarction in the DM without MI, non-DM with MI, and DM with MI groups with respect to the non-DM without MI group was 2511 (1592-3960), 2682 (1739-4138), and 5036 (3221-7876), respectively. The HR (95% CI) for the risk of readmission for heart failure in the DM without MI, non-DM with MI, and DM with MI groups with respect to the non-DM without MI group was 2663 (1825-3886), 2562 (1753-3744) and 4292 (2936-6274), respectively. CONCLUSIONS: The association of DM and MI in patients treated in an Emergency Service identifies patients at very high risk of mortality and cardiovascular events.

Soluble urokinase plasminogen activator receptor as a long-term prognostic biomarker in acute coronary syndromes.

Purpose: The aim of our study was to analyse the long-term prognostic value of soluble urokinase plasminogen activator receptor (suPAR) in the setting of an acute coronary syndrome (ACS).Methods: We included 340 patients with an ACS who underwent coronary angiography and plasma suPAR concentration was measured. Patients were classified into low suPAR concentrations (<2.6 ng/mL) and high suPAR concentrations (≥2.6 ng/mL) and long-term events were evaluated. suPAR prognostic value was assessed beyond a clinical model that included age, GRACE score, estimated glomerular filtration rate, cardiac troponin-I peak and left ventricular ejection fraction <40%.Results: Higher suPAR concentrations were associated with an increased prevalence of cardiovascular risk factors. After multivariate adjustment, suPAR ≥2.6 ng/mL were independently associated with an increased risk of all-cause death (HR 2.3; 95%CI 1.2-4.4; p = .017), major adverse cardiovascular events (MACE) (HR 1.7; 95%CI 1.1-2.5; p = .020) and heart failure (HR 4.1; 95%CI 1.3-12.6; p = .015), but not with myocardial infarction. For long-term all-cause death significant improvement of reclassification and discrimination were seen after addition of suPAR to a clinical model.Conclusions: In the setting of an ACS, suPAR is associated with long-term all-cause death, heart failure and MACE, and provides incremental prognostic value beyond traditional risks factors.

Comorbidity and low use of new antiplatelets in acute coronary syndrome.

INTRODUCTION: Despite the use of the new generation P2Y12 inhibitors (Ticagrelor and Prasugrel) with aspirin is the recommended therapy in acute NSTE-ACS patients, their current use in clinical practice remains quite low and might be related, among several variables, with increased comorbidity burden. We aimed to assess the prevalence of these treatments and whether their use could be associated with comorbidity. METHOD: A multicentric prospective registry was conducted at 8 Cardiac Intensive Care Units (October 2017-April 2018) in patients admitted with non ST elevation myocardial infarction. Antithrombotic treatment was recorded and the comorbidity risk was assessed using the Charlson Comorbidity Index. We created a multivariate model to identify the independent predictors of the use of new inhibitors of P2Y12. RESULTS: A total of 629 patients were included, median age 67 years, 23.2% women, 359 patients (57.1%) treated with clopidogrel and 40.6% with new P2Y12 inhibitors: ticagrelor (228 patients, 36.2%) and prasugrel (30 patients, 4.8%). Among the patients with very high comorbidity (Charlson Score > 6) clopidogrel was the drug of choice (82.6%), meanwhile in patients with low comorbility (Charlson Score 0-1) was the ticagrelor or prasugrel (63.6%). Independent predictors of the use of ticagrelor or prasugrel were a low Charlson Comorbidity Index, a low CRUSADE score and the absence of prior bleeding. CONCLUSION: Antiplatelet treatment with Ticagrelor or Pasugrel was low in patients admitted with NSTE-ACS. Comorbidity calculated with Charlson Comorbidity Index was a powerful predictor of the use of new generation P2Y12 inhibitors in this population.

Prognostic implications of detectable cardiac troponin I below the 99th percentile in patients admitted to an emergency department without acute coronary syndrome.

BACKGROUND: Detectable troponin below the 99th percentile may reflect an underlying cardiac abnormality which might entail prognostic consequences. This study aimed to investigate the prognosis of patients admitted to an emergency department (ED) with detectable troponin below the 99th percentile reference limit who did not present with an acute coronary syndrome (ACS). METHODS: We analysed the clinical data of all consecutive patients admitted to the ED during the years 2012 and 2013 in whom cardiac troponin was requested by the attending clinician (cTnI Ultra Siemens, Advia Centaur). Patients with troponin below the 99th percentile of the reference population (40 ng/L) and who did not have a diagnosis of ACS were selected, and their mortality was evaluated in a 2-year follow-up. RESULTS: A total of 2501 patients had a troponin level below the reference limit, with 43.9% of those showing detectable levels (>6 ng/L and <40 ng/L). Patients with detectable levels were elderly and had a higher prevalence of cardiovascular history and more comorbidities. The total mortality in the 2-year follow-up was 12.4% in patients with detectable troponin and 4.5% in patients with undetectable troponin (p<0.001). In the Cox multivariate regression analysis, the detectable troponin was an independent marker of mortality at 2 years (HR 1.62, 95% CI 1.07-2.45, p=0.021). CONCLUSIONS: Detectable troponin I below the 99th percentile is associated with higher mortality risk at 2-year follow-up in patients admitted to the ED who did not present with ACS.

Bile Acids and Risk of Adverse Cardiovascular Events and All-Cause Mortality in Patients with Acute Coronary Syndrome.

The relationship between bile acids (BAs) and adverse cardiovascular events following acute coronary syndrome (ACS) have been little investigated. We aimed to examine the associations of BAs with the risk of cardiovascular events and all-cause mortality in ACS. We conducted a prospective study on 309 ACS patients who were followed for 10 years. Plasma BAs were quantified by liquid chromatography coupled to tandem mass spectrometry. Cox regression analyses with elastic net penalties were performed to associate BAs with MACE and all-cause mortality. Weighted scores were computed using the 100 iterated coefficients corresponding to each selected BA, and the associations of these scores with these adverse outcomes were assessed using multivariable Cox regression models. A panel of 10 BAs was significantly associated with the increased risk of MACE. The hazard ratio of MACE per SD increase in the estimated BA score was 1.35 (95% CI 1.12-1.63). Furthermore, four BAs were selected from the elastic net model for all-cause mortality, although their weighted score was not independently associated with mortality. Our findings indicate that primary and secondary BAs may play a significant role in the development of MACE. This insight holds potential for developing strategies to manage ACS and prevent adverse outcomes.

Parallel evolution of circulating FABP4 and NT-proBNP in heart failure patients.

BACKGROUND: Circulating adipocyte fatty acid-binding protein (FABP4) levels are considered to be a link between obesity, insulin resistance, diabetes, and cardiovascular (CV) diseases. In vitro, FABP4 has exhibited cardiodepressant activity by suppressing cardiomyocyte contraction. We have explored the relationship between FABP4 and the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) as a clinical parameter of heart failure (HF). METHODS: We included 179 stable HF patients who were referred to a specialized HF unit, 108 of whom were prospectively followed for up to 6 months. A group of 163 non-HF patients attending a CV risk unit was used as the non-HF control group for the FABP4 comparisons. RESULTS: In the HF patients, FABP4 and NT-proBNP were assayed, along with a clinical and functional assessment of the heart at baseline and after 6 months of specialized monitoring. The FABP4 levels were higher in the patients with HF than in the non-HF high CV risk control group (p<0.001). The FABP4 levels were associated with the NT-proBNP levels in patients with HF (r=0.601, p<0.001), and this association was stronger in the diabetic patients. FABP4 was also associated with heart rate and the results of the 6-minute walk test. After the follow-up period, FABP4 decreased in parallel to NT-proBNP and to the clinical parameters of HF. CONCLUSIONS: FABP4 is associated with the clinical manifestations and biomarkers of HF. It exhibits a parallel evolution with the circulating levels of NT-proBNP in HF patients.

TCA cycle metabolites associated with adverse outcomes after acute coronary syndrome: mediating effect of renal function.

Aims: To examine relationships of tricarboxylic acid (TCA) cycle metabolites with risk of cardiovascular events and mortality after acute coronary syndrome (ACS), and evaluate the mediating role of renal function in these associations. Methods: This is a prospective study performed among 309 ACS patients who were followed for a mean of 6.7 years. During this period 131 patients developed major adverse cardiovascular events (MACE), defined as the composite of myocardial infarction, hospitalization for heart failure, and all-cause mortality, and 90 deaths were recorded. Plasma concentrations of citrate, aconitate, isocitrate, succinate, malate, fumarate, α-ketoglutarate and d/l-2-hydroxyglutarate were quantified using LC-tandem MS. Multivariable Cox regression models were used to estimate hazard ratios, and a counterfactual-based mediation analysis was performed to test the mediating role of estimated glomerular filtration rate (eGFR). Results: After adjustment for traditional cardiovascular risk factors and medications, positive associations were found between isocitrate and MACE (HR per 1 SD, 1.25; 95% CI: 1.03, 1.50), and between aconitate, isocitrate, d/l-2-hydroxyglutarate and all-cause mortality (HR per 1 SD, 1.41; 95% CI: 1.07, 1.84; 1.58; 95% CI: 1.23, 2.02; 1.38; 95% CI: 1.14, 1.68). However, these associations were no longer significant after additional adjustment for eGFR. Mediation analyses demonstrated that eGFR is a strong mediator of these associations. Conclusion: These findings underscore the importance of TCA metabolites and renal function as conjunctive targets in the prevention of ACS complications.

Plasma trimethylamine-N-oxide, its precursors and risk of cardiovascular events in patients with acute coronary syndrome: Mediating effects of renal function.

Aims: To examine associations of the gut microbial metabolite trimethylamine-N-oxide (TMAO) and its precursors with risk of cardiovascular events in acute coronary syndrome (ACS), and determine whether these associations were mediated by renal function. Methods: In this prospective cohort study, we included 309 patients with ACS. During a mean follow-up of 6.7 years, 131 patients developed major adverse cardiovascular events (MACE) (myocardial infarction, hospitalization for heart failure, and all-cause mortality). Plasma concentrations of TMAO, trimethylamine (TMA), choline, betaine, dimethylglycine and L-carnitine were profiled by liquid chromatography tandem mass spectrometry. Hazard ratios were estimated with multivariable Cox regression models. The mediating role of estimated glomerular filtration rate (eGFR) was tested under a counterfactual framework. Results: After adjustment for traditional cardiovascular risk factors and medications, participants in the highest tertile vs. the lowest tertile of baseline TMAO and dimethylglycine concentrations had a higher risk of MACE [(HR: 1.83; 95% CI: 1.08, 3.09) and (HR: 2.26; 95% CI: 1.17, 3.99), respectively]. However, with regards to TMAO these associations were no longer significant, whereas for dimethylglycine, the associations were attenuated after additional adjustment for eGFR. eGFR mediated the associations of TMAO (58%) and dimethylglycine (32%) with MACE incidence. The associations between dimethylglycine and incident MACE were confirmed in an internal validation. No significant associations were found for TMA, choline, betaine and L-carnitine. Conclusion: These findings suggest that renal function may be a key mediator in the association of plasma TMAO with the development of cardiovascular events after ACS. The present findings also support a role of dimethylglycine in the pathogenesis of MACE, which may be mediated, at least partially, by renal function.

Performance of Coronary Angiography in the Detection of Coronary Artery Disease in Patients with Systolic Left Ventricular Dysfunction and No Prior Ischemic Heart Disease.

The diagnosis of ischemic cardiomyopathy is not well established. Our objective is to determine predictive variables of coronary disease in unselected patients with ventricular dysfunction. This study is a retrospective cohort study of consecutive patients with left ventricular dysfunction and no known history of ischemic heart disease. We analyse the demographic variables, clinical data, electrocardiogram, and echocardiogram that are associated with the presence of coronary stenosis on coronary angiography. A total of 536 patients with left ventricular dysfunction were studied, with 135 (25.2%) of them having significant coronary lesions. In the multivariate logistic regression analysis, age ≤ 50 years, female gender, and the presence of atrial fibrillation on the electrocardiogram (ECG) were predictors of the absence of coronary lesions. Diabetes, hypercholesterolemia, the existence of Q waves in the ECG, and segmental alterations in contractility in the echocardiogram were predictors of coronary heart disease (C-Statistics 0.771, 95% CI 0.727 to 0.814). The information obtained from the clinical history, the ECG, and the echocardiogram of patients with ventricular dysfunction allows us to select subjects in whom coronary angiography has shown poor performance in diagnosing coronary disease.

Gut Microbiota-Derived Metabolites and Cardiovascular Disease Risk: A Systematic Review of Prospective Cohort Studies.

Gut microbiota-derived metabolites have recently attracted considerable attention due to their role in host-microbial crosstalk and their link with cardiovascular health. The MEDLINE-PubMed and Elsevier's Scopus databases were searched up to June 2022 for studies evaluating the association of baseline circulating levels of trimethylamine N-oxide (TMAO), secondary bile acids, short-chain fatty acids (SCFAs), branched-chain amino acids (BCAAs), tryptophan and indole derivatives, with risk of cardiovascular disease (CVD). A total of twenty-one studies were included in the systematic review after evaluating 1210 non-duplicate records. There were nineteen of the twenty-one studies that were cohort studies and two studies had a nested case-control design. All of the included studies were of high quality according to the "Newcastle-Ottawa Scale". TMAO was positively associated with adverse cardiovascular events and CVD/all-cause mortality in some, but not all of the included studies. Bile acids were associated with atrial fibrillation and CVD/all-cause mortality, but not with CVD. Positive associations were found between BCAAs and CVD, and between indole derivatives and major adverse cardiovascular events, while a negative association was reported between tryptophan and all-cause mortality. No studies examining the relationship between SCFAs and CVD risk were identified. Evidence from prospective studies included in the systematic review supports a role of microbial metabolites in CVD.

[Prognostic implications of myocardial injury in patients with and without COVID-19 infection treated in a university hospital]. / Implicaciones pronósticas del daño miocárdico en pacientes con y sin diagnóstico confirmado de COVID-19 atendidos en un hospital universitario.

INTRODUCTION AND OBJECTIVES: Cardiac troponin, a marker of myocardial injury, is frequently observed in patients with COVID-19 infection. Our objective was to analyze myocardial injury and its prognostic implications in patients with and without COVID-19 infection treated in the same period of time. METHODS: The present study included patients treated in a university hospital with cardiac troponin I measurements and with suspected COVID-19 infection, confirmed or ruled out by polymerase chain reaction analysis. The impact was analyzed of cardiac troponin I positivity on 30-day mortality. RESULTS: In total, 433 patients were distributed among the following groups: confirmed COVID-19 (n = 186), 22% with myocardial injury (n = 41); and ruled out COVID-19 (n = 247), 21.5% with myocardial injury (n = 52). The confirmed and ruled out COVID-19 groups had a similar age, sex, and cardiovascular history. Mortality was significantly higher in the confirmed COVID-19 group than in the ruled out group (19.9% vs 5.3%, P < .001). In Cox multivariate regression analysis, cardiac troponin I was a predictor of mortality in both groups (confirmed COVID-19 group: HR, 3.54; 95%CI, 1.70-7.34; P = .001; ruled out COVID-19 group: HR, 5.57; 95%CI, 1.70-18.20; P = .004). The predictive model analyzed by ROC curves was similar in the 2 groups (P = .701), with AUCs of 0.808 in the confirmed COVID-19 group (0.750-0.865) and 0.812 in the ruled out COVID-19 group (0.760-0.864). CONCLUSIONS: Myocardial injury is detected in 1 in every 5 patients with confirmed or ruled out COVID-19 and predicts 30-day mortality to a similar extent in both circumstances.

Prognostic implications of myocardial injury in patients with and without COVID-19 infection treated in a university hospital.

INTRODUCTION AND OBJECTIVES: Cardiac troponin, a marker of myocardial injury, is frequently observed in patients with COVID-19 infection. Our objective was to analyze myocardial injury and its prognostic implications in patients with and without COVID-19 infection treated in the same period of time. METHODS: The present study included patients treated in a university hospital with cardiac troponin I measurements and with suspected COVID-19 infection, confirmed or ruled out by polymerase chain reaction analysis. The impact was analyzed of cardiac troponin I positivity on 30-day mortality. RESULTS: In total, 433 patients were distributed among the following groups: confirmed COVID-19 (n=186), 22% with myocardial injury (n=41); and ruled out COVID-19 (n=247), 21.5% with myocardial injury (n=52). The confirmed and ruled out COVID-19 groups had a similar age, sex, and cardiovascular history. Mortality was significantly higher in the confirmed COVID-19 group than in the ruled out group (19.9% vs 5.3%, P <.001). In Cox multivariate regression analysis, cardiac troponin I was a predictor of mortality in both groups (confirmed COVID-19 group: HR, 3.54; 95%CI, 1.70-7.34; P=.001; ruled out COVID-19 group: HR, 5.57; 95%CI, 1.70-18.20; P=.004). The predictive model analyzed by ROC curves was similar in the 2 groups (P=.701), with AUCs of 0.808 in the confirmed COVID-19 group (0.750-0.865) and 0.812 in the ruled out COVID-19 group (0.760-0.864). CONCLUSIONS: Myocardial injury is detected in 1 in every 5 patients with confirmed or ruled out COVID-19 and predicts 30-day mortality to a similar extent in both circumstances.

Lack of Association of Initial Viral Load in SARS-CoV-2 Patients with In-Hospital Mortality.

Controversy exists in the literature regarding the possible prognostic implications of the nasopharyngeal SARS-CoV-2 viral load. We carried out a retrospective observational study of 169 patients, 96 (58.9%) of whom had a high viral load and the remaining had a low viral load. Compared with patients with a low viral load, patients with a high viral load did not exhibit differences regarding preexisting cardiovascular risk factors or comorbidities. There were no differences in symptoms, vital signs, or laboratory tests in either group, except for the maximum cardiac troponin I (cTnI), which was higher in the group with a higher viral load (24 [interquartile range 9.5-58.5] versus 8.5 [interquartile range 3-22.5] ng/L, P = 0.007). There were no differences in the need for hospital admission, admission to the intensive care unit, or the need for mechanical ventilation in clinical management. In-hospital mortality was greater in patients who had a higher viral load than in those with low viral load (24% versus 10.4%, P = 0.029). High viral loads were associated with in-hospital mortality in the binary logistic regression analysis (odds ratio: 2.701, 95% Charlson Index (CI): 1.084-6.725, P = 0.033). However, in an analysis adjusted for age, gender, CI, and cTnI, viral load was no longer a predictor of mortality. In conclusion, an elevated nasopharyngeal viral load was not a determinant of in-hospital mortality in patients with COVID-19, as much as age, comorbidity, and myocardial damage determined by elevated cTnI are.

Anemia in patients with high-risk acute coronary syndromes admitted to Intensive Cardiac Care Units.

BACKGROUND: Little information exists about the role of anemia in patients with acute coronary syndromes (ACS) admitted to Intensive Cardiac Care Units (ICCU). The aim of this study was to assess the prevalence of anemia and its impact on management and outcomes in this clinical setting. METHODS: All consecutive patients admitted to eight different ICCUs with diagnosis of non-ST segment elevation ACS (NSTEACS) were prospectively included. Anemia was defined as hemoglobin < 130 g/L in men and < 120 g/L in women. The association between anemia and mortality or readmission at six months was assessed by the Cox regression method. RESULTS: A total of 629 patients were included. Mean age was 66.6 years. A total of 197 patients (31.3%) had anemia. Coronary angiography was performed in most patients (96.2%). Patients with anemia were significantly older, with a higher prevalence of comorbidities, poorer left ventricle ejection fraction and higher GRACE score values. Patients with anemia underwent less often coronary angiography, but underwent more often intraaortic counterpulsation, non-invasive mechanical ventilation and renal replacement therapies. Both ICCU and hospital stay were significantly longer in patients with anemia. Both the incidence of mortality (HR = 3.36, 95% CI: 1.43-7.85, P = 0.001) and the incidence of mortality/readmission were significantly higher in patients with anemia (HR = 2.80, 95% CI: 2.03-3.86, P = 0.001). After adjusting for confounders, the association between anemia and mortality/readmission remained significant (P = 0.031). CONCLUSIONS: Almost one of three NSTEACS patients admitted to ICCU had anemia. Most patients underwent coronary angiography. Anemia was independently associated to poorer outcomes at 6 months.

Prognostic implications of troponin I elevation in emergency department patients with tachyarrhythmia.

BACKGROUND: Tachyarrhythmias are very common in emergency medicine, and little is known about the long-term prognostic implications of troponin I levels in these patients. HYPOTHESIS: This study aimed to investigate the correlation of cardiac troponin I (cTnI) levels and long-term prognosis in patients admitted to the emergency department (ED) with a primary diagnosis of tachyarrhythmia. METHODS: A retrospective cohort study was conducted between January 2012 and December 2013, enrolling patients admitted to the ED with a primary diagnosis of tachyarrhythmia and having documented cTnI measurements. Clinical characteristics and 5-year all-cause mortality were analyzed. RESULTS: Of a total of 222 subjects with a primary diagnosis of tachyarrhythmia, 73 patients had elevated levels of cTnI (32.9%). Patients with elevated cTnI levels were older and presented significantly more cardiovascular risk factors. At the 5-year follow-up, mortality was higher among patients with elevated cTnI levels (log-rank test P < 0.001). In the multivariable Cox regression analysis, elevated cTnI was an independent predictor of all-cause death (hazard ratio, 1.95, 95% confidence interval: 1.08-3.50, P = 0.026), in addition to age and prior heart failure. CONCLUSION: Patients admitted to the ED with a primary diagnosis of tachyarrhythmia and high cTnI levels have higher long-term mortality rates than patients with low cTnI levels. cTnI is thus a biomarker with predictive capacity for mortality in late follow-up, conferring utility in the risk stratification of this population.

Long-term prognostic value of growth differentiation factor-15 in acute coronary syndromes.

BACKGROUND: Growth Differentiation Factor-15 (GDF-15) predicts death and cardiovascular events in acute coronary syndromes (ACS). We aimed to assess the long-term prognostic value of GDF-15 in ACS. METHODS: We included 358 patients with ACS who underwent coronary angiography. Plasma GDF-15 was measured and clinical data and long-term events were registered. Incremental value of GDF-15 for prognosing all-cause death above a clinical model including GRACE score, left ventricular ejection fraction <40%, prior myocardial infarction and age was assessed. RESULTS: GDF-15 concentrations >1800 ng/L were associated with an increased prevalence of cardiovascular risk factors. During 6.5 years of follow-up 56 patients died, 7 had values of GDF-15 < 1200 ng/L, 7 between 1200 and 1800 ng/L and 42 > 1800 ng/L. After adjustment for potential confounders, GDF-15 > 1800 ng/L were independently associated with all-cause death (HR 4.09; 95% CI 1.57-10.71; p = .004) and the composite of major adverse cardiovascular events (MACE) (HR 2.48; 95% CI 1.41-4.34; p = .001). For long-term all-cause death a significant increase of ROC curve was seen after addition of GDF-15 to a clinical model 0.876 (95% CI 0.823-0.928; p = .014). Same improvements were found for net reclassification improvement (0.776; 95% CI 0.494-1.037; p < .001) and integrated discrimination improvement (0.112; 95% CI 0.055-0.169; p < .001). Multivariate competing risk model showed a significant association between GDF-15 > 1800 ng/L and the incidence of heart failure but not of myocardial infarction. CONCLUSIONS: In the setting of ACS, GDF-15 is associated with long-term all-cause death, MACE and heart failure and provides incremental prognostic value beyond traditional risks factor.