Elevated cTnI Research Articles

The Main Causes and Mechanisms of Increase in Cardiac Troponin Concentrations Other Than Acute Myocardial Infarction (Part 1): Physical Exertion, Inflammatory Heart Disease, Pulmonary Embolism, Renal Failure, Sepsis

The causes and mechanisms of increased cardiac troponin T and I (cTnT and cTnI) concentrations are numerous and are not limited to acute myocardial infarction (AMI) (ischemic necrosis of cardiac myocytes). Any type of reversible or irreversible cardiomyocyte injury can result in elevated serum cTnT and cTnI levels. Researchers and practitioners involved in the diagnosis and treatment of cardiovascular disease, including AMI, should know the key causes and mechanisms of elevated serum cTnT and cTnI levels. This will allow to reduce or completely avoid diagnostic errors and help to choose the most correct tactics for further patient management. The purpose of this article is to discuss the main causes and mechanisms of increase in cardiac troponins concentrations in frequently occurring physiological (physical exertion, psycho-emotional stress) and pathological conditions (inflammatory heart disease, pulmonary embolism, chronic renal failure and sepsis (systemic inflammatory response)) not related to myocardial infarction.

Determinants of Interindividual Variation in Exercise-Induced Cardiac Troponin I Levels.

BackgroundPostexercise cardiac troponin levels show considerable interindividual variations. This study aimed to identify the major determinants of this postexercise variation in cardiac troponin I (cTnI) following 3 episodes of prolonged high‐intensity endurance exercise.Methods and ResultsStudy subjects were recruited among prior participants in a study of recreational cyclists completing a 91‐km mountain bike race in either 2013 or 2014 (first race). In 2018, study participants completed a cardiopulmonary exercise test 2 to 3 weeks before renewed participation in the same race (second race). Blood was sampled before and at 3 and 24 hours following all exercises. Blood samples were analyzed using the same Abbot high‐sensitivity cTnI STAT assay. Fifty‐nine individuals (aged 50±9 years, 13 women) without cardiovascular disease were included. Troponin values were lowest before, highest at 3 hours, and declining at 24 hours. The largest cTnI difference was at 3 hours following exercise between the most (first race) (cTnI: 200 [87–300] ng/L) and the least strenuous exercise (cardiopulmonary exercise test) (cTnI: 12 [7–23] ng/L; P<0.001). The strongest correlation between troponin values at corresponding times was before exercise (r=0.92, P<0.0001). The strongest correlations at 3 hours were between the 2 races (r=0.72, P<0.001) and at 24 hours between the cardiopulmonary exercise test and the second race (r=0.83, P<0.001). Participants with the highest or lowest cTnI levels showed no differences in race performance or baseline echocardiographic parameters.ConclusionsThe variation in exercise‐induced cTnI elevation is largely determined by a unique individual cTnI response that is dependent on the duration of high‐intensity exercise and the timing of cTnI sampling.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT02166216.

Duchenne muscular dystrophy patients: troponin leak in asymptomatic and implications for drug toxicity studies.

Cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD), but studies suggest heart failure biomarkers correlate poorly with cardiomyopathy severity. DMD clinical trials have used troponin I (cTnI) as a biomarker of toxicity, but it is unclear if asymptomatic DMD patients have elevated cTnI. We longitudinally evaluated cTnI, brain natriuretic peptide (BNP), and N-terminal pro-BNP (NT-proBNP) in a DMD cohort. DMD patients were prospectively enrolled and followed for 3 years. Serum was drawn at the time of cardiac magnetic resonance (CMR). Normal biomarker values were derived from healthy subjects. Biomarkers were correlated with CMR markers. All subjects were asymptomatic at the time of enrollment. Several DMD subjects had transiently elevated cTnI. Those with elevated cTnI were more likely to have late gadolinium enhancement on baseline CMR. NT-proBNP correlated with indexed left ventricular end diastolic and maximum left atrial volumes. Otherwise, standard cardiac biomarkers did not correlate with CMR markers of cardiomyopathy. CTnI, BNP, and NT-proBNP do not correlate with CMR assessment of cardiomyopathy progression. A subset of DMD patients have asymptomatic cTnI leak of uncertain clinical significance, though of critical importance if cTnI is used to assess for cardiac toxicity in future drug trials. Asymptomatic patients with Duchenne muscular dystrophy (DMD) exhibit transient troponin I leak. NT-proBNP correlated with indexed left ventricular end diastolic volume and indexed maximum left atrial volume. Other cardiac biomarkers did not correlate with cardiac magnetic resonance (CMR) markers of cardiomyopathy.

Prognostic Value of Cardiac Troponin and Risk Assessment in Pediatric Supraventricular Tachycardia.

Cardiac troponin I (cTnI) elevation is common in an acute episode of supraventricular tachycardia (SVT). However, there is limited evidence regarding the prognostic value of cTnI and the predictors of SVT recurrence in pediatric patients. We screened the electronic medical records of all pediatric patients presenting to the emergency departments at five Taiwanese hospitals from 1 January 2010 to 31 May 2021. Our primary outcomes were the occurrence of major adverse cardiac events (MACEs) during the follow-up period and 30-day SVT recurrence. A total of 112 patients were included in our study. Of these, 29 (25.9%) patients had positive cTnI values. Patients with cTnI elevation had significantly more complaints of dyspnea (27.6% vs. 7.2%, p = 0.008) and gastrointestinal discomfort (24.1% vs. 4.8%, p = 0.006). There were significantly more intensive care unit admissions (41.4% vs. 16.9%, p = 0.007) among the cTnI-positive group. One MACE was found in the cTnI-negative group. For 30-day SVT recurrence, the cTnI-positive group had a higher recurrence rate, without a statistically significant difference (20.7% vs. 7.2%, p = 0.075). Multivariable logistic regression analysis showed hypotension as an independent predictor of 30-day SVT recurrence (OR = 4.98; Cl 1.02–24.22; p = 0.047). Troponin had low value for predicting the outcomes of pediatric patients with SVT. The only significant predictor for recurrent SVT was initial hypotension.

Implications of Periprocedural Myocardial Biomarker Elevations and Commonly Used MI Definitions After Left Main PCI.

The aim of this study was to: 1) assess the relationship of different thresholds of creatine kinase-myocardial band (CK-MB) and cardiac troponin with subsequent mortality; and 2) evaluate the prognostic significance of periprocedural myocardial infarction (PMI) according to various definitions of myocardial infarction in patients with left main (LM) coronary artery disease. The magnitude of postprocedural biomarker elevation representing a clinically meaningful PMI after percutaneous coronary intervention (PCI) is controversial. A total of 4,013 consecutive patients undergoing LM PCI at a single center from January 2004 to December 2016 were enrolled. CK-MB and cardiac troponin I (cTnI) were routinely collected at baseline and at frequent intervals between 8 and 48 hours after PCI. The primary and secondary outcomes were the covariate-adjusted 3-year rates of cardiovascular (CV) and all-cause mortality, respectively. The 3-year rate of CV mortality progressively increased with higher peak CK-MB values. CV mortality was first independently predicted by postprocedural CK-MB 3 to 5 times the upper reference limit (URL) (adjusted hazard ratio [aHR]: 2.93; 95% confidence interval [CI]: 1.02-8.40), whereas all-cause death was independently predicted only by CK-MB≥ 10×URL (aHR: 3.25; 95%CI: 1.37-7.70). In contrast, no level of peak postprocedural cTnI was associated with CV or all-cause death. PMI by the Society for Cardiovascular Angiography and Interventions (SCAI), Academic Research Consortium-2 (ARC-2), and fourth universal definition of myocardial infarction (UDMI) occurred in 1.3%, 3.1%, and 5.1% of patients, respectively. The SCAI definition was significantly associated with 3-year CV mortality (aHR: 4.93; 95%CI: 1.92-12.69) and all-cause mortality (aHR: 3.11; 95%CI: 1.33-7.27), whereas the ARC-2 and fourth UDMI definitions were not. In a large cohort of consecutive patients undergoing LM PCI, intermediate (≥3× URL) and high (≥10× URL) levels of peak postprocedural CK-MB independently predicted 3-year CV and all-cause mortality, respectively, whereas even large elevations of post-PCI cTnI did not. The SCAI definition (but not the ARC-2 or fourth UDMI) ofPMIwas independently associated with mortality after LM PCI.

Indicators and prediction models for the severity of Covid-19.

ObjectivesCoronavirus disease 2019 (Covid‐19) is outbreaking globally. We aimed to analyse the clinical characteristics, cardiac injury, electrocardiogram and computed tomography (CT) features of patients confirmed Covid‐19 and explored the prediction models for the severity of Covid‐19.MethodsA retrospective and single‐centre study enrolled 98 laboratory‐confirmed Covid‐19 patients. Clinical data, electrocardiogram and CT features were collected and analysed using Statistical Package for the Social Sciences software.ResultsThere were 46 males and 52 females, with a median age of 44 years, categorised into three groups, including mild, moderate and severe/critical Covid‐19. The rate of abnormal electrocardiograms in severe/critical group (79%) was significantly higher than that in the mild group (17%) (P = .027), which (r = 0.392, P = .005) positively related to the severity of Covid‐19 (OR: 5.71, 95% CI: 0.45‐3.04, P = .008). Age older than 60 years old, comorbidities, whether had symptoms on admission, fatigue, CT features, laboratory test results such as platelet count, lymphocyte cell count, eosinophil cell count, CD3+ cell count, CD4+ cell count, CD8+ cell count, the ratio of albumin/globulin decreased and D‐dimer, C‐reactive protein (CRP), B‐type natriuretic peptide (BNP), cardiac troponin I (cTnI) elevated were the risk factors for the increased severity of Covid‐19. The logistic model, adjusted by age, lobular involvement score and lymphocyte cell count, could be applied for assessing the severity of Covid‐19 (AUC, 0.903; Sensitivity, 90.9%; Specificity, 78.1%).ConclusionsAge >60 years old, chronic comorbidities, lymphocytopoenia and lobular involvement score were associated with the Covid‐19 severity. The inflammation induced by Covid‐19 caused myocardial injury with elevated BNP and cTnI level and abnormal electrocardiograms.

Troponin I as an Independent Biomarker of Outcome in Children with Systemic Inflammatory Response.

Cardiac troponin-I (cTnI) is a biomarker of myocardial injury with implications for clinical outcomes. May other contributing factors that could affect outcomes have not been uniformly considered in pediatric studies. We hypothesized that there is an association between admission serum cTnI and outcomes in critically ill children taking into account the magnitude of the acute systemic inflammatory response syndrome (SIRS), serum lactate concentrations, and nutritional status. Second, we tested for potential factors associated with elevated serum cTnI. This was a prospective cohort study in 104 children (median age: 21.3 months) consecutively admitted to a pediatric intensive care unit (PICU) of a teaching hospital with SIRS and without previous chronic diseases. Primary outcome variables were PICU-free days, ventilator-free days, and 30-day mortality. Exposure variables were serum cTnI concentration on admission, revised pediatric index of mortality (PIM2), pediatric logistic organ dysfunction (PELOD-2), hypotensive shock, C-reactive protein, procalcitonin, and serum lactate on admission, and malnutrition. Elevated cTnI (>0.01 μg/L) was observed in 24% of patients, which was associated with the reduction of ventilator-free days (β coefficient = - 4.97; 95% confidence interval [CI]: -8.03; -1.91) and PICU-free days (β coefficient = - 5.76; 95% CI: -8.97; -2.55). All patients who died had elevated serum cTnI. The increase of 0.1 μg/L in cTnI concentration resulted in an elevation of 2 points in the oxygenation index (β coefficient = 2.0; 95% CI: 1.22; 2.78, p < 0.001). The PIM2 score, hypotensive shock in the first 24 hours, and serum lactate were independently associated with elevated cTnI on admission. We conclude that elevated serum cTnI on admission is independently associated with adverse outcomes in children with SIRS and without associated chronic diseases.

Prognostic Value of Elevated Cardiac Troponin I After Aneurysmal Subarachnoid Hemorrhage.

Object: Patients with aneurysmal subarachnoid hemorrhage (aSAH) have an increased incidence of cardiac events and short-term unfavorable neurological outcomes during the acute phase of bleeding. We studied whether troponin I elevation after ictus can predict future major adverse cardiac events (MACEs) and long-term neurological outcomes after 2 years.Methods: Consecutive aSAH patients within 3 days of bleeding were eligible for review from a prospective observational cohort (ClinicalTrials.gov Identifier: NCT04785976). Potential predictors of future MACEs and unfavorable long-term neurological outcomes were calculated by Cox and logistic regression analyses. Additional Kaplan–Meier curves were performed.Results: A total of 213 patients were enrolled with an average follow-up duration of 34.3 months. Individuals were divided into two groups: elevated cTnI group and unelevated cTnI group. By the last available follow-up, 20 patients had died, with an overall all-cause mortality rate of 9.4% and an annual all-cause mortality rate of 3.8%. Patients with elevated cTnI had a significantly higher risk of future MACEs (10.6 vs. 2.1%, p = 0.024, and 95% CI: 1.256–23.875) and unfavorable neurological outcomes at discharge, 3-month, 1-, 2-years, and last follow-up (p = 0.001, p < 0.001, p = 0.001, p < 0.001, and p < 0.001, respectively). In the Cox analysis for future MACE, elevated cTnI was the only independent predictor (HR = 5.980; 95% CI: 1.428–25.407, and p = 0.014). In the multivariable logistic analysis for unfavorable neurological outcomes, peak cTnI was significant (OR = 2.951; 95% CI: 1.376–6.323; p = 0.005). Kaplan–Meier analysis indicated that the elevated cTnI was correlated with future MACE (log-rank test, p = 0.007) and subsequent death (log-rank test, p = 0.004).Conclusion: cTnI elevation after aSAH could predict future MACEs and unfavorable neurological outcomes.

Clinical Utilities of Electrocardiography in the Diagnosis of Myocardial Ischemia in Children With Sickle Cell Anemia: Correlation With Serum Cardiac Troponin I.

Sickle cell anemia (SCA) is associated with recurrent vaso-occlusive crisis (VOC) and the risk of myocardial ischemia (MI). This study investigated the utility of electrocardiography (ECG) and cardiac troponin I (cTnI) in diagnosing MI during VOC. Children with SCA 5 to 15 years of age in VOC (patients) and age-matched and sex-matched steady-state controls were studied. Their ECG and cTnI levels were measured at contact and after 4 to 6 weeks. One hundred eighty-six children (93 patients and 93 controls) were studied. The mean (SD) ages of the patients and controls were 8.8 (3.2) and 9.0 (3.1) years, respectively. The mean MI score was significantly higher for the patients, 1.7 (1.2), than the controls, 1.3 (1.0), P=0.002. A significantly higher proportion of the patients, 18 (19.4%), also had significant ischemia compared with the controls, 8 (8.6%), P=0.016. The median (interquartile range) serum cTnI level was significantly higher in the patients than the controls, P=0.006. All 7 of the patients with elevated cTnI had VOC. No significant correlation was found between MI score and cTnI in both groups. cTnI is elevated and ECG features of MI worsen during VOC. Longitudinal studies to investigate their evolvement over time are advocated.

Prevalence and prognostic value of cardiac troponin in elderly patients hospitalized for COVID-19.

BACKGROUNDIncreases in cardiac troponin (cTn) in coronavirus disease 2019 (COVID-19) have been associated with worse prognosis. Nonetheless, data about the significance of cTn in elderly subjects with COVID-19 are lacking.METHODSFrom a registry of consecutive patients with COVID-19 admitted to a hub hospital in Italy from 25/02/2020 to 03/07/2020, we selected those ≥ 60 year-old and with cTnI measured within three days from the molecular diagnosis of SARS-CoV-2 infection. When available, a second cTnI value within 48 h was also extracted. The relationship between increased cTnI and all-cause in-hospital mortality was evaluated by a Cox regression model and restricted cubic spline functions with three knots.RESULTSOf 343 included patients (median age: 75.0 (68.0−83.0) years, 34.7% men), 88 (25.7%) had cTnI above the upper-reference limit (0.046 µg/L). Patients with increased cTnI had more comorbidities, greater impaired respiratory exchange and higher inflammatory markers on admission than those with normal cTnI. Furthermore, they died more (73.9%vs. 37.3%, P < 0.001) over 15 (6−25) days of hospitalization. The association of elevated cTnI with mortality was confirmed by the adjusted Cox regression model (HR = 1.61, 95%CI: 1.06−2.52, P = 0.039) and was linear until 0.3 µg/L, with a subsequent plateau. Of 191 (55.7%) patients with a second cTnI measurement, 49 (25.7%) had an increasing trend, which was not associated with mortality (univariate HR = 1.39, 95%CI: 0.87−2.22, P = 0.265). CONCLUSIONSIn elderly COVID-19 patients, an initial increase in cTn is common and predicts a higher risk of death. Serial cTn testing may not confer additional prognostic information.

Inductive camrelizumab and apatinib for patients with locally advanced and resectable oral squamous cell carcinoma: A single-arm trial (Icemelting trial).

6052 Background: In patients with locally advanced oral squamous cell carcinoma (LAOSCC), major pathologic response (MPR) to induction therapy may translate into improved survival. The induction therapy using chemo-free drugs, such as the combination of anti-PD1 and anti-VEGFR drugs, has not been well issued in LAOSCC. Methods: A prospective single arm trial (NCT04393506) has been performed to evaluate the induction therapy of anti-PD1 and anti-VEGFR protocol in LAOSCC patients at clinical stage III and IVA. The patients received three cycles of intravenous Camrelizumab (PD-1 antibody, 200mg) on d1, d15, d29; and oral Apatinib (anti-VEGFR inhibitor, 250mg) daily, initiating on d1, ending on the 5th day before surgery. Radical surgery was planned on d42-d45. Post-operative radiotherapy was planned within 1.5 months after surgery, based on clinical and pathological stage. The primary endpoints were MPR and safety; primary tumors were assessed for the percentage of residual viable tumor that was identified on HE staining, and tumors with no more than 10% viable tumor cells were considered as MPR. This study has been approved by institutional ethics committee at Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine. Results: From April to December 2020, 21 patients were enrolled in this trial, and one patient withdraw from the trial at the beginning of treatment. The induction therapy was well-tolerated with no grade 3-4 toxicity or serve induction therapy-related AEs. One patient required surgery delay for 7 days due to unexplainable cTnI elevation. One patient put off Camrelizumab for 14 days due to grade 2 thrombocytopenia. One patient suspended Apatinib for 21 days due to grade 2 Hyperbilirubinemia. The induction therapy did not effect on the subsequent standard treatment. MPR rate was 40% (8/20), including 5% (1/20) pCR. Radiological evaluation of response to induction therapy showed 3 PR, 10 SD, 5 PD and 2 NA. Weak correlation was found between pathologic and radiological evaluation on induction therapy. Combined positive score (CPS) of PD-L1 expression in biopsy was evaluated in 19 patients; all 4 patients with CPS≥ 20 had MPR, 3 out of 11 patients with 1≤CPS &lt; 20 had MPR, and 1 out of 4 patients with CPS &lt; 1 had MPR. Conclusions: The chemo-free protocol of induction therapy using Camrelizumab and Apatinib is safe and well-tolerated for the patients with LAOSCC. The MPR rate is much higher using the anti-PD1 and anti-VEGFR protocol than the traditional induction chemotherapy protocol in LAOSCC. Clinical trial information: NCT04393506.

IMPLICATIONS OF PERIPROCEDURAL MYOCARDIAL BIOMARKER ELEVATIONS AND COMMONLY USED MI DEFINITIONS AFTER LEFT MAIN PCI

Abstract Objectives The aim of this study was to: 1) assess the relationship of different thresholds of creatine kinase–myocardial band (CK-MB) and cardiac troponin with subsequent mortality; and 2) evaluate the prognostic significance of periprocedural myocardial infarction (PMI) according to various definitions of myocardial infarction in patients with left main (LM) coronary artery disease. Background The magnitude of postprocedural biomarker elevation representing a clinically meaningful PMI after percutaneous coronary intervention (PCI) is controversial. Methods A total of 4,013 consecutive patients undergoing LM PCI at a single center from January 2004 to December 2016 were enrolled. CK-MB and cardiac troponin I (cTnI) were routinely collected at baseline and at frequent intervals between 8 and 48 hours after PCI. The primary and secondary outcomes were the covariate-adjusted 3-year rates of cardiovascular (CV) and all-cause mortality, respectively. Results The 3-year rate of CV mortality progressively increased with higher peak CK-MB values. CV mortality was first independently predicted by postprocedural CK-MB 3 to 5 times the upper reference limit (URL) (adjusted hazard ratio [aHR]: 2.93; 95% confidence interval [CI]: 1.02-8.40), whereas all-cause death was independently predicted only by CK-MB ≥ 10 × URL (aHR: 3.25; 95% CI: 1.37-7.70). In contrast, no level of peak postprocedural cTnI was associated with CV or all-cause death. PMI by the Society for Cardiovascular Angiography and Interventions (SCAI), Academic Research Consortium-2 (ARC-2), and fourth universal definition of myocardial infarction (UDMI) occurred in 1.3%, 3.1%, and 5.1% of patients, respectively. The SCAI definition was significantly associated with 3-year CV mortality (aHR: 4.93; 95% CI: 1.92-12.69) and all-cause mortality (aHR: 3.11; 95% CI: 1.33-7.27), whereas the ARC-2 and fourth UDMI definitions were not. Conclusions In a large cohort of consecutive patients undergoing LM PCI, intermediate (≥3 × URL) and high (≥10 × URL) levels of peak postprocedural CK-MB independently predicted 3-year CV and all-cause mortality, respectively, whereas even large elevations of post-PCI cTnI did not. The SCAI definition (but not the ARC-2 or fourth UDMI) of PMI was independently associated with mortality after LM PCI.

Hypertension as a sequela in patients of SARS-CoV-2 infection.

COVID-19 is a respiratory infectious disease caused by SARS-CoV-2, and cardiovascular damage is commonly observed in affected patients. We sought to investigate the effect of SARS-CoV-2 infection on cardiac injury and hypertension during the current coronavirus pandemic. The clinical data of 366 hospitalized COVID-19-confirmed patients were analyzed. The clinical signs and laboratory findings were extracted from electronic medical records. Two independent, experienced clinicians reviewed and analyzed the data. Cardiac injury was found in 11.19% (30/268) of enrolled patients. 93.33% (28/30) of cardiac injury cases were in the severe group. The laboratory findings indicated that white blood cells, neutrophils, procalcitonin, C-reactive protein, lactate, and lactic dehydrogenase were positively associated with cardiac injury marker. Compared with healthy controls, the 190 patients without prior hypertension have higher AngⅡ level, of which 16 (8.42%) patients had a rise in blood pressure to the diagnostic criteria of hypertension during hospitalization, with a significantly increased level of the cTnI, procalcitonin, angiotensin-II (AngⅡ) than those normal blood pressure ones. Multivariate analysis indicated that elevated age, cTnI, the history of hypertension, and diabetes were independent predictors for illness severity. The predictive model, based on the four parameters and gender, has a good ability to identify the clinical severity of COVID-19 in hospitalized patients (area under the curve: 0.932, sensitivity: 98.67%, specificity: 75.68%). Hypertension, sometimes accompanied by elevated cTnI, may occur in COVID-19 patients and become a sequela. Enhancing Ang II signaling, driven by SARS-CoV-2 infection, might play an important role in the renin-angiotensin system, and consequently lead to the development of hypertension in COVID-19.

Novel Cardiac Troponin I S43/45N Substitution does not Cause Aberrant Cardiac Remodeling or Dysfunction in Mice

Elevated protein kinase C (PKC) expression and activity, along with downstream phosphorylation of cardiac troponin I (cTnI) are linked to cardiac dysfunction. Specifically, elevated cTnI S43/45 phosphorylation is reported in human and rodent models of heart failure, but the exact role of phosphorylation at this site is still debated. Transgenic (tg) mice expressing cardiac-specific phospho-mimetic S43/45D develop contractile dysfunction, followed by cardiac hypertrophy, fibrosis, and progressive heart failure. Thus, S43/45 phosphorylation is postulated to be a sarcomeric node for modulating contractile function in the heart. To further test this idea, it is critical to show that a phospho-null substitution at this site does not alter wild-type function. Multiple groups have used the conventional nonpolar alanine (A) phospho-null substitution at S43/45 and report diminished myocyte and contractile function, which resembles the outcome after phosphorylation. We postulate the nonpolar properties of A potentially alter interactions between cTnI, troponin T (TnT) and C (TnC). As a result, the amide R side chain in asparagine (N), with a polarity somewhat similar to the hydroxyl group in S, could make N a reasonable non-phosphorylatable residue without overt effects on wild-type function. Previously, adult rat myocytes virally transduced with S43/45N (SN)in our laboratory did not display overt changes in contractile function compared to wild-type myocytes. In ongoing experiments, generation of tg mice expressing a cardiac-specific cTnISN also show no changes in in vivo cardiac contractile function or evidence of remodeling in mice up to at least four months of age. These findings suggest the novel N substitution acts as a “functionally conservative” phospho-null substitution at cTnIS43/45 in myocardium.

Chronic elevation of cardiac troponin I predicts the extent of coronary disease in hemodialysis patients presenting with acute enzyme elevation

IntroductionElevation of cardiac troponin I (cTn-I) is associated with coronary artery disease (CAD) in asymptomatic patients with end-stage renal disease (ESRD) receiving hemodialysis. We aim to investigate the diagnostic value of chronically elevated cTn-I in ESRD patients presenting with an acute rise in serum cTn-I levels. MethodsWe performed a retrospective analysis of 364 patients. Using coronary angiography, we correlated baseline elevation of cTn-I with the severity of CAD when hemodialysis patients present with acute symptomatic elevation in serum cTn-I. ResultsIn hemodialysis patients presenting with a rise in serum cTn-I above baseline levels, 59% had severe CAD, and 17% had no angiographic evidence of CAD. Hemodialysis patients with severe CAD had significantly higher baseline cTn-I levels compared to patients with non-severe CAD or normal coronaries (p < 0.0001). Baseline elevation of cTn-I in the severe CAD group was correlated with the degree of CAD occlusion (r2 0.56, p < 0.0001), fitting a positive linear model. Furthermore, baseline cTn-I differentiates between patients with and without severe CAD with a test accuracy of 0.72 (95% CI, 0.69–0.75, p < 0.001). At a value of ≥0.2 ng/mL (cutoff for myocardial necrosis), the specificity of baseline cTn-I for underlying severe CAD was 0.95. ConclusionsElevated baseline cTn-I has good accuracy for anticipating more advanced angiographic CAD when hemodialysis patients present with a symptomatic rise in serum cTn-I above baseline levels. Baseline elevation of cTn-I can be used for cardiac disease risk management in hemodialysis patients presenting with symptoms suggestive of CAD.

Cardiac Complications in COVID-19: A Systematic Review and Meta-analysis.

The newly emerged coronavirus disease 2019 (COVID-19) seems to involve different organs, including the cardiovascular system. We systematically reviewed COVID-19 cardiac complications and calculated their pooled incidences. Secondarily, we compared the cardiac troponin I (cTnI) level between the surviving and expired patients. A systematic search was conducted for manuscripts published from December 1, 2019 to April 16, 2020. Cardiovascular complications, along with the levels of cTnI, creatine kinase (CK), and creatine kinase MB (CK-MB) in hospitalized PCR-confirmed COVID-19 patients were extracted. The pooled incidences of the extracted data were calculated, and the unadjusted cTnI level was compared between the surviving and expired patients. Out of 1094 obtained records, 22 studies on a total of 4,157 patients were included. The pooled incidence rate of arrhythmia was 10.11%. Furthermore, myocardial injury had a pooled incidence of 17.85%, and finally, the pooled incidence for heart failure was 22.34%. The pooled incidence rates of cTnI, CK-MB, and CK elevations were also reported at 15.16%, 10.92%, and 12.99%, respectively. Moreover, the pooled level of unadjusted cTnI was significantly higher in expired cases compared with the surviving (mean difference = 31.818, 95% CI = 17.923-45.713, P value <0.001). COVID-19 can affect different parts of the heart; however, the myocardium is more involved.

Autopsy Cardiac Troponin I Plasma Levels Can Be Elevated in Myocardial Infarction Type 3: A Proposal to Modify the Definition of Myocardial Infarction Type 3.

The definition of myocardial infarction (MI) type 3 does not include the possible elevation of postmortem biomarkers if measured at autopsy. We determined postmortem cardiac troponin I (cTnI) levels in plasma samples obtained at autopsy in patients who died from MI type 3 to determine whether cTnI plasma levels may be elevated. Using a chemiluminescent microparticle immunoassay system, we determined postmortem cTnI plasma levels at autopsy performed within 24 hours of death in every decedent who died from MI type 3, confirmed by an autopsy. Over 2 years, autopsy confirmed 52 decedents who died from MI type 3 due to coronary atherosclerotic disease. The age range and mean age were 40 to 78 and 60.6 years, respectively, 38 (73%) men and 14 (27%) women. Ten percent of the decedents exhibited postmortem cTnI plasma levels that were within the normal reference levels (0.01-0.30 ng/mL). Ninety percent of the decedents exhibited elevated cTnI plasma levels at autopsy, which ranged from 0.31 to greater than 4400 ng/mL. Sixty-nine percent of our decedents showed severe/significant (75%-100%) luminal occlusion in 2 or 3 major coronary arteries. If cTnI plasma levels are measured in autopsy blood samples after sudden and unexpected death due to MI type 3, highly elevated cTnI plasma levels may be detected. We propose that the current MI type 3 definition be slightly modified to include the possible elevation of cTnI plasma levels if measured at autopsy in the immediate postmortem period.

Recent myocardial ischemia in patients presented with upper gastrointestinal bleeding with and without portal hypertension

ObjectiveTo assess the relationship between upper gastrointestinal bleeding (UGIB) in both cirrhotic and noncirrhotic groups and the development of acute myocardial infarction (AMI).BackgroundUGIB can cause myocardial ischemia and necrosis. Both UGIB and liver cirrhosis have a higher mortality with the development of AMI, than either of them alone.Patients and methodsA cross-sectional comparative study was done on 263 patients who presented with UGIB, and they were divided into four groups: GI (n = 118), cirrhotic patients; GII (n = 85), noncirrhotic patients; GIII (n = 30), cirrhotic patients with no history of UGIB; and GIV (n = 30), the control group. They were all subjected to history taking, examination, and investigations.ResultsAge was higher in GI than GII (P = 0.0001). Cardiac troponin I (cTn-I) was positive for MI in 18/118 (15.3%) in GI, 20/85 (23.5%) in GII, and 0% in GIII and GIV (P = 0.001). Mortality rate was 11/118 (9.3%) in GI and 4/85 (4.7%) in GII and 0% in GIII and GIV (P = 0.0001). Length of hospital stay (LOS) was higher in GI than GII. There was a positive correlation between Glasgow-Blatchford score and cTn-I elevation (R=+0.19, P = 0.003) (P = 0.0001). Odds ratio of smoking, viral hepatitis, and LOS in cTn-I-positive patients was 12.61, 14.49, and 2.76 times higher than troponin-negative patients, respectively (P = 0.0001).ConclusionPatients with cirrhosis when developing UGIB may be predisposed to AMI especially older ages, men, comorbid diseases, patients with increased LOS;in addition to more complications and higher mortality rate than non-cirrhotic patients.

POTENTIAL ROLE OF VITAMIN D3 IN AMELIORATING DOXORUBICIN INDUCED CARDIOTOXICITY IN MALE RATS

The aim: The goal of this study was to asses if vitamin D3 protect rats against doxorubicin-induced cardiotoxicity. Materials and methods: Overall twenty-one male rats were divided randomly into three groups (7 rats in each group). Control group in which rats received 0.9% normal saline for two weeks. Doxorubicin group (induced group): rats received 2.5mg/kg three times a week for two weeks and Vitamin D3 group (treated group): vitamin D3 was given in a dose 60000 IU/kg IP as single dose on the first day of the procedure. Results: Doxorubicin caused cardiotoxicity as indicated by a significant elevation (P &lt; 0.01) in TNF-α, IL-6, MDA, cTnI and caspase-3 level, while TAC and Bcl-2 levels significantly (P &lt; 0.01) reduced in cardiac tissues of rats in the doxorubicin group as compared with control group, also doxorubicin caused histological lesions. Vitamin D3 administration show cardioprotective effect reported by significant decrease (P &gt;0.01) incTnI, Bcl2 and TAO as compared with DOX group, also show significant improvement (P &gt;0.01) in cardiomyopathy histological lesions score. Conclusions: At their applied doses in the present study, vitamin D3 exerted a significant heart protective effect against cardiotoxicity induced by doxorubicin in rats probably by intrusive with Oxidative-stress, inflammatory response in addition to apoptotic pathway

511. Hospitalized COVID-19 Patients with Elevated Cardiac Troponin I Have Increased Length Of Stay But Similar Ventilation Time

BackgroundCoronavirus disease 2019 (COVID-19) causes increased mortality and morbidity in patients with underlying cardiovascular disease. Elevated cardiac troponin I (cTnI) can suggest either a co-concurrent myocarditis or acute myocardial infarction. Understanding how laboratory values predict disease severity is important for clinicians to guide therapy and triage patients.MethodsA cross sectional study was performed utilizing the 184 hospital United States database of HCA. Patients were selected based on inpatient visits to HCA facilities from February 2020 to May 2020 with a COVID-19 diagnosis and at least one cTnI lab test. Patients were divided according to an elevated or normal cTnI value based on the 99th percentile reference range of the test. Outcomes, such as length of stay, disposition, and time on the ventilator, were compared.Results3968 patients hospitalized with COVID-19 were identified. Of those, 3158 patients had at least one cTnI test throughout their hospitalization. 829 (26%) had at least one positive cTnI during their hospitalization. Patients with at least one positive cTnI were hospitalized on average for 8.7 days, whereas patients without positive cTnI were hospitalized on average for 6.3 days (p< 0.0001). 1499 patients without positive cTnI were sent home without health care, but only 196 with positive cTnI were discharged home without requiring home health (p < 0.0001). Need for mechanical ventilation was also higher in the elevated cTnI group. If intubated, patients in both groups required on average the same amount of ventilator time, 7 days (p = 0.7263).Ventilation time between COVID-19 patients with and without elevated Troponins Length of hospitalization stay between COVID-19 patient with and without elevated Troponins Differences in discharge between COVID-19 patients with and without elevated Troponins ConclusionPatients with at least one positive cTnI during their hospitalization had increased length of stay and decreased likelihood of being discharged home without home health. Using a large nationwide database we confirmed previously published findings in smaller patient populations associating cardiovascular disease with COVID-19 severity. Once patients were intubated, both subsets of patients with and without elevated cTnI had similar days on the ventilator, suggesting the COVID-19 acute respiratory distress syndrome (ARDS) has a more complicated relationship to troponin levels. These findings suggest that patients with an increased cTnI should be triaged to receive aggressive management.Disclosures All Authors: No reported disclosures