Cardiac Injury Biomarkers Research Articles

Long-term cardiac pathology in individuals with mild initial COVID-19 illness

Cardiac symptoms are increasingly recognized as late complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in previously well individuals with mild initial illness, but the underlying pathophysiology leading to long-term cardiac symptoms remains unclear. In this study, we conducted serial cardiac assessments in a selected population of individuals with Coronavirus Disease 2019 (COVID-19) with no previous cardiac disease or notable comorbidities by measuring blood biomarkers of heart injury or dysfunction and by performing magnetic resonance imaging. Baseline measurements from 346 individuals with COVID-19 (52% females) were obtained at a median of 109 days (interquartile range (IQR), 77–177 days) after infection, when 73% of participants reported cardiac symptoms, such as exertional dyspnea (62%), palpitations (28%), atypical chest pain (27%) and syncope (3%). Symptomatic individuals had higher heart rates and higher imaging values or contrast agent accumulation, denoting inflammatory cardiac involvement, compared to asymptomatic individuals. Structural heart disease or high levels of biomarkers of cardiac injury or dysfunction were rare in symptomatic individuals. At follow-up (329 days (IQR, 274–383 days) after infection), 57% of participants had persistent cardiac symptoms. Diffuse myocardial edema was more pronounced in participants who remained symptomatic at follow-up as compared to those who improved. Female gender and diffuse myocardial involvement on baseline imaging independently predicted the presence of cardiac symptoms at follow-up. Ongoing inflammatory cardiac involvement may, at least in part, explain the lingering cardiac symptoms in previously well individuals with mild initial COVID-19 illness.

EP05.01-012 Avoiding Cardiac Toxicity in Lung Cancer Radiotherapy (ACcoLade) Trial - Initial Results

Increasing cardiac radiation dose is associated with worse survival and cardiac events following thoracic radiotherapy however, the mechanism of injury is unknown. High sensitivity cardiac troponin I (hsTnI) and N-terminal pro-B-type natriuretic peptide (NT pro-BNP) are established blood biomarkers of cardiac injury. Cardiac CT (CCT) is a non-invasive method of assessing coronary artery disease and echocardiography assesses cardiac structure and function. We present initial results of a prospective cohort study of cardiac blood and imaging biomarkers in patients undergoing lung cancer radiotherapy.

Gongronema latifolium leaf extract protects against dexamethasone-induced myocardial cell injury via cardiac oxido-inflammatory molecules modulation.

The use of glucocorticoids in the treatment of inflammatory disorders can result in myocardial injury. This study was carried out to investigate the protective effects of ethanolic leaf extract of Gongronema latifolium (GL) in dexamethasone (DEX)-induced myocardial injury. Wistar rats were assigned to 4 groups (n=6) namely, control, GL, DEX, and DEX+GL groups. DEX (35 μg/kg body weight) was administered subcutaneously to induce myocardial injury, while GL leaf extract (200 mg/kg body weight) was administered orally. Both agents were administered to their respective groups for 14 days. DEX (p < .05) decreased nitric oxide and increased angiotensin-converting enzyme activity compared with the control. Serum superoxide dismutase activity and bilirubin level were decreased (p < .05), while malondialdehyde level was increased (p < .05) in the DEX group. Serum liver enzymes, inflammatory biomarkers (C-reactive protein and interleukin-6), and cardiac injury biomarkers (creatinine kinase, cardiac troponin-T, and lactate dehydrogenase) were significantly (p < .05) increased in the DEX group relative to the control. Administration of GL leaf extract attenuated these changes significantly. The study therefore suggests that GL is beneficial in the treatment of myocardial injury via the downregulation of high serum concentration of cardiac biomarkers, oxidative stress markers, and inflammatory biomarkers released as a result of the insult caused by glucocorticoid administration. PRACTICAL APPLICATIONS: In this study, we demonstrated that prolonged use of dexamethasone resulted in myocardial cell injury via increased production of reactive oxygen species, inflammatory biomarkers, and inhibition of nitric oxide, a potent vasodilator. The leaves extract of Gongronema latifolium elicits the anti-inflammatory and cardioprotective potential as an efficient inhibitor of free radicals with good antioxidant properties. The study provides scientific evidence of the therapeutic ability of the extract of G. latifolium in the treatment of DEX-induced myocardial injury and could be a drug candidate for the treatment of myocardial injury and inflammation in humans.

Strenuous Endurance Exercise and the Heart: Physiological versus Pathological Adaptations.

Although the benefits of regular physical activity on cardiovascular health are well established, the effects of strenuous endurance exercise (SEE) have been a matter of debate since ancient times. In this article, we aim to provide a balanced overview of what is known about SEE and the heart-from epidemiological evidence to recent cardiac imaging findings. Lifelong SEE is overall cardioprotective, with endurance master athletes showing in fact a youthful heart. Yet, some lines of research remain open, such as the need to elucidate the time-course and potential relevance of transient declines in heart function (or increases in biomarkers of cardiac injury) with SEE. The underlying mechanisms and clinical relevance of SEE-associated atrial fibrillation, myocardial fibrosis, or high coronary artery calcium scores also remain to be elucidated. © 2022 American Physiological Society. Compr Physiol 12:1-19, 2022.

Cardioprotective Effects and in-silico Antioxidant Mechanism of L-Ergothioneine in Experimental Type-2 Diabetic Rats.

Diabetic cardiotoxicity is commonly associated with oxidative injury, inflammation, and endothelial dysfunction. L-ergothioneine (L-egt), a diet-derived amino acid, has been reported to decrease mortality and risk of cardiovascular injury, provides cytoprotection to tissues exposed to oxidative damage, and prevents diabetes-induced perturbation. This study investigated the cardioprotective effects of L-egt on diabetes-induced cardiovascular injuries and its probable mechanism of action. Twenty-four male Sprague-Dawley rats were divided into non-diabetic (n = 6) and diabetic groups (n = 18). Six weeks after the induction of diabetes, the diabetic rats were divided into three groups (n = 6) and administered distilled water, L-egt (35mg/kg), and losartan (20mg/kg) by oral gavage for six weeks. Blood glucose and mean arterial pressure (MAP) were recorded pre-and post-treatment, while biochemical, ELISA, and RT-qPCR analyses were conducted to determine inflammatory, injury-related and antioxidant biomarkers in cardiac tissue after euthanasia. Also, an in-silico study, including docking and molecular dynamic simulations of L-egt toward the Keap1- Nrf2 protein complex, was done to provide a basis for the molecular antioxidant mechanism of Legt. Administration of L-egt to diabetic animals reduced serum triglyceride, water intake, MAP, biomarkers of cardiac injury (CK-MB, CRP), lipid peroxidation, and inflammation. Also, Legt increased body weight, antioxidant enzymes, upregulated Nrf2, HO-1, NQO1 expression, and decreased Keap1 expression. The in-silico study showed that L-egt inhibits the Keap1-Nrf2 complex by binding to the active site of Nrf2 protein, thereby preventing its degradation. L-egt protects against diabetes-induced cardiovascular injury via the upregulation of the Keap1-Nrf2 pathway and its downstream cytoprotective antioxidants.

An Improved Monkey Model of Myocardial Ischemic Infarction for Cardiovascular Drug Development.

Non-human primate monkey model of myocardial ischemic infarction is precious for translational medicine research. Ligation of the left anterior descending (LAD) artery is a common procedure to induce myocardial ischemic infarction. However, the consistency of the myocardial infarction thus generated remains problematic. The present study was undertaken to critically evaluate the monkey model of myocardial ischemic infarction to develop a procedure for a consistent cross-study comparison. Forty male Rhesus monkeys were divided into 4 groups and subjected to LAD artery ligation at different levels along the artery. In addition, the major diagonal branch was selectively ligated parallel to the ligation site of the LAD artery according to the diagonal branch distribution. Analyses of MRI, echocardiography, cardiac hemodynamics, electrocardiography, histopathology, and cardiac injury biomarkers were undertaken to characterize the monkeys with myocardial infarction. Ligation at 40% of the total length of the artery, measured from the apex end, produced variable infarct areas with inconsistent functional alterations. Ligation at 60% or above coupled with selective ligation of diagonal branches produced a consistent myocardial infarction with uniform dysfunction. However, ligation at 70% caused a lethal threat. After a thorough analysis, it is concluded that ligation at 60% of the total length coupled with selective ligation of diagonal branches, enables standardization of the location of occlusion and the subsequent ischemic area, as well as avoids the influence of the diagonal branches, are ideal to produce a consistent monkey model of myocardial ischemic infarction.

Identification of Adamts4 as a novel adult cardiac injury biomarker with therapeutic implications in patients with cardiac injuries

Pathological cardiac remodeling as an aftermath of a severe cardiac injury can lead to ventricular dysfunction and subsequent heart failure. Adamts4, a metalloproteinase, and disintegrin with thrombospondin-like motif, involved in the turnover of certain extracellular matrix molecules and pathogenesis of osteoarthritis, also plays a role in cardiac remodeling although little is presently known about its expression and function in the heart. Here, we have investigated the dynamic expression pattern of Adamts4 during cardiogenesis and also in the adult heart. To our surprise, adult cardiac injury reactivated Adamts4 expression concomitant with fibrosis induction. To better understand the mechanism, cultured H9c2 cardiomyocyte cells were subjected to ROS injury and Hypoxia. Moreover, through combinatorial treatment with SB431542 (an inhibitor of Tgf-β1), and Adamts4 siRNA mediated gene knockdown, we were able to decipher a regulatory hierarchy to the signal cascade being at the heart of Tgf-β regulation. Besides the hallmark expression of Adamts4 and Tgf-β1, expression of other fibrosis-related markers like Collagen-III, alpha-SMA and Periostin were also assessed. Finally, increased levels of Adamts4 and alpha-SMA proteins in cardiac patients also resonated well with our animal and cell culture studies. Overall, in this study, we highlight, Adamts4 as a novel biomarker of adult cardiac injury.

Longitudinal Changes in Cardiac Troponin and Risk of Heart Failure Among Black Adults

BackgroundAmong Black adults, high-sensitivity cardiac troponin I (hs-cTnI) is associated with heart failure (HF) risk. The association of longitudinal changes in hs-cTnI with risk of incident HF, HF with reduced and preserved ejection fraction (HFrEF and HFpEF, respectively), among Black adults is not well-established. Methods and ResultsThis study included Black participants from the Jackson Heart Study with available hs-cTnI data at visits 1 (2000–2004) and 2 (2005–2008) and no history of cardiovascular disease. Cox models were used to evaluate associations of categories of longitudinal change in hs-cTnI with incident HF risk. Among 2423 participants, 11.6% had incident elevation in hs-cTnI at visit 2, and 16.9% had stable or improved elevation (≤50% increase in hs-cTnI), and 4.0% had worsened hs-cTnI elevation (>50% increase). Over a median follow-up of 12.0 years, there were 139 incident HF hospitalizations (64 HFrEF, 58 HFpEF). Compared with participants without an elevated hs-cTnI, those with incident, stable or improved, or worsened hs-cTnI elevation had higher HF risk (adjusted hazard ratio 3.20 [95% confidence interval, 1.92–5.33]; adjusted hazard ratio 2.40, [95% confidence interval, 1.47–3.92]; and adjusted hazard ratio 8.10, [95% confidence interval, 4.74–13.83], respectively). Similar patterns of association were observed for risk of HFrEF and HFpEF. ConclusionsAmong Black adults, an increase in hs-cTnI levels on follow-up was associated with a higher HF risk. Lay SummaryThe present study included 2423 Black adults from the Jackson Heart Study with available biomarkers of cardiac injury and no history of cardiovascular disease at visits 1 and 2. The majority of participants did not have evidence of cardiac injury at both visits (67.5%), 11.6% had evidence of cardiac injury only on follow-up, 14.5% had stable elevations, 4.0% had worsened elevations, and 2.4% had improved elevations of cardiac injury biomarkers during follow-up. Compared with participants without evidence of cardiac injury, those with new, stable, and worsened levels of cardiac injury had a higher risk of developing heart failure. TweetAmong Black adults, persistent or worsening subclinical myocardial injury is associated with an elevated risk of HF.

5-Methoxytryptophan pretreatment alleviates lipopolysaccharide-induced cardiac injury and dysfunction

Reducing inflammation is a promising therapeutic approach for sepsis-induced cardiomyopathy (SIC). The 5-Methoxytryptophan (5-MTP) is a tryptophan metabolite that demonstrates anti-inflammatory, anti-fibrosis, anti-tumorigenesis, and anti-senescence features. Current investigations aimed to assess the 5-MTP pretreatment impacts on lipopolysaccharide (LPS)-induced cardiac injury and dysfunction. For in vivo studies, the mice were categorized randomly into four groups: control, LPS, LPS+5-MTP (25 mg/kg) and LPS+5-MTP (50 mg/kg). The mice in the LPS+5-MTP groups were given 5-MTP intraperitoneally once a day for 7 days. LPS (10 mg/kg) was then administered intraperitoneally for 24 h. Echocardiography, cardiac injury biomarkers, and H & E staining evaluated heart anatomy and function. The findings indicate that 5-MTP pretreatment significantly reduced LPS-induced heart dysfunction and morphological alterations. Western blot assay was used for investigating molecular mechanisms. After LPS stimulation, the pro-inflammatory cytokines (IL-1β, IL-6, TNF-α and NLRP3) protein levels increased while anti-inflammatory cytokine (IL-10) decreased; however, 5-MTP pretreatment mitigated this response by suppressing the stimulation of the NF-κB signaling pathway. Furthermore, 5-MTP administration reduced LPS-induced cardiac apoptosis, as demonstrated by increased protein levels of cleaved-Casepase-1, cleaved-Casepase-3 and Bax, and decreased protein level of Bcl-2 after LPS stimulation, whereas LPS-induced cardiac apoptosis was reversed by 5-MTP pretreatment. In vitro, 5-MTP pretreatment had a similar cardioprotective effect on cultured cardiac fibroblasts challenged with LPS. In conclusion, 5-MTP pretreatment can reduce LPS-induced cardiac inflammation and apoptosis, implying that 5-MTP is a possible therapeutic option for SIC.

1081-P: Blood Pressure Variability Is Associated with Risk of Heart Failure, Elevated NT-proBNP, and High-Sensitivity Troponin: Results from MESA

The association between blood pressure variability (BPv) and heart failure (HF) is incompletely studied. This association, and its links with biomarkers of HF and cardiac injury, were examined in the community-based Multi-Ethnic Study of Atherosclerosis (MESA) . Resting seated BP was measured thrice; the average of the last two measures was used for analysis, and visit-to-visit BPv (coefficient of variation-CV) was assessed over 5 visits. Biomarkers of HF (N-terminal B-type natriuretic peptide: NT-proBNP) and cardiac injury (high-sensitivity troponin-T: hs-cTnT) , respectively, at exams 1, 3 and 5 were ascertained. With 9.4 years median follow-up in 6,785 individuals, 385 HF events occurred. In adjusted time-dependent models including CVD risk factors, BMI, BP medications, and cumulative mean BP, BPv (CV-SBP and CV-DBP) was associated with risk of clinical HF (e.g., CV-SBP HR=1.16, p=0.03) . Similar patterns were seen regardless of T2D status. The associations were stronger for HF with reduced ejection fraction (EF) vs. preserved EF. When excluding those with baseline NT-proBNP &amp;gt;450 pg/mL or hs-cTnT &amp;gt;14 ng/L, the association between BPv and HF became stronger. CV-SBP and CV-DBP were also associated with elevated exam 5 NT-proBNP (&amp;gt;450 pg/mL: OR=1.74, and OR = 1.32, p&amp;lt;0.001) . We saw a positive relationship between CV-SBP and exam 1 to exam 5 changes in NT-proBNP (p=0.001) and hs-cTnT (p&amp;lt;0.001) as well as elevated hs-cTnT (&amp;gt;14 ng/L; OR=1.18, p&amp;lt;0.001) . Our data strongly support an association between BPv and both clinical HF and elevated NT-proBNP, and the association was greater in those with reduced vs. preserved EF. The association between BPv and clinical HF was related to deleterious changes in subclinical markers of myocardial injury and heart failure. Disclosure D.S.Nuyujukian: None. J.Zhou: Research Support; Dexcom, Inc. J.Koska: None. C.Nwabuo: None. A.Bertoni: None. S.Shea: Research Support; National Heart, Lung, and Blood Institute. P.Reaven: Research Support; AstraZeneca, Dexcom, Inc. Funding NIH/NHLBI (F32HL156626) NIH/NHLBI (R21HL150374) NIH/NHLBI (R21HL150268) NIH/NHLBI (R01HL138969)

Aspergillus awamori attenuates ochratoxin A-induced renal and cardiac injuries in rabbits by activating the Nrf2/HO-1 signaling pathway and downregulating IL1β, TNFα, and iNOS gene expressions.

Ochratoxin A (OTA) is one of the most dangerous and that pollute agricultural products, inducing a variety of toxic effects in humans and animals. The current study explored the protective effect of different concentrations of Aspergillus awamori (A. awamori) against OTA (0.3 mg/kg diet) induced renal and cardiac damage by exploring its mechanism of action in 60 New Zealand white male rabbits. Dietary supplementation of A. awamori at the selected doses of 50, 100, and 150 mg/kg diet, respectively, for 2 months significantly improved the rabbit’s growth performance; modulated the suppressed immune response and restored the altered hematological parameters; reduced the elevated levels of renal injury biomarkers such as urea, creatinine, and alkaline phosphatase; and increased serum total proteins concentrations. Moreover, it also declined enzymatic activities of cardiac injury biomarkers, including AST, LDH, and CK-MB. A. awamori alleviated OTA-induced degenerative and necrotic changes in the kidney and heart of rabbits. Interestingly, A. awamori upregulated Nrf2/OH-1 signaling pathway. Therefore enhanced TAC, CAT, and SOD enzyme activities and reduced OTA-induced oxidative and nitrosative stress by declining iNOS gene expression and consequently lowered MDA and NO levels. In addition to attenuating renal and cardiac inflammation via reducing IL-1β, TNF-α gene expressions in a dose-dependent response. In conclusion,this is the first report to pinpoint that dietary incorporation of A. awamori counteracted OTA-induced renal and cardiac damage by potentiating the rabbit’s antioxidant defense system through its potent antioxidant, free radical scavenging, and anti-inflammatory properties in a dose-dependent response. Based on our observations, A. awamori could be utilized as a natural protective agent against ochratoxicosis in rabbits.Graphical abstract

New aspects in cardiorenal syndrome and HFpEF.

ABSTRACTCardiorenal syndrome (CRS) is a complex disease in which the heart and kidneys are simultaneously affected, and subsequently, the malfunction of one organ promotes the deterioration of the other. Heart failure (HF) with preserved ejection fraction (HFpEF) is the most common form of HF. The pathophysiology of CRS is not well known and several mechanisms have been proposed. An elevation of central venous pressure seems to be one of the key points to consider, among others such as an increase in intraabdominal pressure. Several diagnostic tools have been identified to establish the diagnosis of CRS in patients with HFpEF. Currently, the availability of biomarkers of renal and cardiac injury, the use of pulmonary ultrasound, the monitoring of the size of the inferior vena cava and the study of the renal venous pattern offer a new dimension in accurately diagnosing and quantifying organ damage in CRS. Beyond the symptomatic treatment of congestion, until recently specific therapeutic tools for patients with CRS and HFpEF were not available. Interestingly, the development of new drugs such as the angiotensin/neprilysin inhibitors and sodium-glucose cotransporter-2 (SGLT-2) inhibitors offer new therapeutic strategies with potential benefits in reduction of cardiorenal adverse outcomes in this population. Randomized clinical trials that focus on patients with HFpEF are currently ongoing to delineate optimal new treatments that may be able to modify their prognosis. In addition, multidisciplinary teamwork (nephrologist, cardiologist and nurse) is expected to decrease the number of visits and the rate of hospitalizations, with a subsequent patient benefit.

Ameliorative Effect of Morinda Lucida on L‐nitro Arginine Methyl Ester (L‐name) Induced Hypertension in Male Wistar Rats

Hypertension is a chronic cardiovascular disease of extreme and important global concern. It has been established as a leading cause of death especially in humans. The aim of this study was to evaluate the possible antihypertensive effect of a common locally available plant Morinda lucidaagainst L‐Nitro‐Arginine‐Methyl‐Ester (L‐NAME)‐induced hypertension in male Wistar rats.Forty‐eight rats were used for the experiment. They were divided into six groups labelled A‐F, each containing eight animals. The animals were dosed for six weeks with group A being the control group (normotensive) given feed and water ad libitun; Group B animals were administered L‐NAME only, 40 mg/kg (hypertensive); Groups C, D and E were simultaneously treated with L‐NAME (40 mg/kg) and Morinda lucida extract in increasing doses of 100 mg/kg, 200 mg/kg and 400 mg/kg, respectively, while Group F were given lisinopril at 20 mg/kg for a period of 6 weeks. From the result, there was significant increase in systolic, diastolic, and mean arterial blood pressure in the hypertensive group compared to the normotensive group and hypertensive treated groups. Hypertension caused significant (p&lt;0.05) increases in oxidative stress markers, including malondialdehyde (MDA), protein carbonyl (PC), hydrogen peroxide (H2O2), while reducing the activities of superoxide dismutase (SOD), and serum nitric oxide (NO) levels. Also, serum myeloperoxidase (MPO), blood urea nitrogen and creatinine were increased with high expression of cardiac injury biomarkers such as cardiac troponin and angiotensin 2 type 1 receptor. These indicated oxidative stress, cardiac damage because of hypertension, most especially in the untreated hypertensive group. The co‐treatment of hypertensive rats with Morinda lucida extract caused reduction in markers of oxidative stress and inflammation and normalized blood pressure parameters. The findings from this study suggest the possibility of using Morinda lucida extract as a novel antihypertensive agent.

Biomarkers of Cardiac Injury, Renal Injury, and Inflammation Are Strong Mediators of Sex-Associated Death in COVID-19.

BackgroundStudies examining outcomes among individuals with COronaVIrus Disease 2019 (COVID-19) have consistently demonstrated that men have worse outcomes than women, with a higher incidence of myocardial injury, respiratory failure, and death. However, mechanisms of higher morbidity and mortality among men remain poorly understood. We aimed to identify mediators of the relationship between sex and COVID-19-associated mortality.MethodsPatients hospitalized at two quaternary care facilities, New York Presbyterian Hospital (CUIMC/NYPH) and Massachusetts General Hospital (MGH), for SARS-CoV-2 infection between February and May 2020 were included. Five independent biomarkers were identified as mediators of sex effects, including high-sensitivity cardiac troponin T (hs-cTNT), high sensitivity C-reactive protein (hs-CRP), ferritin, D-dimer, and creatinine.ResultsIn the CUIMC/NYPH cohort (n = 2,626, 43% female), male sex was associated with significantly greater mortality (26 vs. 21%, p = 0.0146) and higher peak hs-cTNT, hs-CRP, ferritin, D-dimer, and creatinine (p < 0.001). The effect of male sex on the primary outcome of death was partially mediated by peak values of all five biomarkers, suggesting that each pathophysiological pathway may contribute to increased risk of death in men. Hs-cTnT, creatinine, and hs-CRP were the strongest mediators. Findings were highly consistent in the MGH cohort with the exception of D-dimer.ConclusionsThis study suggests that the effect of sex on COVID-19 outcomes is mediated by cardiac and kidney injury, as well as underlying differences in inflammation and iron metabolism. Exploration of these specific pathways may facilitate sex-directed diagnostic and therapeutic strategies for patients with COVID-19 and provides a framework for the study of sex differences in other complex diseases.

The Additive Value of Cardiovascular Magnetic Resonance in Convalescent COVID-19 Patients.

In COVID-19 the development of severe viral pneumonia that is coupled with systemic inflammatory response triggers multi-organ failure and is of major concern. Cardiac involvement occurs in nearly 60% of patients with pre-existing cardiovascular conditions and heralds worse clinical outcome. Diagnoses carried out in the acute phase of COVID-19 rely upon increased levels of circulating cardiac injury biomarkers and transthoracic echocardiography. These diagnostics, however, were unable to pinpoint the mechanisms of cardiac injury in COVID-19 patients. Identifying the main features of cardiac injury remains an urgent yet unmet need in cardiology, given the potential clinical consequences. Cardiovascular magnetic resonance (CMR) provides an unparalleled opportunity to gain a deeper insight into myocardial injury given its unique ability to interrogate the properties of myocardial tissue. This endeavor is particularly important in convalescent COVID-19 patients as many continue to experience chest pain, palpitations, dyspnea and exertional fatigue, six or more months after the acute illness. This review will provide a critical appraisal of research on cardiovascular damage in convalescent adult COVID-19 patients with an emphasis on the use of CMR and its value to our understanding of organ damage.

Prognostic Value of Serum Cardiac Troponin in Acute Ischemic Stroke: An Updated Systematic Review and Meta-Analysis

Background and purposeCardiac troponin (cTn) is a specific biomarker of cardiac injury and elevation of cTn is related to increased mortality. However, prognostic value of cTn in patients with acute ischemic stroke (AIS) still remains to be elucidated. The aim of this review is to explore the strength of association between elevated cTn and mortality after AIS onset. MethodsPubMed, EMBASE, and Cochrane Library were searched from inception to July 12, 2021 without language restriction. All studies reporting the association between cTn on admission and mortality in AIS patients have been included in this review. Meta-analysis was performed for overall and pre-specified subgroup risk ratios (RR) were obtained using a random effect model. Study quality was assessed for each included study. ResultsThere were 20 studies included in this meta-analysis with 9779 AIS patients met the inclusion criteria. There was significant association between elevated cTn and mortality in patients with AIS (RR 3.87; 95% CI 3.24-4.63). The association was consistent across the pre-specified subgroup analyses by type of troponin (cTnT or cTnI), assay of troponin (conventional or high-sensitivity), region (Asian or Non-Asian), definite exclusion of ACS/AMI patients or not (yes or not mentioned), adjusted AF, HF and impaired renal function or not (yes or no). ConclusionsAIS patients with elevated cTn at baseline has an increased risk of mortality. Early and routine evaluation of cTn may contribute to timely detection of comorbid cardiac injury and prevent unfavorable outcomes in patients with AIS. PROSPERO registration numberCRD42020160912

Is high sensitive-troponin I a reliable biomarker for cardiac injury in methadone toxicity? A prospective cross-sectional study

BackgroundMethadone is a synthetic opioid mostly used for detoxification therapy, as its use increases; the possibility for methadone-induced cardiotoxicity may rise. The aim of this study was to determine the association of high-sensitivity troponin I levels as a predictor of cardiac injury in methadone toxicity.MethodsSixty methadone toxicity patients included in this prospective cross-sectional study from October 2018–November 2020. High-sensitivity troponin I level and electrocardiogram were assessed in patients at admission. All patients underwent echocardiography at admission and 30 days later and compared this finding between two groups based on high-sensitivity troponin I results.ResultsMean age of the patients was 34.5 ± 11.1 years (males: 67%). Twenty (20%) patients had positive high sensitive-troponin results. Long QT interval and inverted T in precordial leads were mostly observed in individuals with positive high-sensitivity troponin I (75% vs. 35%, P = 0.013 and 83% vs. 16%, P < 0.001, respectively). Patients with elevated troponin had reduced left ventricular ejection fraction in comparison to normal group during admission (43.1 ± 15.4% vs. 55%, P < 0.001) and this left ventricular ejection fraction remained abnormal after 30 days (43.7 ± 21.6%). Patients in positive high-sensitivity troponin I group had higher regional wall motion abnormality frequency both at admission and 30 days later compared to the other group (0 day: 42% vs. 0, P < 0.001, 30th days: 25% vs. 4%, P = 0.020).ConclusionPatients with simultaneous methadone toxicity and positive high-sensitivity troponin I had worse cardiac outcomes and this biomarker could be probably used for better implementation of therapeutic interventions and prognosis.

Effect of positive airway pressure on cardiac troponins in patients with sleep-disordered breathing: A meta-analysis.

BackgroundCardiac troponins are highly sensitive and specific biomarkers for cardiac injury. Previous studies evaluating the effect of positive airway pressure (PAP) on cardiac troponins in patients with sleep‐disordered breathing (SDB) have yielded conflicting results. The meta‐analysis was performed to examine the effect of PAP on cardiac troponins in SDB patients.MethodsPubMed, Web of Science, and EMBASE before September 2021 on original English language studies were searched. The data on cardiac troponins in both baseline and post‐PAP treatment were extracted from all studies. The data on the change of cardiac troponins in both PAP and control group were extracted from randomized controlled trials. Standardized mean difference (SMD) was used to synthesize quantitative results.ResultsA total of 11 studies were included. PAP treatment was not associated with a significant change in cardiac troponin T between the baseline and post‐PAP treatment (SMD = −0.163, 95% confidence interval [CI] = −0.652 to 0.326, z = 0.65, p = .514). The pooled estimate of SMD of cardiac troponin I between the pre‐ and post‐PAP treatment was 0.287, and the 95% CI was −0.586 to 1.160 (z = 0.64, p = .519). The pooled SMD of change of cardiac troponin T between the PAP group and control group was −0.473 (95% CI = −1.198 to 0.252, z = 1.28, p = .201).ConclusionsThis meta‐analysis revealed that PAP treatment was not associated with any change of cardiac troponin in SDB patients.

Abstract 047: Effects Of The Dash Diet On Change In High-Sensitivity Cardiac Troponin I Over Time: Results From The Dash-Sodium Trial

Background: The DASH (Dietary Approaches to Stop Hypertension) diet has been shown to reduce high-sensitivity cardiac troponin I (hs-cTnI), a biomarker of subclinical cardiac injury. However, the time course of the DASH diet’s effects on this biomarker has not been determined. Hypothesis: The DASH diet lowers hs-cTnI within 4 weeks and the effects gradually increase over time. Methods: We analyzed data from the DASH-Sodium trial, a randomized controlled feeding study of healthy adults with systolic blood pressure 120 to 159 mm Hg and diastolic blood pressure 80 to 95 mm Hg. Participants were randomly assigned to the DASH diet or a typical American diet (control). Within each arm of the study, participants were assigned three sodium levels, in random order, changed every 4 weeks. Hs-cTnI was measured from serum collected at baseline and at 4, 8, and 12 weeks of feeding. Energy intake was adjusted to maintain body weight throughout the trial. Results: Of the 411 participants included in the final analysis, their mean age was 48 years, 56% were women, and 56% were Black. The mean baseline systolic/diastolic blood pressure was 135/86 mm Hg. Compared with baseline, the control diet did not have a significant effect on hs-cTnI at any of the measured time points. In contrast, the DASH diet reduced hs-cTnI by 0.18 ng/l (95% CI: -0.32, -0.04) at 4 weeks, 0.14 ng/l (95% CI: -0.29, 0.00) at 8 weeks, and 0.33 ng/l (95% CI: -0.48, -0.18) at 12 weeks ( Figure ; P -trend = 0.025). The %-difference in mean change from baseline of hs-cTnI for DASH vs. control was -13.30% (95% CI: -25.34, 0.69), -10.47% (95% CI: -23.08, 4.21), and -17.78% (95% CI: -29.51, -4.09) at 4, 8, and 12 weeks, respectively. Conclusions: The DASH diet reduced hs-cTnI within 4 weeks of feeding with greater diet effects occurring at 12 weeks of feeding. These results suggest that the DASH diet has both early and cumulative effects on subclinical cardiac injury.

Serum Myoglobin Is Associated With Postoperative Acute Kidney Injury in Stanford Type A Aortic Dissection.

BackgroundThe correlation between rhabdomyolysis and postoperative acute kidney injury has been reported in several surgical procedures. As a good predictor of rhabdomyolysis-related acute kidney injury, an elevated serum myoglobin level was often observed after total aortic arch replacement combined with frozen elephant trunk implantation. However, the correlation between serum myoglobin and acute kidney injury in such patients had not been established.MethodsTotally 398 stanford type A aortic dissection patients who underwent total aortic arch replacement combined with frozen elephant trunk implantation were enrolled in this retrospective study. The correlations between serum myoglobin and acute kidney injury as well as the 30-day mortality were assessed.ResultsOverall, 268(67.3%) patients had acute kidney injury (KDIGO stage 1 or higher) and 75(18.8%) had severe acute kidney injury (KDIGO stage 2&3). Patients who developed acute kidney injury had higher level of perioperative serum myoglobin than patients without acute kidney injury. After adjusting for known acute kidney injury risk factors, logarithmically transformed preoperative serum myoglobin [OR = 1.58 (95% CI, 1.26–1.95), P < 0.001] and postoperative day 1 serum myoglobin [OR = 3.47 (95%CI, 2.27–5.29), P < 0.001] were associated with severe acute kidney injury. These correlation persisted after adjustment for decline in filtration via change in serum creatinine (ΔCr) and biomarkers of cardiac and kidney injury, including N-terminal prohormone of brain natriuretic peptide, cardiac troponin I, creatine kinase-MB, serum creatinine and Cystatin C. Compared with the clinical model, sMb considerably improved the risk discrimination and reclassification for AKI.ConclusionFor stanford type A aortic dissection patients underwent total aortic arch replacement with frozen elephant trunk implantation, serum myoglobin can improve postoperative acute kidney injury risk classification. Rhabdomyolysis may be an important supplement to the existing knowledge on the mechanism of acute kidney injury.