Elevated Creatine Kinase-myocardial Band Research Articles

Elevated CK-MB levels are associated with adverse clinical outcomes in acute pancreatitis: a propensity score-matched study.

Cardiac injury, reflected by the measured concentrations of chemicals released from injured cardiac muscle, is common in acute pancreatitis (AP). However, there is no adequate evidence assessing the impact of cardiac injury on AP-related outcomes. Creatine kinase-myocardial band (CK-MB) mainly exists in the myocardium. Therefore, we sought to evaluate the relationship between the increase in CK-MB and the adverse clinical outcomes of AP. This propensity score-matched study analyzed AP patients admitted to the Department of Gastroenterology in the First Affiliated Hospital of Nanchang University from June 2017 to July 2022. Propensity score matching and multivariate logistic regression analysis were used to explore the relationship between CK-MB elevation and AP outcome variables. A total of 5,944 patients were screened for eligibility, of whom 4,802 were ultimately enrolled. Overall, 896 (18.66%) of AP patients had elevated (>24 U/ml) CK-MB levels, and 895 (99.89%) were paired with controls using propensity score matching. The propensity score-matched cohort analysis demonstrated that mortality (OR, 5.87; 95% CI, 3.89-8.84; P < 0.001), severe acute pancreatitis (SAP) (OR, 2.74; 95% CI, 2.23-3.35; P < 0.001), and infected necrotizing pancreatitis (INP) (OR, 3.40; 95% CI, 2.34-4.94; P < 0.001) were more frequent in the elevated CK-MB (>24 U/ml) group than in the normal CK-MB (≤ 24 U/ml) group. Using the multivariate logistic regression analysis, elevated CK-MB levels were independently associated with increased mortality (OR, 2.753, 95% CI, 2.095-3.617, P < 0.001), SAP incidence (OR, 2.223, CI, 1.870-2.643, P < 0.001), and INP incidence (OR, 1.913, 95% CI, 1.467-2.494, P < 0.001). CK-MB elevation was an independent risk factor for adverse clinical outcomes in AP patients. CK-MB elevation was significantly related to adverse outcomes in AP patients, which makes it a potentially useful laboratory parameter for predicting adverse clinical outcomes of AP.

C84 OUTCOME AND MORPHO–FUNCTIONAL CHANGES ON CARDIAC MAGNETIC RESONANCE IN PATIENT WITH ACUTE MYOCARDITIS FOLLOWING MRNA COVID 19 VACCINATION

Abstract Background MessengerRNA (mRNA) COVID–19 vaccination has been associated with a higher–than–expected occurrence of acute myocarditis. Scarce information is available on mid–term prognosis and changes in cardiac function, volumes, and tissue characterization on cardiac magnetic resonance (CMR). Methods Retrospective, multicenter study including patients with a definite diagnosis of acute myocarditis within 30 days from mRNA COVID–19 vaccination. The diagnosis is based on endomyocardial biopsy (EMB) or autopsy or by the coexistence of positive biomarkers (troponin &amp;gt;99th upper reference limit or elevated creatine kinase myocardial band [CK–MB]) and cardiac MRI findings consistent with AM according to the 2018 updated Lake Louise Criteria. Results 77 patients (median age 25 years [IQR 20–35], 15% female) were included and followed–up for 147 days [IQR 74–215]. Follow–up CMR was available in n=49 patients and showed no changes in biventricular ejection fraction (EF) as compared to CMR at diagnosis (left ventricular EF: 59%[55–65]vs. 60%[57–64], p=0.507, right ventricular EF: 56%[52–62]vs. 57%[52–61], p=0.563, respectively). Late gadolinium enhancement was present in all patients at diagnosis and persisted in only n=39 (79.6%) at follow–up (p=0.001), generally sparing the anterior wall and the septum. N=10 (20.4%) had a persistent edema based on T2–weighted short tau inversion recovery (STIR) sequences, with predominant involvement of inferior or inferior–lateral walls. The proportion of patients with increased T1 and T2 mapping signals significantly decreased at follow–up (n=13 (68%) vs. n=4 (13%),p&amp;lt;0.001, and n=21 (84%) vs. n=3 (10%),p&amp;lt;0.001, respectively), as well as the presence of pericardial effusion (n=16 (33%) vs. n=3 (6%),p=0.004). No differences in morpho–functional CMR parameters based on the type of vaccine administered were found (BNT162b2 Pfizer/BioNTech®, n=36, 73.5%, m–RNA–1273 Moderna®, n=13, 26.5%). Among patients with available follow–up (N=75, 97.4%), no major adverse cardiovascular events nor myocarditis recurrence or death were reported. Conclusions At mid–term follow–up, patients who experienced an acute myocarditis after a mRNA COVID–19 vaccine had preserved biventricular EF. The rate and localization of residual scar or edema on CMR is in line with classic viral myocarditis with a good prognosis. This new piece of information should further reassure patients who experience acute myocarditis after mRNA COVID–19 vaccination.

138 OUTCOME AND MORPHO-FUNCTIONAL CHANGES ON CARDIAC MAGNETIC RESONANCE IN PATIENT WITH ACUTE MYOCARDITIS FOLLOWING MRNA COVID 19 VACCINATION

Abstract Background MessengerRNA (mRNA) COVID-19 vaccination has been associated with a higher-than-expected occurrence of acute myocarditis. Scarce information is available on mid-term prognosis and changes in cardiac function, volumes, and tissue characterization on cardiac magnetic resonance (CMR). Methods Retrospective, multicenter study including patients with a definite diagnosis of acute myocarditis within 30 days from mRNA COVID-19 vaccination, with a confirmed myocarditis diagnosis based on endomyocardial biopsy (EMB) or autopsy or by the coexistence of positive biomarkers (troponin &amp;gt;99th upper reference limit or elevated creatine kinase myocardial band [CK-MB]) and cardiac MRI findings consistent with AM according to the 2018 updated Lake Louise Criteria. Results 77 patients (median age 25 years [IQR 20-35], 15% female) were included and followed-up for 147 days [IQR 74-215]. Follow-up CMR was available in n=49 patients and showed no changes in biventricular ejection fraction (EF) as compared to CMR at diagnosis (left ventricular EF: 59%[55-65]vs. 60%[57-64], p=0.507, right ventricular EF: 56%[52-62]vs. 57%[52-61], p=0.563, respectively). Late gadolinium enhancement was present in all patients at diagnosis and persisted in only n=39 (79.6%) at follow-up (p=0.001), generally sparing the anterior wall and the septum. N=10 (20.4%) had a persistent edema based on T2-weighted short tau inversion recovery (STIR) sequences, with predominant involvement of inferior or inferior-lateral walls. The proportion of patients with increased T1 and T2 mapping signals significantly decreased at follow-up (n=13 (68%) vs. n=4 (13%),p&amp;lt;0.001, and n=21 (84%) vs. n=3 (10%),p&amp;lt;0.001, respectively), as well as the presence of pericardial effusion (n=16 (33%) vs. n=3 (6%),p=0.004). No differences in morpho-functional CMR parameters based on the type of vaccine administered were found (BNT162b2 Pfizer/BioNTech®, n=36, 73.5%, m-RNA-1273 Moderna®, n=13, 26.5%). Among patients with available follow-up (N=75, 97.4%), no major adverse cardiovascular events nor myocarditis recurrence or death were reported. Conclusions At mid-term follow-up, patients who experienced an acute myocarditis after a mRNA COVID-19 vaccine had preserved biventricular EF. The rate and localization of residual scar or edema on CMR is in line with classic viral myocarditis with a good prognosis. This new piece of information should further reassure patients who experience acute myocarditis after mRNA COVID-19 vaccination.

Activation of autophagy inhibits nucleotide-binding oligomerization domain-like receptor protein3 inflammasome activation and attenuates myocardial ischemia-reperfusion injury in diabetic rats.

Aims/IntroductionDiabetic hearts are more vulnerable to ischemia‐reperfusion injury (I/RI). The activation of nucleotide‐binding oligomerization domain‐like receptor protein 3 (NLRP3) inflammasome can mediate the inflammatory process, and hence might contribute to myocardial I/RI. Activation of autophagy can eliminate excess reactive oxygen species and alleviate myocardial I/RI in diabetes. The present study aimed to investigate whether the activation of autophagy can alleviate diabetic myocardial I/RI through inhibition of NLRP3 inflammasome activation.Materials and MethodsA dose of 65 mg/kg streptozotocin was given by tail vein injection to establish a type 1 diabetes model in the rats. The left anterior descending coronary artery was ligated for 30 min followed by reperfusion for 2 h to establish a myocardial I/RI model. H9C2 cardiomyocytes were exposed to high glucose (33 mmol/L) and subjected to hypoxia–reoxygenation (6 h hypoxia followed by 4 h reoxygenation).ResultsThe diabetic rats showed significant inhibition of cardiac autophagy (decreased LC3‐II/I and increased p62) that was concomitant with increased activation of NLRP3 inflammasome (increased NLRP3, apoptosis‐related spots protein cleaved caspase‐1, interleukin‐18, interleukin‐1β) and more severe myocardial I/RI (elevated creatine kinase myocardial band, lactate dehydrogenase and larger infarct size). However, administration of rapamycin, an inhibitor of the autophagy, to activate autophagy resulted in the inhibition of NLRP3 inflammasome, and finally alleviated myocardial I/RI. In vitro, high glucose inhibited autophagy, while activating NLRP3 inflammasome in H9C2 cardiomyocytes and aggravating hypoxia–reoxygenation injury, but rapamycin reversed these adverse effects of high glucose.ConclusionActivation of autophagy can suppress the formation of NLRP3 inflammasome, which in turn attenuates myocardial ischemia‐reperfusion injury in diabetic rats.

1215P - Sequential blockade of PD-1 and PD-L1 causes fulminant cardiotoxicity: From case report to mice model validation

Background: In clinical practice, the sequential use of shifting from a programmed cell death 1 (PD-1) inhibitor to its ligand 1 (PD-L1) inhibitors in consideration of ineffectiveness or toxicity is becoming more common due to prolonged survival. We report a patient in whom fatal myocarditis developed after sequential use of PD-1 and PD-L1 inhibitors. To validate this finding, a syngeneic tumor-bearing mice model was used. Methods: A 61-year-old woman with metastatic lung adenocarcinoma, who had received 5 doses of nivolumab (3 mg/kg) and then 1 dose of atezolimumab (1200 mg), complained of chest tightness and dyspnea 4 weeks later. The workup revealed sinus tachycardia, a normal Troponin I level (< 0.01 ng/mL), an elevated creatine kinase-myocardial band (CK-MB) level (10 ng/mL), and an elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) level (2960 ng/mL). Serial echocardiograms revealed left ventricular ejection fractions declining from 66.3 to 59.2 %. Under a diagnosis of myocarditis, she was treated with intravenous methylprednisolone at 5 mg/kg/day and oral mycophenolate mofetil at 1000 mg/day. The progressive clinical deterioration was noted with serial elevation of Troponin I, CK-MB and NT-proBNP levels up to 1.3, 24 and 15738 ng/mL, respectively. Cardiac arrest was noted later. The Balb/c mice bearing lung metastasis of CT26 colon cancer cells were treated with PD-1 and PD-L1 inhibitors for pathological and immuohistochemical studies. Results: The pathology shows that the combination of anti-PD-1 and anti-PD-L1, either sequentially or simultaneously administered, caused myocarditis lesions with myocyte injury and patchy mononuclear infiltrates in the myocardium in all combination group mice (n = 3 for each). The myocarditis lesions were not seen in mice treated with anti-PD-1 or anti-PD-L1 alone. Marked expression of PD-L1 in infiltrating lymphocytes and expression of PD-1 in myocytes was noted only in mice with combination blockade, implying a possible role for pathogenesis of myocarditis. Conclusions: The combinatory use of PD-1 and PD-L1 blockade, either sequentially or concurrently, may cause fulminant cardiotoxicity, and such usage should be cautious. Legal entity responsible for the study: Mackay Memorial Hospital, Taipei, Taiwan. Funding: Mackay Memorial Hospital, Taipei, Taiwan. Disclosure: All authors have declared no conflicts of interest.

Kudiezi injection mitigates myocardial injury induced by acute cerebral ischemia in rats

BackgroundKudiezi (KDZ) injection is commonly used in traditional Chinese medicine as treatment for cerebral infarction and angina pectoris. The present study investigated the therapeutic effects of KDZ injection on myocardial injury induced by acute cerebral ischemia and the possibly protective mechanisms.MethodsRats were divided into three groups: sham, 6h-ischemia, and KDZ treatment (KDZ). The neurological deficits were determined by the Garcia score. The cerebral infarct volume was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and brain water content was also evaluated. Serum creatinine kinase (CK), lactate dehydrogenase (LDH), and creatine kinase-myocardial band (CK-MB) activity, myocardial tissue malondialdehyde (MDA) levels, L-Glutathione (GSH) levels, and superoxide dismutase (SOD) activity as well as mitochondrial cytochrome c oxidase (COX) activity were determined. Mitochondrial COX I and COX III mRNA expressions of myocardial tissues were measured by RT-PCR.ResultsImpaired neurological function and brain edema were observed in the 6h-ischemia group. TTC staining showed that the 6h-ischemia group had larger infarct zones than the sham group. Myocardial ischemic changes (widened myocardial cell gap, cracks, and obvious edema) were detected in the 6h-ischemia group compared with the sham group, with elevated serum CK-MB activity and CK and LDH levels. Electrocardiography showed lower medium frequency (MF) and high frequency (HF) in the 6h-ischemia group compared with the sham group. In myocardial tissue, COX activity was elevated in the 6h-ischemia compared with the sham group, while SOD, GSH, and MDA levels, and COX I and COX III mRNA expressions remained unchanged. KDZ injection decreased neurological impairment, brain edema, gaps between cells, and infarct size. Compared with the 6h-ischemia group, it reduced serum CK-MB activity and CK and LDH levels, and MDA levels in myocardial tissue. KDZ significantly increased GSH levels, SOD activity, and mitochondria COX activity and the expression of COX I and COX III mRNA in myocardial tissue compared with the sham group.ConclusionKDZ injection had a protective effect against cerebral ischemia in rats. KDZ injection could also alleviate myocardial injury after acute cerebral ischemia in rats. The possible mechanisms involve the regulation of the oxidative stress/antioxidant capacity after cerebral ischemia.

Blunt Traumatic Cardiac Rupture: Single-Institution Experiences over 14 Years

BackgroundBlunt traumatic cardiac rupture is rare. However, such cardiac ruptures carry a high mortality rate. This study reviews our experience treating blunt traumatic cardiac rupture.MethodsThis retrospective study included 21 patients who experienced blunt traumatic cardiac rupture from 1999 to 2015. Every patient underwent surgery. Several variables were compared between survivors and fatalities.ResultsSixteen of the 21 patients survived, and 5 (24%) died. No instances of intraoperative mortality occurred. The most common cause of injury was a traffic accident (81%). The right atrium was the most common location of injury (43%). Ten of the 21 patients were suspected to have cardiac tamponade. Significant differences were found in preoperative creatine kinase–myocardial band (CK-MB) levels (p=0.042) and platelet counts (p= 0.004) between the survivors and fatalities. The patients who died had higher preoperative Glasgow Coma Scale scores (p=0.007), worse Trauma and Injury Severity Scores (p=0.007), and higher Injury Severity Scores (p=0.004) than those who survived.ConclusionWe found that elevated CK-MB levels, a low platelet count, and multi-organ traumatic injury were prognostic factors predicting poor outcomes of blunt cardiac rupture. If a patient with blunt traumatic cardiac rupture has these factors, clinicians should be especially attentive and respond promptly in order to save the patient’s life.

Elevation of Cardiac Troponin T, But Not Cardiac Troponin I, in Patients With Neuromuscular Diseases: Implications for the Diagnosis of Myocardial Infarction

This study sought to determine the clinical and biological significance of elevated cardiac troponin T (cTnT) in patients with neuromuscular diseases. Practice guidelines regard cTnT and cardiac troponin I (cTnI) as equally sensitive and specific for the diagnosis of myocardial injury. Although cTnI is unique to myocardium, cTnT can be re-expressed in skeletal muscle in response to injury. The commercial cTnT assay is claimed to be cardiac specific. Fifty-two patients with 20 different types of acquired and inherited neuromuscular diseases underwent full clinical assessment, cardiac investigations, and measurements of serum cTnT, cTnI, creatine kinase (CK), creatine kinase myocardial band (CK-MB), and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Serial measurements (265 samples) in 25 initially hospitalized patients taken during a mean of 2.4 years showed persistent elevation of cTnT (median: 0.08 μg/l; interquartile range: 0.06 to 0.14 μg/l), CK (582 U/l; 303 to 3,662 U/l), and CK-MB (24 μg/l; 8 to 34 μg/l). In contrast, cTnI, measured using 2 sensitive assays, was persistently normal throughout the study in 22 patients. Electrocardiograms (ECGs) and echocardiograms were normal in 16 and 17 patients, respectively, and no serial changes were observed. Therapeutic interventions in patients with reversible myopathies normalized cTnT, CK, and CK-MB in unison. Single measurements in 27 ambulatory patients showed elevated CK (953 U/l; 562 to 1,320 U/l), CK-MB (18 μg/l; 11 to 28 μg/l), and cTnT (0.03 μg/l; 0.02 to 0.05 μg/l) in 21, 22, and 18 patients respectively. cTnI was abnormal in only 1 patient. NT-proBNP (41 pg/ml; 35 to 97 pg/ml) was normal in all but 2 patients. ECGs were normal in 15 patients. No patients with elevated cTnT, but with normal cTnI, had any cardiovascular events in either group during follow-up. Patients with a wide spectrum of neuromuscular diseases commonly have persistent elevation of cTnT and CK-MB in the absence of clinical and cTnI evidence of myocardial injury. Re-expressed cTnT in diseased skeletal muscle appears to be the source of the elevated cTnT detected in the circulation of these patients.

Attenuated plaque is associated with plaque prolapse accompanied by cardiac enzyme elevation after drug-eluting stent implantation

This study aimed to evaluate the relationship between grayscale intravascular ultrasound-attenuated plaque (AP) and poststenting plaque prolapse (PP) as well as their influence on creatine kinase-myocardial band (CK-MB) elevation after drug-eluting stent (DES) implantation. The relationship between baseline AP and poststenting PP and their impacts on percutaneous coronary intervention (PCI) are not well known. A total of 141 single, native, de-novo coronary lesions in 141 patients with normal pre-PCI CK-MB levels who underwent intravascular ultrasound before and after DES implantation were studied. AP was found in 72 (51.1%) lesions and PP occurred in 43 (30.5%) lesions. Baseline AP was associated with greater plaque area, lesion eccentricity, and positive remodeling, and was associated with higher frequency of poststenting PP (47.2 vs. 13.0%, P<0.001) as well as greater poststenting PP volume (2.2±1.3 vs. 1.9±1.1 mm, P=0.045). Elevated CK-MB levels were observed in 34 (24.1%) lesions and significantly more frequently in patients with baseline AP and poststenting PP than without both of these findings. Multivariate analysis indicated that AP with PP was the predictor of post-PCI CK-MB elevation. Baseline AP was associated with high-risk characteristics, higher frequency, and greater volume of poststenting PP accompanied by CK-MB elevation in patients with DES implantation.

Assessment of Echo-Attenuated Plaque by Optical Coherence Tomography and its Impact on Post-Procedural Creatine Kinase-Myocardial Band Elevation in Elective Stent Implantation

This study examined morphological characteristics of echo-attenuated plaques by optical coherence tomography (OCT) and evaluated their influence on creatine kinase-myocardial band (CK-MB) elevation after percutaneous coronary intervention (PCI) in patients with elective stent implantation. Recent intravascular ultrasound studies have described atherosclerotic plaques with echo attenuation (EA) without associated bright echoes that are correlated with no-reflow phenomenon after PCI. We studied 135 native de novo culprit coronary lesions in 135 patients with normal pre-PCI CK-MB levels (28 with unstable angina; 107 with stable angina) who underwent intravascular ultrasound and OCT examinations before elective stent implantation. The lesions were divided into 2 groups based on the presence or absence of EA, and OCT findings were compared. We then determined predictors of post-PCI CK-MB elevation. EA was found in 47 (34.8%) lesions and was associated with the presence of OCT-derived thin-capped fibroatheroma, ruptured plaques, greater lipid content, intravascular ultrasound-derived large reference and plaque area, lesion eccentricity, and microcalcification. Elevated CK-MB levels were observed in 36 (26.7%) lesions, and significantly more frequently in lesions with EA than without. In multivariable analysis, EA (odds ratio [OR]: 3.49; 95% confidence interval [CI]: 1.53 to 7.93; p = 0.003) and OCT-derived ruptured plaque (OR: 2.92; 95% CI: 1.21 to 7.06; p = 0.017) were independent predictors of post-PCI CK-MB elevation. Atherosclerotic plaques with EA were associated with characteristics considered to be high risk or unstable. OCT examination showed an additive predictive value to the presence of EA for post-PCI CK-MB elevation.

Elevated Biochemical Markers of Myocardial Injury are not Associated with Postoperative Cognitive Dysfunction after Coronary Artery Surgery

Background: The systemic inflammatory response to cardiopulmonary bypass (CPB) and organ hypoperfusion during CPB contribute to cerebral and myocardial dysfunction in patients undergoing cardiac surgery. We hypothesized that biochemical markers of myocardial injury [creatine kinase - myocardial band (CK-MB), troponin-I] may be independently associated with postoperative cognitive dysfunction (POCD; an indicator of cerebral dysfunction) in patients undergoing coronary artery bypass graft (CABG) surgery using CPB. Methods: Eighty-eight age- and education-balanced patients=55 years of age undergoing elective CABG with CPB and 28 nonsurgical controls with coronary artery disease were enrolled. Recent verbal and nonverbal memory and executive functions were assessed before surgery, 1 week, and 3 months after surgery using a standard psychometric test battery. Plasma CK-MB and troponin-I concentrations were determined before and at the end of surgery. Plasma troponin-I concentrations were also measured 24 hours after surgery. Results: Performance on two cognitive tests decreased at least two standard deviations (SD) from baseline and performance on five additional tests decreased 1 SD 1 week after surgery. After 3 months, performance on six tests was at least a 1 SD below baseline. CK-MB and troponin-I concentrations were significantly (p<0.00001) elevated after surgery. There was no correlation between overall cognitive function (measured by average z-score) and postoperative CK-MB or troponin-I concentrations 1 week or 3 months after surgery. Conclusion: The results suggest that elevated postoperative CK-MB or troponin-I concentration alone is not associated with the subsequent development of short- and medium-term impairment of cognitive functions after CABG.

The prevalence and prognosis of minimally elevated creatine kinase-myocardial band activity in elderly patients with syncope

The prevalence and prognosis of minimally elevated creatine kinase-myocardial band activity in elderly patients with syncope