Significant Creatine Kinase Elevation Research Articles

Twenty-Four Percent of Wildland Firefighters Reach Critical Levels of Serum Creatine Kinase During 80-Hour Critical Training.

Wildland firefighters (WLFFs) must undergo a 2-wk critical training (CT) period prior to deployment to the field. This stress may result in clinical risks, including severe muscle damage and rhabdomyolysis. We aimed to document the effects of WLFFs' CT on physiologic markers of muscle damage and soreness. Two interagency hotshot crews (n=25) were followed during spring 2022 for 80 h of training. Activity counts as well as records of upper-body (US) and lower-body (LS) muscle soreness were collected daily. Body weight (BW) and skinfold measurements were recorded on Day 1 (D1) and D11 to estimate body fat (BF) and lean body weight (LBW). Blood was collected on D1 and D11 to measure muscle and liver damage markers. Critical training resulted in significant elevations in creatine kinase (CK) (216.9±57.4 U/L vs 5166.4±1927.8 U/L, P=0.017) and lactate dehydrogenase (LDH) (175.5±4.0 IU/L vs 340.0±42.6 IU/L, P=0.001) despite no significant changes in BW, BF, LBW, cortisol, or testosterone. Main effects of time were seen in US and LS, peaking on D11 (US: 5.2±0.4 cm, P<0.001; LS: 5.5±0.4 cm, P<0.001). Those who spent the most minutes with activity counts of >1500 counts/min showed the greatest increase in CK and LDH. These data suggest that WLFFs undergo significant physiologic stressors, resulting in muscle soreness and damage during CT, with 6 of the 25 subjects reaching critical levels of serum CK. It appears that much of the muscle damage and soreness occurred because of unaccustomed WLFF job-specific tasks.

Prognostic and predictive impact of creatine kinase level in non-small cell lung cancer treated with tyrosine kinase inhibitors.

BackgroundThe use of tyrosine kinase inhibitors (TKIs) is associated with incident creatine kinase (CK) elevation in the treatment of advanced non-small cell lung cancer (NSCLC) patients. However, whether higher CK levels are associated with better antitumor responses or survival remains to be explored. We intend to investigate the clinical correlation between CK levels and TKI efficacy in advanced NSCLC.MethodsIn this retrospective study, we enrolled 135 patients with stage IV NSCLC receiving TKI-based therapy in our center between June 2012 to July 2020. CK levels were monitored from the initiation of TKI medication and during the administration period. An X-tile analysis provided the optimal cutoff point for higher baseline CK. Patients were identified and grouped according to their baseline CK level and fold changes during TKI therapy. The primary endpoints included progression-free survival (PFS) and overall survival (OS), and the objective response rate (ORR) was calculated as the secondary endpoint.ResultsAmong the 135 patients included in our study, those with higher baseline CK levels (≥70 U/L) had favorable PFS (15.2 vs. 8.8 months; P=0.028), while patients with significantly elevated CK (the highest CK value/baseline CK value ≥2 times) appeared to gain better PFS (14.6 vs. 10.0 months; P=0.139). The overall ORR was 67.4%. Patients with higher baseline CK levels had numerically higher ORR (74.6% vs. 60.3%; P=0.076). Similarly, patients with significant CK elevation had a superior 4-month PFS rate (77.6% vs. 59.7%; P=0.029). Results from the subgroup analyses were identical to the overall ones. For patients with higher baseline CK levels, those experiencing significant CK elevation had prolonged PFS (17.2 vs. 14.2 months; P=0.038); a same trend was obtained from the lower baseline CK group (<70 U/L) (9.4 vs. 7.9 months; P=0.038). In multivariable analysis, higher baseline CK level and significant CK elevation remained statistically associated with PFS, with hazard ratios of 0.48 and 0.59, respectively.ConclusionsBoth higher baseline CK levels and significant CK elevation after treatment were correlated with prolonged PFS in NSCLC treated with TKIs, suggesting the potential prognostic and predictive impact of CK level on these patients.

An unusual case of recurrent episodes of muscle weakness: Co-occurrence of Andersen-Tawil syndrome and glycogen storage disease type IXd

A 25-year-old male patient presented with periodic paralysis that increased in severity and frequency with age, accompanied with muscle pain and significantly elevated creatine kinase (CK) levels. Initial clinical and genetic examination confirmed Andersen-Tawil syndrome. Although his father carried the same genetic mutation (p.G300A), he experienced minor and infrequent attacks of paralysis. A change in the patient's symptoms, such as accompanying pain, contracture, and significant CK elevation, lead to a reconsideration of the diagnosis. A muscle biopsy of the biceps brachii in the patient revealed glycogen storage, but no tubular aggregates. Analysis of the phosphorylase kinase regulatory subunit alpha 1 (PHKA1) gene revealed a pathogenic mutation (p.C1082X), indicating glycogen storage disease type Ⅸd. The case demonstrates that co-occurrence of glycogen storage disease type Ⅸd may prolong attacks of muscle weakness, and cause serious muscle pain in patients with Andersen-Tawil syndrome.

High intensity resistance training causes muscle damage and increases biomarkers of acute kidney injury in healthy individuals.

PurposeHigh-intensity interval resistance training (HIIRT) is an increasingly popular exercise program that provides positive results with short sessions. This study aimed to evaluate whether an HIIRT session causes muscle and kidney damage.MethodsFifty-eight healthy volunteers (median age 24 years, 50% women) participated in this study and performed a HIIRT session. The Borg CR10 scale for pain (CR10P) and blood and urine samples were collected before (baseline) and 2 and 24 hours after the HIIRT session. Blood samples were analyzed for serum creatinine (SCr), creatine kinase (CK) and myoglobin. Urine samples were assessed for creatinine, neutrophil gelatinase-associated lipocalin, interleukin 18, calbindin, microalbuminuria, trefoil factor-3 and β-2 microglobulin.ResultsCR10P had a significant increase at 2 and 24 hours post-workout, and CK increased significantly at 2 hours and increased further at 24 hours. Myoglobin increased significantly at 2 hours and remained elevated at 24 hours. SCr increased modestly but significantly at 24 hours only in men. Three men met the KDIGO diagnostic criteria for acute kidney injury. The urinary kidney injury biomarkers increased significantly at 2 hours and returned to the baseline values 24 hours after HIIRT.ConclusionsA single HIIRT session caused early and significant elevations in CK, myoglobin, SCr, microalbuminuria and urinary biomarkers indicative of kidney tubular injury, suggesting the occurrence of muscle and kidney damage.

Genetic and Clinical Factors Are Associated With Statin-Related Myotoxicity of Moderate Severity: A Case-Control Study.

We evaluated the contribution of patient-specific clinical and genetic factors to statin-related muscle toxicity (SRM) without a significant creatine kinase elevation (125 cases related to simvastatin or atorvastatin and 481 controls). The association between 12 single nucleotide polymorphisms (SNPs) in nine candidate genes and clinical factors with SRM was evaluated. Of the 12 SNPs genotyped, only rs4149056 in SLCO1B1 was associated with SRM in univariate analysis (with any statin, odd ratio (OR) = 1.73, 95% confidence interval (CI) = 1.14-2.62, P = 0.010) and this association was influenced by sex (P = 0.006) and BMI (P = 0.02). In multivariate and binary logistic regression analyses, SLCO1B1 rs4149056 genotype (OR = 1.66, 95% CI: 1.08-2.54, P = 0.014) and sex (OR = 1.72, 95% CI = 1.15-2.59, P = 0.006) were independently associated with muscle toxicity related to statin treatment. Patient-specific genetic and clinical factors associated with increased systemic exposure to statins are implicated in the full spectrum of SRM, including myalgia in addition to severe myopathy.

Curcumin: An effective adjunct in patients with statin-associated muscle symptoms?

In spite of the unequivocal efficacy of statins in reducing primary and secondary cardiovascular events, the use of these drugs in a considerable number of patients is limited because of statin intolerance, mainly statin‐associated muscle symptoms (SAMS). SAMS encompass a broad spectrum of clinical presentations, including mild muscular aching and other types of myalgias, myopathy with the significant elevation of creatine kinase, and the rare but life‐threatening rhabdomyolysis. Among several pathophysiologic mechanisms of SAMS, mitochondrial dysfunction is thought to be one of the main one. Curcumin is the polyphenolic ingredient of Curcuma longa L., which has various pharmacological properties against a vast range of diseases. Curcumin has several mechanisms of actions relevant to the treatment of SAMS. These effects include the capacity to prevent and reduce delayed onset muscle soreness by blocking the nuclear factor inflammatory pathway, attenuation of muscular atrophy, enhancement of muscle fibre regeneration following injury, and analgesic and antioxidant effects. Curcumin can also increase the levels of cyclic adenosine monophosphate, which leads to an increase in the number of mitochondrial DNA duplicates in skeletal muscle cells. Finally, owing to its essential lipid‐modifying properties, curcumin might serve as an adjunct to statin therapy in patients with SAMS, allowing for effective lowering of low‐density lipoprotein cholesterol and possibly for statin dose reduction. Owing to the paucity of effective treatments, and the safety of curcumin in clinical practice, proof‐of‐concept trials are recommended to assess the potential benefit of this phytochemical in the treatment of SAMS.

Discordant cardiac biomarker levels independently predict outcome in ST-segment elevation myocardial infarction.

To investigate the prognostic relevance of elevated Troponin T (cTnT) levels in patients with ST-segment elevation myocardial infarction (STEMI) without significant creatine kinase (CK) elevation on admission. From January 1, 2002 to December 31, 2006 patients with STEMI without significant CK elevation (<2-fold) on admission treated with percutaneous coronary intervention (PCI) were included and stratified according to cTnT plasma levels. Univariate and multivariate regression analyses were used to find independent predictors for mortality. During the 5-year period 514 patients with STEMI and normal CK plasma levels were included. 308 (59.9%) patients had cTnT levels <0.1μg/l and 206 (40.1%) patients had cTnT levels ≥0.1μg/l. Multivariate logistic regression analysis identified cTnT levels ≥0.1μg/l and 3-vessel disease as positive, and hemoglobin levels as negative independent predictors for long-term mortality. Discordantly elevated cTnT plasma levels independently predicted higher mortality rates in the first year (HR 3.9, 95% CI 1.7-9.1, p=0.002) and during 5years (HR 2.3, 95% CI 1.4-3.9, p=0.002) after PCI for STEMI. Discordant elevation of cTnT in the presence of normal CK plasma levels on admission is associated with increased mortality in STEMI patients undergoing primary PCI. This may be due to preceding microembolization.

Therapeutic Potential and Critical Analysis of the PCSK9 Monoclonal Antibodies Evolocumab and Alirocumab

To review the mechanism of action for PCSK9 monoclonal antibodies and critically evaluate the therapeutic potential of evolocumab and alirocumab in the treatment of hypercholesterolemia. Ovid MEDLINE search from 1980 to August 2015 using the terms PCSK9, evolocumab, and alirocumab with forward and backward citation tracking. English-language trials and studies assessing the mechanism, efficacy, or safety of PCSK9 monoclonal antibodies were included. PCSK9 monoclonal antibodies have a potent ability to reduce low-density lipoprotein (LDL) by almost 50% in controlled trials: -47.49% (95% CI = -69.6% to -25.4%). They have an acceptable safety profile with no significant elevations in Creatine Kinase (CK) (odds ratio [OR] = 0.72; 95% CI = 0.54 to 0.96) or serious adverse events (OR = 1.01; 95% CI = 0.87 to 1.18), and preliminary evidence suggests reductions in myocardial infarction (OR = 0.49; 95% CI = 0.26 to 0.93). Although it is effective in several familial hypercholesterolemia (FH) patient types, it does not work in homozygous patients with dual allele LDL receptor negative polymorphisms or those who are homozygous for autosomal recessive hypercholesterolemia. Although not preferred over statins because of limited clinical trial evidence of cardiovascular event reductions, dosing convenience, and expense, PCSK9 monoclonal antibodies will have a prominent role to play in the treatment of hypercholesterolemia, especially in patients needing large LDL reductions, including patients with many types of FH.

Skeletal Muscle Toxicity in HIV-1-Infected Patients Treated with a Raltegravir-Containing Antiretroviral Therapy: A Cohort Study

To evaluate the frequency of myopathy and serum creatine kinase (CK) elevation associated with the use of the integrase inhibitor raltegravir we conducted a retrospective, cohort analysis assessing the incidence of skeletal muscle toxicity among HIV-infected patients treated with raltegravir. Adult HIV-infected patients who started a raltegravir-containing therapy were enrolled into the study. The skeletal muscle toxicity was defined by the presence of one or more of the following parameters: (1) isolated and significant CK elevation without signs or symptoms; (2) diffuse myalgia without weakness; (3) proximal muscle weakness; (4) rhabdomyolysis. On the whole, 155 patients were included in the study, with a mean age of 49.2 years; the median duration of the raltegravir treatment was 30.7 months. The overall frequency of skeletal muscle toxicity was 23.9%, with an incidence of 4.7/100 person-years. An isolated CK elevation was reported in 21.3% of cases, while less than 3% of patients complained of myalgia or muscle weakness. The CK elevation was usually of grade 1 or 2 and self-limiting, and laboratory or clinical abnormalities did not require discontinuation of raltegravir in any patient. Factors significantly associated with skeletal muscle toxicity were previous use of zidovudine, higher baseline CK levels, previous increase of the CK levels, and a higher body mass index. Skeletal muscle toxicity is not an unusual adverse event in subjects receiving raltegravir, but it is usually represented by a mild-to-moderate increase in CK concentration, while clinical symptoms of myopathy are very uncommon.

Antipsychotic-induced elevation of creatine kinase: a systematic review of the literature and recommendations for the clinical practice.

The primary antipsychotic-induced creatine kinase elevation (i.e., not due to neuroleptic malignant syndrome, extrapyramidal symptoms, etc.) is a poorly studied condition. The aims of the present study were to provide an overview of published cases with antipsychotic-induced creatine kinase elevation and give recommendations for the clinical practice. PubMed and EMBASE were searched for eligible trials, case series, and case reports. We set a threshold at ten times the upper normal limit of the creatine kinase value in order to define an elevation as significant. The prevalence of significant creatine kinase elevation ranged between 2 and 7%. We found a total of 42 eligible cases. Men were overrepresented in our sample (81%). Patients with myoglobinuria were more likely to be symptomatic (Fisher's exact test, p = 0.006), whereas neither myoglobinuria (Mann-Whitney test, p > 0.10) nor symptoms (Mann-Whitney test, p = 0.64) were related to the magnitude of the creatine kinase (CK) elevation. In the majority of the cases, the antipsychotic medication was discontinued (86%). Forced diuresis was given in 36% of the patients. Eighty-three percent of the patients had no further complications. Only one case was found with a de novo acute renal failure. The discontinuation of the antipsychotic medication was a sufficient measure for the CK elevation to subside in the majority of the cases. Cases with myoglobinuria should eventually be treated more aggressively. Further recommendations for the clinical practice are presented.

Músculo e pele em equação, relato de caso

Introduction: Dermatomyositis is an inflammatory myopathy with characteristic cutaneous manifestations and a prevalence of 1-10 per million adults. Timely recognition has prognostic implications. The general practitioner has an important role to play in both diagnosis and follow-up of the patient. Case report: A 50 year-old woman with a previous history of subclinical hypothyroidism came to her Family Physician complaining of muscle weakness and redness of the face and neck. Dermatomyostitis was suspected and laboratory tests showed significant elevation of creatine kinase and transaminases. She was referred to Internal Medicine for consultation. Additional tests confirmed the initial suspicion. She began treatment with corticosteroids with gradual improvement in her condition. She returned to her Family Physician to obtain a renewal of the certificate of incapacity for work. This was opportunity to explore ways to help the patient cope with the disease. Comment: This is a rare disease with a prevalence of 1-10 cases per million. Early recognition and treatment of dermatomyositis are important in decreasing morbidity from systemic complications. The association of dermatomyositis with other connective tissue diseases and neoplasms gives greater importance to this diagnosis. For the Family Physician, care is not limited only to the physical manifestations. Dealing with all aspects of the disease and helping patients adapt to it are equally important.

Creatine kinase elevation in HIV-1-infected patients receiving raltegravir-containing antiretroviral therapy: a cohort study

To evaluate the incidence and risk factors for significant creatine kinase elevation in HIV-1-infected patients who were prescribed a raltegravir-containing antiretroviral therapy. A retrospective analysis of a prospectively collected cohort involving all consecutive patients who were prescribed a raltegravir-containing antiretroviral regimen between June 2005 and December 2010. Significant creatine kinase elevation was defined as an elevation of at least 3-fold from the upper limit of normal (ULN) (grade 2, WHO classification) while receiving raltegravir. Blood analysis at each visit included at least creatine kinase, as well as plasma HIV-1 RNA and CD4 cell count. There were 475 patients who had been exposed to raltegravir for a median of 11.5 (IQR 8.2-15.2) months. An increase of creatine kinase ≥ 3-fold ULN was detected in 53 (11.2%) patients, representing an incidence of 3.8/100 person-years. Symptoms were reported by seven patients (1.5%), they showed either grade 1 (n = 3) or 2 (n = 4) creatine kinase increases. The median duration of raltegravir therapy before creatine kinase elevation was 5.9 (IQR 3.3-9.3) months. Evidence of creatine kinase elevation prior to raltegravir therapy [hazard ratio (HR) 3.30; 95% CI 1.59 ± 6.86; P = 0.001], abnormal baseline creatine kinase (HR 3.24; 95% CI 1.63 ± 6.45; P = 0.001) and male gender (HR 4.17; 95% CI 1.33 ± 1.27; P = 0.001) were identified as independent risk factors for creatine kinase elevation during raltegravir treatment. Although ≈ 1 in 10 patients on raltegravir therapy developed significant creatine kinase elevation as defined in this study, symptoms were uncommon, not severe and occurred in patients with easily identifiable risk factors.

Paraneoplastic necrotizing myopathy and dermatomyositis in a patient with rectosigmoid carcinoma

An 81-year-old woman with adenocarcinoma of the rectosigmoid presented with progressive muscle weakness and difficulty swallowing, with symptoms worsening following successful resection of the tumor. On examination, she had weakness primarily of lower limb proximal muscles, with no other abnormal findings. Laboratory tests showed significant elevation of creatine kinase, and EMG findings indicated myositis of the proximal muscles. While MRI showed increased signal intensity on T2-weighted images of the leg muscles, indicating inflammation, muscle biopsy found widespread necrosis with only weak and focal lymphocytic infiltration. A diagnosis of paraneoplastic necrotizing myopathy (PNM) was made, and immunomodulatory treatment initiated, with little response. Four months later she returned with exacerbation of symptoms, this time with skin changes pathognomonic of dermatomyositis (DM). A repeat MRI showed progression of inflammation, as well as necrotic foci. It is important to distinguish between paraneoplastic myopathies such as DM and PNM, with implications regarding treatment and prognosis.

The Risk for Significant Creatine Kinase Elevation with Statins

The HMG-CoA reductase inhibitors (statins) are effective for reducing long-term cardiovascular morbidity and mortality in both primary and secondary prevention. The most serious adverse reaction is significant elevation of creatine kinase (CK) leading to rhabdomyolysis. The incidence of CK elevation is low in randomized, controlled trials. The rate may be higher in 'real-world', less controlled settings. Data on the risks of statin-associated rhabdomyolysis in 'real-world' practice settings are limited. The aim of this study was to examine the risk for CK elevation among statin users in a clinical practice setting. Potential risk factors were identified and evaluated to quantify the risk for CK elevation with statins. This case-control study was conducted at Kaiser Permanente Colorado. Patients with prescriptions for lovastatin or simvastatin between 1 January 1999 and 30 June 2006 were identified. Cases (n = 183), i.e. patients with a CK > or =10x the upper limit of normal (ULN) while receiving a statin during this time period, were each matched on the date of statin purchase to ten control patients (n = 1830) without CK > or =10x ULN while receiving a statin. Multivariate, conditional logistic regression was used to assess the associations between the statin, statin dose, demographic, co-morbidity, laboratory, and medication factors potentially associated with CK >or =10x ULN. he mean (SD) age of patients was 64.9 (11.5) years and 56.9% were male. Overall, simvastatin use was associated with a higher likelihood for CK > or =10x ULN than lovastatin (adjusted odds ratio [OR] 4.6; 95% CI 1.1, 12.4). Using simvastatin 40 mg daily as the referent, and in the absence of interacting medications, only simvastatin 80 mg was associated with a higher likelihood for CK > or =10x ULN (OR 2.7; 95% CI 1.1, 6.9). In the presence of interacting medications, all doses of simvastatin and only lovastatin 80 mg were associated with a higher likelihood for CK > or =10x ULN. In this study, simvastatin was associated with a higher likelihood for CK > or =10x ULN than lovastatin. High-dose simvastatin, in particular, appears to confer a greater risk than lower doses of either simvastatin or lovastatin.

The SLCO1B1*5Genetic Variant Is Associated With Statin-Induced Side Effects

We sought to identify single nucleotide polymorphisms associated with mild statin-induced side effects. Statin-induced side effects can interfere with therapy. Single nucleotide polymorphisms in cytochrome P450 enzymes impair statin metabolism; the reduced function SLCO1B1*5 allele impairs statin clearance and is associated with simvastatin-induced myopathy with creatine kinase (CK) elevation. The STRENGTH (Statin Response Examined by Genetic Haplotype Markers) study was a pharmacogenetics study of statin efficacy and safety. Subjects (n = 509) were randomized to atorvastatin 10 mg, simvastatin 20 mg, or pravastatin 10 mg followed by 80 mg, 80 mg, and 40 mg, respectively. We defined a composite adverse event (CAE) as discontinuation for any side effect, myalgia, or CK >3x upper limit of normal during follow-up. We sequenced CYP2D6, CYP2C8, CYP2C9, CYP3A4, and SLCO1B1 and tested 7 reduced function alleles for association with the CAE. The CAE occurred in 99 subjects (54 discontinuations, 49 myalgias, and 9 CK elevations). Sex was associated with CAE (percent female in CAE vs. no CAE groups, 66% vs. 50%, p < 0.01). SLCO1B1*5 was associated with CAE (percent with > or = 1 allele in CAE vs. no CAE groups, 37% vs. 25%, p = 0.03) and those with CAE with no significant CK elevation (p < or = 0.03). Furthermore, there was evidence for a gene-dose effect (percent with CAE in those with 0, 1, or 2 alleles: 19%, 27%, and 50%, trend p = 0.01). Finally, the CAE risk appeared to be greatest in those carriers assigned to simvastatin. SLCO1B1*5 genotype and female sex were associated mild statin-induced side effects. These findings expand the results of a recent genome-wide association study of statin myopathy with CK >3x normal to milder, statin-induced, muscle side effects.

Serum cardiac markers response to biphasic and monophasic electrical cardioversion for supraventricular tachyarrhythmia—a randomised study

Electrical cardioversion in patients with various types of supraventricular tachyarrhythmia (SVT) may induce serum cardiac markers elevation. Only a few studies have evaluated the impact of the type of shock waveform on electrical myocardial injury. The aim of our study was to compare the response of serum cardiac markers to biphasic and monophasic cardioversion for SVT. One hundred and forty one patients with various SVTs referred for electrical cardioversion were randomised to monophasic (MP) or biphasic (BP) cardioversion. Serum levels of creatine kinase (CK), MB fraction of CK (CK-MB), myoglobin and troponin I were analysed before cardioversion and 254+/-58 min after the procedure. Average age of the patients was 67.9+/-11.3 years, 71 underwent BP and 70 MP cardioversion. In MP group, cumulative energy (CE)>150J was associated with significant elevation of CK and myoglobin levels after cardioversion (1.52+/-3.81 microkat/l and 187+/-433 microg/l), while CE<150J was not (-0.04+/-0.34 and 4+/-11, p<0.05). In BP group, CE>150J was associated with significant but smaller CK elevation (0.27+/-1.09 microkat/l, p<0.05) and comparable myoglobin elevation (80.7+/-21.4 microg/l, p<0.05). CE>150J was the only independent positive predictor for CK and myoglobin elevation in both groups. No significant changes in CK-MB and Troponin I levels after cardioversion were identified. According to our study, electrical cardioversion for SVTs is not associated with biochemical signs of myocardial injury. Application of CE>150J can be followed by CK and myoglobin elevation most likely due to skeletal muscle damage. This reaction is more pronounced in MP than in BP cardioversion.

Dual-isotope myocardial SPECT in patients with redefined myocardial infarction

Background According to the redefinition of myocardial infarction (MI) by the ESC/ACC Committee, patients with unstable angina (UA) without significant elevation of creatine kinase (CK) but with elevation of troponin T should be diagnosed as MI. Methods One hundred and forty-six consecutive patients formerly diagnosed as UA, with peak CK levels<twice upper normal level, who underwent myocardial Thallium-201 (Tl; perfusion tracer) and 123I-15-iodophenyl 3-methyl pentadecanoic acid (BMIPP; metabolism tracer) dual isotope single-photon emission computed tomography (SPECT), were retrospectively reclassified into redefined MI and UA groups according to the redefinition (troponin T: rapid bedside assay positive or quantitative level >0.10 ng/ml). Dual SPECT findings were analyzed qualitatively and quantitatively in blinded manner. Results Forty-seven patients (32%) were redefined as MI and 99 patients (68%) were redefined as UA. On admission, there were small but statistically significant elevations in laboratory parameters such as white blood cell count, C-reactive protein, CK and CK-MB in the redefined MI group compared with the redefined UA group. The proportion of patients with perfusion and metabolic abnormalities was significantly higher in the redefined MI group (Tl defect 36% vs. 4%, odds ratio: 13.5, p<0.001; BMIPP defect 64% vs. 23%, odds ratio: 5.8, p<0.001). Semi-quantitative evaluation revealed that the total Tl and BMIPP scores were significantly higher in the redefined MI patients ( p<0.001). Conclusions In the redefined MI patients, perfusion and metabolic abnormalities occurred frequently and more extensively. However, Tl/BMIPP dual SPECT had limited ability to detect minor myocardial infarcts classified as redefined MI. A more sensitive stratification combined with troponin T directed assignment should be established to incorporate the ongoing minor infarcts which could not be assessed by serial dual-scintigraphic evaluations.

Impact of the Revised Criteria for Acute Myocardial Infarction Using Cardiac Troponins in a Japanese Population With Acute Coronary Syndromes

The clinical implications of applying the new criteria of acute myocardial infarction (AMI) with cardiac troponins in terms of their diagnostic and prognostic impact in patients with suspected acute coronary syndromes (ACS) have not been well evaluated. The study group comprised 973 consecutive patients who were diagnosed as having ACS with or without ST elevation (STE). They were divided into 3 groups: unstable angina (UA) group (n=195) representing patients with no significant elevations of creatine kinase (CK) and troponin T (TnT); TnT-myocardial infarction (MI) group (n=170) with TnT elevation and no CK elevation (additionally detected AMI by the new criteria); CK-MI group (n=608) with significant elevation of CK (AMI by the old criteria). In the TnT-MI group, 140 (76%) patients had non-STE ACS. In-hospital mortality rates for STE ACS were 0%, 2.5% and 9.7% in the UA, TnT-MI and CK-MI groups, respectively. The corresponding values for non-STE ACS were 1.8%, 4.6%, and 16.5%, respectively (p<0.0001), suggesting a pivotal role of TnT. In multiple logistic regression analysis, significant CK elevation was selected as an independent predictor of in-hospital death in concurrence with age > or =75 years, prior MI, shock and low left ventricular ejection fraction in non-STE ACS. The new criteria result in a substantial increase in the diagnosis of AMI from non-STE ACS in particular. They assist greatly in detailed risk stratification of ACS patients, notably in cooperation with the old CK criteria.

Acute Coronary Syndrome

Acute coronary syndrome consists of acute myocardial infarction associated with electrocardiographic ST segment elevation (STEMI) and unstable angina/non-ST segment elevation myocardial infarction (UA/NSTEMI). Theses three conditions are differentiated primarily by clinical, electrocardiographic, and laboratory presentations correlating with the duration and extent of thrombotic occlusion as a consequence of plaque rupture. Acute coronary syndrome is now the most prevalent presentation of ischemic heart disease in Korea as well as developed countries. Q-wave acute myocardial infarction is the most easily identified syndrome ; persistent angina and ST-segment elevation are characteristic of sudden total or near-total thrombotic arterial occlusion. Urgent reperfusion is the mainstay of therapy, whereas UA/NSTEMI is usually associated with severe coronary obstruction but not total occlusion of the culprit coronary artery. The distinction between unstable angina and non-Q wave, non-ST segment elevation myocardial infarction is often not clear at the initial presentation of patients. Unstable angina is defined as angina pectoris with at least one of the following three features : ① It occurs at rest usually lasting more than 20 minutes. ② It is severe and described as frank pain and of new onset within 1 month. ③ It occurs with a crescendo pattern (more severe, prolonged, or frequent than previously). Some patients with this pattern of ischemic discomfort, especially those with prolonged rest pain, develop evidence of myocardial necrosis on the basis of the release of cardiac markers and thus have a diagnosis of NSTEMI. This diagnosis has been based on the elevation of serum creatine kinase (CK)-MB, level but recently troponin T and I assays are used to define ischemic myocardial damage based on their higher sensitivity for myocardial necrosis and prognostic implication. Troponin has become the standard myocardial marker. A certain number of patients have elevated levels of troponins in the absence of significant CK elevation. Several studies have shown that despite nondiagnostic CK levels, an elevated troponin level often indicates a poor prognosis.Successful treatment strategies for acute coronary syndrome that improve survival include anticoagulant, antiplatelet, thrombolytic, and interventional approaches.

Increased Serum Total Creatine Kinase and Creatine Kinase Isoenzyme MB After Cryosurgical Ablation of the Prostate

Purpose Several reports have documented that the MB isoenzyme of creatine kinase is present in prostatic tissue. However, since it has been shown that lower urinary tract manipulations, including transurethral prostatectomy, do not significantly increase serum creatine kinase isoenzyme MB levels, such elevations, which are found in patients after prostatic surgery, are believed to be specific for myocardial infarction. We examined whether cryosurgical ablation of the prostate altered serum creatine kinase or isoenzyme MB levels. Materials and Methods In 81 consecutive patients undergoing routine cryosurgical ablation of the prostate serum levels of creatine kinase and creatine kinase isoenzyme MB were measured from peripheral blood specimens drawn preoperatively, in the recovery room and at 8 and 24 hours postoperatively. Postoperative electrocardiograms were compared to the preoperative study. Results In 72 of 81 patients (89%) significant elevations in creatine kinase and creatine kinase isoenzyme MB levels were noted at all time points after cryosurgical ablation of the prostate and appeared to reach a peak at 16 hours postoperatively. The mean increases within the first 8 hours after cryosurgical ablation of the prostate were 1,355 units per 1. for creatine kinase and 46.6 ng./ml. for creatine kinase isoenzyme MB. No patient had any significant changes on the postoperative electrocardiogram. All 9 patients (11%) who did not have significant creatine kinase or creatine kinase isoenzyme MB levels after cryosurgery had undergone prior cryosurgery or combined radiation and hormonal therapy. Conclusions Cryosurgical ablation of the prostate appears to produce elevations in serum creatine kinase and creatine kinase isoenzyme MB, which are specific to the procedure. Assays for creatine kinase isoenzyme MB are unreliable to render a diagnosis of myocardial infarction after cryosurgical ablation of the prostate.