Markers Of Myocyte Necrosis Research Articles

Cardiac biomarkers in acute coronary syndromes

Cardiac biomarkers play a significant role in the diagnosis, risk assessment, and management of patients with acute coronary syndromes (ACS). Several biomarkers identify different components of the pathophysiology of ACS: troponins are markers of myocyte necrosis, natriuretic peptides reflect neurohormonal activation and myocardial dysfunction, and C-reactive protein reflects various inflammatory processes. Whilst there are a number of established and novel biomarkers to assess ischemia, necrosis and myocardial dysfunction in coronary artery disease, it is probable that no single biomarker will emerge that provides appropriate information for all clinical settings of ACS. This suggests that ongoing efforts in plasma-based biomarker research should concentrate on the use of a multimarker approach to enhance our diagnosis, prognostic assessment, and management of patients with suspected ACS, as compared with using individual markers alone. It is recommended that current practice involve the selective use of biomarkers in patients in whom a more complete assessment of risk is desired. At present, routine biomarker measurement is not advocated until further data become available, which will support the benefit of specific therapeutic interventions.

Heart fatty acid–binding protein in combination with the 80-lead body surface potential map improves early detection of acute myocardial infarction in patients who are cardiac troponin T–negative at presentation

Of patients who present with ischemic-type chest pain and a negative cardiac troponin T (cTnT) at first medical contact, there are patients at a very early stage of infarction. The aim of this research was to assess heart fatty acid–binding protein (H-FABP), a novel marker of myocyte necrosis, in combination with the 80-lead body surface potential map (BSPM) in the early diagnosis of acute myocardial infarction (AMI). Methods In this prospective study, consecutive patients presenting with acute ischemic-type chest pain between 2003 and 2006 were enrolled. At first medical contact, blood was sampled for cTnT and H-FABP; in addition, a 12-lead electrocardiogram (ECG) and BSPM were recorded. A second cTnT was sampled 12 hours or more after presentation. Peak cTnT 0.03 μg/L or higher diagnosed AMI. Elevated H-FABP was 5 ng/mL or higher. A cardiologist blinded to both the clinical details and 12-lead ECG interpreted the BSPM. Results Enrolled were 407 patients (age 62 ± 13 years; 70% men). Of these 407, 180 had cTnT less than 0.03 μg/L at presentation. Acute myocardial infarction occurred in 52 (29%) of 180 patients. Of these 180 patients, 27 had ST-segment elevation (STE) on ECG, 104 had STE on BSPM (sensitivity, 88%; specificity, 55%), and 95 (53%) had H-FABP elevation. The proportion with elevated H-FABP was higher in the AMI group compared with non-AMI group ( P < .001). Body surface potential map STE was significantly associated with H-FABP elevation ( P < .001). Of those with initial cTnT less than 0.03 μg/L, the c-statistic for the receiver operating characteristic curve distinguishing AMI from non-AMI using H-FABP alone was 0.644 (95% confidence interval [CI], 0.521-0.771), using BSPM alone was 0.716 (95% CI, 0.638-0.793), and using the combination of BSPM and H-FABP was 0.812 (95% CI, 0.747-0.876; P < .001). Conclusion In patients with acute ischemic-type chest pain who have a normal cTnT at presentation, the combination of H-FABP and BSPM at first assessment identifies those with early AMI (c-statistic, 0.812; P < .001), thus allowing earlier triage to reperfusion therapy and secondary prevention.

Urinary Methylmalonic Acid in Patients with Acute Myocardial Infarction

Objective: To investigate urinary methylmalonic acid (uMMA) levels and their relationship with markers of myocyte necrosis and inflammation in patients with acute myocardial infarction (AMI). Subjects and Methods: The study participants consisted of 80 consecutive patients with AMI and 72 age- and sex-matched consecutive controls. Of the patients, 38 had ST segment elevation myocardial infarction (STEMI) and 42 had non-ST segment elevation. All patients with STEMI underwent fibrinolytic therapy. Routine laboratory tests included troponin-I, creatinine phosphokinase MB (CK-MB), high-sensitivity C-reactive protein (hs-CRP), vitamin B₁₂, folate, homocysteine and methylmalonic acid analyses. uMMA measurements were made by a spectrophotometric method. Results: uMMA levels were significantly higher in patients with AMI than in controls (10.1 vs. 5.2 mmol/mol creatinine, p < 0.001) and higher in patients with anterior MI compared to those with non-anterior MI (18.9 vs. 8.7 mmol/mol creatinine, p < 0.001). In addition, uMMA levels were significantly higher in patients without successful reperfusion compared to those with successful reperfusion. In patients with STEMI, a strong positive association was found between urinary MMA and plasma hs-CRP levels (r = 0.81, p < 0.001), symptom duration (r = 0.91, p < 0.001) and wall motion score (r = 0.60, p = 0.006). More importantly, a strong positive association was observed between uMMA and the size of myocardial infarction in patients without successful reperfusion (for CK-MB r = 0.81, p = 0.013; for wall motion score r = 0.82, p = 0.012). Conclusion: uMMA levels were elevated in patients with AMI and, as such, may be a candidate biochemical indicator of larger infarct size and enhanced inflammation in patients with AMI.

SPIRONOLACTONE IN THE PREVENTION OF SKELETAL MUSCLE ATROPHY AND BONE LOSS IN RATS WITH ALDOSTERONISM.

Purpose Congestive heart failure (CHF), with its classic signs and symptoms, has its origins rooted in a salt-avid state mediated largely by effector hormones of the renin-angiotensin-aldosterone system (RAAS). CHF is accompanied by a systemic illness that features oxidative stress and a progressive loss of soft tissues and bone that eventuates in a wasting syndrome termed cardiac cachexia. To simulate the inappropriate (relative to dietary Na+) aldosteronism found in human CHF, rats receive aldosterone (0.75 μg/h), together with 1% NaCl in drinking water (ALDOST). Skeletal muscle wasting and bone loss are found in ALDOST and associated with secondary hyperparathyroidism (SHPT). Herein we hypothesized that these responses could be attenuated by cotreatment with spironolactone (Spiro), an ALDO receptor antagonist. Methods and Results Eight-week-old male Sprague-Dawley rats received ALDOST alone for 4 weeks or together with Spiro (150 mg/kg/d by gavage). We monitored: body weight and skeletal muscle morphology, including scarring, a marker of myocyte necrosis, and the presence of apoptosis (TUNEL assay); femoral bone mineral density (BMD) and content (BMC); plasma α1-antiproteinase activity (AP), an inverse correlate of oxidative stress; and plasma parathyroid hormone (PTH). Compared with age-/gender-matched controls, with ALDOST we found (mean ± SEM): inadequate weight gain (81 ± 5 vs 22 ± 6 g; p Conclusions In rats with aldosteronism, cotreatment with an ALDO receptor antagonist, Spiro, prevents the appearance of SHPT and accompanying skeletal muscle atrophy, bone loss, and oxidative stress. The use of Spiro in human CHF may offer advantages that extend beyond its diuretic properties.

Inflammatory Biomarkers in Acute Coronary Syndromes

Acute coronary syndromes (ACS) are multifactorial and occur in response to inflammation, plaque rupture and subsequent thrombosis, progressive mechanical obstruction, and dynamic obstruction.1 Patients with ACS span a large spectrum of risk that progresses from unstable angina (UA) to non–ST-elevation myocardial infarction (NSTEMI) to ST-elevation myocardial infarction (STEMI). ECG findings and markers of myocyte necrosis are used to define the type of ACS and guide reperfusion strategy in ST-elevation myocardial infarction. For patients with non–ST-elevation (NSTE) ACS, however, a large degree of uncertainty remains regarding long-term risk and optimal secondary prevention for the individual patient. Increasingly, biomarkers are being used as tools to identify subgroups of patients with ACS who are at increased risk for subsequent cardiovascular events. Among potential biomarkers, much interest has focused on biomarkers of inflammation. The process that leads to eventual plaque erosion or rupture involves a number of inflammatory mechanisms, including endothelial dysfunction, leukocyte migration, extracellular matrix degradation, and platelet activation (Figure).2 The optimal inflammatory biomarker would provide a method for quantitating cardiovascular-specific inflammation, thereby predicting the risk of recurrent atherothrombosis and its clinical sequelae. Because they address a separate aspect of ACS pathophysiology, biomarkers of inflammation may provide unique information to the clinician separate from that provided by biomarkers of myocyte necrosis and hemodynamic stress. Pathophysiological sequence of inflammatory biomarkers in ACS. In this schematic diagram showing the development of an atherosclerotic plaque and the local vascular events that surround an ACS, the inflammatory biomarkers are superimposed with a semiquantitative representation of their relative importance during the sequence of events shown. Cytokines and acute-phase reactants such as IL-6, MCP-1, TNF-α, IL-18, IL-10, CRP, and serum amyloid A (SAA) may establish or be surrogate markers for basal inflammation that leads to development of atherosclerotic plaque. Activation of endothelial adhesion molecules such as …

Electrocardiographic changes in acute coronary syndromes

Acute coronary syndromes (ACS) remain one of the greatest global causes of mortality and morbidity. Rapid diagnosis and treatment are paramount. Despite scientific advances, the electrocardiogram (ECG) remains the cornerstone of ACS diagnosis, classification, risk stratification and management. In 2002, an expertcommittee of the American College of Cardiology and the European Society of Cardiology redefined ACS. The new definition incorporated the new diagnostic markers of myocyte necrosis, troponins, and also redefined the electrocardiographic criteria for ACS diagnosis (Alpert et al, 2000).

Potential value for new diagnostic markers in the early recognition of acute coronary syndromes

The diagnostic approach to acute coronary syndromes (ACS) remains one of the most difficult and controversial challenges facing emergency physicians. In recent years, cardiac troponins have emerged as the biochemical "gold standard" for diagnosis of patients with acute chest pain, enhancing our ability to recognize ACS. Early diagnosis and treatment of myocardial ischemia improve patient outcomes, but conventional markers are often nondiagnostic at the time of arrival at the emergency department. Promising new biomarkers, which appear earlier after the onset of ischemia, are being studied and integrated into clinical practice. Some are markers of myocyte necrosis, but others, including ischemia-modified albumin and natriuretic peptides, detect myocardial ischemia and myocardial dysfunction. The aim of the present article is to review the diagnostic approach to ACS, focusing on recent literature describing novel biochemical markers. If ongoing and future studies confirm their role in probability-based models risk assessment, a new era in the diagnostic approach to ACS may be dawning.

IMMEDIATE POST-TRANSPLANT MYOCYTE NECROSIS DETECTED BY ELEVATED SERUM LEVELS OF TROPONIN I IS ASSOCIATED WITH AN ADVERSE LONG TERM GRAFT OUTCOME

407 Early following cardiac transplantation a characteristic early peak, then a gradual decline in serum levels of troponin I, a marker of myocyte necrosis is seen. This elevation has been shown not to be associated with cellular rejection, but we postulated that it may be indicative of early immunologically-mediated small vessel injury. We therefore evaluated whether the peak serum level of troponin I, as well as the area under the troponin versus time curve, were associated with long term graft performance. Serum troponin I levels were determined in 18 patients receiving a cardiac transplant between January and August of 1994. Specimens were obtained on the initial post-operative day and then daily thereafter until return to undetectable levels. Long term outcomes were evaluated through routine clinical follow up and yearly coronary angiography and ventriculography. At a mean follow-up of 37 months post-transplantation, 15 patients (83%) had survived. Among the surviving patients, 26% had coronary artery disease by angiography and 20% had some degree of left ventricular systolic dysfunction. The combined endpoint of death, coronary artery disease, or ventricular dysfunction had occurred in 44% of the 18 patients studied. For the entire group the mean peak troponin I level was 11.7 (range 2.8 -50). Troponin I was undetectable by 9 - 25 days, and the mean area under the troponin I vs. time curve was 31.9 (range 7.1 - 112.6). There was no correlation between donor heart ischemia time and troponin levels. The combined endpoint occurred in 83% of patients with troponin vs. time areas of > 30, and only 25% of those with values <30 (P= 0.045). Conclusion: Myocardial necrosis of a strikingly variable degree, as detected through troponin I elevations, is found immediately following cardiac transplantation in all patients and is not necessarily related to rejection. Early elevation is of an unknown etiology, but is associated with a significantly increased incidence of long term adverse outcomes. Early serial troponin levels following transplantation may be a useful tool for helping predict long term outcome as well as in the evaluation of new therapies in the peri-transplant period.

Intérêt de la scintigraphie myocardique aux anticorps anti-myosine dans le diagnostic d'une atteinte myocardique au cours d'une polymyosite

In a patient with polymyositis, specific myocardial involvement was determined by myocardiac scintigraphy using radio-labelled antimyosin antibodies, a specific marker of myocyte necrosis.