Troponin T in patients with low grade or atypical angina. Identification of a high risk group for short- and long-term cardiovascular events

AIMS: Cardiac troponin T is an established marker of cardiovascular risk in patients with severe angina pectoris. Data are scarce on patients admitted to a coronary care unit with low grade or atypical angina pectoris to rule out myocardial infarction. METHODS AND RESULTS: We investigated 106 patients (57.4 SD 11.6 years) with low grade (Braunwald class I) or atypical symptoms out of 702 patients admitted to the coronary care unit with suspected acute myocardial infarction. Serum concentrations of troponin T were measured at admission and 4 h later. In hospital cardiovascular events including acute myocardial infarction, life threatening cardiac arrhythmias, congestive heart failure, and death were recorded. Patients were additionally observed after 3 and 6 months post-discharge regarding acute myocardial infarction, unstable angina, rehospitalization for cardiac causes and death. The patients were divided into a troponin T positive (> or =0.2 microg x 1(-1) at admission or 4 h later; n=11) and a troponin T negative group. The mean value of troponin T 4 h after admission in the positive group was 0.58 microg x 1(-1). Of the troponin T positive patients, 0.82 (0.95 CI: 0.48-0.98) had a cardiovascular event during their stay in hospital vs 0.41 (0.95 CI: 0.31-0.52) of troponin T negative patients (P<0.05). In the troponin T positive group 0.64 (0.95 CI: 0.31-0.89) developed myocardial infarction in hospital vs 0.07 (0.95 CI: 0.03-0.15) in the troponin T negative group (P<0.001). Troponin T predicts outcome after 3 and 6 months significantly (P<0.05). CONCLUSION: Troponin T identifies patients with low grade or atypical angina at risk of severe short- and long-term cardiovascular events. Therefore, troponin T adds substantial information in patients with ruled out acute myocardial infarction. Troponin T positive patients have to be observed carefully regardless of their symptom intensity and may have to receive early cardiac catheterization; troponin T negative patients could be released safely from the coronary care unit early.     

Assay of cardiac troponin T on Elecsys 2010: comparison with cardiac troponin I

Cardiac troponin T (troponin Tc) of second generation has been measured on the Boehringer Elecsys 2010 analyzer. Cardiac specificity has been studied in patients presenting a rhabdomyolysis syndrome and the results compared with those obtained for cardiac troponin I (troponin Ic) measured on the Dade-Behring Stratus analyzer. The results clearly demonstrated that both troponin Tc and Ic showed similar cardiac specificity. Moreover, troponin Tc and troponin Ic can be indifferently used for the biological diagnostic of myocardial infarction or to asses reperfusion after percutaneous transluminal coronary angioplasty for acute myocardial infarction. In renal disease, troponin Tc was upper the reference limit (0.10 microgram/l) in 25% of the patients studied (20 patients). By contrast, troponin Ic was upper the reference limit (0.6 microgram/l) in only one patient.     

Troponin T as a marker for myocardial ischemia in patients undergoing major noncardiac surgery

To assess the diagnostic performance of cardiac troponin T as a marker for myocardial injury in patients undergoing major noncardiac surgery, we prospectively collected preoperative and postoperative clinical data, including measurements for creatine kinase (CK), CK-MB, and troponin T for 1,175 patients undergoing major noncardiac surgery. Acute myocardial infarction was diagnosed in 17 patients (1.4%) by a reviewer who was blinded to troponin T data and who used CK-MB and electrocardiographic criteria to define acute myocardial infarction. Other predischarge major cardiac complications were detected for another 17 patients. Troponin T elevations (>0.1 ng/ml) occurred in 87% of patients with and in 16% of patients without myocardial infarction. Among patients without myocardial infarction, troponin T was elevated in 62% of patients with and in 15% of patients without major cardiac complications. Receiver-operating characteristic analysis indicated that troponin T had a performance for the diagnosis of acute myocardial infarction similar to CK-MB, and a significantly better correlation with other major cardiac complications in patients without definitive infarction. Future research should seek to determine the significance of troponin T elevations in patients without complications.     

Diagnosis of perioperative myocardial infarction by cardiac troponin T following coronary artery bypass grafting

The determinations of cardiac troponin T provide the highest diagnostic efficiency for the detection of myocardial cell necrosis. To assess perioperative myocardial infarction, serum levels of cardiac troponin T were determined in 14 patients undergoing coronary artery bypass grafting (CABG). The patients were divided into two groups: group I (n = 9), those whose troponin T was less than 1.00 ng/ml on the first postoperative day; group II (n = 5), those whose troponin T was more than 1.00 ng/ml on the first postoperative day. Troponin T levels in group II patients were significantly higher than in group I from the second to the seventh postoperative day. Two patients in group II had specific changes on the electrocardiogram detecting perioperative myocardial infarction as a new Q wave and R wave reduction. These results suggest that troponin T is a valuable marker of perioperative myocardial infarction following CABG.     

Cardiac troponin I in patients receiving renal replacement therapy

Current markers of myocardial injury lack specificity in patients with end-stage renal disease (ESRD). In particular, a false positive creatine kinase-MB (CKMB) elevation occurs in 5-10% of patients with ESRD. The aim of this study was to ascertain the relationship between CKMB and cardiac troponin I (cTnI), a new, highly sensitive and specific marker for myocardial injury, in the authors' dialysis population and compare their specificities. Blood samples were obtained from 112 dialysis patients (35 in peritoneal dialysis; 77 in hemodialysis). Patients were asymptomatic for cardiac ischemia and skeletal muscle injury. Mean +/- SD CKMB mass was 3.16 +/- 2.26 microg/L (range, 0.34-13.62), and cTnI was 0.025 +/- 0.061 ng/ml (range, 0.001-0.496). CKMB and cTnI levels did not correlate (r2 = 0.002; p = 0.61). CKMB mass concentration was significantly higher in men and in diabetics. No patient had a cTnI level greater than 1.5 microg/L, and eight asymptomatic patients had a CKMB mass greater than 6.7 microg/L. These data suggest a specificity of 100% for cTnI vs 94.6% for CKMB at these cutoff values. It is suggested that cTnI replace CKMB as a marker of myocardial injury in patients with ESRD.     

Accumulation of amphotericin B in human macrophages enhances activity against Aspergillus fumigatus conidia: quantification of conidial kill at the single-cell level

Several cardiac serum markers such as cardiac myosin light chain, creatine kinase MB, and cardiac troponins have been shown to be elevated in patients with acute myocardial infarction. These markers are well utilized as clinical indicators for diagnosis and prognosis of myocardial necrosis. Recent studies have strongly indicated that cardiac structural protein troponin T and I are predictive of future cardiac events in patients with acute coronary syndromes including unstable angina pectoris. Immunoassays have also been developed to measure serum levels of cardiac troponins in recent years. These biochemical markers may be useful as a guide for intervention in the near future.     

Elevated serum cardiac markers in asymptomatic marathon runners after competition: is the myocardium stunned?

Prolonged strenuous exercise may trigger acute myocardial infarction (AMI), as exemplified by the occurrence of sudden cardiac death during marathon running. Serum creatine kinase MB (CK-MB) may be elevated in asymptomatic marathon runners after competition from exertional rhabdomyolysis of skeletal muscle altered by training, limiting its utility for evaluating acute cardiac injury in such athletes. Myoglobin and CK-MB2 isoform levels are emerging as earlier markers of AMI and troponin subunits as more specific than serum CK-MB mass. We tested runners before and sequentially after the 1995 Boston Marathon for conventional and newer markers including myoglobin, CK-MB mass and isoforms, cardiac troponin T, and cardiac troponin I using standard laboratory methods and rapid format assays if available. The mean serum values for myoglobin, CK-MB mass, CK-MB/myoglobin rapid panel tests, and CK-MB2 isoforms were normal or negative pre-race and elevated or positive 4 and 24 h after competition. These markers lack specificity for acute cardiac injury in trained runners. While the mean serum values for cardiac troponins T and I remained normal, 9 of 45 runners (20%) showed an increase in subunits by first-generation assays. All runners remained asymptomatic for cardiac disease and completed subsequent marathons 1 year later, making reversible myocardial injury or stunning unlikely. Elevated values of serum markers for AMI, including first-generation assays for both troponin subunits should be interpreted with caution in trained runners.     

Analysis of creatine kinase, CK-MB, myoglobin, and troponin T time-activity curves for early assessment of coronary artery reperfusion after intravenous thrombolysis

BACKGROUND: Thrombolysis has become the standard therapeutic approach in patients with acute myocardial infarction. To identify patients who may benefit from early invasive procedures, reliable noninvasive assessment of success or failure of thrombolytic therapy is mandatory. METHODS AND RESULTS: In a prospective study in 63 consecutive patients undergoing thrombolysis for their first myocardial infarction, serial measurements of creatine kinase (CK), its isoenzyme CK-MB, myoglobin, and troponin T were done to determine their value for noninvasive prediction of coronary artery patency. Blood samples were drawn every 15 minutes during the first 90 minutes, every 30 minutes during the first 4 hours, every 4 hours during the first 24 hours, and every 8 hours during the first 72 hours. The perfusion status of the infarct-related artery was assessed angiographically 90 minutes after initiation of thrombolysis. For each marker, time to its peak concentration and its early initial slope (start of thrombolysis to 90 minutes thereafter) were determined. Areas under receiver operator characteristic (ROC) curves were 0.83, 0.76, 0.82, and 0.80 for maxima of CK, CK-MB, myoglobin, and troponin T, respectively (p = NS by univariate Z test). The corresponding values for early slopes of CK, CK-MB, myoglobin, and troponin T were 0.79, 0.82, 0.89, and 0.80 (p = 0.23 for comparison between myoglobin and CK-MB; p = 0.07 between myoglobin and CK). Sensitivity, specificity, and positive and negative predictive values regarding noninvasive prediction of coronary artery patency after 90 minutes were 80%, 82%, 95%, and 61% for time to CK maximum; 91%, 77%, 91%, and 77% for time to myoglobin maximum; 87%, 71%, 89%, and 67% for early CK slope; and 94%, 88%, 94%, and 82% for myoglobin slope, respectively. When myoglobin slope was assessed together with other clinical reperfusion markers (resolution of chest pain or ST segment elevation, occurrence of reperfusion arrhythmias) by logistic regression analysis, only the myoglobin slope was an independent predictor of coronary artery patency (p < 0.0001). CONCLUSIONS: With regard to noninvasive prediction of coronary artery patency after thrombolytic therapy, measurement of the early initial slopes of the serum markers within only 90 minutes after the initiation of therapy is as accurate as the determination of the time to their peak concentration. Compared with the other markers examined, myoglobin appears to have advantages because of its earlier rise, yielding a better negative predictive value and a higher area under the ROC curve for determination of its early initial slopes.     

Monocyte chemotactic protein expression in allergy and non-allergy-associated chronic sinusitis

The recently developed whole blood rapid assay for cardiac troponin T (TROP T) was evaluated by a cooperative study of general practitioners and office cardiologists in the Tokyo area (Tokyo TROP T Trial). Seventy patients with suspected acute myocardial infarction treated at 14 medical clinics were enrolled in this study. The diagnostic efficacy of troponin T was compared with that of electrocardiographic evaluations and clinical standards for diagnosis of acute myocardial infarction. Twelve of the 70 patients (17.1%) had final diagnoses of acute myocardial infarction or severe unstable angina necessitating emergency coronary intervention. Troponin T was judged as positive when simultaneously measured serum troponin T was more than 0.25 ng/ml. Sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 58.6%, 33.3%, and 100% for electrocardiographic evaluation, and 58.3%, 100%, 100%, and 92.1% for troponin T, respectively. Presence of bundle branch block (11/70 cases) or previous myocardial infarction (14/70 cases) caused false positive readings on electrocardiography, and resulted in the lower positive predictive value. In contrast, troponin T was false in patients admitted within 4 hours after the onset, or patients with smaller infarct. The Tokyo TROP T Trial by general practitioners and office cardiologists concluded that the combination of electrocardiographic evaluation and use of troponin T is a rapid and efficient diagnostic method for the evaluation of patients with suspected acute myocardial infarction.     

Serum levels of cardiac troponin I and troponin T in estimating myocardial infarct size soon after reperfusion

BACKGROUND: Cardiac troponin I (TnI) and troponin T (TnT) are highly specific myocardial markers. OBJECTIVE: To determine whether their serum levels can be used to estimate myocardial infarct size soon after reperfusion. METHODS: We measured the serum levels of TnI, TnT, and creatine kinase every 3 h, and the serum cardiac myosin light chain I (MLCI) every 24 h, in 42 patients with acute myocardial infarction in whom reperfusion therapy had successfully been performed. We calculated the severity of regional hypokinesis by analyzing the follow-up ventriculograms with the centerline method. RESULTS: The time from reperfusion to the peak level for TnI was 6.1 +/- 3.5 h, significantly shorter than those for creatine kinase (7.5 +/- 4.1 h) and MLCI (55 +/- 28 h). The time to peak level for TnT (6.8 +/- 4.0 h) differed significantly from that for MLCI but not from that for creatine kinase. There was a significant correlation between the peak levels of TnI and TnT (r = 0.86). The peak TnI and TnT levels were correlated well to the peak creatine kinase level (r = 0.67 and 0.69, respectively), total creatine kinase release (r = 0.66 and 0.66), and the peak MLCI level (r = 0.71 and 0.80). We observed excellent correlations between the peak levels of TnI and TnT, and regional hypokinesis (r = -0.84 and -0.85, respectively). These were comparable to the correlations between regional hypokinesis and the peak creatine kinase level (r = 0.75), total creatine kinase release (r = -0.72), and the peak MLCI level (r = -0.76). CONCLUSIONS: These results suggest that the peak serum levels of TnI and TnT in patients with successful reperfusion are accurate and early indices of infarct size.     

Management and outcomes for black patients with acute myocardial infarction in the reperfusion era. National Registry of Myocardial Infarction 2 Investigators

Data from a national registry of myocardial infarction patients from June 1994 to April 1996 were analyzed to compare the presenting characteristics, acute reperfusion strategies, treatment patterns, and clinical outcomes among black and white patients. Blacks presented much later to the hospital after the onset of symptoms (median 145 vs 122 minutes, p <0.001), were more likely to have atypical cardiac symptoms (28% vs 24%, p <0.001), and nondiagnostic electrocardiograms during the initial evaluation period compared with whites (37% vs 31%, p <0.001). Also, blacks were less likely to receive intravenous thrombolytic therapy (adjusted odds ratio [OR] 0.76, 95% confidence intervals [CI] 0.71 to 0.80), coronary arteriography (adjusted OR 0.85, 95% CI 0.77 to 0.95), other elective catheter-based procedures (adjusted OR 0.87, 95% CI 0.78 to 0.96), and coronary artery bypass surgery (adjusted OR 0.66, 95% CI 0.58 to 0.75) than their white counterparts. Despite these differences in treatment, there were no significant differences in hospital mortality between blacks and whites.     

Normal frontal perfusion in patients with frozen gait

With the aim to compare the diagnostic efficacy as regards acute myocardial infarction of two rapid dry-strip tests, one with both creatine kinase MB (CK-MB) and myoglobin (C + M) and the other with troponin T, and to test the reliability of bedside diagnosis by the coronary care unit (CCU) nurse, 151 patients with acute chest pain admitted to the CCU were investigated. There was no difference in diagnostic performance between rapid tests and quantitative determinations. With <6-hour duration of symptoms, the sensitivity was better for C + M than for troponin T (72% vs 33%, p < 0.05). With symptoms lasting >12 hours on arrival, troponin T performed better, with 100% sensitivity and a negative predictive value of 100% in the 6-hour retest. For exclusion of damage, the two tests have similar and reliable diagnostic capacities 12 hours after the onset of symptoms. The bedside diagnosis or exclusion of acute myocardial infarction was carried out rapidly (within 20 minutes) and reliably by the CCU nurses.     

Control of gene expression in Plasmodium falciparum

Myocardial contusion is an infrequent, but sometimes serious complication in patients who experienced deceleration (blunt) trauma. We investigated the assessment of the new cardiac markers troponin I (cTnI) and troponin T (cTnT) in relation to the conventional CKMB-activity, the CKMB-activity/CK-total ratio, CKMB-mass and the CKMB-mass/CK-total ratio for the detection of myocardial contusion in 89 patients with blunt trauma (38 patients with thoracic injuries and 51 patients without thoracic injuries). All parameters were analysed at admission (t1) and 24 h after admission (t2). For the patients with thoracic injuries, at t1 cTnI was elevated in three, and cTnT in four patients; at t2 both cTnI and cTnT were elevated in nine patients. At t1, eighteen to thirty patients had increased levels of the conventional parameters; at t2 this was true for six to thirty-five patients. For the patients without thoracic injuries all cTnI and cTnT levels were within the reference ranges at t1. At t2 one patient, who experienced an acute myocardial infarction, had elevated cTnI and cTnT levels. At t1, five to thirty-five patients had increased levels of the conventional parameters; at t2 this was true for four to forty-two patients. From this study we conclude that the conventional parameters are not useful for the detection of myocardial contusion in patients experiencing blunt trauma. The parameters cTnI and cTnT are equally accurate and more reliable for the selection of patients who require intensive cardiac monitoring. If at admission the cTnI or the cTnT levels are within the reference ranges, a second analysis after admission is necessary to reach a reliable conclusion concerning myocardial contusion as a result of trauma on basis of the troponin levels.     

Troponin T and creatinine kinase isoenzyme MB mass in the diagnosis of myocardial infarction

The aim of this study was to compare troponin T (TnT) and creatine kinase isoenzyme MB mass (CK-MBm) with conventional enzymes, ie CK, CK-MB activity and lactate dehydrogenase isoenzyme 1, in the diagnosis of myocardial infarction (MI). 624 patients (351 men and 273 women, median age 69 years) were admitted to hospital with suspicion of an acute coronary heart disease event. TnT was elevated (> 0.10 microg/L) in 100%, CK-MBm (> 5.0 microg/L) in 99%, and both markers in 99% of the 89 patients with the diagnosis of a definite MI according to modified FINMONICA criteria. In the 60 patients with the diagnosis of a probable MI, TnT was elevated in 65%, CK-MBm in 67% and both markers in 60%. In the patients with unstable coronary artery disease (unstable angina or prolonged chest pain attack) and conventional enzymes within normal limits, TnT was elevated in 14%, CK-MBm in 17% and both markers in 9%. The use of TnT and CK-MBm did not lead to a major change in the diagnostics of definite MI. However, TnT and CK-MBm did not confirm the diagnosis of probable MI in one-third of the events. These new markers revealed a myocardial injury in about 15% of those patients who had unstable coronary artery disease and conventional enzymes within normal limits.     

Real-time visualization of PH domain-dependent translocation of phospholipase C-delta1 in renal epithelial cells (MDCK): response to hypo-osmotic stress

BACKGROUND: The aim of this study was to compare the prognostic efficacy of cardiac troponin T (cTnT) and I (cTnI) in patients with clinical unstable angina. METHODS: We studied 74 patients with chest pain at rest, electrocardiographic evidence of myocardial ischemia, and normal (<6.7 ng/mL) values of creatine kinase-MB. cTnT was measured with a commercial assay (cutoff level 0.1 ng/mL) and cTnI with a preliminary research application (cutoff level 3.1 ng/mL). All patients had blood drawn at baseline and 8 hours thereafter. The prospectively defined end point was the proportion of patients identified by each assay as having myocardial damage. RESULTS: cTnT and cTnI were elevated in the same percentage of patients (18 of 74; 24%). Overall, 23 patients had elevations of 1 or both markers. In 13 there were elevations of both. Ten patients had elevations of only one (5 for each marker). In 51 patients, no elevations were present. Death or nonfatal myocardial infarction was more frequent in patients with elevated cTnI (27.7% vs 5.3%; P =.02) than those with normal values. The prognostic influence of cTnT was less (17% vs 8.5%; P =.2). However, the difference between the 2 markers when compared directly was not statistically significant (27.7% vs 17%; P = NS). CONCLUSIONS: These data indicate that both markers identify myocardial damage in equal numbers of patients with clinical unstable angina. Patients with elevations had a worse short-term outcome. The significance of the minor differences in prognostic value will require additional studies.     

Comparison of myoglobin, creatine kinase-MB, and cardiac troponin I for diagnosis of acute myocardial infarction

Serial plasma concentrations of myoglobin, creatine kinase MB (CK-MB) isoenzyme, and cardiac troponin I (cTnI) were measured in 25 patients with a confirmed diagnosis of acute myocardial infarction (AMI), and 74 patients who were suspected of AMI but were subsequently ruled out for this diagnosis. The cutoff concentration for the cTnI assay was optimally determined to be 2.5 ng/mL. Of the three markers, myoglobin had the highest clinical sensitivity (50 percent) when blood was collected between 0 to 6 h after the onset of chest pain. Assays for all serum markers used had high clinical sensitivity (> 93 percent) 6 to 24 h after onset. The CK-MB remained highly sensitive for 48 h, while cTnI was sensitive for up to 72 h. Between 72 and 150 h, cTnI had a clinical sensitivity of 70 percent as compared to 21 percent and 18 percent for myoglobin and CK-MB, respectively. The clinical specificity of cTnI for non-AMI patients was equivalent to CK-MB and significantly higher than for myoglobin. The clinical efficiency of cTnI for all samples was better than either CK-MB or myoglobin, owing mainly to the wider diagnostic window. The specificity of cTnI for 59 patients with chronic renal failure, skeletal muscle trauma and disease was better than all of these markers including cardiac troponin T (cTnT). Results of this study show that cTnI is an effective marker for the retrospective diagnosis of AMI, and consideration should be given to its use in place of CK-MB.     

Improved detection of minor ischemic myocardial injury with measurement of serum cardiac troponin I

This study compared the diagnostic accuracy of the measurement of serum cardiac troponin I (cTnI) with creatine kinase (CK) MB mass in patients with minor myocardial injury whose measured total CK activity did not exceed twice the upper reference limit (300 U/L for men; 200 U/L for women). Forty-eight consecutive patients presenting with chest pain and with in-hospital documentation of myocardial injury were enrolled. Electrocardiogram, echocardiogram, and serial serum CK-MB mass, cTnI, and total CK were measured over 36 h after admission. Peak total CK activity was within normal limits in 28 patients (58%). The mean (+/- SD) peak CK-MB mass and cTnI concentrations were: 16.4 (11.8) micrograms/L and 132 (13.0) micrograms/L; respectively. The peak biochemical marker index (defined as CK-MB or cTnI divided by its respective upper reference limit) was significantly (P < 0.05) higher for cTnI than for CK-MB from 7 to 36 h. The clinical sensitivity for detection of myocardial injury for cTnI was 100% [95% confidence interval (CI): 87.2% to 100%], compared with 81.8% (CI: 67.3% to 91.8%) for CK-MB. Thus, cTnI was more sensitive than CK-MB mass for detection of myocardial injury in patients with small increases of total CK.     

Subcortical vascular dementia: survey of treatment patterns and research considerations

OBJECTIVE: The purpose of this study was to evaluate retrospectively the efficacy of a proposed panel of three cardiac markers (myoglobin, creatine kinase-MB mass [CK-MB], and cardiac troponin I) in the diagnosis of acute myocardial infarction (AMI) in patients with atraumatic chest pain. DESIGN: A total of 110 patients admitted for the evaluation of atraumatic chest pain were examined. Forty-one of these patients were diagnosed with AMI. RESULTS: Five of the 41 patients with AMI had abnormally elevated myoglobin levels, whereas values of CK-MB and/or cardiac troponin I remained negative. Creatine kinase-MB mass alone had a sensitivity of 92.7%, a specificity of 89.9%, a positive predictive value of 84.4%, and a negative predictive value of 95.0% for the diagnosis of AMI. Cardiac troponin I alone had a sensitivity of 90.2%, a specificity of 95.7%, a positive predictive value of 92.5%, and a negative predictive value of 94.3% for the diagnosis of AMI. Cardiac troponin I is a more specific marker for the diagnosis of AMI than CK-MB, particularly in patients with chronic renal failure who are evaluated for chest pain. The combination of CK-MB and cardiac troponin I increased the sensitivity to 100% and the negative predictive value to 100% and had a specificity of 88.4% and a positive predictive value of 83.7%. The panel was diagnostic for all patients with AMI within 12 hours after admission. CONCLUSIONS: Our preliminary results indicate that this panel is highly effective for evaluation of AMI in patients with atraumatic chest pain. Elevated myoglobin levels were useful in detecting patients at high risk for AMI who initially were not detected with other markers. The combination of CK-MB and cardiac troponin I provided much higher sensitivity and had a much higher negative predictive value for the evaluation of AMI than cardiac troponin I or CK-MB alone. The 100% negative predictive value is particularly important because it indicates that patients with negative CK-MB and cardiac troponin I values 12 hours after admission have a negligible likelihood of AMI.     

Antiarrhythmic therapies for the prevention of sudden cardiac death

Despite remarkable advances in cardiovascular therapeutics, sudden cardiac death remains a significant problem. In this review, data from clinical trials and other studies on antiarrhythmic therapies have been evaluated in order to determine effective strategies for the prevention of sudden cardiac death in high risk patients. Overall, routine prophylactic use of class I antiarrhythmic agents in high risk patients, mostly survivors of acute myocardial infarction, is associated with increased risk of death [61 trials, 23,486 patients: odds ratio (OR) 1.13; 95% confidence interval (CI) 1.01 to 1.27, p < 0.05]. Conversely, beta-blockers are associated with highly significant reductions in risk of death in postinfarction patients (56 trials, 53,521 patients: OR 0.81; 95% CI 0.75 to 0.87, p < 0.00001). Overall data from the amiodarone trials on high risk patients, including postinfarction patients, patients with congestive heart failure or survivors of cardiac arrest, suggest that this agent is effective in reducing the risk of death (14 trials, 5713 patients: OR 0.83; 95% CI 0.72 to 0.95, p = 0.01) although further studies are needed to better define which types of patients will potentially benefit most from this agent. No benefits were seen with calcium channel blockers (26 trials, 21,644 patients: OR 1.03; 95% CI 0.94 to 1.13, p = NS). The implantable cardioverter-defibrillator is a promising option for high risk patients, but definition of its role awaits the completion of ongoing clinical trials. Since causes of sudden death are heterogeneous, the clinician should pursue a multifactorial approach to its prevention. Primary and secondary prevention of cardiac ischaemia, through the treatment of cardiovascular risk factors and maximising the use of aspirin, beta-blockers, lipid-lowering drugs, and angiotensin converting enzyme inhibitors after acute myocardial infarction, should lead to a future decrease in the incidence of sudden cardiac death.     

Insertion/deletion polymorphism in the angiotensin-converting enzyme gene and risk of and prognosis after myocardial infarction

OBJECTIVES: We sought to prospectively investigate whether genetic variation at the angiotensin-converting enzyme gene locus defined by an insertion (I)/deletion (D) polymorphism influences the risk of myocardial infarction or prognosis after infarction, or both. BACKGROUND: It has been suggested that the deletion allele of the angiotensin-converting enzyme gene, and specifically the DD genotype, may increase the risk of myocardial infarction, although previous studies have produced conflicting reports. No studies have yet examined the effect of I/D polymorphism on survival after infarction. METHODS: Angiotensin-converting enzyme genotypes in 684 patients with myocardial infarction recruited at the time of the acute event through coronary care units in two centers were compared with those of 537 control subjects recruited from the base populations. All patients were followed up to assess the impact of the angiotensin-converting enzyme genotype on prognosis. RESULTS: We found no difference (p = 0.89) in the genotype distribution between patients and control subjects (patients DD 31%, ID 47%, II 22%; control subjects DD 30%, ID 48%, II 22%). The odds ratio for myocardial infarction for DD compared with II/ID genotype adjusted for age, gender and center was 1.16 (95% confidence interval [CI] 0.82 to 1.65, p = 0.44). The study had 90% power to detect a 1.5-fold increase in risk of myocardial infarction associated with the DD genotype. For one center, data were available for other risk factors (hypertension, diabetes, angina, previous myocardial infarction, smoking, body mass index, total and high density lipoprotein cholesterol) in both patients and control subjects. In a stepwise logistic regression analysis the odds ratio for DD versus ID/II genotypes remained nonsignificant (1.44, 95% CI 0.84 to 2.46, p = 0.20) for these subjects. Over a median follow-up period of 15 months (range 3 to 22), 155 patients (22.7%) died. There was no difference in mortality between subjects with the DD genotype and those with ID/II genotypes. (21.8% vs. 23.1%, p = 0.25). Likewise, there was no difference in the distribution of survival times in the two groups (p = 0.62). The study had 70% power to detect a 1.5-fold increase in mortality during follow-up associated with the DD genotype. CONCLUSIONS: We conclude that in the groups studied, genetic variation at the angiotensin-converting enzyme gene locus defined by I/D polymorphism does not significantly influence either the risk of or the short- to medium-term prognosis after myocardial infarction.