Chest sonography in the diagnosis of pulmonary embolism: a comparison with MRI angiography and ventilation perfusion scintigraphy.

AIM: To compare the diagnostic performance of chest sonography, MRI angiography and ventilation/perfusion intigraphy in pulmonary embolism (PE). METHOD: In a prospective clinical study, 55 patients (41 women, 14 men, age 23 - 91 years) with clinical signs of PE were investigated within 48 hours of the onset of symptoms. The final diagnosis was made by MRI angiography (reference method). RESULTS: PE was diagnosed in a total of 36 patients. Chest sonography revealed rounded or wedge-shaped hypoechoic lesions in 30 patients. On ventilation/perfusion (V/P) scintigraphy, 41 patients had positive V/P scans, but only 23 were of high probability. Chest ultrasound had a positive predictive value of 97 % to diagnose PE. The sensitivity, specificity, the negative predictive value and accuracy were 81 %, 84 %, 84 % and 82 %, respectively. As 18 patients had inconclusive scans, the diagnostic performance of ventilation/perfusion scintigraphy was poor. The positive predictive value, sensitivity and specificity were 58 %, 42 % and 91 %, respectively. Patients in whom PE was excluded mainly suffered from congestive heart failure, bronchopulmonary infections or pulmonary hypertension. CONCLUSION: A negative sonographic study cannot rule out PE with certainty. However, a chest sonography is of acceptable diagnostic value in patients with suspected PE and may be used as an adjunct or guide to more established methods.

Lung sonographic findings in patients with suspected pulmonary embolism.

PURPOSE: To assess the feasibility and diagnostic performance of lung transthoracic sonography in patients with suspected pulmonary embolism. METHOD: In a prospective clinical study we compared sonographic findings of the peripheral lung with various scintigraphic gradings and D-dimer plasma concentrations. One hundred and nineteen consecutive patients with clinical signs of pulmonary embolism were investigated within 24 hours of the onset of symptoms. RESULTS: Seventy patients with suspected pulmonary embolism (59%) had sonographic lesions, which were echo poor, homogeneous and rounded or wedge-shaped with a hyperechoic reflexion in the centre. Of the patients with high-probability scintigraphic scans 86% had such sonographic lesions as had 79% with intermediate, 64% with low-probability and 33% with normal scintigraphic scans. Of the patients with positive sonographic findings and normal or low-probability scans only a minority (14%) had negative D-dimer tests. CONCLUSION: We found a high rate of specific sonographic lesions in patients with suspected pulmonary embolism when investigating the peripheral lung with ultrasound.

Rebound increase of plasminogen activator inhibitor type I after cessation of thrombolytic treatment for acute myocardial infarction is independent of type of plasminogen activator used.

Plasma concentrations of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor type 1 (PAI-1), and D-dimer were investigated in 50 patients treated intravenously for acute myocardial infarction with either streptokinase (n = 23), urokinase (n = 17), or recombinant t-PA (rt-PA, n = 10). The fibrinolytic variables were measured by enzyme immunoassay on admission; 1, 2, 4, 6, 8, 12, and 24 h later; and then daily until day 7 after admission. In each subgroup of patients treated with different thrombolytic agents, PAI-1 increased significantly (P < 0.01) approximately 3 h after cessation of thrombolytic therapy. PAI-1 peak concentrations did not differ significantly (P = 0.82) among these three subgroups. t-PA and D-dimer did not differ significantly (P > 0.14) among subgroups except for higher t-PA in the rt-PA group attributable to detection of the therapeutically administered exogenous rt-PA by the t-PA assay. Our findings demonstrate a marked PAI-1 increase after thrombolytic therapy for acute myocardial infarction, which seems to be a common, drug-independent antifibrinolytic rebound phenomenon in response to thrombolytic treatment.

The prognostic significance of coma-rating, duration of anoxia and cardiopulmonary resuscitation in out-of-hospital cardiac arrest.

Early determination of outcome after successful prehospital cardiopulmonary resuscitation (CPR) is a common problem with great ethical, economic, social, and legal consequences. We prospectively investigated 112 adult patients who had been resuscitated after out-of-hospital cardiac arrest (CA). The aim of our study was to determine whether coma rating by the mobile intensive care unit (MICU) is a useful tool for outcome prediction. For neurological assessment the Innsbruck Coma Scale (ICS) was used initially and after return of spontaneous circulation (ROSC) or 20-30 min after the start of CPR, before any sedating drugs were given. The duration of anoxia and CPR were determined with the automatically recorded emergency call protocol of the dispatch centre and the protocol of the MICU. For estimation of cerebral outcome at the time of discharge from hospital we used the Glasgow-Pittsburgh Cerebral Performance Categories (CPC). Restoration of spontaneous circulation was achieved in 42 patients (37%), and 15 (13%) were discharged from hospital. The first coma rating performed immediately at the time of arrival on scene had no significant prognostic value for prediction of neurological outcome (P = 0.204) and survival (P = 0.103). The second coma rating (performed after ROSC or 20-30 min after the start of CPR), however, demonstrated a significant correlation with neurological outcome (P = 0.0000) and survival (P = 0.0000), a correlation which was comparable to both duration of anoxia and duration of CPR. In patients with out-of-hospital cardiac arrest prognostic information could be obtained with the ICS as early as 20-30 min after the start of cardiopulmonary resuscitation.

Markers of activated coagulation for early diagnosis of acute myocardial infarction.

Intracoronary thrombosis plays a key role in the pathogenesis of acute myocardial infarction (AMI), and the formation of an occlusive thrombus usually precedes the development of myocardial damage. Therefore we evaluated and compared the early sensitivities of thrombin-antithrombin III complex (TAT), D-dimer, myoglobin, creatine kinase (CK) MB mass concentration, and cardiac troponin T (cTnT) on admission to a coronary care unit (CCU) before heparin or thrombolytic therapy was started. We investigated 31 consecutive patients admitted to CCU for evolving AMI within 6 hours from the onset of infarct-related symptoms; the median delay from chest pain onset to CCU admission was 135 minutes. Of all biochemical markers tested TAT had the highest early sensitivity on admission to the CCU, and TAT was significantly more sensitive than cTnT, CKMB mass, myoglobin, and D-dimer. However, TAT increases give no information about the location of clot formation in the body, and the diagnosis of AMI must be subsequently verified by an increase in more cardiac specific proteins, such as troponins or CKMB.

Usefulness of a new rapid bedside troponin T assay in patients with chest pain.

We evaluated the usefulness of a rapid, qualitative, bedside immunoassay for cardiac-specific troponin T in patients with chest pain. A concordant result between quantitative troponin T and qualitative troponin T assay was observed in 183 (96%) tests. The sensitivity of the rapid troponin T assay for detecting acute myocardial infarction increased significantly according to the number of hours elapsed after onset of chest pain from 17% for patients presenting within 4 h to 71% for patients presenting in the time interval of greater than 8 h from onset of chest pain (P < 0.001). Specificity ranged from 83 to 93% in the three time intervals evaluated. A concordant result between CK-MB-measurement and rapid troponin T assay was observed in 159 (83%) tests. In 14/191 tests a positive rapid troponin T and a negative CK-MB assay was observed. In 9/14 (64%) cases this result was true positive for the rapid troponin T assay and in 5/14 (36%) cases false negative. As sensitivity and specificity of the rapid troponin T assay are comparable with CK-MB measurements, rapid troponin T assay is a simple and useful laboratory tool for the bedside triage in patients with chest pain.

Cardiac troponin I in the diagnosis of myocardial injury and infarction.

We used a cardiospecific enzymoimmunometric assay to measure cardiac troponin I (cTnI) in samples serially drawn from 78 patients with acute myocardial infarction (AMI), 7 patients with unstable angina (Braunwald class III), 22 multi-traumatized patients, and in 30 athletes after eccentric exercise, as well as in 101 non-traumatic chest pain patients on admission to the emergency department. cTnI assay crossreactivity with crude human skeletal muscle homogenates was < 0.1%. cTnI could not be detected in athletes or multi-traumatized patients except for 2 trauma patients with myocardial damage. Increased cTnI concentrations were found in 6 of 7 patients with unstable angina at rest and in all AMI patients. After AMI, cTnI increased about 3.5 h (median) after the onset of chest pain, reached peak values parallel to CKMB, and stayed increased for at least 4 days. Cardiac troponin T (cTnT) increased and mostly peaked parallel to cTnI. cTnT sensitivity on the 7th day after AMI was significantly higher than that of cTnI. In contrast to cTnI, cTnT mostly showed a second, usually smaller, peak about day 4 after AMI. During the first 4 h after the onset of chest pain and before thrombolytic therapy the sensitivities of myoglobin (0.43) and CKMB mass (0.56) were significantly higher than those of both troponins (cTnI, 0.29; cTnT, 0.25). Areas under receiver operator characteristic curves indicated only moderate diagnostic accuracies of bio-chemical markers for early AMI diagnosis in non-traumatic chest pain patients that cTnI is a highly sensitive and specific marker for myocardial damage which is suitable for early and late diagnosis.

A decision tree for the early diagnosis of acute myocardial infarction in nontraumatic chest pain patients at hospital admission.

STUDY OBJECTIVE: To find an accurate algorithm for the diagnosis of acute myocardial infarction in nontraumatic chest pain patients on presentation to the emergency department. DESIGN: In a prospective clinical study, we compared the diagnostic performances of clinical symptoms, presenting ECG, creatinine kinase, creatine kinase MB activity and mass concentration, myoglobin, and cardiac troponin T test results of hospital admission blood samples. By classification and regression trees, a decision tree for the diagnosis of acute myocardial infarction was developed. SETTING: Emergency room of a Department of Internal Medicine (University Hospital). PATIENTS: One hundred fourteen nontraumatic chest pain patients (median delay from onset of chest pain to hospital admission, 3 h; range, 0.33 to 22): 26 Q-wave and 19 non-Q-wave myocardial infarctions, 49 patients with unstable angina pectoris, and 20 patients with chest pain caused by other diseases. MEASUREMENTS AND RESULTS: Of each parameter taken by itself, the ECG was tendentiously most informative (areas under receiver operating characteristic plots: 0.87 +/- 0.04 [ECG], 0.80 +/- 0.08 [myoglobin], 0.80 +/- 0.04 [creatine kinase MB mass], 0.77 +/- 0.04 [creatine kinase activity], 0.69 +/- 0.06 [clinical symptoms] 0.67 +/- 0.06 [creatine kinase MB activity], 0.67 +/- 0.05 [troponin T]). In patients presenting 3 h or less after the onset of chest pain, ECG signs of acute transmural myocardial ischemia were the best discriminator between patients with and without myocardial infarction. In patients presenting more than 3 h, however, creatine kinase MB mass concentrations (discriminator value, 6.7 micrograms/L) were superior to the ECG, clinical symptoms, and all other biochemical markers tested. This algorithm for diagnosing acute myocardial infarction was superior to each parameter by itself and was characterized by 0.91 sensitivity, a 0.90 specificity, a 0.90 positive and negative predictive value, and a 0.90 efficiency. CONCLUSIONS: We found an algorithm that could accurately separate the myocardial infarction patients from the others on admission to the emergency department. Therefore, this classifier could be a valuable diagnostic aid for rapid confirmation of a suspected myocardial infarction.

Cardiac troponin I release correlates with myocardial infarction size.

Cardiac troponin I, creatine kinase, and creatine kinase MB activity were tested in serial blood samples from 15 patients with first-time Q wave acute myocardial infarction (2 anterior and 13 inferior wall infarctions). All patients received intravenous thrombolytic therapy. Cardiac troponin I and creatine kinase MB activity were compared with scintigraphic estimates of myocardial scar (single photon emission computed tomography [SPECT] with 99mTechnetium-isonitrile [Tc-sestamibi]) on late images at rest about 5 weeks after myocardial infarction. Scintigraphic defect sizes ranged from 3.2 to 41.2% (median: 27.3%) of left ventricle. Cardiac troponin I increased and peaked in parallel with creatine kinase MB activity, and the peak values correlated with each other (r = 0.76, p = 0.002). Troponin I stayed increased for several days longer than creatine kinase and creatine kinase MB activity. It could be detected at least until the 4th day after admission. Significant correlation coefficients were found between 99mTc-isonitrile defect sizes and areas under cardiac troponin I curves (r = 0.53, p = 0.042) and between 99mTc-isonitrile defect sizes and cumulative creatine kinase MB activity release (r = 0.64, p = 0.01). Animal studies have already shown a very close correlation between histologic infarct size and SPECT 99mTc-isonitrile defect size. Therefore, our results indicate that cardiac troponin I release in patients with acute myocardial infarction is also correlated with infarct size.

Equivalent early sensitivities of myoglobin, creatine kinase MB mass, creatine kinase isoform ratios, and cardiac troponins I and T for acute myocardial infarction.

Early sensitivities of creatine kinase (CK), CKMB (activity and mass), CKMM and CKMB isoform ratios, myoglobin, cardiac troponin I (cTnI), and cardiac troponin T (cTnT) were compared to find the most sensitive serum marker for acute myocardial infarction (AMI) during the first hours after onset of chest pain. In a prospective study we investigated 37 consecutive patients with AMI who were admitted to the coronary care unit within 4 h after onset of chest pain. Blood samples were drawn every hour for the first 10 h after admission. CKMB mass concentrations, CKMM and CKMB isoform ratios, myoglobin, cTnI, and cTnT increased significantly (P < or = 0.0067) earlier than CK and CKMB activity and were also significantly (P < or = 0.046) and markedly more sensitive on admission. Differences in early sensitivities of myoglobin, CKMB mass, CK isoform ratios, cTnI, and cTnT were small and not significant. Therefore, turnaround time and practicality for emergency determination of methods, specificities of markers, the required specificity in the individual patient, and costs mainly determine the choice among myoglobin, CKMB mass, CK isoforms, cTnI, and cTnT.

Immunoenzymometric assay of human glycogen phosphorylase isoenzyme BB in diagnosis of ischemic myocardial injury.

With a new immunoenzymometric assay we measured human glycogen phosphorylase isoenzyme BB (GPBB) in 116 healthy individuals, 14 patients with stable angina, 107 nontraumatic chest pain patients on admission to the emergency department [45 acute myocardial infarction (AMI), 49 unstable angina, 13 other diseases], and in serial samples from 41 AMI patients. GPBB was compared with creatine kinase (CK), CKMB mass, myoglobin, and cardiac troponin T. Receiver-operating characteristic plots demonstrated the significantly greater (P < or = 0.012) discriminatory power of GPBB to detect acute ischemic coronary syndromes compared with all other tested markers. GPBB was the most sensitive marker for detection of AMI during the first 4 h after onset of chest pain, and only GPBB was increased above the upper reference limit (7 micrograms/L) on admission in patients who had unstable angina at rest and reversible ST-T alterations. This and the high early sensitivity of GPBB are most likely explained by its function as a key enzyme of glycogenolysis.

Rapid accurate diagnosis of acute myocardial infarction in patients with non-traumatic chest pain within 1 h of admission.

BACKGROUND: Accurate diagnosis of impending acute myocardial infarction (AMI) in patients presenting at an emergency department with acute chest pain is essential for proper triage and treatment. We have developed an algorithm for the early diagnosis of AMI. METHODS: The diagnostic performances of ECG, creatine kinase (CK) and creatine kinase isoenzyme MB (CKMB) activities, CKMB mass, myoglobin, and cardiac troponin T (cTnT) were compared for early diagnosis of AMI in 60 non-traumatic chest pain patients (22 AMI, 29 unstable angina, nine other diseases) on presentation to an internal medicine emergency department and 1 h thereafter. The classification and regression trees method was used for data analysis and revealed the following results. RESULTS: In patients with electrocardographic signs of acute transmural myocardial ischaemia on admission (mostly regional ST-segment elevations), biochemical markers could not improve the diagnostic accuracy either on admission or 1 h later. By contrast, in patients with non-diagnostic ECG, CKMB mass concentration measured 1h after admission was the best discriminator between AMI and non-AMI patients (discriminator value 5.8 micrograms/l) and was superior to ECG and all other biochemical markers tested. This algorithm for diagnosing AMI is characterized by 96% sensitivity, 90% specificity, 84% positive predictive value, 97% negative predictive value, 92% accuracy, 0.05 negative likelihood ratio, and 9.1 positive likelihood ratio. CONCLUSION: The classification procedure obtained allows accurate rapid and early diagnosis of AMI and could therefore be a valuable diagnostic aid to physicians of emergency medicine.

Early determination of neurological outcome after prehospital cardiopulmonary resuscitation.

BACKGROUND AND PURPOSE: Although there are various methods of determining neurological prognosis after cardiopulmonary resuscitation, the final outcome of patients often remains unclear for quite a long time. METHODS: We investigated 30 consecutively admitted patients who had been successfully resuscitated by the team of the local mobile intensive care unit after cardiac arrest. Determinations of the period of anoxia and of the cardiopulmonary resuscitation time, clinical investigation, echocardiography, electroencephalography, evoked potentials, magnetic resonance imaging, and magnetic resonance spectroscopy were performed. RESULTS: Demonstration of brain lactate in proton magnetic resonance spectroscopy (P < .01) and absent N20 waves in short-latency somatosensory evoked potentials (P < .01) proved to be significant in terms of a poor prognosis. Correlations between both duration of anoxia and cardiopulmonary resuscitation time and neurological outcome could be shown as well (both P < .05). CONCLUSIONS: Proton magnetic resonance spectroscopy and short-latency evoked potentials are of great benefit in the prognostic evaluation after cardiopulmonary resuscitation.

Cyclic phenomena in early myocardial infarction.

It has been shown by a number of authors that early myocardial infarction constitutes a dynamic process of cyclic oscillation between coronary occlusion and spontaneous coronary reopening. Infarct-markers, such as ST-segment elevation, serum-creatine kinase isoenzyme MB, the atrionatriuretic peptide (ANP) and serum-myoglobin (Mb) exhibit cyclic behaviour pattern during early AMI and thus reflect episodes of intermittent, spontaneous reperfusion. The latter have recently been verified by angiography. The mechanism underlying the phenomena seen in early myocardial infarction is likely to be based on a constant vasoconstrictive stimulus, deriving from aggregating platelets. The vasoconstriction subsequent to platelet aggregation produces an initial episode of myocardial ischemia. This episode is followed by a hypoxia of the artery wall. Reactive coronary dilation secondary to ischemia is than promoted by the release of vasoactive by-products of anaerobic glycolysis as well as changes in the open propability of certain transmembrane ion channels. Thereafter, the initial coronary occlusion is interrupted by transient vasodilation. A wave of reperfusion follows and leads to reoxygenation and wash-out of ischemia-induced vasodilative components as well as biochemical markers. The vasoconstrictive forces then take over again. This results in repeated waves of reperfusion. A number of arguments in favour of this concepts are discussed in this paper.

Different time courses of cardiac contractile proteins after acute myocardial infarction.

For the first time we have compared time courses of cardiac myosin light chain-1 (MLC-1), beta-type myosin heavy chain (MHC), troponin T (TnT), myoglobin, creatine kinase (CK) and CKMB in the same patients with acute myocardial infarction (AMI). Blood samples were serially collected in 23 patients with first-time AMI. All but 3 patients received intravenous thrombolytic treatment. TnT and MLC-1 time courses were biphasic in most patients and showed two distinct peaks in 13 and 8 patients, respectively. MHC time courses were usually monophasic. Only 1 patient showed a biphasic MHC time course with two distinct peak values. Although MHC and MLC were lower by about the fourth day after onset of AMI in early reperfused patients, reperfusion did not qualitatively alter MLC and MHC release (no significant influence on the first appearance in blood or on time to peak). MLC and MHC peaks correlated closely (r = 0.75, P = 0.0001), whereas TnT peaks were correlated less closely with MLC or MHC peaks (r = 0.58 each, P < 0.007). Peak values of all cardiac contractile proteins correlated closely and significantly with CKMB peaks (0.75 < or = r < or = 0.81, P < or = 0.0006). Myoglobin was the first marker to increase in blood after AMI and showed the earliest peaks, whereas MHC increased latest showing the latest peaks. TnT increased significantly (P = 0.0001) earlier than MLC and MHC. These results can be explained by the impact of the intracellular compartmentation of a cardiac protein on the rapidity with which it is released after AMI.

Concentration time courses of troponin and myosin subunits after acute myocardial infarction.

BACKGROUND: As a result of the limited sensitivity and specificity of creatine kinase and lactate dehydrogenase (LDH) as well as their isoenzymes, there is increasing interest in the use of cardiac contractile proteins for the diagnosis of acute myocardial infarction (AMI) and myocardial damage. METHODS: This study compared the release of creatine kinase, creatine kinase MB, myoglobin, cardiac troponin I (cTnI), cardiac troponin T (cTnT), cardiac myosin light chain-1 (cMLC-1), and beta-type myosin heavy chains (bMHC) in serial blood samples from 13 patients (10 men, three women; median age 54 years, range 40-74 years) with first-time AMI (11 Q-wave, two non-Q-wave AMI; three anterior and 10 inferior wall AMI). All but one patient received intravenous thrombolytic treatment. RESULTS: Myoglobin was the first marker to increase in blood after AMI and showed the earliest peak levels, whereas bMHC increased latest, showing the latest peak levels. cTnI and cTnT increased significantly earlier than cMLC-1 and bMHC. cTnI and cTnT increased and reached peak levels parallel to each other, but the latter tended to stay increased longer. cTnT time courses were biphasic in the majority of AMI patients, unlike cTnI time courses. cMLC-1 release was mostly biphasic. cMLC-1 allows diagnosis during the acute phase as well as several days after the onset of AMI. The time courses of bMHC were usually monophasic. Its delayed appearance makes it useful for the diagnosis of remote infarction. In contrast to cTnI and cTnT, cMLC-1 and bMHC time courses were not significantly influenced by early reperfusion. CONCLUSION: Our results demonstrate the impact of the intracellular compartmentation of an intramyocardial protein (cytosolic, structurally bound, or structurally bound with soluble pool) on its concentration time course after AMI, particularly on the rapidity of its release.

Early release of glycogen phosphorylase in patients with unstable angina and transient ST-T alterations.

OBJECTIVE: To determine whether transient ST-T alterations in patients with unstable angina are associated with an increase in plasma glycogen phosphorylase BB concentrations on admission to hospital. DESIGN: Prospective screening of patients with unstable angina for markers of myocardial cell damage. SETTING: Accident and emergency department of university hospital. PATIENTS: 48 consecutive patients admitted for angina pectoris (18 with transient ST-T alterations). None of the patients had acute myocardial infarction according to standard criteria. MAIN OUTCOME MEASURES: Creatine kinase and creatine kinase MB activities, creatine kinase MB mass concentration, and myoglobin, cardiac troponin T, and glycogen phosphorylase BB concentrations on admission. RESULTS: All variables except for creatine kinase and creatine kinase MB activities were significantly higher on admission in patients with unstable angina and transient ST-T alterations than in patients without. However, glycogen phosphorylase BB concentration was the only marker that was significantly (p = 0.0001) increased above its discriminator value in most patients (16). In the 18 patients with transient ST-T alterations creatine kinase MB mass concentration and troponin T and myoglobin concentrations were significantly (p = 0.0001) less commonly increased on admission (in five, three, and two patients, respectively). CONCLUSIONS: The early release of glycogen phosphorylase BB may help to identify high risk patients with unstable angina even on admission to an emergency department. Glycogen phosphorylase BB concentrations could help to guide decisions about patient management.

Bone mineral densitometry in dialyzed patients: quantitative computed tomography versus dual photon absorptiometry.

Reduced bone mineral density (BMD) increases risk of fractures, thus making it necessary to monitor patients suffering from chronic renal failure and consecutive disturbance of bone metabolism. In order to evaluate the reliability of available methods, bone mineral density of the lumbar spine assessed with single energy computed tomography (QCT) was compared with bone mineral density of the lumbar spine, femoral neck, Ward's triangle and trochanteric region measured by dual energy photon absorptiometry (DPA) in 45 hemodialyzed patients with a mean hemodialysis duration of 35 +/- 26 months (SD). Depending on the measurement site and method 4-34% of dialyzed patients suffered from reduced BMD (z-score < -2). The highest correlation (r = 0.61, p < 0.01) was found between QCT of the spine, trabecular bone, and DPA of Ward's triangle. One year after baseline measurement bone mineral density was reassessed after randomization to either QCT or DPA in 14 and 18 patients, respectively. Whereas lumbar spine and femoral neck did not change, mean BMD showed a decrease at the measurement sites of Ward's triangle (DPA), trochanteric region (DPA) and trabecular bone of the spine (QCT), which, however, was statistically not significant. Cortical BMD of the spine assessed with QCT showed an increase. Although there is some reduction in bone density at most sites in hemodialyzed patients, no significant bone loss could be demonstrated over the course of 1 year.