Prognostic factors in infective endocarditis in general hospitals in the Netherlands.

INTRODUCTION: Despite advances in treatment, infective endocarditis (IE) still ranks amongst the most lethal infectious diseases. We sought to determine prognostic factors in general hospitals in the Netherlands as research in this setting is scarce. RESULTS: Between 2004 and 2011, we identified 216 cases of IE, 30.1 % of which were prosthetic valve IE. This leads to an annual incidence of IE of 5.7 new cases per 100,000 persons per year. Women were less likely to undergo surgical intervention (OR = 1.96, 95 % CI 1.06-3.61, p = 0.031). Also, ageing was an independent prognostic factor for not receiving surgery in a multivariate analysis (annual OR = 1.04, 95 % CI 1.02-1.06, p < 0.001). Female sex was a prognostic factor for mortality (OR = 2.35, 95 % CI 1.29-4.28, p = 0.005). Age was also an independent prognostic factor for mortality (OR = 1.05, 95% CI 1.03-1.08, p < 0.001). Conservative treatment was a prognostic factor for mortality (OR = 3.39, 95 % CI 1.80-6.38, p < 0.001) whereas surgical intervention was an independent prognostic factor for adverse events (OR = 3.03, 95% CI 1.64-5.55, p < 0.001). Staphylococcus aureus was an independent prognostic factor for adverse events (OR = 2.05, 95 % CI 1.10-3.84, p = 0.024) but not for mortality. CONCLUSION: This study shows that endocarditis in general hospitals has a high rate of morbidity and mortality. Even when treated, it ranks as one of the most lethal infectious diseases in the Netherlands, especially in women and the elderly.

Neuronal dysfunction in heart failure assessed by cardiac 123-iodine metaiodobenzylguanidine scintigraphy.

In patients with chronic heart failure, increased sympathetic activity and cardiac sympathetic neuronal dysfunction are present and have been related to unfavourable clinical outcome. Modification of these alterations with the objective to improve prognosis has become an important aim of pharmacological therapy for these patients. A noninvasive technique to assess sympathetic neuronal function at the cardiac level may be valuable in evaluating newly developed therapeutic strategies. 123-iodine metaiodobenzylguanidine can be used to visualize cardiac sympathetic nerve function and activity. Single photon emission computerized tomographic is preferred to planar scintigraphy since it does not depend on superposition of other anatomical structures and may allow assessment of regional cardiac 123-iodine metaiodobenzylguanidine uptake. Although the quantitation of cardiac uptake in these tomographic images has several limitations, the use of the left ventricular cavity as a reference, calibrated by the 123-iodine activity in a blood sample drawn at the time of acquisition, may have clinical applications, with respect to the evaluation of therapeutical intervention in patients with heart failure.

Increased myocardial [123I]-metaiodobenzylguanidine uptake after enalapril treatment in patients with chronic heart failure.

OBJECTIVE: To assess non-invasively the effect of enalapril on cardiac sympathetic neuronal uptake function in patients with congestive heart failure, by using [123I]-metaiodobenzylguanidine (MIBG), which is a noradrenaline analogue. Cardiac MIBG uptake was visualised by single photon emission tomography (SPET). In addition, plasma noradrenaline concentration, indicating systemic sympathetic activity, was measured to see whether it was related to cardiac MIBG uptake. DESIGN: Consecutive patients were treated with enalapril and served as their own controls. SETTING: Cardiac unit of a tertiary care centre. PATIENTS: 23 Patients with chronic, mild to moderate, stable congestive heart failure, and a left ventricular ejection fraction less than 40%. Heart failure was caused by ischaemic heart disease or was idiopathic. INTERVENTIONS: Cardiac MIBG SPET was performed and plasma noradrenaline concentration was measured before and after 6 weeks treatment with enalapril. MAIN OUTCOME MEASURES: Cardiac uptake of MIBG was measured by using the left ventricular cavity and a venous blood sample as a reference. RESULTS: Cardiac uptake of MIBG increased significantly after enalapril treatment, indicating improved cardiac neuronal uptake function. Plasma noradrenaline concentration did not decrease significantly. Cardiac MIBG uptake was not related to plasma noradrenaline concentration. CONCLUSIONS: Cardiac MIBG SPET can be used to assess changes in cardiac sympathetic neuronal uptake function caused by pharmacological intervention. Enalapril seemed to improve cardiac sympathetic neuronal uptake function but did not significantly affect plasma noradrenaline concentrations in a group of patients with predominantly moderate heart failure. These results accord with the hypothesis that restoration of cardiac neuronal uptake of noradrenaline is one of the beneficial effects of enalapril in such patients.

Quantitation of myocardial iodine-123 MIBG uptake in SPET studies: a new approach using the left ventricular cavity and a blood sample as a reference.

In patients with chronic heart failure increased sympathetic activity is related to unfavourable prognosis. Since myocardial iodine-123 metaiodobenzylguanidine ([123I]MIBG) uptake is related to myocardial noradrenaline content, i.e. cardiac sympathetic activity, measurement of myocardial [123I]MIBG uptake may be of clinical use in determining prognosis or the effect of pharmacological intervention in these patients. The aim of the present study was to evaluate a new method to quantitate myocardial [123I]MIBG uptake with respect to reproducibility and accuracy. Eighteen [123I]MIBG planar and single-photon emission tomographic (SPET) studies of patients with chronic heart failure were evaluated. Myocardial uptake was calculated from the myocardial (MYO) to left ventricular cavity (C) count density ratio and the 123I activity in a blood sample. This was performed employing planar LAO images, a single-slice SPET method using the midventricular myocardial short-axis slice, and finally a multi-slice SPET method analysing semi-automatically drawn volumes of interest (VOIs). The accuracy of the multi-slice SPET method was verified using a cardiac phantom. The planar method was found to be reproducible [intra- and interobserver coefficients of variation (IACV and IRCV) were 0.025 and 0.012 respectively] but the mean MYO/C count density ratio was only 1.31 +/- 0.16 as a consequence of overprojection. For the single-slice SPET method IACV was 0.2 and IRCV was 0.13, representing poor reproducibility. For the multi-slice SPET method IACV was 0.051, IRCV was 0.047 and the mean MYO/C count density ratio was 5.4 +/- 2.42. Accuracy was 81% at a true MYO/C count density ratio of 6 in the phantom. It is concluded that the multi-slice SPET method using the left ventricular cavity VOI and a blood sample as a reference is a reproducible and accurate method for assessing myocardial [123I]MIBG uptake.

Exclusion of acute myocardial infarction. The value of measuring creatine kinase slope.

For the exclusion (and diagnosis) of acute myocardial infarction, we studied timed sequential (slope) measurements of creatine kinase and creatine kinase-MB catalytic activity concentration, creatine kinase-MB mass concentration, troponin T and myoglobin, using data from 242 patients consecutively admitted for evaluation of suspected acute myocardial infarction in the 12 hours before admission. Three biochemical strategies based on measurements in two consecutive samples obtained within 12 hours after admission were evaluated. The highest sensitivities were encountered for a biochemical strategy based on the sole measurement of creatine kinase mass concentration (98%) or troponin T (96%) and a strategy based on measurements of creatine kinase activity concentrations, which includes creatine kinase slope calculation and measurement of creatine kinase mass concentration (95%). Both strategies were applied in subgroups of patients based on the electrocardiographic findings. In patients with a normal electrocardiogram, the sensitivity of the strategy using sole measurements of creatine kinase mass concentration was 100%, but this was true for the strategy based on creatine kinase slope measurements, which is the cheaper and therefore preferred procedure for excluding myocardial infarction. This approach, however, does not account for detecting minor myocardial cell damage in patients not yet fulfilling the criteria of the World Health Organization for diagnosing acute myocardial infarction.

Assessment of anthracycline-related myocardial adrenergic derangement by [123I]metaiodobenzylguanidine scintigraphy.

Myocardial adrenergic neuron integrity and function were evaluated in 21 patients who had received doxorubicin or epirubicin for various malignancies. Myocardial uptake of iodine-123 metaiodobenzylguanidine ([123I]MIBG), a marker suitable for the study of myocardial neuron injury, was calculated from planar scintigraphic images after 4 h and the washout between 15 min and 4 h. In 13 patients with normal left ventricle ejection fraction (LVEF) analysed at three cumulative dose levels (no, low and middle dose), [123I]MIBG uptake tended to be significantly impaired (z = -2.772, P = 0.0056), at higher cumulative dose levels, before significant LVEF changes were observed. [123I]MIBG values were considerably decreased in 2/7 patients investigated at low cumulative dose and in 3/8 cases at the middle dose level. On follow-up, 1 of these patients, who had normal LVEF after completion of chemotherapy but whose [123I]MIBG values had progressively deteriorated during anthracycline therapy, subsequently developed congestive heart failure; another patient, whose [123I]MIBG values were impaired at the middle dose level, developed persistent reduced LVEF 5 months after completing therapy. In 8 patients, who had developed persistently, reduced LVEF at high doxorubicin cumulative dose levels, [123I]MIBG, performed in the period after chemotherapy discontinuation, was invariably abnormal. These data suggest that myocardial adrenergic derangement plays a role in anthracycline-associated cardiotoxicity: its appearance, even at low cumulative anthracycline dose levels, may reflect impairment of the intravesicular norepinephrine storage by incipient anthracycline-associated cardiac neuron injury. [123I]MIBG scintigraphy may be useful to assess myocardial adrenergic derangement during and in the follow-up of anthracycline therapy and potentially detect patients who are at risk.

Usefulness of indium-111 antimyosin scintigraphy in confirming myocardial injury in patients with anthracycline-associated left ventricular dysfunction.

BACKGROUND: In patients with cardiac dysfunction due to anthracycline-induced myocyte damage, continuation of anthracyclines carries a high risk, and modification of chemotherapy is thus indicated. The condition, however, must be distinguished from other causes of cardiac dysfunction, e.g., the transient negative inotropic effect which may accompany and follow the intravenous administration of anthracyclines. In the present study the efficacy of 111In-antimyosin in confirming myocyte injury and its potential applicability in differentiating causes of cardiac dysfunction during anthracycline therapy are evaluated. PATIENTS AND METHODS: Twenty-seven patients with asymptomatic left ventricle ejection fraction (LVEF) decrease (median LVEF 47%, range 38%-50%) during chemotherapy with anthracyclines (dose range 100-700 mg/m2 doxorubicin or equivalent) were subsequently studied with 111In-antimyosin cardiac scintigraphy. The degree of myocardial uptake, an indicator of heart muscle cell injury, evaluated both visually and quantitatively by means of heart-to-lung ratios (HLR) obtained from 48-hour planar images, was analyzed in relation to the further clinical and LVEF course. The results were also compared with 111In-antimyosin data from 5 patients who had normal LVEF during chemotherapy and 5 patients who had received no anthracyclines. The distribution pattern of myocardial uptake was assessed by means of single photon emission computed tomography (SPECT). RESULTS: a) Fourteen patients presented with persistent LVEF decrease (median LVEF 42.5%, range 32%-47%) after discontinuation of anthracycline therapy. In 11 of these patients intense and diffuse, as shown by SPECT, cardiac uptake of 111In-antimyosin (HLR 1.87-2.45) was observed. In two patients with intense antimyosin cardiac uptake, spurious HLR values (1.23-1.55) were found which were caused by unexpected lung uptake and focal heart uptake, respectively. All patients with intense cardiac 111In-antimyosin uptake showed persistently decreased LVEF on follow-up (4-26 weeks) and 4 of them subsequently developed congestive heart failure. In another patient with no intense uptake (HLR 1.15) and persistent decrease in LVEF, metastatic cardiac involvement was found. b) In 13 patients with improvement or normalisation of the LVEF (median LVEF 53%, range 51%-63%), generally less intense or slight cardiac uptake (HLR range: 1.20-1.88) was seen; the HLR in these patients, who continued chemotherapy without complications, was consistently lower (p < 0.01) than in patients with persistently decreased LVEF, and comparable to values of patients who had normal LVEF. CONCLUSIONS: 111In-antimyosin scintigraphy can be useful to differentiate cardiac dysfunction caused by severe myocardial injury from temporary decreases in LVEF, without severe concomitant myocyte damage, which may occur during anthracycline therapy. Intense myocardial uptake of 111In-antimyosin can be used as an important confirmatory criterium for the clinical decision to discontinue anthracycline therapy.

Contribution of creatine kinase MB mass concentration at admission to early diagnosis of acute myocardial infarction.

OBJECTIVE: To assess the diagnostic value at admission of creatine kinase MB mass concentration, alone or in combination with electrocardiographic changes, in suspected myocardial infarction. DESIGN: Prospective study of all consecutive patients admitted within 12 hours after onset of chest pain to a coronary care unit for evaluation of suspected myocardial infarction. SETTING: Large regional hospital. PATIENTS: In 297 patients creatine kinase and creatine kinase MB activities and creatine kinase MB mass concentration were determined. Myocardial infarction according to the criteria of the World Health Organisation was diagnosed in 154 patients and excluded in 143 patients (including 70 with unstable angina pectoris). RESULTS: Sensitivity/specificity for creatine kinase MB mass concentration in patients admitted within 4 hours and 4-12 hours after onset of chest pain were 45%/94% and 76%/79% respectively. Corresponding values for creatine kinase activity were 20%/89% and 59%/83%, and for creatine kinase MB activity 16%/87% and 53%/87%. Raised creatine kinase MB mass concentration was seen in 17% of patients with unstable angina pectoris. Stepwise logistic regression analysis showed that independent predictors of acute myocardial infarction in patients admitted within 4 hours after onset of chest pain were electrocardiographic changes and creatine kinase MB mass concentration on admission; in patients admitted 4-12 hours after the onset of pain independent predictors were electrocardiographic changes and creatine kinase MB mass concentration and activity. CONCLUSION: Creatine kinase MB mass concentration is a more sensitive marker for myocardial infarction than the activity of creatine kinase and its MB isoenzyme. Electrocardiographic changes on admission in combination with creatine kinase MB mass concentration (instead of creatine kinase and creatine kinase MB activities) are best in diagnosing myocardial infarction.

Troponin T and myoglobin at admission: value of early diagnosis of acute myocardial infarction.

We studied the predictive power at admission of troponin T and myoglobin and compared them with that of CK and CK-MB activity and ECG in 290 consecutive patients admitted for evaluation of a suspected AMI. The likelihood ratio for an ischaemic ECG at admission < 4 h (between 4 and 12 h) after onset of chest pain was 2.85 (1.92), for a inconclusive ECG 1.53 (1.98) and for a normal ECG 0.27 (0.35). In patients admitted < 4 h after onset of chest pain, the likelihood ratio for abnormal and normal myoglobin concentrations (8.06 and 0.67) was considerably better for detection of AMI as defined by the WHO criteria than for the other markers, including the ECG. In patients admitted 4-12 h after onset of chest pain, the likelihood ratios for abnormal and normal myoglobin concentrations were 4.88 and 0.42; for troponin T 3.11 and 0.31; for CK activity 3.44 and 0.49 and for CK-MB activity 4.08 and 0.54 respectively. The sensitivity for troponin T (64%) was better than that of the other markers but its specificity (74%) was worse, because in patients with unstable angina troponin T was frequently elevated (37%). Stepwise logistic regression analysis showed that the best predictors of AMI within 4 h after onset of chest pain were the ECG and myoglobin and between 4-12 h after onset of chest pain the ECG, CK-MB activity and myoglobin.

The mass concentrations of serum troponin T and creatine kinase-MB are elevated before creatine kinase and creatine kinase-MB activities in acute myocardial infarction.

The time-related frequency of elevated results for the mass concentrations of the MB isoenzyme of creatine kinase and of troponin T were compared with that of creatine kinase and creatine kinase-MB activity in patients with acute myocardial infarction. Patients (322; 175 with and 147 without myocardial infarction) consecutively admitted for evaluation of possible acute myocardial infarction were investigated. Reference limits for troponin T (0.1 microgram/l) and creatine kinase-MB mass concentration (5.0 micrograms/l) were exceeded frequently in patients with unstable angina pectoris (troponin T 43%, creatine kinase-MB mass concentration 24%) in contrast to patients with no acute ischaemic heart disease (both < 5%). Within 4 and between 4-8 hours after onset of chest pain, the frequency of elevated results for creatine kinase-MB mass concentration and troponin T in patients with acute myocardial infarction was considerably higher (20-30%) than for creatine kinase and creatine kinase-MB activity. Creatine kinase-MB mass concentration and troponin T both allowed earlier diagnosis of acute myocardial infarction than creatine kinase and creatine kinase-MB activity, but troponin T was not elevated before the creatine kinase-MB mass concentration.

Failure of new biochemical markers to exclude acute myocardial infarction at admission.

In a substantial proportion of patients with suspected myocardial infarction, biochemical markers are needed for clinical decision-making at the time of admission, because electrocardiographic (ECG) recordings are inconclusive. We have assessed the usefulness for exclusion of myocardial infarction at admission of the newer markers creatine kinase MB (CK-MB) mass concentration, troponin T, and myoglobin in comparison with the routinely used markers creatine kinase (CK) and CK-MB activity. 290 consecutive patients were enrolled. Acute myocardial infarction was diagnosed on the basis of clinical history, ECG criteria, and time-dependent changes in CK and CK-MB activity. 153 patients had definite acute myocardial infarction. Troponin T had the highest sensitivity for prediction of acute myocardial infarction; high concentrations (above the upper reference limits) were found in 98 (64%) of the patients with infarctions compared with 92 (60%) for CK-MB mass concentration, 76 (50%) for myoglobin, 61 (40%) for CK activity, and 53 (35%) for CK-MB activity. However, troponin T also had the highest "false-positive" rate; of 137 patients without myocardial infarction, 36 (26%) had high troponin T concentrations. Sensitivity, specificity, and positive and negative predictive values were calculated in relation to time between onset of chest pain and hospital admission. Although CK-MB mass concentration was, by a small margin, the best marker in patients admitted within 8-10 h of onset of chest pain, all the markers had negative predictive values too low to allow exclusion of acute myocardial infarction at admission in patients with symptoms suggestive of myocardial infarction of less than 10 h duration.

Frequency of myocardial indium-111 antimyosin uptake after uncomplicated coronary artery bypass grafting.

The reported incidence of myocardial damage after coronary artery bypass grafting (CABG) is highly related to the methods used. Since indium-111 monoclonal antimyosin antibody scintigraphy has been shown to be highly specific and sensitive for myocardial necrosis, even in small lesions, uptake of this radiotracer was evaluated after CABG. In 23 consecutive patients without previous myocardial infarction who underwent CABG for stable angina, 80 MBq indium-111 antimyosin was injected on the third postoperative day. Planar images were obtained 48 hours later and analyzed for myocardial uptake of indium-111 antimyosin. Scintigraphic results were related to creatine kinase MB levels, duration of both aortic cross-clamping and cardiopulmonary bypass, and electrocardiographic changes. In all patients surgical procedure and postoperative course was uncomplicated. Indium-111 antimyosin uptake was present in 19 of 23 patients (82%). It was diffused in 7 patients and localized in 12. No pathologic Q waves occurred postoperatively. Fourteen patients exhibited ST-segment changes. No good relation was found among indium-111 antimyosin uptake and creatine kinase MB levels, duration of cross-clamping or bypass, and ST-T changes. It is concluded that some degree of myocardial damage, though silent, is common after CABG.

Early Indium-111 antimyosin scintigraphy for assessment of regional wall motion asynergy on discharge after myocardial infarction.

To assess the relation between early Indium-111 monoclonal antimyosin antibody scintigraphy and degree of regional asynergy on discharge, 38 patients with a first acute myocardial infarct were studied (18 anterior, 20 inferoposterior infarctions). In 21 patients thrombolytic therapy was administered. On the first day of myocardial infarction, 80 MBq Indium-111 Antimyosin was injected. Planar images, anterior, lateral and left anterior oblique, were made 24 hours later. Localized myocardial uptake was present in 37/38 patients, and was evaluated for Count Density Index (count density of infarct zone/left lung count density) in the left anterior oblique images, which displayed the infarct zone well. Regional asynergy on discharge was evaluated by cross-sectional echocardiography and defined mild (hypokinesia) or severe (akinesia or dyskinesia). Count density index was significantly lower in 15 patients with mild asynergy, compared with 22 patients with severe asynergy (1.61 +/- 0.25 vs. 2.42 +/- 0.40, p less than 0.001). This difference was present in both patient groups treated with or without thrombolysis. We conclude that early count density index, reflecting the amount of local necrosis, is highly correlated to the ultimate degree of wall motion impairment.

Predictive value of indium-111 antimyosin uptake for improvement of left ventricular wall motion after thrombolysis in acute myocardial infarction.

In 21 patients treated with thrombolysis for acute myocardial infarction (AMI), the degree of myocardial uptake of indium-111 monoclonal antimyosin antibodies injected within 24 hours after onset of AMI was compared with the degree and extent of regional asynergy on admission and discharge, as assessed by 2-dimensional echocardiography. On the first day of AMI, 80 MBq of indium-111 antimyosin was injected and planar images were made 24 hours later. Indium-111 antimyosin uptake was evaluated for count density index (count density of infarct zone/left lung count density) in the left anterior oblique projection, in which the infarction zone was well displayed in all patients. Using 2-dimensional echocardiography, the left ventricle was divided into 13 segments and evaluated for regional asynergy, which was considered severe (akinesia or dyskinesia) or mild (hypokinesia). The extent of regional asynergy was measured by the number of asynergic segments. All 21 patients had severe regional asynergy on admission. Nine of 21 showed only mild regional asynergy on discharge and 12 of 21 had persistent severe regional asynergy in at least 1 segment. The count density index was significantly lower in patients with mild regional asynergy on discharge compared with patients with severe regional asynergy (1.63 +/- 0.27 vs 2.50 +/- 0.42, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)