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Sequential risk stratification using TIMI risk score and TIMI flow grade among patients treated with fibrinolytic therapy for ST-segment elevation acute myocardial infarction.

In the setting of ST-segment elevation myocardial infarction (STEMI), the Thrombolysis In Myocardial Infarction (TIMI) risk score (TRS) and indexes of epicardial and myocardial perfusion are associated with mortality. The association between TRS at presentation and angiographic indexes of epicardial and myocardial perfusion after reperfusion therapy has not been investigated. We hypothesized that TRS, TIMI flow grade (TFG), and TIMI myocardial perfusion grade (TMPG) would provide independent prognostic information and that angiographic indexes of poor flow and perfusion would be associated with a higher TRS. TRS and angiographic data were evaluated in 3,801 patients from the TIMI 4, 10A, 10B, 14, 20, 23, and 24 trials. Within each TRS stratum (TRS 0 to 2, 3 to 4, >/=5), 30-day mortality increased stepwise among patients with impaired TFG at 60 minutes after fibrinolytic administration. In a multivariate model adjusting for the TRS strata, impaired TMPG (0/1) was independently associated with higher mortality (odds ratio 2.28, p = 0.018). In a multivariate model adjusting for the TFG and infarct location, the likelihood of impaired TMPG (0/1) was greater among intermediate-risk (TRS 3 to 4) and high-risk (TRS >/=5) patients than among low-risk (TRS 0 to 2) patients (odds ratio 1.43, p = 0.019 and 1.50, p = 0.055, respectively). Thus, impaired epicardial flow and myocardial perfusion are independently associated with increased 30-day mortality among patients identified by TRS as high risk, although there is no synergism between either TFG or TMPG and TRS. High TRS at presentation is associated with abnormal myocardial perfusion, even after adjusting for possible confounders.

Aged↗

Usefulness of procainamide challenge for electrophysiologic arrhythmia risk stratification.

Among 58 consecutive patients who underwent electrophysiologic testing for risk assessment and who subsequently received a third-generation implantable cardioverter-defibrillator, 39 had ventricular tachycardia induced in the baseline state and 19 had ventricular tachycardia induced only after administration of intravenous procainamide, increasing the yield of electrophysiologic risk assessment by 49%. At follow-up, ventricular arrhythmias requiring implantable cardioverter-defibrillator termination occurred in 14 of 39 patients inducible in the baseline state and in 7 of 19 patients inducible only with intravenous procainamide. The provocative use of intravenous procainamide during electrophysiologic risk assessment increases the detection rate for risk of sustained ventricular arrhythmias with no loss of positive predictive value.

Aged↗

Preoperative risk stratification for endovascular surgery using pharmacologic stress myocardial imaging.

To stratify perioperative cardiac risk for endovascular surgery, pharmacologic stress single-photon emission computed tomography (SPECT) was performed in 206 patients. Of 8 patients who had cardiac events, 7 occurred in 67 patients with positive SPECT results, whereas only 1 occurred in 139 patients with negative SPECT results (7 of 67 vs 1 of 139, p <0.002). Furthermore, a scintigraphic marker of a summed stress score >/=14 was the most important factor identifying patients who subsequently had cardiac events by multivariate analysis.

Aged↗

Validation of peak exercise oxygen consumption and the Heart Failure Survival Score for serial risk stratification in advanced heart failure.

The Heart Failure Survival Score (HFSS) and peak exercise oxygen consumption (VO2) accurately assess mortality in ambulatory patients who have advanced heart failure and are referred for initial cardiac transplant evaluation. We investigated the prognostic value of the HFSS and peak VO2 when applied serially to these patients. This study included 227 adults (mean age +/- SD 52 +/- 10 years old) who presented for reevaluation >60 days after initial evaluation (352 +/- 238 days). The HFSS was determined from mean arterial blood pressure, heart rate, left ventricular ejection fraction, serum sodium, peak VO2, heart failure etiology, and width of QRS complex. Survival without reevaluation, United Network of Organ Sharing 1 transplant, or left ventricular assist device was determined by the Kaplan-Meier method with censoring at United Network of Organ Sharing 2 transplant. Survival differed by HFSS stratum (p <0.001) and by peak VO2 stratum (p <0.001). Patients whose HFSS or peak VO2 deteriorated from low risk to medium or high risk had lower survival rates than did patients whose values remained at low risk (p <0.01 and p <0.001, respectively). Patients who started at medium or high risk and improved to low risk tended to have higher survival rates than those who remained medium or high risk (p = 0.06 and p <0.16, respectively). Patients who improved to low risk had a 1-year survival rate of 72% for HFSS and peak VO2. However, patients who improved to low risk and were treated with beta blockers had a 1-year survival rate (89% for HFSS and 83% for peak VO2) comparable to that after transplant (84%). Peak VO2 and the HFSS can be successfully used for serial evaluation of mortality risk in ambulatory patients who have advanced heart failure.

Adult↗

Efficacy of myocardial contrast echocardiography in the diagnosis and risk stratification of acute coronary syndrome.

We examined the hypothesis that myocardial contrast echocardiography (MCE) is superior to conventional electrocardiographic, echocardiographic, and troponin I criteria for the diagnosis of acute coronary syndrome. We prospectively enrolled 114 consecutive patients (60+/-10 years of age, 73 men) who presented to the emergency room with chest pain on exertion and at rest. Exclusion criteria included an age<40 years, presence of Q wave or ST-segment elevation, and a poor echocardiographic window. Echocardiography and MCE were performed to assess regional wall motion abnormalities (RWMAs) and myocardial perfusion defects by using continuous infusion of perfluorocarbon-exposed sonicated dextrose albumin. Acute coronary syndrome was confirmed in 87 patients. There were no deaths; 46 patients had acute myocardial infarction, and 41 patients required urgent revascularization. On multiple logistic regression analysis, myocardial perfusion defect (odd ratio 87, p<0.001) was the only independent variable for diagnosing acute coronary syndrome. Myocardial perfusion defect (odd ratio 21, p=0.001) and troponin I levels (odd ratio 3, p=0.009) were independent predictors for acute myocardial infarction. The sensitivity of myocardial perfusion defect for diagnosing acute coronary syndrome was 77%, which is significantly higher than the sensitivities of ST change, troponin I increase, and RWMA (28%, 34%, and 49%, respectively), with similar specificities of 85% to 96%. In conclusion, MCE is more sensitive than the currently used electrocardiographic and troponin I criteria, and evaluation of myocardial perfusion defect by MCE complements RWMA analysis by conventional echocardiography for accurate diagnosis of acute coronary syndrome.

Acute Disease↗

Triiodothyronine levels for risk stratification of patients with chronic heart failure.

PURPOSE: We sought to explore the use of triiodothyronine (T(3)) concentrations as an adjunct to clinical and functional parameters when estimating prognosis in patients with chronic heart failure. METHODS: We enrolled 281 patients with postischemic (n = 153) or nonischemic (n = 128) dilated cardiomyopathy. Total and free T(3) concentrations, and traditional clinical and functional cardiac parameters, were measured 2 to 5 days after hospital admission. A multivariate model was utilized to predict all-cause and cardiac mortality. RESULTS: All-cause mortality was 23% (n = 64) after a mean (+/-SD) of 12 +/- 7 months of follow-up; 47 (73%) of the patients died from cardiac causes. The mean ejection fraction was lower in those patients who died than in those who survived (26% +/- 8% vs. 31% +/- 8%, P < 0.001), as were levels of total T(3) (1.0 +/- 0.4 nmol/L vs. 1.3 +/- 0.3 nmol/L, P < 0.001) and free T(3) (3.2 +/- 1.4 pmol/L vs. 3.7 +/- 1.0 pmol/L, P < 0.001). In a multivariate model, ejection fraction (odds ratio [OR] = 2.0 per 10% decrease; 95% confidence interval [CI]: 1.4 to 2.8 per 10% decrease; P < 0.001) and total T(3) level (OR = 0.3 per 1-nmol/L increase; 95% CI: 0.1 to 0.5 per 1-nmol/L increase; P < 0.001) were the only independent predictors of all-cause mortality. In an alternative model using free T(3) levels, ejection fraction (OR = 1.9; 95% CI: 1.4 to 2.7; P < 0.001) and free T(3) level (OR = 0.6 per 1 pmol/L; 95% CI: 0.5 to 0.8 per 1 pmol/L; P <0.02) were associated with all-cause mortality. When we considered cardiac mortality alone, male sex (OR = 3.5; 95% CI: 1.7 to 13; P < 0.04), ejection fraction (OR = 1.7; 95% CI: 1.2 to 2.5; P < 0.006), and total T(3) level (OR = 0.3; 95% CI: 0.2 to 0.7; P < 0.002) were independent predictors with the multivariate model. CONCLUSION: Low T(3) levels are an independent predictor of mortality in patients with chronic heart failure, adding prognostic information to conventional clinical and functional cardiac parameters.

Aged↗

The impact of B-type natriuretic peptide in addition to troponin I, creatine kinase-MB, and myoglobin on the risk stratification of emergency department chest pain patients with potential acute coronary syndrome.

STUDY OBJECTIVE: The emergency department (ED) evaluation of chest pain patients with potential acute coronary syndrome is limited by the initial sensitivity of cell injury markers. BNP is increased during myocardial ischemia and is associated with adverse outcomes. We determine whether the addition of B-type natriuretic peptide (BNP) to troponin I, creatine kinase-MB (CK-MB), and myoglobin increases the sensitivity and negative predictive value (NPV) for acute myocardial infarction, acute coronary syndrome, and 30-day adverse events among chest pain patients with potential acute coronary syndrome. METHODS: A convenience sample of patients aged 30 years or older and presenting to an urban academic ED with nontraumatic chest pain, thus prompting an ECG, was enrolled, and consent was obtained. Blood samples were drawn at 0 and 90 minutes. Thirty-day follow-up was performed for all enrolled patients. Main outcomes were acute myocardial infarction, acute coronary syndrome, and 30-day events (death, acute myocardial infarction, or revascularization). BNP cutoffs were derived from receiver operator characteristics curves. The sensitivity, specificity, positive predictive value (PPV), and NPV with 95% confidence intervals (CIs) were calculated with and without BNP. Differences in sensitivity and specificity with the addition of BNP were calculated with 95% CIs, and McNemar's test was performed to compare sensitivities and specificities. RESULTS: Four hundred twenty-six patients were enrolled and analyzed. The cohort was 54.7+/-13.9 years old, 47.7% men, and 63.5% black. The outcomes were acute myocardial infarction, 39 (9.2%), acute coronary syndrome, 101 (23.7%), and 30-day adverse cardiovascular events 52 (12.2%). BNP cutoffs derived were 51, 31, and 31 pg/mL for acute myocardial infarction, acute coronary syndrome, and 30-day events, respectively. The addition of BNP showed increased sensitivity at the cost of decreased specificity for all 3 outcomes, as follows: (1) acute myocardial infarction: sensitivity: 87.2% (95% CI 72.6% to 95.7%) to 97.4% (95% CI 86.5% to 100%), difference 10.3% (95% CI-0.2% to 24.6%), P=.125; specificity: 62.3% (95% CI 57.2% to 67.1%) to 47.8% (95% CI 42.7% to 52.9%), difference 14.5% (95% CI 11.1% to %18.4), P<.0001; (2) acute coronary syndrome: sensitivity: 75.2% (95% CI 65.7% to 83.3%) to 88.1% (95% CI 80.2% to 93.7%), difference 12.9% (95% CI 7.0% to 21.0%), P=.0002; specificity: 68.0% (95% CI 62.6% to 73.0%) to 48.6% (95% CI 43.1% to 54.2%), difference 19.4% (95% CI 15.2% to 24.1%), P<.0001; (3) 30-day events: sensitivity: 71.2% (95% CI 56.9% to 82.9%) to 88.5% (95% CI 76.6% to 95.7%), difference 17.3% (95% CI 7.7% to 30.3%), P=.004; specificity: 61.8% (95% CI 56.6% to 66.7%) to 43.9% (95% CI 38.8% to 49.0%), difference 17.9% (95% CI 14.2% to 22.2%), P<.0001. There were trends toward increased NPV and decreased PPV for all outcomes, and the addition of BNP achieved a NPV of 99.5% (95% CI 97.0% to 100%) compared with 98.0% (95% CI 95.3% to 99.3%) for acute myocardial infarction. CONCLUSION: The addition of BNP as a dichotomous test to troponin I, CK-MB, and myoglobin produces increased sensitivity at a cost of decreased specificity for acute myocardial infarction, acute coronary syndrome, and 30-day adverse events. Because of this tradeoff, BNP cannot be recommended for use among all ED chest pain patients. However, the improved sensitivity may make this test useful in selected cohorts when the decreased specificity is less important.

Angioplasty, Balloon, Coronary↗

Cardiac troponin T levels for risk stratification in pediatric open heart surgery.

BACKGROUND: Cardiac troponin T has been found to be accurate predictor of complications and adverse clinical events after pediatric cardiac surgery. Contrary to adult cardiac surgery, the relationship of troponin T to patient survival after pediatric heart surgery has not been previously studied. The purpose of this study was to determine whether troponin T could predict death after pediatric open cardiac surgery. METHODS: This was a retrospective cohort study in which data from 1001 consecutive children having cardiac surgery during a 5-year period were studied. Perioperative variables that could influence death at 30 postoperative days were evaluated. RESULTS: Multivariate analysis, using a forward stepwise logistic regression, showed that troponin T measured on the first postoperative day was a strong independent predictor of death at 30 days. Level of troponin T greater than 5.9 microg/L on the first postoperative day predicted death (odds ratio, 10.7; 95% confidence interval: 5.2 to 22.1) as did admission lactate level greater than 5.2 mmol/L (odds ratio, 22.2; 95% confidence interval: 9.7 to 50.8) No other variable, including postoperative creatine kinase-MB mass concentration, age, diagnosis, surgical procedure, presence of cyanosis, chromosomal anomaly or ventriculotomy, duration of cardiopulmonary bypass, or aortic cross-clamp, had any independent effect on 30-day survival. CONCLUSIONS: Cardiac troponin T level on the first postoperative day is a powerful independent risk marker of death in pediatric cardiac surgery.

Cardiac Surgical Procedures↗

Microarray studies of prognostic stratification and transformation of follicular lymphomas.

Follicular lymphoma (FL) is a common, indolent malignancy with a natural history of transformation to the more aggressive form of diffuse large B-cell lymphoma (DLBCL) in 25-60% of cases. In order to understand the pathogenesis of lymphoma genesis and evolution, the molecular changes characteristic of FL and transformed DLBCL are being studied. The most common abnormality associated with FL is the t(14;18)(q32;q21) chromosomal translocation, but many more molecular aberrations have been found in patient subgroups. The study of gene expression profiling using DNA microarrays enables large scale, comparative analyses of gene expression. Its implementation in the research on FL has led to advances in disease diagnosis and classification and has the potential to lead to pathogenesis-based individualised therapies.

Cell Transformation, Neoplastic↗

The role of age in neuroblastoma risk stratification: the German, Italian, and children's oncology group perspectives.

Recent evidence suggests that the cut-off for age utilized in neuroblastoma risk groups should be increased from the 365-day cut-off currently in use. Separate cooperative group analyses were performed by German and Italian groups and two analyses by the Children's Oncology Group (North America, Australia, New Zealand, Switzerland, Netherlands). In general, the results are in agreement regarding the prognostic contribution of age. There is strong evidence to support an increase in the age cut-off to a value in the range of 15-18 months based on the results from the German analysis and two COG analyses. However, Italian results in INSS stage 4 patients show that outcome in patients 12-17 months is not better than that of older patients. Further analyses are warrented.

Age Factors↗

Superoxide dismutase activity in adriamycin-induced cardiotoxicity in humans: a potential novel tool for risk stratification.

BACKGROUND: Oxidative stress has been implicated in Adriamycin cardiotoxicity experimentally. We evaluated whether changes in systemic markers of antioxidant reserve occur and are associated with left ventricular (LV) dysfunction during Adriamycin use in humans. METHODS AND RESULTS: We prospectively evaluated oncology patients eligible for Adriamycin chemotherapy. Blood samples for enzymatic (erythrocyte superoxide dismutase activity [SOD-U SOD/mg protein]) and nonenzymatic antioxidants (total radical trapping antioxidant potential [TRAP-U of Trolox/microL plasma]) were collected at baseline (B), intermediate (I), and final (F) cycles. LV ejection fraction (LVEF) was assessed by radionuclide ventriculography. Fifty-one patients (49 +/- 12 years, 90% female) underwent 5.9 +/- 0.9 chemotherapy cycles and received 301 +/- 52 mg/m 2 of Adriamycin. LVEF decreased from 61 +/- 6% (B) to 56 +/- 7% (F) ( P < .001), but only 6 (12%) patients developed significant LV systolic dysfunction (LVEF < 50%). SOD activity increased significantly during treatment (4.5 +/- 1.8 [B], 6.0 +/- 2.1 [I], 5.6 +/- 2.2 [F]; P < .01), whereas TRAP values were unchanged. Baseline SOD activity from patients who developed LV systolic dysfunction was significantly higher than from those who maintained normal LVEF (5.9 +/- 1.8 versus 4.3 +/- 1.7; P < .05). In multivariate analysis, baseline SOD levels remained independently associated with LV dysfunction ( P = .05). CONCLUSION: Erythrocyte SOD activity increases after Adriamycin treatment and high baseline levels predicts Adriamycin-induced cardiotoxicity in humans.

Antibiotics, Antineoplastic↗

Risk stratification of chest pain patients by point-of-care cardiac troponin T and myoglobin measured in the emergency department.

A prospective multicenter study including 1410 chest pain patients with suspected acute coronary syndromes was carried out to examine the predictive value of biological cardiac markers for adverse events measured by a point-of-care system. Admission cardiac troponin T (cTnT) and myoglobin were measured in parallel on a point-of-care system in the emergency department and -- together with CK-MB mass -- on lab analyzers. In a one-year follow-up, cardiac and non-cardiac death, acute myocardial infarction, unstable angina pectoris and need for revascularization were registered. Median time between onset of symptoms and admission was 285 min; 172 patients (12.2%) had no event during follow-up. If the cTnT, measured either by the point-of-care system or a conventional lab analyzer, was >0.05 microg/L, then the chance of a cardiac event during the follow-up period was doubled (18% vs. 9%). Serial cTnT measurement did not add any further value to the predictive power of the admission cTnT. Myoglobin and CK-MB mass identified increasing risk with increasing concentration quartiles; cardiac event rates were 2.8- to 4.4-fold higher between the quartiles with the lowest and those with the highest analyte concentration, respectively. There was no difference in non-cardiac death rates between any concentration quartiles. In conclusion, the prediction of clinical events by cardiac troponin T and myoglobin measured with a point-of-care analyzer in the emergency department was as good as that of the same cardiac markers and CK-MB mass measured on lab analyzers.

Aged↗

Analytical performance of the Synchron LX20 Pro, BN trade mark II and IMMAGE high sensitivity C-reactive protein assays and concordance in cardiovascular risk stratification.

BACKGROUND: C-reactive protein (CRP) can provide valuable prognostic information for risk of cardiovascular events. Several automated high sensitivity CRP immunoassays are currently available for risk assessment. METHODS: The analytical performance of the Synchron LX20 Pro, BN II and IMMAGE high sensitivity CRP assays were evaluated and concordance within cardiovascular risk tertiles was examined for 529 serum samples. RESULTS: All three assays exhibited satisfactory between-run imprecision based on CVs< or =9.0% over a wide range of CRP concentrations. The LX20 Pro and BN II were linear over an extensive measuring range, whereas the IMMAGE exhibited a slight deviation from linearity producing results with a positive bias at CRP levels between 0.7 and 2.6 mg/l. Moderately hemolyzed samples interfered with the LX20 Pro and IMMAGE CRP assays, whereas moderate lipemia interfered with the BN II. Correlation studies revealed that the LX20 Pro and IMMAGE produced results 8.2% lower and 5.1% lower, respectively, compared with the BN II. There was good agreement among methods for cardiovascular risk assessment. CONCLUSIONS: All three CRP assays exhibited acceptable analytical performance for cardiovascular risk assessment. Although results by the LX20 Pro and IMMAGE were lower than the BN II, there was good agreement within each cardiovascular risk assessment tertile.

Animals↗

Mild and moderate aortic stenosis. Natural history and risk stratification by echocardiography.

AIMS: To define the natural history and predictors of outcome in mild and moderate aortic stenosis (AS). METHODS AND RESULTS: One hundred and seventy-six consecutive asymptomatic patients (73 women, age 58+/-19 years) with mild to moderate AS (jet velocity 2.5 to 3.9m/s) were followed for 48+/-19 months. Haemodynamic progression and clinical outcome was analysed. Event-free survival with end-points defined as death (n=34) or aortic valve surgery (n=33), was 95+/-2%, 75+/-3% and 60+/-5% at 1, 3 and 5 years, respectively. Both, cardiac and non-cardiac mortality were significantly increased, resulting in a 1.8 times higher mortality than expected (P<0.005). By multivariate analysis, moderate to severe aortic valve calcification, coronary artery disease (CAD) and peak jet velocity were independent predictors of outcome. Event-free survival for patients with moderate or severe valve calcification was 92+/-4%, 61+/-7% and 42+/-7% at 1, 3 and 5 years versus 100%, 90+/-4% and 82+/-5% for patients with no or mild calcification. Patients with calcified aortic valves, CAD or with an event had a significantly faster haemodynamic progression. Of 129 patients with a follow-up echocardiographic exam, 59 (46%) developed severe stenosis during follow-up. CONCLUSION: Outcome of mild and moderate AS is worse than commonly assumed. Rapid progression and excess mortality have to be considered. Significant valve calcification, CAD and rapid progression of aortic jet velocity indicate poor outcome. Patients with these characteristics may require closer follow-up than generally assumed.

Aged↗