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Biomedical subjects

Allan S Jaffe

Publications and source records attributed to Allan S Jaffe.

At least 55 records · Page 3Linked to original sources

Biomarker responses during and after treatment with nesiritide infusion in patients with decompensated chronic heart failure.

BACKGROUND: Objective methods to assess the adequacy of medication therapy for patients with advanced heart failure are lacking. Serial measurements of biomarkers might be beneficial. Therapy guided by N-terminal pro-B-type natriuretic peptide (NT-proBNP) might be helpful because NT-proBNP should be lowered by therapies that decrease endogenous BNP secretion. METHODS: NT-proBNP and BNP were measured in a nonconsecutive patient cohort receiving clinically indicated intravenous nesiritide. Blood samples were drawn before, at 6 and 24 h during, and at 6 h after infusion. A reduction in NT-proBNP was defined as a decrease from baseline during infusion ("infusion responders") of >3 SD of the variability of the assay measurement (approximately 20%). Patients with decreases >20% in both NT-pro BNP and BNP at 6 h post infusion were designated "biochemical responders". RESULTS: Forty patients [27 males; mean (SE) age, 68 (2) years; mean (SE) left ventricular ejection fraction, 25 (1.4)%] were studied. All patients improved clinically. Overall, the changes in NT-proBNP were a 18 (4.6)% [mean (SE)] and 19.8% (median) decrease from baseline at 24 h of infusion and a 22 (6.0)% and 17.8% decrease at 6 h post infusion (P <0.001 compared with baseline). In a large number of patients, decreases in NT-proBNP were, however, within the variability of the assay. Subgroup analysis showed that 22 of 40 patients were infusion responders with a >20% decrease from baseline in NT-proBNP during nesiritide infusion, whereas only 12 patients were biochemical responders with >20% decreases from baseline postinfusion for both NT-proBNP and BNP. CONCLUSIONS: In this study, many patients had decreased NT-proBNP and BNP values after therapy with nesiritide, but the majority of patients did not demonstrate biochemically significant decreases in analytes despite a clinical response. Until we know more about the responses of natriuretic peptides to therapies such as nesiritide, a strategy of monitoring NT-proBNP and BNP to guide therapy cannot be universally advocated.

Aged↗

The quantification of infarct size.

We sought to summarize the published evidence regarding the measurement of infarct size by serum markers, technetium-99m sestamibi single-photon emission computed tomography (SPECT) myocardial perfusion imaging, and magnetic resonance imaging. The measurement of infarct size is an attractive surrogate end point for the early assessment of new therapies for acute myocardial infarction. For each of these three approaches, we reviewed reports published in English providing the clinical validation for the measurement of infarct size and the relevant clinical trial experience. The measurement of infarct size by serum markers has multiple theoretical and practical limitations. The measurement of troponin is promising, but the available data validating this marker are limited. Sestamibi SPECT imaging has five separate lines of published evidence supporting its validity and has received extensive study in multicenter trials. Magnetic resonance imaging has great promise but has less clinical validation and no multicenter trial experience. Therefore, SPECT sestamibi imaging is currently the best available technique for the quantitation of infarct size to assess the incremental treatment benefit of new therapies in multicenter trials of acute myocardial infarction.

Biomarkers↗

Impact of contemporary guideline compliance on risk stratification models for acute coronary syndromes in The Registry of Acute Coronary Syndromes.

We compared the predictive value of the Rush score with the Thrombolysis In Myocardial Infarction (TIMI) risk score in unselected patients with an acute coronary syndrome and evaluated the effect of compliance with established guidelines on the accuracy of these models. The Registry of Acute Coronary Syndromes is a retrospective registry of 3,754 consecutive patients (38% women; mean age 67 years) who presented with acute coronary syndrome to the emergency department between April 1, 1999, and December 31, 2000, at 9 hospitals. The primary end point was death, myocardial infarction, or urgent revascularization during hospitalization. Rush classification was based on quartiles of predicted risk of cardiac complication (<2% for class I vs >15% for class IV). The TIMI score was implemented as published. Compliance with guidelines for acute coronary syndrome was assessed with a 4-point scale based on the aggregate use of aspirin, beta blockers, heparin, and glycoprotein IIb/IIIa inhibitors. Fifteen percent of patients met the primary end point. The primary end point rates for TIMI scores 0/1, 2, 3, 4, 5, and 6/7 were 11%, 14%, 13%, 11%, 14%, and 12%, respectively (p = NS). The primary end point rates for Rush classes I, II, III, and IV were 6%, 8%, 9%, and 17%, respectively (p <0.001). After controlling for compliance with established guidelines, the odds ratio of an event increased by 46% for each unit increase in Rush score (p <0.001). After adjusting for the Rush score, the odds ratio decreased by 54% for each unit increase in compliance (p <0.001). Thus, compliance with current American College of Cardiology/American Heart Association guidelines significantly improves prognosis, regardless of the risk score. The use of established risk scores may overestimate event rates in unselected populations.

Adrenergic beta-Antagonists↗

Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: a staging system for primary systemic amyloidosis.

PURPOSE: Primary systemic amyloidosis (AL) is a multisystemic disorder resulting from an underlying plasma cell dyscrasia. There is no formal staging system for AL, making comparisons between studies and treatment centers difficult. Our group previously identified elevated serum cardiac troponin T (cTnT) as the most powerful predictor of overall survival. Others have reported that N-terminal pro-brain natriuretic peptide (NT-proBNP) is a valuable prognostic marker. We sought to develop a staging system for patients with AL. PATIENTS AND METHODS: Two hundred forty-two patients with newly diagnosed AL who were seen at the Mayo Clinic between April 1979 and November 2000, and who had echocardiograms and stored serum samples at presentation were eligible for this retrospective review. NT-proBNP measurements were performed on 242 patients in whom cTnT and cardiac troponin I (cTnI) had been previously run. Two prognostic models were designed using threshold values of NT-proBNP and either cTnT or cTnI (NT-proBNP < 332 ng/L, cTnT < 0.035 microg/L, and cTnI < 0.1 microg/L). Depending on whether NT-proBNP and troponin levels were both low, were high for only one level, or were both high, patients were classified as stage I, II, or III, respectively. RESULTS: Using the cTnT+NT-proBNP model 33%, 30%, and 37% of patients were stages I, II, and III, respectively, with median survivals of 26.4, 10.5, and 3.5 months, respectively. The alternate cTnI+NT-proBNP model predicted median survivals of 27.2, 11.1, and 4.1 months, respectively. CONCLUSION: Stratification of AL patients into three stages is possible with two readily available and reproducible tests setting the stage for more consistent and reliable cross comparisons of therapeutic outcomes.

Adult↗

Effect of doxorubicin plus cyclophosphamide on left ventricular ejection fraction in patients with breast cancer in the North Central Cancer Treatment Group N9831 Intergroup Adjuvant Trial.

PURPOSE: To evaluate changes in left ventricular ejection fraction (LVEF) after four cycles of adjuvant doxorubicin plus cyclophosphamide (AC) in women with human epidermal growth factor receptor 2-positive (node-positive or node-negative) breast cancer enrolled onto the North Central Cancer Treatment Group N9831 Intergroup Adjuvant Trial. PATIENTS AND METHODS: Patients were randomly assigned to receive standard doxorubicin (60 mg/m2) plus cyclophosphamide (600 mg/m2) every 3 weeks for four cycles followed by (1) weekly paclitaxel for 12 weeks; (2) weekly paclitaxel for 12 weeks, then weekly trastuzumab for 52 weeks; or (3) weekly paclitaxel plus trastuzumab for 12 weeks, then weekly trastuzumab for 40 weeks. LVEF was monitored before and after AC. RESULTS: Of the 1,576 eligible patients who completed AC, 1,458 had pre- and post-AC LVEF measurements taken using the same methodology (multiple-gated acquisition in 1,153 patients and echocardiogram in 305 patients). Among these 1,458 patients, 745 (51.1%) had < or = 15% decrease in LVEF and LVEF that remained at or above the radiologic lower limit of normal (LLN); 42 patients (2.9%) had < or = 15% decrease in LVEF and LVEF that decreased to or below the LLN; and 37 patients (2.5%) had an LVEF decrease of more than 15%. There was grade 2 LVEF toxicity in 96 (6.6%) of the 1,458 patients. CONCLUSION: Standard AC chemotherapy is associated with frequent decreases in LVEF, which are noted when measured 3 weeks after completion of the fourth cycle. Patients are being observed to determine the long-term significance of this and the potential impact on subsequent treatment options.

Adolescent↗

Clinical characteristics and thrombolysis in myocardial infarction frame counts in women with transient left ventricular apical ballooning syndrome.

The characteristics of 16 women with transient left ventricular (LV) apical ballooning syndrome in a United States population are presented. Additionally, Thrombolysis In Myocardial Infarction (TIMI) frame counts were evaluated during the acute period. Patients generally presented with anterior ST-elevation acute coronary syndrome in the absence of obstructive coronary disease. All patients had LV apical wall motion abnormalities. An acute emotional or physiologic stressor preceded most cases. TIMI frame counts were abnormal in all patients and often abnormal in all 3 major coronary vessels, suggesting that the diffuse impairment of coronary microcirculatory function may play a role in the pathogenesis of the syndrome.

Aged↗

Prognostication of survival using cardiac troponins and N-terminal pro-brain natriuretic peptide in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation.

Primary systemic amyloidosis (AL) is a fatal plasma cell disorder. Pilot data suggest survival is better in patients undergoing peripheral blood stem cell transplantation (PBSCT), but the selection process makes the apparent benefit suspect. We have reported that circulating cardiac biomarkers are the best predictors of survival outside of the transplantation setting. We now test whether cardiac troponins (cTnT and cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are prognostic in transplant recipients. In 98 patients with AL undergoing PBSCT, serum cardiac biomarkers were measured (cTnT, 98 patients; cTnI, 65 patients; and NT-proBNP, 63 patients). Elevated levels of cTnT, cTnI, and NT-proBNP were present in 14%, 43%, and 48% of patients, respectively. At 20 months median follow-up, median survival has not been reached for patients with values below the thresholds; in patients with values above the thresholds, median survival is 26.1 months, 66.1 months, and 66.1 months, respectively. Our previously reported risk systems incorporating these markers were also prognostic, notably the cTnT/NT-proBNP staging. Using this system, 49%, 38%, and 13% of patients were in stage I, stage II, and stage III, respectively. Determining levels of circulating biomarkers may be the most powerful tool for staging patients with AL undergoing PBSCT.

Adult↗

Timing of peak troponin T and creatine kinase-MB elevations after percutaneous coronary intervention.

STUDY OBJECTIVE: The prognostic significance of elevations in creatine kinase-MB and troponin T (cTnT), which have been conventionally measured 6 to 8 h after percutaneous coronary intervention (PCI), has been established. However, the time to peak biomarker appearance in the circulation has not been defined and is the purpose of this pilot study. DESIGN: Nonrandomized, nonconsecutive patient cohort. SETTING: Clinical practice, Mayo Clinic, Rochester, MN. PATIENTS: Cohort (n = 57) undergoing elective PCI. INTERVENTIONS: cTnT and creatine kinase (CK)-MB measured at baseline, 2 h, 4 h, 8 h, and > or = 2 h (mean +/- SEM, 18 +/- 5 h) after PCI. MEASUREMENTS AND RESULTS: Postprocedure cTnT elevations were detected in 30 of 57 patients (53%). Of these, 4 of 30 patients (13%) had peak cTnT at 4 h (0.80 +/- 0.40 ng/mL), 5 of 30 patients (17%) had peak cTnT at 8 h (1.07 +/- 0.48 ng/mL), and 21 of 30 patients (70%) had peak cTnT at > or = 12 h (0.21 +/- 0.06 ng/mL); 22 of 30 patients received abciximab. Elevations in CK-MB occurred in 14 of 57 patients (25%). Of these, 3 of 14 patients (21%) demonstrated peak CK-MB at 2 h (18.5 +/- 7.9 ng/mL) and the remainder (11 of 14 patients, 79%) during the 12- to 20-h interval (20.2 +/- 4.4 ng/mL); 12 of 14 patients received abciximab. CONCLUSION: More cTnT than CK-MB elevations occur after PCI; however, both biomarkers demonstrate a longer time to peak value than anticipated in clinical practice. Early surveillance monitoring (< 12 h) does not detect peak biomarker levels, especially in patients with normal baseline values. If peak levels are to be used to determine prognosis, then longer time intervals should be used for post-PCI surveillance. The timing of peak elevations appears to be influenced by baselines values as well. Early elevations may reflect the conjoint effects of injury associated with the disease process and the intervention itself. These data suggest that a re-evaluation of surveillance monitoring to account for the variability reported and the influence of baseline elevations of biomarkers may improve the prognostic power of the measurements.

Aged↗

Cardiac troponin T in obstructive sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with nocturnal angina and ST-segment depression, which are relieved by treatment with continuous positive airway pressure (CPAP). We tested the hypothesis that severe nocturnal hypoxia in patients with OSA causes myocyte necrosis as evidenced by increases in cardiac troponin T. DESIGN: Prospective cohort study. SETTING: Cardiovascular physiology and sleep research laboratory. PARTICIPANTS: Fifteen male volunteers with coronary artery disease (CAD) and moderate or severe OSA (apnea-hypopnea index [AHI] > 15). MEASUREMENTS AND RESULTS: Polysomnography and measurement of serum cardiac troponin T before sleep, after 4 h of untreated OSA, and in the morning after 4 h of treatment with CPAP. The mean AHI for the group was 41 (SD 16), and the mean oxygen saturation nadir during sleep was 83% (SD 8%). All measurements of cardiac troponin T were < 0.010 ng/mL. CONCLUSIONS: Despite the fact that some patients with OSA may experience nocturnal ischemia, this study shows that patients with severe OSA and coexisting CAD do not have nightly episodes of myocardial injury detectable by the current-generation cardiac troponin T assay.

Aged↗

Depression as a risk factor for mortality after acute myocardial infarction.

The ENRICHD clinical trial, which compared an intervention for depression and social isolation to usual care, failed to decrease the rate of mortality and recurrent acute myocardial infarction (AMI) in post-AMI patients. One explanation for this is that depression was not associated with increased mortality in these patients. The purpose of this study was to determine if depression was associated with an increased risk of mortality in a subsample of the ENRICHD trial's depressed patients compared with a group of nondepressed patients recruited for an ancillary study. Three hundred fifty-eight depressed patients with an acute AMI from the ENRICHD clinical trial and 408 nondepressed patients who met the ENRICHD medical inclusion criteria were followed for up to 30 months. There were 47 deaths (6.1%) and 57 nonfatal AMIs (7.4%). After adjusting for other risk factors, depressed patients were at higher risk for all-cause mortality (hazard ratio 2.4, 95% confidence interval 1.2 to 4.7) but not for nonfatal recurrent infarction (hazard ratio 1.2, 95% confidence interval 0.7 to 2.0) compared with nondepressed patients. In conclusion, depression was an independent risk factor for death after AMI, but it did not have a significant effect on mortality until nearly 12 months after the acute event, nor did it predict nonfatal recurrent infarction.

Aged↗

Survival in patients with primary systemic amyloidosis and raised serum cardiac troponins.

Patients with primary systemic amyloidosis that affects the heart have a poor outlook. Cardiac troponins T and I (cTnT, cTnI) are highly specific and sensitive biomarkers of myocardial injury. Values of these troponins provide quantitative information about the disease. We retrospectively assessed 261 patients newly diagnosed as having primary systemic amyloidosis. Median survival for patients with detectable cTnT and cTnI (6 and 8 months, respectively), was worse than that for those with undetectable values (22 and 21 months, respectively). Median and 25th and 75th percentile values for cTnT were 0.024 microg/L, less than 0.01 microg/L, and 0.084 microg/L, and for cTnI were 0.1 microg/L, 0.05 microg/L, and 0.24 microg/L, respectively. After multivariate analysis, cTnT proved a better predictor of survival than cTnI.

Adult↗