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James L Januzzi

Publications and source records attributed to James L Januzzi.

At least 19 recordsLinked to original sources

Racial outcomes in patients with diabetic cardiomyopathy treated with an aldose reductase inhibitor: the ARISE-HF trial.

BACKGROUND: Racial and ethnic differences in diabetic cardiomyopathy (DbCM) exist, with black and Hispanic participants showing poorer health status. It remains unclear whether these differences affect the natural progression of the disease. We aimed to evaluate disease progression in individuals with DbCM, as well as racial differences in the response to AT-001. METHODS: A total of 625 participants with DbCM were randomised to either placebo or AT-001 and followed for 15 months. The primary outcome was change in peak oxygen uptake (peak VO2) and secondary outcomes included Kansas City Cardiomyopathy Questionnaire (KCCQ) and Physical Activity Scale for the Elderly scores. Analyses were stratified by race and ethnicity (black, Hispanic, white). RESULTS: Black and Hispanic participants who received placebo experienced greater declines in peak VO2 (-0.74 and -1.67 mL/kg/min, respectively) compared with white participants (-0.23 mL/kg/min, p=0.005). AT-001 demonstrated a non-statistically significant trend towards slower declines in peak VO2 in black and Hispanic participants (-0.31 and -0.62 mL/kg/min, p=0.29, respectively). Black participants who received placebo had the largest declines in most KCCQ scores. CONCLUSION: Black and Hispanic participants with DbCM experienced faster disease progression, with black participants showing the most pronounced functional and quality of life declines. The effect of AT-001 on peak VO2 changes was not statistically significant with similar effects between racial and ethnic groups (NCT04083339). TRIAL REGISTRATION NUMBER: NCT04083339.

Aged↗

The effect of zalunfiban on high sensitivity cardiac troponin and the association with clinical outcomes in patients with STEMI.

BACKGROUND: Among individuals with ST-segment elevation myocardial infarction (STEMI), a single subcutaneous injection of the short-acting glycoprotein IIb/IIIa receptor blocker antagonist zalunfiban at first medical contact significantly improved the primary outcome including clinical endpoints. The impact of zalunfiban on Myocardial Infarction (MI) size and association with downstream outcomes remains unclear. METHODS: In a prespecified analysis, we studied results among study participants treated with 2 doses of zalunfiban who had core laboratory measurements concentrations of hs-cTnT. RESULTS: More elevated hs-cTnT concentrations at presentation were associated with less resolution of ST deviation (P = .006) and more frequent Q wave development (P < .001). At coronary angiography more elevated hs-cTnT at presentation was associated with higher thrombus grade and worse epicardial and myocardial perfusion (all P < .05). In multivariable analyses, higher hs-cTnT concentrations at 24 hours were associated with greater adjusted risk for all-cause death (odds ratio [OR] 1.83 per log unit increase; P = .03), cardiovascular death (OR 1.83 per log unit increase; P = .03), heart failure (OR 2.74 per log unit increase; P < .001) or the composite of death and heart failure (P < .001) by 30 days. At 24 hours, those treated with zalunfiban had lower hs-cTnT compared to placebo (P = .04) and across multiples &#x2265; 10 to &#x2265; 1,000 times elevation, treatment with zalunfiban resulted in smaller hs-cTnT determined MI size. CONCLUSIONS: Among patients with STEMI, more elevated concentrations of hs-cTnT are associated with worse measures of reperfusion and higher-risk for short-term death or heart failure. A single dose of zalunfiban at first medical contact reduced MI size. TRIAL REGISTRATION: A phase 3 study of zalunfiban in subjects with ST-elevation MI (CELEBRATE); NCT04825743.

Humans↗

Subgroups and Special Populations in Heart Failure Clinical Trials: Insights From the HFC-ARC Expert Consensus Panel.

In the evolving landscape of heart failure (HF) management, the identification and analysis of subgroups and special populations within clinical trials are crucial for enhancing clinical decision-making, guiding further research, and understanding heterogeneity in study outcomes. This expert consensus document results from the collaborative efforts of the Heart Failure Collaboratory and the Heart Failure Collaboratory Academic Research Consortium, which brought together stakeholders from academia, industry, the U.S. Food and Drug Administration, and patient representatives. The purpose of this assembly was to propose standardized definitions and critical endpoint considerations essential for shaping the design and conduct of clinical trials for drugs and devices in the field of HF. In this context, we propose definitions and endpoints for specific subgroups and special populations in the spectrum of HF. We enhanced the precision, efficacy, and applicability of clinical research and promote more "personalized" approaches to interpretation of clinical trials. Furthermore, we explore the burgeoning field of gene therapy as a promising avenue for addressing the genetic basis of certain cardiomyopathies within these specialized patient groups. We focus especially on methodological considerations for subgroup analyses in large-scale trials, highlighting the importance of proper interpretation of subgroups and best practices for identifying heterogeneity suggestive of differential treatment effects, including when these analyses should be considered hypothesis-generating and requiring subsequent validation. We advocate for a methodical approach to clinical trial design, one that prioritizes the strategic identification of subgroups and employs appropriate statistical methodologies to ensure the reliability and clinical relevance of findings. Through this lens, we envision a pathway toward more personalized and effective treatments for HF, ultimately aiming to improve patient outcomes by leveraging the insights garnered from meticulously designed and comprehensively analyzed clinical trials.

Humans↗

Association of atrial fibrillation and amino-terminal pro-brain natriuretic peptide concentrations in dyspneic subjects with and without acute heart failure: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) study.

BACKGROUND: Amino-terminal pro-brain natriuretic peptide (NT-proBNP) testing is useful for diagnosis or exclusion of heart failure (HF) in dyspneic patients. Atrial fibrillation (AF) may cause dyspnea in the absence of acute HF and may also affect plasma levels of NT-proBNP. METHODS: We prospectively enrolled 599 patients presenting with dyspnea to the emergency department and obtained a blood sample for NT-proBNP measurement. The diagnosis of AF was identified via presentation electrocardiogram. A final diagnosis of HF was determined by blinded study physicians using all available hospital records for each subject through 60 days of follow-up. We assessed the association between the presence of AF and level of NT-proBNP in subsets of patients with and without HF. RESULTS: Of 599 dyspneic patients, 75 (13%) were in AF at presentation; these patients had significantly higher median NT-proBNP levels when compared with those without AF (2934 vs 294 pg/mL, P < .0001). Among patients with acute HF, AF was present in 28%; NT-proBNP levels were lower in those with AF versus those without (3488 vs 4492 pg/mL, P < .001), but AF was not independently associated with NT-proBNP after multivariable adjustment. In patients without acute HF, median NT-proBNP concentrations were significantly higher in those with AF than in those without (932 vs 121 pg/mL, P = .02); in these subjects, AF was the strongest predictor of an NT-proBNP concentration in a range consistent with acute HF (odds ratio 9.94, 95% CI 2.97-33.3, P < .001). CONCLUSION: Atrial fibrillation is associated with higher NT-proBNP concentrations in dyspneic patients, particularly in those without acute HF.

Aged↗

Long-term survival in patients presenting with type B acute aortic dissection: insights from the International Registry of Acute Aortic Dissection.

BACKGROUND: Follow-up survival studies in patients with acute type B aortic dissection have been restricted to a small number of patients in single centers. We used data from a contemporary registry of acute type B aortic dissection to better understand factors associated with adverse long-term survival. METHODS AND RESULTS: We examined 242 consecutive patients discharged alive with acute type B aortic dissection enrolled in the International Registry of Acute Aortic Dissection (IRAD) between 1996 and 2003. Kaplan-Meier survival curves were constructed, and Cox proportional hazards analysis was performed to identify independent predictors of follow-up mortality. Three-year survival for patients treated medically, surgically, or with endovascular therapy was 77.6+/-6.6%, 82.8+/-18.9%, and 76.2+/-25.2%, respectively (median follow-up 2.3 years, log-rank P=0.61). Independent predictors of follow-up mortality included female gender (hazard ratio [HR],1.99; 95% confidence interval [CI], 1.07 to 3.71; P=0.03), a history of prior aortic aneurysm (HR, 2.17; 95% CI, 1.03 to 4.59; P=0.04), a history of atherosclerosis (HR, 2.48; 95% CI, 1.32 to 4.66; P<0.01), in-hospital renal failure (HR, 2.55; 95% CI, 1.15 to 5.63; P=0.02), pleural effusion on chest radiograph (HR, 2.56; 95% CI, 1.18 to 5.58; P=0.02), and in-hospital hypotension/shock (HR, 12.5; 95% CI, 3.24 to 48.21; P<0.01). CONCLUSIONS: Contemporary follow-up mortality in patients who survive to hospital discharge with acute type B aortic dissection is high, approaching 1 in every 4 patients at 3 years. Current treatment and follow-up surveillance require further study to better understand and optimize care for patients with this complex disease.

Acute Disease↗

Myocardial injury and ventricular dysfunction related to training levels among nonelite participants in the Boston marathon.

BACKGROUND: Multiple studies have individually documented cardiac dysfunction and biochemical evidence of cardiac injury after endurance sports; however, convincing associations between the two are lacking. We aimed to determine the associations between the observed transient cardiac dysfunction and biochemical evidence of cardiac injury in amateur participants in endurance sports and to elicit the risk factors for the observed injury and dysfunction. METHODS AND RESULTS: We screened 60 nonelite participants, before and after the 2004 and 2005 Boston Marathons, with echocardiography and serum biomarkers. Echocardiography included conventional measures as well as tissue Doppler-derived strain and strain rate imaging. Biomarkers included cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP). All subjects completed the race. Echocardiographic abnormalities after the race included altered diastolic filling, increased pulmonary pressures and right ventricular dimensions, and decreased right ventricular systolic function. At baseline, all had unmeasurable troponin. After the race, > 60% of participants had increased cTnT > 99th percentile of normal (> 0.01 ng/mL), whereas 40% had a cTnT level at or above the decision limit for acute myocardial necrosis (> or = 0.03 ng/mL). After the race, NT-proBNP concentrations increased from 63 (interquartile range [IQR] 21 to 81) pg/mL to 131 (IQR 82 to 193) pg/mL (P<0.001). The increase in biomarkers correlated with post-race diastolic dysfunction, increased pulmonary pressures, and right ventricular dysfunction (right ventricular mid strain, r=-0.70, P<0.001) and inversely with training mileage (r=-0.71, P<0.001). Compared with athletes training > 45 miles/wk, athletes who trained < or = 35 miles/wk demonstrated increased pulmonary pressures, right ventricular dysfunction (mid strain 16+/-5% versus 25+/-4%, P<0.001), myocyte injury (cTnT 0.09 versus < 0.01 ng/mL, P<0.001), and stress (NT-proBNP 182 versus 106 pg/mL, P<0.001). CONCLUSIONS: Completion of a marathon is associated with correlative biochemical and echocardiographic evidence of cardiac dysfunction and injury, and this risk is increased in those participants with less training.

Athletic Injuries↗

Amino-terminal pro-brain natriuretic Peptide, renal function, and outcomes in acute heart failure: redefining the cardiorenal interaction?

OBJECTIVES: We sought to study the individual and integrative role of amino-terminal pro-brain natriuretic peptide (NT-proBNP) and parameters of renal function for prognosis in heart failure. BACKGROUND: Amino-terminal pro-BNP and renal impairment both predict death in patients with heart failure. Worsening of renal function in heart failure even defines the "cardiorenal syndrome." METHODS: Seven hundred twenty subjects presenting with acute heart failure from 4 university-affiliated medical centers were dichotomized according to NT-proBNP concentration and baseline glomerular filtration rate. In addition, patients were divided according to changes in renal function. The primary end point was 60-day mortality. RESULTS: The combination of a glomerular filtration rate (GFR) <60 ml/min/1.73 m2 with an NT-proBNP >4,647 pg/ml was the best predictor of 60-day mortality (odds ratio 3.46; 95% confidence interval 2.13 to 5.63). Among subjects with an NT-proBNP above the median, those with a GFR <60 ml/min/1.73 m2 or a creatinine rise > or =0.3 mg/dl had the worst prognosis, whereas in subjects with a NT-proBNP below the median, prognosis was not influenced by either impaired renal function at presentation or the development of renal impairment during admission. CONCLUSIONS: The combination of NT-proBNP with measures of renal function better predicts short-term outcome in acute heart failure than either parameter alone. Among heart failure patients, the objective parameter of NT-proBNP seems more useful to delineate the "cardiorenal syndrome" than the previous criteria of a clinical diagnosis of heart failure.

Acute Disease↗

Utility of amino-terminal pro-brain natriuretic peptide, galectin-3, and apelin for the evaluation of patients with acute heart failure.

OBJECTIVES: This study sought to explore the role of new biomarkers in heart failure (HF). BACKGROUND: We investigated the utility of novel serum markers alone or together with natriuretic peptide testing for diagnosis and short-term prognosis estimation in subjects with acute HF. METHODS: Plasma levels of amino-terminal pro-brain natriuretic peptide (NT-proBNP), apelin, and galectin-3 were measured in 599 patients presenting with dyspnea at the emergency department, of which 209 (35%) had acute HF. RESULTS: The NT-proBNP was superior to either apelin or galectin-3 for diagnosis of acute HF, although galectin-3 levels were significantly higher in subjects with HF compared with those without. Receiver operating characteristic analysis for mortality prediction showed that, for 60-day prognosis, galectin-3 had the greatest area under the curve (AUC) at 0.74 (p = 0.0001), whereas NT-proBNP and apelin had an AUC of 0.67 (p = 0.009) and 0.54 (p = 0.33). In a multivariate logistic regression analysis, an elevated level of galectin-3 was the best independent predictor of 60-day mortality (odds ratio 10.3, p < 0.01) or the combination of death/recurrent HF within 60 days (odds ratio 14.3, p < 0.001). The Kaplan-Meier analyses showed that the combination of an elevated galectin-3 with NT-proBNP was a better predictor of mortality than either of the 2 markers alone. CONCLUSIONS: Our data show potential utility of galectin-3 as a useful marker for evaluation of patients with suspected or proven acute HF, whereas apelin measurement was not useful for these indications. Moreover, the combination of galectin-3 with NT-proBNP was the best predictor for prognosis in subjects with acute HF.

Acute Disease↗

Cost-effectiveness of using N-terminal pro-brain natriuretic peptide to guide the diagnostic assessment and management of dyspneic patients in the emergency department.

The cost-effectiveness of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in dyspneic patients in emergency departments (EDs) is unknown. The objective of this study was to assess the cost-effectiveness of NT-pro-BNP testing for the evaluation and initial management of patients with dyspnea in the ED setting. A decision model was developed to evaluate the cost-effectiveness of diagnostic assessment and patient management guided by NT-pro-BNP, compared with standard clinical assessment. The model includes the diagnostic accuracy of the 2 strategies for congestive heart failure and resulting events at 60-day follow-up. Clinical data were obtained from a prospective blinded study of 599 patients presenting to the ED with dyspnea. Costs were based on the Massachusetts General Hospital cost accounting database. The model predicted serious adverse events during follow-up (i.e., urgent care visits, repeat ED presentations, rehospitalizations) and direct medical costs for echocardiograms and hospitalizations. NT-pro-BNP-guided assessment was associated with a 1.6% relative reduction of serious adverse event risk and a 9.4% reduction in costs, translating into savings of $474 per patient, compared with standard clinical assessment. In a sensitivity analysis considering mortality, NT-pro-BNP testing was associated with a 1.0% relative reduction in post-discharge mortality. The optimal use of NT-pro-BNP guidance could reduce the use of echocardiography by up to 58%, prevent 13% of initial hospitalizations, and reduce hospital days by 12%. In conclusion, on the basis of this model, the use of NT-pro-BNP in the diagnostic assessment and subsequent management of patients with dyspnea in the ED setting could lead to improved patient care while providing substantial cost savings to the health care system.

Biomarkers↗

Recognition and treatment of depression and anxiety in patients with acute myocardial infarction.

The objective of this study was to determine the ability of providers (medical residents and nurse practitioners) on inpatient cardiac units to recognize and appropriately treat patients with clinically significant depression and anxiety among a cohort admitted with acute myocardial infarction. Patients within 72 hours of acute myocardial infarction underwent screening with the Standardized Clinical Instrument for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition module for major depressive disorder (MDD), the Beck Depression Inventory (BDI-II), and the Beck Anxiety Inventory (BAI). In addition, the study psychiatrist and a treatment team clinician independently assessed whether they believed that patients had clinically significant depression or anxiety. Prescription of antidepressants and benzodiazepines during hospitalization was recorded by chart review. Assessments were completed for 74 patients. Providers identified < 15% of patients with current MDD or with a BDI score > or = 10; 11% of patients with current MDD had appropriate treatment with antidepressants. There was no significant correlation of providers' assessment of depression with current MDD, BDI scores, or psychiatrists' clinical assessment of depression. In contrast, providers identified 31% of patients with a BAI score > or = 10 and 50% of patients who were assessed by psychiatrists as anxious; > 80% of patients with high anxiety received benzodiazepines. Providers' assessments of anxiety were significantly correlated with BAI scores and with psychiatrists' clinical assessments. In conclusion, medical residents and nurse practitioners routinely under-recognize and undertreat depression among patients with acute myocardial infarction on inpatient cardiac units. Recognition and treatment of anxiety is substantially better, up to 50% of patients who are found to be anxious by psychiatrists after acute myocardial infarction remain unrecognized.

Anti-Anxiety Agents↗

Usefulness of intermediate amino-terminal pro-brain natriuretic peptide concentrations for diagnosis and prognosis of acute heart failure.

Age-stratified cutpoints for aminoterminal pro-brain natriuretic peptide (NT-pro-BNP) concentrations are diagnostic in 83% of all subjects with acute dyspnea. This study analyzed subjects with NT-pro-BNP concentrations between the "rule-out" and "rule-in" cutpoints, the so-called natriuretic peptide gray zone. NT-pro-BNP concentrations, clinical characteristics, and 60-day mortality were studied in 1,256 acutely dyspneic patients from an international multicenter study. Of all subjects, 215 had gray-zone NT-pro-BNP concentrations, 116 of whom (54%) were diagnosed with heart failure (HF). Among these subjects, patients with HF were more likely to be older, to have a history of HF, to be in atrial fibrillation, and to have elevated troponin T concentrations compared with those without HF. In multivariate analysis, the use of loop diuretics on presentation (odds ratio [OR] 3.99, 95% confidence interval [CI] 1.58 to 10.1, p = 0.003), paroxysmal nocturnal dyspnea (OR 4.50, 95% CI 1.31 to 15.4, p = 0.02), jugular venous distention (OR 3.05, 95% CI = 1.06 to 8.79, p = 0.04), and the absence of cough (OR 0.18, 95% CI 0.06 to 0.52, p = 0.001) were associated with a diagnosis of acute HF in gray-zone patients. Subjects with HF and diagnostically elevated NT-pro-BNP concentrations had the highest mortality rates, subjects without HF and NT-pro-BNP concentrations < 300 ng/L had the lowest mortality rates, and subjects with gray-zone NT-pro-BNP had intermediate outcomes, irrespective of their final diagnoses. Adding specific clinical information to NT-pro-BNP improves diagnostic accuracy in subjects with intermediate NT-pro-BNP concentrations. Mortality rates in subjects with intermediate NT-pro-BNP concentrations are lower than in those with NT-pro-BNP concentrations diagnostic for HF but are higher than in subjects with NT-pro-BNP concentrations less than the gray zone.

Acute Disease↗

NT-proBNP levels, echocardiographic findings, and outcomes in breathless patients: results from the ProBNP Investigation of Dyspnoea in the Emergency Department (PRIDE) echocardiographic substudy.

AIMS: The objective of this study was to determine the integrative utility of measuring plasma NT-proBNP levels with echocardiography in the evaluation of dyspnoeic patients. METHODS AND RESULTS: Of 599 emergency department patients enrolled in a clinical study of NT-proBNP at a tertiary-care hospital, 134 (22%) had echocardiographic results available for analysis. Echocardiographic parameters correlating with NT-proBNP levels were determined using multivariable linear-regression analysis. Independent predictors of 1-year mortality were determined using Cox-proportional hazard analysis. Independent relationships were found between NT-proBNP levels and ejection fraction (P = 0.012), tissue Doppler early and late mitral annular diastolic velocities (P = 0.007 and 0.018), right ventricular (RV) hypokinesis (P = 0.006), and tricuspid regurgitation severity (P < 0.001) and velocity (P = 0.007). An NT-proBNP level <300 pg/mL had a negative predictive value of 91% for significant left ventricular systolic and diastolic dysfunction. Overall 1-year mortality was 20.1% and was independently predicted by NT-proBNP level [HR 8.65, 95% confidence interval (CI) 2.7-27.8, P = 0.0003], ejection fraction (HR 0.95, 95% CI 0.91-0.99, P = 0.009), RV dilation (HR 2.98, 95% CI 1.05-12.8, P = 0.04), and systolic blood pressure (HR 0.97, 95% CI 0.96-0.99, P = 0.01). CONCLUSION: NT-proBNP levels correlate with, and provide important prognostic information beyond, echocardiographic parameters of cardiac structure and function. Routine NT-proBNP testing may thus be useful to triage patients to more timely or deferred echocardiographic evaluation.

Dyspnea↗

Amino-terminal pro-brain natriuretic peptide for the diagnosis of acute heart failure in patients with previous obstructive airway disease.

STUDY OBJECTIVE: We evaluate results from amino-terminal pro-brain natriuretic peptide (NT-proBNP) testing with or without those of clinical judgment for the evaluation of dyspneic patients with previous chronic obstructive pulmonary disease or asthma. METHODS: As a secondary analysis of previously collected observational data from a convenience sample of 599 breathless patients, 216 patients with previous chronic obstructive pulmonary disease or asthma who presented to the emergency department were analyzed according to results of NT-proBNP, clinical impression, and their final diagnosis. Test performance of NT-proBNP in these patients with chronic obstructive pulmonary disease or asthma was examined for the group as a whole, as well as in patients with and without previous heart failure. NT-proBNP results were compared to clinician-estimated likelihood for heart failure using receiver operating curves and as a function of NT-proBNP plus clinical evaluation. The final diagnosis was determined by 2 independent cardiologists blinded to NT-proBNP using all available data from the 60-day follow-up period. RESULTS: Overall, 55 patients (25%) had acute heart failure; the median value of NT-proBNP was higher in these patients compared with those without acute heart failure (2,238 vs 178 pg/mL); use of cut points of 450 pg/mL for patients younger than 50 years and 900 pg/mL for patients 50 years or older yielded a sensitivity of 87% (95% confidence interval [CI] 72% to 93%) and a specificity of 84% (95% CI 76% to 88%). In patients without previous heart failure (n=164), median NT-proBNP levels were also higher in patients with heart failure of new onset compared with those with chronic obstructive pulmonary disease or asthma exacerbation (1561 versus 168 pg/mL). High clinical suspicion for acute heart failure (probability >80%) detected only 23% of patients with new-onset heart failure, whereas 82% of these patients had elevated NT-proBNP levels. In patients who had both previous acute heart failure and chronic obstructive pulmonary disease or asthma (n=52), median NT-proBNP levels were significantly higher in those with acute heart failure (4,435 pg/mL) than patients with chronic obstructive pulmonary disease or asthma exacerbation (536 pg/mL). In patients with acute-on-chronic heart failure, NT-proBNP levels were elevated in 91%, whereas clinical impression considered only 39% of cases as high likelihood for acute heart failure. CONCLUSION: NT-proBNP may be a useful adjunct to standard clinical evaluation of dyspneic patients with previous obstructive airway disease.

Acute Disease↗

Utility of amino-terminal pro-brain natriuretic peptide testing for prediction of 1-year mortality in patients with dyspnea treated in the emergency department.

BACKGROUND: Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is useful for diagnosis and triage of patients with dyspnea, but its role for predicting outcomes in such patients remains undefined. METHODS: A total of 599 breathless patients treated in the emergency department were prospectively enrolled, and a sample of blood was obtained for NT-proBNP measurements. After 1 year, the vital status of each patient was ascertained, and the association between NT-proBNP values at presentation and mortality was assessed. RESULTS: At 1 year, 91 patients (15.2%) had died. Median NT-proBNP concentrations at presentation among decedents were significantly higher than those of survivors (3277 vs 299 pg/mL; P<.001). The optimal NT-proBNP cut point for predicting 1-year mortality was 986 pg/mL. In a multivariable model, an NT-proBNP concentration greater than 986 pg/mL at presentation was the single strongest predictor of death at 1 year (hazard ratio [HR], 2.88; 95% confidence interval, 1.64-5.06; P<.001), independent of a diagnosis of heart failure. Other factors associated with death included age (by decade; HR, 1.20), heart rate (by decile; HR, 1.13), urea nitrogen level (by decile; HR, 1.20), systolic blood pressure less than 100 mm Hg (HR, 1.94), heart murmur (HR, 1.92), and New York Heart Association classification (HR, 1.38 for each increase in class). The NT-proBNP concentration alone had an area under the receiver operating characteristic curve (AUC) of 0.76 for predicting mortality; the other significant covariates combined had an AUC of 0.80. The final model for predicting death, combining NT-proBNP with other covariates associated with mortality, had a superior AUC of 0.82. CONCLUSION: In addition to assisting in emergency department diagnosis and triage, NT-proBNP concentrations at presentation are strongly predictive of 1-year mortality in dyspneic patients.

Age Factors↗

A validated clinical and biochemical score for the diagnosis of acute heart failure: the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) Acute Heart Failure Score.

BACKGROUND: No method integrating amino-terminal pro-brain natriuretic peptide (NT-proBNP) testing with clinical assessment for the evaluation of patients with suspected acute heart failure (HF) has been described. METHODS: Amino-terminal pro-brain natriuretic peptide results and clinical factors from 599 patients with dyspnea were analyzed. The beta coefficients of the 8 independent predictors of HF were used to assign a weighted integeric score for predictor. The sum of these integers provided a diagnostic HF "score" for each patient. Receiver operating characteristic curve analysis determined the optimal cut point for the diagnosis of acute HF. The performance of the score was evaluated in the development cohort and subsequently in a patient population from a separate clinical trial of patients with dyspnea conducted in Christchurch, New Zealand. RESULTS: Eight factors comprised the score: elevated NT-proBNP (4 points), interstitial edema on chest x-ray (2 points), orthopnea (2 points), absence of fever (2 points), loop diuretic use, age > 75 years, rales, and absence of cough (all 1 point). Median scores in patients with acute HF were higher than those without acute HF (9 vs 3 points, P < .001). At a cut point of > or = 6 points, the score had a sensitivity of 96% and a specificity of 84% for the diagnosis of acute HF (P < .001). The score improved diagnostic accuracy over NT-proBNP testing alone and retained discriminative capacity in patients in whom clinical uncertainty was present. Lastly, the accuracy of the score was validated in the external data set of patients with suspected acute HF. CONCLUSION: We report a simple and accurate scoring system combining NT-proBNP testing and clinical assessment for the diagnosis or exclusion of acute HF in patients with dyspnea.

Acute Disease↗

Predicting a late positive serum troponin in initially troponin-negative patients with non-ST-elevation acute coronary syndrome: clinical predictors and validated risk score results from the TIMI IIIB and GUSTO IIA studies.

BACKGROUND: Troponin testing is useful for evaluating patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS); however, a significant percentage of patients are troponin negative at presentation and develop late rise of the marker. METHODS: Patients in the TIMI IIIB study were assessed with respect to their troponin I (TnI) status at presentation and 12 hours. Multivariable analysis identified independent clinical factors associated with TnI rise at 12 hours among subjects initially TnI negative. A score predicting late TnI rise in TIMI IIIB was developed using these factors and validated among patients in the GUSTO IIA study. RESULTS: Of 1342 subjects in TIMI IIIB, 200 (14.9%) were negative at baseline, but developed an elevated TnI (> or = 0.4 ng/mL) at 12 hours. Six independent predictors of late TnI rise were identified: ST-segment deviation (odds ratio [OR] 3.52, 95% CI 2.38-5.23, P < .001), presentation < 8 hours from symptom onset (OR 2.91, 95% CI 1.92-4.40, P < .001), no prior percutaneous coronary intervention (OR 2.88, 95% CI 1.54-5.39, P = .001), no prior beta-blocker use (OR 1.74, 95% CI 1.15-2.63, P = .008), unheralded angina (OR 1.65, 95% CI 1.12-2.42, P = .01), and a history of myocardial infarction (OR 1.59, 95% CI 1.06-2.37, P = .02). ST deviation, presentation < 8 hours from symptoms, and no prior percutaneous coronary intervention were given a score of 2 points, whereas a score of 1 point was assigned to the other factors. Among baseline TnI-negative patients, a rising score was paralleled by an increasing prevalence of late TnI rise from 0% (with a score of 0) to 69% (with a score of 9) (P < .001). In confirmation, the score was able to similarly predict late troponin T rise among 855 patients in the GUSTO IIA study (P < .0001). CONCLUSION: Development of late troponin rise is common in non-ST-segment elevation acute coronary syndromes. Six easily ascertained variables may be used to identify those at higher risk for late rise in troponin levels after an initially negative presentation.

Aged↗