Biomedical subjects

Paul Clopton

Publications and source records attributed to Paul Clopton.

At least 19 recordsLinked to original sources

PubMed2004

Primary results of the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT). A multicenter study of B-type natriuretic peptide levels, emergency department decision making, and outcomes in patients presenting with shortness of breath.

OBJECTIVES: The purpose of this study was to examine the relationships among B-type natriuretic peptide (BNP) levels within the diagnostic range, perceived congestive heart failure (CHF) severity, clinical decision making, and outcomes of the CHF patients presenting to emergency department (ED). BACKGROUND: Since BNP correlates with the presence of CHF, disease severity, and prognosis, we hypothesized that BNP levels in the diagnostic range offer value independent of physician decision making with regard to critical outcomes in emergency medicine. METHODS: The Rapid Emergency Department Heart failure Outpatient Trial (REDHOT) study was a 10-center trial in which patients seen in the ED with shortness of breath were consented to have BNP levels drawn on arrival. Entrance criteria included a BNP level >100 pg/ml. Physicians were blinded to the actual BNP level and subsequent BNP measurements. Patients were followed up for 90 days after discharge. RESULTS: Of the 464 patients, 90% were hospitalized. Two-thirds of patients were perceived to be New York Heart Association (NYHA) functional class III or IV. The BNP levels did not differ significantly between patients who were discharged home from the ED and those admitted (976 vs. 766, p = 0.6). Using logistic regression analysis, an ED doctor's intention to admit or discharge a patient had no influence on 90-day outcomes, while the BNP level was a strong predictor of 90-day outcome. Of admitted patients, 11% had BNP levels <200 pg/ml (66% of which were perceived NYHA functional class III or IV). The 90-day combined event rate (CHF visits or admissions and mortality) in the group of patients admitted with BNP <200 pg/ml and >200 pg/ml was 9% and 29%, respectively (p = 0.006). CONCLUSIONS: In patients presenting to the ED with heart failure, there is a disconnect between the perceived severity of CHF by ED physicians and severity as determined by BNP levels. The BNP levels can predict future outcomes and thus may aid physicians in making triage decisions about whether to admit or discharge patients. Emerging clinical data will help further refine biomarker-guided outpatient therapeutic and monitoring strategies involving BNP.

Biomarkers↗

PubMed2004

Prognostic role of B-type natriuretic peptide levels in patients with type 2 diabetes mellitus.

OBJECTIVES: We hypothesized that B-type natriuretic peptide (BNP) levels can predict cardiac mortality in diabetic patients. BACKGROUND: Detection of cardiovascular disease in diabetics can be difficult until overt events occur. METHODS: A total of 482 diabetics (majority male with type 2 diabetes) at the Veterans Affairs Medical Center San Diego were divided into two groups: 1) referred patients for echocardiogram on the basis of clinical suspicion of cardiac dysfunction (referred [R], n = 180); 2) patients randomly selected from the diabetic clinic without any suspicion of cardiac dysfunction (not referred [N-R], n = 302). We examined cardiac events and all-cause mortality in relation to initial BNP levels during the follow-up. RESULTS: A total of 71 (14.7%) patients died during this period: 52 of 180 (29%) in the R group (30 of 52 [58%] cardiac, 10 of 52 [19%] non-cardiac, 2 of 52 [4%] renal, 10 of 52 [19%] unknown cause) and 19 of 302 (6%) in N-R group (6 of 19 [32%] cardiac). The median BNP level in the R and N-R groups who died of cardiac, non-cardiac, and unknown cause was 537 and 87, 80 and 53, and 343 and 38 pg/ml, respectively. The receiver-operating characteristic (ROC) values for mortality in two groups in relation to BNP revealed the area under the curve to be 0.720 and 0.691, respectively (p < 0.01 in both). Among commonly used prognostic indicators in diabetics, only the ROC for triglycerides was significant. The most accurate cut-point in both the N-R group (87%) and R group (61%) was 120 pg/ml of BNP. Cox regression analysis showed BNP to be the most significant predictor of all-cause mortality in the R group. There was a marked decrease in survival in the patient group with BNP >120 pg/ml. CONCLUSIONS: B-type natriuretic peptide appears to be a reliable predictor of future cardiac and all-cause mortality in diabetic patients.

Adult↗

PubMed2004

Intracoronary adenovirus encoding adenylyl cyclase VI increases left ventricular function in heart failure.

BACKGROUND: We tested the hypothesis that intracoronary delivery of an adenovirus encoding adenylyl cyclase type VI (Ad.AC(VI)) would be associated with increased left ventricular (LV) function in pigs with congestive heart failure. METHODS AND RESULTS: Pigs (52+/-6 kg; n=16) underwent placement of pacemakers, LV pressure transducers, and left atrial and aortic catheters. Physiological and echocardiographic studies were obtained from conscious animals 13 days later, and pacing was initiated (220 bpm). Seven days later, measures of LV function were reduced, documenting severe LV dysfunction and dilation. Pigs then received intracoronary Ad.AC(VI) (1.4x10(12) vp; n=7) or saline (PBS; n=9) (randomized, blinded), with concomitant infusion of nitroprusside (50 microg/min, 6.4 minutes) to increase gene transfer. Pacing was continued for 14 days, and final studies were obtained. The a priori key end point was change in LV dP/dt during isoproterenol infusion (pre-Ad.AC(VI) value minus value after 21 days of pacing). Pigs receiving Ad.AC(VI) showed a smaller decrease in both LV +dP/dt (P=0.0014) and LV -dP/dt (P=0.0008). Serial echocardiography showed that Ad.AC(VI) treatment was associated with increased LV function and reduced LV dilation and that end-systolic wall stress was reduced. AC-stimulated cAMP production was increased 1.7-fold in LV samples from Ad.AC(VI)-treated pigs (P=0.006), and B-type natriuretic peptide was reduced (0.035). Gene transfer was confirmed by polymerase chain reaction. CONCLUSIONS: AC(VI) gene transfer increases LV function and attenuates deleterious LV remodeling in congestive heart failure.

Adenoviridae↗

PubMed2004

Utility of B-type natriuretic peptide in predicting postoperative complications and outcomes in patients undergoing heart surgery.

OBJECTIVES: The purpose of the present study was to assess whether preoperative and postoperative B-type natriuretic peptide (BNP) levels could be used as predictors of postoperative complications and outcomes in patients after open-heart surgery. BACKGROUND: A variety of multifactor indexes have been proposed for preoperative risk assessment of patients undergoing cardiac surgery, but they have shown limited ability and utility in accurately predicting postoperative complications, hospital stay, and mortality. METHODS: Subjects consisted of 98 male patients (63 +/- 9.1 years) undergoing open-heart surgery at the San Diego Veterans Administration Health System during a 19-month period. B-type natriuretic peptide levels were analyzed, and postoperative data recorded. RESULTS: There was a higher preoperative BNP level in patients requiring the use of intra-aortic balloon pumps (IABPs) (mean BNP = 387 +/- 112 pg/ml vs. 181 +/- 25 pg/ml), in patients who died within one year (357 +/- 93 pg/ml vs. 184 +/- 26 pg/ml), and in patients with postoperative hospital stays of 10 days or more (307 +/- 68 pg/ml vs. 179 +/- 27 pg/ml). Receiver operating characteristic curves demonstrated preoperative BNP levels as predictors of postoperative IABP use, hospital stay 385 pg/ml predict the postoperative complications and one-year mortality after heart surgery. Postoperatively, elevated peak BNP levels and elevated change to peak BNP levels were associated with prolonged hospital stay and mortality within one year.

Aged↗

PubMed2004

Diagnostic value of B-Type natriuretic peptide and chest radiographic findings in patients with acute dyspnea.

PURPOSE: To compare chest radiographic findings and circulating B-type natriuretic peptide (BNP) levels as an adjunct to clinical findings in the diagnosis of heart failure in patients presenting with acute dyspnea. METHODS: The diagnostic performance of radiographic evidence of cardiomegaly/redistribution and BNP levels > or =100 pg/mL as indicators of heart failure were assessed in 880 patients presenting with acute dyspnea to the emergency departments of five U.S. and two European teaching hospitals. BNP levels were determined by a rapid, point-of-care device. Two blinded cardiologists reviewed all clinical data and categorized patients as to whether they had acute heart failure (n = 447) or not (n = 433). RESULTS: Three-factor analyses showed that BNP levels > or =100 pg/mL contributed significantly to the prediction of heart failure over each of the radiographic indicators. In a multivariate logistic regression analysis, both BNP levels > or =100 pg/mL (odds ratio [OR] = 12.3; 95% confidence interval [CI]: 7.4 to 20.4) and radiographic findings of cardiomegaly (OR = 2.3; 95% CI: 1.4 to 3.7), cephalization (OR = 6.4; 95% CI: 3.3 to 12.5), and interstitial edema (OR = 7.0; 95% CI: 2.9 to 17.0) added significant, predictive information above historical and clinical predictors of heart failure. CONCLUSION: In patients presenting to the emergency department with acute dyspnea, BNP levels and chest radiographs provide complementary diagnostic information that may be useful in the early evaluation of heart failure.

Acute Disease↗

PubMed2004

Impact of age, race, and sex on the ability of B-type natriuretic peptide to aid in the emergency diagnosis of heart failure: results from the Breathing Not Properly (BNP) multinational study.

BACKGROUND: B-type natriuretic peptide (BNP) is secreted from the cardiac ventricles in response to increased wall tension. METHODS: The Breathing Not Properly Multinational Study was a 7-center, prospective study of 1586 patients who presented to the Emergency Department with acute dyspnea and had BNP measured with a point-of-care assay upon arrival. The gold standard for congestive heart failure (CHF) was adjudicated by two independent cardiologists, blinded to BNP results, who reviewed all clinical data and standardized scores. The current study explores the effect of these variables on BNP decision statistics as well as the impact that changing cutoffs might have on the cost-effectiveness of diagnostic decisions that use BNP information. RESULTS: Significant differences in CHF rates were found on the basis of age (P <.001) and racial group (P =.020) but not sex (P =.424). BNP levels increased with increasing age (P <.001). To evaluate potential differences in the diagnostic utility of BNP levels as a function of demographic variables, separate receiver operating characteristic curves were performed. BNP was a stronger predictor in younger subjects than in older subjects and slightly weaker for female patients than for male patients (area under the curve = 0.918 and 0.870, respectively). An even smaller difference was noted between the white and black racial groups (area under the curve = 0.888 and 0.903, respectively). The differences in specificity as a function of age are larger than other differences in specificity or sensitivity. When logistic regression was used in a multivariate approach to combine the demographic variables with BNP information in the prediction of CHF, only BNP contributed significantly to the prediction of acute CHF. When the model was expanded to include terms for the interaction of each of the demographic variables with log(10) BNP, a significant interaction was found for sex. Since the relative consequences of false-positives and false-negatives are unlikely to be equivalent, the BNP cut-points that would be selected based on the current data as a function of relative costs are presented. Sharply rising consequences are seen for BNP cut-points >100 pg/mL. CONCLUSIONS: If one assumes that failing to treat cases of CHF is worse than treating negative cases, then relatively low BNP cut-points (eg, not >100 pg/mL) should be used in patients presenting to the Emergency Department with a chief complaint of dyspnea, regardless of age, sex, or ethnicity.

Age Distribution↗

PubMed2004

Utility of B-natriuretic peptide in the evaluation of left ventricular diastolic function: comparison with tissue Doppler imaging recordings.

BACKGROUND: Although Doppler echocardiography provides assessment of abnormal left ventricular (LV) diastolic filling dynamics, its inherent limitations suggest the need for additional measures of diastolic dysfunction. The ratio of mitral velocity to early diastolic velocity of the mitral annulus (E/E') derived from tissue Doppler imaging is associated with the mean LV end diastolic pressure (LVEDP). Because data suggest that B-natriuretic peptide (BNP) reflects ventricular pressure, we hypothesized that BNP levels correlate with indices of LV diastolic function by tissue Doppler imaging. METHODS AND RESULTS: Doppler recordings of the mitral inflow and tissue Doppler imaging of the mitral annulus were obtained in 108 patients referred for echocardiography. BNP levels were measured by a rapid immunoassay and blinded to cardiologists making the assessment of LV function. BNP levels were higher when elevated E/E' ratios derived from tissue Doppler imaging were identified. Patients identified with elevated LVEDP, defined as E/E' >15 (n = 16), had the highest BNP levels (463 +/- 80 pg/mL). Those with normal LVEDP, as predicted by E/E' <8 (n = 36), had a mean BNP concentration of 97 +/- 27 pg/mL. Those with E/E' of 8 to 15 (n = 48) had a mean BNP level of 122 +/- 24 pg/mL. The area under the receiver-operating curve for BNP to detect E/E' >15 was 0.89 (95% CI, 0.82 to 0.96; P < .001). A BNP value of 173 pg/mL had a sensitivity of 88%, a specificity of 82%, and an accuracy of 83% for predicting E/E' >15. CONCLUSIONS: BNP levels correlate with the E/E' ratios from tissue Doppler imaging (r = 0.48) and can reliably provide estimation of LV filling pressures. Although BNP levels do not correlate well with E/E' ratios across the full spectrum of values, the combination of BNP levels along with E/E' ratios from tissue Doppler imaging may be a better predictor of elevated LV filling pressures in patients with suspected diastolic dysfunction.

Adult↗

PubMed2004

A prospective study in search of an optimal B-natriuretic peptide level to screen patients for cardiac dysfunction.

BACKGROUND: Although echocardiography is the gold standard test for suspected left ventricular dysfunction, its cost and availability limits its use as a routine screening tool. The high negative predictive value of B-natriuretic peptide (BNP) in dyspneic patients suggests its possible utility in screening patients prior to echocardiography. Determining an appropriate BNP level below which the need for echocardiography is precluded would be valuable. We hypothesized that a fixed plasma BNP level of 20 pg/mL and simple clinical parameters are an effective pre-echocardiographic screening tool for left ventricular dysfunction. METHODS: Two hundred and two patients at a Veterans Administration facility with symptoms suggestive of heart disease (male to female ratio 193:9, mean age 65 years) were screened prior to echocardiography. Patients with known cardiac dysfunction were excluded. RESULTS: BNP levels of > or =20 pg/mL were 79% sensitive and 44% specific in screening for any abnormality of ventricular function. The negative predictive value was 69%. When broken down into categories of dysfunction, the cutoff point of 20 pg/mL had a better negative predictive value for those with systolic dysfunction (96%) or systolic plus diastolic dysfunction (100%) if patients with diastolic dysfunction were excluded. The majority of patients with falsely low BNP levels (<20 pg/mL with positive echocardiographic findings) had mild diastolic dysfunction, with 3 patients exhibiting mild systolic dysfunction. CONCLUSIONS: BNP may be a useful screening tool for left ventricular dysfunction in patients with history suggestive of heart disease and be used to assist in forming a pretest probability, which in turn could greatly assist in appropriateness of patient referral and in optimization of drug therapy.

Adult↗

PubMed2004

The extracellular matrix differentially regulates the expression of PTHrP and the PTH/PTHrP receptor in FG pancreatic cancer cells.

OBJECTIVES: Previous studies by our laboratory have demonstrated that parathyroid hormone-related protein (PTHrP) and its receptor (PTH/PTHrP receptor) are commonly expressed in pancreatic cancer and suggest their participation in the progression of this devastating disease. It has also been demonstrated that one of the major hallmarks of pancreatic adenocarcinoma is an increased production of the extracellular matrix (ECM), a critical regulator of diverse cellular processes such as differentiation, proliferation, and angiogenesis. The present study focused on the relationship between the PTHrP and ECM axes in the pathobiology of pancreatic cancer. METHOD AND RESULTS: Using the FG pancreatic adenocarcinoma cell line, we demonstrate a significant inverse correlation between FG cell proliferation and PTHrP expression that depended on the ECM protein on which the cells were cultured (P < 0.05). Generally, ECM proteins that promoted the strongest proliferation, including type I collagen, type IV collagen, and laminin, resulted in decreased expression of PTHrP. Conversely, ECM proteins that promoted the weakest proliferation, including fibronectin, vitronectin, and BSA, resulted in increased expression of PTHrP. A similar trend was found between FG cell proliferation and the PTH/PTHrP receptor expression, with Pearson correlation coefficients of 0.480 (mRNA) and -0.591 (protein). CONCLUSION: These observations demonstrate a unique functional relationship between the ECM and PTHrP axes and have important implications for our understanding of the complex mechanisms responsible for the progression of pancreatic cancer and its metastases.

Adenocarcinoma↗

PubMed2004

Intervertebral disk calcification of the spine in an elderly population: radiographic prevalence, location, and distribution and correlation with spinal degeneration.

PURPOSE: To determine the prevalence, distribution, and location of intervertebral disk calcification (IDC) in the thoracic and lumbar spine and the association of IDC with radiographically evident spinal degenerative changes in cadavers. MATERIALS AND METHODS: Anterior vertebral columns comprising T1 through L5 were removed from 223 cadavers (183 men, 40 women; mean age at death, 67 years; range, 37-94 years). Approximately 5-mm-thick parasagittal sections were investigated with high-contrast radiography. The presence of IDC, osteophytes, vertebral endplate abnormalities, and vacuum phenomena was recorded, and the height of disk space was measured at 3,568 intervertebral levels. Logistic regression analysis was performed. RESULTS: IDC was identified in 178 (80%) of the 223 cadavers. Of 3,568 disks, 459 (13%) had IDC, and 289 cases (63%) were located in the annulus fibrosus. IDC was most common in the lower thoracic spine, occurring in 275 (60%) of 459 disks. IDC occurred in 159 (87%) of 183 men and 19 (48%) of 40 women. Logistic regression analysis was adjusted for age, and results showed that the frequency of IDC was significantly higher in men in upper, middle, and lower segments of the thoracic spine (P <.05) but not in the lumbar spine (P =.09). IDC correlated with increasing age (P <.001) and disk space loss (P <.001) at all spinal levels. There was no association of IDC with vacuum phenomena or vertebral endplate abnormalities at any spinal level. CONCLUSION: IDC is common in elderly persons, especially in the annulus fibrosus and lower thoracic spine. The prevalence of IDC increases with age and extent of disk space loss.

Adult↗

PubMed2004

The effect of diabetes on B-type natriuretic peptide concentrations in patients with acute dyspnea: an analysis from the Breathing Not Properly Multinational Study.

OBJECTIVE: Diabetes has been implicated in reduced myocardial compliance and changes in the intercellular matrix of the myocardium. We determined the effect of diabetes on B-type natriuretic peptide (BNP) concentrations in patients presenting to the emergency department with dyspnea. RESEARCH DESIGN AND METHODS: The Breathing Not Properly Multinational Study was a prospective evaluation of 1,586 patients. A subset of 922 patients was obtained and subdivided into the following groups: group 1 (n = 324), neither diabetes nor heart failure; group 2 (n = 107), diabetes and no heart failure; group 3 (n = 247), no diabetes and heart failure; group 4 (n = 183), both diabetes and heart failure; group 5 (n = 41), heart failure history with no diabetes; and group 6 (n = 20), heart failure history with diabetes. Patients from groups 1, 3, and 5 were matched to groups 2, 4, and 6, respectively, to have the same mean age, sex distribution, BMI, renal function, and New York Heart Association (NYHA) classification (for heart failure). RESULTS: There was no significant difference in median BNP levels between diabetes and no diabetes among no heart failure patients (32.4 vs.32.9 pg/ml), heart failure patients (587 vs. 494 pg/ml), and those with a heart failure history (180 vs. 120 pg/ml). Receiver-operating characteristic curve analysis of the area under the curve for BNP was not different in diabetic versus nondiabetic patients (0.888 vs. 0.878, respectively). However, in a multivariate model, diabetes was an independent predictor of a final diagnosis of heart failure (odds ratio 1.51, 95% CI 1.03-2.02; P < 0.05). CONCLUSIONS: History of diabetes does not impact BNP levels measured in patients with acute dyspnea in the emergency department. Despite the impact of diabetes on the cardiovascular system, diabetes does not appear to confound BNP levels in the emergency department diagnosis of heart failure.

Acute Disease↗

PubMed2003

Bedside B-Type natriuretic peptide in the emergency diagnosis of heart failure with reduced or preserved ejection fraction. Results from the Breathing Not Properly Multinational Study.

OBJECTIVES: This study examines B-type natriuretic peptide (BNP) levels in patients with systolic versus non-systolic dysfunction presenting with shortness of breath. BACKGROUND: Preserved systolic function is increasingly common in patients presenting with symptoms of congestive heart failure (CHF) but is still difficult to diagnose. METHODS: The Breathing Not Properly Multinational Study was a seven-center, prospective study of 1,586 patients who presented with acute dyspnea and had BNP measured upon arrival. A subset of 452 patients with a final adjudicated diagnosis of CHF who underwent echocardiography within 30 days of their visit to the emergency department (ED) were evaluated. An ejection fraction of greater than 45% was defined as non-systolic CHF. RESULTS: Of the 452 patients with a final diagnosis of CHF, 165 (36.5%) had preserved left ventricular function on echocardiography, whereas 287 (63.5%) had systolic dysfunction. Patients with non-systolic heart failure (NS-CHF) had significantly lower BNP levels than those with systolic heart failure (S-CHF) (413 pg/ml vs. 821 pg/ml, p < 0.001). As the severity of heart failure worsened by New York Heart Association class, the percentage of S-CHF increased, whereas the percentage of NS-CHF decreased. When patients with NS-CHF were compared with patients without CHF (n = 770), a BNP value of 100 pg/ml had a sensitivity of 86%, a negative predictive value of 96%, and an accuracy of 75% for detecting abnormal diastolic dysfunction. Using Logistic regression to differentiate S-CHF from NS-CHF, BNP entered first as the strongest predictor followed by oxygen saturation, history of myocardial infarction, and heart rate. CONCLUSIONS: We conclude that NS-CHF is common in the setting of the ED and that differentiating NS-CHF from S-CHF is difficult in this setting using traditional parameters. Whereas BNP add modest discriminatory value in differentiating NS-CHF from S-CHF, its major role is still the separation of patients with CHF from those without CHF.

Adolescent↗

PubMed2003

B-type natriuretic peptide and renal function in the diagnosis of heart failure: an analysis from the Breathing Not Properly Multinational Study.

BACKGROUND: Both B-type natriuretic peptide (BNP) and renal function are prognostic indicators of survival in patients with congestive heart failure (CHF). However, relationships between BNP, renal function, and heart failure as an emergency diagnosis are unknown. METHODS: The Breathing Not Properly Multinational Study was a prospectively designed diagnostic test evaluation study conducted in seven centers. Of 1,586 participants who presented with acute dyspnea, 1,452 patients (91.6%) had both BNP level and baseline estimated glomerular filtration rate (eGFR) available. Patients with an eGFR less than 15 mL/min/1.73 m2 and those on dialysis therapy were excluded. The final diagnosis was adjudicated by two independent cardiologists who were blinded to BNP results. RESULTS: The final diagnosis was CHF in 715 patients (49.2%). Raw and log-log transformed correlations between BNP and eGFR values were r = -0.19 and r = -0.17 for those with CHF and r = -0.20 and r = -0.31 for those without CHF (both P < 0.0001 for r not equal 0). Mean BNP levels were 561.6 pg/mL (162.3 fmol/mL), 647.5 pg/mL (187.1 fmol/mL), 745.6 pg/mL (215.5 fmol/mL), and 850.7 pg/mL (245.8 fmol/mL) for those with CHF and 85.4 pg/mL (24.7 fmol/mL), 131.7 pg/mL (38.1 fmol/mL), 297.2 pg/mL (85.9 fmol/mL), and 285.0 pg/mL (82.3 fmol/mL) for those without CHF in eGFR categories of 90 or greater, 89 to 60, 59 to 30, and less than 30 mL/min/1.73 m2, respectively. The area under the receiver operating characteristic curve and optimum cut points for BNP were 0.91 and 70.7 pg/mL (20.4 fmol/mL), 0.90 and 104.3 pg/mL (30.1 fmol/mL), 0.81 and 201.2 pg/mL (58.1 fmol/mL), and 0.86 and 225.0 pg/mL (65.0 fmol/mL) for the eGFR categories of 90 or greater, 89 to 60, 59 to 30, and less than 30 mL/min/1.73 m2, respectively. CONCLUSION: Renal function correlates weakly with BNP and influences the optimal cut point for BNP, particularly in those with an eGFR less than 60 mL/min/1.73 m2.

Acute Disease↗

PubMed2003

PRC bisection tests.

This communication presents a new method for evaluating phase response curves (PRCs). A PRC describes the phase shifts produced in an oscillator by stimuli applied at different initial phase-states of that oscillator. In the PRC bisection tests, we repeatedly cut in half the circular distribution of the initial phase-states of the oscillator when stimuli are given. Empirically, we locate that optimal diameter which best bisects the circular distribution of phase responses into arcs of relative phase advance and phase delay. We compute a D score reflecting the success of the best bisection. The null hypothesis of a random distribution of phase responses by initial phase is tested with a Monte Carlo procedure, which computes Dr scores from random combinations of phase shifts with initial phases, thus determining the probability, given the null hypothesis, that the observed D score was from a random distribution. The bisection procedure can be extended to examine whether stronger phase shifts are produced in one phase response curve than in contrasting curves. Also, the bisection procedure yields an estimate of the inflection point of the phase response curve. A method is given to estimate the power of the PRC bisection test.

Animals↗

PubMed2003

Uncovering heart failure in patients with a history of pulmonary disease: rationale for the early use of B-type natriuretic peptide in the emergency department.

UNLABELLED: Plasma B-type natriuretic peptide (BNP) can reliably identify acute congestive heart failure (CHF) in patients presenting to the emergency department (ED) with acute dyspnea. Heart failure, asthma, and chronic obstructive pulmonary disease (COPD) are syndromes where dyspnea and wheezing are overlapping signs, and hence, these syndromes are often difficult to differentiate. OBJECTIVE: To determine whether BNP can distinguish new-onset heart failure in patients with COPD or asthma presenting with dyspnea to the ED. METHODS: The BNP Multinational Study was a seven-center prospective study of 1,586 adult patients presenting to the ED with acute dyspnea who had blinded BNP levels measured on arrival with a rapid, point-of-care device. This study evaluated the 417 patients with no previous history of heart failure and a history of asthma or COPD as a subgroup from the 1,586 adult patients in the BNP Multinational Study. The reference standard for CHF was adjudicated by two independent cardiologists, also blinded to BNP results, who reviewed all clinical data and standardized CHF scores. RESULTS: A total of 417 subjects (mean age 62.2 years, 64.4% male) had a history of asthma or COPD without a history of CHF. Of these, 87/417 (20.9%, 95% CI = 17.1% to 25.1%) were found to have CHF as the final adjudicated diagnosis. The emergency physicians identified a minority, 32/87 (36.8%), of these patients with CHF. The mean BNP values (+/- SD) were 587.0 +/- 426.4 and 108.8 +/- 221.3 pg/mL for those with and without CHF (p < 0.0001). At a cutpoint of 100 pg/mL, BNP had the following decision statistics: sensitivity 93.1%, specificity 77.3%, positive predictive value 51.9%, negative predictive value 97.7%, accuracy 80.6%, positive likelihood ratio 4.10, and negative likelihood ratio 0.09. If BNP would have been added to clinical judgment (high > or = 80% probability of CHF), at a cutpoint of 100 pg/mL, 83/87 (95.4%) of the CHF subjects would have been correctly diagnosed. Multivariate analysis found BNP to be the most important predictor of CHF (OR = 12.1, 95% CI = 5.4 to 27.0, p < 0.0001). In the 87 subjects found to have CHF, 39.0%, 22.2%, and 54.8% were taking angiotensin-converting enzyme inhibitors (ACEIs), beta-blockers (BBs), and diuretics on a chronic basis, respectively. CONCLUSIONS: The yield of adding routine BNP testing in patients with a history of asthma or COPD in picking up newly diagnosed CHF is approximately 20%. This group of patients presents a substantial therapeutic opportunity for the initiation and chronic administration of ACEI and BB therapy, as well as other CHF management strategies.

Aged↗

PubMed2003

Utility of B-type natriuretic peptide (BNP) as a screen for left ventricular dysfunction in patients with diabetes.

OBJECTIVE: Routine screening of diabetic patients with echocardiography is not feasible due to its limited availability and high cost. B-type natriuretic peptide (BNP) is secreted from the left ventricle in response to pressure overload and is elevated in both systolic and diastolic dysfunction. RESEARCH DESIGN AND METHODS: BNP levels were compared to echocardiographic findings in 263 patients. Patients were divided into two groups: clinical indication for echocardiography (CIE) (n = 172) and those without clinical indication for echocardiography (no-CIE) (n = 91). Cardiologists making the assessment of left ventricular function were blinded when measuring plasma levels of BNP. RESULTS: The 91 patients with no-CIE with echoes had similar BNP levels (83 +/- 16 pg/ml) to the 215 patients with no-CIE without echoes (63 +/- 10, P = 0.10). Patients with CIE and subsequent abnormal left ventricular function (n = 112) had a mean BNP concentration of 435 +/- 41 pg/ml, compared with those with no-CIE, but had abnormal left ventricular function on echo (n = 32) (161 +/- 40 pg/ml). Twenty-one of 32 patients with no-CIE but with abnormal left ventricular function had diastolic dysfunction (BNP 190 +/- 60 pg/ml). A receiver-operating characteristic (ROC) curve revealed that the area under the curve was 0.91 for CIE patients and 0.81 for no-CIE patients (P < 0.001). For those with no congestive heart failure (CHF) symptoms, BNP levels showed a high negative predictive value (91% for BNP values <39 pg/ml), while in those patients who had a CIE, BNP levels showed a high positive predictive value for the detection of left ventricular dysfunction (96% with BNP levels >90 pg/ml). CONCLUSIONS: BNP can reliably screen diabetic patients for the presence or absence of left ventricular dysfunction.

Atrial Fibrillation↗

PubMed2002

B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure: analysis from Breathing Not Properly (BNP) Multinational Study.

BACKGROUND: We sought to determine the degree to which B-type natriuretic peptide (BNP) adds to clinical judgment in the diagnosis of congestive heart failure (CHF). METHODS AND RESULTS: The Breathing Not Properly Multinational Study was a prospective diagnostic test evaluation study conducted in 7 centers. Of 1586 participants who presented with acute dyspnea, 1538 (97%) had clinical certainty of CHF determined by the attending physician in the emergency department. Participants underwent routine care and had BNP measured in a blinded fashion. The reference standard for CHF was adjudicated by 2 independent cardiologists, also blinded to BNP results. The final diagnosis was CHF in 722 (47%) participants. At an 80% cutoff level of certainty of CHF, clinical judgment had a sensitivity of 49% and specificity of 96%. At 100 pg/mL, BNP had a sensitivity of 90% and specificity of 73%. In determining the correct diagnosis (CHF versus no CHF), adding BNP to clinical judgment would have enhanced diagnostic accuracy from 74% to 81%. In those participants with an intermediate (21% to 79%) probability of CHF, BNP at a cutoff of 100 pg/mL correctly classified 74% of the cases. The areas under the receiver operating characteristic curve were 0.86 (95% CI 0.84 to 0.88), 0.90 (95% CI 0.88 to 0.91), and 0.93 (95% CI 0.92 to 0.94) for clinical judgment, for BNP at a cutoff of 100 pg/mL, and for the 2 in combination, respectively (P<0.0001 for all pairwise comparisons). CONCLUSIONS: The evaluation of acute dyspnea would be improved with the addition of BNP testing to clinical judgment in the emergency department.

Adolescent↗

PubMed2002

Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure.

BACKGROUND: B-type natriuretic peptide is released from the cardiac ventricles in response to increased wall tension. METHODS: We conducted a prospective study of 1586 patients who came to the emergency department with acute dyspnea and whose B-type natriuretic peptide was measured with a bedside assay. The clinical diagnosis of congestive heart failure was adjudicated by two independent cardiologists, who were blinded to the results of the B-type natriuretic peptide assay. RESULTS: The final diagnosis was dyspnea due to congestive heart failure in 744 patients (47 percent), dyspnea due to noncardiac causes in 72 patients with a history of left ventricular dysfunction (5 percent), and no finding of congestive heart failure in 770 patients (49 percent). B-type natriuretic peptide levels by themselves were more accurate than any historical or physical findings or laboratory values in identifying congestive heart failure as the cause of dyspnea. The diagnostic accuracy of B-type natriuretic peptide at a cutoff of 100 pg per milliliter was 83.4 percent. The negative predictive value of B-type natriuretic peptide at levels of less than 50 pg per milliliter was 96 percent. In multiple logistic-regression analysis, measurements of B-type natriuretic peptide added significant independent predictive power to other clinical variables in models predicting which patients had congestive heart failure. CONCLUSIONS: Used in conjunction with other clinical information, rapid measurement of B-type natriuretic peptide is useful in establishing or excluding the diagnosis of congestive heart failure in patients with acute dyspnea.

Acute Disease↗