Increased circulating pro-brain natriuretic peptide (proBNP) and brain natriuretic peptide (BNP) in patients with cirrhosis: relation to cardiovascular dysfunction and severity of disease

BACKGROUND AND AIMS: Cardiac dysfunction may be present in patients with cirrhosis. This study was undertaken to relate plasma concentrations of cardiac peptides reflecting early ventricular dysfunction (pro-brain natriuretic peptide (proBNP) and brain natriuretic peptide (BNP)) to markers of severity of liver disease, cardiac dysfunction, and hyperdynamic circulation in patients with cirrhosis. PATIENTS AND METHODS: Circulating levels of proBNP and BNP were determined in 51 cirrhotic patients during a haemodynamic investigation. RESULTS: Plasma proBNP and BNP were significantly increased in cirrhotic patients (19 and 12 pmol/l, respectively) compared with age matched controls (14 and 6 pmol/l; p<0.02) and healthy subjects (<15 and <5.3 pmol/l; p<0.002). Circulating proBNP and BNP were closely correlated (r = 0.89, p<0.001), and the concentration ratio proBNP/BNP was similar to that of control subjects (1.8 v 2.3; NS). Circulating proBNP and BNP were related to severity of liver disease (Child score, serum albumin, coagulation factors 2, 7, and 10, and hepatic venous pressure gradient) and to markers of cardiac dysfunction (QT interval, heart rate, plasma volume) but not to indicators of the hyperdynamic circulation. Moreover, in multiple regression analysis, proBNP and BNP were also related to arterial carbon dioxide and oxygen tensions. The rate of hepatic disposal of proBNP and BNP was not significantly different in cirrhotic patients and controls. CONCLUSION: Elevated circulating levels of proBNP and BNP in patients with cirrhosis most likely reflects increased cardiac ventricular generation of these peptides and thus indicates the presence of cardiac dysfunction, rather than being caused by the hyperdynamic circulatory changes found in these patients.     

B-type natriuretic peptide and its precursor in cardiac venous blood from failing hearts

BACKGROUND: Plasma concentrations of B-type natriuretic peptide (BNP-32) and its precursor (proBNP) are increased in chronic heart failure. Accordingly, BNP-32 and proBNP are both being implemented as clinical markers. AIM: To determine the molar relation of BNP-32 and proBNP in different cardiovascular regions. METHODS AND RESULTS: Blood samples were obtained from different cardiovascular regions during right heart catheterization in heart failure patients, and from normal subjects. Plasma BNP-32 and proBNP concentrations were measured using sequence-specific radioimmunoassays. Patients with severe left ventricular dysfunction (n=21) displayed increased peripheral plasma concentrations of both BNP-32 (four-fold, P=0.0008) and proBNP (seven-fold, P=0.0002) compared with normal subjects. Moreover, the peripheral concentrations were highly correlated with the corresponding concentrations in the coronary sinus (BNP-32: r=0.97, P<0.0001; proBNP: r=0.94, P<0.0001). Despite comparable peripheral concentrations of BNP-32 and proBNP, the BNP-32 concentration was higher than the proBNP concentration in the coronary sinus (median 126 pmol/l (21-993) vs. 103 pmol/l (16-691), P=0.035). CONCLUSIONS: The BNP-32 and proBNP concentrations are closely related in venous cardiac blood. The findings suggest an overall constitutive secretion of processed proBNP, i.e. an N-terminal precursor fragment and BNP-32, in chronic heart failure.     

Association between extent of coronary artery disease and ventricular premature beat frequency after myocardial infarction

Severe coronary artery disease (CAD) and frequent ventricular premature beats (VPBs) on ambulatory ECG monitoring in the late hospital phase after myocardial infarction are independent predictors of prognosis. To study the relationship between extent of CAD and VPB frequency, 128 consecutive (91 men, 37 women) patients surviving 6 days after myocardial infarction underwent 24-hour ECG, coronary angiography, and left ventriculography. CAD was graded as zero to one-, two-, and three-vessel (V), and also by a previously validated "jeopardy score" with 0 to 12 as grades of incremental CAD severity. Average VPB frequency was significantly correlated with CAD by V, CAD by jeopardy score, and by left ventricular ejection fraction (p less than 0.01 for all three). With the use of a multivariate ordinal logistic regression model, both VPB frequency and left ventricular ejection fraction were found to have independent association with CAD. The median VPB frequency was 1/hr, 0.6/hr, and 6/hr in zero to one-, two-, and three-V CAD, respectively (zero to one- and two-V CAD vs three-V CAD p less than 0.01, one-V CAD vs two-V CAD p = NS). In conclusion, frequent VPBs following myocardial infarction are associated with extensive CAD and are independent of left ventricular ejection fraction. Therefore, the prognostic value of frequent VPBs may be related to severe underlying ischemic disease.     

Plasma adrenomedullin as an indicator of prognosis after acute myocardial infarction

OBJECTIVE: To elucidate whether prognosis after acute myocardial infarction can be predicted by measuring plasma adrenomedullin, a novel vasorelaxant peptide. PATIENTS AND DESIGN: Plasma adrenomedullin concentrations on day 2 after myocardial infarction were measured in 113 patients with myocardial infarction with other clinical and haemodynamic variables related to mortality. RESULTS: During a mean follow up period of 25 months, 16 patients died of cardiac causes. Plasma adrenomedullin concentrations on day 2 increased significantly in patients with myocardial infarction compared with controls (mean (SD), 12.3 (8.8) v 4.9 (1.0) pmol/l, p < 0.001). Plasma adrenomedullin correlated negatively with left ventricular ejection fraction on admission (r = -0.47, p < 0.001), although it did not significantly correlate with any other haemodynamic variable. By univariate Cox proportional hazards analysis, plasma adrenomedullin, age, coronary reperfusion, maximum creatine kinase concentrations, pulmonary congestion, pulmonary capillary wedge pressure, cardiac index, and left ventricular ejection fraction were all significantly related to mortality. Among the non-invasive variables, only plasma adrenomedullin was an independent predictor of mortality after myocardial infarction (p < 0.05). The Kaplan-Meier survival curves based on the median plasma adrenomedullin concentration (10.3 pmol/l) showed that patients with high plasma adrenomedullin had a higher mortality than those with low plasma adrenomedullin (p < 0.01). CONCLUSIONS: Plasma adrenomedullin on day 2 after myocardial infarction is strongly associated with long term mortality, and thus may complement standard prognostic indicators.     

Direct comparison of brain natriuretic peptide (BNP) and N-terminal pro-BNP secretion and extent of coronary artery stenosis in patients with stable coronary artery disease.

BACKGROUND: It is unclear whether coronary artery stenosis affects the secretion of N-terminal pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) from the heart independent of ventricular dysfunction. Therefore, this study evaluated the relationship between BNP and NT-proBNP secretion, plasma levels and the severity of coronary artery stenosis in patients with stable coronary artery disease (CAD). METHODS AND RESULTS: Plasma levels of BNP and NT-proBNP in the aortic root (AO) and coronary sinus (CS) in 251 consecutive patients with stable CAD were measured. The transcardiac increase of NT-proBNP was significantly increased with the severity of coronary artery stenosis (p=0.012), but that of BNP was not (p=0.116). The molar ratio of the (CS-AO) NT-pro-BNP/(CS-AO) BNP increased with the severity of coronary artery stenosis (p=0.019) and decreased after coronary revascularization (p=0.018, n=36). Step-wise multivariate linear regression analyses were used to detect independent predictors of the (CS-AO) NT-proBNP among 10 variables including hemodynamic parameters and the Gensini score, which is a measure of the extent and severity of CAD. Among these variables, left ventricular ejection fraction (p<0.0001), left ventricular end-diastolic pressure (p=0.003) and log Gensini score (p=0.008) were significant independent predictors. CONCLUSION: These findings suggest that the transcardiac increase of NT-proBNP from the heart increases with the severity of coronary artery stenosis independent of hemodynamic overload, and plasma NT-proBNP may be superior to BNP to assess disease severity in CAD patients.     

Transcardiac gradients of N-terminal B-type natriuretic peptide in aortic valve stenosis

BACKGROUND: Plasma B-type natriuretic peptide (BNP), as well as the N-terminal part of the prohormone (Nt-BNP), are frequently elevated in aortic valve stenosis (AS). Yet, their release from the heart into the circulation has never been directly studied in AS. AIM: To assess the release of Nt-BNP in AS with focus on the identification of its main determinants. METHODS: We studied 49 adult patients undergoing preoperative cardiac catheterization for isolated AS. Blood was sampled from the aortic root and the coronary sinus for Nt-BNP determination by immunoassay. RESULTS: The mean (+/-S.E.) transcardiac Nt-BNP step-up averaged 79+/-53 pmol/l in 11 control patients free of structural heart disease, 75+/-32 pmol/l in 31 AS patients free of heart failure (HF), 236+/-62 pmol/l in 8 AS patients with diastolic HF (ejection fraction > or = 50%, pulmonary wedge pressure > 14 mm Hg) and 469+/-66 pmol/l in 7 AS patients with systolic HF (ejection fraction < 50%, wedge pressure > 14 mm Hg) (p<0.001). The transcardiac Nt-BNP gradient was independently associated with left ventricular (LV) end-diastolic pressure (beta=0.47, p<0.001) and ejection fraction (beta=-0.29, p<0.019) and with co-existent coronary artery disease (beta=0.23, p=0.050). CONCLUSION: LV diastolic and systolic dysfunction along with coronary artery disease are likely to be the key determinants of cardiac Nt-BNP release in AS. The transcardiac Nt-BNP gradient increases on average three-fold with the development of diastolic HF and six-fold in systolic HF.     

Evaluation of prognosis after Q wave myocardial infarction. Comparison of invasive and noninvasive diagnostic strategies

The predictive value of several diagnostic strategies after myocardial infarction was assessed in 178 patients (mean age 55 +/- 9 years) treated medically after a primary Q wave myocardial infarction. Within 6 weeks of onset of symptoms the authors performed exercise stress test coupled with Thallium 201 scintigraphy, isotopic left ventriculography and conventional coronary angiography with ventriculography. The average left ventricular ejection fraction was 45 +/- 12%. Two non-invasive diagnostic strategies with and without results of scintigraphy and two invasive strategies with and without ventricular volumes were studied. The average follow-up period was 58 +/- 22 months. Sixteen cardiac deaths occurred. Multivariate Cox analysis showed that, in contrast to left ventricular volumes, coronary angiography did not provide additional prognostic value compared with the non-invasive model with Thallium scintigraphy and did not appear to be essential in terms of predictive value in this population. Moreover, the size of reversible defect on Thallium scintigraphy was an independent predictive factor of cardiac death and provided additional and independent prognostic information in the non-invasive and invasive strategies. Therefore, the reduction of residual ischaemia by coronary revascularisation could improve the long-term prognosis after myocardial infarction.     

Comparison of LVEF Obtained with Single-Plane RAO Ventriculography and Echocardiography in Patients with and without Obstructive Coronary Artery Disease

The left ventricular ejection fraction (LVEF) determined by invasive ventriculography (routine cardiac cath; LV-gram) was compared with that determined by echocardiography in 100 patients scheduled for angiography (86% had LV-gram and 2DE during same hospital admission). Seventy percent of patients had at least single-vessel obstructive coronary artery disease, defined as more than 50% stenosis. By all estimates, the LVEF was higher in patients without coronary artery disease (CAD) compared to patients with CAD. There was an excellent correlation between the LVEF by cath and echo, but this correlation was noticeably less strong in patients with CAD, especially with involvement of the left circumflex artery.     

Prevalence and prognostic significance of exercise-induced ventricular arrhythmias after coronary artery bypass grafting

Exercise-induced ventricular arrhythmias occur often after coronary artery bypass grafting (CABG), but their prognostic significance is unknown. Two hundred patients examined by exercise electrocardiography and cardiac catheterization (including left ventriculography, bypass graft and native coronary artery angiography) before and 3 months after CABG were prospectively followed up. Exercise-induced ventricular arrhythmias occurred more often after (49 of 200 patients, 24.5%) than before (32 of 200 patients, 16.0%) CABG (p less than 0.05). There were no differences between the patients with and without ventricular arrhythmias in the prevalence of graft patency (79 vs 80%) or the postoperative ejection fraction (57 +/- 9 vs 57 +/- 12%). Ten cardiac deaths occurred during the mean follow-up time of 61 +/- 19 months, 8 of which were witnessed sudden cardiac deaths. All cardiac deaths occurred in patients who did not have exercise-induced ventricular arrhythmias after CABG. The postoperative ejection fraction was lower in the cardiac death patients (42 +/- 16%) than in the survivors (58 +/- 10%) (p less than 0.01). No other clinical or angiographic variable predicted the occurrence of cardiac death. Thus, the prevalence of exercise-induced ventricular arrhythmias increases after CABG, but the occurrence of ventricular arrhythmias does not indicate an increased risk of cardiac death.     

Increased brain and atrial natriuretic peptides in patients with chronic right ventricular pressure overload: correlation between plasma neurohormones and right ventricular dysfunction

OBJECTIVE—To evaluate the role of plasma neurohormones in the diagnosis of asymptomatic or minimally symptomatic right ventricular dysfunction.
SETTING—Tertiary cardiovascular referral centre.
METHODS—Plasma brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) concentrations were measured in 21 asymptomatic or minimally symptomatic patients with chronic right ventricular pressure overload caused by congenital heart disease, and in seven healthy volunteers. Right ventricular ejection fraction was determined using magnetic resonance imaging.
RESULTS—Right ventricular ejection fraction in the volunteers was higher than in the patients (69.0 (8.2)% v 58.0(12.0)%, respectively; p < 0.006). Left ventricular ejection fraction was 72.3(7.8)% in volunteers and 68.1(11.0)% in patients (NS). There was a significant difference between patients and volunteers in the plasma concentrations of BNP (5.3 (3.5) v 2.3 (1.7) pmol/l, respectively; p < 0.009) and ANP (7.3 (4.5) v 3.6 (1.4) pmol/l; p < 0.05). In both patients and volunteers, mean plasma ANP was higher than mean plasma BNP. Right ventricular ejection fraction was inversely correlated with BNP and ANP (respectively, r = 0.65; p < 0.0002 and r = 0.61; p < 0.002). There was no correlation between left ventricular ejection fraction and BNP (r = 0.2; NS) or ANP (r = 0.52; NS). Similarly, no correlation was shown between the level of right ventricular systolic pressure and either plasma BNP (r = 0.20) or plasma ANP (r = 0.07).
CONCLUSIONS—There was a significant inverse correlation between right ventricular ejection fraction and the plasma neurohormones BNP and ANP in asymptomatic or minimally symptomatic patients with right ventricular pressure overload and congenital heart disease. Monitoring changes in BNP and ANP may provide quantitative follow up of right ventricular dysfunction in these patients.


Keywords: natriuretic peptides; right ventricle; pressure overload; congenital heart disease     

The differing prognostic utility of exercise radionuclide ventriculography in coronary artery disease patients with and without prior myocardial infarction

Previous studies have documented the prognostic utility of left ventricular ejection fraction response to exercise primarily in populations without prior myocardial infarction. We undertook a study to assess the prognostic utility of exercise left ventricular ejection fraction and segmental wall motion response during exercise radionuclide ventriculography in coronary artery disease patients with and without prior myocardial infarction. Methods. We examined the comparative prognostic utility of left ventricular ejection fraction and segmental wall motion response during upright bicycle exercise radionuclide ventriculography in 419 coronary artery disease patients with (n=217) and without (n=202) prior myocardial infarction using univariate and multivariate hierarchical regression analyses. Results. During an average followup period of 61 months, 96 patients (23%) suffered cardiac events, including 55/217 (25%) of the patients with prior myocardial infarction and 41/200 (21%) of the patients without prior myocardial infarction (p=ns). Both cumulative Kaplan-Meier survival analyses and stepwise hierarchical Cox survival analyses demonstrated that peak left ventricular ejection fraction <55% was a significant predictor of cardiac events in patients without prior myocardial infarction (p=0.04), whereas an exercise wall motion worsening score 2 was a significant predictor in patients with a prior myocardial infarction (p=0.0001). Conclusions. The prognostic utility of exercise radionuclide ventriculography variables differ according to the presence or absence of prior myocardial infarction. Global function, assessed by peak left ventricular ejection fraction, adds the greatest prognostic information in patients without prior myocardial infarction, whereas regional function, assessed by exercise wall motion worsening, is the best predictor among patients with prior myocardial infarction.     

Natriuretic peptides as markers of cardiotoxicity during doxorubicin treatment for non-Hodgkin's lymphoma

Thirty adult patients with non-Hodgkin's lymphoma who were planned to receive up to 8-10 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) to a cumulative doxorubicin dose of 400-500 mg/m2 were studied to evaluate the value of serial plasma atrial natriuretic peptide (ANP), N-terminal pro-ANP (NT-proANP) and brain natriuretic peptide (BNP) measurements in the early detection of doxorubicin-induced left ventricular dysfunction. Plasma levels of natriuretic peptides were measured before every treatment course and 4 wk after the last one. Cardiac function was monitored with serial radionuclide ventriculography. Twenty-eight patients were evaluable for cardiotoxicity. Clinical heart failure developed in 2 patients (7%). Left ventricular ejection fraction (LVEF) decreased from 58.0+/-1.3% to 49.6+/-1.7% (p <0.001). Plasma levels of ANP increased from 16.4+/-1.3 pmol/l to 22.7+/-2.4 pmol/l (p= 0.002), NT-proANP from 288+/-22 to 380+/-42 pmol/l (p = 0.019) and BNP from 3.3+/-0.4 to 8.5+/-2.0 pmol/l (p = 0.020). There was a significant correlation between the increase in plasma ANP and the decrease in LVEF (r = -0.447, p = 0.029), and a trend towards significance between the increase in NT-proANP and the decrease in LVEF (r=-0.390, p=0.059). The decrease in LVEF started very early and could already be seen after the cumulative doxorubicin dose of 200 mg/m2, whereas the increase in plasma natriuretic peptides was not evident until the cumulative doxorubicin dose of 400 mg/m2. Our results show that neuroendocrine activation - increased concentrations of plasma natriuretic peptides - occurs when left ventricular function has reduced substantially and its compensatory capacity has been exceeded resulting in atrial and ventricular overload. Thus, serial natriuretic peptide measurements cannot be used in predicting the impairment of left ventricular function. On the other hand, our study suggests that natriuretic peptides are useful in the detection of subclinical left ventricular dysfunction in patients receiving doxorubicin therapy.     

Plasma brain natriuretic peptide after long-term treatment for heart failure in general practice

AIM: Plasma brain natriuretic peptide (BNP) concentrations are known to have high sensitivity and specificity in the diagnosis of heart failure in newly symptomatic patients. The relationship of plasma BNP to cardiac function in stable patients on long-term established treatment for heart failure is unknown. Plasma BNP was assessed for its ability to predict echocardiographic abnormality in 100 patients receiving long-term treatment in general practice for a provisional diagnosis of heart failure. METHODS AND RESULTS: BNP >35 pmol/l had a sensitivity and specificity of 69% and 67%, respectively, for a left ventricular ejection fraction of <45%. However, 19% of patients had an LVEF of below 45% whilst BNP was below 35 pmol/l. These patients, in whom a diagnosis of heart failure had been made years previously (mean 3.9 years), were all clinically stable on treatment. CONCLUSION: These findings support the view that BNP can be restored to normal levels in well-compensated patients despite persisting significant systolic dysfunction and suggest that BNP assays may be helpful for monitoring adequacy of therapy. BNP assays will have limited utility in the diagnosis of cardiac impairment once anti-failure therapy is well established and symptoms have been abolished.     

Neuroendocrine prediction of left ventricular function and heart failure after acute myocardial infarction

Objective—To determine the relations of plasma levels of brain natriuretic peptide (BNP), atrial natriuretic factor (ANF), N-terminal ANF (N-ANF), cyclic guanosine monophosphate (cGMP; the cardiac peptide second messenger), and plasma catecholamines to left ventricular function and to prognosis in patients admitted with acute myocardial infarction.
Design—Plasma hormones and ventricular function (radionuclide ventriculography) were measured 1-4 days after myocardial infarction in 220 patients admitted to a single coronary care unit. Radionuclide scanning was repeated 3-5 months after infarction. Clinical events were recorded over a mean period of 14 months.
Results—Both early and late left ventricular ejection fraction (LVEF) were most closely related to plasma BNP (r = −0.60, n = 220, p < 0.001; and r = −0.53, n = 192, p < 0.001, respectively), followed by ANF, N-ANF, cGMP, and the plasma catecholamines. Early plasma BNP concentrations less than twofold the upper limit of normal (20 pmol/l) had 100% negative predictive value for LVEF < 40% at 3-5 months after infarction. In multivariate analysis incorporating all the neurohormonal factors, only BNP remained independently predictive of LVEF < 40% (p < 0.005). Survival analysis by median levels of candidate predictors identified BNP as the most powerful discriminator for death (p < 0.0001). No early deaths (within 4 months) occurred in patients with plasma BNP concentrations below the group median (27 pmol/l), and over follow up only three of 26 deaths occurred in this subgroup. Of all episodes of left ventricular failure, 85% occurred in patients with plasma BNP above the median (p < 0.001). In multivariate analyses, BNP alone gave additional predictive information beyond sex, age, clinical history, LVEF, and plasma noradrenaline for both subsequent onset of LVF and death.
Conclusions—Plasma BNP measured within 1-4 days of acute myocardial infarction is a powerful independent predictor of left ventricular function, heart failure, or death over the subsequent 14 months, and superior to ANF, N-ANF, cGMP, and plasma catecholamines.

Keywords: cardiac natriuretic peptides; noradrenaline; myocardial infarction; heart failure     

Left ventricular dilatation. Prognostic value in severe left ventricular dysfunction secondary to coronary artery disease

This study determines the noninvasive prognostic predictors (using radionuclide angiography) in patients with severe left ventricular dysfunction (resting ejection fraction less than or equal to 35 percent) secondary to coronary artery disease. We retrospectively evaluated 94 such patients using rest and exercise radionuclide ventriculography. At a mean follow-up of 16 months, cardiac events occurred in 22 patients: ten patients died of cardiac causes, five patients sustained nonfatal myocardial infarction, and seven patients developed severe congestive heart failure (class 4). Results indicate that patients with severe left ventricular dysfunction may be stratified into different risk groups according to left ventricular size. Marked left ventricular dilatation identifies a subgroup at high risk.     

Clinical significance of acute-phase brain natriuretic peptide in acute myocardial infarction treated with direct coronary angioplasty

OBJECTIVES: To investigate the relationship between brain natriuretic peptide (BNP) plasma concentration levels and the clinical course, mortality and success of left ventricular remodeling by direct percutaneous coronary intervention (PCI) in patients with acute myocardial infarction. METHODS: One hundred thirty consecutive first-acute myocardial infarction patients were successfully reperfused by direct PCI. BNP plasma concentration levels were assessed at 24 hr from onset, and patients were divided into the high (> or = 290 pg/ml) plasma BNP group (H-BNP group; n = 65) or low (< 290 pg/ml) plasma BNP subset (L-BNP group; n = 65). Left ventriculography was performed in both the acute (following reperfusion therapy) and chronic (20 +/- 8 days after onset) stages to evaluate left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI) and regional wall motion (RWM). Differences between the parameters at the two stages (chronic stage--acute stage) were expressed as delta LVEF, delta LVEDVI, and delta RWM. RESULTS: There were significantly more major complications in the H-BNP group than in the L-BNP group. There was significantly higher mortality in the H-BNP group (p < 0.01). Multivariate analysis identified only BNP plasma concentration as an independent predictor of mortality (p < 0.05). There were no significant differences in left ventricular function in the acute stage between the groups, but LVEF, LVEDVI, and RWM were all significantly worse in the chronic stage in the H-BNP group compared with the L-BNP group. Moreover, delta LVEF (p < 0.001), delta LVEDVI (p < 0.05), and delta RWM (p < 0.01) were also significantly worse in the H-BNP group. CONCLUSIONS: Early-phase BNP plasma concentrations after successful PCI in patients with acute myocardial infarction may be correlated closely with major complications, and may be of prognostic importance. BNP plasma concentration may also be an indicator of left ventricular remodelling.     

B-type natriuretic peptide and its molecular precursor in myocardial infarction complicated by cardiogenic shock

BackgroundPlasma measurement of cardiac natriuretic peptides and their biosynthetic precursors is helpful in chronic heart failure patients. In contrast, information on circulating B-type natriuretic peptide (BNP) and its molecular precursor (proBNP) in patients with cardiogenic shock is scarce. We therefore examined proBNP-derived peptides in plasma from patients with myocardial infarction complicated by cardiogenic shock.Methods and ResultsPatients were referred for early, invasive therapy because of myocardial infarction complicated by cardiogenic shock (n = 13). Plasma proBNP was measured with an automated assay (NT-proBNP) and an in-house radioimmunoassay (proBNP); BNP concentrations were quantitated with an immunoradiometric assay. The median NT-proBNP concentration was 8.2-fold higher than the corresponding BNP concentration (873 pmol/L [range 41–12,486] versus 107 pmol/L [1–1041], P < .001). Moreover, the NT-proBNP concentration was 3.3-fold higher compared with proBNP (268 pmol/L [19–12,220], P < .01). Despite the molar differences, there was a strong correlation between NT-proBNP and proBNP (r = 0.84, P < .0001) and BNP (r = 0.82, P < .0001) concentrations. Gel filtration chromatography suggested that the proBNP immunoreactivity reflect a molecular form larger than the N-terminal 1-76 fragment.ConclusionsThe study reveals the plasma profile of proBNP-derived peptides during myocardial infarction complicated by cardiogenic shock. Peripheral concentrations of NT-proBNP, proBNP, and BNP were highly correlated despite marked differences between assays. The results also suggest an increase in cardiac proBNP processing after myocardial infarction and cardiogenic shock.     

Plasma proatrial natriuretic factor (1-98) concentration after myocardial infarction: relation to indices of cardiac and renal function.

OBJECTIVES--(a) To assess the relation between plasma concentrations of proatrial natriuretic factor (1-98) and non-invasively derived indices of left ventricular systolic and diastolic performance and (b) to assess the potential confounding effect of renal function and age on this relation in patients with acute myocardial infarction. DESIGN--Cross sectional comparison of biochemical and echocardiographic indices of cardiac function. SETTING--Norwegian central hospital. PATIENTS--Sixty four patients with acute myocardial infarction. MAIN OUTCOME MEASURES--Relation between plasma proatrial natriuretic factor (1-98) concentrations and echocardiographic indices of left ventricular systolic function as assessed by univariate and multivariate linear regression analysis. Sensitivity and specificity of plasma proatrial natriuretic factor (1-98) concentration as a measure of left ventricular systolic and diastolic dysfunction. RESULTS--Plasma proatrial natriuretic factor (1-98) concentrations were significantly related to left ventricular ejection fraction (r = -0.33; P = 0.008), age (r = 0.43; P < 0.001), and creatinine clearance (r = - 0.53; P < 0.001). In a multivariate model left ventricular ejection fraction and creatinine clearance were both independently related to plasma values. The mean concentration of proatrial natriuretic factor (1-98) was significantly higher in patients with an ejection fraction of < 40% than in those with an ejection fraction of > or = 40% (1876 (1151) v 1174 (530) pmol/l; P = 0.03) and in patients with an abnormal transmitral E/A ratio ( < 0.65 or > 1.65, where E/A is ratio of peak early filling velocity to peak atrial component) compared with those with a normal ratio (1572 (895) v 1137 (523) pmol/l, respectively; P = 0.02). When patients were subdivided according to the median concentration of proatrial natriuretic factor (1192 pmol/l) the sensitivity and specificity were 89% and 56% respectively for detecting a left ventricular ejection fraction of < 40% and 75% and 61% respectively for detecting an abnormal E/A ratio. Concentrations below the median had a negative predictive value of 97% in excluding an ejection fraction of < 40% and of 84% in excluding an abnormal E/A ratio. CONCLUSION--These results suggest that soon after myocardial infarction left ventricular ejection fraction and indices of renal function are independently related to plasma concentrations of proatrial natriuretic factor (1-98). Plasma concentrations of proatrial natriuretic factor (1-98) seem to reflect renal and cardiac performance rather than specific haemodynamic variables assessed by noninvasive methods. Plasma proatrial natriuretic factor (1-98) measurements may be a useful screening tool to identify patients with normal cardiac function soon after myocardial infarction.     

Coronary sinus and ascending aortic levels of aldosterone, angiotensin II, and B-type natriuretic peptide in patients with aortic stenosis and in patients with coronary heart disease

Demonstration that aldosterone synthesis occurs in the myocardium would suggest that the clinical benefits of aldosterone receptor antagonists may extend to patients with normal circulating plasma levels of aldosterone. Previous studies have reported myocardial aldosterone synthesis in patients with heart failure. This study determined whether myocardial aldosterone and angiotensin II release occurs in patients with aortic stenosis (AS) and/or coronary heart disease (CHD) with normal left ventricular ejection fractions and no clinical heart failure. In 19 patients with severe AS and 18 patients with stable CHD, plasma levels of aldosterone, angiotensin II, B-type natriuretic peptide (BNP), and procollagen type III amino terminal peptide (PIIINP) were measured in blood samples taken from the coronary sinus and aortic root before diagnostic coronary angiography. Plasma aldosterone was approximately 20% greater in the coronary sinus than the aorta, respectively, in the 2 patient groups (AS: 120 vs 102 pmol/L, p <0.001; CHD: 94 vs 77 pmol/L, p <0.001). Plasma angiotensin II was also greater in the coronary sinus (AS: 16 vs 11 pmol/L, p <0.001; CHD: 12 vs 9 pmol/L, p <0.001). Plasma levels of BNP in the coronary sinus were approximately double those in the aorta in the 2 groups of patients (p <0.001). In contrast, there was no transmyocardial gradient in the plasma level of PIIINP for either AS or CHD. In conclusion, these results indicate that aldosterone, angiotensin II, and BNP are released into the coronary sinus in severe AS and in stable CHD, even when the left ventricular ejection fraction is normal and there is no clinical heart failure.     

Anatomic and functional significance of a hypotensive response during supine exercise radionuclide ventriculography

The significance of a decline in systolic blood pressure (BP) during supine exercise was examined in 820 patients who underwent both supine exercise gated equilibrium radionuclide ventriculography and coronary angiography. Twenty-seven patients, 3% of the study population, had a decrease in systolic BP at peak exercise of more than 10 mm Hg from the systolic BP at rest. Other indicators of ischemia--angina, ST-segment depression, a decrease in ejection fraction and wall motion abnormality during exercise--were present frequently but not uniformly in these patients. Although most patients had a decline in ejection fraction and a new wall motion abnormality with exercise, 4 patients had an increase in ejection fraction with exercise without any regional wall motion abnormalities. Coronary angiography in the 27 patients with systolic hypotension demonstrated severe coronary artery disease (CAD). Twenty-two patients (81%) had 3-vessel or left main CAD. Twenty of these 22 patients with 3-vessel CAD had at least 2 arteries with 90% or more diameter stenoses. Systolic hypotension during supine exercise radionuclide angiography is infrequent, usually associated with evidence of global and regional left ventricular dysfunction, and a marker of very severe CAD.