Left ventricular systolic dysfunction in 75-year-old men and women; a population-based study.

AIMS: To determine the prevalence of left ventricular systolic dysfunction in 75-year-old men and women. METHODS AND RESULTS: In a population-based random sample of 75-year-old subjects (n=433; response rate 70.1%) the left ventricular systolic function was determined using two echocardiographic methods: (1) wall motion in nine left ventricular segments was visually scored and wall motion index was calculated as the mean value of the nine segments and (2) ejection fraction as measured by the disc summation method. Presence of heart failure was determined by a cardiologist's clinical evaluation. Wall motion index was achievable in 95% of the participants while ejection fraction was measurable in 65%. Normal values were obtained from a healthy subgroup (n=108) and left ventricular systolic dysfunction was defined as the 0.5th percentile of the wall motion index (i.e. <1.7). In participants in whom both ejection fraction and wall motion index were achievable, wall motion index <1.7 predicted ejection fraction <43% with a sensitivity and specificity of 84.0% and 99.6%, respectively. The prevalence of left ventricular systolic dysfunction was 6.8% (95% CI, 5.6--8.0%) and was greater in men than in women (10.2% vs 3.4%, P=0.006). Clinical evidence of heart failure was absent in 46% of the participants with left ventricular systolic dysfunction. CONCLUSIONS: Left ventricular systolic dysfunction is common among 75-year-olds with a prevalence of 6.8% in our estimate. The condition is more likely to affect men than women. In nearly half of 75-year-olds with left ventricular systolic dysfunction there is no clinical evidence of heart failure.     

Screening for left ventricular systolic dysfunction: the use of B-type natriuretic peptide

Congestive heart failure (CHF) is a disease condition that is increasing in prevalence and is associated with significant morbidity and mortality. Left ventricular systolic dysfunction (LVSD) is a treatable precursor of CHF, but remains asymptomatic in about half of the individuals afflicted. This observation has spurred interest in screening for LVSD. Plasma B-type natriuretic peptide (BNP) is a widely accepted test for the diagnosis of overt CHF. In this review, we examine the potential role for plasma BNP as a screening tool for asymptomatic LVSD. The performance of any screening test depends on its accuracy, the prevalence of the disease condition screened for, and the availability of resources for follow-up of individuals in whom the disease was detected. In the context of community-wide screening for LVSD, a test with high specificity would be important so as to minimize the costs of expensive definitive follow-up tests (i.e. echocardiography). The prevalence of significant LVSD (ejection fraction 20.40) is low, limiting the enthusiasm for a screening program targeting the general population. This is especially true for women, in whom the condition is rare, and the performance characteristics of plasma BNP are sub-optimal. In men, plasma BNP may be a useful screening test in high-risk individuals in whom there are no other clinical indications for echocardiography. The choice of the appropriate plasma BNP threshold that triggers further work-up in such high-risk individuals may vary according to the availability of resources, and with the healthcare priorities of a community.     

Elevated B-type natriuretic peptide in asymptomatic men with chronic aortic regurgitation and preserved left ventricular systolic function

Serum B-type natriuretic peptide (BNP) levels reflect myocardial strain and are known to be elevated in patients with heart failure. To determine if BNP levels are elevated in patients with aortic regurgitation, we measured BNP levels in patients with chronic asymptomatic aortic regurgitation and normal left ventricular systolic function.     

Use of B-type natriuretic peptide as a screening tool for left ventricular diastolic dysfunction in rheumatoid arthritis patients without clinical cardiovascular disease

Objective

Patients with rheumatoid arthritis (RA) are at an increased risk for heart failure and left ventricular diastolic dysfunction (LVDD). B‐type natriuretic peptide (BNP) may be useful to screen for LVDD in the general population. We compared the effectiveness of BNP as a screening tool for LVDD in RA and non‐RA subjects without cardiovascular disease (CVD).

Methods

Study subjects were recruited from population‐based samples with and without RA, excluding subjects with CVD. LVDD was assessed by 2‐dimensional and Doppler echocardiography and categorized as none, mild, moderate/severe, or indeterminate. Linear regression and proportional odds models evaluated the association between LVDD and BNP, adjusting for age, sex, and body mass index.

Results

Among 231 RA and 1,730 non‐RA subjects without CVD, BNP was significantly higher in subjects with moderate/severe LVDD compared to those with no or mild LVDD (P = 0.02 for RA and P < 0.001 for non‐RA subjects). More RA subjects had elevated BNP than non‐RA subjects (16% versus 9%; P < 0.001). Positive predictive value (25% in RA and 18% in non‐RA subjects) and sensitivity (40% in RA and 26% in non‐RA subjects) were similarly low in both cohorts, but specificity was significantly lower in RA than in non‐RA subjects (89% versus 94%; P = 0.02).

Conclusion

While RA subjects were more likely to have elevated BNP, few RA patients with elevated BNP actually have LVDD. Also, normal BNP levels are less likely to rule out LVDD in RA than in non‐RA subjects. Therefore, BNP may be less effective for screening in RA subjects compared to the general population.     

N-端心房利钠肽与N-端脑利钠肽对预测左室收缩功能障碍的价值

目的比较N-端心房利钠肽(心钠素NT-proANP)和N-端脑钠肽(NT-proBNP)对左室收缩功能障碍(LVSD)预测效率,依据二者特性确定适用范围并界定最佳下限(cut-off)值。方法入选心血管病患者380例(病例组),依据左室射血分数(LVEF)将患者划分为LVSD组(LVEF≤40%,n=90)及非LVSD组(LVEF40%,n=290)。另选136名健康体检者作为对照组。超声心动图测定LVEF;ELISA法测定血浆NT-proANP和NT-proB-NP浓度。描记NT-proANP和NT-proBNP预测左室收缩功能障碍受试者工作特征(ROC)曲线。依据年龄(以65岁为分界)、性别及原发心血管疾病种类划分亚组,分别描记各组患者NT-proANP和NT-proBNP预测左室收缩功能障碍ROC曲线;确定最佳cut-off值。结果病例组血浆NT-proANP和NT-proBNP浓度均显著高于对照组log(NT-proANP):(3.30±0.41)vs(2.98±0.16),P0.01;log(NT-proBNP):(2.71±0.30)vs(2.49±0.13),P0.01。NT-proANP和NT-proBNP对不同程度LVSD(LVEF≤40%或LVEF≤30%)患者诊断ROC曲线下面积(AUC)均大于0.73(P0.01);对LVEF≤40%的患者,NT-proANPAUC大于NT-proBNP(0.820vs0.738);对LVEF≤30%的患者,NT-proANPAUC明显小于NT-proBNP(0.853vs0.877)。根据各亚组ROC曲线确定cut-off值,NT-proANP为1676.92pmol/L时对各组LVSD预测敏感度88.9%～100%;特异度14.0%～58.7%;阳性预测值9.04%～30.04%;阴性预测值96.96%～98.77%。NT-proBNP为417.37pmol/L时,敏感度77.8%～94.4%;特异度10.0%～55.8%;阳性预测值7.07%～48.88%;阴性预测值94.46%～98.87%。结论 NT-proBNP与NT-proANP均能够反映心力衰竭高危人群心脏功能状态,可作为LVSD的诊断指标,对于LVEF≤40%的预测,NT-proANP效果优于NT-proBNP,有助于早期发现LVSD患者。     

Value of B-type natriuretic peptide in diagnosing left ventricular dysfunction in dialysis-dependent patients

Background: B‐type natriuretic peptide (BNP) is elevated in patients with end‐stage renal failure. The reported accuracy of BNP in diagnosing left ventricular dysfunction in these patients has been inconsistent. Aim: To investigate the diagnostic values of BNP for left ventricular dysfunction in patients undergoing haemodialysis for chronic renal failure. Methods: We measured plasma BNP before and at 10 min and 3, 6 and 24 h after haemodialysis in 56 patients. Results: The average plasma BNP before haemodialysis was 284 ± 369 pg/mL, which was higher than that of healthy subjects (37 ± 37 pg/mL; n = 32, P < 0.01). The average plasma BNP in patients with left ventricular dysfunction (n = 21) was substantially higher than that in those with normal ventricular function before and at 10 min and 3, 6 and 24 h after haemodialysis (P < 0.001). The area under the receiver operating characteristic curves was greater than 0.895 before and at the four time points after haemodialysis (P < 0.01). Using 152 pg/mL as a cut‐off value, predialysis BNP has 81% sensitivity and 83% specificity in diagnosing left ventricular dysfunction in these patients. Conclusion: We concluded that plasma BNP offers a good sensitivity and specificity in diagnosing left ventricular dysfunction in patients with dialysis‐dependent renal failure.     

Plasma pro-B-type natriuretic peptide in the general population: screening for left ventricular hypertrophy and systolic dysfunction.

AIMS: B-type natriuretic peptide (BNP) measurement in screening for left ventricular hypertrophy (LVH) and left ventricular systolic dysfunction (LVSD) has been evaluated in the general population, but corresponding information on proBNP and the N-terminal proBNP fragment is still limited. We therefore examined whether proBNP measurement is useful for LVH and LVSD screening in the general population. METHODS AND RESULTS: In the 4th Copenhagen City Heart Study, 3497 participants underwent echocardiography with assessment of left ventricular ejection fraction (LVEF) and mass. The impact of gender and age was determined and the diagnostic performance of the plasma proBNP concentration was evaluated using receiver operating characteristic (ROC) curves. Of 1502 men and 1995 women, 4.1 and 2.6% had LVSD defined as an LVEF<60% whereas only 0.4% displayed LVEF<40%. The proBNP concentration was 1.7-fold higher in women compared with men (P<0.0001) and related to age in both genders. The mean proBNP plasma concentration was two-fold higher in subjects with LVSD than without LVSD (P<0.0001). Likewise, LVH imposed a 1.9-fold increase in the proBNP concentration (P<0.0001): Both differences persisted after adjusting for ischaemic heart disease, hypertension, diabetes, gender, and age. The diagnostic performance of proBNP in detecting LVEF<40% was high with an area under the ROC curves of 0.92 (95% CI 0.79-1.00) in women and 0.85 (95% CI 0.74-0.96) in men. CONCLUSION: We have established the impact of age and gender on the proBNP concentration in a large, community-based cohort. The diagnostic performance for proBNP measurement in screening for LVH and LVSD in the general population parallels the reported data for BNP.     

Community screening for left ventricular systolic dysfunction using plasma and urinary natriuretic peptides

OBJECTIVES: We sought to compare urinary and plasma N-terminal pro-brain natriuretic peptide (N-BNP) in left ventricular systolic dysfunction (LVSD) diagnosis. BACKGROUND: Plasma N-BNP is elevated in LVSD. Renal tubule cells produce BNP. We tested the incremental value of urinary N-BNP in LVSD diagnosis. METHODS: In this prospective, community-screening study of undiagnosed LVSD, 1,360 subjects (45 to 80 years of age) were invited, and 1,308 had analyzable echocardiographic scans and urine and plasma specimens. The criterion standard for LVSD was defined as a wall motion score over 1.8 (ejection fraction < or =40%). RESULTS: Twenty-eight patients with LVSD had elevated urinary and plasma N-BNP levels compared with normal subjects (p < 0.0005). Receiver-operating characteristic (ROC) areas under the curve (AUCs) for urinary and plasma N-BNP were 0.831 and 0.840, respectively. Both tests had high negative predictive values (>99%) for excluding LVSD. Urinary N-BNP was more specific (67.2%) than plasma N-BNP (41%). The plasma/urinary N-BNP product yielded a higher ROC-AUC (0.923) and specificity (78%), reducing the number of cases to scan to detect one case of LVSD to 11.4 (compared with 16.6 [urinary N-BNP] and 29.0 [plasma N-BNP]). Sequential application of tests (urinary N-BNP, then plasma N-BNP in the urine-"positive" cases) achieved similar reductions in the number of cases to scan (10.8), while limiting the number of N-BNP tests to be performed. Urinary N-BNP performed poorly in detection of other cardiac abnormalities with preserved systolic function. It was less costly to test urinary N-BNP in the whole population as compared with other strategies, including scanning high-risk cases with N-BNP testing in the remainder. CONCLUSIONS: Urinary N-BNP used together with plasma N-BNP could reduce the echocardiographic burden in screening programs.     

QRS prolongation on surface ECG and brain natriuretic peptide as indicators of left ventricular systolic dysfunction

OBJECTIVE: To determine whether the combination of prolonged QRS duration and brain natriuretic peptide (BNP) levels predicts left ventricular systolic dysfunction (LVSD) with a higher accuracy compared with QRS duration or BNP alone. SETTING: University hospital. METHODS: We studied 128 consecutive patients with suspected cardiac disease. At rest the QRS duration on 12-lead ECG and BNP levels were determined. A left ventricular ejection fraction (LVEF) <50% at echocardiography was defined as LVSD. RESULTS: QRS duration in the LVSD group (n = 66, LVEF 30 +/- 8%) was longer than in the group without LVSD (n = 62, LVEF 60 +/- 5%; QRS 129 +/- 34 vs. 96 +/- 20 ms, P < 0.001). BNP was higher in the LVSD group compared with controls (467 +/- 397 vs. 169 +/- 242 pg mL(-1), P < 0.001). A QRS duration of >0.1, >0.11 or >0.12 s was highly specific (63, 90 and 98%) but less sensitive (84, 81 and 75%) for the prediction of LVSD. A QRS cut-off value of 106 ms was moderately sensitive (65%) but very specific (87%) for the prediction of LVSD, whereas a BNP cut-off value of >84 pg mL(-1) was highly sensitive (89%) but only modestly specific (58%). The positive likelihood ratio for LVSD of abnormal BNP (2.0) and QRS prolongation >0.1 s (2.3) was improved by the combination of both criteria (5.1). In multivariate analysis, BNP and QRS duration were independent predictors of LVSD. CONCLUSIONS: The combination of abnormal BNP and QRS prolongation yields a higher positive likelihood ratio for the detection of LVSD compared with the two criteria alone.     

Plasma B-type natriuretic peptide levels in systolic heart failure: importance of left ventricular diastolic function and right ventricular systolic function

OBJECTIVES: This study was designed to characterize the importance of echocardiographic indexes, including newer indexes of diastolic function, as determinants of plasma B-type natriuretic peptide (BNP) levels in patients with systolic heart failure (SHF). BACKGROUND: Plasma BNP levels have utility for diagnosing and managing heart failure. However, there is significant heterogeneity in BNP levels that is not explained by left ventricular size and function alone. METHODS: In 106 patients with symptomatic SHF (left ventricular ejection fraction [LVEF] <0.35), we measured plasma BNP levels and performed comprehensive echocardiography with assessment of left ventricular diastolic function, including color M-mode (CMM) and tissue Doppler imaging (TDI), and of right ventricular (RV) function. RESULTS: Median plasma BNP levels were elevated and increased with greater severity of diastolic dysfunction. We found significant correlations (p < 0.001 for all) between BNP and indexes of myocardial relaxation (early diastolic velocity: r = -0.26), compliance (deceleration time: r = -0.55), and filling pressure (early transmitral to early annular diastolic velocity ratio: r = 0.51; early transmitral flow to the velocity of early left ventricular flow propagation ratio: r = 0.41). In multivariate analysis, overall diastolic stage, LVEF, RV systolic dysfunction, mitral regurgitation (MR) severity, age and creatinine clearance were independent predictors of BNP levels (model fit r = 0.8, p < 0.001). CONCLUSIONS: Plasma BNP levels are significantly related to newer diastolic indexes measured from TDI and CMM in SHF. Heterogeneity of BNP levels in patients with SHF reflects the severity of diastolic abnormality, RV dysfunction, and MR in addition to LVEF, age, and renal function. These findings may explain the powerful relationship of BNP to symptoms and prognosis in SHF.     

Amino-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide in the general community: determinants and detection of left ventricular dysfunction.

OBJECTIVES: This study sought to characterize factors influencing amino-terminal pro-B-type natriuretic peptide (NT-proBNP) and to evaluate the ability of NT-proBNP to detect left ventricular (LV) dysfunction in a large community sample. BACKGROUND: Secretion of BNP increases in cardiac disease, making BNP an attractive biomarker. Amino-terminal proBNP, a fragment of the BNP prohormone, is a new biomarker. We evaluated factors influencing NT-proBNP in normal patients and compared the ability of NT-proBNP and BNP to detect LV dysfunction in a large community sample. METHODS: Amino-terminal pro-BNP was determined in plasma samples of a previously reported and clinically and echocardiographically characterized random sample (n = 1,869, age > or =45 years) of Olmsted County, Minnesota. RESULTS: In normal patients (n = 746), female gender and older age were the strongest independent predictors of higher NT-proBNP. Test characteristics for detecting an LV ejection fraction < or =40% or < or =50% were determined in the total sample with receiver operating characteristic curves. Amino-terminal pro-BNP had significantly higher areas under the curve for detecting an LV ejection fraction < or =40% or < or =50% than BNP in the total population and in several male and age subgroups, whereas areas were equivalent in female subgroups. Age- and gender-adjusted cutpoints improved test characteristics of NT-proBNP. Both assays detected patients with systolic and/or moderate to severe diastolic dysfunction to a similar degree, which was less robust than the detection of LV systolic dysfunction alone. CONCLUSIONS: Amino-terminal pro-BNP in normal patients is affected primarily by gender and age, which should be considered when interpreting values. Importantly, in the entire population sample NT-proBNP performed at least equivalently to BNP in detecting LV dysfunction and was superior in some subgroups in detecting LV systolic dysfunction.     

Meta-analysis of B type natriuretic peptide and N-terminal pro B natriuretic peptide in the diagnosis of clinical heart failure and population screening for left ventricular systolic dysfunction

Background:  We set out to review the validity of tests for B type natriuretic peptide (BNP) and N-terminal pro BNP (NTproBNP) in the diagnosis of clinical heart failure (HF) in primary care and hospital settings and to examine the effect of age. We also examined the accuracy of the test in population screening for left ventricular systolic dysfunction.
Methods:  Medline and Embase were searched systematically till June 2005. Forty-seven studies were identified for systematic review and 27 were included in meta-analyses. Test performance was summarized as the diagnostic odds ratio (DOR). As a secondary data analysis, this paper does not require ethical approval.
Results:  In groups of symptomatic patients with average age less than 80 years, the summary DOR of 27 for BNP equates to a sensitivity of 85% and specificity of 84% in the detection of clinical HF. Summary of head-to-head studies shows BNP is a better indicator than NTproBNP. The performance of both tests decreased with the age of patients, the DOR declining by a factor of 2.0 for BNP and 2.5 for NTproBNP for each decade of increasing age. BNP correlated better to clinical status than to echocardiographic parameters, and test performance was similar in acute inpatient and general practice settings.
Conclusion:  Tests for BNP are helpful in the diagnosis of clinical HF or in screening for left ventricular systolic dysfunction and are superior to NTproBNP. In the clinical setting, test performance declined with increasing patient age.     

B-type natriuretic peptide: practical diagnostic use for evaluating ventricular dysfunction

Assessment of brain natriuretic peptide levels may provide important information that can be used in the evaluation of patients with dyspnea and follow-up of heart failure. Brain natriuretic peptide levels have been shown to be useful for evaluating patients in the emergency department and for evaluating patients complaining of dyspnea in the outpatient setting. Brain natriuretic peptide assessment also provides an adjunct to diagnosis of both systolic and diastolic dysfunction, has prognostic value for heart failure and in acute coronary syndromes, and may be a useful measure to guide therapy. Further work needs to be done to establish the best type of assay to use, to determine the optimal cutoff point for what is considered abnormal, and to determine how conditions other than ventricular dysfunction affect brain natriuretic peptide levels.