Table 3.
| Author, date and country | Patient group | Study type (level of evidence) | Outcomes | Key results | Study weaknesses |
|---|---|---|---|---|---|
| Mukoyama et al, 1991, Japan | 13 consecutive patients with AMI <12 hours from symptom onset. | Prospective diagnostic cohort | BNP levels | Rose after AMI (within “hours” of onset of AMI). | Small numbers |
| Blood samples at enrollment and every 4–24 hours over 4 days. | Correlation of BNP with PCWP and CIn | No correlation with PCWP. Highly correlated inversely with CIn (r = −0.81, P<0.01). | Subopimal reporting of results. Little statistical analysis. Meaningful conclusions cannot be drawn about the value of BNP as a diagnostic test. | ||
| Horio et al, 1993, Japan | 16 patients admitted to CCU with AMI within 9 hours of symptom onset. All patients had right‐sided cardiac catheterisation, coronary angiography and primary angioplasty. 16 normal subjects. | Prospective observational cohort | BNP levels on day 1 | Higher in AMI patients than controls (4.5 fold on day 1). No P value. | Small numbers |
| BNP levels at follow up | Significantly elevated in AMI patients at 14 days; still “abnormally elevated” at 4 weeks (no P values). | Method of identification of normal subjects not described. | |||
| Blood taken on admission and serially on days 3, 7, 14 and 28 | Correlation between BNP and haemodynamic variables | No correlation with PCWP, right atrial pressure or CIn. Significant inverse correlation with LVEF (r = −0.67, P<0.01). | Not all pertinent P values given. | ||
| This study suggests raised BNP in AMI but, because of the design, data cannot be used to evaluate BNP as a diagnostic test for AMI. | |||||
| Morita et al, 1993, Japan | 50 consecutive patients with AMI within 8 hours of symptom onset. 30 age‐ and sex‐matched controls. | Prospective diagnostic cohort | BNP level on admission | Significantly increased with AMI v. controls (92+/−28 v. 5.2+/−0.5 pg/ml; P<0.01) | Diagnosis of MI had already been ruled in at enrollment. Investigating application in an undifferentiated group would be more clinically relevant. |
| Peak BNP level in MI patients | Peak level at 16.4+/−0.7 hours after admission | ||||
| Blood taken on admission. All patients had coronary angiography on admission. 10 had intracoronary thrombolysis, 11 had IV thrombolysis; 26 had PTCA. | BNP levels at four weeks | Still significantly higher in MI group than controls (149+/−47 v. 5.2+/−0.5 pg/ml; P<0.001). | |||
| Correlation between BNP and haemodynamic parameters | No correlation with PCWP; No correlation with CIn in 1st 2 days; Significant inverse correlation with CIn at time of peak BNP level (r = −0.476, P<0.01). | ||||
| Kikuta et al, 1995, Japan | 73 patients (already diagnosed) with either UA (n = 33), SA (n = 20) or atypical chest pain with normal coronary angiogram, stress test and hyperventilation test (n = 20). | Prospective diagnostic cohort | BNP levels | Significantly higher in UA group compared with SA and controls (P<0.01 for each). No significant difference between SA and controls. | 16 of UA group had ST elevation on ECG. CK‐MB < twice normal but no troponin testing. These patients may actually have had MI. |
| BNP levels according to ST elevation or depression | No significant difference | ||||
| Blood taken within 24 hours of last attack in UA group. | BNP levels following treatment | BNP decreased significantly (P<0.01) in UA group but not SA group. | Results not useful for clinical evaluation of BNP as a diagnostic test (sensitivities, specificities, etc, cannot be calculated; patients had already been diagnosed at enrollment). | ||
| Regional wall motion abnormalities on echocardiography | Significantly higher BNP if +ve for this outcome (P<0.01). | ||||
| de Lemos et al, 2001, United States | 2525 patients with ACS (825 STEMI, 565 NSTEMI, 1133 UA) enrolled into another study investigating GPIIb/IIIa inhibitors. | Prospective observational cohort | Baseline characteristics | Patients with higher BNP more likely to be older (P<0.001), male (P<0.001), hypertensive (P<0.003), have CHF (P<0.001, hypercholesterolaemia (P<0.001), smokers (P<0.001), to have reduced creatinine clearance (P<0.001), CK‐MB > upper limit of normal (P<0.001) or ST segment depression (P<0.001). | Very late sampling time. |
| Correlation of BNP with angiography/stress test | Patients with higher BNP more likely to have >50% stenosis (P<0.001) or +ve stress test (P<0.01) than patients with low levels | ACS had already been ruled in for this patient group at time of inclusion (by ECG or cardiac marker testing). | |||
| Blood sent at a mean of 40+/−20 hours from symptom onset. | BNP as an independent predictor of death (after adjustment using logistic regression) | Adjusted OR's for death at 10 months in 2nd, 3rd & 4th quartiles of BNP were 3.8 (95% CI 1.1–13.3), 4.0 (1.2–13.7) and 5.8 (1.7–19.7), respectively. | Inadequate reporting of data to allow calculation of sensitivities, specificities, PPVs, NPVs or likelihood ratios. | ||
| Value of a BNP cutoff of 80 pg/ml as an independent predictor of mortality (adjusted) | BNP remain significantly associated with increased 10‐month mortality (P = 0.04). | ||||
| Morrow et al, 2003, USA | 1676 patients (of 2220), enrolled in TACTICS‐TIMI 18 (early invasive v. conservative strategy), with non‐ST elevation acute coronary syndromes (NSTACS) and symptoms in the last 24 hours. | Nested prospective observational cohort | Elevated plasma BNP in UA (>80 pg/ml) | Raised in 15.6% (n = 167) [i.e. sensitivity 15.6%], and 10.1% (n = 67) of those with ‐ve baseline TnI. Elevated BNP in 13.6% (n = 135) of patients with UA and no history or current evidence of HF. | Patients enrolled having already been diagnosed with ACS (an undifferentiated group of patients would have enabled more clinically relevant conclusions to be drawn). |
| Blood taken “at enrolment”. Follow‐up at 6 months. | Elevated plasma BNP in NSTEMI (>80 pg/ml) | Raised in 25.2% [i.e. sensitivity 25.2%] (n = 153) | Insufficient data reported to allow calculation of specificities, PPV's, NPV's or LR's. | ||
| Death at 30 days (BNP cut‐off 80 pg/ml) | 5.0% raised v. 1.2% not raised (P<0.0001). Calculated sensitivity 80.6%. | ||||
| Death at 6 months (BNP cut‐off 80 pg/ml) | 8.4% raised v. 1.8% not raised (P<0.0001). Calculated sensitivity 82%. | ||||
| Death at 7 days (BNP cut‐off 80 pg/ml) | 2.5% raised v. 0.74% not raised. Calculated sensitivity 77%. | ||||
| Association between BNP and 6/12 mortality after adjustment for important clinical predictors available at presentation | Remained an independent predictor of mortality (OR 3.3, 95% CI 1.7–6.3). | ||||
| BNP for prediction of recurrent MI | Not predictive (5.3% v. 5.2%, p = 1.0) | ||||
| BNP for prediction of hospitilisation with recurrent ACS | Not predictive (13.4% v. 12.2%, p = 0.6). | ||||
| BNP for prediction of new or worsening CHF | 30 days: Significantly increased risk with raised BNP (5.9% v. 1.0%, p<0.0001). 6 months: Risk persisted (9.1% v. 1.8%, P<0.0001). | ||||
| BNP + TnI for prediction of 6/12 mortality | Both ‐ve: 0.7% risk of death. | ||||
| Death with conservative/early invasive treatment according to BNP results | No appreciable difference (p = 0.6 for 6/12 mortality). | ||||
| Mega et al, 2004, USA | 438 eligible (of 483) patients enrolled in the ENTIRE‐TIMI 23 trial (full v. half dose thrombolysis + abciximab and LMWH or heparin in STEMI <6 hours). Blood sampling on admission, before thrombolysis. | Nested prospective observational cohort | 30‐day mortality (reported results) | Significantly higher BNP among those who died (P<0.0001). BNP>80 pg/ml associated with significantly higher risk of death (P<0.0001). | All patients had STEMI already ruled in by ECG ‐ the study is not helpful to evaluate BNP as a diagnostic test for MI. |
| 30‐day mortality (values calculated using reported data) | BNP>80 pg/ml: Sensitivity 53%, specificity 91%, PPV 17%, NPV 98.2% (i.e. 1.8% chance of death despite ‐ve BNP); LR+ 5.9; LR‐ 0.5 | ||||
| New or worsening CHF at 30 days | More frequent if BNP>80 pg/ml (8.7% v. 3.3%, p = 0.09). | ||||
| New or worsening CHF at 30 days (calculated) | BNP>80 pg/ml: Sensitivity 23.5%; Specificity 90%; PPV 8.7%; NPV 96.7% (i.e. probability of CHF despite ‐ve BNP 3.3%); LR+ 2.35; LR‐ 0.7. | ||||
| Independent predictors of mortality following logistic regression | BNP remained independently associated with mortality (OR 7.2, 95% CI 2.1–24.5, P = 0.001). | ||||
| BNP as a predictor of successful myocardial reperfusion | Elevated BNP associated with incomplete reperfusion (impaired flow, P = 0.04; poor myocardial perfusion, P = 0.06; Failed ST‐segment resolution, P = 0.005). | ||||
| Bassan et al, 2005, Brazil | 631 consecutive patients presenting to the Emergency Department with suspected cardiac chest pain <12 hours and no ST elevation on ECG. Blood taken on admission. | Prospective observational cohort | Association between BNP and diagnosis | Significantly higher BNP in MI patients (P<0.0001). Increasing risk of MI with increasing BNP (divided into quartiles; P<0.0001). | No follow‐up following hospital discharge. 30‐day and 6‐month follow‐up would be desirable. |
| Diagnostic accuracy of BNP for MI (optimal 100 pg/ml cut‐off) | Area under ROC curve 0.710. Sensitivity 70.8%; Specificity 68.9%; PPV 22.7%; NPV 94.8%; LR+ 2.28; LR‐ 0.42. RR 4.38 | ||||
| Raised BNP, CK‐MB or TnI (on admission) for diagnosis of MI | Sensitivity 87.3%; Specificity 65.7%; PPV 27.0%; NPV 97.3%; LR+ 2.55; LR‐ 0.19. RR 9.91 | ||||
| Follow‐up through in‐patient stay. | Logistic regression model for association with MI | BNP an independent predictor for diagnosis of MI (P = 0.0026). | No firm diagnosis in 202 (32%) patients (MI excluded but not UA). | ||
| Clinical utility of BNP to rule in MI | Authors' note: 72 patients had MI, 37 of whom had raised CK‐MB or TnI on admission. Raised BNP would have allowed detection of 22 more MI's [albeit at a cost of 163 false +ve diagnoses!] | ||||
| Value of BNP in ruling out MI (calculated) | For every 100 patients treated according to BNP levels on admission (cut‐off 100 pg/ml), 3 MI's would be missed. |
AMI, acute myocardial infarction; CCU, coronary care unit; PTCA, per cutaneous coronary angioplasty; IV, intravenous; UA, unstable angina; BNP, brain natriuretic peptide; PCWP, pulmonary capillary wedge pressure; MI, myocardial infarction; SA, stable angina