NT-proBNP: a Marker for Successful Myocardial Reperfusion in AMI Patients Treated with Primary Percutaneous Coronary Intervention

The cardiac natriuretic peptide system is activated in left ventricular (LV) dysfunction and has been evaluated in patients after acute myocardial infarction (AMI) 1–3. Higher levels of BNP and NT-proBNP in the first few days after AMI is a powerful predictor of LV dysfunction, prognosis in heart failure and death 4–8. In patients with AMI, early restoration of antegrade flow in the infarct-related artery reduces infarct size and LV dysfunction, improving both short- and long-term outcome 9,10. Accordingly, BNP kinetics could reflect the success of myocardial reperfusion. Some studies indicate that early reperfusion of the infarct-related area could suppress the increase in BNP level 8,11,12. We studied NT-proBNP kinetics in ST elevation AMI patients after percutaneous coronary intervention (PCI). We hypothesized that successful reperfusion by primary PCI would decrease NT-proBNP levels, compared to unsuccessful reperfusion. From June to August 2002, we studied 30 consecutive patients with ST elevation AMI, treated with primary PCI (27 men and 3 women; mean age 63.3±9.3 years, range 44–79). We excluded patients with severe heart failure or cardiogenic shock (Killip class 3 or 4). For the purpose of this study, successful PCI was defined by angiographic criteria. Thrombolysis in myocardial infarction (TIMI) flow grade 3 and myocardial blush grade (MBG) 2 or 3 as described earlier 13. The patients were divided into two groups according to successful or non-successful reperfusion. Blood samples for assessment of NT-proBNP and the (cardiac) enzymes CK, CK-MB and LDH were taken on admission (15 min prior to PCI), 12, 24 and 48 h after PCI. To measure infarct size, the cumulative LDH from the onset of the typical chest pain until 36 h after admission (LDHQ36) was calculated with a special algorithm as described earlier 10. Peak CK and peak CK-MB were determined. Four days after admission nuclear ejection fraction was measured by radionuclide technique as described previously 10. Data were expressed as mean±S.D. and as delta's. Comparisons between the two groups were performed with unpaired t-tests and analysis of variance (ANOVA) for continuous variables and χ2-test for categorical variables. The Fisher exact test was used when the expected value of cells was less than five. Correlation between the NT-proBNP levels and infarct size was assessed by linear regression analysis. A P-value <0.05 was considered to be significant. Twelve patients had anterior infarction and 18 patients had non-anterior infarction. None of the patients had a history of previous infarction. Only one patient belonged to Killip class 2. The other patients belonged to Killip class 1. No patients had recurrent infarction. None of the patients died during hospital stay. Table 1 shows the baseline characteristics of the two groups. There were no significant differences between the two groups. Successful reperfusion was achieved in 26 of the 30 patients. Infarct size is shown in Table 2. Infarct size, according to peak CK-MB was significantly larger in the unsuccessful PCI group (P=0.04). At admission the mean baseline NT-proBNP level in the successful PCI group was 34±41 and 15±12 pmol/l in the unsuccessful PCI group. In the successful PCI group the mean NT-proBNP level increased to 126±90 pmol/l at 12 h (P<0.001), to 183±113 pmol/l at 24 h (P<0.05) and then decreased to 163±142 pmol/l at 48 h after admission (P=0.59). In the unsuccessful PCI group, the level increased to 119±95 pmol/l at 12 h after admission (P=0.16), to 220±90 pmol/l at 24 h (P=0.17), and continued increasing to 249±124 pmol/l at 48 h (P=0.71). The levels of the NT-proBNP at admission, 12, 24 and 48 h after admission were not significantly different in the two groups (fig. Fig. 1). Enzymatic infarct size (LDHQ36) in all 30 patients showed a linear relation with mean NT-proBNP levels at 24 and 48 h (P=0.04, P=0.03, respectively) (fig. Fig. 2). After myocardial infarction, BNP is mainly secreted from the left ventricle. Increased wall stress directly related to the infarction appears to be the responsible stimulus 14,15. This study shows that during the acute phase of myocardial infarction NT-proBNP levels increase within 24–48 h, confirming the results of previous studies on BNP and NT-proBNP. Also, we showed that successful angiographic reperfusion therapy after ST elevation AMI suppresses further NT-proBNP rise, trendwise. In unsuccessful reperfusion the NT-proBNP level continues to increase more than 24 h after admission, whereas in successful reperfusion NT-proBNP levels reach a maximum at 24 h. This observation might be useful in clinical practice: an increasing NT-proBNP level at 48 h, compared to the level at 24 h might reveal the success of myocardial reperfusion at cellular level and may reflect long term clinical outcome in LV function. Therefore, an increasing NT-proBNP level after 24 h may be useful for clinical risk stratification in patients with ST elevation AMI treated by primary PCI. Also, we found a significant correlation between enzymatic infarct size and NT-proBNP levels. The main limitations of our study were the relatively small number of patients and the fact that we were not able to identify a biphasic pattern of NT-proBNP levels which is considered to be caused by ventricular remodeling 1,16,17, as we only measured until 48 h after admission. However, these results may have clinical implication and warrant further investigation in a larger cohort.