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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 8  |  Issue : 1  |  Page : 30-34

DoEs NTproBNP predict NO flow phenomenon IN patients undergoing coronary Angioplasty in IHD amongst Asian Indians? (DENOMINATE Study)


1 Department of Cardiology, U. N. Mehta Institute of Cardiology and Research Centre, Civil Hospital Campus, Ahmedabad, Gujarat, India
2 Department of Cardiology, King George's Medical University, Lucknow, Uttar Pradesh, India
3 Department of Research, U. N. Mehta Institute of Cardiology and Research Centre, Civil Hospital Campus, Ahmedabad, Gujarat, India

Date of Submission07-Aug-2019
Date of Decision27-Sep-2019
Date of Acceptance18-Jan-2020
Date of Web Publication03-Apr-2020

Correspondence Address:
Dr. Kamal Sharma
Department of Cardiology, U. N. Mehta Institute of Cardiology and Research Centre, Civil Hospital Campus, Asarwa, Ahmedabad - 380 016, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/heartindia.heartindia_36_19

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  Abstract 


Context: No-flow phenomenon during percutaneous coronary intervention (PCI) is a complex and multifactorial phenomenon with often devastating complications during PCI, especially in acute coronary syndrome (ACS) settings. There is paucity of data on serological predictors of the same.
Materials and Methods: This was an open-label, all-comers, observational, prospective study done on 175 patients covering the whole spectrum of coronary artery disease, undergoing PCI at the center. On admission detailed clinical history , general and systemic examination and laboratory investigations in form of hemoglobin, blood urea, serum creatinine, serum sodium, serum potassium, random blood sugar, electrocardiogram(ECG) and tropinin T were also done. Post procedure creatinine protein kinase MB (CPK MB) was done after 24 hrs, and thrombolysis in myocardial infarction (TIMI) flow was assessed during PCI in all patients by the operating interventional cardiologist.
Results: The mean value of NT-proBNP among patients with TIMI flow <3 was 3384.43 ± 1837.48 pg/ml, whereas among patients with TIMI flow 3, it was 894.64 ± 580.90 pg/ml. The difference between the two groups was statistically significant (P < 0.001), with TIMI flow 3 Group showing significantly lower mean NT-proBNP values as compared to the TIMI flow <3 category. There was no significant correlation between the mean NT-proBNP levels in various TIMI flow, that is, 0 and 2. In each quartile of NT-proBNP, there was a marked difference in the quartile value of the two TIMI <3 and TIMI 3 categories. Presence of angiographic thrombus was significantly associated with no-flow phenomenon.
Conclusion: Our study shows that higher NT-proBNP levels in patients with ACS who undergo PCI have higher likelihood of developing no-flow phenomenon during PCI.

Keywords: No-flow phenomenon, percutaneous coronary intervention, thrombus


How to cite this article:
Bhatia S, Sharma K, Narain V S, Sethi R, Jain S, Meniya J, Jhameria J, Panwar J, Patel K. DoEs NTproBNP predict NO flow phenomenon IN patients undergoing coronary Angioplasty in IHD amongst Asian Indians? (DENOMINATE Study). Heart India 2020;8:30-4

How to cite this URL:
Bhatia S, Sharma K, Narain V S, Sethi R, Jain S, Meniya J, Jhameria J, Panwar J, Patel K. DoEs NTproBNP predict NO flow phenomenon IN patients undergoing coronary Angioplasty in IHD amongst Asian Indians? (DENOMINATE Study). Heart India [serial online] 2020 [cited 2020 Aug 11];8:30-4. Available from: http://www.heartindia.net/text.asp?2020/8/1/30/281879




  Introduction Top


Reperfusion therapy for patients with acute myocardial infarction (MI) using primary percutaneous coronary intervention (PCI) has shown to improve the clinical outcome compared with thrombolysis.[1] However, despite the achievement of optimal epicardial coronary artery patency, 30%–40% of patients show the no-reflow phenomenon.[2]

No–reflow is complex and multifactorial. Microembolic debris from dilated target sites, sustained diffuse microvascular spasm, and pathophysiologic alterations from initial ischemic insults and subsequent reperfusion injuries result in the persistence of myocardial ischemia despite angiographic evidence of restored vessel patency.[3] Novel biomarkers are assessed to predict the no-reflow phenomenon in patients with acute coronary syndrome (ACS) undergoing PCI.[4] N-terminal pro-brain natriuretic peptide (NT-proBNP) is one such marker and has been studied widely.[5],[6]

This study was designed to assess the effectiveness of NT-proBNP as a predictor of no-flow phenomenon in patients with ischemic heart disease undergoing PCI among Asian Indians.


  Materials and Methods Top


The present study was conducted in the Department of Cardiology, CSMMU, Lucknow, between October 2007 and September 2008, on 175 consecutive patients in a prospective manner covering the whole spectrum of coronary artery disease (CAD), undergoing PCI at the center.

Inclusion criteria

All adult Asian Indians ≥18 years of age with unstable angina, ST-segment elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and chronic stable angina undergoing PCI who were willing to give written consent were included in the study.

Methodology

At admission, a detailed clinical history and general and systemic including hemoglobin, blood urea, serum creatinine, serum sodium, serum potassium, random blood sugar, electrocardiogram (ECG), and troponin T were also done. Post procedure, creatine protein kinase-MB was done after 24 h. Biochemical estimation of NT-proBNP was done using peripheral blood samples for NT-proBNP which were obtained before PCI using direct venipuncture of the antecubital vein after the patient had rested in the supine position for 30 min. Blood samples were collected in tubes without anticoagulant, centrifuged, and frozen. NT-proBNP was measured by electrochemiluminescence immunoassay (ECLIA) intended for use on Elecsys or cobase immunoassay analyzers (Abbott Architect ci8200, Japan).

The test was done using sandwich principle. The total duration of the assay was 18 min. The results were determined through calibration curve which is instrument generated by two-point calibration and a master curve provided through the reagent barcode. For diagnostic purposes, the results were assessed in conjunction with the patient's medical history, clinical examination, and other findings.

Cutoff values

NT-proBNP <125 pg/ml excludes cardiac dysfunction with a high level of certainty in patients with symptoms suggestive of heart failure, for example, dyspnea.

The relationship between preprocedural NT-proBNP and angiographic no-reflow phenomenon was assessed. Angiographic no reflow after PCI is defined in terms of thrombolysis in myocardial infarction (TIMI) blood flow grades, as follows:[7]

  • Grade 0 refers to no flow at all after the obstruction points
  • Grade 1, the contrast material flows beyond the area of obstruction but fails to opacify the entire artery
  • Grade 2 refers to opacification of the entire artery distal to the occlusion site but at a slower rate than normal
  • Grade 3 refers to normal coronary flow
  • All patients with no reflow received intracoronary adenosine, nitroglycerin, or intracoronary diltiazem, or a combination of these.


Data analysis

Statistical correlation was done for TIMI flow grade and NT-proBNP levels for all the patients using SPSS software version 20.0 (Chicago, IL, USA). Continuous variables were compared using the unpaired Student's t-test or one-way analysis of variance. Continuous variables were summarized as mean ± standard deviation, whereas categorical variables were expressed as percentage of the sample. Group differences associated with P < 0.05 were considered statistically significant.


  Results Top


Majority of the patients enrolled were within the age group of 41–70 years. There were only eight (4.6%) patients in the age group of 31–40 years and seven (4%) in the age group of >70 years. There were 36 (20.6%) females and 139 (79.4%) males. The male-to-female prevalence was 3.86:1. There were 58 (33.1%) patients with diabetes mellitus (DM) and 50 (28.57%) with hypertension. STEMI was the most common diagnosis seen in 101 (57.7%) patients followed by NSTEMI/UA (unstable angina) in 52 (29.7%) patients. Chronic stable angina (CSA) was seen only in 22 (12.6%) patients. Angiographic findings revealed single-vessel disease among 108 (61.71%) patients, double-vessel disease in 39 (22.29%) patients, and triple-vessel disease in 28 (16%) patients. Thus, single-vessel disease was the most commonly found angiographic finding.

TIMI flow <3 was seen in 39 (22.29%) patients, whereas in 136 (77.71%) patients, TIMI flow rate was 3. The mean value of NT-proBNP among patients with TIMI flow <3 was 3384.43 ± 1837.48 pg/ml, whereas among patients with TIMI flow 3, it was 894.64 ± 580.90 pg/ml. The difference between the two groups was statistically significant (P < 0.001), with TIMI flow 3 group showing significantly lower mean NT-proBNP values as compared to TIMI flow <3 category. In TIMI flow <3 category, the minimum NT-proBNP value recorded was 1021.80 pg/ml and the maximum value was 9981.00 pg/ml, whereas in TIMI flow 3 category, the minimum value recorded was 54.00 pg/ml and the maximum value was 3010.00 pg/ml. As a trend, the TIMI flow <3 category had lower NT-proBNP value as compared to TIMI flow 3 category (median: TIMI <3 = 3211.00 pg/ml and TIMI 3 = 782.00 pg/ml).

There were five patients with TIMI flow 0 category, 20 with TIMI flow 1 category, and 14 with TIMI flow 2 category – a randomized trend of NT-proBNP values was seen among these – category 0 had mean NT-proBNP value of 2824.00 ± 1128.63 pg/ml; category 1 had mean value of 3021.74 ± 1321.02 pg/ml; and category 2 had a mean value of 4102.39 ± 2459.44 pg/ml, each showing high degree of variability. In categories 0, 1, 2, and 3, the median values were 2543.70 pg/ml, 2763.00 pg/ml, and 3420.00 pg/ml, respectively, much different from the mean values, thus showing in [Table 1] that the smaller groups could not yield a normal distribution.
Table 1: Relation between N-terminal pro-brain natriuretic peptide levels and various categories of thrombolysis in myocardial infarction flow

Click here to view


As there were wide variations in NT-proBNP values between the minimum and maximum values in both TIMI <3 and TIMI 3 categories, an attempt was made to explore new possibilities. For this purpose, the quartile values of the two groups were derived. It was seen that in TIMI <3 category, the 25th percentile, 50th percentile, and 75th percentile values were 2341.00 pg/ml, 3211.00 pg/ml, and 3981.00 pg/ml, respectively, and the corresponding values in TIMI 3 category were 537.40 pg/ml, 782.00 pg/ml, and 1231.00, respectively, thus showing that in each quartile, there was a marked difference in the quartile value of the two TIMI flow rate categories. Although among patients with single-vessel involvement the mean NT-proBNP levels were found to be lower as compared to those with multiple-vessel involvement, yet the difference between the two groups was not statistically significant (P = 0.305), as shown in [Table 2]. The maximum proportion of patients with no reflow were seen in Left anterior descending artery (LAD) (23.58%), followed by Right coronary artery (RCA) (19.64%) and Left circumflex artery (LCX) (13.04%). However, no statistically significant association could be derived (P > 0.05). A positive significant association of TIMI flow <3 was seen with thrombus. It was seen in [Table 3] that among those TIMI flow <3, there were 38.46% patients with thrombus, whereas among patients with TIMI flow 3, there were only 9.55% of patients with thrombus. A statistically significant difference was seen between two TIMI flow categories (P < 0.001).
Table 2: Relation between N-terminal pro-brain natriuretic peptide levels and angiographic vessel involvement

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Table 3: Association of no reflows with presence of thrombus on angiography

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  Discussion Top


Our study clearly shows that elevated preprocedural NT-proBNP is a predictor of no-flow phenomenon during PCI irrespective of clinical presentation in Asian Indians also. The presence of angiographic thrombus was an independent predictor of no flow in this study with trends, but there was no statistically significant difference between single- and multi-vessel diseases. Another study by Hong et al.[8] proposed the usefulness of preprocedural NT-proBNP in predicting angiographic no-reflow phenomenon during stent implantation in patients with ST-segment elevation acute MI. They measured preprocedural serum NT-proBNP level in 159 consecutive patients with acute STEMI before PCI. NT-proBNP was significantly higher in the no-reflow group than the normal reflow group. In the no-reflow group, NT-proBNP was much higher in patients with TIMI flow Grade 0 than those with TIMI Grade 1 or 2 although not statistically significant. At the standard cutoff value of >500 pg/ml, increased NT-proBNP showed a high probability of no-reflow phenomenon. They also reported that NT-proBNP was a valuable screening test for CAD in patients with abnormal ECG, echocardiogram, and cardiac enzymes.

Grabowski et al.[9] obtained BNP levels in 126 patients with STEMI. Higher BNP levels were observed among patients with TIMI <3 after PCI than among those with TIMI 3 (356.7 ± 350.8 pg/ml vs. 144.9 ± 191.2 pg/ml; P < 0.0001). Admission BNP was the independent predictor for the following: death, TIMI Grade <3 after PCI, and the no-reflow phenomenon.

According to the study on 382 patients by Kirma et al.,[10] clinical and procedural predictors of no-reflow phenomenon after primary PCIs were advanced age (>60 years), delayed reperfusion (≥4 h), low (≤1) TIMI flow prior to PCI, cutoff-type total occlusion, high thrombus burden on baseline angiography, long target lesion (>13.5 mm), and large vessel diameter.

Galvani et al.[11] collaborated that NT-proBNP on admission has prognostic value across the whole spectrum of ACS. Mortality rate, incidence of subsequent MI, recurrent ischemic events, and incidence of severe heart failure increased according to NT-proBNP quartiles.

Another prospective study by Wu et al.[12] on 242 patients with STEMI of onset <12 h who underwent primary PCI, demonstrated that the 30-day composite major adverse clinical outcomes (advanced Kilip score=3, or functional class ≥3 of CHF, and 30-day mortality) were strongly associated with elevated NT-proBNP (>243 pg/ml) (P < 0.0001), unsuccessful reperfusion (final TIMI flow ≤2) (P < 0.0001), left ventricular ejection fraction <45% (P < 0.0001), DM (P = 0.0004), and multi-vessel disease.


  Conclusion Top


Our study shows that higher NT-proBNP level in Asian Indians with ACS who undergo PCI has higher likelihood of developing no-flow phenomenon during PCI. Presence of angiographic thrombus was an independent predictor of no-flow phenomenon. There was a trend toward multi-vessel disease being associated with no-flow phenomenon, but it did not reach a statistical significance.

Acknowledgments

The authors are grateful to the Director, Dr. R. K. Patel, and other interventional cardiologists for their valuable support in the completion of this project.

Statement of ethics

This study is approved by the institutional ethics committee. All patients gave written informed consent for enrollment in this study.

Financial support and sponsorship

This work was supported by the UN Mehta Institute of Cardiology and Research Centre itself and received no specific grant from any funding agency, commercial or not-for-profit sectors.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
van't Hof AW. Successful reperfusion therapy: From epicardial to myocardial salvage. Rev Esp Cardiol 2010;63:757-9.  Back to cited text no. 1
    
2.
Gupta S, Gupta MM. No reflow phenomenon in percutaneous coronary interventions in ST-segment elevation myocardial infarction. Indian Heart J 2016;68:539-51.  Back to cited text no. 2
    
3.
Fischell TA. Pharmaceutical interventions for the management of no-reflow. J Invasive Cardiol 2008;20:374-9.  Back to cited text no. 3
    
4.
Harigaya H, Motoyama S, Sarai M, Inoue K, Hara T, Okumura M, et al. Prediction of the no-reflow phenomenon during percutaneous coronary intervention using coronary computed tomography angiography. Heart Vessels 2011;26:363-9.  Back to cited text no. 4
    
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James SK, Lindahl B, Siegbahn A, Stridsberg M, Venge P, Armstrong P, et al. N-terminal pro-brain natriuretic peptide and other risk markers for the separate prediction of mortality and subsequent myocardial infarction in patients with unstable coronary artery disease: A Global Utilization of Strategies to Open occluded arteries (GUSTO)-IV substudy. Circulation 2003;108:275-81.  Back to cited text no. 5
    
6.
Dai DF, Hwang JJ, Lin JL, Lin JW, Hsu CN, Lin CM, et al. Joint effects of N-terminal pro-B-type-natriuretic peptide and C-reactive protein vs. angiographic severity in predicting major adverse cardiovascular events and clinical restenosis after coronary angioplasty in patients with stable coronary artery disease. Circ J 2008;72:1316-23.  Back to cited text no. 6
    
7.
TIMI Study Group. The thrombolysis in myocardial infarction (TIMI) trial. Phase I findings. N Engl J Med 1985;312:932-6.  Back to cited text no. 7
    
8.
Hong SN, Ahn Y, Hwang SH, Yoon NS, Lee SR, Moon JY, et al. Usefulness of preprocedural N-terminal pro-brain natriuretic peptide in predicting angiographic no-reflow phenomenon during stent implantation in patients with ST-segment elevation acute myocardial infarction. Am J Cardiol 2007;100:631-4.  Back to cited text no. 8
    
9.
Grabowski M, Filipiak KJ, Karpinski G, Wretowski D, Rdzanek A, Huczek Z, et al. Serum B-type natriuretic peptide levels on admission predict not only short-term death but also angiographic success of procedure in patients with acute ST-elevation myocardial infarction treated with primary angioplasty. Am Heart J 2004;148:655-62.  Back to cited text no. 9
    
10.
Kirma C, Izgi A, Dundar C, Tanalp AC, Oduncu V, Aung SM, et al. Clinical and procedural predictors of no-reflow phenomenon after primary percutaneous coronary interventions: Experience at a single center. Circ J 2008;72:716-21.  Back to cited text no. 10
    
11.
Galvani M, Ottani F, Oltrona L, Ardissino D, Gensini GF, Maggioni AP, et al. N-terminal pro-brain natriuretic peptide on admission has prognostic value across the whole spectrum of acute coronary syndromes. Circulation 2004;110:128-34.  Back to cited text no. 11
    
12.
Wu CJ, Chang HW, Hung WC, Yang CH, Chen YH, Su CY, et al. N-terminal pro-brain natriuretic peptide is a biomarker of congestive heart failure and predictive of 30-day untoward clinical outcomes in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention. Circ J 2006;70:163-8.  Back to cited text no. 12
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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