Prophylactic use of intracoronary sodium nitroprusside decreases incidence of no reflow after primary angioplasty in acute myocardial infarction

Sujith Kumar; Jaime S Varghese

doi:10.4103/khj.khj_8_21

ORIGINAL ARTICLE

Year : 2021 | Volume : 10 | Issue : 2 | Page : 1-7

Prophylactic use of intracoronary sodium nitroprusside decreases incidence of no reflow after primary angioplasty in acute myocardial infarction

Sujith Kumar, Jaime S Varghese
Department of Cardiology, Lourdes Hospital, Pachalam P.O., Ernakulam 682012, Kerala, India

Date of Web Publication

14-Feb-2022

Correspondence Address:
Dr. Sujith Kumar
Department of Cardiology, Lourdes Hospital, Pachalam P.O., Ernakulam 682012, Kerala.
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/khj.khj_8_21

Abstract

Background: Intracoronary vasodilators are used in various stages of primary angioplasty, either to treat no reflow or prophylactically to prevent no reflow. Vasodilators were ineffective during primary angioplasty to treat no reflow likely because the drug was used after plaque modification. We evaluated the intracoronary use of sodium nitroprusside (SNP) before plaque modification and microembolization. Materials and Methods: We conducted a retrospective case–control study of all primary angioplasty cases done at Lourdes Hospital, Kerala, India, from March 2016 to May 2018 by two operators at the hospital. We retrospectively collected the data for primary angioplasty at the hospital and analyzed the data into two groups: one operator routinely used prophylactic intracoronary SNP in stable primary percutaneous coronary intervention (PCI) patients, whereas the other used it only if there was no reflow. The drug was delivered prophylactically through guiding catheter once at least TIMI I flow was present. We compared the effect of prophylactic vs. therapeutic use of intracoronary SNP on no reflow during primary percutaneous transluminal coronary angioplasty (PTCA). Results: Incidence of no reflow was significantly less in the group in which SNP was used at the onset of primary PTCA when compared with those patients in whom it was not used at the onset (6.5% vs. 28.4%, P < 0.001). The TIMI frame count (21.7 vs. 24, P = 0.22) and low TIMI myocardial perfusion grade (<2) (14% vs. 20%, P = 0.272) did not reach statistical significance. Conclusion: Prophylactic intracoronary use of SNP, before plaque modification, reduces the incidence of no reflow phenomenon after primary angioplasty.

Keywords: Intracoronary sodium nitroprusside, no reflow, primary angioplasty, prophylaxis

How to cite this article:
Kumar S, Varghese JS. Prophylactic use of intracoronary sodium nitroprusside decreases incidence of no reflow after primary angioplasty in acute myocardial infarction. KERALA HEART J 2021;10:1-7

How to cite this URL:
Kumar S, Varghese JS. Prophylactic use of intracoronary sodium nitroprusside decreases incidence of no reflow after primary angioplasty in acute myocardial infarction. KERALA HEART J [serial online] 2021 [cited 2023 Oct 2];10:1-7. Available from: http://www.csikhj.com/text.asp?2021/10/2/1/337625

Brief Summary
Sodium nitroprusside (SNP) has been used during various stages of percutaneous transluminal coronary angioplasty (PTCA), with intention to treat or prevent no reflow with variable results. Use of the drug, after no flow has set in, may not allow the drug to reach the microvasculature in all cases, making the drug not very effective in the treatment of no flow. So we compared the effect of prophylactic SNP before plaque modification in preventing no reflow after primary percutaneous coronary intervention.

Introduction

Primary angioplasty is the treatment of choice for the acute ST-elevation myocardial infarction. The aim of primary percutaneous coronary intervention (PCI) is to achieve TIMI 3 (thrombolysis in myocardial infarction) flow with normal myocardial perfusion. But despite being able to relieve the anatomical lesions in the epicardial coronaries, TIMI 3 flow is not always achieved. This phenomenon, known as the no reflow or no flow phenomenon, is found to occur in 5–30% of the patients undergoing primary percutaneous transluminal coronary angioplasty (PTCA).^{[1],[2],[3],[4]} The occurrence of no reflow has been described in revascularization in cerebral and coronary circulation in dogs and humans.^[5] No reflow is associated with increased mortality and morbidity.^{[2],[6],[7],[8],[9]}

No reflow has been attributed to reperfusion injury, endothelial dysfunction, distal thromboembolism,^[10],[11] and microvascular spasm.^[10] The pathophysiology of no reflow has been classified by Galiuto.^[13] Accordingly, no reflow is attributed pathophysiologically to structural or functional defects. Structural no reflow is related to damage to capillary integrity or microvascular obstruction. Functional no reflow may be related to microvascular spasm and reperfusion injury. Microvascular embolism and occlusion is a major component of the pathophysiology of no reflow.^{[14],[15],[16]} Various agents have been used to treat no reflow; once it has occurred with variable success rates.^{[10],[17],[18]} Sodium nitroprusside (SNP) is a direct donor of nitric oxide and a vasodilator used in the treatment of no reflow. SNP has been used by various operators at various stages of PTCA, with intention to treat or prevent no reflow.

SNP has been tried in earlier studies in the prevention of no reflow with variable results.^{[19],[20],[21]} The drug may be able to prevent the microvascular spasm and also dilates the myocardial microvasculature, thus allowing the microemboli particles to be washed out of the coronary circulation. This might prevent the clogging of the microcirculation with embolic particles. Hence, we postulated that intracoronary use of SNP, before plaque or thrombus manipulation, might dilate the microvasculature and thus relieve microvascular spasm and prevent or reduce the clogging of microcirculation with embolic particles, thus decreasing incidence of no reflow. The use of SNP, once TIMI 1 flow is present and before the microvasculature is clogged by embolic particles, allowed the drug to reach the distal microvascular site of action. The use of the drug, after no flow has set in, may not allow the drug to reach the microvasculature in all cases, making the drug not very effective in the treatment of no flow.

Materials and Methods

We conducted a retrospective case–control study to assess the effect of prophylactic intracoronary SNP in preventing the occurrence of no reflow in primary PCI. The timing of use of prophylactic intracoronary SNP was after at least TIMI 1 flow was present. The data for primary angioplasty done in Lourdes Hospital, Ernakulam, India (a tertiary referral Hospital in Kerala, India) from March 2016 to May 2018 was reviewed. We retrospectively collected the data for all primary angioplasties at the hospital. We could analyze the data into two groups: one operator at the hospital routinely used prophylactic intracoronary SNP in stable primary PCI patients, whereas the other used it only if there was no reflow. Hence, a similar number of cases were accumulated in both the groups that could be compared. The drug was delivered through the guiding catheter once at least TIMI I flow was present. Those patients who were hemodynamically unstable at presentation were excluded from the analysis. The data from the hospital records of the remaining patients were grouped into two. In group 1 or cases, SNP was used before balloon dilatation. In these cases, SNP was injected intracoronary, once at least TIMI 1 flow was present during the angioplasty. TIMI 1 flow may be present either at presentation or after crossing the lesion with the guide wire or passing a low profile balloon across the lesion. In very few cases, the flow could be established only after balloon inflation. The dose used was a bolus of 100 mcg of SNP which was diluted in 5 mL of normal saline. In group 2, the drug was not used routinely before balloon dilatation and stenting. Both groups had used intracoronary vasodilators, NTG, or SNP, once no reflow was detected during the procedure [Figure 1]. All the patients were on dual antiplatelet therapy with aspirin and clopidogrel.

Figure 1: Flow chart summarizing the study and results
SNP = sodium nitroprusside

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The authors reviewed the angiographic recording of the included cases and controls in a blinded manner. The films were reviewed and those with angiographically visible dissection or thrombus at the stented or plain old balloon angioplasty (POBA) site were excluded. The study was approved by local Ethics Committee.

Study endpoints

Primary endpoints

The study endpoints analyzed were incidence of no-reflow, corrected TIMI frame count (CTFC), and myocardial perfusion grade. TIMI flow 3 was taken as normal flow. The no-reflow was defined as TIMI flow ≤ 2. These parameters were analyzed immediately after POBA and completion of stenting/post-dilatation. The final incidence of no reflow was taken as TIMI flow ≤ 2 at the end of procedure with use of intracoronary drugs also, if necessary.

Secondary endpoints

Secondary endpoints studied were the need to use intracoronary drugs during PCI, need for inotropic support, mortality, duration of PCI, and need for thrombus aspiration.

Statistical analysis

All categorical variables are presented as number (percentage) and continuous variables are presented as mean ± SD. Pearson’s χ² test or Fisher’s exact test was used to compare the categorical variables by the case–control group and subgroups. Independent sample t-test was used to compare the continuous variables among cases and controls and by subgroups. Statistical analyses were conducted using SPSS Version 20.0 for Windows (IBM Corporation, Armonk, NY, USA).

Results

A total of 244 patients had undergone primary PCI at Lourdes Hospital during the period March 2016 to May 2018. Forty-two were excluded from the analysis due to hemodynamic instability, and 14 were excluded due to unsuccessful PCI or persistent angiographic thrombus or dissection after PCI. Among the remaining patients, 93 patients were included in the case group and 95 patients were included in the control group. There was no difference in baseline clinical, demographic, and angiographic characteristics of the two groups [Table 1]. There was no difference in the number of cases with high or low thrombus (thrombus score <3 vs. >3) load between the two groups. The mean thrombus load, at presentation, was 4.38 in cases, whereas it was 4.13 in the control group (P = 0.17).

Table 1: Baseline clinical, demographic, and angiographic parameters

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Incidence of no reflow

No reflow occurred in 8 (8.6%) of cases and 35 (36.8%) of controls (P<0.001) on completion of stenting/POBA [Table 2]. The operators had used intracoronary drugs (due to no reflow) in 8 (8.6%) of cases and 35 (36.8%) of controls (P < 0.001), with successful reflow occurring in 2 of cases and 8 of controls. Thus, final no reflow at the completion of primary PCI occurred in 6 (6.5%) of cases and 27 (28.4%) of controls (P < 0.001) [Table 2] and [Figure 2].

Table 2: Incidence of no reflow during and at completion of PCI

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Figure 2: Final TIMI flow in the two groups

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CTFC and myocardial blush grading

There was no statistically significant difference in CTFC among the cases and controls (21.7 vs. 24, P = 0.22) [Table 3]. The CTFC was also similar among the subgroups for analysis of vessels involved, collaterals, thrombus grade, post-dilatation, or ectasia. The incidence of TIMI myocardial blush grading ≤ 2 was also similar between the cases and control group (14% vs. 20%, P = 0.272).

Table 3: Comparison of primary and secondary endpoints studied between the two groups and subgroup analysis

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Subgroup analysis

In the subgroup analysis, the incidence of no reflow was significantly different in the right coronary artery and left circumflex artery [Table 4], although it did not reach significance in the left anterior descending lesions (P = 0.11). There was a significant difference between the two groups in stented vs. non-stented patients and those with low or high thrombus load. So, despite having a slightly higher or similar initial thrombus load in the case group, the benefits were more significant in the subgroup analysis. The benefits were more in the high thrombus group. There was no statistically significant difference in TIMI frame count and myocardial perfusion grade, in subgroup analysis for vessel distribution (P = 0.672), stenting vs. non-stenting (POBA only) (P = 0.880), presence or absence of collaterals (P = 0.227), use or non-use of post-dilatation of the stent (P = 0.475), or presence or absence of ectasia (P = 0.767).

Table 4: Incidence of no reflow-subgroup analysis

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Despite having similar thrombus grade (P = 0.17) or ectasia, need for thrombus aspiration was done more frequently in the control group (n = 18) (18.9%) vs. the case group (n = 3) (3.2%), which was done mostly in response to no reflow occurring during angioplasty.

The procedure duration for primary PTCA was significantly lesser in the cases when compared with controls (37.77 vs. 47.35 min, P = 0.001).

Discussion

In this retrospective case–control study, use of prophylactic SNP was associated with a lesser incidence of no reflow (6.5% vs. 28.4%, P < 0.001). The CTFC was 21.7% in cases and 24% in controls (P = 0.22). In this study, the operators had used intracoronary SNP at the onset of primary PCI; once at least TIMI I flow was present distally. The drug was used intracoronary before the thrombus or plaque was manipulated with balloon dilatation. The presence of at least TIMI I flow, before injecting the drug, made the drug available to the distal microvascular circulation. Also, the use of SNP before distal embolization occurred (which occurs mostly after thrombus/plaque manipulation) might have resulted in microcirculatory vasodilatation, thus at least partially decreasing the clogging of microvasculature with thrombus. These made sure that SNP reached the site of action in the microvasculature and hence the drug was effective in decreasing the incidence of no reflow. In the study by Shinozaki^[22] and Fischer et al.,^[23] the incidence of no reflow was reduced by the use of intracoronary SNP before balloon dilatation. But, in both these studies, the drug was used via a drug delivery catheter to the distal bed. In our study, the drug was directly injected through the guiding catheter only, thus saving time during primary PCI. Also, the use of drug delivery catheters and thrombus aspiration catheters may cause the thrombus to be pushed distally.^[24] Direct stenting, especially once the distal vessel can be visualized, has been shown in some to decrease infarct size and microvascular obstruction on MRI.^[25] This might also be due to decreased effect of distal embolization. In the current study, the CFTC and TIMI blush grading did not reach statistical significance, although they were numerically more [Table 3]. Similar results for TIMI flow grade were observed by Fischer et al. also.^[23] This may be because of the lesser number of patients included in the study. The no reflow occurred during the procedure in 43 of the 188 total patients; only 10 out of these 43 patients (23.26%) had restoration of TIMI flow with use of intracoronary drugs and thrombus aspiration. This may be explained by the pathophysiology of no reflow,^[13] with only the functional no reflow responding to the further use of vasodilators and other drugs. The clogging of the microvasculature by the emboli or the structural damage to the microvasculature due to ischemia in some of these patients might have prevented the vasodilator drug from reaching its site of action distally and exerting the vasodilatory effect.

In the subgroup analysis, the incidence of no reflow was significantly higher in the control group, irrespective of the vessel involved, collaterals, post-dilatation, or stenting, but the difference was more pronounced among the group with high thrombus load. The parameters did not reach significance in the subgroup analysis for CFTC and TIMI blush grading. This may be due to the smaller number of patients in the groups.

The need for thrombus aspiration and intracoronary drugs was significantly higher in the control group. This is due to the increased incidence of microembolization and no reflow in them, necessitating the use of these. This also led to increased procedural duration in the control group. Intracoronary use of SNP in this hemodynamically stable cohort was well tolerated as evidenced by no significant difference in the use of inotropes in the study group.

Tirofiban was used in about 40% in both the cases and control groups which is similar to recent data on primary PCI which reported about 40% use GpIIb/IIIa inhibitors in ST-elevation myocardial infarction.^[26],[27]

Thus, the use of intracoronary SNP prophylactically through the guiding catheter itself, without use of other hardware or time, during primary PCI, decreases the incidence of no reflow.

Study limitations

This was a retrospective study. A prospective randomized study would have been more conclusive.

The relatively small number of patients studied could have influenced the results of the study.

Conclusions

Intracoronary SNP is being used for the treatment of no reflow during primary PCI, once it has set in, with often disappointing success rates. Prophylactic intracoronary SNP during routine primary PCI, before plaque modification, once at least TIMI 1 flow is attained, decreases incidence of no reflow after primary PCI. This is well tolerated, requires no extra hardware or time, and hence may be routinely recommended before primary PCI in stable patients. A prospective randomized study is necessary for further evaluation of a routine prophylactic intracoronary use of nitroprusside and its effects on no reflow during primary PCI.

Prophylactic intracoronary SNP, before plaque modification, was found to decrease the incidence of no reflow after primary angioplasty in this study.

Acknowledgements

None.

Financial support and sponsorship

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflicts of interest

Both the authors have no conflicts of interest to declare.

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