Skip to main content
Download PDF

Intracoronary injection of nitroglycerine can prevent unnecessary percutaneous coronary intervention

BMC Cardiovascular Disorders volume 22, Article number: 416 (2022) Cite this article

Abstract

Background

Despite the recommendation of the current guidelines, intracoronary administration of nitroglycerine during coronary angiography is often neglected. We investigated the effect of intra-coronary nitroglycerin on the relief of coronary artery stenosis in the candidates for percutaneous coronary intervention (PCI).

Methods

We included patients with angina pectoris or myocardial infarction who were candidates for PCI. In the coronary angiography, the culprit vessel involved was evaluated, and bolus nitroglycerin at a dose of 25–200 mcg was injected into the affected coronary artery. A significant change in the percentage of coronary artery stenosis was considered a positive response, and these patients were then compared with patients who did not have a substantial change in the percentage of stenosis at the same time. Univariate analysis and then multivariate logistic regression analysis was performed to determine the predictors of response to intracoronary nitroglycerin.

Results

Among 360 patients, 27 (7.5%) responded to nitroglycerine, and 333 (92.5%) were non-responsive. The mean age of patients was 60.2 ± 11.6 years, ranging from 23 to 93 years, and 265 (73.6%) were men. The study groups were not significantly different in the baseline demographic characteristics. The presence of multivessel disease (Odds ratio (OR) = 16.26, 95% confidence interval (CI):2.07–127.6; P = 0.008) and stenosis in the left circumflex artery (OR = 3.62, 95% CI: 1.03–12.70; P = 0.044) were the independent predictors for nonresponse to nitroglycerine, leading to PCI.

Conclusion

In some cases, especially those without multivessel diseases, intracoronary nitroglycerine administration can efficiently relieve coronary stenosis and prevent unnecessary PCI.

Peer Review reports

Introduction

Acute coronary syndrome (ACS) is a common clinical condition in the emergency departments, and patients with elevation of cardiac biomarkers, electrocardiographic changes, or typical clinical symptoms of unstable angina are directed for further evaluation by coronary angiography [1, 2]. Percutaneous coronary intervention (PCI) is currently the mainstay of treatment for symptomatic coronary artery disease [3, 4]. However, this safe procedure is not free of complications, and it can sometimes fail to reach complete revascularization [5, 6]. On the other hand, not all patients with ACS have coronary stenosis, and current evidence shows that up to 30% of them do not require PCI [7]. Among the probable causes, coronary spasm is a frequent mechanism for ACS, causing ischemia at rest.

Coronary artery spasm, a reversible, focal, and severe vasoconstriction, could happen in almost 1.5% of PCI procedures [8, 9]. Coronary artery spasm was observed in 25% of patients who presented with stable angina and almost 49% of those with ACS [7]. Also, it is more probable to occur at the site of a recent myocardial infarction and complicates fixed coronary lesions in up to 60% of acute coronary syndrome cases [10]. Previous studies have shown that intra-coronary injection of nitroglycerin has been effective in relieving stenosis in patients with coronary vasospasm and, in some cases, in reducing atherosclerotic stenosis [11,12,13]. Moreover, it is noteworthy that many patients with coronary vasospasm are treated invasively as an atherothrombotic coronary event [8]. However, the effect of intra-coronary nitroglycerin administration during angiography has not received much attention in clinical practice yet, and despite the recommendation of the current guidelines, it is often neglected in clinical practice [3, 14, 15]. We believe administering intracoronary nitroglycerins during diagnostic coronary angiography and before PCI may significantly reduce unnecessary invasive coronary revascularization. Therefore, we investigated the effect of intra-coronary nitroglycerin administration on coronary artery stenosis in patients undergoing PCI in our hospital.

Materials and methods

In this prospective cohort study, we evaluated the effect of intra-coronary nitroglycerin on the relief of coronary artery stenosis in patients undergoing PCI. Participants in this study were selected from PCI candidates referred to Imam Khomeini Hospital between 2018 and 2019. Patients with angina pectoris or myocardial infarction and having significant coronary stenosis (> 70%) were included in the study. Two independent interventional cardiologists reviewed coronary arteriograms. The percentage of stenosis was calculated as follows using the Cardiovascular measurement software (QAngio XA 7.2, MEDIS): 100 × [1- (stenosis diameter/reference diameter)]. In these measurements, the minimum lesion diameter was used to calculate the percentage of stenosis diameter relative to the reference vessel diameter [16].

The research board of the cardiology department and the committee of medical ethics at our center approved the protocol of this study (IR.TUMS.IKHC.REC.1397.252). All participants gave informed consent to take part in the study.

Before enrolment, patients' characteristics, including age, sex, cardiovascular risk factors, and the diagnosis at presentation, including stable angina, unstable angina, non-ST elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI) were recorded. Risk factors for coronary artery disease included hypercholesterolemia, hypertension, smoking, chronic kidney disease, and diabetes mellitus [17, 18].

In the case of significant stenosis during angiography, nitroglycerin at a dose of 25–200 mcg was injected into the affected coronary arteries as a bolus dose. The dosage was decided individually for every patient based on the type of vessel, its diameter, and hemodynamics of the patient at the discernment of the interventionist. The percentage of stenosis before and after intra-coronary nitroglycerin injection was assessed. Response to nitroglycerine was defined as the reduction of the stenosis below 70% of the lumen. Unresponsive patients to intracoronary nitroglycerine injection with significant coronary stenosis (> 70%) or with moderate coronary stenosis (40–70%) but fractional flow reserve (FFR) less than 0.8 underwent PCI. The planned PCI was suspended in responsive patients to intracoronary nitroglycerine with stenosis below 40% or with moderate coronary stenosis (40–70%) but FFR more than 0.8.

Statistical analysis

The categorical data were expressed as frequency (percentage) and were compared between the groups using the Chi-square test. Numeric data were shown as mean ± standard deviation and were compared between the group using the student's t-test. We performed univariable and multivariable logistic regression analyses to determine the predictors for response to nitroglycerine. For the multivariable regression model, variables with a P-value < 0.2 in the univariable model were included. Odds ratios (OR) and 95% confidence intervals (CI) were calculated and reported for every variable. The statistical analysis was performed using SPSS version 24.0 (IBM, USA), and a P-value of < 0.05 was considered significant.

Results

In this study, we evaluated the clinical and angiographic data of 366 patients. In total, 27 (7.5%) patients were responsive to intracoronary nitroglycerine (responsive group), and 333 (92.5%) patients were unresponsive (unresponsive group). The mean age of the patients was 60.2 ± 11.6 years, ranging from 23 to 93 years. Men constituted 73.6% of the patients. There was no significant difference between the study groups in the baseline demographic characteristics. However, a history of atherosclerotic cardiovascular disease seemed to be more frequent in the unresponsive group (P = 0.081). Multivessel disease was more frequent in the unresponsive group (P = 0.002) and the stenosis in the left anterior descending artery (P = 0.006). Table 1 summarizes the details of the baseline and angiographic characteristics of the study population and their comparison between the responsive and nonresponsive groups. Response and nonresponse to intracoronary nitroglycerine in two identical patients are depicted in Fig. 1

Table 1 Baseline characteristics of the study population, their comparison between the responsive and unresponsive patients to nitroglycerine, and the univariable logistic regression analysis
Full size table
Fig. 1
figure 1

A Coronary angiography of a 74 year old man showing stenosis in the mid section of the left anterior descending artery that resolved after intracoronary nitroglycerine injection (B). C Coronary angiography of a 75 year old woman showing stenosis in the mid section of the left anterior descending artery that did not resolve after administration of intracoronary nitroglycerine (D)

Full size image

The multivariate analysis showed the presence of multivessel disease (OR = 16.26, 95% CI:2.07–127.6; P = 0.008) and stenosis in the left circumflex artery (OR = 3.62, 95% CI: 1.03–12.70; P = 0.044) were the independent predictors for nonresponse to nitroglycerine, leading to PCI (Table 2). Nonetheless, presenting with STEMI was a borderline predictor for nonresponse to nitroglycerin (OR: 3.02, 95% CI: 0.98–9.36; P = 0.055).

Table 2 Predictors of response to intracoronary nitroglycerine based on the multivariable logistic regression analysis
Full size table

Discussion

This study investigated the effect of intracoronary nitroglycerin administration on relieving coronary artery stenosis in PCI candidates. All patients had significant coronary stenosis (> 70%) before injection and were candidates for revascularization. Nevertheless, 7.5% of patients responded to it after intracoronary administration of nitroglycerine and did not require PCI. The independent predictors for response to nitroglycerin included multivessel disease and stenosis in the left circumflex artery.

Coronary vasospasm is a reversible, focal, and intense coronary vasoconstriction, and the diagnosis is generally made in people without significant coronary stenosis [8]. As far as the prognosis of patients with coronary artery spasm is excellent [17], diagnosis before performing any coronary procedure is essential. Reactivity of the coronary artery to antispasmodic agents can be a helpful way to diagnose coronary vasospasm and prevent unnecessary stenting and the resulting complications and costs [19, 20]. For this reason, intracoronary administration of nitroglycerine leads to increased coronary flow through spasm relief [21], which was also confirmed in our study.

Several case reports in the literature address the benefit of the administration of intracoronary nitroglycerine in patients who presented with ACS, and this action deferred them from PCI [22,23,24,25]. In a case series study by Vishnevsky et al. [14], intracoronary nitroglycerine administration during angiography prior to a scheduled PCI resulted in the resolution of stenosis in all patients. In this study, none of the six patients who responded to intracoronary nitroglycerine had STEMI and were finally treated with calcium channel blockers with or without long-acting nitrates. Vishnevsky's study showed that the possibility of coronary spasm should be considered in patients with coronary artery stenosis on angiography, especially in young people, smokers, or positive history of migraine. However, we did not observe any association between smoking and response to nitroglycerine in the present study. Vishnevsky et al. noted that coronary spasm could be present in severe cases during coronary angiography, even those without symptoms of angina or electrocardiographic changes, although ECG changes were not studied in the present study. Therefore, an intracoronary nitroglycerine bolus in cases of suspected vasospasm will be both diagnostic and therapeutic, as confirmed by our study.

Mohammad et al. also reported 16 patients with left main coronary artery vasospasm who were falsely diagnosed with stenosis and underwent coronary artery bypass graft surgery [26]. To prevent unnecessary bypass surgery, the authors recommended intracoronary nitroglycerin as "a reasonable routine in hemodynamically stable patients with significant LM stenosis."

In a study on patients who presented with myocardial infarction, one patient responded to nitroglycerine and did not require fibrinolytic [27]. Based on the CASPAR study (7), 28% of the patients who presented with ACS did not have any significant lesion after intracoronary injection of nitroglycerine. In another study from the same dataset and after three years of follow-up, none of these patients developed nonfatal myocardial infarction or cardiac death. Nonetheless, 50% continued to have persistent angina, and angiography was repeated in three cases (3.9%). The authors concluded that patients with ACS who show no culprit lesion and suffer coronary spasm have an excellent and significantly better prognosis for survival and coronary events compared with patients with a culprit lesion. In a unique piece of evidence, a patient with multiple narrowings in the coronary artery angiography responded well to intracoronary nitroglycerine and was deferred from PCI [28]. In our study, out of 140 patients with STEMI, 5 (3.5%) responded to nitroglycerine and were treated medically. Considering the massive number of patients who undergo PCI annually, this small percentage can dramatically reduce the costs and complications.

Study limitations

As mentioned above, the number of patients previously examined was very small. While in this cross-sectional study, 360 patients were studied, of whom 27 were responsive to nitroglycerine, and therefore, previous studies are not comparable to our study in terms of sample size. In addition, these patients were carefully analyzed for details such as risk factors, clinical syndrome, and type of vessel involved. Nonetheless, our study has some shortcomings. First, this was a single-center study performed in a university hospital. Also, we did not follow up with the patients for a more extended period to observe the recurrence of the symptoms or progression to CAD.

Conclusion

Intracoronary nitroglycerin administration can relieve coronary artery stenosis in the candidates for PCI and prevent unnecessary procedures. The presence of multivessel disease and stenosis in the left circumflex artery were the independent predictors for non-responders. A further large-scale study might clarify the definite predictors of response to intracoronary nitroglycerine.

Availability of data and materials

The datasets generated and analyzed during the current study are not publicly available due to the policy of our department but are available from the corresponding author on reasonable request.

References

  1. McConaghy JR, Sharma M, Patel H. Acute chest pain in adults: OUTPATIENT EVALUATION. Am Fam Physician. 2020;102(12):721–7.

    PubMed  Google Scholar 

  2. Barstow C, Rice M, McDivitt JD. Acute coronary syndrome: diagnostic evaluation. Am Fam Physician. 2017;95(3):170–7.

    PubMed  Google Scholar 

  3. Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, Chambers CE, Ellis SG, Guyton RA, Hollenberg SM, et al. 2015 ACC/AHA/SCAI focused update on primary percutaneous coronary intervention for patients with st-elevation myocardial infarction: an update of the 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention and the 2013 ACCF/AHA Guideline for the management of ST-elevation myocardial infarction. Circulation. 2016;133(11):1135–47.

    Article  Google Scholar 

  4. Epstein AJ. Coronary revascularization trends in the United States, 2001–2008. JAMA. 2011;305(17):1769–76.

    Article  CAS  Google Scholar 

  5. Abtan J, Wiviott SD, Sorbets E, Popovic B, Elbez Y, Mehta SR, Sabatine MS, Bode C, Pollack CV, Cohen M, et al. Prevalence, clinical determinants and prognostic implications of coronary procedural complications of percutaneous coronary intervention in non-ST-segment elevation myocardial infarction: Insights from the contemporary multinational TAO trial. Arch Cardiovasc Dis. 2021;114(3):187–96.

    Article  Google Scholar 

  6. Giannini F, Candilio L, Mitomo S, Ruparelia N, Chieffo A, Baldetti L, Ponticelli F, Latib A, Colombo A. A practical approach to the management of complications during percutaneous coronary intervention. JACC Cardiovasc Interv. 2018;11(18):1797–810.

    Article  Google Scholar 

  7. Ong P, Athanasiadis A, Hill S, Vogelsberg H, Voehringer M, Sechtem U. Coronary artery spasm as a frequent cause of acute coronary syndrome. J Am Coll Cardiol. 2008;52(7):523–7.

    Article  Google Scholar 

  8. Konidala S, Gutterman DD. Coronary vasospasm and the regulation of coronary blood flow. Prog Cardiovasc Dis. 2004;46(4):349–73.

    Article  Google Scholar 

  9. Moukarbel GV, Dakik HA. Diffuse coronary artery spasm induced by guidewire insertion. J Invasive Cardiol. 2003;15(6):353–4.

    PubMed  Google Scholar 

  10. Bertrand ME, LaBlanche JM, Tilmant PY, Thieuleux FA, Delforge MR, Carre AG, Asseman P, Berzin B, Libersa C, Laurent JM. Frequency of provoked coronary arterial spasm in 1089 consecutive patients undergoing coronary arteriography. Circulation. 1982;65(7):1299–306.

    Article  CAS  Google Scholar 

  11. Moukarbel GV, Weinrauch LA. Disruption of coronary vasomotor function: the coronary spasm syndrome. Cardiovasc Ther. 2012;30(2):e66–73.

    Article  Google Scholar 

  12. Heidari R, Sadeghi M, Sanei H, Rabie K. The effect of trinitroglycerine injection on angiographic complications. J Inflamm Dis. 2010;14(3):5–10.

    Google Scholar 

  13. Balaban Y, Kaya A, Satilmisoglu MH, Balaban MB. Intracoronary focal nitroglycerin injection through drilled balloon is very effective in the resolution of coronary spasm versus into proximal coronary artery: A prospective randomized comparison study. J Interv Cardiol. 2018;31(6):765–74.

    Article  Google Scholar 

  14. Vishnevsky A, Julien HM, Fischman DL, Walinsky P, David Ogilby J, Ruggiero NJ, Jasti B, Savage MP. Unrecognized coronary vasospasm in patients referred for percutaneous coronary intervention: Intracoronary nitroglycerin, the forgotten stepchild of cardiovascular guidelines. Catheter Cardiovasc Interv. 2017;90(7):1086–90.

    Article  Google Scholar 

  15. Neumann F-J, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, Byrne RA, Collet J-P, Falk V, Head SJ, et al. 2018 ESC/EACTS guidelines on myocardial revascularization. EuroIntervention. 2019;14(14):1435–534.

    Article  Google Scholar 

  16. Zhang H, Mu L, Hu S, Nallamothu BK, Lansky AJ, Xu B, Bouras G, Cohen DJ, Spertus JA, Masoudi FA, et al. Comparison of physician visual assessment with quantitative coronary angiography in assessment of stenosis severity in China. JAMA Intern Med. 2018;178(2):239–47.

    Article  Google Scholar 

  17. Lin MJ, Yang WC, Chen CY, Huang CC, Chuang HY, Gao FX, Wu HP. Hypertension and chronic kidney disease affect long-term outcomes in patients with stable coronary artery disease receiving percutaneous coronary intervention. Sci Rep. 2018;8(1):17673.

    Article  Google Scholar 

  18. Lin MJ, Lee J, Chen CY, Huang CC, Wu HP. Chronic kidney disease and diabetes associated with long-term outcomes in patients receiving percutaneous coronary intervention. BMC Cardiovasc Disord. 2017;17(1):242.

    Article  Google Scholar 

  19. Matta A, Bouisset F, Lhermusier T, Campelo-Parada F, Elbaz M, Carrié D, Roncalli J. Coronary artery spasm: new insights. J Interv Cardiol. 2020;2020:1–10.

    Article  Google Scholar 

  20. Vishnevsky A, Fischman DL, Savage MP. Intracoronary nitroglycerin: recognizing coronary spasm first and foremost to avoid unnecessary coronary stents. Expert Rev Cardiovasc Ther. 2017;15(10):727–8.

    Article  CAS  Google Scholar 

  21. Galassi AR, Tomasello SD, Crea F, Costanzo L, Campisano MB, Marzá F, Tamburino C. Transient impairment of vasomotion function after successful chronic total occlusion recanalization. J Am Coll Cardiol. 2012;59(8):711–8.

    Article  Google Scholar 

  22. Haruta S, Arai K. Acute myocardial infarction caused by coronary spasm and dissection treated with medical therapy. Int Heart J. 2020;61(1):169–73.

    Article  Google Scholar 

  23. Parikh A, Vacek TP. Spontaneous left main and right coronary artery spasm in a patient with vasospastic Angina. J Investig Med High Impact Case Rep. 2017;5(3):2324709617732796.

    PubMed  PubMed Central  Google Scholar 

  24. Parikh PB, Clerkin K, Mancini D, Kirtane AJ. Severe coronary artery spasm presenting as Prinzmetal’s angina following cardiac transplantation. Cardiovasc Revasc Med. 2018;19(8):13–5.

    Article  Google Scholar 

  25. Esenboga K, Baskovski E, Ozyuncu N, Tutar E. Catheter-induced multiple non-proximal coronary spasm in a patient presenting with myocardial infarction. Cureus. 2020;12(3):e7456.

    PubMed  PubMed Central  Google Scholar 

  26. Mohammed AA, Yang A, Shao K, DiSabatino A, Blackwell R, Banbury M, Weintraub WS, Doorey A. Patients with left main coronary artery vasospasm inadvertently undergoing coronary artery bypass grafting surgery. J Am Coll Cardiol. 2013;61(8):899–900.

    Article  Google Scholar 

  27. Rentrop KP, Feit F, Blanke H, Stecy P, Schneider R, Rey M, Horowitz S, Goldman M, Karsch K, Meilman H, et al. Effects of intracoronary streptokinase and intracoronary nitroglycerin infusion on coronary angiographic patterns and mortality in patients with acute myocardial infarction. N Engl J Med. 1984;311(23):1457–63.

    Article  CAS  Google Scholar 

  28. Ostovan MA, Khanian MS, Hamidi S, Fattahi M, Dehghani P. Spontaneous multi-focal coronary artery spasm: a case report. J Cardiovasc Thorac Res. 2016;8(3):137–9.

    Article  Google Scholar 

Download references

Acknowledgements

The authors sincerely thank all nursing and administrative staff of the catheterization laboratory of Imam Khomeini Hospital for their cooperation.

Funding

This study was supported by the Tehran University of Medical Sciences.

Author information

Authors and Affiliations

  1. Department of Cardiology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Dr. Gharib st, Keshavarz Blvd, Tehran, 1419733141, Iran

    Amirhossein Nasiri-Partovi & Reza Rahmani

  2. Department of Cardiovascular Research, Tehran Heart Center, Cardiovascular Research Institute, Tehran University of Medical Sciences, Tehran, Iran

    Akbar Shafiee

Authors
  1. Amirhossein Nasiri-Partovi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akbar Shafiee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Reza Rahmani
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

ANP: Wrote the proposal, collected data, and revised the initial and final version of the manuscript. AS: Did the data analysis and drafted the manuscript. RR: Hypothesised the study and supervised all the stages of the study. All the authors reviewed the manuscript and approved it.

Corresponding author

Correspondence to Reza Rahmani.

Ethics declarations

Ethics approval and consent to participate

The ethical committee of Imam Khomeini Hospital approved this study (IR.TUMS.IKHC.REC.1397.252). The study protocol was designed in accordance with the Declaration of Helsinki and its updates. Additionally, all patients signed a written informed consent at admission and consented that their clinical data could be used anonymously for research purposes.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Nasiri-Partovi, A., Shafiee, A. & Rahmani, R. Intracoronary injection of nitroglycerine can prevent unnecessary percutaneous coronary intervention. BMC Cardiovasc Disord 22, 416 (2022). https://doi.org/10.1186/s12872-022-02823-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12872-022-02823-2

Keywords

  • Intracoronary nitroglycerine
  • Coronary artery disease
  • Percutaneous coronary intervention

BMC Cardiovascular Disorders

ISSN: 1471-2261

Contact us