Duration of Hyperemia With Intracoronary Administration of Papaverine
2021; Wiley; Volume: 10; Issue: 3 Linguagem: Inglês
10.1161/jaha.120.018562
ISSN2047-9980
AutoresTakuya Mizukami, Jeroen Sonck, Emanuele Gallinoro, Monika Kodeboina, Alessandro Canvedra, Sakura Nagumo, Jozef Bartúnek, Eric Wyffels, Marc Vanderheyden, Toshiro Shinke, Bernard De Bruyne, Carlos Collet,
Tópico(s)Cardiac pacing and defibrillation studies
ResumoHomeJournal of the American Heart AssociationVol. 10, No. 3Duration of Hyperemia With Intracoronary Administration of Papaverine Open AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citations ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toOpen AccessLetterPDF/EPUBDuration of Hyperemia With Intracoronary Administration of Papaverine Takuya Mizukami, MD, PhD, Jeroen Sonck, MD, Emanuele Gallinoro, MD, Monika Kodeboina, MD, Alessandro Canvedra, MD, Sakura Nagumo, MD, PhD, Jozef Bartunek, MD, PhD, Eric Wyffels, MD, Marc Vanderheyden, MD, Toshiro Shinke, MD, PhD, Bernard De Bruyne, and MD, PhD, and Carlos ColletMD, PhD Takuya MizukamiTakuya Mizukami https://orcid.org/0000-0003-1086-8746 Cardiovascular Center Aalst, , Onze‐Lieve‐Vrouw Clinic, , Aalst, , Belgium Clinical Research Institute for Clinical Pharmacology and Therapeutics, , Showa University, , Tokyo, , Japan Department of Cardiology, , Gifu Heart Center, , Gifu, , Japan , Jeroen SonckJeroen Sonck Cardiovascular Center Aalst, , Onze‐Lieve‐Vrouw Clinic, , Aalst, , Belgium Department of Advanced Biomedical Sciences, , University of Naples, Federico II, , Naples, , Italy , Emanuele GallinoroEmanuele Gallinoro https://orcid.org/0000-0002-5519-2818 Cardiovascular Center Aalst, , Onze‐Lieve‐Vrouw Clinic, , Aalst, , Belgium , Monika KodeboinaMonika Kodeboina https://orcid.org/0000-0002-4756-3244 Cardiovascular Center Aalst, , Onze‐Lieve‐Vrouw Clinic, , Aalst, , Belgium , Alessandro CanvedraAlessandro Canvedra Cardiovascular Center Aalst, , Onze‐Lieve‐Vrouw Clinic, , Aalst, , Belgium , Sakura NagumoSakura Nagumo Department of Cardiology, , Showa University Fujigaoka Hospital, , Kanagawa, , Japan , Jozef BartunekJozef Bartunek Cardiovascular Center Aalst, , Onze‐Lieve‐Vrouw Clinic, , Aalst, , Belgium , Eric WyffelsEric Wyffels Cardiovascular Center Aalst, , Onze‐Lieve‐Vrouw Clinic, , Aalst, , Belgium , Marc VanderheydenMarc Vanderheyden Cardiovascular Center Aalst, , Onze‐Lieve‐Vrouw Clinic, , Aalst, , Belgium , Toshiro ShinkeToshiro Shinke https://orcid.org/0000-0001-7349-7538 Division of Cardiology, , Department of Medicine, , Showa University School of Medicine, , Tokyo, , Japan , Bernard De BruyneBernard De Bruyne https://orcid.org/0000-0001-6567-168X Cardiovascular Center Aalst, , Onze‐Lieve‐Vrouw Clinic, , Aalst, , Belgium Department of Cardiology, , Lausanne University Center Hospital, , Lausanne, , Switzerland , and Carlos ColletCarlos Collet * Correspondence to: Carlos Collet, MD, PhD, Cardiovascular Center Aalst, OLV Hospital, Moorselbaan 164, Aalst 9300, Belgium. E‐mail: E-mail Address: [email protected] https://orcid.org/0000-0003-0227-0082 Cardiovascular Center Aalst, , Onze‐Lieve‐Vrouw Clinic, , Aalst, , Belgium Originally published17 Jan 2021https://doi.org/10.1161/JAHA.120.018562Journal of the American Heart Association. 2021;10:e018562Fractional flow reserve (FFR) and pressure pullback gradient (PPG) are 2 hyperemic indices used in clinical practice to determine the hemodynamic significance of coronary stenoses and distribution of epicardial resistance. The PPG is calculated using FFR values along the coronary vessels during a pullback maneuver for determination of the pattern (eg, focal or diffuse) of coronary artery disease.1 Insufficient hyperemia may minimize pressure … drops and affecting pressure gradients quantification.Papaverine has been validated for FFR measurements in several studies.2, 3, 4 However, despite its relatively long duration of action, a detailed analysis of the vessel‐specific dose–response and steady hyperemic state duration stratified by severity of coronary artery disease is still lacking.The data that support the findings of this study are available from the corresponding author upon reasonable request. This was a prospective, single‐center study of patients undergoing coronary angiography with an indication for FFR measurement. Approval was obtained from the local Ethics Committee (OLV‐74690), and the study protocol was in accordance with the Declaration of Helsinki. Written informed consent was obtained from all patients before enrollment in this study. A 6F guiding catheter was inserted through the femoral or radial artery. A pressure guidewire (PressureWire X, Abbott Vascular, USA) was advanced in the distal part of the vessel to obtain (distal mean coronary pressure [Pd]) at least 30 mm beyond the epicardial lesion. Pd/mean aortic pressure (Pd/Pa) values were recorded. The contrast was flushed from the guiding catheter and hyperemia was induced with intracoronary papaverine at a dose of 12 to 16 mg for the left coronary artery and 8 to 12 mg for the right coronary artery. The time to maximal hyperemia (time needed to reach 80% [T80] and 90% [T90] of the minimal value of Pd/Pa after the injection of papaverine) and plateau phase (time during which Pd/Pa remained at >90% of its minimal value) were computed (Figure A).3 Variability during the plateau phase was assessed extracting 1 FFR value per second. Groups were stratified according to the FFR value of ≤0.80. Statistical comparisons between groups were performed using the Mann‐Whitney U test.Download figureDownload PowerPointFigure 1. Case example of a pressure tracing after induction of hyperemia with papaverine and duration of hyperemic effect stratified by FFR.A, An Pd/Pa tracing after the administration of intracoronary papaverine. The dashed green lines denote the plateau phase and 80%, 90%, and 100% of maximal hyperemia. The solid green areas represent the plateau phase. B, The duration of hyperemic plateau stratified by FFR 0.80. Pd/Pa values in the vessel with FFR ≤0.80 and FFR >0.80 are shown by red and blue curves, respectively; the shaded red and blue areas correspond to the 95% CIs. The solid green area represents the plateau phase. C, Correlation between distal FFR value and duration of maximal hyperemia. The gray area corresponds to the 95% CIs. FFR indicates fractional flow reserve; Pa, aortic pressure; and Pd, diastolic pressure.Overall, 46 patients (51 vessels) were included. Vessel types were 32 left anterior descending coronary arteries, 11 left circumflex coronary arteries, and 8 right coronary arteries. The mean diameter stenosis was 43.5±13.0%. The mean pressure tracing recording time after papaverine injection was 1.72±0.65 minutes. The mean FFR was 0.82±0.09 and 23 vessels had an FFR ≤0.80. There were no adverse effects or complications observed during the administration of papaverine.Median T80 and T90 were 9.2 (IQR 7.4–11.9) seconds and 11.4 (IQR 9.2–16.4) seconds, respectively. The plateau phase lasted for 40.5 (IQR 22.2–49.8) seconds. The changes of Pd/Pa value during the plateau phase was 0.001 (IQR −0.016 to 0.019; coefficient of variation of 11.4%).The median plateau phase was significantly longer in vessels with an FFR value ≤0.80 compared with vessels with FFR >0.80 (43.6 [IQR 36.1–60.7] seconds versus 32.6 [IQR 18.3–42.1] seconds, P value 0.027; Figure B). Distal FFR values were significantly correlated with the duration of the hyperemic plateau phase (ρ=−0.33 [95% CI −0.56 to −0.07]; Figure C).Papaverine has been used as a hyperemic agent for the assessment of coronary flow reserve and FFR. Previous studies reported a mean time to onset of 17 to 23 seconds and the mean hyperemic duration of 22 to 51 seconds.2, 3 In the present study, using standardized papaverine doses, we found time to 90% of the hyperemic onset of 12.4 (IQR 8.8–19.2) seconds and a hyperemic plateau duration of 43.6 (IQR 36.1–60.7) seconds. We found an interaction between functional severity and time of microvascular dilation. The precise mechanisms behind this phenomenon remain to be elucidated. Concerns have been raised about the safety of intracoronary papaverine administration in terms of ventricular arrhythmias. Papaverine transitorily prolongs the QTc interval. Ventricular arrhythmias are observed in ≈1.4% of the cases.5 In the present report there were no adverse events related to the use of papaverine.The present analysis expands our knowledge by ascertaining that vessels with hemodynamically significant lesions, based on a contemporary criterion (ie, FFR ≤0.80), have similar time to hyperemic onset and longer stable‐state hyperemic duration compared with vessels with nonsignificant lesions. These findings portray clinical implications given the increased use of the FFR pullbacks to evaluate the functional pattern of coronary artery disease using PPG and refine percutaneous coronary intervention indication and strategy. Recently, PPG was described as potentially influencing percutaneous coronary intervention outcomes. In clinical practice, vessels with an FFR ≤0.80 will be considered for PPG measurement. Based on the results of the present study, papaverine provides sufficient time to perform a pullback maneuver for at least 30 seconds under maximal hyperemic conditions. Therefore, the current study provides the foundations for the recommendation of a pullback technique using intracoronary papaverine administration.Intracoronary administration of papaverine provides rapid onset hyperemia with a duration of steady‐state sufficient for pullback maneuvers with minimal variability. The duration of steady‐state hyperemia is longer in vessels with hemodynamically significant lesions.Sources of FundingThis work has been supported by VZW Cardiovascular Research Centre Aalst, Belgium.DisclosuresMizukami reports receiving consultancy fees from Heart Flow Inc. Sonck reports research grants provided by Cardiopath PhD program. Collet reports receiving research grants from Biosensor, Heart Flow Inc., and Abbott Vascular; and consultancy fees from Heart Flow Inc, Opsens, and Philips Volcano. De Bruyne reports receiving consultancy fees from Boston Scientific Abbott Vascular. The remaining authors have no disclosures to report.Footnotes* Correspondence to: Carlos Collet, MD, PhD, Cardiovascular Center Aalst, OLV Hospital, Moorselbaan 164, Aalst 9300, Belgium. E‐mail: [email protected]comFor Sources of Funding and Disclosures, see page 3.References1 Collet C, Sonck J, Vandeloo B, Mizukami T, Roosens B, Lochy S, Argacha J‐F, Schoors D, Colaiori I, Di Gioia G, et al. Measurement of hyperemic pullback pressure gradients to characterize patterns of coronary atherosclerosis. J Am Coll Cardiol. 2019; 74:1772–1784. DOI: 10.1016/j.jacc.2019.07.072.CrossrefMedlineGoogle Scholar2 Wilson RF, White CW. Intracoronary papaverine: an ideal coronary vasodilator for studies of the coronary circulation in conscious humans. Circulation. 1986; 73:444–451. DOI: 10.1161/01.CIR.73.3.444.LinkGoogle Scholar3 De Bruyne B, Pijls NH, Barbato E, Bartunek J, Bech JW, Wijns W, Heyndrickx GR. Intracoronary and intravenous adenosine 5'‐triphosphate, adenosine, papaverine, and contrast medium to assess fractional flow reserve in humans. Circulation. 2003; 107:1877–1883. DOI: 10.1161/01.CIR.0000061950.24940.88.LinkGoogle Scholar4 van der Voort PH, van Hagen E, Hendrix G, van Gelder B, Bech JW, Pijls NH. Comparison of intravenous adenosine to intracoronary papaverine for calculation of pressure‐derived fractional flow reserve. Cathet Cardiovasc Diagn. 1996; 39:120–125. DOI: 10.1002/(SICI)1097‐0304(199610)39:2 3.0.CO;2‐H.CrossrefMedlineGoogle Scholar5 Okabe Y, Otowa K, Mitamura Y, Murai H, Usui S, Kaneko S, Takamura M. Evaluation of the risk factors for ventricular arrhythmias secondary to QT prolongation induced by papaverine injection during coronary flow reserve studies using a 4 Fr angio‐catheter. Heart Vessels. 2018; 33:1358–1364.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails February 2, 2021Vol 10, Issue 3Article InformationMetrics Download: 1,139 Copyright © 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley BlackwellThis is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.https://doi.org/10.1161/JAHA.120.018562PMID: 33459027 Manuscript receivedAugust 10, 2020Manuscript acceptedNovember 23, 2020Originally publishedJanuary 17, 2021 Keywordsfractional flow reservehyperemiapapaverinecoronary physiologyPDF download SubjectsCatheter-Based Coronary and Valvular InterventionsPercutaneous Coronary InterventionPharmacology
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