Abstract View largeDownload slide View largeDownload slide This editorial refers to ‘Identification of capillary rarefaction using intracoronary wave intensity analysis with resultant prognostic implications for cardiac allograft patients’†, by C.J. Broyd et al., on page 1807. Wave intensity analysis (WIA) is a mathematical-based approach which through the interpretation of intracoronary measured blood pressure can assess capillary rarefraction. In this issue, Broyd et al.1 applied this relatively novel analysis in a cohort of 52 allograft patients with the aim of identifying those with vasculopathy remodelling at the earliest possible moment of presentation. In this well conducted study, data were acquired from imaging, using angiography and intravascular ultrasound (IVUS), while additional data were acquired via histology, using myocardium material collected by biopsies and, in some cases, by using explanted hearts. The authors then developed a new mathematical method and collected data to corroborate their analysis (validation), an aspect which requires not only skilled but also determined scientists. The prevailing evolution of invasive coronary physiology for revascularization guidance, and its remarkable capacity to discriminate patients at risk for a cardiovascular event, has led to its prominent role as a decision modality for treatment strategies in daily clinical practice. The success of this evolution has many fathers, including early pioneers such as Richard Kirkeeide and Lance Gould, to the more recent endeavours of Nico Pijls, Bernard de Bruyne, and Justin Davies. Yet, intriguingly, the earliest recorded characterization of coronary physiology was actually by Scaramucci in 1695 who introduced the theory of filling and emptying of coronary arteries in relation to myocardial contractions.2 Almost two centuries later, Porter corroborated this theory in animal models in 1898.3 Remarkably, Porter, unassisted both editorially and financially, founded a year earlier the American Journal of Physiology. Two decades earlier, Rebatel described in a milestone publication the coronary pressure and flow relationship in 1872.4 The pressure–flow field was further advanced by Green in 19335 and Gregg in 1940.6 Wiggers added his observations to the debate in 1954,7 namely that when arterial pressure is high in the systolic phase, the coronary flow is low; this in contrast to a low arterial pressure, associated with an increased coronary flow. This observation was attributed to the inverse relationship of ‘impeded’ myocardial flow during the systolic phase, although at that time there was still debate concerning the underlying mechanisms. The early instrumentation involved in hemodynamics research was elementary and somewhat crude. However, with the introduction of the electromagnetic flow meter in the coronary arena, a seismic shift took place.8 For instance, in a canine model, high-frequency recordings of coronary flow could be obtained during simple manipulations of cardiac function, making inferences from minor changes in the complex flow patterns of the coronary artery tree. Mathematical models of the myocardium were introduced in the early 1970s but with the caveat of unrealistic assumptions and coupled with the insufficient computer processing power of that era.9 By the late 1980s, a new dawn had arrived when it became possible to measure the coronary blood flow velocity both invasively by a Doppler catheter as well by applying computer-assisted processing of cineangiography using digital subtraction technology.10 However, the comparison between the differently applied methods resulted in mixed outcomes. Possibly the most important landmark in the physiology field was Nico Pijls’ fractional flow reserve (FFR) method, an index that identified the functional significance of a coronary stenosis. This was a significant improvement on the previous methods for analysis of coronary stenosis.11 FFR has fulfilled its rite of passage—after many protracted scientific debates and thorough validation—and has now become a standard tool for clinical decision in the cathlab, as witnessed in FAME.12 However, FFR does have some limitations of application with respect to diffuse disease, serial lesions, and acute coronary syndromes.13 A new kid on the block arrived in 2000 in the form of WIA.14 This analysis was the foundation to develop the instantaneous wave-free pressure ratio (iFR) method.15 The iFR method is based on the instantaneous ratio of translesional pressures acquired during a specific period during diastole where the coronary resistance is minimal and constant. The additional benefit of no induced hyperaemia makes for a more comfortable experience for the patient. It is thus not surprising that the same iFR group have gone further in their explorations with their paper on WIA and its application to identify coronary artery disease, in this case the early detection of cardiac allograft vasculopathy (CAV) in allograft patients. The concept of WIA and the methodology required to analyse the pressure signals might be complex at first to understand. An elegant overview of both the mathematical models applied and the possible application in a number of cardiac pathologies was recently presented by Broyd.16 Indeed, as the authors state, the application is currently limited to invasive measurements. However, advancements in technology and particularly those within the field of cardiovascular imaging and computer technology are accelerating exponentially,17 providing hopefully in the near future a non-invasive set-up. The results of early experiments are quite promising.18 In the current paper, Broyd et al. applied the WIA method for the detection of early signs of vasculopathy in allograft patients.1 Haemodynamic measurements in this patient group have previously been scarcely reported. Earlier investigations mostly applied invasive methods such as angiography or IVUS to measure coronary vessel wall irregularities. However, angiography does not perform well in the cases of diffuse intimal thickening, and studies involving IVUS19 showed that despite coronary wall changes, no functional impairment was detected. The addition of WIA has the potential to become the missing link in combining data derived from different methodologies in order to identify allograft patients at risk at the earliest possible moment. As mentioned above and as the authors state: ‘the WIA method might also lend weight to its use for other disease processes in which capillary rarefraction is involved’. To maximize its full potential and accessibility in the cathlab, it should become an online integrated tool, an analogue to the present day FFR and iFR measurements. Furthermore, the underlying applied mathematics could be standardized. This would allow uniform outcome comparisons of studies performed at different centres, which will be necessary for further validation. Multicentre trials are certainly necessary in patient cohorts such as the reported allograft patients, as most of the available studies in the literature currently are reporting small numbers. To paraphrase the famous Spanish philosopher, Jorge Agustín Nicolás Ruiz de Santayana y Borrás, otherwise known as George Santayana, ‘to know your future, you must know your past’. Although the field of human haemodynamics has been studied since 1695 (Take home figure), one could argue that only in the last two decades have we been truly in the technological position to translate this acquired knowledge for detection and treatment of cardiovascular disease. Although it took 300 years to go from Scaramucci to Pijls, it took only 15 years for FFR to become standard practice and added to the guidelines. How long will it take for coronary wave intensity analysis to become an enrichment to the ever-expanding coronary haemodynamics armamentarium? Take home figure View largeDownload slide Historic overview of the developments of coronary haemodynamics from early theory up to current daily clinical practice. Take home figure View largeDownload slide Historic overview of the developments of coronary haemodynamics from early theory up to current daily clinical practice. Conflict of interest: none declared References 1 Broyd CJ, , Hernández-Pérez F, , Sergovia J, , Echavarría-Pinto M, , Quirós-Carretero A, , Salas C, , Gonzalo N, , Jiménez-Quevedo P, , Nombela-Franco L, , Salinas P, , Núñez-Gil I, , Del Trigo M, , Goicolea J, , Alonso-Pulpón L, , Fernández-Ortiz A, , Parker K, , Hughes A, , Mayet J, , Davies J, , Escaned J. Identification of capillary rarefaction using intracoronary wave intensity analysis with resultant prognostic implications for cardiac allograft patients . Eur Heart J 2018 ; 39 : 1807 – 1814 . 2 Scaramucci J. Theoremata familiaria viros eruditos consulentia de variis physico-medicis lucubrationibus juxta leges mecanicas. Apud Joannem Baptistam Bustum; 1695 . p70–81. 3 Porter WT. The influence of the heartbeat on the flow of blood through the walls of the heart . Am J Physiol 1898 ; 1 : 145 – 163 . 4 Rebatel F. Recherces Experimentales sur la Circulation dans les Arteries Coronaires . Paris ; 1872 . 5 Green HD , Gregg DE , Wiggers CI. The phasic changes in coronary flow established by differential pressure curves . Am J Physiol 1935 ; 112 : 627 – 639 . 6 Gregg DE , Green HD. Effects of viscosity, ischemia, cardiac output and aortic pressure on coronary blood flow measured under a constant perfusion pressure . Am J Physiol 1940 ; 130 : 108 – 113 . 7 Wiggers CJ. The interplay of coronary vascular resistance and myocardial compression in regulating coronary flow . Circ Res 1954 ; 2 : 271 – 279 . Google Scholar CrossRef Search ADS PubMed 8 Khouri EM , Gregg DE. Miniature electromagnetic flow meter applicable to coronary arteries . J Appl Physiol 1963 ; 18 : 224 – 227 . Google Scholar CrossRef Search ADS PubMed 9 Mirsky I. Effects of anisotropy and nonhomogeneity on left ventricular stresses in the intact heart . Bull Math Biophys 1970 ; 32 : 197 – 213 . Google Scholar CrossRef Search ADS PubMed 10 Serruys PW , Zijlstra F , Laarman GJ , Reiber HH , Beatt K , Roelandt J. A comparison of two methods to measure coronary flow reserve in the setting of coronary angioplasty: intracoronary blood flow velocity measurements with a Doppler catheter, and digital subtraction cineangiography . Eur Heart J 1989 ; 10 : 725 – 736 . Google Scholar CrossRef Search ADS PubMed 11 Pijls NH , Van Gelder B , Van der Voort P , Peels K , Bracke FA , Bonnier HJ , el Gamal MI. Fractional flow reserve. A useful index to evaluate the influence of an epicardial coronary stenosis on myocardial blood flow . Circulation 1995 ; 92 : 3183 – 3193 . Google Scholar CrossRef Search ADS PubMed 12 Tonino PA , Fearon WF , De Bruyne B , Oldroyd KG , Leesar MA , Ver Lee PN , Maccarthy PA , Van’t Veer M , Pijls NH. Angiographic versus functional severity of coronary artery stenoses in the FAME study fractional flow reserve versus angiography in multivessel evaluation . J Am Coll Cardiol 2010 ; 55 : 2816 – 2821 . Google Scholar CrossRef Search ADS PubMed 13 Kern MJ. An adenosine-independent index of stenosis severity from coronary wave-intensity analysis: a new paradigm in coronary physiology for the cath lab? J Am Coll Cardiol 2012 ; 59 : 1403 – 1405 . Google Scholar CrossRef Search ADS PubMed 14 Sun YH , Anderson TJ , Parker KH , Tyberg JV. Wave-intensity analysis: a new approach to coronary hemodynamics . J Appl Physiol 2000 ; 89 : 1636 – 1644 . Google Scholar CrossRef Search ADS PubMed 15 Sen S , Escaned J , Malik IS , Mikhail GW , Foale RA , Mila R , Tarkin J , Petraco R , Broyd C , Jabbour R , Sethi A , Baker CS , Bellamy M , Al-Bustami M , Hackett D , Khan M , Lefroy D , Parker KH , Hughes AD , Francis DP , Di Mario C , Mayet J , Davies JE. Development and validation of a new adenosine-independent index of stenosis severity from coronary wave-intensity analysis: results of the ADVISE (ADenosine Vasodilator Independent Stenosis Evaluation) study . J Am Coll Cardiol 2012 ; 59 : 1392 – 1402 . Google Scholar CrossRef Search ADS PubMed 16 Broyd CJ , Davies JE , Escaned JE , Hughes A , Parker K. Wave intensity analysis and its application to the coronary circulation . Glob Cardiol Sci Pract 2017 ; 2017 : e201705 . Google Scholar PubMed 17 Bruining N , Barendse R , Cummins P. The future of computers in cardiology: ‘the connected patient’? Eur Heart J 2017 ; 38 : 1781 – 1794 . Google Scholar CrossRef Search ADS PubMed 18 Broyd CJ , Rigo F , Davies J. Non-invasive coronary wave intensity analysis . Int J Cardiovasc Imaging 2017 ; 33 : 1061 – 1068 . Google Scholar CrossRef Search ADS PubMed 19 Julius BK , Attenhofer Jost CH , Sutsch G , Brunner HP , Kuenzli A , Vogt PR , Turina M , Hess OM , Kiowski W. Incidence, progression and functional significance of cardiac allograft vasculopathy after heart transplantation . Transplantation 2000 ; 69 : 847 – 853 . Google Scholar CrossRef Search ADS PubMed Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: firstname.lastname@example.org. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)
European Heart Journal – Oxford University Press
Published: Jan 16, 2018
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