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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">&#8220;Coronary pressure never lies&#46;&#8221;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">1</span></a> This was what we were told 10 years ago&#44; just a few months before the publication of the seminal FAME trial&#44;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">2</span></a> arguably one of the most important physiology trials ever published and surely the one that had the biggest impact on daily practice and revascularization guidelines&#46; It clearly demonstrated the superiority of fractional flow reserve &#40;FFR&#41; over the common practice of visual estimation of stenosis severity by angiography to guide percutaneous coronary intervention of coronary lesions&#46; Also&#44; at some point during the learning process of FFR measurement&#44; the dogma was also implanted that &#8220;neither blood flow nor trans-stenotic pressure gradient at rest can determine whether a stenosis in a coronary artery will limit myocardial perfusion under conditions of increasing demand&#46; Only when hyperemia is induced and coronary flow reserve is measured can a relationship between stenosis severity and the presence of ischemia be demonstrated&#46;&#8221;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">For this reason&#44; research examining other pressure indices&#44; such as resting Pd&#47;Pa<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">4</span></a> or contrast-induced low-intensity hyperemia&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">5</span></a> was paid little attention for many years&#46; Still&#44; it must be admitted that the idea was attractive from a practical standpoint&#58; all one needed to do was to push a pressure wire through the lesion&#44; induce hyperemia with adenosine and calculate FFR&#46; If it was over 0&#46;80&#44; operators could be confident that coronary revascularization could be safely postponed every time&#59; on the other hand&#44; they could be sure that ischemia was present in all cases when it was 0&#46;80 or less&#44; and proceed with treatment&#46; Even if Pd&#47;Pa was completely normal or a very high contrast FFR reading was obtained&#44; we were told that there should be no doubt concerning the indication for revascularization as long as adenosine FFR was below 0&#46;80&#46; FFR thrived for years &#40;even if possibly not as much as it should have&#41; in this black vs&#46; white scenario&#44; one that we&#44; as physicians&#44; would love to have for all medical conditions&#58; being able to make the right decision for each and every patient based on a simple yes-or-no measurement&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">End of story&#63; No&#58; iFR enters the picture&#46; In their first major paper&#44; the ADVISE study&#44; published in 2012&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">6</span></a> the group headed by Justin Davies &#40;Imperial College&#44; London&#44; UK&#41; challenged the dogma of mandatory hyperemia and proposed a new index &#8211; the instantaneous wave-free ratio &#40;iFR&#41; &#8211; as an alternative to hyperemic adenosine FFR&#46; Measurement of iFR is based on the concept of the diastolic wave-free period&#44; during which coronary resistance remains low and stable&#46; This enables the pressure gradient measured during this interval to be used as a surrogate for coronary flow&#44; in exactly the same way as FFR&#44; according to its underlying theory&#44; but without the need to induce hyperemia&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">6</span></a> After the publication of the ADVISE study&#44; a long and interesting discussion ensued between classical FFR &#8216;believers&#8217;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">7&#8211;9</span></a> and the newcomer iFR investigators&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">10&#44;11</span></a> Several papers were published in major cardiology journals on both sides arguing the relative merits of each of the pressure indices&#46; From a clinical perspective &#8211; probably the most important &#8211; this discussion was settled in 2017 with the presentation at the American College of Cardiology annual meeting &#40;and simultaneous publication in the <span class="elsevierStyleItalic">New England Journal of Medicine</span>&#41; of two major randomized trials&#58; DEFINE-FLAIR<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">12</span></a> and iFR-SWEDEHEART&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">13</span></a> These two trials&#44; which recruited a combined total of over 4500 patients&#44; clearly demonstrated that iFR &#40;with a cut-off set at 0&#46;89&#41; was as good as FFR for guiding revascularization decisions&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">However&#44; the introduction of iFR as an invasive assessment tool had another important consequence&#58; there were patients and lesions in which the results of iFR and FFR would not be concordant&#46; In some&#44; iFR would be &#62;0&#46;89 &#40;suggesting absence of inducible ischemia&#41;&#44; but FFR would be &#8804;0&#46;80 &#40;suggesting it was present&#41;&#44; and also&#44; although less often&#44; the opposite &#40;iFR&#60;0&#46;89 and FFR&#62;0&#46;80&#41;&#46; Why was this important&#63; Because it clearly highlighted the obvious question some of us had had from the beginning&#58; could FFR sometimes lie&#63; In fact&#44; this is exactly what has been observed when using resting full-cycle Pd&#47;Pa and contrast FFR together with adenosine FFR&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">14</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In the current issue of the <span class="elsevierStyleItalic">Journal</span>&#44; Menezes et al&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">15</span></a> describe their experience with more than 150 patients assessed by both FFR and iFR&#46; Not surprisingly&#44; they found a similar pattern&#46; In a proportion of cases &#40;13&#37;&#41;&#44; iFR and FFR did not agree&#44; even when using different cut-offs in a hybrid strategy&#44; in which iFR is positive or negative when below or above the gray area of 0&#46;86-0&#46;93&#44; respectively&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The underlying mechanisms and the implications of this apparent disagreement between iFR and FFR have been the subject of intense debate&#46; In a recent analysis of the IDEAL study<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">16</span></a> &#8211; the largest registry to date in which both pressure and flow velocity were measured at rest and during hyperemia &#8211; Cook et al&#46; suggested that disagreement would be a reflection of baseline flow and microvascular resistance and their response to adenosine&#46; According to the authors&#44; iFR would be a better indicator of coronary flow &#40;and flow reserve&#41;&#44; and discordance with FFR would be the consequence of both false positive &#40;probably due to excessive increase in coronary flow or to excessive decrease in microcirculatory resistance&#44; both induced by adenosine&#41; and false negative FFR &#40;for example&#44; due to inadequate hyperemia&#41;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Notwithstanding this interesting theoretical discussion&#44; the clinical relevance of these discordant FFR&#47;iFR patterns appears to be less than expected&#46; As showed in a recent Korean study&#44; deferred lesions with discordant results &#40;both FFR&#43;&#47;iFR- and FFR-&#47;iFR&#43;&#41; had a similar prognosis to lesions with negative results in both tests&#44; and only deferring lesions with concordant positive FFR and iFR was associated with a worse prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">17</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Yet&#44; despite the clinical evidence from the two above-mentioned randomized clinical trials&#44; iFR is still not widely accepted in the interventional cardiology community&#46; There is skepticism concerning the use of a resting index&#44; since it challenges the fundamentals underlying both vasodilator non-invasive stress testing and FFR&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">18</span></a> Additionally&#44; the two iFR trials have been criticized for including less severe patients and lesions &#40;the mean FFR was 0&#46;83&#44; compared to 0&#46;71 in the FAME trial&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">18</span></a> Also&#44; evidence for iFR is still relatively scarce in specific settings such as complex patients and acute coronary syndromes&#46; However&#44; being easier to measure&#44; iFR is particularly appealing in these situations&#44; particularly in patients with ST-elevation myocardial infarction and multivessel disease&#46; In these patients&#44; the use of iFR to assess non-culprit lesions in the acute phase has recently been analyzed&#44;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">19</span></a> and a major international randomized trial comparing acute iFR-guided full functional revascularization with deferred stress cardiac magnetic resonance imaging &#8211; iMODERN &#40;iFR Guided Multi-vessel Revascularization During Percutaneous Coronary Intervention for Acute Myocardial Infarction&#59; ClinicalTrials&#46;gov identifier <a id="intr0005" class="elsevierStyleInterRef" href="https://clinicaltrials.gov/NCT03298659">NCT03298659</a>&#41; &#8211; is ongoing and has just started enrolling patients&#46; Portuguese investigators contributed significantly to the trial design and several Portuguese centers will participate actively in the study&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">But is iFR the last cookie in the jar&#63; Likely no&#46; Other resting indices are currently being developed&#46; Most of them rely on the fact that it is apparently not necessary to measure the pressure gradient strictly within the wave-free period&#44; as iFR does&#58; measurements performed using several different time intervals in diastole showed similar results to iFR using the Volcano system&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">20</span></a> Thus&#44; it is only to be expected that other companies may use this concept to create their own &#8216;diastolic flow reserve&#8217; indices&#46; Determination of the largest resting pressure gradient across the full cardiac cycle &#40;regardless of its location&#41; is another approach currently being evaluated&#46; Portuguese investigators lead the first-in-man international prospective study to test this technology&#44; PREDICT &#40;Performance of a New REsting Pressure Index During Invasive Angiography Compared To Adenosine Hyperemic FFR&#59; ClinicalTrials&#46;gov identifier <a id="intr0010" class="elsevierStyleInterRef" href="https://clinicaltrials.gov/NCT03237169">NCT03237169</a>&#41;&#46; Results will soon be available&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">We have definitely moved forward from the 2008 statement that &#8220;Coronary pressure never lies&#8221;&#46; However&#44; there is undoubtedly still much more to learn in coronary physiology&#44; especially about microvascular function&#46; Having Portuguese centers involved in this field of research is very important and surely a goal that is worth pursuing&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0055" class="elsevierStylePara elsevierViewall">Dr&#46; Baptista has received consultancy and speaker fees from Abbott and Boston Scientific and research grants from <span class="elsevierStyleGrantSponsor" id="gs1">Abbott</span> and <span class="elsevierStyleGrantSponsor" id="gs2">Volcano</span>&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Dr&#46; Raposo has received consultancy and speaker fees from Abbott&#44; Boston Scientific and Volcano and research grants from Abbott and Volcano&#46;</p></span></span>"
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Editorial comment
Coronary pressure (sometimes) lies…
A pressão coronária (às vezes) mente…
Sérgio Bravo Baptistaa,
Autor para correspondência
sergio.b.baptista@gmail.com

Corresponding author.
, Luís Raposob
a Hospital Prof. Doutor Fernando Fonseca, Amadora, Portugal
b Centro Hospitalar de Lisboa Ocidental EPE, Hospital de Santa Cruz, Carnaxide, Portugal
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">&#8220;Coronary pressure never lies&#46;&#8221;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">1</span></a> This was what we were told 10 years ago&#44; just a few months before the publication of the seminal FAME trial&#44;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">2</span></a> arguably one of the most important physiology trials ever published and surely the one that had the biggest impact on daily practice and revascularization guidelines&#46; It clearly demonstrated the superiority of fractional flow reserve &#40;FFR&#41; over the common practice of visual estimation of stenosis severity by angiography to guide percutaneous coronary intervention of coronary lesions&#46; Also&#44; at some point during the learning process of FFR measurement&#44; the dogma was also implanted that &#8220;neither blood flow nor trans-stenotic pressure gradient at rest can determine whether a stenosis in a coronary artery will limit myocardial perfusion under conditions of increasing demand&#46; Only when hyperemia is induced and coronary flow reserve is measured can a relationship between stenosis severity and the presence of ischemia be demonstrated&#46;&#8221;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">For this reason&#44; research examining other pressure indices&#44; such as resting Pd&#47;Pa<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">4</span></a> or contrast-induced low-intensity hyperemia&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">5</span></a> was paid little attention for many years&#46; Still&#44; it must be admitted that the idea was attractive from a practical standpoint&#58; all one needed to do was to push a pressure wire through the lesion&#44; induce hyperemia with adenosine and calculate FFR&#46; If it was over 0&#46;80&#44; operators could be confident that coronary revascularization could be safely postponed every time&#59; on the other hand&#44; they could be sure that ischemia was present in all cases when it was 0&#46;80 or less&#44; and proceed with treatment&#46; Even if Pd&#47;Pa was completely normal or a very high contrast FFR reading was obtained&#44; we were told that there should be no doubt concerning the indication for revascularization as long as adenosine FFR was below 0&#46;80&#46; FFR thrived for years &#40;even if possibly not as much as it should have&#41; in this black vs&#46; white scenario&#44; one that we&#44; as physicians&#44; would love to have for all medical conditions&#58; being able to make the right decision for each and every patient based on a simple yes-or-no measurement&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">End of story&#63; No&#58; iFR enters the picture&#46; In their first major paper&#44; the ADVISE study&#44; published in 2012&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">6</span></a> the group headed by Justin Davies &#40;Imperial College&#44; London&#44; UK&#41; challenged the dogma of mandatory hyperemia and proposed a new index &#8211; the instantaneous wave-free ratio &#40;iFR&#41; &#8211; as an alternative to hyperemic adenosine FFR&#46; Measurement of iFR is based on the concept of the diastolic wave-free period&#44; during which coronary resistance remains low and stable&#46; This enables the pressure gradient measured during this interval to be used as a surrogate for coronary flow&#44; in exactly the same way as FFR&#44; according to its underlying theory&#44; but without the need to induce hyperemia&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">6</span></a> After the publication of the ADVISE study&#44; a long and interesting discussion ensued between classical FFR &#8216;believers&#8217;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">7&#8211;9</span></a> and the newcomer iFR investigators&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">10&#44;11</span></a> Several papers were published in major cardiology journals on both sides arguing the relative merits of each of the pressure indices&#46; From a clinical perspective &#8211; probably the most important &#8211; this discussion was settled in 2017 with the presentation at the American College of Cardiology annual meeting &#40;and simultaneous publication in the <span class="elsevierStyleItalic">New England Journal of Medicine</span>&#41; of two major randomized trials&#58; DEFINE-FLAIR<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">12</span></a> and iFR-SWEDEHEART&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">13</span></a> These two trials&#44; which recruited a combined total of over 4500 patients&#44; clearly demonstrated that iFR &#40;with a cut-off set at 0&#46;89&#41; was as good as FFR for guiding revascularization decisions&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">However&#44; the introduction of iFR as an invasive assessment tool had another important consequence&#58; there were patients and lesions in which the results of iFR and FFR would not be concordant&#46; In some&#44; iFR would be &#62;0&#46;89 &#40;suggesting absence of inducible ischemia&#41;&#44; but FFR would be &#8804;0&#46;80 &#40;suggesting it was present&#41;&#44; and also&#44; although less often&#44; the opposite &#40;iFR&#60;0&#46;89 and FFR&#62;0&#46;80&#41;&#46; Why was this important&#63; Because it clearly highlighted the obvious question some of us had had from the beginning&#58; could FFR sometimes lie&#63; In fact&#44; this is exactly what has been observed when using resting full-cycle Pd&#47;Pa and contrast FFR together with adenosine FFR&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">14</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In the current issue of the <span class="elsevierStyleItalic">Journal</span>&#44; Menezes et al&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">15</span></a> describe their experience with more than 150 patients assessed by both FFR and iFR&#46; Not surprisingly&#44; they found a similar pattern&#46; In a proportion of cases &#40;13&#37;&#41;&#44; iFR and FFR did not agree&#44; even when using different cut-offs in a hybrid strategy&#44; in which iFR is positive or negative when below or above the gray area of 0&#46;86-0&#46;93&#44; respectively&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The underlying mechanisms and the implications of this apparent disagreement between iFR and FFR have been the subject of intense debate&#46; In a recent analysis of the IDEAL study<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">16</span></a> &#8211; the largest registry to date in which both pressure and flow velocity were measured at rest and during hyperemia &#8211; Cook et al&#46; suggested that disagreement would be a reflection of baseline flow and microvascular resistance and their response to adenosine&#46; According to the authors&#44; iFR would be a better indicator of coronary flow &#40;and flow reserve&#41;&#44; and discordance with FFR would be the consequence of both false positive &#40;probably due to excessive increase in coronary flow or to excessive decrease in microcirculatory resistance&#44; both induced by adenosine&#41; and false negative FFR &#40;for example&#44; due to inadequate hyperemia&#41;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Notwithstanding this interesting theoretical discussion&#44; the clinical relevance of these discordant FFR&#47;iFR patterns appears to be less than expected&#46; As showed in a recent Korean study&#44; deferred lesions with discordant results &#40;both FFR&#43;&#47;iFR- and FFR-&#47;iFR&#43;&#41; had a similar prognosis to lesions with negative results in both tests&#44; and only deferring lesions with concordant positive FFR and iFR was associated with a worse prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">17</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Yet&#44; despite the clinical evidence from the two above-mentioned randomized clinical trials&#44; iFR is still not widely accepted in the interventional cardiology community&#46; There is skepticism concerning the use of a resting index&#44; since it challenges the fundamentals underlying both vasodilator non-invasive stress testing and FFR&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">18</span></a> Additionally&#44; the two iFR trials have been criticized for including less severe patients and lesions &#40;the mean FFR was 0&#46;83&#44; compared to 0&#46;71 in the FAME trial&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">18</span></a> Also&#44; evidence for iFR is still relatively scarce in specific settings such as complex patients and acute coronary syndromes&#46; However&#44; being easier to measure&#44; iFR is particularly appealing in these situations&#44; particularly in patients with ST-elevation myocardial infarction and multivessel disease&#46; In these patients&#44; the use of iFR to assess non-culprit lesions in the acute phase has recently been analyzed&#44;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">19</span></a> and a major international randomized trial comparing acute iFR-guided full functional revascularization with deferred stress cardiac magnetic resonance imaging &#8211; iMODERN &#40;iFR Guided Multi-vessel Revascularization During Percutaneous Coronary Intervention for Acute Myocardial Infarction&#59; ClinicalTrials&#46;gov identifier <a id="intr0005" class="elsevierStyleInterRef" href="https://clinicaltrials.gov/NCT03298659">NCT03298659</a>&#41; &#8211; is ongoing and has just started enrolling patients&#46; Portuguese investigators contributed significantly to the trial design and several Portuguese centers will participate actively in the study&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">But is iFR the last cookie in the jar&#63; Likely no&#46; Other resting indices are currently being developed&#46; Most of them rely on the fact that it is apparently not necessary to measure the pressure gradient strictly within the wave-free period&#44; as iFR does&#58; measurements performed using several different time intervals in diastole showed similar results to iFR using the Volcano system&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">20</span></a> Thus&#44; it is only to be expected that other companies may use this concept to create their own &#8216;diastolic flow reserve&#8217; indices&#46; Determination of the largest resting pressure gradient across the full cardiac cycle &#40;regardless of its location&#41; is another approach currently being evaluated&#46; Portuguese investigators lead the first-in-man international prospective study to test this technology&#44; PREDICT &#40;Performance of a New REsting Pressure Index During Invasive Angiography Compared To Adenosine Hyperemic FFR&#59; ClinicalTrials&#46;gov identifier <a id="intr0010" class="elsevierStyleInterRef" href="https://clinicaltrials.gov/NCT03237169">NCT03237169</a>&#41;&#46; Results will soon be available&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">We have definitely moved forward from the 2008 statement that &#8220;Coronary pressure never lies&#8221;&#46; However&#44; there is undoubtedly still much more to learn in coronary physiology&#44; especially about microvascular function&#46; Having Portuguese centers involved in this field of research is very important and surely a goal that is worth pursuing&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0055" class="elsevierStylePara elsevierViewall">Dr&#46; Baptista has received consultancy and speaker fees from Abbott and Boston Scientific and research grants from <span class="elsevierStyleGrantSponsor" id="gs1">Abbott</span> and <span class="elsevierStyleGrantSponsor" id="gs2">Volcano</span>&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Dr&#46; Raposo has received consultancy and speaker fees from Abbott&#44; 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Informação do artigo
ISSN: 08702551
Idioma original: Inglês
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