Comment on:
Comparative analysis of fractional flow reserve and instantaneous wave-free ratio: Results of a five-year registry. [Rev Port Cardiol. 2018]info:eu-repo/semantics/publishedVersio

Baptista, SB

Raposo, L

English

Unidade Local de Saúde Amadora / Sintra

Rev Port Cardiol. 2018;37(6):521--523www.revportcardiol.orgRevista Portuguesa deCardiologiaPortuguese Journal of CardiologyEDITORIAL COMMENTCoronary  pressure  (sometimes)  lies. .  .A  pressão  coronária  (às  vezes)  mente. . .Sérgio Bravo Baptistaa,∗, Luís Raposoba Hospital  Prof.  Doutor  Fernando  Fonseca,  Amadora,  Portugalb Centro  Hospitalar  de  Lisboa  Ocidental  EPE,  Hospital  de  Santa  Cruz,  Carnaxide,  PortugalAvailable  online  24  May  2018ytteoctwirnl(vtrymhlna‘‘Coronary  pressure  never  lies.’’1 This  was  what  we  weretold  10  years  ago,  just  a  few  months  before  the  publica-tion  of  the  seminal  FAME  trial,2 arguably  one  of  the  mostimportant  physiology  trials  ever  published  and  surely  the  onethat  had  the  biggest  impact  on  daily  practice  and  revascula-rization  guidelines.  It  clearly  demonstrated  the  superiorityof  fractional  ﬂow  reserve  (FFR)  over  the  common  practiceof  visual  estimation  of  stenosis  severity  by  angiographyto  guide  percutaneous  coronary  intervention  of  coronarylesions.  Also,  at  some  point  during  the  learning  processof  FFR  measurement,  the  dogma  was  also  implanted  that‘‘neither  blood  ﬂow  nor  trans-stenotic  pressure  gradient  atrest  can  determine  whether  a  stenosis  in  a  coronary  arterywill  limit  myocardial  perfusion  under  conditions  of  increas-ing  demand.  Only  when  hyperemia  is  induced  and  coronaryﬂow  reserve  is  measured  can  a  relationship  between  stenosisseverity  and  the  presence  of  ischemia  be  demonstrated.’’3For  this  reason,  research  examining  other  pressureindices,  such  as  resting  Pd/Pa4 or  contrast-induced  low-intensity  hyperemia,5 was  paid  little  attention  for  manyDOI of original article: https://doi.org/10.1016/j.repc.2017.11.011∗ Corresponding author.E-mail address: sergio.b.baptista@gmail.com(S. Bravo Baptista).opsthttps://doi.org/10.1016/j.repc.2018.05.0010870-2551/© 2018 Sociedade Portuguesa de Cardiologia. Published by Elears.  Still,  it  must  be  admitted  that  the  idea  was  attrac-ive  from  a  practical  standpoint:  all  one  needed  to  do  waso  push  a pressure  wire  through  the  lesion,  induce  hyper-mia  with  adenosine  and  calculate  FFR.  If  it  was  over  0.80,perators  could  be  conﬁdent  that  coronary  revascularizationould  be  safely  postponed  every  time;  on  the  other  hand,hey  could  be  sure  that  ischemia  was  present  in  all  caseshen  it  was  0.80  or  less,  and  proceed  with  treatment.  Evenf  Pd/Pa  was  completely  normal  or  a  very  high  contrast  FFReading  was  obtained,  we  were  told  that  there  should  beo  doubt  concerning  the  indication  for  revascularization  asong  as  adenosine  FFR  was  below  0.80.  FFR  thrived  for  yearseven  if  possibly  not  as  much  as  it  should  have)  in  this  blacks.  white  scenario,  one  that  we,  as  physicians,  would  loveo  have  for  all  medical  conditions:  being  able  to  make  theight  decision  for  each  and  every  patient  based  on  a  simplees-or-no  measurement.End  of  story?  No:  iFR  enters  the  picture.  In  their  ﬁrstajor  paper,  the  ADVISE  study,  published  in  2012,6 the  groupeaded  by  Justin  Davies  (Imperial  College,  London,  UK)  chal-enged  the  dogma  of  mandatory  hyperemia  and  proposed  aew  index  --  the  instantaneous  wave-free  ratio  (iFR)  --  asn  alternative  to  hyperemic  adenosine  FFR.  Measurementf  iFR  is  based  on  the  concept  of  the  diastolic  wave-freeeriod,  during  which  coronary  resistance  remains  low  andtable.  This  enables  the  pressure  gradient  measured  duringhis  interval  to  be  used  as  a  surrogate  for  coronary  ﬂow,  insevier Espan˜a, S.L.U. All rights reserved.5ettdtpiF-t(oactgmpni(ttsluadasdsaatIpiwrtﬂbeiahtaKFwwwmaiittp0tampttbcwiPIoisstotaeutol(bmPiFsmuecaCDfAfgRCardiovasc Interv. 2008;72:248--56.22  xactly  the  same  way  as  FFR,  according  to  its  underlyingheory,  but  without  the  need  to  induce  hyperemia.6 Afterhe  publication  of  the  ADVISE  study,  a  long  and  interestingiscussion  ensued  between  classical  FFR  ‘believers’7--9 andhe  newcomer  iFR  investigators.10,11 Several  papers  wereublished  in  major  cardiology  journals  on  both  sides  argu-ng  the  relative  merits  of  each  of  the  pressure  indices.rom  a  clinical  perspective  --  probably  the  most  important-  this  discussion  was  settled  in  2017  with  the  presenta-ion  at  the  American  College  of  Cardiology  annual  meetingand  simultaneous  publication  in  the  New  England  Journalf  Medicine)  of  two  major  randomized  trials:  DEFINE-FLAIR12nd  iFR-SWEDEHEART.13 These  two  trials,  which  recruited  aombined  total  of  over  4500  patients,  clearly  demonstratedhat  iFR  (with  a  cut-off  set  at  0.89)  was  as  good  as  FFR  foruiding  revascularization  decisions.However,  the  introduction  of  iFR  as  an  invasive  assess-ent  tool  had  another  important  consequence:  there  wereatients  and  lesions  in  which  the  results  of  iFR  and  FFR  wouldot  be  concordant.  In  some,  iFR  would  be  >0.89  (suggest-ng  absence  of  inducible  ischemia),  but  FFR  would  be  ≤0.80suggesting  it  was  present),  and  also,  although  less  often,he  opposite  (iFR<0.89  and  FFR>0.80).  Why  was  this  impor-ant?  Because  it  clearly  highlighted  the  obvious  questionome  of  us  had  had  from  the  beginning:  could  FFR  sometimesie?  In  fact,  this  is  exactly  what  has  been  observed  whensing  resting  full-cycle  Pd/Pa  and  contrast  FFR  together  withdenosine  FFR.14In  the  current  issue  of  the  Journal,  Menezes  et  al.15escribe  their  experience  with  more  than  150  patientsssessed  by  both  FFR  and  iFR.  Not  surprisingly,  they  found  aimilar  pattern.  In  a  proportion  of  cases  (13%),  iFR  and  FFRid  not  agree,  even  when  using  different  cut-offs  in  a  hybridtrategy,  in  which  iFR  is  positive  or  negative  when  below  orbove  the  gray  area  of  0.86-0.93,  respectively.The  underlying  mechanisms  and  the  implications  of  thispparent  disagreement  between  iFR  and  FFR  have  beenhe  subject  of  intense  debate.  In  a  recent  analysis  of  theDEAL  study16 --  the  largest  registry  to  date  in  which  bothressure  and  ﬂow  velocity  were  measured  at  rest  and  dur-ng  hyperemia  --  Cook  et  al.  suggested  that  disagreementould  be  a  reﬂection  of  baseline  ﬂow  and  microvascularesistance  and  their  response  to  adenosine.  According  tohe  authors,  iFR  would  be  a  better  indicator  of  coronaryow  (and  ﬂow  reserve),  and  discordance  with  FFR  woulde  the  consequence  of  both  false  positive  (probably  due  toxcessive  increase  in  coronary  ﬂow  or  to  excessive  decreasen  microcirculatory  resistance,  both  induced  by  adenosine)nd  false  negative  FFR  (for  example,  due  to  inadequateyperemia).Notwithstanding  this  interesting  theoretical  discussion,he  clinical  relevance  of  these  discordant  FFR/iFR  patternsppears  to  be  less  than  expected.  As  showed  in  a  recentorean  study,  deferred  lesions  with  discordant  results  (bothFR+/iFR-  and  FFR-/iFR+)  had  a  similar  prognosis  to  lesionsith  negative  results  in  both  tests,  and  only  deferring  lesionsith  concordant  positive  FFR  and  iFR  was  associated  with  aorse  prognosis.17Yet,  despite  the  clinical  evidence  from  the  two  above-entioned  randomized  clinical  trials,  iFR  is  still  not  widelyccepted  in  the  interventional  cardiology  community.  Theres  skepticism  concerning  the  use  of  a  resting  index,  sinceS.  Bravo  Baptista,  L.  Raposot  challenges  the  fundamentals  underlying  both  vasodila-or  non-invasive  stress  testing  and  FFR.18 Additionally,  thewo  iFR  trials  have  been  criticized  for  including  less  severeatients  and  lesions  (the  mean  FFR  was  0.83,  compared  to.71  in  the  FAME  trial).18 Also,  evidence  for  iFR  is  still  rela-ively  scarce  in  speciﬁc  settings  such  as  complex  patientsnd  acute  coronary  syndromes.  However,  being  easier  toeasure,  iFR  is  particularly  appealing  in  these  situations,articularly  in  patients  with  ST-elevation  myocardial  infarc-ion  and  multivessel  disease.  In  these  patients,  the  use  of  iFRo  assess  non-culprit  lesions  in  the  acute  phase  has  recentlyeen  analyzed,19 and  a  major  international  randomized  trialomparing  acute  iFR-guided  full  functional  revascularizationith  deferred  stress  cardiac  magnetic  resonance  imaging  --MODERN  (iFR  Guided  Multi-vessel  Revascularization  Duringercutaneous  Coronary  Intervention  for  Acute  Myocardialnfarction;  ClinicalTrials.gov  identiﬁer  NCT03298659)  --  isngoing  and  has  just  started  enrolling  patients.  Portuguesenvestigators  contributed  signiﬁcantly  to  the  trial  design  andeveral  Portuguese  centers  will  participate  actively  in  thetudy.But  is  iFR  the  last  cookie  in  the  jar?  Likely  no.  Other  res-ing  indices  are  currently  being  developed.  Most  of  them  relyn  the  fact  that  it  is  apparently  not  necessary  to  measurehe  pressure  gradient  strictly  within  the  wave-free  period,s  iFR  does:  measurements  performed  using  several  differ-nt  time  intervals  in  diastole  showed  similar  results  to  iFRsing  the  Volcano  system.20 Thus,  it  is  only  to  be  expectedhat  other  companies  may  use  this  concept  to  create  theirwn  ‘diastolic  ﬂow  reserve’  indices.  Determination  of  theargest  resting  pressure  gradient  across  the  full  cardiac  cycleregardless  of  its  location)  is  another  approach  currentlyeing  evaluated.  Portuguese  investigators  lead  the  ﬁrst-in-an  international  prospective  study  to  test  this  technology,REDICT  (Performance  of  a  New  REsting  Pressure  Index  Dur-ng  Invasive  Angiography  Compared  To  Adenosine  HyperemicFR;  ClinicalTrials.gov  identiﬁer  NCT03237169).  Results  willoon  be  available.We  have  deﬁnitely  moved  forward  from  the  2008  state-ent  that  ‘‘Coronary  pressure  never  lies’’.  However,  there  isndoubtedly  still  much  more  to  learn  in  coronary  physiology,specially  about  microvascular  function.  Having  Portugueseenters  involved  in  this  ﬁeld  of  research  is  very  importantnd  surely  a  goal  that  is  worth  pursuing.onﬂicts of  interestr.  Baptista  has  received  consultancy  and  speaker  feesrom  Abbott  and  Boston  Scientiﬁc  and  research  grants  frombbott  and  Volcano.Dr.  Raposo  has  received  consultancy  and  speaker  feesrom  Abbott,  Boston  Scientiﬁc  and  Volcano  and  researchrants  from  Abbott  and  Volcano.eferences1. Koolen JJ, Pijls NHJ. Coronary pressure never lies. Catheter2. Tonino PAL, De Bruyne B, Pijls NHJ, et al. Fractional ﬂow reserveversus angiography for guiding percutaneous coronary interven-tion. N Engl J Med. 2009;360:213--24.11111111Interv. 2017;10:2528--35.20. van’t Veer M, Pijls NHJ, Hennigan B, et al. Comparison of dif-ferent diastolic resting indexes to iFR: are they all equal? J AmColl Cardiol. 2017;70:3088--96.Coronary  pressure  (sometimes)  lies.  .  .  3. Berry C, Van ‘T Veer M, Witt N, et al. VERIFY (VERiﬁcation ofinstantaneous wave-free ratio and fractional ﬂow reserve forthe assessment of coronary artery stenosis severity in everydaypractice): a multicenter study in consecutive patients. J AmColl Cardiol. 2013;61:1421--7.4. Baptista SB, Loureiro J, Brizida L, et al. Resting Pd/Pa and frac-tional ﬂow reserve: do we need to obtain maximal hyperemiain all patients? Eur Heart J. 2013;34 Suppl. 1:714.5. Baptista SB, Loureiro J, Brizida L, et al. Contrast-induced hyper-emia in the functional evaluation of coronary lesions with apressure wire. Eur Heart J. 2013;34 Suppl. 1:716.6. Sen S, Escaned J, Malik IS, et al. Development and validationof a new adenosine-independent index of stenosis severity fromcoronary wave-intensity analysis: results of the ADVISE (ADeno-sine Vasodilator Independent Stenosis Evaluation) study. J AmColl Cardiol. 2012;59:1392--402.7. Fearon WF, Low AF, Yong ASC, et al. Prognostic value of the indexof microcirculatory resistance measured after primary percuta-neous coronary intervention. Circulation. 2013:2436--42.8. Hennigan B, Oldroyd KG, Berry C, et al. Discordance betweenresting and hyperemic indices of coronary stenosis severity:the VERIFY 2 study (A Comparative Study of Resting Coro-nary Pressure Gradient, Instantaneous Wave-Free Ratio andFractional Flow Reserve in an Unselected Population Referredfor Invasive Angiography). Circ Cardiovasc Interv. 2016;9:1--10.9. Jeremias A, Maehara A, Généreux P, et al. Multicenter core lab-oratory comparison of the instantaneous wave-free ratio andresting Pd/Pa with fractional ﬂow reserve: the RESOLVE study.J Am Coll Cardiol. 2014;63:1253--61.10. Escaned J, Echavarría-Pinto M, Garcia-Garcia HM, et al.Prospective assessment of the diagnostic accuracy of instan-taneous wave-free ratio to assess coronary stenosis relevance:results of ADVISE II international, multicenter study (ADenosinevasodilator independent stenosis evaluation II). JACC Cardio-vasc Interv. 2015;8:824--33.11. Sen S, Asrress KN, Nijjer S, et al. Diagnostic classiﬁcation ofthe instantaneous wave-free ratio is equivalent to fractionalﬂow reserve and is not improved with adenosine administration:523results of CLARIFY (Classiﬁcation Accuracy of Pressure-OnlyRatios Against Indices Using Flow Study). J Am Coll Cardiol.2013;61:1409--20.2. Davies JE, Sen S, Dehbi H-M, et al. Use of the instantaneouswave-free ratio or fractional ﬂow reserve in PCI. N Engl J Med.2017;376.3. Götberg M, Christiansen EH, Gudmundsdottir IJ, et al. Instan-taneous wave-free ratio versus fractional ﬂow reserve to guidePCI. N Engl J Med. 2017;376:1813--23.4. Baptista S, Augusto J, Magno P, et al. Using all the informa-tion available: PdPa, FFR contrast and FFR adenosine in theevaluation of intermediate coronary lesions. J Am Coll Cardiol.2017;70:B304--5.5. Menezes MN, Francisco AR, Ferreira PC, et al. Análise com-parative do fractional ﬂow reserve (FFR) e do instantaneouswave-free ratio (iFR): resultados de um registo de 5 anos. RevPort Cardiol. 2018;37:511--20.6. Cook CM, Jeremias A, Petraco R, et al. Fractional ﬂowreserve/instantaneous wave-free ratio discordance in angio-graphically intermediate coronary stenoses: an analysis usingDoppler-derived coronary ﬂow measurements. JACC CardiovascInterv. 2017;10:2514--24.7. Lee JM, Shin ES, Nam CW, et al. Clinical outcomes accordingto fractional ﬂow reserve or instantaneous wave-free ratio indeferred lesions. JACC Cardiovasc Interv. 2017;10:2502--10.8. Kern MJ, Seto AH. Is instantaneous wave-free ratio a newstandard of care for physiologic assessment of coronary lesions?Circulation. 2017;136:2295--7.9. Thim T, Götberg M, Fröbert O, et al. Nonculprit stenosis eval-uation using instantaneous wave-free ratio in patients withST-segment elevation myocardial infarction. JACC Cardiovasc

A pressão coronária (às vezes) mente. . .

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A pressão coronária (às vezes) mente. . .

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