İNTRAKORONER FİZYOLOJİ

İNTRAKORONER FİZYOLOJİ DOPPLER Bekir Sıtkı Cebeci GATA Haydarpaşa,İstanbul,Haziran 2010.

1-Kateter Laboratuvarında Koroner İçi Fizyolojik Verilere Niçin İhtiyaç Duyarız? Revaskülarizasyon kararı primer olarak koronerdeki darlığın iskemi oluşturma yönündeki hemodinamik etkisine göre verilmelidir. Koroner anjiyografi lezyonun hemodinamik önemini ortaya koymada her zaman yeterli olamaz.

Koroner anjiyografinin kısıtlılıkları nelerdir? Lezyonun yetersiz görüntülenmesi.(egzantrik lezyon, damarın açılanım nedeni ile olduğundan kısa görünmesi,damar görüntülerinin üst üste gelmesi) Damarın kontrast madde ile yeterli doldurulamaması. Uygun açının bulunamaması. Lezyon öncesi-sonrası damarın ektazik olması. Yaygın aterosklerotik hastalık. Uzun lezyonlar. Ana koroner,ostial ve bifurkasyon lezyonlarını görüntüleme ve karar verme zorluğu. Lezyon ciddiyeti hakkında karar vermede kişinin kendi içinde ve kişiler arasındaki değişkenlik. Orta düzey lezyonların ( 40-70%) hemodinamik etkilerini öngörme zorluğu.

Lezyonun hemodinamik önemi hakkında bilgi veren yöntemler nelerdir? İnvazif olmayan yöntemler. MRI Echo-Doppler CFR PET İskemiyi uyaran testler.(farmakolojik/egzersiz) Elektrokardiyografi Echo Myokard perfüzyon sintigrafisi.(spect) Katater temelli invazif olan yöntemler.

SPECT in tek damar hastalığını saptamadaki duyarlılığı 70%. SPECT imajlarının çok damar hastalığını saptama duyarlılığı 85-90% fakat çok damar iskemi paternini saptama duyarlılığı ise 50% dir.

İnvazif temelli yöntemler ile koroner damarlarda hangi fizyolojik ölçümleri yapabiliyoruz? Basınç Akım hızı Rezistans ölçümleri yapabiliyoruz.

Koroner içi doppler kaydı. Kılavuz tellerin ucundaki transducer den gönderilen ve geri alınan ultrasound sinyallerinde oluşan frekans değişikliğinden yararlanılarak damar içi akım hızı ölçümü yapılmaktadır.

Bu verinin koroner fizyolojisini anlamamızda ve karar vermemizdeki katkısının nedeni nedir? Akım Hız=(f1-f0) c/(2f0) cosø Akım volümü=damar alanı ortalama akım hızı. KAR = Hiperemik akım volümü istirahat akım volümü KAR= Alan ortalama hiperemik akım hızı Alan ortalama istirahat akım hızı.

Koroner dolaşım fizyolojisi.

Koroner akım rezervi.

Koroner akım rezervi - daralma oranı ilişkisi.

Koroner doppler kayıt cihazı ve teli.

Hangi durumlarda koroner akım rezervi azalır? Epikardiyal koroner damarlardaki darlıklarda Hipertansiyon/sol ventrikül hipertrofisi Diabetes Mellitus Hipertrofik kardiyomyopati Vaskülitler Myokard infarktüsü Koroner vazospazm Tekrarlayan iskemiler Vazoaktif maddelere anormal duyarlılık Transplant vaskülopatisi

Maksimal hiperemi için kullanılan ilaçlar. Adenozin Adenozin Papaverin Yol İV İK İK Doz 140 mic/kg/dk 30/60mcg sol 20/30mcgsağ 15 sol 10 sağ Yarılanma 1-2 dakika 30-60 saniye 2 dakika zamanı Maksimum etki 1-2 dakika 5-10 saniye 30-60 saniye Avantaj Altın standart Kısa etki Kısa etki Dezavantaj TA,Ağrı TA,AV blok TA,Torsades

Adenozin.

Koroner damar darlığı hakkında karar verdirici değer nedir?

Basınç verisine ( FFR ) göre CFR ın avantaj ve dezavantajları nelerdir? FFR CFR rcfr Sadece epikardiyal damar hastalığını saptama +++ - ++ Mikrovasküler hastalığı saptama - +++ - Santral hemodinamiklerden bağımsız olma ++ - + İskemi için iyi tanımlanmış eşik değerin olması ++ - + Kollateral akımı göz önüne alması +++ + - Kolay tekrarlanabilme +++ + + Kolay ve hızlı yapılabilme ++ + - Çok damar hastalığını değerlendirebilme ++ ++ -

KAR nin duyarlılığını arttırmak için ne gibi modifikasyonlar yapılmıştır? Gould ve arkadaşları nisbi koroner akım rezervi konseptini geliştirmişlerdir.(rkar) rkar=hedef damar KAR / Referans damar KAR.Değerin > 0,8 olması ciddi epikardiyal daralmayı ekarte ettirir. Burada mikrovasküler rezistansın homojen dağıldığı varsayılmıştır. Sağlıklı bir damardan veri kaydı gerekir Üç damar hastalığında kullanılamaz.

İşlemlere bağlı komplikasyonlar. Kullanılan ilaca bağlı Adenozin.Geçici AV blok,anjinal ağrı Papaverin.QT uzaması,torsades Pointes. Tellere bağlı Spazm Disseksiyon

İntrakoroner doppler ile yapılan çalışmalar.

Correlation of pharmacological 99mTc-sestamibi myocardial perfusion imaging with poststenotic coronary flow reserve in patients with angiographically intermediate coronary artery stenoses. Miller DD, Donohue TJ, Younis LT, Bach RG, Aguirre FV, Wittry MD, Goodgold HM, Chaitman BR, Kern MJ. CONCLUSIONS: Two technologically diverse functional measures of stenosis severity--doppler-derived poststenotic hyperemic intracoronary flow reserve and vasodilator stress 99mTc-sestamibi myocardial perfusion imaging--are highly (89%) correlated. The physiological assessment of coronary stenoses of angiographically intermediate severity may be improved by the use of these techniques. Circulation. 1994 May;89(5):2150-60.

Intracoronary Doppler guide wire versus stress singlephoton emission computed tomographic thallium-201 imaging in assessment of intermediate coronary stenoses. Joye JD, Schulman DS, Lasorda D, Farah T, Donohue BC, Reichek N. CONCLUSIONS: In appropriately selected patients with intermediate coronary artery stenoses, Doppler guide wire determination of lesion significance provides equivalent data to those acquired by stress SPECT thallium-201 imaging. Am Coll Cardiol. 1994 Oct;24(4):940-7.

Doppler guide wire flow-velocity indexes measured distal to coronary stenoses associated with reversible thallium perfusion defects. Deychak YA, Segal J, Reiner JS, Rohrbeck SC, Thompson MA, Lundergan CF, Ross AM, Wasserman AG. A coronary flow reserve of < 1.8 and a diastolic/systolic flow-velocity ratio of < 1.7 predicted a reversible thallium perfusion scintigram (concordance 96% and 88%, respectively). Distal coronary flow velocity indexes may provide an alternative means of physiologic assessment of lesion severity during coronary angiography. Am Heart J. 1995 Feb;129(2):219-27.

Fizyolojik ölçümler ve noninvazif Stress test sonuçları. n İskemik test Eşik değer doğruluk % Joye 30 SPECT 2 94 Miller 33 SPECT 2 89 Deychak 17 SPECT 1,8 96 Tron 62 SPECT 2 84 Donohue 50 SPECT 2 88 Heller 55 SPECT 1,7 92 Schulman 35 X-EKG 2 86 Danzi 30 DSE 2 87 Verberne 37 SPECT 1,9 85 Piek 225 X-EKG 2,1 76 Abe 46 SPECT 2 92 Chamuleau 127 SPECT 1,7 76 Duffy 28 DSE 2 88 El-Schafei 48 SPECT 1,9 77 Meuwissen 151 SPECT 1,7 75 Vuodris 48 SPECT 1,7 75

Fizyolojik ölçümler ve noninvazif Stress test sonuçları. rcfr n İskemik test Eşik değer Doğruluk % Verberne 37 SPECT 0,65 85 Chamuleau 127 SPECT 0,60 78 Duffy 28 DSE 0,75 81 El-Shafei 48 SPECT 0,75 75 Voudris 48 SPECT 0,64 92

Orta dereceli lezyonlarda koroner girişimin ertelenme sonuçları. CFR n Eşik MACE T.ay değer Kern 88 2 %7 9 Ferrari 22 2 %9 17 Chamuleau 143 2 %6 12

The Doppler flow wire in acute myocardial infarction. Claessen BE, Bax M, Delewi R, Meuwissen M, Henriques JP, Piek JJ. Contemporary mechanical reperfusion therapy for acute myocardial infarction is aimed at early and complete restoration of myocardial perfusion. However, successful restoration of epicardial blood flow does not guarantee restoration of flow at the myocardial tissue level. The incidence of inadequate myocardial reperfusion after primary percutaneous coronary intervention (PCI) varies from 15-70%, based upon the diagnostic modality used. The Doppler flow guidewire can be used immediately after primary PCI to identify patients with apparently restored epicardial flow but impaired reperfusion at the myocardial microcirculatory and tissue level. Characteristic findings by intracoronary Doppler flow velocity measurements such as a reduced coronary flow velocity reserve, and, in particular, systolic flow velocity reversal and a short diastolic deceleration time are associated with the presence of microvascular obstruction. Detection of microvascular obstruction by the Doppler flow wire directly after primary PCI can identify patients who may benefit from adjunctive therapy after primary PCI. Heart. 2010 Apr;96(8):631-5.

Comparison of coronary flow reserve and fractional flow reserve in patients with versus without diabetes mellitus and having elective percutaneous coronary intervention and abciximab therapy (from the PREDICT Trial). Kini AS, Kim MC, Moreno PR, Krishnan P, Ivan OC, Sharma SK. Patients with diabetes mellitus (DM) have poor long-term outcome after percutaneous coronary intervention (PCI) partly because of microvascular disease and distal embolization. Microvascular obstruction can be assessed by measuring coronary flow reserve (CFR). The Prediction of CK-MB RElease During Successful Stenting Correlating with Indicators of Microvascular ObstruCTion (PREDICT) trial compared the CFR in patients with versus without DM during PCI. Patients undergoing elective PCI were prospectively enrolled according to diabetic (n = 36) and nondiabetic (n = 36) status. All patients received drug-eluting stent with abciximab and were followed for 30-day major adverse cardiac events. CFR and FFR (fractional flow reserve) before and after stenting were measured before and after intracoronary adenosine bolus. Procedural success, MB enzyme of creatine-kinase (CK-MB), troponin I, and high-sensitive C-reactive protein elevation, vascular complications, and major adverse cardiac events were not different. FFR before stenting was 0.77 +/- 0.03 in patients with DM versus 0.76 +/- 0.02 in patients without DM (p = 0.69). FFR after stenting was 0.97 +/- 0.03 and 0.99 +/- 0.01 (p = 0.26), respectively. CFR before stenting was 1.36 +/- 0.31 in patients with DM versus 1.49 +/- 0.25 in patients without DM (p = 0.064). However, CFR after stenting was significantly lower in patients with versus without DM (1.89 +/- 0.30 versus 2.44 +/- 0.67, p <0.001, respectively). CFR after stenting only moderately correlated with CK-MB and high-sensitive C- reactive protein after PCI but did not correlate with 30-day major adverse cardiac events. In conclusion, patients with DM have significantly lower CFR after stenting despite equivalent FFR and myonecrosis compared with patients without DM, indicating greater microvascular obstruction after PCI despite abciximab. Am J Cardiol. 2008 Mar 15;101(6):796-800. Epub 2008 Jan 14.

Restoration of microvascular function in the infarct-related artery by intracoronary transplantation of bone marrow progenitor cells in patients with acute myocardial infarction: the Doppler Substudy of the Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) trial. Erbs S, Linke A, Schächinger V, Assmus B, Thiele H, Diederich KW, Hoffmann C, Dimmeler S, Tonn T, Hambrecht R, Zeiher AM, Schuler G. BACKGROUND: The Doppler Substudy of the randomized, double-blind, placebo-controlled Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) trial aimed to investigate the effects of intracoronary infusion of bone marrow-derived progenitor cells (BMCs) on coronary blood flow regulation in patients with reperfused acute myocardial infarction. METHODS AND RESULTS: In a total of 58 patients (BMC group, n=30; placebo group, n=28), coronary flow reserve (CFR) in the infarct artery and a reference vessel was assessed by intracoronary Doppler at the time of study therapy (4.2+/-0.1 days after acute myocardial infarction) and at the 4-month follow-up. Initial CFR was reduced in the infarct artery compared with the reference vessel in both groups (BMC: 2.0+/-0.1 versus 2.9+/-0.2, P<0.05; placebo: 1.9+/-0.1 versus 2.8+/-0.2; P<0.05). At the 4-month follow-up, CFR in the infarct artery had slightly improved in the placebo group (+0.88+/- 0.18; P<0.001 versus initial) but was markedly increased by 90% (+1.80+/-0.25; P=0.005 versus placebo) in BMCtreated patients, resulting in a normalization of CFR (3.8+/-0.2; P<0.001 versus initial and placebo at 4 months). In the infarct vessel, adenosine-induced minimal vascular resistance index declined slightly in the placebo group (from 1.77+/-0.12 to 1.52+/-0.15 mm Hg x s/cm; P<0.05) but considerably decreased by -29+/-6% in the BMC group (from 1.86+/-0.19 to 1.20+/-0.12 mm Hg x s/cm; P<0.05 versus initial and placebo at 4 months). CONCLUSIONS: Intracoronary BMC therapy after acute myocardial infarction restores microvascular function of the infarct-related artery, which is associated with a significant improvement in maximal vascular conductance capacity. These data provide clinical proof of concept that progenitor cell transplantation promotes vascular repair. Circulation. 2007 Jul 24;116(4):366-74. Epub 2007 Jul 9.

Basınç ve hızı aynı anda elde etmenin faydası olurmu? Günümüzde lezyon distalinden basınç ve hızı aynı anda kayıtlamaya. imkan veren kılavuz teller mevcuttur.

Bu ölçümlerden elde edilen parametreler nelerdir? HSR = Basınç gradienti / Ortalama pik hız. FFR ve KAR ne göre reversibl iskemiyi öngörmede daha güçlüdür. Başlangıç hemodinamik durumdan etkilenmez.stenoz yokluğundaki değeri sıfırdır. Hiperemik akım hızındaki değişimlerden,yetersiz ilaç verimi ve mikrosirkülasyondaki disfonksiyondan az etkilenir.çünkü peak akımda basınç ve hız aynı şekilde etkilenir. Aynı zamanda başlangıç ve maksimal hiperemideki V/P oranı FFR ve KAR den iskemi için daha duyarlıdır.

The prognostic value of combined intracoronary pressure and blood flow velocity measurements after deferral of percutaneous coronary intervention. Meuwissen M, Chamuleau SA, Siebes M, de Winter RJ, Koch KT, Dijksman LM, van den Berg AJ, Tijssen JG, Spaan JA, Piek JJ. OBJECTIVES: We evaluated deferral of PCI of intermediate coronary lesions (IL) using fractional (FFR) and coronary flow reserve (CFR) hyperemic stenosis resistance index (HSR) in patients with a negative or nondiagnostic and noninvasive stress tests. BACKGROUND: Outcome after deferral of PCI of IL with discordant results between FFR and CFR is unknown. METHODS: PCI was deferred in 186 IL (mean diameter stenosis: 52%). Patients were divided according to the results of FFR and CFR in group A; FFR >or= 0.75 and CFR >or= 2.0 (n = 129), group B; FFR >or= 0.75 and CFR 2.0 (n = 28), group C; FFR 0.75 and CFR >or= 2.0 (n = 23) and group D; FFR 0.75 and CFR 2.0 (n = 6). Patients were followed for one year to document major adverse cardiac events (MACE). RESULTS: Nineteen MACEs (0 deaths, 4 myocardial infarctions, 1 CABG, and 14 PCIs) occurred during a follow up of 323 +/- 88 days. MACE rate was lowest (4.7%) when FFR, CFR, and HSR were normal. A higher MACE rate was observed when concordant abnormal (group D) or discordant results between FFR and CFR (group B and C) were compared to concordant normal values (group A, 33.3% vs. 19.7% vs. 5.4%, P = 0.008). Multivariate regression analysis showed a higher predictive power for HSR than for FFR and CFR. CONCLUSIONS: Abnormal FFR or abnormal CFR was documented in 31% of intermediate coronary lesions. Deferral of PCI in this group was associated with a high MACE rate, which underscores the rationale of combined pressure and flow measurements providing a stenosis resistance index that is better suited for clinical decision making in these lesions. Catheter Cardiovasc Interv. 2008 Feb 15;71(3):291-7.

Single-Wire Pressure and Flow Velocity Measurement to Quantify Coronary Stenosis Hemodynamics and Effects of Percutaneous Interventions Maria Siebes, PhD; Bart-Jan Verhoeff, MSc; Martijn Meuwissen, MD; Robbert J. de Winter, MD;Jos A.E. Spaan, PhD; Jan J. Piek, MD Background Lack of high-fidelity simultaneous measurements of pressure and flow velocity distal to a coronary artery stenosis has hampered the study of stenosis pressure drop velocity (P-v) relationships in patients. Methods and Results A novel 0.014-inch dual-sensor (pressure and Doppler velocity) guidewire was used in 15 coronary lesions to obtain per-beat averages of pressure drop and velocity after an intracoronary bolus of adenosine. P-v relations from resting to maximal hyperemic velocity were constructed before and after stepwise executed percutaneous coronary intervention (PCI). Before PCI, half of the P-v relations revealed the presence of a compliant stenosis, which was stabilized by angioplasty. Fractional flow reserve (FFR), coronary flow reserve (CFVR), and velocity-based indices of stenosis resistance (h-srv) and microvascular resistance (h-mrv) at maximal hyperemia were compared. Stepwise PCI significantly lowered h-srv, with an initial marked reduction in hyperemic pressure drop followed by further gains in velocity. A concomitant significant reduction of h-mrv accounted for half of the gain in velocity after PCI. The average magnitude of absolute incremental hemodynamic changes was highest for h-srv (56.839.2%) compared with CFVR (35.334.5%, P0.005) or FFR (19.525.2%, P0.0001). Conclusions P-v relations comprehensively visualize improvements in coronary hemodynamics after PCI. h-srv is a powerful and sensitive descriptor of the functional gain achieved by PCI, combining information about both pressure gradient and velocity, which are oppositely affected by PCI. Simultaneous assessment of stenosis and microvascular resistance may provide a valuable tool for guidance of PCI. (Circulation. 2004;109:756-762.)

Assessment of microcirculatory remodeling with intracoronary flow velocity and pressure measurements: validation with endomyocardial sampling in cardiac allografts. Escaned J, Flores A, García-Pavía P, Segovia J, Jimenez J, Aragoncillo P, Salas C, Alfonso F, Hernández R, Angiolillo DJ, Jiménez-Quevedo P, Bañuelos C, Alonso-Pulpón L, Macaya C. BACKGROUND: Intracoronary physiology techniques have been validated extensively for the assessment of epicardial stenoses but not for the lone study of coronary microcirculation. We performed a comparison between 4 intracoronary physiological indices with the actual structural microcirculatory changes documented in transplanted hearts. METHODS AND RESULTS: In 17 cardiac allograft patients without coronary stenoses, ECG, intracoronary Doppler flow velocity, and aortic pressure were digitally recorded before and during maximal hyperemia with a dedicated system. Postprocessing of data yielded 4 indices of microcirculatory status: coronary flow velocity reserve (2.13+/-0.59), instantaneous hyperemic diastolic velocity pressure slope (2.33+/-1.25 cm x s x (-1)mm Hg(-1)), coronary resistance index (1.65+/-0.88 mm Hg x cm(-1) x s(- 1)), and coronary resistance reserve (2.36+/-0.65). Quantitative morphometry was performed in endomyocardial biopsies during the same hospital intake; arteriolar obliteration (76.57+/-6.95%) and density (2.00+/-1.22 arterioles per 1 mm(2)) and capillary density (645+/-179 capillaries per 1 mm(2)) were measured. Univariate regression analysis between intracoronary measurements and histological findings revealed that instantaneous hyperemic diastolic velocity-pressure slope correlated with arteriolar obliteration (r=0.58, P=0.014) and capillary density (r=0.60, P=0.012). Statistical adjustment revealed an independent contribution of arteriolar obliteration (beta=0.61, P=0.0009) and capillary density (beta=-0.60, P=0.0008) to instantaneous hyperemic diastolic velocity-pressure slope values, resulting in an excellent predictive model (r=0.84, P=0.0002). Coronary resistance index correlated only with capillary density (r=0.70, P=0.019). Relative indices (coronary flow velocity reserve and coronary resistance reserve) did not correlate significantly with arteriolar obliteration, capillary density, or arteriolar density. CONCLUSIONS: Intracoronary indices derived from pressure and flow, particularly instantaneous hyperemic diastolic velocity-pressure slope, appear to be superior to coronary flow velocity reserve in detecting structural microcirculatory changes. Both arteriolar obliteration and capillary rarefaction seem to influence microcirculatory hemodynamics independently. Circulation. 2009 Oct 20;120(16):1561-8. Epub 2009 Oct 5.

Sonuç olarak. Sonuç olarak koroner fizyolojiyi daha iyi anlamada,kateter laboratuvarında işlem kararı vermede ve işlem etkinliğini değerlendirmede hibrit tellerin önemli bir yeri vardır.seçilmiş hasta gruplarında maliyet etkinlik analizi de göz önünde bulundurularak kullanılabilirler.