ΙΓΝΑΤΙΟΣ ΟΙΚΟΝΟΜΙΔΗΣ,MD,FESC ΕΠΙΚΟΥΡΟΣ ΚΑΘΗΓΗΤΗΣ ΚΑΡΔΙΟΛΟΓΙΑΣ Β ΠΑΝΕΠΙΣΤΗΜΙΑΚΗ ΚΑΡΔΙΟΛΟΓΙΚΗ ΚΛΙΝΙΚΗ ΕΚΠΑ ΝΟΣΟΚΟΜΕΙΟ ΑΤΤΙΚΟΝ

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1 ΙΓΝΑΤΙΟΣ ΟΙΚΟΝΟΜΙΔΗΣ,MD,FESC ΕΠΙΚΟΥΡΟΣ ΚΑΘΗΓΗΤΗΣ ΚΑΡΔΙΟΛΟΓΙΑΣ Β ΠΑΝΕΠΙΣΤΗΜΙΑΚΗ ΚΑΡΔΙΟΛΟΓΙΚΗ ΚΛΙΝΙΚΗ ΕΚΠΑ ΝΟΣΟΚΟΜΕΙΟ ΑΤΤΙΚΟΝ

2 Mildly depressed Moderately depressed Eyeball assessment Severely depressed Normal Lang et al. Eur J Echocardiogr 2006; 7:79-108

3 Βiplane method of discs (modified Simpson s rule) Άθροισμα όγκων ελλειπτικών δίσκων Συνιστώμενη μέθοδος για τον υπολογισμό του EF Forshortening κορυφής Υποεκτίμηση όγκων ΑΚ EFA4C = LVEDVA4C- LVESV A4C/LVEDVA4C X 100 EFA2C = LVEDVA2C- LVESV A2C/LVEDVA2C X 100 Lang et al. Eur J Echocardiogr 2006; 7:79-108

4 Baseline F/U1 F/U2

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7 MV PM Apex 4CH

8 EF=23% EDV=260ML, ESV=200 ML J Am Coll Cardiol 2012;59:179

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10 Sicari et al European Heart Journal 2009;

11 1 = normal motion 2 = hypokinesis 17-segment model 3 = akinesis 4 = dyskinesis WMSI= sum of all scores/ total number of segments visualized Cerqueira et al Circulation 2002;105:

12 Treadmill test Supine bicycle

13 European Heart Journal 2013;4:

14 European Heart Journal 2013;4:

15 Senior et al. European Journal of Echocardiography 2009; 10:

16 Normal coronary arteries

17 Significant LAD stenosis

18 DSE + MC contrast PD

19 DEATH OR MI Siu-Sun Yao, Am J Cardiol 2012;109: SE added significant incremental prognostic value to coronary angiography and can identify patients with angiographic CAD at highest cardiac risk.

20 Incremental values (expressed on y axis as x2 values Tsutsui et al Circulation. 2005;112:

21 High risk: annual mortality > 3% European Heart Journal 2013;4:

22 Rest CFR <2.0 for the detection of diameter stenosis >75% Adenosine, dipyridamole Peak stress Sensitivity 86%, Specificity, 70% Vegsundvag et al. J Am Soc Echocardiogr 2011;24:758-67

23 The feasibility of determining CFR in LAD during DSE was 94%. Mean CFR = 2.67 at peak DSE When HR increased by 50 beats, CFR was 2 (CI %) 96.4% of patients reached a CFR 2 (CI %) at 75% of their predicted maximum heart rate It was necessary to achieve a difference of 50 bpm from baseline HR or at least 75% of the maximum predicted heart rate to consider sufficient the test for the analysis of CFR. Cardiovasc Ultrasound Apr 4;9:10.

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25 Concordant results between FFR and CFR were seen in 44 patients (88%) and discordant results in six patients (12% ) The sensitivity, specificity, and positive and negative predictive values of CFR >2 to detect a nonsignificant lesion defined by normal FFR (>0.8) were 95%, 69%, 90%, and 82%, respectively. J Am Soc Echocardiogr Apr;24(4):374-81

26 by Tim P. van de Hoef, Martijn A. van Lavieren, Peter Damman, Ronak Delewi, Martijn A. Piek, Steven A.J. Chamuleau, Michiel Voskuil, José P.S. Henriques, Karel T. Koch, Robbert J. de Winter, Jos A.E. Spaan, Maria Siebes, Jan G.P. Tijssen, Martijn Meuwissen, and Jan J. Piek Circ Cardiovasc Interv Volume 7(3): June 17, intermediate coronary stenoses in 157patients 10 year f/u: cardiac death, myocardial infarction, or target vessel revascularization

27 Kaplan Meier curves according to concordance with normal FFR and CFVR, and the different discordance groups according to an FFR cut-off value of (A) 0.75 (B) van de Hoef T P et al. Circ Cardiovasc Interv. 2014;7:

28 Discordance of CFVR/FFR (30%) originates from the involvement of the coronary microvasculature. The risk for major adverse CV events associated with FFR/CFVR discordance is mainly attributable to stenoses where CFVR is abnormal. This emphasizes the requirement of intracoronary flow assessment in addition to coronary pressure for optimal risk stratification in stable CAD van de Hoef T P et al. Circ Cardiovasc Interv. 2014;7:

29 Among RHI,IMT,PWV Ikonomidis I, Lekakis J Atherosclerosis 2014

30 Stress echocardiogram was positive for ischemia in 480 patients (30%). Obstructive (>70% vessel stenosis) CAD was present in 650 patients (40%) Cortigiani L. et al Am J Cardiol. 2010;105:

31 A lower rate of urgent revascularization in the PCI group with no significant between-group differences in the rates of death and AMI 4.0% vs. 16.3%; HR, 0.23; 95%CI ( ), P<0.001, Urgent revascularizations that were triggered by AMI or ECG ischemic changes were less frequent in the PCI group 3.4% vs. 7.0%, P=0.01. In patients with stable CAD, FFR-guided PCI, as compared with medical therapy alone, improved the outcome. Patients without ischemia had a favorable outcome with medical therapy alone N Engl J Med Sep 25;371(13):

32 FAME 2 In a landmark analysis, the rate of death or MI from 8 days to 2 years was lower in the PCI group than in the medical-therapy group (4.6% vs. 8.0%, P = 0.04). N Engl J Med Sep 25;371(13):

33 Eur Heart J :

34 Eur Heart J :

35 ESC Guidelines for chronic stable CAD. Eur Heart J : ECHO CFR?

36 β-microbubble velocity Rest A A= plateau VI= Myocardial Blood Volume β = rate of VI rise = Myocardial Flow Velocity A * ß = Myocardial Blood Flow Peak stress

37 Rest Adenosine 140μ/kg/min CFR > 3 Peak

38 Total 1-year event rate 718 patients with known or suspected CAD f/ufor 16 months Gaibazzi et al JACC Cardiovasc Imaging. 2013

39 Reproducibility of Regional and Global Longitudinal Strains Derived from 2D Speckle-Tracking and DTI between Expert and Novice Readers during Quantitative DSE Interobserver variability rest low dose Global LS is highly reproducible during all stages of DSE. This variable is a potentially reliable and reproducible measure of myocardial deformation peak dose Yamada et al. J Am Soc Echocardiogr 2014;27:880-7

40 Diagnostic accuracy of 2 D-strain lower in right coronary territory No incremental accuracy to visual interpretation Hanekom Eur H J 2007

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42 Viability-DSE diagnostic criteria rest low peak Normal Improvement Improvement normal Normal Improvement Deterioration ischemia Hypokinetic/akinetic Improvement Deterioration hibernating Hypokinetic/akinetic Improvement Improvement Stunning vs sub.scar Akinetic No change No change scar Hypokinetic No change Deterioration ischemia

43 Patients with >10% of dysfunctional but viable LV myocardium may be more likely to benefit from myocardial revascularization and those with 10% less likely to benefit European Heart Journal (2012) 33,

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45 MVO Baseline MVO 30γ PSS MVO 40γ PSS

46 MRI+ΓΑΔΟΛΙΝΙΟ 2D-STRAIN 4CH 2CH 3CH Το επίμηκες strain (-4%) είναι ο δείκτης απουσίας βιωσιμότητας μετά OEM Migrino R Am J Cardiol 2009;104:

47 REST

48 MYOCARDITIS DD FROM AMI admission 2 months

49 PATIENT WITH ALCHOHOL ABUSE AND 2VESSEL CAD LOW DSE PEAK DSE

50 Baseline LDSE Low dose Peak DSE Peak dose

51 ΔΙΑΚΟΠΗ ΑΛΚΟΟΛ ΦΑΡΜΑΚΕΥΤΙΚΗ ΑΓΩΓΗ F/U1

52 BASELINE LOW DOB F/U1 ΤΙΜΕΣ LGS < -5% ΑΝΤΙΣΤΟΙΧΟΥΝ ΣΕ ΟΥΛΗ (>75% ΙΝΩΣΗ ΣΕ MRI)

53 F/U1 CONSERVATIVE LOW DOB F/U2 PCI INTERVENTION

54 -Better visualization of the LV apex -Rapid acquisition of peak stress images -Evaluation of multiple segments from different planes Lower spatial resolution and lower frame rates. Lang et al. J Am Soc Echocardiogr 2012;25:3-46

55 H Δυναμική ηχωκαρδιογραφια αποτελεί μια ασφαλή χαμηλού κόστους και ελεύθερη ακτινοβολίας τεχνική για την εκτίμηση της ισχαιμίας και της βιωσιμότητας Η εκτίμηση της στεφανιαίας εφεδρείας ροής και η χορήγηση παραγόντων αντιθεσης βελτιώνουν την διαγνωστική και προγνωστική αξία της μέθοδου Η τριδιαστατη 3D και speckle tracking echocardiography αποτελούν μια νεότερη εξέλιξη της μεθόδου

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57 Triplane base Triplane stress

58 Alman J Am Coll Cardiol 2002;39: Camici Circulation 2008;117:

59 Gaetano Nucifora, Am Heart J 2010;159: GLS:-17.4 sens:83%,spec:77%

60 Anakinra:IL-1ra Ikonomidis I Kremastinos DT Lekakis J. Circulation Cardiovasc Imaging 2014

61 An example of a RA patient with CAD (LAD and D1)

62 Pre anakinra 3h after anakinra rest adenosine

63 An example of a RA patient with CAD (LAD and D1) and impaired baseline mean longitudinal strain (-6%) After 3-hours of anakinra injection there was an improvement in mean longitudinal strain (-10%) Baseline IL-1=3.8 pg/ml (normal value 0,2 pg/ml)

64 Conceptual plot of the fractional flow reserve (FFR) coronary flow velocity reserve (CFVR) relationship. abnormal FFR and a normal CFVR:predominant focal epicardial, but nonflow-limiting CAD normal FFR and an abnormal CFVR: predominant microvascular involvement in CAD Discordance between FFR and CFVR occurred in 31% and 37% of stenoses at the 0.75, and 0.80 FFR cut-off value, respectively, was characterized by microvascular resistances during basal and hyperemic conditions van de Hoef T P et al. Circ Cardiovasc Interv. 2014;7:

65 4,313 patients J Am Coll Cardiol Img 2012;5:

66 Eur Heart J :

67 Eur Heart J :

68 Ikonomidis I, Makavos G, Nikitas N, Ilias I, Paraskevaidis J, Diamantakis A, Kopterides P, Lekakis J, Dimopoulou I 2nd Cardiology Department, National and Kapodistrian University of Athens, Medical School, Attikon Hospital, Athens - Greece 2nd Department of Critical Care Medicine, National and Kapodistrian University of Athens, Medical School, Attikon Hospital, Athens - Greece International Journal of Cardiology 2014

69 Kaplan-Maier analysis confirmed an increased mortality in patients with a CFR value of < 1.9 compared to those with CFR 1.9 (log-rank = 4.2, p = 0.03)

70 12 10 Chi-square change: (p 0.03) Chi-square for MODEL1 Chi-square for APACHE II MODEL 1: Including APACHE II and CFR 2 0 APACHE II MODEL Chi-square change: (p 0.04) Chi-square for MODEL 2 Chi-square for SOFA MODEL 2: Including SOFA and CFR 0 SOFA MODEL 2

71 Mattoso et al. J Am Soc Echocardiogr 2013;26:539-47

72 Analysis of 24 studies -79,6% mortality for revascularization after detection of viability Allman et al.j Am Coll Cardiol 2002;39:1151 8

73 Circulation. 2005;112:

74 Assessment of Myocardial Viability at DSE by Deformation Analysis Using Tissue Velocity and Speckle-Tracking Longitudin al strain Circumferential strain In the presence of ischemia, longitudinal and circumferential abnormalities precede the decrease in radial deformation. TDI S,SR more accurate than STE for viability detection. TDI measures can predict viability in all teritories but STE measurements predict viability only in the anterior segments Bansal J Am Coll Cardiol Img 2010;3:121 31

75 REST CONTRACTILE RESERVE -IMPROVED AFTER LEVOSIMENDAN DOB DOB Paraskevaidis I Ikonomidis I, et al. Am J Cardiol 2008;102:

76 ROC Curve 1,0 Source of the Curve resting Radial strain 0,8 Δ Radial strain resting Radial SR Δ Radial SR Sensitivity 0,6 0,4 resting Longitundinal strain Δ Longitundinal strain resting Longitundinal SR Δ Longitundinal SR resting Circumferential strain 0,2 Δ Circumferential strain resting Circumferential SR Δ Circumferential SR 0,0 Reference Line 0,0 0,2 0,4 0,6 0,8 1,0 1 - Specificity Diagonal segments are produced by ties. Paraskevaidis J, Ikonomidis I et al Int J Cardiol 2014

77 sensitivity and specificity of 2D to detect CAD were 80 and 82% and of RT3D echocardiography were 82 and 64%, respectively, whereas in the per patient perfusion analysis the respective percentages were 88, 64% for 2D and 90, 73% for RT3D. Aggeli et al. European Journal of Echocardiography 2011;12:

78 ΙΓΝΑΤΙΟΣ ΟΙΚΟΝΟΜΙΔΗΣ MD, PhD, FESC ΕΠΙΚΟΥΡΟΣ ΚΑΘΗΓΗΤΗΣ ΚΑΡΔΙΟΛΟΓΙΑΣ Β ΚΑΡΔΙΟΛΟΓΙΚΗ ΚΛΙΝΙΚΗ, εθνικό και καποδιστριακό ΠΑΝΕΠΙΣΤΗΜΙΟ ΑΘΗΝΩΝ ΝΟΣΟΚΟΜΕΙΟ ΑΤΤΙΚΟΝ

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80 J Am Coll Cardiol 2010;56:

81 ADMISSION 5 DAYS AFTER

82 Admission 5 Days after

83 Mortality Morbidity Intervention LV-RV function (systolic-diastolic) Ischemia/viability

84 GLS> - 12% MMD >61,5ms GLS< -15.5% MMD <49ms Ersbøll J Am Coll Cardiol Img 2013;6:851 60

85 CAD, previous MI, HF ECHO Global and segmental function SCAR? (Thinned, highly echogenic, akinetic segment) No Yes Viability test Novel techniques No Graftable or plastable vessel? Yes CABG or PTCA

86 Patients with >10% of dysfunctional but viable LV myocardium may be more likely to benefit from myocardial revascularization and those with 10% less likely to benefit European Heart Journal (2012) 33,

87 Dr. Ignatios Ikonomidis MD,FESC, EACVI Assistant Professor 2 nd Cardiology Department, Attikon Hospital, University of Athens

88 4D LV VOLUME QUANTIFICATION (4DLVQ) TomTec 4D Analysis 3D QUANTIFICATION ADVANCED

89

90 MV PM Apex 4CH

91 The absolute Bland-Altman difference between 3DE and CMR, expressed as bias 2 SDs for each substudy. J Am Coll Cardiol 2012;59:1799

92 EF=23% EDV=260ML, ESV=200 ML

93 Caseli et al. European Journal of Echocardiography (2010) 11,

94 529 patients with CV risk factors the effects of clinical variables (age, advanced renal disease, and heart failure) were augmented more by 3DEEF (incremental χ2=14.04, P<.0001) than 2DE EF (incremental χ2=5.13, P =.024). Stanton T J Am Soc Echocardiogr 2013

95 pre 3D-LV function 5m after

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97 ΙΓΝΑΤΙΟΣ ΟΙΚΟΝΟΜΙΔΗΣ,MD,FESC ΕΠΙΚΟΥΡΟΣ ΚΑΘΗΓΗΤΗΣ ΚΑΡΔΙΟΛΟΓΙΑΣ 2 η ΚΑΡΔΙΟΛΟΓΙΚΗ ΚΛΙΝΙΚΗ ΠΑΝΕΠΙΣΤΗΜΙΟΥ ΑΘΗΝΩΝ ΝΟΣΟΚΟΜΕΙΟ ΑΤΤΙΚΟΝ

98 ANTERIOR MI Primary PCI Pre PCI Immediately after 48h Effects of post conditioning 30 days after Ikonomidis I, Paraskevaidis J, Iliodromitis E Heart 2010

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100 30 days Post PCI

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108 AMI COMPLICATIONS PSEUDOANEURYSM

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110 Gaetano Nucifora, Am Heart J 2010;159:

111 Ερωτήματα Έναρξη β αναστολέων ποια δόση Έναρξη αναστολέων μετατρεπτικου ένζυμου Διουρητική αγωγή όχι,ναι, ποια δόση Απάντηση Κλάσμα εξώθησης ΑΚ, λειτουργικότητα δ κοιλιας Πίεση στην πνευμονική Τύπος διαμιτροειδικης ροής Διάμετρος κ.κ.φλέβας Στόχος πρόληψη ισχαιμίας, καρδιακής ανεπάρκειας βελτίωση πρόγνωσης

112

113

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115 Eur Heart J :

116 Eur Heart J :

117 Eur Heart J :

118 Eur Heart J :

119 ADMISSION F/U

120 ADMISSION F/U

121 ADM ADM F/U

122 POST-KINA REST ADEN

123 PRE-KINA POST-KINA

124 ADMISSION F/U

125 ΕΥΧΑΡΙΣΤΩ

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127

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129 Gaibazzi et al. J Am Coll Cardiol Img 2013;6:1 12)

130 CFR= 1,5

131 The sensitivity, specificity, and positive of CFR >2 to detect a no by normal FFR were 95 respectively Mwimoun et al J Am Soc Echocardiogr 2011;24:374-81

132 Dipyridamole and dobutamine showed similar accuracy (87%, 95% confidence intervals, CI, 83 90, vs. 84% CI, 80 88, p = 0.48), sensitivity (85%, CI 80 89, vs. 86%, CI 78 91, p = 0.81) and specificity (89% CI 82 Picano et al. Cardiovasc Ultrasound 94 vs. 2008;6:30. 86%, CI 75 89, p = 0.15).

133 Geleinjnse M JACC 1997;30: Sensitivity, specificity and accuracy of DSE (open bars) versus dipyridamole echocardiography (hatched bars) for detection of CAD

134 Salustri Am H J 1992;124:75

135 The viability sub-study of the STICH trial found viable myocardium in 487 of 601 patients (81%) and no viable myocardium in 114 (19%).289 Among patients without viability, 60 were allocated to CABG and 54 to medical therapy and, among the 487 patients with myocardial viability, 244 were assigned to CABG and 243 to medical therapy. The differences in baseline characteristics, between patients who underwent myocardial viability testing and those who did not, indicate some selection bias driven by clinical factors. Viability was arbitrarily defined using different cut-off values for the different tests used. By univariate analysis, there was a significant association between myocardial viability and outcome; however, this associationwas not significant on multivariable analysis that included other prognostic variables. It is likely that other variables, such as LV volumes and ejection fraction, are causally determined by the extent of viable myocardium. The lack of correlation between myocardial viability status and benefit from CABG in this study indicates that assessment of myocardial viability should not be the sole factor in selecting the best therapy for these patients.

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138 hing the maximum protocol dose tient discomfort definite wall motion abnormality lving two or more adjacent segments -segment elevation on ECG aching 85% of maximum predicted t rate for age systolic blood pressure >200 or <100 Hg or a diastolic blood pressure >120 mm gnificant ventricular arrhythmias

139 i) patients in whom the exercise stress test is contraindicated (e.g. patients with severe arterial hypertension); (ii) patients in whom the exercise stress test is not feasible (e.g. those with intermittent claudication); (iii) patients in whom the exercise stress test was non-diagnostic or yielded ambiguous results; (iv) left bundle branch block or significant resting ECG changes that makes any ECG interpretation during stress difficult; (v) submaximal stress ECG. stress echocardiography should not be used as a first-line imaging technique for diagnostic and prognostic purposes in patients with known or suspected coronary artery disease, but only when the exercise ECG stress test is either non-diagnostic or non-interpretable (e.g. for left bundle branch block or pacemaker). The less informative and/or interpretable exercise electrocardiography is, the higher is the level of appropriateness to stress echocardiography. No new technology application to stress echocardiography is routinely recommended.

140 Stunning: sustained improvement during stress Hibernating (jeopardized): improve during early stress with subsequent deterioration at peak (biphasic response) This response would indicate a jeopardized region (hibernating myocardium) often improving after revascularization.19,38

141 Dobutamine SE Vasodilators SE Arterial vasodilators the ideal agents Senior et al, 2009, Contrast Echocardiography: Evidence based recommendations Simultaneous assesment of wall motion and perfusion Tαυτόχρονη εκτίμηση WM (απεικόνιση ενδοκαρδίου) και αιμάτωσης Στην υπεραιμία αύξηση 4-5 φορές της μυοκαρδιακής ροής (MBF) Ταχύτητα μικροφυσσαλίδων 5mm/s επαναπλήρωση σε 1sec

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145 Sensitivity 85% specificity 70% Η διατήρηση της μικροκυκλοφορίας προβλέπει την αποκατάσταση της λειτουργικότητας της ΑΚ μετά ΟΕΜ Janardahan Am J Cardiol 2003;92:493-7 Υψηλή ευαισθησία (88%) στην ανίχνευση βιώσιμου (χειμάζοντος) μυοκαρδίου, προβλέπει τη βελτίωση της λειτουργικότητας της ΑΚ 3 μήνες μετά CABG. Aggeli et al Am J Cardiol :

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148 The sensitivity, specificity, <2.0 for the detection of diameter stenosis >75% Sensitivity, specificity, of 86%, 70%

149 CFR # 2.5 detected 1 month after PCI in the left anterior descending coronary artery has the potential to identify patients at higher risk for developing coronary restenosis and indicates the need for close clinical follow-up. (J Am Soc Echocardiogr 2012;25: )

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151 rest stress

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153 cardiac death or nonfatal AMI cardiac death, nonfatal AMI, or unstable angina requiring urgent revascularization Gaibazzi et al J Am Soc Echocardiogr 2011;24:

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155 REST L.DOB

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157 H ανίχνευση ελλείμματος αιμάτωσης, επιπρόσθετη αξία στις διαταραχές κινητικότητας Το έλλειμμα αιμάτωσης προηγείται των τμηματικών διαταραχών κινητικότητας (ιστική ισχαιμία με ή χωρίς επηρεασμένη συστολική πάχυνση). Η έκταση του ελλείμματος αιμάτωσης είναι μεγαλύτερη από την έκταση της τμηματικής έκπτωσης συσταλτικότητας Μεγαλύτερη ευαισθησία 83% (78-88) μικρότερη ειδικότητα 80% (73-87) από DSE για ανάδειξη τμηματικών διαταραχών μόνο

158 17-segment model Lang et al. Eur J Echocardiogr 2006; 7:79-108

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161 90% 87% 63% 82% 74% 85% 67% Marwick et al J Am Coll Cardiol 1992;19:74 81

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167 Dobutamine SE Vasodilators SE Arterial vasodilators the ideal agents Simultaneous assesment of wall motion and perfusion Senior et al, 2009, Contrast Echocardiography: Evidence based recommendations

168 17-segment model PLAX PSAX 4CH 2CH 3CH

169 Sicari et al European Heart Journal 2009;

170 Sensitivity of peak UBE vs TE 88%vs 66% Sensitivity for single-vessel subgroup 72% vs 44% No worsening in specificity 89% vs 89% Caiati et al. J Am Soc Echocardiogr 2013;26:

171 Segments visualized 67% 96 % at stress Interpretation of wall motion with high confidence with contrast agent 36% 74% Sensitivity significantly higher for LCX (62% vs. 49% p=0.0009) και LCX ή RCA (64% vs.52% p = 0.016) Plana et al J Am Coll Cardiol Img 2008;1:145 52

172 JACC Cardiovasc Imaging Dec patients for 16 months