CON - In clinical practice: function yes, perfusion no. Prof Dr G Van Camp Eurecho 2011

Transcription

1 CON - In clinical practice: function yes, perfusion no Prof Dr G Van Camp Eurecho 2011

2 Declaration of Conflict of Interest None in relation to this talk Speakers fee: Astra Zeneca, Pfizer, MSD, GE, Philips Educational \ Research Grant - Small Animal Lab: Astra Zeneca, Pfizer

3 CON - In clinical practice: function yes, perfusion no Introduction What is the real question? What is the easy answer? Which technique has entered the field of EBM? Why should we anno 2011 focus on function and not perfusion? Potential benefits of perfusion imaging proven merits of MCE Does it work in clinical practice? Why doesn t it work? Why focusing on function analysis? Echo in CAD in competition with other imaging techniques

4 Introduction: What is the real question? Has myocardial perfusion evaluated by MCE proven to be superior to function analysis of the LV in routine clinical practice By demonstrating mortality benefit In randomized clinical trials With a positive cost-benefit analysis Resulting in class I indications in ESC guidelines for diagnosis of CAD/ischaemia Scar detection Viability/hibernation

5 Introduction: What is the easy answer? Has myocardial perfusion evaluated by MCE proven to be superior to function analysis of the LV in routine clinical practice By demonstrating mortality benefit In randomized clinical trials With a positive cost-benefit analysis Resulting in class I indications in ESC guidelines for diagnosis of CAD/ischaemia Scar detection Viability/hibernation NO!

6 Introduction: Functional analysis - EBM EHJ 2010: Guidelines on myocardial revascularization

7 Introduction: Functional analysis - EBM EHJ 2010: Guidelines on myocardial revascularization

8 Introduction: Functional analysis - EBM Pre-test likelihood of CAD after RF evaluation, rest ECG, ergometry Low Low to intermediate Intermediate to high High MCE is not existing! Ischaemia? CAD imaging MSCT Stress echo / Nuclear testing No CAD Treat the existing RF - + Coronary angiography ESC Textbook 2010: cardiac imaging in CAD

9 CON - In clinical practice: function yes, perfusion no Introduction What is the real question? What is the easy answer? Which technique has entered the field of EBM? Why should we anno 2011 focus on function and not perfusion? Potential benefits of perfusion imaging proven merits of MCE Does it work in clinical practice? Why doesn t it work? Why focusing on function analysis? Echo in CAD in competition with other imaging techniques

10 Potential benefits of perfusion imaging proven merits of MCE Thanks to MCE, harmonic imaging and LVO has been introduced into the clinical arena Harmonic imaging and LVO however are not the topic of this talk MCE has increased our knowledge of the physiology and pathology of the coronary micro-circulation dramatically. This deserves the greatest respect towards investigators having done tremendous work in this field (S Kaul and others) Physiology however is not the topic of this talk MCE opens also the gate towards drug/gene delivery in coronary/vascular applications This topic is even farther away from this talk

11 Temporal sequence of ischemic events Potential benefits of perfusion imaging proven merits of MCE Theoretically perfusion has an advantage in comparison with function evaluation The ischemic cascade Chest Pain ECG changes X-ECG Regional dyssynergy Stressecho Diastolic dysfunction Metabolic alteration Nuclear Perfusion heterogeneity Cardiology MCE Rest Stress However: 1.Stressechocardiography +LVO has already a high diagnostic accuracy: bonus of perfusion? 2.Feasibility of MCE in daily practice?

12 Potential benefits of perfusion imaging proven merits of MCE The basis for scar detection, the diagnosis of viability and ischaemia by echocardiography is based on function imaging or even better contractility or deformation imaging Literature is overwhelming : echocardiography has comparable accuracy compared to nuclear imaging, still the most important competitor in imaging techniques used for the detection/evaluation of CAD The main question is: does MCE add important, necessary supplementary information on top of tissue harmonic imaging with deformation information given by TDI or 2D strain, and this without a unnecessary cost and without side-effects?

13 With solution Does MCE work in clinical practice? A lot of artefacts can interfere with a correct MCE study Setting artefacts Inadequate focus position Inadequate US transmit frequency, excessive gain settings Expertise is a prerequisite Attenuation Overabundance of contrast agents in LV cavity, focus position in the near field Blooming Cavity signals of neighbouring compartments exceed endocardial borders Swirling High MI Focus position in the near field Insufficient contrast agents LV dysfunction JL Zamorano, MA Garcia Fernandez; Contrast Echocardiography in Clinical practice 2004

14 Does MCE work in clinical practice? A lot of artifacts can interfere with a correct MCE study Setting artefacts Inadequate focus position Inadequate US transmit frequency, excessive gain settings Expertise is a prerequisite Attenuation Overabundance of contrast agents in LV cavity, focus position in the near field Blooming Cavity signals of neighbouring compartments exceed endocardial borders Swirling High MI Focus position in the near field Insufficient contrast agents LV dysfunction JL Zamorano, MA Garcia Fernandez; Contrast Echocardiography in Clinical practice 2004

15 Without solution Does MCE work in clinical practice? A lot of artifacts can interfere with a correct MCE study Chest wall artefacts Ribs or pulmonary tissue artefact Wall motion artefacts Respiratory or thoracic movement If the acoustic window is poor, MCE usually is suboptimal This results in exclusion of a considerable amount of patient/segments in most studies examining MCE: JL Zamorano, MA Garcia Fernandez; Contrast Echocardiography in Clinical practice 2004

16 Does MCE work in clinical practice? This results in exclusion of a considerable amount of patient/segments in most studies examining MCE: 1. Am J Cardiol 2003; Hillis et al. Patients were excluded if they required mechanical ventilation, were receiving intravenous pressors or hemodynamic support with an intra-aortic balloon pump, or if the motion of segments within the territory of the infarct-related artery could not be accurately determined at rest 2. Heart 2003; Greaves et al (R Senior). Of the total of 64 dysfunctional segments on baseline echocardiography, eight could not be analysed by MCE because of artefacts 3. Am J Cardiol 2004; R Senior et al. N= 55 en 110 coronary artery territories. When artifacts were seen in 1 myocardial segments in either the anterior or posterior myocardium with all other segments in those regions being normal, the region was considered to be normal. MCE data interpreted blindly by another observer showed sensitivity of 77% and a specificity 75% for detection of 50% CAD on a patient basis. Artifacts caused by attenuation and bubble destruction are another limitation of MCE. With greater clinical experience, we have been able to identify these more accurately 4. JACC 2005; Tong et al (Wei-Kaul). 12% of examinations excluded because of insuff MCE quality. Studies were classified as normal if RF or MP in the majority of segments within each perfusion territory were normal. Studies were called abnormal if RF or MP was abnormal in one or more territories, even if all territories were not visualized. If a study could not be classified as previously mentioned, it was deemed not assessable. 4% misclassified: perfusion defects with normal function.

17 Does MCE work in clinical practice? This results in the failure of introducing MCE in most of the echolabs world-wide: 2005: British Society Echocardiography proposed MCE as a technique ready to be introduced into the everyday clinical arena 2011: Not in the guidelines nor in the ESC/EAE recommendations for imaging of CAD

18 Does MCE work in clinical practice? Quantification?? Video intensity Quantification of MCE in clinical practice Baseline Non Flow Limiting stenosis at Rest Time (s) Van Camp et al, JASE 2002

19 Does MCE work in clinical practice? Quantification?? Video intensity Quantification of MCE in clinical practice Stenosis + Adenosine Non Flow Limiting stenosis + Adenosine Van Camp et al, JASE Time (s)

20 Does MCE work in clinical practice? Quantification?? Video intensity Quantification of MCE in clinical practice Total occlusion Coronary Occlusion Van Camp et al, JASE Time (s)

21 Does MCE work in clinical practice? Quantification?? Dog Experiment Quantification of MBF: Results Microbubble velocity ß NS P < P < ß slope (cm/s) NIZ IZ baseline NIZ IZ hyperhemia NIZ IZ occlusion Van Camp et al, JASE 2002

22 Does MCE work in clinical practice? Quantification?? ß slope (cm/s) Dog Experiment even than Quantification of MBF: Results r = 0.83 MCE ß versus microspheres (all segments) y = 2.14x MBF (ml.min -1.gr -1 ) Van Camp et al, JASE 2002

23 Does MCE work in clinical practice? Quantification?? ß slope (cm/s) Quantification of MBF: Results MCE ß versus microspheres (only proximal segments) Dog Experiment even than MBF (ml.min -1.gr -1 ) Van Camp et al, JASE 2002

24 Does MCE work in clinical practice? Quantification?? Limitations of Quantification Possible lack of linearity between video intensity and the concentration of contrast agent (1) Intensity values may differ greatly among subjects or even among repetitions of the experiment, as a consequence of the depth-dependent attenuation of reflected US (relative measurements: cavity-myocardium) Limitations of reperfusion parametric quantification Uncertainty about the position of the initial point (2) Subtraction of pre-contrast image: correct realignment! Curve filtering (time curve) Validity of the exponential model (3) Motion problems: transducer - patient respiration (movement correction techniques are only an approximation (only in plane correction) 1. Mor-Avi et al Ultrasound Med Biol , Wei et al Circulation , Jayaweera Circ Res 1994

25 Does MCE work in clinical practice? Quantification?? Finally it should be underlined that the difficult introduction of these techniques into routine clinical practice depends mainly on the lack of standardized procedures, both for the acquisition and for the quantitative analysis JL Zamoranao, MA Garcia Fernandez Contrast Echocardiography in Clinical Practice 2004 The additional clinical benefit of myocardial perfusion contrast echocardiography has been inconsistent to date, expert consensus statement R Sicari et al Eur J Echocardiography 2008 Myocardial perfusion: Although there is growing evidence of the usefulness of quantitative analysis, myocardial contrast signals are currently judged using visual assessment EAE recommendations R Senior et al 2009

26 Does MCE work in clinical practice? If quantitative MCE doesn t work, what about semi-quanitative MCE?

27 Does MCE work in clinical practice? If quantitative MCE doesn t work, what about semi-quanitative MCE? Same artefacts are of course encountered

28 Does MCE work in clinical practice? Delayed and incomplete refilling It can work!..sometimes Defect on rest MIBI SPECT But do we need it? UZB 17/08/00

29 Why focusing on function analysis? Because we should use it: it is EBM! Dobutamine echocardiography Ischaemia inferior

30 Why focusing on function analysis? Because we should use it: it is EBM! Exercise echocardiography Viability and ischaemia

31 Why focusing on function analysis? Because we should use it: it is EBM! LVO yes; MCE - no

32 Why focusing on function analysis? Because we should use it: it is EBM! Quantification can help: more precise more objective European Heart Journal (2004) 25, By courtesy: JU Voigt: Advanced Course Echocardiography BWGNICI 2011

33 Why focusing on function analysis? Because we should use it: it is EBM! Quantification can help: more precise more objective 2D strain is operator independent and automated Gotte JACC 2001; Kenya Kusunose Circulation 2011

34 Echo in CAD in competition with other imaging techniques However: Echocardiography is not the only one player Clinical setting The patient with AMI diagnosis risk complication The patient with stable angina ischaemia extent of ischaemia The patient with chronic ischaemic heart disease Ischaemia Viability Prognosis MR Asynchrony - CRT Imaging tool Echocardiography HI LVO, MCE TDI, S, SR, 2Ds Nuclear imaging SPECT PET CMR Anatomy Perfusion LE Multi-slice CT Calciumscoring (EBCT,MSCT) Coronary FFR during coronarography

35 Echo in CAD in competition with other imaging techniques:mce introduces a new cost Echocardiography Nuclear Imaging CMRI Multi-slice CT B/W, Doppler, Color D, TEE, TDI, strain, 2D strain, LVO, MCE SPECT, gated SPECT, PET Function, perfusion, LE, coronary Function, calcium score, coronary $ Evolution in CAD imaging: does it result in better outcome? Budget for imaging in USA: 2000: 6.89 billion $ 2006: billion $ 33% for cardiac imaging!!! An unanswered question!!! Although unanswered: new techniques are already widely implemented Financial and Need to publish

36 Echo in CAD in competition with other imaging techniques:mce introduces a new cost Echocardiography Nuclear Imaging CMRI Multi-slice CT B/W, Doppler, Color D, TEE, TDI, strain, 2D strain, LVO, MCE SPECT, gated SPECT, PET Function, perfusion, LE, coronary Function, calcium score, coronary $ Budget for imaging in USA: 2000: 6.89 billion $ 2006: billion $ 33% for cardiac imaging!!! Evolution in CAD imaging: does it result in better outcome? An unanswered question!!! FFR is an example from our invasive friends: FAME Although unanswered: new techniques are already widely implemented Financial and Need to publish

37 MCE - In clinical practice: function yes, perfusion no Conclusions 1. The basic technique in the diagnosis of CAD remains Defining pre-test probability Physical exam ECG Exercise test.often this is enough for clinical decision making 2. If another imaging test is needed (intermediate risk or inaccuracy of exercise testing) non-invasive stresstesting before the patient is sent to the cathlab is needed Stressechocardiography (SH + LVO) Nuclear imaging

38 MCE - In clinical practice: function yes, perfusion no Conclusions 3. If pre-test probability is low---coronary CT 4. If pre-test probability is high---coronary angiography (FFR) 5. Deformation imaging is a new tool that can be integrated in the echolab without any cost and no special expertise is necessary on the contrary it helps the new echocardiographist in its interpretation 6. If MCE wants to obtain a place in this clinical arena it should prove that it is cost-effective, not in soft end-points such as detection of ischaemia, but in mortality data it should be more reproducible, more reliable, more standardized automated, more easy to be integrated in the world-wide echolab New technical developments are needed! No new technical developments were introduced since real-time low MI MCE

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40 Role of Echocardiography in CAD stable angina The interesting field for cardiac imaging in CAD Sens/spec 75% Sens/spec 90% Intermediate risk Dobutamine/exercise echocardiography

41 Role of Echocardiography in CAD stable angina Pre-test likelihood of CAD after RF evaluation, rest ECG, ergometry Low Low to intermediate Intermediate to high High Ischaemia? CAD imaging MSCT Stress echo / Nuclear testing No CAD Treat the existing RF??? - + Coronary angiography

42 Echocardiography in stable angina Dobutamine/exercise echocardiography: LVO-MCE Piece of cake Difficult

43 Echocardiography in stable angina Dobutamine/exercise echocardiography: TDI European Heart Journal (2004) 25,

44 Imaging in CAD We don t have any trial proving that new upcomming imaging techniques changes patient outcome compared to current standard echocardiography We do have information about the enormous cost in cardiac imaging We do have information about radiation hazard KEEP IT SIMPLE: You just need a good bike and a good echocardiographist with a good echomachine Echo remains the most important imaging technique in CAD imaging in 2009 Of course: Nuclear imaging, MRI and CT can be integrated in a multimodality setting but only after clinical evaluation, stress-ecg testing and echo.