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MINISTRY OF EDUCATION AND TRAINING MINISTRY OF DEFENSE 108 INSTITUTE O F C LINICAL MEDICAL AND PHARMACEUTICAL SCIENC E LE MANH HA STUDYING THE CLINICAL, PARACLINICAL CHARACTERISTICS AND SPECT MYOCARDIAL PERFUS ION IMAGING IN PATIENTS AFTER CORONARY REVASCULARIZATION Spe cialty: Cardiology Code : 62720141 ABSTRAC T O F PHD THESIS HANO I - 2020 T HE THESIS WAS DONE IN: 108 INSTITUT E OF CLINICAL MEDICAL AND P HARMACEUT ICAL SCIENCES Scientific Supe rvisor: Ass Prof PHD Le Ngoc Ha Re viewe r: This thesis will be presented at Institute Council at: 108 Institute of Clinical Medical and Pharmaceutical Sciences Day Month Year The thesis can be found at: Nat ional Library of Vietnam Library of 108 Institute of Clinical Medical and Pharmaceutical Sciences Central Institute for Medical Science Infomation and T echnology INTRO DUCTIO N Rationale of the Study The main methods of coronary revascularization include coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) to improve quality of life, reduce mortality, myocardial infarction rate and increase survival time of patients with chronic coronary artery disease However, 20 - 50% of patients after PCI and 10 - 25% of patients after CABG expressed angina within years, should be assessed, followed up, following treatment Myocardial Perfusion Imaging (MPI) is a valuable method for diagnosing coronary artery disease and prognosis in patients with suspected or confirmed coronary artery disease With imaging principles related to perfusion - myocardial metabolism under the influence of stress, MPI allows differentiation of normal myocardium from ischemic damage, myocardial scarring Based on the characteristics of the MPI, the patient is stratified risks of cardiovascular events to guide appropriate treatment Clinical trials COURAGE (2008), BARI 2D (2012) showed significant changes in MPI lesions before and after treatment in patients with chronic coronary artery disease T he change in the extension of defect between the two scans is also a prognostic value for cardiovascular events In Vietnam, MPI use in evaluation and monitoring after coronary revascularization treatment is increasing However, the characteristics of a MPI in patients after coronary revascularization and changes in the image of MPI before and after coronary revascularization have not been studied in detail 2.O bjective s of the Study To evaluateseveralclinical, paraclinical characteristics andSPECT myocardial perfusion imagesin patients of chronic coronary disease after coronary revascularization To evaluatethe changes of SPECT myocardial perfusion images before and after coronary revascularization Scientific significance - Assessing the characteristic image of MPI is the basis for evaluating and monitoring patients with chronic coronary artery disease after reperfusion with signs of suspected myocardial ischemia (angina, ECG change) - Purpose of coronary revascularization in patients with chronic coronary artery disease for clinical improvement and myocardial perfusion T he study showed that changing characteristics of qualitative and quantitative MPI images before and after coronary revascularization Practical significance According to the major studies in the world, the image features of MPI after perfusion of coronary arterial perfusion and changes of MP I lesions before and after reperfusion have a prognostic value of cardiovascular events These characteristics help guide appropriate treatment for patients with chronic coronary artery disease after reperfusion with signs of ischemic heart disease suspected The structure of the thesis The thesis consists of 124 pages: 2-page question, 36-page overview, 20-page research object and method, 31-page research results, 32page discussion, 2-page conclusion, 1-page recommendation The thesis consists of 168 references, including 30 Vietnamese documents and 138 English documents CHAPTER O VERVIEW 1.1 Chronic coronary arte ry disease after coronary re vascularization Pathophisiological changes after percutaneous coronary intervention: pathophisiological changes, coronary damage after early intervention: stent thrombosis Alteration, damage coronary artery after late intervention: narrowing due to "repairing artery spasm" Narrow stenosis due to endothelial hyperplasia in the heart The process of atherosclerosis leads to a narrowing in the far reaches of coronary arteries that have been previously interfered or narrowed in other coronary arteries Pathophisiological changes after coronary bypass bypass surgery: thromboembolism, inadequate bridging, stenosis of the bridge, spasm of the bridge, incorrectly inserted bridges, incomplete reperfusion, atherosclerosis at the bridge Stenosis of the coronary artery due to atherosclerosis progression Cardiomyopathy status after coronary revascularization: normal cardiac muscle Myocardial damage, but potentially viable: myocardial ischemia residuals due to incomplete reperfusion and atherosclerosis resulting in progressive or newly emerging coronary stenosis The hibernating or stunning myocardium The inviable myocardium Diagnosis and evaluation of chronic coronary artery disease Diagnosis and evaluation of chronic coronary artery disease based on clinical symptoms of angina, risk factors and main subclinical diagnostic methods to evaluate before and after coronary revascularization: + Functional evaluation method: ECG, Holter ECG, EKG, Echocardiography, Echocardiography, Nuclear Cardiology (PET , SPECT , myocardial perfusion), magnetic resonance imaging for myocardial perfusion, evaluating motor wall to heart + Methods based on coronary anatomy images: magnetic resonance imaging,computer tomography, coronary angiography, coronary intravascular ultrasound + Hybrid method based on combining functional and anatomical images of SPECT / CT , PET / CT and PET / CMR 1.2 SPECTmyocardial pe rfusion imagingin patients with chronic coronary arte ry dise ase 1.2.1 Principles of SPECT myocardial perfusion imaging Myocardial ability to uptake radioactive tracer T c99m-MIBI depends on coronary flow and metabolic disorders related to myocardial viability The image obtained through the SPECT system is the radioactive density at the myocardium region based on the application of the radioactive emission of radioactive tracer 1.2.2 Analysis of SPECT myocardial perfusion Normal SPECT myocardial perfusion image: linear radioactive traceruptake for myocardial perfusion flow in the resting and the stress phase Radiopharmaceutical was distributed throughout the myocardiumperfused by the normal coronary artery in both resting and stress phases Defect in MPI is the area of the myocardium that reduces radioactive tracer uptake That expresses the abnormality of themyocardial perfusion and / or t he number of viablecardiomyocytes, the stability and integrity of cardiomyocytes relativelycompared to normal myocardium Defect in rest imagemay be the manifestation of the myocardial infarction scarand/or the ischemic myocardium in resting phase (severe ischemic or hibernating myocardium) Defect in rest image expressed theischemic myocardiumbefore coronary revascularization may decrease or no longer after coronary revascularization Defect in rest image expressedthe myocardial infarction scarbefore coronary revascularization will not change after coronary revascularization Defect in stress imagemay be the manifestation of the myocardial infarction scarand/or the ischemic myocardium influenced by stress Reversible defect related to the ischemic myocardium is thedefect in stress image but recovers (significantly decreasedseverity, size) in rest image 1.3 SPECTmyocardial pe rfusion in patients with chronic coronary artery disease afte r coronary re vascularization 1.3.1 Clinical, subclinical and SPECT myocardial perfusion imaging in patients with chronic coronary artery disease after coronary revascularization According to " Guideline for the diagnosis and management of patients with stable ischemic heart disease" ofcardiovascular and cardiovascular imaging associationsin the United States in 2012, the characteristics of lesions inMPI imagesallowed diagnosis of chronic coronary artery disease and riskstratification, prognosis T hose may orient the appropriate treatment Shaw (2008), Farzaneh-Far (2012) found that angina and ECG changes were the main criteriaforindicating MPI in patients with chronic coronary artery disease after coronary revascularization Elhendy (2003), Zellweger (2014) found that qualitative characteristics of defect in stress image, defect in rest image, reversible defect are prognostic factors of myocardial infartion, cardiovascular death in patients with chronic coronary artery disease after coronary revascularization Large, moderate reversible defect anddefect in stress imagewasassociated with a high risk of cardiovascular events Mahmarian (2006), Shaw (2012) found that the sizedefined in % of left ventricular myocardium of defect in stress image, defect in rest image was related to the risk of cardiovascular events in patients after coronary revascularization Shaw (2008), Shaw (2012), Farzaneh-Far (2012) found that the size of reversible defect ≥ 10% was associated with a higher incidence of cardiovascular events, but it was not yet a significant independent factor 1.3.2 Evaluation of the difference in images of Tc99m-MIBI SPECT myocardial perfusion imaging before and after coronary revascularization T he qualitative difference in images of T c99m-MIBI SPECT myocardial perfusion imaging between different scans was use d in clinical case analysis According to Iskandrian (2016), SSS, SRS, SDS denote a combination of defectsize and severity, so it does not show significant difference between scans and is not mentioned in the recent studies Berman (2001), Shaw (2008), Shaw (2012), Farzaneh-Far (2012) found thesignificant decrease ofthe meansizedefined in % of left ventricular myocardium of defect in stress image, defect in rest image, reversible defect and the percentage of patients with defect in stress image ≥ 10%, reversible defect ≥ 10% aftercoronary revascularization Shaw (2012) found thechange in size ofdefect in stress image ≥ 5% after and before coronary revascularizationwas an significantly independent factor related to MI, cardiovascular death Farzaneh-Far (2012) found that the change in size of reversible defect ≥ 5% was an significant independent prognostic factor Shaw (2008), FarzanehFar (2012) found that the change in sizereversible defect ≤ -5% was associated with a reduction in the incidence of cardiovascular events in but not yet an independentprognostic factorin multivariate analysis CHAPTER SUBJECTS AND METHO DS 2.1 Studying subje cts Including106 patients with chronic coronary artery disease were underwent SPECT MPIscans before and after coronary revascularization (85 patients after PCI and 21 patients after CABG) Thestudying patientswere as inpatient and outpatient of central military Hospital108 from 11/2011 to 05/2015 2.1.1 Selection criteria for study patients - Patients with chronic coronary artery disease after conventional coronary revascularization - Patientsare prescribed SPECT MPI according to ACCF/ ASNC/ ACR/ AHA/ ASE/ SCCT / SCMR/ SNM 2009 Appropriate Use Criteria for Cardiac Radionuclide Imaging for patients after coronary revascularization: + Patients have angina or equivalent expression (fatigue, shallow breathing) + or ECG characteristics suspection of myocardial ischemia - Patients have archived the dataofMPI scanunderwent within monthbefore coronary revascularization - Patient whoagree to participate in the study 2.1.2 Exclusion criteria - Patients with valvular disease, non-ischemic cardiomyopathy -Patients does not comply with optimal medical treatment after coronary revascularization -Patients with severesystemic disease or cardiovascular disease contraindicated for performing physical exercise test and use of dipyridamole, dobutamine (According to ASNC imaging guidelines in 2010 for nuclear cardiology procedures: stress protocols and tracers) T he patient did not follow the stress procedure correctly - Patients with poorMPI image thatmay not beanalyzed 2.2 Rese ach methodology 2.2.1 Research design A prospective, cross-sectional, before-and-after study (Data of MPI scan before coronary revascularization was retrospective) 2.2.2 Research steps The patients were studied according to the following steps - Ask the patient, clinical examination and laboratory tests on patient samples studied - Conduct SPECT MPIfor all patients aftercoronary revascularization - Analyse comparativelybetween SPECT MPI and coronary angiography in patients after percutaneous coronary intervention - Evaluate the difference in images of Tc99m-MIBI SPECT MPI before and after coronary revascularization 2.2.3 History taking, clinical examination and laboratory tests - History of chronic coronary artery disease underwentcoronary revascularization Records of procedures:PCI, CABG - Angina: as recommended by the Vietnam Heart Association (2008) and according to the practical guidelines (2012) of the American Heart Association and the American Heart College - Hypertension (WHO / ISH 2003), Diabetes mellitus (WHO2006/2011), Dyslipidemia (ATPIII 2002), History of MI before coronary revascularization - Diagnosis of myocardial ischemia on ECG: according to Minesota standard - Criteria for coronary artery significant stenosis according to ACC / AHA: stenosis at the main coronary artery (LAD, LCx, RCA) 70% diameter coronary artery 2.2.4 SPECT myocardial perfusion imaging scan * The steps ofpatients preparationg, the procedure of aquisation and processing images according tothe American Society of Nuclear Cardiology imaging guidelines (2010)for nuclear cardiology procedures: stress protocols and tracers.Single photon-emission computed tomography * Procedure:ECG gated SPECT with T c99m - MIBI at 0.31 mCi / kg body weight A twodays procedure followed the guidelines of the American Nuclear Card Association (2010) Day - rest phase: patient was injected with T c99m - MIBI during rest Day - stress phase: patient was injected with T c99m - MIBI during stress test with physical exercise or Dipyridamole transfusion (if patient is contraindicated or unable to perform physical exercise) * Facility: SPECT Gamma camera Infinia from GE (USA) and specialized image processing software: GE's Myometrix and Cedar Sinai's QGS / QPS * Evaluate images and image parameters of interest MPIimageis analyzed and agreed by nuclear medicine doctors According to the guidelines of the American Nuclear Heart Association (2010), tomographical images was discribed along the short axis, horizon long axis, vertical long axis and divided into 17 segments of the left ventricular myocardium corresponding to the region of perfusion of dominant coronary arteries - Evaluation of defect in regions corresponding to the dominant coronary arteries: LAD, LCx, RCA and the coronary artery branch placed stent, bridged T he defectsevertity: mild, moderate, severe The defect size:small, medium, large The defectreversibility between resting and stress phases: reversible, partial, fixed - LV perfusion quantitation: SSS ( Summed Stress Score), SRS (Summed Rest Score), SDS ( Summed Difference Score) 3.1.2.2 Feature of reversibledefect Table 18 Features of re ve rsible defe ct involve d coronary arte ry branches in patients afte r PCI Myocardium Myocardium regions uninvolved stented regions involved coronary branches All stented coronary Coronary branches Coronary branches branches (1) stenosis< 70% (2) stenosis ≥ 70% (3) Def ect n n n n % % % % extension (n=122) (n=110) (n=23) (n=255) 66 54,1 78 70,9 12 52,2 156 61,2 No def ect Small Medium Large 21 20 15 17,2 16,4 12,3 12 14 10,9 12,7 5,5 8,7 26,1 13,0 35 40 24 13,7 15,7 9,4 p (1-2) > 0,05; p (1-3) > 0,05; p (2-3) > 0,05 LV myocardium devided to regions involved main coronary artery branches: LAD, LCx, RCA 25.1% (64 /255) myocardium regions presented medium,large reversbiledefect(15.7% regionspresentedmedium defect, 9.4% regions presented large defect) Table 21 Proportion of patients according to extension ofre ve rsible de fe ct Def ect extension P ts after P CI n (n=85) 0,05 3.1.2.3 Comparative analysis between SPECT MPI and coronary angiography in patients after percutaneous coronary intervention Table 3.26 Comparative analysis between SPECT MPI and coronary angiography in patients afte r PCI Pts af ter PCI (n = 36) Coronary artery stenosis ≥ 70% in Angiography Yes No Positive 22 28 Negative 25 11 36 SPECT Kappa 0,36 p < 0,05 SPECT MPI detected 88% (22/25) pts with coronary artery stenosis ≥ 70% in angiography Kappa: 0.36 for agreement between results of SPECT MPI and Coronary angiography(p < 0,05) 13 3.2 Evaluation of the change s of SPECT myocardial pe rfusion images be fore and afte r coronary re vascularization 3.2.1 Comparison of results of SPECT myocardial perfusion imaging before and after coronary revascularization Table 28 Comparison of re sults of SPECT myocardial pe rfusion imaging be fore and afte r PCI No defect in SP ECT image before and after P CI Defect in SPECT image before but no longer in SPECT image after P CI Def ect in SPECT image before but significantly reduced extension, severity in SP ECT image after P CI Defect in SPECT image before and unsignificantly changed in SP ECT images after P CI Persistent Def ect in SPECT image before but def ect significantly increased extension, severity in SPECT image after P CI Def ect involved one coronary branchesignificantly reduced extension, severity while Def ect involved others increased NormalSPECT af ter PCI Abnormal SPECTaf te r PCI Def ect newly presented (n=85) % 2,4 14 16,5 22 25,9 14 16,5 13 15,3 10 11,8 10 11,8 14/85(16,5%) Pts had a normal SPECT result and defect presented in SPECT image before PCI but no longer in SPECT imageafter PCI 10 BN (11,8%) Pts had defect newly presented in SPECT image after PCI 14 3.2.2 Comparison of defect in stress images before and after coronary revascularization Table 3.33 Comparison of patientproportion by the extension of de fect in stress images before and afte r coronary re vascularization Af er revascularization Pts (n = 106) B efore revascularization Stress defect extension< 10 Stress defect extension ≥ 10 p > 0,05 Stress defect extension< 10 25 (23,6%) 17 (16,0%) 42 (39,6%) Stress defect extension ≥ 10 12 (11,3%) 52 (49,1% ) 64 (60,4%) 37 (34,9%) 69 (65,1%) 106 (100%) Median(percentile 25 – 75%) X ± SD Before revascularization 16 (9 - 29) 19,8 ± 15,1 Afer revascularization 14 (7 – 25) 16,5 ± 11,9 Stress def ect extension p < 0,01 52 / 106 (49,1%) pts had stress defect extension ≥ 10 (% LV myocardium) before and after coronary revascularization.Mean of stress defect extension before revascularization 16,5 ± 11,9 % was statistically significant decreased after revascularization19,8 ± 15,1 %(p < 0,01) 15 3.3.3 Comparison of defect in rest images before and after coronary revascularization Bảng 36 Correlationof MI history to the change of re st de fect extension before and afte r re vascularization Pts without Pts with All p MI Hx (1) MI Hx (2) (1 - 2) (n=38) % (n = 68) % (n=106) % X ± SD -2,2 ± 6,5 1,3 ± 10,8 0,1 ± 9,6 >0,05 ≥5% 15 39,5 19 27,9 34 32,1 -5% 0,05 * Rest defect change = Rest defect extenssion after revas - Rest defect extenssion before revas Rest def ect change 34 (32,1%) Pts had rest defect change≥ 29 (27,4%) Pts had rest defect change ≤ - 3.3.4 Comparison of reversible defect before and after coronary revascularization Table 3.40 Comparison of patientproportion by the extension of re ve rsible de fe ct be fore and afte r coronary re vascularization Pts (n= 106) reversible defect extension < 10 B efore revascularization reversible defect extension ≥ 10 Reversible def ect extension Before revascularization Afer revascularization Af er revascularization reversible reversible defectextension defectextension < 10 ≥ 10 p < 0,05 60 (56,6%) 12 (11,3% ) 72 (67,9%) 25 (23,6% ) 9(8,5%) 34 (32,1% ) 85 (80,2%) 21 (19,8% ) 106(100%) Median(percentil e 25 – 75%) 8,8 (4 – 11,8) 4,5 (1 – 7) 16 X ± SD 8,7 ± 6,8 5,5 ± 6,0 p < 0,0001 Proportion of Pts with reversibe defect extension ≥ 10 before revascularization was 32,1%, statistically significant decreased to 23.6% after revascularization(p < 0,05) Mean of reversible defect extension before revascularization was 8,7 ± 6,8%, statistically significant different from 5,5 ± 6,0% after revascularization(p < 0,0001) ≥ 5% 5% >and> -5% ≤ -5% MI Hx (n=68) No MI Hx (n=68) N = 106 Figure 3 Proportion of patients according to the change of re ve rsible de fe ct extensionbefore and afte r coronary re vascularization 44 / 106 BN (41,5%) Pts hadthe reversible defect change ≤ -5 18 / 106 BN (17,0%) Pts hadthe reversible defect change ≥ 17 CHAPTER DISCUSSIO N 4.1 Clinical, paraclinical characte ristics and SPECT myocardial pe rfusion images in patients of chronic coronary dise ase afte r coronary re vascularization 4.1.1 Clinical characteristics of patients after coronary revascularization The mean age of patients studied was 65.9 ± 10.4 70.8% of patients aged> 60, 88.7% pts were male That is rather similar to the studies of Shaw (2008) and Shaw (2012) * Angina in patients after coronary revascularization In the study, the majority of patients showed angina, of which 2.8% was typical angina, 90.6% was atypical angina (Table 3.2) Angina was the main criteria for indicating MPI in patients after coronary revascularizationrather similar to study of Farzaneh-Far (2012) * Risk factors for coronary artery disease In the study, 79.2% of patients had at least one risk factors ofhypertension, diabetes, dyslipidemia (T able 3.3) According to Fihn (2012), not controlling well the risk factors might increase the rate of restenosis of stented coronary arteries, bridge stenosis andstenosisdue to progressiveatherosclerosis at untreated coronary arteries 4.2.3 SPECT myocardial perfusion images in patients after coronary revascularization 4.2.3.1 Defect in stress image * Features of defect in stress image involved coronary artery branches in patients after PCI In the study, 35,3%myocardium regions presented medium, large defect in stress image (15,7% regions presented medium defect, 19,6% regions presented large defect)(T able 3.12) According to the recommendation of the ASNCin2009, the abnormal result of SPECT MPIpresented the medium or large defect in stress image * Stress defect extension defined in LV myocardium 18 In the study, 65,1% pts presented defect in stress image with extension ≥ 10% LV myocardium In study of Shaw (2012), this ratio was 52.9% and the stress defect extension was an independent factor, having a prognostic value for cardiovascular events 4.2.3.3 Reversible defect * Features of reversible defect involved coronary artery branches in patients after PCI 25.1%myocardium regions presented medium,large reversbiledefect(15.7% regionspresentedmedium defect, 9.4% regions presented large defect)(Table 18) According to Mauri L (2014), Meier (2007), reversible defects related to ischemic myocardium were causedby stent restenosis, brigdestenosisand progressive atherosclerosis in coronary arteries Elhendy (2003) found that medium,large reversbiledefecthad prognostic value of cardiovascular events in patients after revascularization * Reversible defect extension defined in LV myocardium In the study, the proportion of patients with reversible defectextension≥ 10 was 19.8% (T able 21) Hachamovitch (2003), Hachamovitch (2006) showed that Coronary revascularizationmight reduce the relative risk of death compared to medical treatment in patients with reversible defect extension ≥ 10 % Mahmarian (2006), Shaw (2012), Farzaneh-Far (2012) found that reversible defect extension ≥ 10 % in patientsaftertreatment was found to be associated with a higher incidence of cardiovascular events but it was not yet a significant independent prognosisfactor for mortality, MI in multivariate analysis 4.2.3.6 Comparative analysis between SPECT MPI and coronary angiography in patients after percutaneous coronary intervention In the study, SPECT MPI detected 88% (22/25) pts with coronary artery stenosis ≥ 70% in angiography with an Kappa coefficient of 0.36 A meta-analysis of studies by Giedd Kenneth (2004) MPI in postoperative coronary arterial reperfusion had sensitivity: 79%, 19 specificity 79% Galassi (2011) foud that the diagnosis value of myocardial ischemia in patient after PCI increases over time due to progressive stenosis in stentedcoronary arteriesas well a s advanced atherosclerosis in untreated coronary arteries 4.2 Evaluation of the changes of SPECT myocardial perfusion images before and after coronary revascularization 4.2.1 Comparison of results of SPECT myocardial perfusion imaging before and after coronary revascularization 16,5% Patients had a normal SPECT result and defect presented in SPECT image before PCI but no longer in SPECT image after PCI That presented clearly effect of coronary revascularization completely resolving the cause of coronary artery stenosis (T able 3.28) Presetation of defect in SPECT images before PCI corresponded to myocardial ischemia, have t he survivalability to be recovery after revascularization T he effect of coronary revascularization maintainesby the time of SPECT scan after coronary revascularization In the study, 15 patients (including 10 patients after PCI, patients after CABG) had abnormal SPECT result with defect newly presented compared to SPECT image before revascularization (T able 3.28, Table 3.29) According to Kikut (2010), defect newly presented might be related to stenosis of coronary arteries different from coronary arteries revascularized previously 4.2.2 Comparison of defect in stress images before and after coronary revascularization * Comparison of the extension of defect in stress images before and after coronary revascularization In the study, mean of stress defect extension before revascularization 16,5 ± 11,9 % was statistically significant decreased after revascularization 19,8 ± 15,1 % (p < 0,01) ( Table 3.33) Berman (2001) found that the stress defect extension decreased significantly (p
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