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Objective: To study the change in left ventricular perfusion as well as functional parameters before and after Coronary Artery Bypass Grafting (CABG) using myocardial perfusion scintigraphy.
Study Design: Prospective observational study.
Place and Duration of Study: Nuclear Medical Centre, Armed Forces Institute of Pathology, Rawalpindi, from Feb 2019 to Jan 2022.
Methodology: A total of 42 patients, scheduled for CABG, underwent myocardial perfusion scintigraphy (MPS) using 99mTc-sestamibi, before and 8-12 weeks after surgery. Pre and post operatively, left ventricular relative perfusion and functional parameters were analyzed using commercially available software by two independent nuclear physicians.
Results: Among the enrolled patients (n=42), 38(90.5%) were male while 4(9.5%) were female with mean age of 61.04±8.82 years. Left ventricular ejection fraction improved and was found to be statistically significant (38.93±8.19 to 46.26±10.46, p-value <0.01). Similarly, wall motion increased significantly in anterior and lateral segments with concomitant decrease in septal wall motion. A correlation was observed post-operatively between change in ejection fraction and wall motion (r=0.76) while significantly improved post-CABG radiotracer uptake was seen in almost all myocardial segments which showed reversible ischemia with resting perfusion ≥50% in 97 segments with fixed perfusion defects on pre-CABG resting perfusion, but ≤50% did not show any significant improvement, while 5 segments with pre-CABG resting perfusion ≤50% showed improvement on post-CABG MPS.
Conclusion: There is significant improvement in left ventricular perfusion and functional parameters after CABG as assessed by myocardial perfusion scintigraphy.
INTRODUCTION
Coronary Artery Diseases (CAD) are among the leading causes of fatalities and recognized as the prime cause of mortality and loss in Disability Adjusted Life Years (DALYs), globally contributing to 8.9 million deaths and 164 million DALYs.1,2 The wide spectrum of outcomes associated with CAD are attributed to underlying insufficient myocardial perfusion leading to regional ischemic changes which may progress to ventricular dysfunctions, arrythmias, infarction and even death--thus, effective revascularization of viable myocardial tissue with either percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) not only restore perfusion but also improve ventricular function.3 A detailed evaluation of myocardial perfusion pattern is vital in order to determine which coronary artery should be revascularized to achieve better outcome as pre-operative localization of viable myocardial tissues with possible reversibility has important clinical implications.4
All these factors together with rising prevalence of CAD lead to enhanced significance of myocardial perfusion single-photon emission computed tomography (MPS) which not only provides diagnostic information but also prognostic values due to which gated-MPS has become part of mainstream cardiology practice,5 as it provides information on extent and severity of perfusion defect including viable ischemic myocardium or infarct, regional or global wall motion and wall thickening, left ventricular (LV) functional assessment and mechanical desynchrony while also providing important prognostic data, including transient ischemic dilation, right ventricular uptake, lung uptake, LV ejection fraction and sphericity index.6 Combined assessment has better sensitivity and accuracy in determining viability and hence carries better prognostic value. Although studies have been done in this regard, no data is currently available in our population and clinical setup.
Keeping this perspective in mind, we conducted this study to evaluate functional outcome in patients who underwent CABG by MPS.
METHODOLOGY
This study was conducted at Nuclear Medical Centre, Armed Forces Institute of Pathology (AFIP), Rawalpindi, Pakistan, from February 2019 to January 2022, over a period of three years. Study protocols were approved by Institutional Ethical Review Board before the start of study (IERB No. FC-NMC 18-10/READ-IRB/19/180). All individuals were selected by non-probability consecutive sampling after informed written consent was obtained from all the participants.
Inclusion Criteria: Patients aged more than 18 years, with angiographically proven CAD, scheduled for CABG and referred for pre-operative MPS were included.
Exclusion Criteria: Patients with previous revascularization, valvular disease requiring surgery, cardiomyopathy, perioperative myocardial infarction, surgical complications, non-sinus rhythm and those with contraindication to pharmacological stress MPS were excluded.
All patients underwent MPS before and 8-12 weeks after surgery. Gated rest/stress MPS was done on same day without attenuation correction. Before scanning, patients were instructed to abstain from coffee and caffeine-containing products for 24 hours, beta blockers, calcium channel blockers and theophylline derivatives for at least 48 hours and to come in fasting state. Single-photon emission computerized tomography (SPECT) was performed using dual head gamma camera (Cor Cam Gamma Camera System, DDD-Diagnostic Denmark) with low energy high resolution parallel hole collimator. The energy window was centered at 140 KeV±20% and 64 x images were obtained in 128 x 128 matrix over 1800 semicircular arc. At rest SPECT was performed 30-90 minutes after injection of 8-12 mCi of Tc-99m sestamibi. After rest imaging, patients were stressed with adenosine (140 mcg/kg/min) followed by Tc-99m sestamibi (3 x resting dose) given intravenously. Adenosine infusion was given under strict monitoring.
Gated stress SPECT was performed 15-30 minutes after Tc-99m sestamibi injection. Frame mode acquisition (8 frames per cardiac cycle) was used for ECG gating. For image reconstruction, iterative reconstruction with Butterworth filter was used with cut off frequency 0.4 Cycles per cm and order of 8. After image reconstruction, data was processed and analyzed by using commercially available automatic-processing software for gated perfusion SPECT; Invia Corridor 4DM SPECT 2015 and Cedars-Sinai Medical Center, Quantitative Gated SPECT (QGS) and Quantitative Perfusion SPECT (QPS) 2012. Twenty myocardial segments model was used for perfusion study in which the basal, mid and distal areas of myocardium are divided into 6 segments each while apex into two segments. Five segments model was used for regional wall motion which divides the LV cavity into anterior, lateral, inferior, septum and apex. Double blinding was ensured, and 2 nuclear medical specialists independently analyzed all the images.
Regional tracer uptake (perfusion) was calculated on non-gated images as percentage myocardial uptake to the maximum counts. Wall motion was expressed as inward movement of endocardium in millimeters from the end of diastolic phase to systolic phase. All data including patients' demographic data was entered and analyzed by using Microsoft Excel 365 and IBM Statistical Package for the social sciences (SPSS) version 25.00. Categorical data was expressed as Mean±SD while the significance of mean difference pre-and post-CABG was analyzed by using paired t-test. Nominal data was expressed as absolute values and percentages where a p-value ≤0.05 was considered as statistically significant.
RESULTS
Out of 42 patients, 38(90.5%) were male while 4(9.5%) were female with male to female ratio of 9.5:1. Age ranged from 40-73 years with mean age of 61.04±8.82 years. Along with CAD, 18(42.86%) patients had diabetes, 25(59.52%) had hypertension, 4(9.52%) had thyroid disease, 5(11.90%) had liver disease and 3(7.14%) had autoimmune disease. Total 109 vascular territories were intervened which included 41(37.61%) left anterior descending (LAD) and right coronary arteries (RCA) each and 27(24.77%) left circumflex (LCx) arteries. Table-I shows the baseline characteristics of all enrolled patients.
The global LV ejection fraction (LVEF) pre and post-CABG and pre and post-CABG wall motion changes in anterior wall, inferior wall, lateral wall, septum and apex are given in Table-II.
The total average wall motion increased slightly from 24.43±8.19 to 27.80±7.71. Overall, wall motion changes revealed a reduction in septum with concomitant significant increase in anterior and lateral wall motion. On analysis of average functional parameters, a good correlation was observed between change in ejection fraction (ΔEF) and change in wall motion (ΔWM) as shown in Figure-1.
Table-I: Baseline Characteristics, (n=42)Characteristics Mean±SDAge (years) 61.04±8.82Gender n(%)Male 38(90.5%)Female 4(9.5%)Comorbid n (%)Coronary Artery Disease 42(100%)Diabetes Mellitus 18(42.86%)Hypertension 25(59.52%)Liver Disease 5(11.90%)Thyroid Disease 4(9.52%)Autoimmune Disease 3(7.14%)Revascularized Territories n (%)LAD 41(37.6%)RCA 41(37.6%)LCx 27(24.8%)
Significantly improved post-CABG radiotracer uptake was seen in almost all myocardial segments that showed reversible ischemia and where resting perfusion is ≥50% as 97 segments that show fixed perfusion defects and pre-CABG resting perfusion ≤50% did not show any significant improvement, however, 5 segments with pre-CABG resting perfusion ≤ 50 % show improvement on post-CABG MPS. Segments with normal perfusion on pre-CABG MPS remained the same on post-CABG MPS. Almost all patients had symptomatic relief after CABG as seen in myocardial relative segmental radiotracer uptake shown in Table-III.
Table-II: Pre and Post CABG Difference in LVEF and Wall Motion, (n=42)Character Pre Post p-value CABG CABG (≤0.05)LVEF 38.93±8.19 46.26±10.46 <0.001 Anterior 6.33±1.47 7.25±1.53 0.006 Inferior 4.50±1.81 5.19±1.84 0.090Wall Lateral 6.43±2.35 7.46±1.86 0.028Motion Septum 3.60±2.12 3.44±2.01 0.708 Apex 3.57±2.67 4.47±2.66 0.123 Total 24.43±8.19 27.80±7.71 0.057
Table-III: Segmental Relative Tracer Uptake on Stress Images, (n=42) Relative Tracer Uptake p-Segment (Mean±SD) value Pre CABG Post CABG (≤0.05)Basal Anterior 71.48±10.86 76.62±10.63 0.019Basal Anterioseptal 63.45±12.54 69.52±12.56 0.029Mid Anterior 66.67±13.50 72.98±12.96 0.031Mid Anterioseptal 64.50±14.78 70.90±14.03 0.045Mid Inferioseptal 67.07±13.07 73.64±11.91 0.018Distal Anterior 57.07±17.50 64.90±17.65 0.040Distal Anterioseptal 55.86±17.63 64.00±18.60 0.043Distal Inferioseptal 61.00±14.07 68.70±14.07 0.014Apicoanterior 50.33±17.26 57.67±19.62 0.073Apicoinferior 47.79±14.83 56.60±17.50 0.015Basal Inferioseptal 58.33±10.16 65.14±9.94 0.002Basal Inferior 54.17±13.3 60.48±14.46 0.039Mid Inferior 60.38±11.87 67.36±10.94 0.006Distal Inferior 55.24±12.47 60.00±13.14 0.007Basal Anteriolateral 80.33±12.31 82.67±9.96 0.343Basal Inferiolateral 58.33±10.16 65.14±9.94 0.220Mid Anteriolateral 81.10±14.44 84.76±11.01 0.194Mid Inferiolateral 70.95±20.36 74.79±19.56 0.381Distal Anteriolateral 68.88±14.23 74.86±12.96 0.048Distal Inferiolateral 64.26±15.61 71.31±13.78 0.031
DISCUSSION
Our study shows positive and significant changes in left ventricular perfusion and functional parameters after CABG as detected by MPS where the LVEF demonstrated a significant improvement 8-12 weeks after surgery and wall motion increased in anterior and lateral wall, however, it decreased in septum with increased myocardial uptake of Tc-99m sestamibi after surgery, signifying improved perfusion. LVEF is an important functional predictor of outcome after CABG and is commonly used for risk stratification before surgery.7 In our study population, LVEF improved significantly after surgery (38.93±8.19 to 46.26±10.46, p-value <0.01) similar to one study, which observed an increase in LVEF in 40% of their patients.8
Similarly, another author reported a significant improvement in LVEF in their study population (p<0.01).9 One study assessed LVEF improvement in patients with severe LVEF dysfunction who underwent CABG at Punjab Institute of Cardiology using echocardiography, with an observed mean LVEF before and after surgery being 23.63±1.17% and 32.11±1.98% respectively while mean improvement post-surgery was 8.5±2.7%.10 This increased LVEF after coronary revascularization procedure is considered due to hibernation meaning resting ischemia in viable tissue. Another explanation for this increased LVEF could be stunning which would appear as stress induced ischemia on MPS with the absence of regional wall motion.11 Pharmacological and physically induced wall motion abnormalities have been documented as one of the most sensitive markers of myocardial ischemia.12 Wall motion analysis combined with perfusion analysis using SPECT MPS provides additional diagnostic and prognostic information.13
Wall motion analysis by gated SPECT has limited role in evaluation of minor CAD.14 In our sample, regional wall motion showed a significant improvement in anterior and lateral segments with concomitant decrease in septal wall motion, similar to another study, which showed a decrease in septal wall motion and an increase in lateral wall motion in post-revascularization analysis.15 It has been postulated that decrease in septal wall motion after coronary revascularization surgery is due to systolic anteromedial translation of heart as septal wall motion was not evaluated because of recurrent wall motion aberrations even in the absence of new perfusion defects, perioperative myocardial insult or complication during post-operative period.16 Myocardial tracer uptake is proportional to preservation of cell membrane integrity and metabolism and has well established role in detecting viability.17
One study, which used Tc-99m myocardial ectomography, also observed immediate post CABG improvement in post adenosine stress myocardial perfusion in reversible perfusion defects.18
LIMITATIONS OF STUDY
Limited follow-up time meant that long term follow up was not done in our study, in terms of left ventricular functions, exercise tolerance and outcome. We also did not compare our results with other modalities and the effect of cardioprotective medications being used by patients was also not recorded in our study.
CONCLUSION
There is significant improvement in left ventricular perfusion and functional parameters, including left ventricular ejection fraction and segmental as well as global wall motion, after CABG as assessed by myocardial perfusion scintigraphy, however, decreased septal wall motion after coronary revascularization was also noted.
Conflict of Interest: None.
Funding Source: None.
Authors' Contribution
Following authors have made substantial contributions to the manuscript as under:
AM and FH: Study design, data interpretation, drafting the manuscript, critical review, approval of the final version to be published.
AT and MA: Conception, data analysis, drafting the manuscript, approval of the final version to be published.
MH and ZS: Data acquisition, critical review, approval of the final version to be published.
Authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
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