Clinical Study Of ¹³N-ammonia Quantitative Gated Myocardial Perfusion Imaging In Diagnosed Or Suspected Coronary Artery Disease

Objectives:（1）To compare the incidence of Coronary Microvascular Dysfunction（CMD）in non-obstructive coronary arteries of patients with different coronary stenosis background;（2）To investigate the impact or predictive value of coronary morphorlogical abnormity,Cardio Vascular Risk Factors（CVRF）,and hemodynamic response during vasodilator stress on Coronary Flow Reserve（CFR）reduction;（3）To explore the relationship between corrected CFR（c CFR）and Supra-normal Left Ventricular Ejection Fraction（sn LVEF）and its prognosis.Methods:（1）Retrospectively analyzed 97 patients with diagnosed or suspected coronary artery disease who successfully underwent the rest/dipyridamole-stress ¹³N-ammonia Positron Emission Tomography/Computed Tomography Quantitative Gated Myocardial Perfusion Imaging（PET/CT QGMPI）.According to the results of coronary stenosis evaluation within90 days,all patients were divided into two groups,non-obstructive group（72 cases,no stenosis≥50%in all three coronary arteries,216 non-obstructive coronary artery）and obstructive group（25 cases,at least one coronary stenosis≥50%;and at least one coronary stenosis<50%,34 non-obstructive coronary artery）.The clinical characteristics including CVRF,Coronary Artery Calcium Score（CACS）,and quantitative parameters concluding rest Myocardial Blood Flow（r MBF）,stress Myocardial Blood Flow（s MBF）,and CFR were analyzed.CMD was defined as CFR<2.90 and s MBF<2.17 ml/min/g.（2）The data of 242 patients（52.6±9.4 years,114 women,136 patients with coronary stenosis assessment）who successfully completed the rest/dipyridamole-stress ¹³N-ammonia PET/CT QGMPI were retrospectively analyzed.The traditional CVRF,underlying CVRF,coronary stenosis,calcification,and hemodynamic response to dipyridamole of patients with reduced CFR were compared with those of patients with normal CFR.The binary logistic regression method was used to analyze the effect of the above factors on CFR.（3）210 patients who were recommended for the rest/dipyridamole-stress ¹³N-ammonia PET/CT QGMPI were followed up（27.3±9.5 months）,and the follow-up Major Adverse Cardiac Events（MACE）,included heart failure,late revascularization,re-coronary angiography,and rehospitalization for cardiac reasons.All patients were divided into three groups according to resting LVEF detected by PET/CT QGMPI:reduced LVEF（rd LVEF,LVEF<55%,n=66）,normal LVEF（n LVEF,55%≤LVEF<65%,n=106）and sn LVEF（LVEF≥65%,n=38）.The clinical characteristics,corrected CFR（c CFR）,and the incidence of MACE among the three groups of patients were compared.A dose-response analysis using a Restricted Cubic Spline（RCS）function was performed to plot the relationship between resting LVEF and c CFR.Multivariate logistic regression was used to analyze the impact factors of sn LVEF.Survival analysis of different LVEF groups was performed using Kaplan-Meier curves.Results:（1）At the patient level,the obstructive group had more severe coronary calcification and stenosis（Coronary Artery Stenosis Score（CASS）:6 vs 0,Coronary Artery Calcium Score（CACS）:73 vs 0,both p<0.001）,more lesion branches（2 vs 0,p<0.001）and more CVRF（5 vs 4,p=0.018）,accordingly,had lower global s MBF（2.65 ml/min/g vs 3.29ml/min/g,p=0.015）and lower global CFR（2.61 vs 3.31,p<0.001）.There was no difference in r MBF（0.96 ml/min/g vs 0.95 ml/min/g,p=0.895）.At the vascular level,non-obstructive coronary arteries in patients with obstructive coronary artery showed higher CACS（0（0,9.23）vs 0（0,0）,p=0.001）,lower s MBF（2.36 ml/min/g vs 3.08 ml/min/g,p=0.019）,and lower CFR（2.69 vs 3.29,p<0.001）.There was no difference in r MBF（0.97ml/min/g vs 0.95 ml/min/g,p=0.867）.Comparing the incidence of CMD in non-obstructive coronary arteries between the two groups,the obstructive group had higher proportion than the non-obstructive group（47.1%（16/34）vs 25.5%（55/216）,χ²=6.738,p=0.009）,but there was no statistical significance between the two groups in r MBF（0.82 ml/min/g vs 0.83ml/min/g）,s MBF（1.91 ml/min/g vs 2.13 ml/min/g）,and CFR（2.48 vs 2.47）in the lesion branch with CMD（p>0.05）.（2）Among all 242 patients,patients with reduced CFR had higher rates of moderate-to-severe calcification（19%vs 9%,p=0.025）,advanced age（66%vs 49%,p=0.006）,overweight（62%vs 49%,p=0.047）,long-term smoking（44%vs 28%,p=0.01）,hypertension（52%vs 37%,p=0.02）and left ventricular dysfunction（8.4%vs 2.2%,p=0.028）ratio,higher CVRF number（4 vs 3,p=0.001）,resting Heart Rate（r HR,70 vs 65,p=0.002）and resting LVEF（60%vs 59%,p=0.015）,as well as lower Heart Rate Reserve（HRR,30%vs 46%,p<0.001）and lowerΔLeft Ventricular End-Systolic Volume（ΔLVESV,-1ml vs-3ml,p=0.002）.There were no differences in rates of other CVRF as well as parameters of blood pressure and left ventricular volume.Among the 136 patients who had assessed for coronary stenosis,patients with reduced CFR（n=62）had a higher proportion of coronary stenosis≥50%（22.6%vs 9.5%,p=0.035）.Multivariate regression analysis showed only blunted HRR（OR:3.869（2.138-7.003）,p<0.001）and sn LVEF（OR:2.868（1.232-6.680）,p=0.015）were independent factors for the reduction of CFR.（3）The dose-response analysis showed an inverted U-shaped curve between resting LVEF and c CFR（p=0.06）.Patients with sn LVEF and rd LVEF had higher proportions of reduced c CFR compared to patients with n LVEF（57.9%vs 54.5%vs 34.3%,p<0.01）.After multivariate adjustment,reduced c CFR（OR:2.695（1.144-6.369）,p=0.023）,small heart（OR:5.076（1.980-12.987）,p=0.001）and hypertension（OR:3.049（1.266-7.353）,p=0.013）were independent predictors of sn LVEF.MACE occurred in 8 patients（4%）at follow-up,and was more common in patients with sn LVEF than that in patients with n LVEF（10.5%vs.0.9%,p=0.008）.Kaplan-meier curve analysis showed that the event-free survival of patients with sn LVEF was significantly lower than that in patients with n LVEF（χ²=6.709,log-rank p=0.01）.Conclusions:（1）CMD can occur in non-obstructive coronary arteries in patients with both non-obstructive and obstructive coronary artery disease,and the latter has a higher incidence of CMD,which is associated with more severe coronary morphological changes and more CVRF;The severity is basically similar.For patients with obstructive coronary artery disease,clinical attention should be paid to the detection and intervention of non-obstructive coronary CMD while paying attention to their obstructive lesions.（2）Coronary morphological abnormalities,CVRF,and hemodynamic parameters during QGMPI examinations can predict CFR reduction to varying degrees.In contrast,the predictive value of coronary stenosis is stronger than coronary calcification,the predictive value of long-term smoking,overweight,advanced age and hypertension is stronger than the other CVRF.HRR and resting LVEF have the closest association with CFR,significantly stronger thanΔLVESV,however,the predictive value of blood pressure-and other volume-parameters is very limited.Focusing on the hemodynamic parameters in QGMPI is meaningful.（3）In patients who are clinically recommended for ¹³N-ammonia PET/CT QGMPI,there is an inverted U-shaped curve between resting LVEF and c CFR.Patients with sn LVEF displayed reduced c CFR indicating the occurance of CMD,which may relate to their poor prognosis.Cardiovascular pathological changes and their clinical significance in patients with sn LVEF warrant further exploration in the future.