Impacts Of T2DM On Subclinical Myocardial Deformation And Perfusion In Patients With Essential Hypertension—A CMR Study

Background and Objective:The heart is consisted of left and right ventricles and atriums(LV,RV,RA and LA),which interact and influence each other in complex pathophysiological and hemodynamic conditions.Hypertension and type 2 diabetes mellitus(T2DM)share common risk factors,they are causally related and often coexisted with each other.T2DM increases the risks of heart failure and mortality in patients with hypertension,however the underlying mechanism is unclear.Many studies have shown that there are structural and functional changes in both ventricles and left atrium in these diseases,which play extremely important role in the prognosis of patients.However,the traditional parameter of ejection fraction cannot detect early myocardial dysfunction;cardiac magnetic resonance feature tracking(CMR-FT)directly evaluating myocardial deformation is conducive to early detection of subclinical myocardial dysfunction.In addition,with the development of technology,CMR myocardial perfusion can reliably evaluated the myocardial microcirculation,which is an important factor affecting cardiovascular prognosis.Therefore,to increase our understanding of the mechanism of T2DM aggravating heart failure in patients with essential hypertension,CMR-FT and myocardial perfusion were used to evaluate the changes of subclinical myocardial deformation and perfusion in patients with essential hypertension and the impacts of T2DM on them.This study is mainly divided into the following three parts:Part one:To evaluate the impacts of T2DM on LV subclinical systolic dysfunction and myocardial microcirculation in patients with essential hypertension and investigate the association between LV function and myocardial perfusion.Part two:To evaluate the changes of RV systolic function in patients with essential hypertension and the impacts of T2DM,and to explore the association between RV systolic dysfunction with LV function.Part three:To evaluate the three phasic LA deformation in patients with essential hypertension and the impacts of diabetes on them,and to investigate the association between LA deformation and LV function.Materials and Methods:A total of 203 essential hypertensive patients with or without T2DM[HTN(T2DM+)and HTN(T2DM-),respectively]who underwent CMR at our institution from January 2016 to December 2020 were recruited.Firstly,the patients were screened according to the common inclusion and exclusion criteria and patients with poor left ventricular cine image quality were excluded,then the cases with poor image quality for myocardial perfusion,right ventricle and left atrium were excluded,respectively.Finally,117 patients including 72 patients with HTN(T2DM-)and 45patients with HTN(T2DM+),123 patients including 75 patients with(HTN(T2DM-)and 48 patients with HTN(T2DM+),and 129 patients including 82 patients with(HTN(T2DM-),47 patients with HTN(T2DM+)were eligible for the myocardial perfusion,right ventricle and left atrium analysis,respectively.In addition,61,45 and69 age-and sex-matched healthy people were included in each part of the study as the control group.The parameters of retesting myocardial perfusion including upslope,time to maximum signal intensity(TTM)and maximum signal intensity(Max SI),and myocardial deformation including LV global radial,circumferential and longitudinal peak strains or strain rates(LV GRS,GCS,GLS,PSSRr,PSSRc,PSSRl,PDSRr,PDSRc,PDSRl),RV global strains including RV GRS,GCS and GLS,regional strains of RV and interventricular septum(IVS),and LA reservoir,conduit,and booster strains and strain rates were measured by two experienced radiologists with Cvi42 software(Circle Cardiovascular Imaging,Calgary,Canada).After adjusting for age,sex,body mass index(BMI))and heart rate,the myocardial perfusion parameters,RV global strains,and LV and LA strains and strain rates were compared among the three groups by analysis of covariance(ANCOVA)followed by Bonferroni’s post hoc test.One-way ANOVA with Bonferroni’s post-test was used to compare the regional myocardial strain of RV and IVS among the three groups.After adjusting for cardiovascular risk factors,backwards stepwise multivariable linear regression analyses were used to investigate the independent predictors for myocardial perfusion,bi-ventricular and LA myocardial deformation in the patients with hypertension and/or whole population.Results:In the first part of the study,compared with the normal controls,HTN(T2DM-)group showed higher resting myocardial perfusion,and HTN(T2DM+)group exhibited lower perfusion than HTN(T2DM-)group and controls.The LV GLS were deteriorated significantly from controls,through HTN(T2DM-),to HTN(T2DM+)group.The LV GRS and GCS in HTN(T2DM+)group were significantly lower than those in the controls and HTN(T2DM-)group,but not significantly decreased in the HTN(T2DM-)group.In the patients with hypertension,multiple linear regression analyses demonstrated that T2DM was independently associated with myocardial perfusion parameters(upslope:p<0.001,model R~2=0.289;TTM:p<0.001,model R~2=0.363;Max SI:p<0.001,model R~2=0.173,respectively)and three dimensional LV strains(LV GRS:p=0.006,model R~2=0.285;GCS:p=0.002,model R~2=0.409;GLS:p=0.001,model R~2=0.488,respectively).When T2DM and perfusion parameters were included in the regression analyses,T2DM and TTM(p=0.014 and p=0.015;model R~2=0.476)were independently associated with LV GLS,TTM(p=0.002,model R~2=0.314)but not T2DM was independently associated with LV GRS.In the second part,the three-dimensional LV strains showed similar trend with the results of the first section.The RV GLS and apical longitudinal strain were deteriorated significantly from controls,through HTN(T2DM-),to HTN(T2DM+)group.Compared with the controls,the middle RV regional longitudinal strains were significantly decreased in both hypertensive groups,but they were not significantly different between the two groups;the basal RV regional longitudinal strain was decreased in the HTN(T2DM+)group but preserved in the HTN(T2DM-)group.Compared with the controls,regional longitudinal strain of IVS was only decreased in some segments in the HTN T2DM-)group,while they were declined in all the IVS segments in the HTN(T2DM+)group and further lower than those in the HTN(T2DM-)group.In addition,HTN(T2DM+)group also showed a decrease in regional radial and circumferential strain in some IVS segments.In the patients with hypertension,multiple linear regression analyses demonstrated that T2DM was independently associated with three dimensional LV strains(LV GRS:p=0.011,model R~2=0.315;GCS:p=0.019,model R~2=0.429;GLS:p=0.01,model R~2=0.438,respectively)and RV GLS(p=0.018,model R~2=0.136).When T2DM and LV GLS were included in multiple regression analysis,LV GLS but not T2DM was independently associated with RV GLSIn the third part,the three-dimensional LV strains showed similar trend with the results of the first and second section.The LV PDSRr and PDSRl,LA reservoir and conduit strain,and LA conduit strain rate were deteriorated significantly from controls,through HTN(T2DM-),to HTN(T2DM+)group.Compared with the controls,the LV PDSRc was significantly declined in both hypertensive groups,but they were not significantly different between the groups;and the LA booster strain and strain rate were significantly decreased in the HTN(T2DM+)group but preserved in the HTN(T2DM-)group.In the whole population,multiple linear regression analyses showed that T2DM,LV GCS and GLS(p=0.015,0.043 and 0.036,model R~2=0.288)were independently associated with LA reservoir strain,LV GLS(p=0.042,model R~2=0.168)but not T2DM was independently associated with LA reservoir strain rate;T2DM and LV PDSRl(p=0.03 and 0.036,model R~2=0.315)were independently associated with LA conduit strain,and LV PDSRc(p<0.001,model R~2=0.403)but not T2DM was independently associated with LA conduit strain rate.In addition,T2DM was independently associated with LA booster strain(p=0.008,model R~2=0.09)and strain rate(p=0.008,model R~2=0.225);HTN,T2DM and LA booster strain(p=0.016,0.018 and 0.008,model R~2=0.390)were independently associated with LV GLS,and T2DM and LA booster strain were independently associated with LV GRS(p=0.002 and 0.019,model R~2=0.327)and GCS(p=0.004 and 0.026,model R~2=0.313).Conclusion:In patients with essential hypertension,T2DM had additive deleterious effects on myocardial perfusion,subclinical biventricular systolic function,LV diastolic function,and LA three phases function.Impaired myocardial perfusion by coexisting T2DM was associated with deteriorated LV systolic dysfunction,aggravated LV systolic dysfunction was associated with deteriorated RV systolic and LA reservoir dysfunction,aggravated LV diastolic dysfunction was associated with deteriorated LA conduit dysfunction,and LA systolic dysfunction was an independent predictor for LV systolic function,suggesting an adverse interventricular and atrioventricular coupling.