| Background and objective:In recent years,the long-term survival rate of tumor patients has been gradually improved with the progress of medical technology.Cardiovascular injury related to tumor treatment has become one of the important factors affecting patient prognosis.A variety of drugs in gynecological cancer chemotherapy could cause cardiac injury which involves a variety of pathophysiological changes,further lead to cardiac remodeling and even adverse cardiovascular events.Myocardial edema and inflammatory infiltration are the early manifestation of chemotherapy-related cardiotoxicity,its imaging examination is helpful to the early detection of myocardial injury after chemotherapy.On the other hand,myocardial microcirculation is the key factor for cardiovascular risk stratification,which influence cardiac blood supply and oxygen metabolism.Under the effect of the above-mentioned harmful factors,left ventricle could develop adaptive remodeling both in morphology and function.The exploration of different influence factors on left ventricular(LV)remodeling is conducive to the management of personalized and specific intervention.At present,there are few studies concentrating on the myocardial edema and myocardial microcirculation after the chemotherapy of gynecological malignant tumors.Moreover,the effects of different pathophysiological mechanisms on LV remodeling after chemotherapy need to be further illuminated.Therefore,this study prospectively enrolled the chemotherapy patients with gynecological malignant tumor to complete multiparametric cardiac magnetic resonance(CMR)imaging,and intended to achieve the following purposes:1)To quantitatively evaluate the myocardial edema and inflammation after chemotherapy using CMR T2 mapping,and to further explore the related influence factors of myocardial edema and inflammation.2)To investigate the changes of myocardial microcirculation in patients and the risk factors of myocardial microcirculation dysfunction with the use of CMR first pass perfusion.3)To evaluate the morphological changes of left ventricle in patients using CMR cine,and to explore the association of left ventricular remodeling with myocardial edema,myocardial microcirculation and myocardial localized fibrosis.Materials and methods:From September 2018 to December 2020,our study prospectively recruited the patients diagnosed with gynecological malignant tumor at the Department of radiotherapy and chemotherapy in our hospital and underwent the chemotherapy.CMR examination and serological test of myocardial injury were conducted in these patients.To establish the normal control group,40 healthy volunteers were also enrolled for CMR examination.For chemotherapy patients,we collected and sorted out the basic clinical data referred to the clinical HIS system or consultation;for volunteers,the basic data is collected by the consultation after CMR examination.Before CMR scanning,all subjects were fully informed with the study content and had signed the informed consent.CMR scanning was performed on Siemens 3.0T MRI scanner(Skyra,Seimens medical solutions,Erlangen,Germany).The CMR sequences mainly included:Cardiac cine sequence,T2 mapping sequence,CMR first pass perfusion sequence and myocardial delayed enhancement sequence.CMR image analysis was performed by two radiologists on cardiac post-processing software CVI42(Circle Cardiovascular Imaging Inc.,Calgary,AB,Canada).Statistical analysis was performed with the use of SPSS(version 24.0,Armonk,NY)and GraphPad(prism version 7.00,San Diego,CA).1)In the first part of this study,77 chemotherapy patients(41 of whom completed CMR follow-up)and 40 healthy volunteers were enrolled.Myocardial T2 was measured on CMR T2 mapping images.One-way Anova or Kruskal Wallis test was used to compare the differences of myocardial T2 between patients and normal controls,and multiple linear regression analysis was used to explore the independent association factors of myocardial T2.2)In the second part of this study,69 chemotherapy patients(34 of whom completed CMR follow-up)and 38 healthy volunteers were included.Myocardial perfusion index(PI)was calculated with the use of CMR first pass perfusion images.One-way Anova or Kruskal Wallis test was used to compare the difference of myocardial PI between patients and normal controls,and multiple linear regression was used to explore the independent association factors of myocardial PI.3)In the third part of this study,77 chemotherapy patients(41 of whom completed CMR follow-up)and 40 healthy volunteers were included.The qualitative diagnosis of myocardial localized fibrosis was defined according to CMR delayed contrast enhance imaging.The global parameters[left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),left ventricular myocardial mass(LV mass),left ventricular concentricity index(LV mass/LVEDV,LVCI)]and segmental parameters(left ventricular wall thickness and left ventricular wall motion index)of LV remodeling were measured on cardiac cine sequence.One-way Anova or Kruskal Wallis test was used to compare the differences of LV remodeling parameters between patients and normal controls.Subsequently,myocardial T2,myocardial PI,myocardial localized fibrosis and other cardiovascular risk factors were included in the multiple linear regression analysis to further explore the risk factors of LV remodeling.Results:There was no significant difference of clinical baseline characteristics between chemotherapy patients and normal controls(all P>0.05).In the first part of this study,the mean myocardial T2 of patients in 1st CMR scan was slightly higher than that of normal controls,but there was no significant statistical difference(40.86±1.92 vs.41.18±3.16 ms,P=0.060);while the myocardial T2 of patients in 2nd CMR scan was significantly higher than that of normal controls(40.86±1.92 vs.42.71±1.92 MS,P<0.001*).During the two CMR scans,serological creatine kinase isoenzyme[0.18(0.18 to 0.18)vs.0.18(0.18 to 0.61)U/L,P<0.001*]and myoglobin[19.75(14.68-26.10)vs.30.6(25.33-38.23)UG/L,P<0.001*]were slightly increased in patients.Moreover,creatine kinase isoenzyme(r=0.201,P=0.043*)and myoglobin(r=0.286,P=0.003*)were correlated with the myocardial T2 of patients.As for chemotherapy courses,the myocardial T2 of patients with long course(times of chemotherapy>6)was higher than those with short course(times of chemotherapy≤6)(41.19±2.31 ms vs.42.91±3.35 ms,P=0.010*).As for different chemotherapy regimens,there were no significant differences in myocardial T2 between anthracycline and non-anthracycline,cyclophosphamide and non-cyclophosphamide,bevacizumab and non-bevacizumab chemotherapy groups(all P>0.05).Uni variable analysis showed that chemotherapy(r=0.225,P=0.004*)and times of chemotherapy(r=0.283,P<0.001*)both had the positive correlation with myocardial T2;multivariate linear regression further demonstrated that times of chemotherapy(β=0.186,P=0.036*)was independently associated with myocardial T2 elevation.In the second part of this study,the mean myocardial PI of patients in 1st CMR scan was slightly lower than that of normal controls,but there was no statistical difference(13.22±2.44 vs.12.63±2.70,P=0.719);while the myocardial PI of patients in 2nd CMR scan was significantly lower than that of normal controls(13.22±2.44 vs.11.63±2.94,P=0.016*).There was no correlation of myocardial PI with creatine kinase isoenzyme and myoglobin(all P>0.05).As for chemotherapy courses,no significant difference of myocardial PI was observed between long course group and short course group(12.13±2.73%vs.13.06±3.11%,P=0.104).There was also no significant difference of myocardial PI between anthracyclines and nonanthracyclines,cyclophosphamide and non-cyclophosphamide,bevacizumab and nonbevacizumab chemotherapy groups(all P>0.05).Multivariate linear regression analysis showed that chemotherapy(β=-0.303,P<0.001*)was the independent association factor of myocardial PI;while the number of chemotherapy(r=-0.142,P=0.106)had no correlation.In the third part of this study,there were no significant differences in LVEDV,LVESV,LV mass and LVCI between chemotherapy patients and normal controls(all P>0.05).Between the two CMR scans in patients,there was no significant change in LVEDV,LVESV and LVCI(all P>0.05),but LV mass was slightly decreased in the 2nd CMR scan(51.36±12.91 vs.44.70±8.28 g/m2,P=0.005*).Simultaneously,no significant differences were observed in left ventricular wall thickness and motion index between patients and normal controls(all P>0.05).Multivariate analysis showed that the elevation of myocardial T2 was independently associated with the decrease both in LV mass(β=-0.318,P<0.001*)and LVCI(β=-0.285,P<0.001*),while diabetes was independently associated with the increase of LVCI(β=0.185,P=0.030*).Conclusion:Chemotherapy for gynecological malignant tumors can cause myocardial edema,inflammation and myocardial microcirculation dysfunction in patients.With the increase of chemotherapy numbers,myocardial edema and inflammation could gradually aggravate,but myocardial microcirculation dysfunction will not further deteriorate.In the early stage of chemotherapy-induced LV remodeling,the manifestation could demonstrate as the decrease of LV mass.In a variety of myocardial pathological changes,myocardial edema and inflammation have the significant influence on LV mass and LVCI.CMR multiparametric imaging,which allows the"one-stop" evaluation of cardiac morphology,function and myocardial tissue changes,is an ideal imaging modality for the investigation of chemotherapy-related cardiotoxicity. |
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