Assessment On Diastolic Dysfunction And Prognosis In Patients With Cardiac Amyloidosis Using Rotation Mechanics By CMR-feature Tracking Imaging

Background Objectives Cardiac amyloidosis(CA),a disease characterized by myocardial extracellular deposition of insoluble fibrillar proteins,can cause interruption and distortion of myocardial contractile elements,ventricle and atria gradually stiffness,and ultimately systolic and diastolic dysfunction.Recently,the assessment of myocardial strain mechanics in patients with CA by CMR-feature tracking(CMR-FT)has become a research hotspot.The three-dimensional torsion has been considered as an important factor to maintain the systolic and diastolic function of the ventricle,which was induced by contracting myofibers in the ventricle wall.The base rotates clockwise while the apex rotates counterclockwise around its long axis during systole which yields torsion.Meanwhile,potential elastic energy is stored as a result of deformation of the interstitial matrix and cytoskeletal proteins by torsion.Subsequently,the release of potential elastic energy causes untwisting that leads to early diastolic suction of the ventricle during isovolumetric relaxation,thus facilitating early diastolic LV filling.The previous study has revealed disease-specific patterns of torsion in hypertrophic cardiomyopathy,suggesting that different cardiomyopathy may have specific characteristic of torsion mechanics.To explore the clinical application of myocardial torsion mechanics in CA patients with preserved systolic function,the study aims to observe the characteristics of myocardial torsion mechanics in patients with CA using CMR-FT technique.Methods The study consecutively recruited 139 CA patients with HF(76%men,age 54±10 years)between June 2010 and October 2019 in our Hospital.Patients with CA were divided into three groups according to 2016 European Society of Cardiology(ESC)HF guidelines:CA with reduced(LVEF<40%),mildly reduced(40%≤LVEF<50%),and preserved ejection fraction(LVEF≥50%),and compared with age-and gender-matched healthy controls.All subjects underwent CMR conventional cine images and late gadolinium-enhancement(LGE).Cine images were analyzed offline using Software CVI42 to determine torsion parameters,including torsion,peak systolic torsion rate(sysTR)and peak diastolic torsion rate(diasTR).In detail,the endocardial and epicardial contours were manually delineated at the end-diastolic and end-systolic images for the short-axis series.Characteristics of torsion parameters among three CA groups and healthy controls were assessed.Results Among the 139 CA-HF patients,33(23.7%)patients had reduced systolic function,51(36.7%)had mildly reduced systolic function,and 55(39.6%)had preserved systolic function.reduced LVEF group exhibited a higher heart rate and lower body mass index than preserved LVEF group or healthy controls(all P<0.05).No other significant clinical differences in hypertension,diabetes mellitus,smoking,or baseline New York Heart Association(NYHA)status were found in reduced LVEF group when compared to preserved LVEF and mildly reduced LVEF groups.Patients with reduced LVEF presented with larger biventricular volumes,worse EF,and higher LV mass(all P<0.05).reduced LVEF group had the lowest proportion of nontransmural LGE when compared with the other groups.Torsion and diasTR were significantly impaired in patients with preserved LVEF compared with healthy controls.In patients with mildly reduced LVEF,torsion was lower compared with those with preserved LVEF group.In patients with reduced LVEF,only sysTR was significantly worse compared with mildly reduced LVEF group.LV torsion performed well(0.71(95%confidence interval[CI]:0.61,0.77))in discriminating transmural LGE in patients with CA-HF,whereas area under the curve(AUC)of sysTR and diasTR were 0.70(95%CI:0.60,0.76),0.66(95%CI:0.56,0.73),respectively.Conclusion Compared with healthy controls,patients with CA-HF have disease-specific torsion mechanics,which can be easily derived from CMR-Feature Tracking techniques.Therefore,it may be a new imaging marker of myocardial diastolic and systolic dysfunction to evaluate extent of amyloid infiltration.Background Objectives Cardiac amyloidosis(CA),that is infiltration of cardiac tissues by amyloid,commonly resulting from extracellular deposition of amyloid fibrils consisted of misfolded immunoglobulin light chain(AL)or transthyretin(TTR)protein with restrictive pathophysiological mechanism.The extent and severity of the infiltration of amyloid fibrils is the principal driver of prognosis in CA patients.Recent study has showed that Mayo Clinic staging based on biomarkers of myocardial injury may not predict outcomes in those patients with HF.In addition,the decreased myocardial strains detected by cardiovascular magnetic resonance feature tracking(CMR-FT)were correlated with the prognosis of Al-CA patients.And previous study showed that impaired left ventricular(LV)torsional mechanics using CMR quantitative technique predict cardiac remodeling progression and prognosis after myocardial infarction.In the part I of this study,our study showed that myocardial torsion and peak diastolic torsion rate decreased significantly in patients with CA.Therefore,this study used torsional mechanics by CMR-FT parameters with the aim to 1)investigate whether cardiac torsional mechanics can predict prognosis in CA patients with heart failure;2)investigate the role of torsional mechanics in CA patients with heart failure risk stratification.Methods 100 patients referred to the National Center for Cardiovascular Diseases,Fuwai Hospital from 2011 to 2019 in whom cardiac AL amyloidosis was confirmed on the basis of validated diagnostic criteria were reviewed to participate in a retrospective protocolized clinical follow-up programme comprising systematic evaluation of cardiac clinical parameters,biomarkers,CMR parameters,and survival.All patients received a CMR scan as part of a standard institutional protocol for the evaluation of cardiomyopathies including conventional CMR parameters,LGE distribution pattern,LGE mass,and torsional mechanics derived from CMR-FT post-processing.Conventional CMR parameters included biventricular function,left ventricular mass index,maximum interventricular septal thickness.All CA patients were followed up by regular telephone or by reviewing electronic inpatient/outpatient medical records.Primary endpoint was defined as all-cause mortality.Independent sample t-test or nonparametric test,chi-square test or Fisher’s exact test were used for comparisons of clinical and CMR parameter in patients with and without events in this study,Kaplan-Meier curves were used to compare the prognostic significance between the event positive group and the event negative group.Cox proportional-hazards regression model was used to determine the independent risk factors of adverse cardiovascular events and the corresponding coefficient hazard ratio(HR).Results The study consists of 100 subjects.The mean age of patients was 57 years(range,36-77 years),75.0%were men(mean age,59 years;range,36-77 years)and 25.0%were women(mean age,54 years;range,38-72 years).During the follow-up period(median duration,16.7 months;25th-75th percentile,4.7-45.9 months),66 out of 100 patients died.Left ventricular(LV)quantitative LGE mass were greater in patients with event positive group than that of the patients with negative group(47.2g vs.38.0g,p=0.032),and torsional mechanics parameters were reduced in patients who met the primary endpoint(torsion 0.88deg/cm vs.1.88deg/cm,peak diastolic torsion rate-6.9 deg/cm*s vs.-8.7 deg/cm*s;P<0.05 for both).In addition,Torsion has the largest area under the curve of 0.70(95%CI,0.59-0.81)to predict all-cause mortality.In unadjusted univariable analysis,NYHA classes Ⅲ-Ⅳ(HR=2.33,p=0.014),Ln NT-pro-BNP(HR=1.55,P=0.012),LV ejection fraction(HR=0.97,P=0.027),LGE mass(HR=1.02,P=0.004),right ventricular end systolic volume index(HR=1.02,P=0.044),torsion(HR=0.49,P=0.008),and peak diastolic torsion rate(HR=0.89,P=0.005).Multivariable proportional-hazards regression model analysis indicated that torsion[HR:0.44(0.23-0.83),p=0.011]and peak diastolic torsion rate[HR:0.87(0.80-0.96),p=0.006]were independent prognostic factors of all-cause mortality and showed incremental prognostic value beyond LGE mass.Conclusions In conclusion,this study showed that the torsion mechanics values derived from cine imaging-based CMR-feature tracking techniques may offer incremental independent prognostic information for all-cause mortality in patients with CA-HF patients beyond in addition to NYHA functional class and quantitative LGE mass.