Study On The Relationship Between Myocardial Fibrosis And Cardiac Remodeling In Hypertrophic Obstructive Cardiomyopathy

Quantitative fragmented QRS has a good diagnostic value on myocardial fibrosis in hypertrophic obstructive cardiomyopathy based on Clinical-Pathological StudyObjectives:Hypertrophic cardiomyopathy(HCM)is a common inherited cardiovascular disease which is characterized as myocardial fibrosis.Fragmented QRS(fQRS)is becoming a novel electrocardiogram finding and has potential use as a predictor to detect myocardial fibrosis.Recently,a study reported a new method to describe the variation of fQRS,which is quantitative fQRS(Q-fQRS),We aimed to investigate the relationship between Q-fQRS and myocardial fibrosis and the diagnostic value of Q-fQRS to detect myocardial fibrosis in hypertrophic obstructive cardiomyopathy(HOCM)patients based on histological validation.Methods:We performed a retrospective study that included 69 patients with HOCM who underwent ventricular septal surgery.Nine individuals who died from accidents were studied as a control reference for the histological parameters.Septal myocardium samples were subjected to Masson's trichrome staining to quantify the collagen volume fraction(CVF).An fQRS pattern was defined as the presence of additional R waves or RSR',evidenced by notched R or S wave on electrocardiography(ECG).The Q-fQRS was quantified as the total amount of deflections in the QRS complex in all 12 routine ECG leads together.Cardiac magnetic resonance imaging was conducted,and late gadolinium enhancement(LGE)was measured at 2,4,6 and 8 standard deviations(SDs).Results:Of the 69 patients,fQRS was documented in 38(55.1%)patients,the mean number of leads with fQRS was 3.7±1.6,and the mean Q-fQRS was 17±7.2.Compared with HOCM patients without fQRS,HOCM patients with fQRS had a higher CVF[9.92%(5.89-13.41%)vs 5.16%(1.98-6.47%),P<0.001]and more LGE at 6 SD[6.7%(3.9-10.8%)vs 4.2%(1.6-7.5%),P=0.040].Q-fQRS was correlated with CVF(r=0.640,P<0.001),and Q-fQRS showed the best correlation with LGE measured at 8 SD(r=0.379,P=0.002).Multivariate regression analyses revealed that Q-fQRS was independently associated with the extent of CVF in HOCM patients after adjusting for age,sex,body surface area and the extent of LGE at 6 SD(P<0.001).When the patients were divided into subgroups with normal CVF or high CVF according to the CVF in controls,Q-fQRS and LGE at 6SD showed similar diagnostic value in detecting patients with high CVF,with sensitivities of 66.7%vs 68.6%,specificities of 76.7%vs 72.4%,and accuracies of 71%vs 70.3%.Conclusions:HOCM patients with fQRS showed more extensive myocardial fibrosis.Q-fQRS was an independent predictor for myocardial fibrosis and had a good diagnostic value,with a sensitivity of 66.7%and specificity of 76.7%,in identifying patients with higher fibrotic burden.Sex Differences in Atrial Function are Associated with Myocardial Fibrosis in Obstructive Hypertrophic CardiomyopathyObjectives:Hypertrophic cardiomyopathy(HCM)is a complicated genetic cardiovascular disease,which is characterized by myocardial fibrosis.Previous studies have demonstrated that sex-related differences in myocardial fibrosis exist.Increased LV filling pressure would lead to adaptive changes in left atrial(LA)occurred as a result of myocardial fibrosis.Our study aimed to explore the effect of sex on LA remodeling and the association between LA remodeling and myocardial fibrosis in patients with obstructive hypertrophic cardiomyopathy(HOCM).Methods:Eighty-five patients(49 males/36 females,mean age 48.4±13.2 years)with HOCM who underwent surgical septal myectomy were enrolled.Nine myocardial samples were studied as control reference for histological study(6 males/3 females,mean age 45.4±14.3years).Thirty-five age-and gender-matched healthy subjects(21 males/14 females,mean age 45.2±8.5 years)were used to for cardiac magnetic resonance imaging(CMR)analysis.Masson's trichrome staining was performed in myocardial samples,and the collagen content per unit area(collagen volume fraction,CVF)was assessed as myocardial fibrosis.LA function was evaluated by CMR-feature tracking analysis.And the parameters represented,including early atrial peak of emptying rate(PER-E)and atrial peak empty rate(PER-A).PER-E index and PER-A index were normalized by left ventricular filling volume.LA deformation rate,The atrial ejection fraction(LAEF)was measured as the ratio in percentage between atrial stroke volumes and maximal atrial volumes.Results:Compared with healthy controls,HOCM patients had lower PER-E index and LAEF(1.2±0.5/s vs 1.6±1.2/s,P=0.012;41.2±12.2%vs 59.4±6.6%,P<0.001).The CVF was higher(8.7%±4.2%vs 6.4±3.3%,P=0.012)in female patients than in male patients,but the PER-E,PER-E index and the ratio of PER-E and PER-A(86.3±47.4ml/s vs 130.6±58.6ml/s,P<0.001;1±0.5/s vs 1.3±0.6/s,P=0.012;0.64±0.42 vs 0.97±0.86,P=0.025)were lower in female patients than in male patients.In CVF-stratified subgroups,sex differences in CVF and PER-E index were eliminated(all P>0.05),but the sex difference in PER-E remained significant in the subgroup with high CVF(77±46ml/s vs 102.3±42.8ml/s,P=0.013).The CVF was correlated with PER-E and PER-E index in both sexes(all P<0.05).According to a multivariate regression analysis,PER-E index(P<0.001)and sex(P=0.048)were independent predictors for identifying patients with high CVF.Receiver-operating characteristic curve analysis showed that PER-E index was a useful tool to predict HOCM patients with high CVF with an area under the curve of 0.789,sensitivity of 80.4%and specificity of 73.5%.Conclusions:LA deformation rate was independently associated with myocardial fibrosis and had a good diagnostic value to identify HOCM patients with a high fibrotic burden.Female patients exhibited susceptibility to impaired LA function,and potential mechanisms might be derived from the vulnerable nature of developing a high fibrotic burden.Collagen cross-linking is associated with cardiac remodeling in hypertrophic obstructive cardiomyopathy.Background:Collagen cross-linking(CCL)is covalent bonds among collagen fibers which greatly increases the tensile strength and stiffness of collagen fibers and makes them more resistant to degradation.There are two major groups of cross-links:those initiated by the enzyme lysyl oxidases(LOXs)and those derived from non-enzymatically glycated lysine and hydroxylysine residues which are called advanced glycation end-products(AGEs).Recent studies show that the degree of collagen cross-linking(CCL)but not collagen amount has a great influence on LV stiffness in patients with heart failure.However,the role of CCL on cardiac remodeling in hypertrophic obstructive cardiomyopathy(HOCM)patients remains unknown.We aimed to evaluate the formation of enzymatic and nonenzymatic CCL and its clinical significance in HOCM patients.Methods:Forty-four HOCM patients who underwent surgical myectomy were consecutively enrolled,including 6 patients with atrial fibrillation(AF).Cardiovascular magnetic resonance(CMR)parameters of left atrial(LA)/left ventricular(LV)function were measured,including peak filling rate(PFR)and early peak empty rate(PER-E).PFR and PER-E were normalized by LV filling volume.,obtaining PFR index,and PERE index.Total collagen was the sum of soluble and insoluble collagen,which were assessed by collagen assay.The fractions of soluble and insoluble collagen were also expressed as the percentage of the total collagen.The myocardial LOX were measured by Western blot.The myocardial AGEs expression and serum LOX were measured by enzyme linked immunosorbent assay.Results:Compared with patients without AF,insoluble collagen(33.1± 17.9?g/mg vs 20.1±8.1 ?g/mg,P=0.018),insoluble collagen fraction(75.3±7.4%vs 64.7±9.9%,P=0.017)and AGEs(1.16±0.29ug/mg vs 0.78±0.42ug/mg,P=0.039)were higher in patients with AF,whereas LOX expression was similar(0.62±0.34 A.D.U vs 0.522±0.31 A.D.U.,P=0.494).The insoluble collagen fraction was correlated with PFR(r=-0.35,P=0.029),PFR index(r=-0.44,p=0.005),LA diameters(r=0.36,p=0.021),PER-E(r=-0.46,P=0.003)and PER-E index(r=-0.49,p=0.001).Myocardial LOX was positively correlated with total collagen(r=0.37,p=0.025),insoluble collagen fraction(r=0.53,p<0.001),collagen type I(r=0.36,P=0.016)and the ratio of collagen type ? and ?(r=0.34,P=0.026),but inversely correlated with PFR index(r=-0.43,p=0.006)and PER-E index(r=-0.35,p=0.027).However,there was no correlations between serum LOX and myocardial LOX or collagen subtypes.In multiple regression analysis,myocardial LOX was independently associated with PFR(P=0.005),while insoluble collagen fraction showed independent correlation with PER-E(P=0.005)after adjusted for clinical confounders.Conclusions:CCL plays an important role on heart remodeling in HOCM.Myocardial LOX expression is independently correlated with LV stiffness,while accumulation of AGEs cross-links might be associated the occurrence of AF in HOCM patients.