The Effect Of Microvessel Density In Hypertrophic Cardiomyopathy On Myocardial Fibrosis And Left Ventricular Remodeling

The first part:The impact of microvascular density on myocardial fibrosis in hypertrophic cardiomyopathyObjective:Hypertrophic cardiomyopathy(HCM)is a myocardial disease characterized by fibrosis and microvascular ischemia.Microvessels play a critical role in myocardial fibrosis in HCM.However,it remains unclear whether or not myocardial fibrosis is associated with microvascular density(MVD)changes.The aim of the present study was to investigated the impact of microvascular density(MVD)on myocardial fibrosis in HCM cardiac samples.Methods:We analyzed the relationship between myocardial fibrosis and microvessels in left ventricular(LV)septal wall specimens from 53 HCM patients by staining microvesseels and myocardial fibrosis.Control myocardium from LV septal wall was collected at autopsy of 9 individuals who died of noncardiac causes.Results:The fibrosis ratio(%area)in HCM was higher and the MVD was lower than that in control subjects(12.7±10.0 vs.4.0±1.4%,p=0.012,and 480.9±206.7 vs.1425±221/mm2,p<0.001).Patients with mild fibrosis had a higher MVD than patients with moderate fibrosis(568.2±214.8 vs.403.2±167.8/mm2,p=0.006)and patients with severe fibrosis(568.2 ± 214.8 vs.378.6 ±154.0/mm2,p=0.024).Furthermore,a significant negative correlation was found between myocardial fibrosis and MVD in all HCM patients(r=-0.40,p=0.003),which was also found in mild fibrosis(r=-0.40,p=0.043),moderate fibrosis(r=-0.50,p=0.024),and severe fibrosis group(r=-0.24,p=0.61),although no significant differences were observed in severe fibrosis.Additionally,we demonstrated that late gadolinium enhancement(LGE)was negatively correlated with MVD(r=-0.41,p=0.02)and positively correlated with fibrosis(r=0.50,p=0.004).Conclusion:HCM patients had a higher myocardial fibrosis ratio and a lower MVD.The severity of myocardial fibrosis was negatively correlated with MVD in HCM.These findings showed that a reduced MVD may contribute to myocardial fibrosis in HCM.The second part:The impact of microvascular density on left ventricular remodeling in hypertrophic obstructive cardiomyopathyObjective:Hypertrophic cardiomyopathy(HCM)is a myocardial disease characterized by left ventricular(LV)asymmetric hypertrophy and LV remodeling.Microvascular disease play a critical role in local myocardial ischemia.However,it remains unclear the impact of microvessels on LV remodeling in HCM.The aim of the present study was to investigated the impact of microvascular density(MVD)on LV remodeling.Methods:We stained microvessels in LV septal wall specimens by immunohistochemical method from 48 HCM patients.All HCM patients were divided into severe LV remodeling group(25 cases)and mild LV remodeling group(23 cases)according to the left ventricular remodeling index(LVRI)measured by cardiovascular magnetic resonance(CMR).Therefore,compared the MVD between the 2 groups and analyzed the impact of MVD on LV remodeling.Results:Compared with the mild LV remodeling group,the MVD(398.7±121.3/mm2 vs.592.0±239.7/mm2,p=0.001)and LVEF(62.2 ± 10.2%vs.69.4±8.3%,p=0.01)in the severe LV remodeling group were significantly lower;LVRI(1.7±0.3 g/ml vs.1.0± 0.1 g/ml,p<0.001)and left ventricular end-diastolic mass index(LVMI)(136.2±36.8g/m2 vs.82.1±18.2 g/m2,p<0.001)and septal thickness(28.5±4.3mm vs.22.1±4.3mm,p<0.001)were significantly higher in the severe LV remodeling group.Pearson correlation analysis showed that LVRI was positively correlated with septal thickness(r=0.63,p<0.001)and LVMI(r=0.81,p<0.001),and negatively correlated with MVD(r=-0.32,p=0.026)and left ventricular ejection fraction(LVEF)(r=-0.35,p=0.02).Subgroup analysis showed that MVD in patients with mild septal hypertrophy was significantly higher than that in patients with severe septal hypertrophy(524.4±220.5/mm2 vs.379.8 ± 117.4/mm2,p=0.007),and MVD in patients with mild LVMI was also higher than that in patients with severe LVMI(517.7 ± 234.0/mm2 vs.433.3 ± 131.0/mm2,p=0.12).In addition,we found that MVD was negatively correlated with LVMI(r=-0.31,p=0.03)and septal thickness(r=-0.42,p=0.003).In a multivariable logistic regression analysis,when adjusting for septal thickness and LVEF,MVD infarction and LVMI were independent determinant of severe LV remodeling in HCM patients(or=0.99,p=0.03 and or=1.1,p=0.03).Conclusion:MVD was lower and LVMI was higher in HCM patients with severe LV remodeling,LVRI was positively correlated with LVMI and negatively correlated with MVD.We suggested that MVD infarction and increased LVMI may contribute to severe LV remodeling in HCM patients.The third part:The impact of left ventricular remodeling on atrial fibrillation in hypertrophic cardiomyopathyObjective:Atrial fibrillation(AF)is the most common complication in hypertrophic cardiomyopathy(HCM).The mechanisms of AF is associated with left atrial(LA)structural remodeling in HCM patients.However,the impact of left ventricular(LV)remodeling on the presence of AF in HCM patients has not been evaluated yet.We sought to investigate effect of LV remodeling on the presence of AF assessed by cardiovascular magnetic resonance(CMR)in HCM patients.Methods:A total of 394 HCM patients were enrolled into this study,including HOCM patients(n=293)and HNCM patients(n=101).Patients were divided into HCM with AF(50)and HCM without AF(n=344).Data were collected from hospital records.Left ventricular remodeling index(LVRI)was calculated as the ratio between left ventricular mass(LVM)and left ventricular end diastolic volume(LVEDV)by CMR.Results:LA diameter and LVRI were significantly higher in HCM patients with AF than that of HCM patients without AF(46.6±7.4 mm versus 39.9±8,0 mm,p<0.001,and 1.46 ±0.6 g/ml versus 1.2±0.4 g/ml,p=0.002,respectively).HCM patients with AF were older than HCM patients without AF(53.6±11.7 years versus 47.7 ± 13.6 years,p=0.002).Additionally,In a multivariable logistic regression analysis,when adjusting for age and LV end diastolic mass index,LVRI and LA size remained an independent determinant of AF in HCM patients(or=4.7,p=0.001 and or=1.13,p<0.001).Conclusion:HCM patients with AF showed significantly more LA diameter,LVRI and age than HCM patients without AF.LVRI and LA size were strong independent predictor of AF in HCM,suggesting LV remodeling may contribute to the occurrence of AF in HCM patients.