| Part One Effect of Atrial Fibrillation on Long-term Clinical Outcomes in Patients With Heart Failure Receiving Cardiac Resynchronization TherapyObjectives:To assess the effect of atrial fibrillation(AF)on long-term clinical outcomes in patients receiving cardiac resynchronization therapy(CRT).Methods:A total of 258 consecutive single-center patients with CRT between January 2010 and December 2014 were retrospectively enrolled.After undergoing median 22-months follow-up,re-hospitalization due to worsening heart failure(HF)or all-cause mortality(including heart transplantation)was analyzed using Kaplan-Meier and log-rank test curves.AF was evaluated in Cox proportional-hazards regression models as an independent prognostic factor.Results:There were 42(16.3%)patients with AF which were older,higher proportion of men,left bundle branch block(LBBB)and prescribed with amiodarone,and had higher endogenous creatinine clearance rate,serum creatinine,serum uric acid,big endothelin-1,left ventricular end diastolic diameter.After the follow-up,33(12.8%)patients died,5(1.9%)underwent heart transplantation and 72(27.9%)had at least one HF readmission.Log-rank test analyses demonstrated that AF was associated with a significantly higher HF re-hospitalization(?2=6.651,p=0.010)but had no effect on all-cause mortality(?2=0.528,P=0.468).Cox univariate analysis showed that AF,LBBB,serum creatinine,big endothelin-1 and left ventricular end diastolic diameter were risk factors for HF re-hospitalization;serum creatinine,big endothelin-1 and left ventricular end diastolic diameter were risk factors for all-cause mortality.Cox multivariate analysis showed that AF was not an independent risk factor for HF re-hospitalization and all-cause mortality;while the left ventricular end diastolic diameter(hazard ratio[HR]=1.041,95%confidence interval[CI]:1.007-1.075,P=0.018)was the independent risk factor for HF re-hospitalization,left ventricular end diastolic diameter(HR=1.045,95%CI:1.001-1.091,P=0.048)and serum creatinine(HR=1.008,95%CI:1.001-1.015,P=0.035)were the independent risk factors for all-cause mortality.Conclusions:In CRT patients,although AF was associated with higher HF re-hospitalization,it was not the independent risk factor for HF re-hospitalization and all-cause mortality.Part Two Baseline Serum High Density Lipoprotein Cholesterol Level Predicts Long-term Clinical Outcomes in Patients with Heart Failure Receiving Cardiac Resynchronization TherapyObjectives:To assess the role of serum high density lipoprotein cholesterol(HDL-C)level on long-term clinical outcomes in patients receiving cardiac resynchronization therapy(CRT).Methods:A total of 357 consecutive single-center patients with CRT between January 2010 and December 2015 were retrospectively enrolled and categorized into 2 groups based on serum HDL-C level(HDL-C?1.0mmol/L?<1.0mmol/L).After the follow-up,re-hospitalization due to worsening heart failure(HF)or all-cause mortality(including heart transplantation)was analyzed using Kaplan-Meier curves and log-rank test.Serum HDL-C level was evaluated in Cox proportional-hazards regression models as an independent prognostic factor.Results:There were 168(47.1%)patients with lower HDL-C which had lower cholesterol,eGFR and proportion prescribed with spironolactone,and had higher body mass index,higher proportion of hypertension,diabetes,fasting blood glucose,alanine aminotransferase,serum creatinine,serum uric acid,high-sensitivity C reactive protein and proportion prescribed with digitalis.After the follow-up,46(12.9%)patients died,6(1.7%)underwent heart transplantation and 103(28.9%)had at least one HF readmission.Log-rank test analyses demonstrated that lower HDL-C was associated with a significantly higher HF re-hospitalization(?2=7.822,P=0.005)and all-cause mortality(?2=16.817,P=0.000).Cox analysis showed that lower HDL-C was the independent risk factor for HF re-hospitalization(hazard ratio[HR]=0.407,95%confidence interval[CI]:0.178-0.933,P=0.096)and all-cause mortality(HR=0.256,95%[CI]:0.076-0.865,P=0.028).Conclusions:In CRT patients,baseline serum HDL-C level was associated with clinical condition.HDL-C level was the independent risk factor for HF re-hospitalization and all-cause mortality.Part Three Establishment of Mitral Regurgitation Model in Swine and Hydrogen Sulfide System Changes in This ModelObjectives:To establish a mitral regurgitation model in swine and explore the change of hydrogen sulfide(H2S)system in this chronic heart failure model.Methods:Miniature pigs were randomly divided into two groups,the control group(n=6)and mitral regurgitation group(n=6).Chronic heart failure models in swine were established by pulling and destroying the mitral chordal through small incision off-pump surgery.After 6 months,echocardiography,in vivo hemodynamics and pathology examination were performed to evaluate the changes of left ventricular structure and function in this animal model.Molecular biology techniques were used to detect protein and mRNA level changes of type ? collagen,type ? collagen,cystathionine-?-synthase(CBS)and cystathionine-?-lyase(CSE).Results:At 6 months after surgery,the LVESV and LVEDV were significantly increased[(18.50±2.88)ml vs(10.50±0.99)ml,P<0.05;(87.50±12.12)ml vs(42.33± 2.04)ml,P<0.01],left ventricle systolic pressure were significantly decreased[(86.66 ± 5.60)mmHg vs.(117.70 ± 5.49)mmHg,P<0.01]in mitral regurgitation group as compared to control group,while left ventricle ejection fraction was similar between the two groups[(78.67±1.87)%vs(75.33±1.87)%,P>0.05].Pathologic evaluation showed disruption of mitral chordal of posterior mitral valve,thickened and curved valve with significant degenerative changes.HE stained myocardial slides revealed cardiomyocyte injury and increased extracellular collagen in left ventricular tissue in mitral value regurgitation group.Plasma H2S level was significantly decreased[(27.48 ± 2.78)?mol/L vs(37.87±3.55)?mol/L,P=0.044],serum NT-proBNP level was significantly increased[(2132.00±212.30)?g/L vs(456.70±40.79)?g/L,P<0.001]in mitral value regurgitation group as compared with control group.Protein and mRNA expressions of collagen type ? and collagen type ? were significantly upregulated,CSE and CBS were significantly down-regulated in mitral value regurgitation group as compared with control group.Conclusions:The downregulation of H2S synthesis system may be involved in the development of myocardial remodeling and heart failure caused by mitral regurgitation in this swine model. |
PDF Full Text Request