[Pathological study on the relationship between nucleic acid oxidative stress and heart failure with preserved ejection fraction in patients aged over 85 years].

Objective: To investigate the level of nucleic acid oxidation in myocardial tissue of patients aged over 85 with heart failure with preserved ejection fraction (HFpEF) and the correlation with myocardial amyloid deposition. Methods: This was a retrospective case-control study. Data of patients≥85 years old who underwent systematic pathological autopsy in Beijing Hospital from 2003 to 2017 were retrospectively collected. Twenty-six patients were included in the HFpEF group and 13 age-and sex-matched patients who had not been diagnosed with heart failure and died of non-cardiovascular diseases served as the control group. The left ventricular myocardium slices of both groups were semi-quantitatively analyzed using immunohistochemical staining of 8-oxidized guanine riboside (8-oxo-G) and 8-oxidized guanine deoxyriboside (8-oxo-dG) to evaluate the oxidation of RNA and DNA in cardiomyocytes. Using the median of the mean absorbance value of 8-oxo-G immunohistochemical staining as the cut-off value, patients were divided into high-absorbance group and low-absorbance group. Congo red staining was used to compare myocardial amyloid deposition between the two groups. Results: The mean age of patients in HFpEF group was (91.8±3.7) years, 24 (92.3%) were males. The mean age of patients in control group was (91.7±3.7) years old, 11 (84.6%) were males. The median mean optical absorbance value of 8-oxo-G immunohistochemical staining of myocardium was significantly higher in HFpEF patients than in control group (0.313 8 (0.302 2, 0.340 6) vs. 0.289 2 (0.276 7, 0.299 4), Z=-3.245, P=0.001). The median mean absorbance value of 8-oxo-dG immunohistochemical staining of myocardial tissue was similar between the two groups (0.300 0 (0.290 0, 0.322 5) vs. 0.300 0 (0.290 0, 0.320 0), Z=-0.454, P=0.661). Proportion of patients with moderate and severe cardiac amyloid deposition was significantly higher in the high-absorbance group than in the low-absorbance group ((85.0%, 17/20) vs. (31.6%, 6/19), P=0.001). Conclusion: The RNA oxidation degree of myocardium in HFpEF patients is higher than that in elderly people without heart failure. Degree of myocardial amyloid deposits is higher in patients with high levels of RNA oxidation.

[Clinical characteristics of heart failure with recovered ejection fraction].

Objective: To summarize the clinical characteristics of heart failure patients with recovered ejection fraction (HFrecEF) and identify variables capable of predicting left ventricular ejection fraction (LVEF) recovery. Methods: This case control study included patients with heart failure, who admitted to Department of Cardiology of Beijing Hospital from January 1, 2009 to December 31, 2017. The patients were divided into 3 groups based on the baseline LVEF and changes of LVEF: heart failure with reduced ejection fraction (HFrEF, baseline LVEF≤40%, follow-up LVEF≤40% or follow-up LVEF>40% but LVEF increase<10% from baseline), HFrecEF(baseline LVEF≤40%, follow-up LVEF>40% and increase≥10% from baseline), and heart failure with preserved ejection fraction (HFpEF, baseline LVEF>40%). Clinical data were collected and endpoint events (all-cause death, cardiovascular death and sudden death) were recorded. The Log-rank test was used to evaluate the differences of terminal events in different groups, and Kaplan-Meier survival analysis was performed. Logistic regression equation was used to identify prognostic factors of HFrecEF. Results: A total of 310 patients with heart failure were included. There were 91(29.4%) HFrEF patients, 38(12.3%) HFrecEF patients and 181(58.4%) HFpEF patients. Compared with HFrEF patients and HFpEF patients, HFrecEF patients were featured by younger age, more likely to be female, higher systolic blood pressure, diastolic blood pressure and resting heart rate (all P<0.05). Dilated cardiomyopathies were more common, while old myocardial infarctions were less common in HFrecEF (both P<0.05). During a median follow-up of 36.7(18.0, 63.9) months, Kaplan-Meier survival analysis found that HFrecEF patients had the lowest all-cause mortality (Log-rank P=0.047, HFrecEF vs. HFpEF P=0.017, HFrecEF vs. HFrEF P=0.016, and HFpEF vs. HFrEF P=0.782).The cardiovascular mortality ranged from low to high was in HFrecEF patients, HFpEF patients, and HFrEF patients (Log-rank P<0.001, HFrecEF vs. HFpEF P=0.029, HFrecEF vs. HFrEF P<0.001, HFrEF vs. HFpEF P=0.005). Sudden death rate was similar among the three groups (Log-rank P=0.520). Logistic regression analysis showed that left ventricular end-diastolic diameter (LVEDD)≤55 mm (OR=5.922, 95%CI 1.685-20.812, P=0.006), higher diastolic blood pressure (OR=1.058, 95%CI 1.017-1.100, P=0.005), faster resting heart rate (OR=1.042, 95%CI 1.006-1.080, P=0.024), absence of old myocardial infarction (OR=5.343, 95%CI 1.731-16.488, P=0.004) were independent prognostic factors of LVEF recovery after clinical treatment. Conclusions: Patients with HFrecEF are associated with a better prognosis as compared to patients with HFrEF and HFpEF. LVEDD≤55 mm, higher diastolic blood pressure, faster heart rate,and absence of old myocardial infarction are independent prognostic factors of LVEF recovery after clinical treatment.

[Myocardial amyloid deposition in patients aged over 85 years with heart failure and preserved ejection fraction].

Objective: To determine the frequency and extent of left ventricular amyloid deposition in patients aged over 85 years with heart failure and preserved ejection fraction (HFpEF). Methods: A total of 43 patients aged 85 to 100 years old were enrolled in this study based on the autopsy database of Beijing Hospital from February 1, 2003 to October 31, 2016. The frequency and extent of left ventricular amyloid deposition and myocardial fibrosis were determined in left ventricular specimens from patients with antemortem diagnosis of HFpEF without clinically apparent amyloid (n=28) and from control subjects (n=15) post Congo red staining and Masson's trichrome staining. Kappa test was used to evaluate the consistency of the myocardial amyloidosis and fibrosis. Results: The heart weight of the patients in HFpEF group and in control group were similar((452.7±107.7)g vs. (415.0±70.8)g, t=-1.218, P=0.23)). Positive Congo-red staining was found in 24 examples (24/28) in HFpEF group and 5 examples (5/15) in the control group; severe amyloid deposition was found in 7 examples (7/28) in HFpEF group, but not in the control group. Amyloid deposition was more severe in HFpEF group than in control group (χ(2)=12.205, P<0.01). Masson's trichrome staining evidenced moderate to severe fibrosis in 19 cases (19/28) in HFpEF group and 8 cases (8/15) in control group (χ(2)=1.019, P=0.35). A consistent evaluation of the degree of myocardial fibrosis and the degree of myocardial amyloid deposition in all selected participants was performed and results showed that these two parameters were not consistent (Kappa value=0.2, P=0.820). Conclusion: Amyloid deposition is common in the elderly patients with heart failure and preserved ejection fraction, suggesting that myocardial amyloidosis may be related to the development of HFpEF. There is no significant correlation between myocardial amyloidosis and myocardial fibrosis in this cohort.