Fifteen-year mortality and prognostic factors in patients with dilated cardiomyopathy: persistent standardized application of drug therapy and strengthened management may bring about encouraging change in an aging society.

BACKGROUND: There is scarce data on the long-term mortality and associated prognostic factors in patients with dilated cardiomyopathy (DCM). The study aimed to investigate the all-cause mortality up to 15 years (mean 7.9 ± 5.7 years) in such patients, and the independent prognostic factors influencing their long-term mortality. METHODS: One hundred and sixty-six consecutive patients with DCM were prospectively enrolled from 2002 to 2003. The mean age of patients was 59.5 ± 10.4 years, and approximately 57% were male. They were followed up by telephone or outpatient visit at least every three months until 2019 or all-cause death occurred. Predictors of mortality were identified using multivariate logistic regression analysis. RESULTS: During the 15 years of follow-up, five patients were lost to follow-up, and the complete data records of 161 patients were included in the analysis. Patients were treated with angiotensin-converting-enzyme inhibitors (ACEI) or angiotensin-receptor blocker (ARB), ß-blockers, mineralocorticoid receptor antagonist (MRA), diuretics and digitalis from 2002 to 2004, and maintained at the maximum tolerated doses between 2004 and 2019. Our safety targets to maintain heart rate and blood pressure at 60-80 beats/min and 90-120/60-80 mmHg, respectively. All-cause mortality in the first five years was 55.9%. The independent risk factors for the 5-year mortality were age ≥ 70 years old (OR = 5.45, P = 0.006), systolic blood pressure (SBP) > 120 mmHg (OR = 3.63, P = 0.004), 6-minute walk distance (6MWD) < 450 m (OR = 3.84, P = 0.001). 15-year all-cause mortality was 65.8%. The independent risk factors for 15-year mortality were age ≥ 70 years old (OR = 16.07, P = 0.009), LVEF ≤ 35% (OR = 5.69, P = 0.003), and SBP > 120 mmHg (OR = 9.56, P < 0.001). CONCLUSIONS: This study was the first to demonstrate the 15-year survival rate of 34% in DCM patients. The DCM patients' first five-year all-cause mortality decreased significantly after continuous standardized treatment and intensive management. The mortality then plateaued in the following 10 years. Age ≥ 70 years, LVEF ≤ 35%, and SBP > 120 mmHg were independent predictors of 15-year all-cause mortality.

Clinical value of detecting autoantibodies against ß1-, ß2,- and α1-adrenergic receptors in carvedilol treatment of patients with heart failure.

OBJECTIVE: To determine the possible association of anti-ß1-adrenergic receptors (anti-ß1-AR), anti-ß2-AR and anti-α1-AR with carvedilol treatment in patients with heart failure (HF). METHODS: A total of 267 HF patients were prospectively enrolled. Blood samples were measured by an enzyme-linked immunosorbent assay. All of the patients received carvedilol for their HF. Each patient was followed up for six months and their cardiac function was measured. RESULTS: The final analysis encompassed 137 patients comprising 65 patients with three autoantibodies (positive group) and 72 patients without all three autoantibodies but with one or two autoantibodies (negative group). The frequency and geometric mean titer of anti-ß1-AR, anti-ß2-AR, and anti-α1-AR were significantly lower in the group without all three autoantibodies after six months of carvedilol treatment (all P < 0.01; from 100% to 57%, 50%, and 49%, respectively; and from 1: 118, 1: 138, and 1: 130 to 1: 72, 1: 61, and 1: 67, respectively). Furthermore, 28 patients in the positive group demonstrated complete ablation of autoantibodies. In addition, left ventricular remodelling and function was significantly improved by the use of carvedilol combined with the standard treatment regime for six months in the positive group (P < 0.01) when compared to the negative group (P < 0.05). CONCLUSIONS: Carvedilol treatment significantly decreases frequency and geometric mean titer in patients with all three autoantibodies, even up to complete ablation, and significantly improved cardiac function and remodelling. The effect of carvedilol is probably correlated to the presence of all three autoantibodies.

A severity index study of long-term prognosis in patients with chronic heart failure.

AIMS: The present study describes the derivation and validation of the Chronic Heart Failure Severity Index (CHFSI). MAIN METHODS: The CHFSI was derived using data obtained from a single-center prospective cohort study (2000-2014) that enrolled 756 patients. Logistic regression was used to identify independent predictors of mortality and quality of life over a 15-year follow-up period. KEY FINDINGS: The score was validated at the first 5-year (n = 644), second 5-year (n = 364), and third 5-year (n = 262). Independent predictors of mortality were older age (OR = 2.04, P < 0.001), etiology score (OR = 2.61, P < 0.001), faster heart rate (OR = 1.46, P = 0.027), higher systolic blood pressure (OR = 2.35, P < 0.001), and left ventricular ejection fraction ≤45% (OR = 1.97, P = 0.018). The derived CHFSI predicted the mortality, and the AUC for the logistic model was 0.78 (95% confidence interval = 0.74-0.81, P < 0.001). Based on the logistic model, an integer scoring system was derived. Patients were classified into three groups: low risk (0-7 points), intermediate risk (8-11 points) and high risk (≥12 points) groups. The cumulative mortality for 15 years was 45.5% (125/275), 84.0% (204/243), and 100% (99/99), respectively (P < 0.001). The 6-min walk test revealed a significant difference in quality of life among patients in the low, medium and high risk groups (all, P < 0.0001). SIGNIFICANCE: The CHFSI is a very useful clinical predictive tool that identifies patients at risk of future mortality and their quality of life across healthcare systems.

Autoantibodies against ß1-adrenergic receptor: response to induction therapy with bortezomib-containing regimens for multiple myeloma patients.

This study aims to investigate the predictive value of pre-chemotherapy ß1R-AABs by evaluating the response of newly diagnosed symptomatic multiple myeloma (MM) patients to their treatment with a bortezomib-containing regimen. Forty-five de novo MM patients and 50 normal controls (NCs) were prospectively enrolled in this study. Serum titers of ß1R-AABs were detected by ELISA. These 45 MM patients were divided into two groups (positive and negative groups) according to their ß1R-AABs. Follow-up examinations were performed on these patients during chemotherapy induction. The final analysis covered all 45 MM patients, including 19 patients who were positive for MM and 26 patients who were negative for MM. Multivariate analysis revealed that pre-chemotherapy ß1R-AABs are possibly independent predictors for less than very good partial response (VGPR) after the bortezomib-containing regimen treatment (odds ratio: 5.967, 95% confidence interval: 1.513-23.531; p = .011). This study demonstrates for the first time that the presence of ß1R-AABs is associated with MM. Pre-chemotherapy ß1R-AABs are independent predictors for less than VGPR in de novo MM patients after the bortezomib-containing regimen was administrated. Bortezomib might not significantly give rise to cardiac impairment in MM patients.

Whole exome sequencing identifies a KCNJ12 mutation as a cause of familial dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is characterized by left ventricular dilation, and is associated with systolic dysfunction and increased action potential duration. Approximately 50% of DCM cases are caused by inherited gene mutations with genetic and phenotypic heterogeneity. Next generation sequencing may be useful in screening unknown mutations in such cases.A family was identified with DCM, in which the affected family members developed heart failure, arrhythmia, and sudden death. Probands and 4 affected family members underwent whole exome sequencing (WES), bioinformatics methods, and gene annotation to identify potentially causative variants. The Sanger sequencing method was used to verify the candidate mutation.WES yielded 2,238,831 variations. KCNJ12 (p.Glu334del) was identified as a candidate mutation, and the heterozygous mutation was verified by Sanger sequencing.Our study emphasizes the application of WES in identifying causative mutations in DCM. This report is the first to describe the KCNJ12 gene as a cause of DCM in patients.

Adipositas cordis sudden death: a series of 79 patients.

BACKGROUND: The principal aim of this study was to investigate the clinical, epidemiological and pathologic features for a series of 79 cases of adipositas cordis sudden death. METHODS: We analyzed clinical and autopsy pathological features of 79 patients (43 females and 36 males) with adipositas cordis who died suddenly between 1975 and 2010. Data were extracted from China National Knowledge Infrastructure and Wan Fang Database. RESULTS: The average age of the 79 cases was 36.6 ± 1.4 years old ranging from 13 to 68, and 82.3% of them were between 20 to 50 years old. Sudden death was the first symptom in 62 (78.5%) of the cases, only 17 (21.5%) had a history of chest distress or dyspnea. More than 4/5 (87.3%) of the cases had no any past medical history. At autopsy, the subjects' heart weight was mild or moderately increased, and a large amount of fatty tissues but not fibrous or fibro fatty was accumulated underneath the epicardium and infiltrated toward the right ventricle walls, and even infiltrated to all layers of the cardiac walls. Regional epidemiological data showed that about 80% of cases were living north and only 20% were living south of the Yangzi River, but not any familial heredity. CONCLUSION: Adipositas cordis sudden death is a very severe disease, it occurs mostly in youth and middle-aged and sudden death is often the first symptom. There is a significant regional difference, but not any genetic correlation. The pathogenesis of adipositas cordis sudden death should to be further explored.

Probing the chemical functionalization of single-walled carbon nanotubes with multiple carbon ad-dimer defects.

Drying-tube-shaped single-walled carbon nanotubes (SWCNTs) with multiple carbon ad-dimer (CD) defects are obtained from armchair (n,n,m) SWCNTs (n=4, 5, 6, 7, 8; m=7, 13). According to the isolated-pentagon rule (IPR) the drying-tube-shaped SWCNTs are unstable non-IPR species, and their hydrogenated, fluorinated, and chlorinated derivatives are investigated. Interestingly, chemisorptions of hydrogen, fluorine, and chlorine atoms on the drying tube-shaped SWCNTs are exothermic processes. Compared to the reaction energies for binding of H, F, and Cl atoms to perfect and Stone-Wales-defective armchair (5,5) nanotubes, binding of F with the multiply CD defective SWCNTs is stronger than with perfect and Stone-Wales-defective nanotubes. The reaction energy for per F(2) addition is between 85 and 88 kcal mol(-1) more negative than that per H(2) addition. Electronic structure analysis of their energy gaps shows that the CD defects have a tendency to decrease the energy gap from 1.98-2.52 to 0.80-1.17 eV. After hydrogenation, fluorination, and chlorination, the energy gaps of the drying-tube-shaped SWCNTs with multiple CD defects are substantially increased to 1.65-3.85 eV. Furthermore, analyses of thermodynamic stability and nucleus-independent chemical shifts (NICS) are performed to analyze the stability of these molecules.

catena-Poly[[[aqua-silver(I)]-µ-4,4'-bipyridine-κN:N'] 4-amino-benzoate nitrate hydrate].

In the structure of the title compound, 2[Ag(C(10)H(8)N(2))(H(2)O)](C(7)H(6)NO(2))(NO(3))·H(2)O, the Ag(I) atom is three-coordinated in a T-shaped configuration by two N atoms from two symmetry-related 4,4'-bipyridine (bipy) ligands at short distances and by one water O atom at a longer distance. Each bipy ligand bridges two neighbouring Ag(I) atoms, forming a chain structure extending parallel to [101]. The complete 4-amino-benzoate anion, the nitrate anion and the uncoordinated water mol-ecule are located on mirror planes: together with the coordinated water mol-ecule, they form N-H⋯O, O-H⋯O and O-H⋯N hydrogen bonds, stabilizing the crystal structure.

Aqua-(3-methyl-isoquinoline-κN)silver(I) 4-amino-benzene-sulfonate.

In the title compound, [Ag(C(10)H(9)N)(H(2)O)](C(6)H(6)NO(3)S), the Ag(I) atom is two-coordinated by one N atom from a 3-methyl-isoquinoline ligand and one water mol-ecule. The 4-amino-benzene-sulfonate counter-anion does not show any bonding inter-actions with the Ag(I) atom. The compound exhibits a three-dimensional supra-molecular structure constructed by hydrogen bonds. Adjacent isoquinoline groups form π-π inter-actions, with a centroid-centroid distance of 3.54 (1) Å. The crystal studied was an inversion twin.

[Simultaneous determination of total flavone and total saponin in Gynostemma pentaphyllum by signal multiplier spectrophotometry].

Important chemical constituents analysis for the total flavone and total saponin in Gynostemma pentaphyllum is described. The colour reactions of flavones and saponines with vanillin-perchloric acid in acetic acid produced the good absorptions at 451 and 547 nm, but the absorption peaks too overlapped to be determined simultaneously. A new method for the total flavone and the total saponin in Gynostemma pentaphyllum to be determined by signal multiplier spectrophotometry simultaneously without any preliminary separation was proposed. For quantitative analysis, the rutinum as a standard of the total flavone and the ginsenoside Rb1 as standard of the total saponin were applied. The experiment results showed that the regression equations of concentration and deltaA were obtained: deltaAflavone = 0.0133+4.417 0Cflavone, relation coefficient rflavone = 0.9994, and the total flavone concentrations were in 0-0. 16 microg x mI(-1) with deltaA obeying linear relation; deltaAsaporin = 2.775 5Csaponin -0.8881 x 10(-2), relation coefficient rsaponin = 0.9991, and the total saponin concentrations were in 0-0.30 microg x mL(-1) with deltaA obeying linear relation respectively. The recovery ratio was 104.0%-113.0% and 86.8%-94.6% respectively. The RSDflavone was less than 0.58% (n = 9) and RSDsaponin was less than 0. 35% (n=9) respectively. The proposed method is simple, rapid accurate and feasible.

[Quantitative determination of total flavonoids in sea-buckthorn fruit juice by three wavelength spectrophotometry].

Numerous studies dealing with the quantitative determination of total flavonoids in sea-buckthorn fruit juice by spectrophotometry are presented. The flavonoids in sea-buckthorn fruit juice and aluminate produce stable complex whose absorption occurred at longer wavelength. To determine the total flavonoids in sea-buckthorn fruit juice by traditional spectrophotometry method, baseline shift and asymmetric absorption peak occurred on the absorption curve. Quantitative determination of flavonoids in sea-buckthorn fruit juice by three wavelength spectrophotometry method can eliminate the absorbance error caused interfering components in turbid solution and the scattering effect. Background changing with the concentration change and asymmetric absorption peak problems can also be solved. The regression equation of concentration vs deltaA was obtained: deltaA = - 0.00703 + 0.00048c with a relation coefficient gamma = 0.9991. The experimental results demostrate the total flavonoids concentrations in 0-800 microg x mL(-1) with deltaA obeying linear relation when the absorbance was measured at wavelength lambda1 = 495 nm, lambda2 = 415 nm and lambda3 = 368 nm. The recovery is 97.0%-101.0% and the coefficient of variation is 0.058% (n = 9). The method is more advantageous than tranditional spectrophotometry method.

[Determination of catechin by three wavelength spectrophotometry and the antioxidation effect in natural teas and their beverages].

OBJECTIVE: To determine the catechin and the antioxidation effect in natural tea and their beverages. METHODS: Three wavelength spectrophotometry can eliminate the absorbance error of interfering components, turbid solution and the scattering effect. Background changedwith concentration changed and asymmetric absorption peak problems can be solved, and the antioxidation effect of natural tea and their beverages was studied by the flow-injection chemiluminescence. RESULTS: The recovery is 95.2%-102.0% and the coefficient of variation is 1.05%. Conclusion The results have shown that natural tea and their beverages are abundant in the catechin compounds and strong antioxidative effect.

[Determination of germanium in A. arborescens by spectrophotometric method].

A new spectrophotometric method for the determination of germanium in A. arborescens was developed. The method was based on the fact that germanium forms a stable complex with phenylfluorone in the acidified solution with CTMAB as solubilization agent. The maximum absorption of association complex is at 530 nm, the linear range is 0.1-0.7 microg x mL(-1), the regression equation is A = 0.0817 + 0.8677c530, (microg x mL(-1)) the correlation coefficient r=0.9177, and the limit of detection is 0.65 microg x mL(-1). The leaves and stems of A. arborescens were determined by the proposed method. The total amount of germanium is 697.0-1219.5 ng x g(-1), and the content of organic Ge is 95.45%-98.99%. The method is suitable for the analysis of samples which contain both organic Ge and inorganic Ge.

[Direct resolution of clenbuterol enantiomers with amide derivative as chiral stationary phase].

A simple and rapid high performance liquid chromatographic method has been developed for the direct resolution of clenbuterol enantiomers. The method involved the use of an amide type chiral stationary phase(CSP) made of (R)-1-naphthylglycine and 3,5-dinitrobenzoic acid known as the Chirex 3005 column. The effects of different contents of n-hexane, 1,2-dichloroethane and methanol in mobile phase on the chiral separation are discussed. The effects of column temperature and flow rate of mobile phase were also studied. The separation factor obtained was 1.32 and the resolution factor was 1.81 when using the optimized mobile phase composed of n-hexane-1,2-dichloroethane-methanol (54:38:8, volume ratio) at 17 degrees C and 1.0 mL/min. The mechanism of separation is also discussed.