Omega-3 fatty acid blood levels are inversely associated with cardiometabolic risk factors in HFpEF patients: the Aldo-DHF randomized controlled trial.

OBJECTIVES: To evaluate associations of omega-3 fatty acid (O3-FA) blood levels with cardiometabolic risk markers, functional capacity and cardiac function/morphology in patients with heart failure with preserved ejection fraction (HFpEF). BACKGROUND: O3-FA have been linked to reduced risk for HF and associated phenotypic traits in experimental/clinical studies. METHODS: This is a cross-sectional analysis of data from the Aldo-DHF-RCT. From 422 patients, the omega-3-index (O3I = EPA + DHA) was analyzed at baseline in n = 404 using the HS-Omega-3-Index® methodology. Patient characteristics were; 67 ± 8 years, 53% female, NYHA II/III (87/13%), ejection fraction ≥ 50%, E/e' 7.1 ± 1.5; median NT-proBNP 158 ng/L (IQR 82-298). Pearson's correlation coefficient and multiple linear regression analyses, using sex and age as covariates, were used to describe associations of the O3I with metabolic phenotype, functional capacity, echocardiographic markers for LVDF, and neurohumoral activation at baseline/12 months. RESULTS: The O3I was below (< 8%), within (8-11%), and higher (> 11%) than the target range in 374 (93%), 29 (7%), and 1 (0.2%) patients, respectively. Mean O3I was 5.7 ± 1.7%. The O3I was inversely associated with HbA1c (r = - 0.139, p = 0.006), triglycerides-to-HDL-C ratio (r = - 0.12, p = 0.017), triglycerides (r = - 0.117, p = 0.02), non-HDL-C (r = - 0.101, p = 0.044), body-mass-index (r = - 0.149, p = 0.003), waist circumference (r = - 0.121, p = 0.015), waist-to-height ratio (r = - 0.141, p = 0.005), and positively associated with submaximal aerobic capacity (r = 0.113, p = 0.023) and LVEF (r = 0.211, p < 0.001) at baseline. Higher O3I at baseline was predictive of submaximal aerobic capacity (ß = 15.614, p < 0,001), maximal aerobic capacity (ß = 0.399, p = 0.005) and LVEF (ß = 0.698, p = 0.007) at 12 months. CONCLUSIONS: Higher O3I was associated with a more favorable cardiometabolic risk profile and predictive of higher submaximal/maximal aerobic capacity and lower BMI/truncal adiposity in HFpEF patients. Omega-3 fatty acid blood levels are inversely associated with cardiometabolic risk factors in HFpEF patients. Higher O3I was associated with a more favorable cardiometabolic risk profile and aerobic capacity (left) but did not correlate with echocardiographic markers for left ventricular diastolic function or neurohumoral activation (right). An O3I-driven intervention trial might be warranted to answer the question whether O3-FA in therapeutic doses (with the target O3I 8-11%) impact on echocardiographic markers for left ventricular diastolic function and neurohumoral activation in patients with HFpEF. This figure contains modified images from Servier Medical Art ( https://smart.servier.com ) licensed by a Creative Commons Attribution 3.0 Unported License.

Coenzyme Q10 in the Treatment of Heart Failure with Preserved Ejection Fraction: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is common in elderly people and is increasing in prevalence. No specific treatment for this condition exists. Coenzyme Q10 (CoQ10) is an essential cofactor for energy production, with reduced levels being noted in HF. Previous studies have suggested a possible role for CoQ10 in the treatment of HF. This study examined the effect of CoQ10 supplementation on diastolic function in HFpEF patients. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled trial including patients aged > 55 years presenting with New York Heart Association class II-IV heart failure symptoms and left ventricular ejection fraction > 50%, with impaired diastolic function. Echocardiography and levels of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) were performed at baseline and following 4 months of CoQ10 or placebo supplementation. RESULTS: A total of 39 patients were enrolled-19 in the CoQ10 group and 20 in the placebo group. Baseline clinical characteristics were similar between groups, while compliance was high and also similar between the CoQ10 and placebo groups. There was no significant effect of treatment on indices of diastolic function (difference in the lateral E/e' ratio: -0.86 ± 6.57 in the CoQ10 group, +0.18 ± 3.76 in the placebo group; p = 0.561) or on serum NT-proBNP levels (- 72 pg/mL vs. - 42 pg/mL; p = 0.195). CONCLUSIONS: In this pilot trial in elderly patients with HFpEF, treatment with CoQ10 did not significantly affect echocardiographic indices of diastolic function and serum NT-proBNP levels. TRIAL REGISTRATION: This trial was registered in the US National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier: NCT02779634).

Improvement of Shen'ge formula on heart function in diastolic heart failure: A protocol for randomized, double-blind, placebo-controlled clinical study.

INTRODUCTION: Diastolic heart failure (DHF) is an important pathological type of heart failure, that involves multiple organ dysfunction and multiple complications. The prevalence of DHF is high, and effective treatments are lacking. Chinese herbs are an alternative therapy for DHF. Shen'ge formula (SGF) is a classical formula from which patients can benefit, but convincing evidence of its efficacy is lacking. Therefore, we designed this randomized controlled trial protocol. METHODS/DESIGN: This randomized, double-blind, placebo-controlled clinical trial will evaluate the efficacy and safety of SGF in the treatment of DHF. A total of 130 patients with DHF will be enrolled in the trial and treated with SGF granules or placebo for 12 weeks and followed up for 12 weeks. The primary outcome measurement will be to changes in plasma N-terminal brain natriuretic peptide precursor before versus after treatment, while the second primary outcome measurement will be changes in heart function before versus after treatment and the 12-week follow-up period. It will also include echocardiography, a cardiopulmonary exercise test, cardiac function grading, traditional Chinese medicine syndrome score, and the Minnesota Heart Failure Quality of Life Scale. Adverse events will be evaluated throughout the trial. DISCUSSION: The results of this trial will demonstrate whether SGF could alleviate symptoms, improve cardiac function, reduce readmission rates, and improve quality of life of patients with DHF. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR2000036533, registered on August 24, 2020.

Randomized controlled clinical study on Yiqi Liangxue Shengji prescription for intervention cardiac function of acute myocardial infarction with ischemia-reperfusion injury.

INTRODUCTION: The morbidity and mortality of acute myocardial infarction patients still remains high after percutaneous coronary intervention (PCI). Myocardial ischemia-reperfusion (MIR) injury is one of the important reasons. Although the phenomenon of MIR injury can paradoxically reduce the beneficial effects of myocardial reperfusion, there currently remains no effective therapeutic agent for preventing MIR. Previous studies have shown that Yiqi Liangxue Shengji prescription (YLS) is effective in improving clinical symptoms and ameliorating the major adverse cardiovascular events of coronary heart disease patients undergoing PCI. This study aims to evaluate the effectiveness and safety of YLS in patients with acute myocardial infarction (AMI) after PCI. METHODS: This study is a randomized, double-blinded, placebo-controlled, single-central clinical trial. A total of 140 participants are randomly allocated to 2 groups: the intervention group and the placebo group. Based on routine medications, the intervention group will be treated with YLS and the placebo group will be treated with YLS placebo. All participants will receive a 8-week treatment and then be followed up for another 12 months. The primary outcome measures are N terminal pro B type natriuretic peptide (NT-proBNP) and left ventricular ejection fraction. Secondary outcomes are plasma levels of microRNA-145, plasma cardiac enzyme, and Troponin I levels in blood samples, changes in ST-segment in ECG, Seattle Angina Questionnaire, the efficacy of angina symptoms, and occurrence of major adverse cardiac events. All the data will be recorded in case report forms and analyzed by SPSS V.17.0. DISCUSSION: The trial will investigate whether the postoperative administration of YLS in patients with AMI after PCI will improve cardiac function. And it explores microRNAs (miRNA)-145 as detection of blood-based biomarkers for AMI by evaluating the relation between miRNAs in plasma and cardiac function. TRIAL REGISTRATION: Chinese Clinical Trials Registry identifier ChiCTR2000038816. Registered on October 10, 2020.

Clinical Characteristics and Outcomes of Patients With Heart Failure With Reduced Ejection Fraction and Chronic Obstructive Pulmonary Disease: Insights From PARADIGM-HF.

Background Chronic obstructive pulmonary disease (COPD) is a common comorbidity in heart failure with reduced ejection fraction, associated with undertreatment and worse outcomes. New treatments for heart failure with reduced ejection fraction may be particularly important in patients with concomitant COPD. Methods and Results We examined outcomes in 8399 patients with heart failure with reduced ejection fraction, according to COPD status, in the PARADIGM-HF (Prospective Comparison of Angiotensin Receptor Blocker-Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. Cox regression models were used to compare COPD versus non-COPD subgroups and the effects of sacubitril/valsartan versus enalapril. Patients with COPD (n=1080, 12.9%) were older than patients without COPD (mean 67 versus 63 years; P<0.001), with similar left ventricular ejection fraction (29.9% versus 29.4%), but higher NT-proBNP (N-terminal pro-B-type natriuretic peptide; median, 1741 pg/mL versus 1591 pg/mL; P=0.01), worse functional class (New York Heart Association III/IV 37% versus 23%; P<0.001) and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (73 versus 81; P<0.001), and more congestion and comorbidity. Medical therapy was similar in patients with and without COPD except for beta-blockade (87% versus 94%; P<0.001) and diuretics (85% versus 80%; P<0.001). After multivariable adjustment, COPD was associated with higher risks of heart failure hospitalization (hazard ratio [HR], 1.32; 95% CI, 1.13-1.54), and the composite of cardiovascular death or heart failure hospitalization (HR, 1.18; 95% CI, 1.05-1.34), but not cardiovascular death (HR, 1.10; 95% CI, 0.94-1.30), or all-cause mortality (HR, 1.14; 95% CI, 0.99-1.31). COPD was also associated with higher risk of all cardiovascular hospitalization (HR, 1.17; 95% CI, 1.05-1.31) and noncardiovascular hospitalization (HR, 1.45; 95% CI, 1.29-1.64). The benefit of sacubitril/valsartan over enalapril was consistent in patients with and without COPD for all end points. Conclusions In PARADIGM-HF, COPD was associated with lower use of beta-blockers and worse health status and was an independent predictor of cardiovascular and noncardiovascular hospitalization. Sacubitril/valsartan was beneficial in this high-risk subgroup. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01035255.

A retrospective study on the short-term effect of high-dose spironolactone (80 mg/d) on chronic congestive heart failure.

ABSTRACT: To explore the short-term effect of high-dose spironolactone (80 mg/d) on chronic congestive heart failure (CHF).The general clinical data of 211 patients with CHF from February 2016 to August 2019 were collected and analyzed. Patients were divided into Low-dose group (taking 40 mg/d spironolactone) and High-dose group (taking 80 mg/d spironolactone) according to the patient's previous dose of spironolactone. The changes of B-type brain natriuretic peptide (BNP), NT-pro BNP (N terminal pro B type natriuretic peptide), echocardiography, 6-minute walking test (6MWT), and comprehensive cardiac function assessment data were collected for analysis.Compared with before treatment, the blood potassium of the two groups increased significantly (P < .05), but the blood potassium did not exceed the normal range. Compared with before treatment, BNP, NT-pro BNP, LVEDD, LVEDV and NYHA grading were significantly decreased (P < .05), LVEF and 6-MWT were significantly increased (P < .05). Compared with the Low-dose group, the high-dose group BNP (117.49 ±â€Š50.32 vs 195.76 ±â€Š64.62, P < .05), NT-pro BNP (312.47 ±â€Š86.28 vs 578.47 ±â€Š76.73, P < .05), LVEDD (45.57 ±â€Š5.69 vs 51.96 ±â€Š5.41, P <.05), LVEDV (141.63 ±â€Š51.14 vs 189.85 ±â€Š62.49, P < .05) and NYHA grading (1.29 ±â€Š0.41 vs 1.57 ±â€Š0.49, P < .05) were significantly reduced, but, 6-MWT (386.57 ±â€Š69.72 vs 341.73 ±â€Š78.62, P < .05), LVEF (41.62 ±â€Š2.76 vs 36.02 ±â€Š2.18, P < .05) and total effective rate (92.68% vs 81.39%, P < .05) increased significantly.Compared with 40 mg spironolactone, 80 mg spironolactone can rapidly reduce BNP and NT-pro BNP concentration, enhance exercise tolerance, improve clinical signs and cardiac function classification, and has better efficacy.

Novel doses of sacubitril/valsartan in patients unable to tolerate traditional therapy: Effects on N-terminal pro B-type natriuretic peptide levels.

BACKGROUND: Widespread use of angiotensin receptor blocker and neprilysin inhibitor (ARNI) remains low, and many patients are unable to tolerate the medication due to hypotension at the currently recommended starting dose. HYPOTHESIS: The aim of this study is to assess if lower than standard doses of ARNI, sacubitril/valsartan (S/V), significantly reduces NT-proBNP and leads to any change in diuretic dose, serum potassium, or creatinine. METHODS: In a retrospective study of 278 patients who were started on a low dose S/V at a single medical center, 45 patients were selected for the study cohort. Patients were subcategorized to Group 1 (n = 10): very low dose S/V (half a tab of 24/26 mg BID), Group 2 (n = 10): very low dose titrated to low dose S/V, and Group 3 (n = 25): low dose S/V (24/26 mg BID). NT-proBNP, diuretic dose, serum potassium, and creatinine were compared before and after initiation of S/V. RESULTS: Among all groups, there was a significant reduction in NT-proBNP level (Group 1: p < .01, Group 2: p < .01, and Group 3: p < .001). In addition, there was a significant reduction in diuretic dose across all groups combined (furosemide 53 mg/day vs. 73 mg/day; p = .03), with 17.8% (8/45) patients being able to discontinue their diuretic completely. There was no significant change in potassium or creatinine. CONCLUSIONS: Lower than standard dose of S/V significantly reduces NT-proBNP and diuretic requirement without change in potassium or creatinine, which provides hope that patients who cannot tolerate standard doses of S/V due to hypotension may be able to receive the benefits of S/V therapy.

The efficacy of baroreflex activation therapy for heart failure: A meta-analysis of randomized controlled trials.

INTRODUCTION: The efficacy of baroreflex activation therapy for heart failure is elusive. This meta-analysis aims to evaluate the impact of baroreflex activation therapy on treatment efficacy of heart failure. METHODS: Several databases including PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases have been searched, and we include randomized controlled trials (RCTs) regarding the efficacy of baroreflex activation therapy for patients with heart failure. RESULTS: This meta-analysis includes 4 RCTs. Baroreflex activation therapy shows significantly positive impact on the quality of life score (standard mean difference SMD = -4.61; 95% confidence interval CI = -6.24 to -2.98; P < .00001), 6-minute hall walk (6MHW) distance (SMD = 2.83; 95% CI = 1.44- 4.22; P < .0001), New York Heart Association (NYHA) Class (SMD = -3.23; 95% CI = -4.76 to -1.69; P < .0001), N-terminal pro-brain natriuretic peptide (NT-proBNP) (SMD = -1.24; 95% CI = -1.58 to -0.89; P < .00001) and the duration of hospitalization (SMD = -1.65; 95% CI = -2.90 to -0.39; P = .01) compared with control group for heart failure, but has no obvious effect on left ventricular ejection fraction (LVEF) (SMD = 1.43; 95% CI = -0.15-3.01; P = .08), or the number of hospitalization per year (SMD = -1.17; 95% CI = -2.56-0.22; P = .10). CONCLUSIONS: Baroreflex activation therapy can improve the treatment efficacy for heart failure.

Ethanol Extract of Chinese Hawthorn (Crataegus pinnatifida) Fruit Reduces Inflammation and Oxidative Stress in Rats with Doxorubicin-Induced Chronic Heart Failure.

BACKGROUND Chinese hawthorn (Crataegus pinnatifida) fruit is a traditional Chinese medicine for treatment of digestive system and cardiovascular diseases. The fruit contains polyphenol compounds, such as epicatechin, that have anti-inflammatory activity. This study aimed to investigate the effects of an alcohol extract of hawthorn fruit (HAE) on inflammation and oxidative stress in rats with doxorubicin-induced chronic heart failure (CHF). MATERIAL AND METHODS Rats were intraperitoneally injected with doxorubicin to induce CHF and subsequently treated with HAE intragastrically once daily for 6 weeks. At the end of the experiment, echocardiographic and hemodynamic parameters were assessed, and enzyme-linked immunoassays were used to detect the levels of cardiac injury markers (brain natriuretic peptide, creatine kinase-MB, aspartate aminotransferase, lactate dehydrogenase, copeptin, and adrenomedullin), oxidative stress markers (glutathione peroxidase and malondialdehyde), and inflammatory cytokines (interleukin [IL]-6, IL-8, IL-1ß, and tumor necrosis factor-a). The IL-1ß, IL-6, glutathione peroxidase-1, and catalase mRNA levels were also measured by quantitative real-time polymerase chain reaction. RESULTS Our findings indicated that HAE exerts a cardioprotective effect, as shown by improved echocardiographic and hemodynamic parameters, decreased activity of serum myocardial enzymes, reduced serum levels of CHF markers, and inhibited inflammatory response in cardiac tissue. In addition, HAE treatment downregulated the mRNA expression of IL-1ß and tumor necrosis factor-alpha and upregulated the mRNA expression of glutathione peroxidase-1 and catalase compared with untreated doxorubicin-induced CHF rats. CONCLUSIONS HAE shows promise for the prevention and treatment of CHF. The cardioprotective effect of HAE appears to be related to inhibition of both the inflammatory response and oxidative stress in vivo.

Efficacy of Qishen Yiqi Drop Pill for Chronic Heart Failure: An Updated Meta-Analysis of 85 Studies.

BACKGROUND: Despite evidence for beneficial effects of Qishen Yiqi Drop Pill (QSYQ) on congestive heart failure, the majority of studies are based on insufficient sample sizes. The aim of this study was to evaluate the therapeutic effects of QSYQ using a meta-analysis approach. Methodology/Principal Findings. All relevant studies published before December 31, 2019, were identified by searches of various databases with key search terms. In total, 85 studies involving 8,579 participants were included. The addition of QSYQ to routine Western medicine increased 6-minute walking distance (SMD = 2.08, 95% CI: 1.72-2.44, p < 0.001), left ventricular ejection fraction (SMD = 1.05, 95% CI: 0.87-1.23, p < 0.001), and cardiac index (SMD = 1.44, 95% CI: 0.92-1.95, p < 0.001) and reduced brain natriuretic peptide (SMD = -2.28, 95% CI: -2.81 to -1.76, p < 0.001), N-terminal prohormone of brain natriuretic peptide (SMD = -2.49, 95% CI: -3.24 to -1.73, p < 0.001), left ventricular end-diastolic dimensions (SMD = -0.92, 95% CI: -1.25 to -0.59, p < 0.001), and left ventricular end-systolic dimensions (SMD = -0.55, 95% CI: -0.89 to -0.21, p < 0.001). The results were stable in subgroup analyses and sensitivity analyses. CONCLUSIONS: Our current meta-analysis indicated that QSYQ combined with Western therapy might be effective in CHF patients. Further researches are needed to identify which subgroups of CHF patients will benefit most and what kind of combination medicines work best.

A Clinical Tool to Predict Low Serum Selenium in Patients with Worsening Heart Failure.

Selenium is an essential micronutrient, and a low selenium concentration (<100 µg/L) is associated with a poorer quality of life and exercise capacity, and an impaired prognosis in patients with worsening heart failure. Measuring selenium concentrations routinely is laborious and costly, and although its clinical utility is yet to be proven, an easy implemented model to predict selenium status is desirable. A stepwise multivariable logistic regression analysis was performed using routinely measured clinical factors. Low selenium was independently predicted by: older age, lower serum albumin, higher N-terminal pro-B-type natriuretic peptide levels, worse kidney function, and the presence of orthopnea and iron deficiency. A 10-points risk-model was developed, and a score of ≥6 points identified >80% of patients with low selenium (sensitivity of 44%, specificity of 80%). Given that selenium and iron overlap in their physiological roles, we evaluated the shared determinants and prognostic associates. Both deficiencies shared similar clinical characteristics, including the model risk factors and, in addition, a low protein intake and high levels of C-reactive protein. Low selenium was associated with a similar or worse prognosis compared to iron deficiency. In conclusion, although it is difficult to exclude low selenium based on clinical characteristics alone, we provide a prediction tool which identifies heart failure patients at higher risk of having a low selenium status.

Prospective Evaluation of Clinico-Pathological Predictors of Postoperative Atrial Fibrillation: An Ancillary Study From the OPERA Trial.

BACKGROUND: Postoperative atrial fibrillation (POAF) occurs in 30% to 50% of patients undergoing cardiac surgery and is associated with increased morbidity and mortality. Prospective identification of structural/molecular changes in atrial myocardium that correlate with myocardial injury and precede and predict risk of POAF may identify new molecular pathways and targets for prevention of this common morbid complication. METHODS: Right atrial appendage samples were prospectively collected during cardiac surgery from 239 patients enrolled in the OPERA trial (Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation), fixed in 10% buffered formalin, and embedded in paraffin for histology. We assessed general tissue morphology, cardiomyocyte diameters, myocytolysis (perinuclear myofibril loss), accumulation of perinuclear glycogen, interstitial fibrosis, and myocardial gap junction distribution. We also assayed NT-proBNP (N-terminal pro-B-type natriuretic peptide), hs-cTnT, CRP (C-reactive protein), and circulating oxidative stress biomarkers (F2-isoprostanes, F3-isoprostanes, isofurans) in plasma collected before, during, and 48 hours after surgery. POAF was defined as occurrence of postcardiac surgery atrial fibrillation or flutter of at least 30 seconds duration confirmed by rhythm strip or 12-lead ECG. The follow-up period for all arrhythmias was from surgery until hospital discharge or postoperative day 10. RESULTS: Thirty-five percent of patients experienced POAF. Compared with the non-POAF group, they were slightly older and more likely to have chronic obstructive pulmonary disease or heart failure. They also had a higher European System for Cardiac Operative Risk Evaluation and more often underwent valve surgery. No differences in left atrial size were observed between patients with POAF and patients without POAF. The extent of atrial interstitial fibrosis, cardiomyocyte myocytolysis, cardiomyocyte diameter, glycogen score or Cx43 distribution at the time of surgery was not significantly associated with incidence of POAF. None of these histopathologic abnormalities were correlated with levels of NT-proBNP, hs-cTnT, CRP, or oxidative stress biomarkers. CONCLUSIONS: In sinus rhythm patients undergoing cardiac surgery, histopathologic changes in the right atrial appendage do not predict POAF. They also do not correlate with biomarkers of cardiac function, inflammation, and oxidative stress. Graphic Abstract: A graphic abstract is available for this article.

A multi-center, randomized, double-blind, placebo-parallel controlled trial for the efficacy and safety of shenfuqiangxin pills in the treatment of chronic heart failure (Heart-Kidney yang deficiency syndrome).

BACKGROUND: Heart failure (HF) is the final stage of various cardiac diseases with poor prognosis. The integrated traditional Chinese medicine (TCM) and western medicine therapy has been considered as a prospective therapeutic strategy for chronic heart failure (CHF). There have been small clinical trials and experimental studies to demonstrate the efficacy of Shenfu Qiangxin Pills (SFQX) for treating CHF, however, there is still a lack of further high-quality trial. This paper describes the protocol for the clinical assessment of SFQX in CHF (heart-kidney Yang deficiency syndrome) patients. METHODS: A randomized, double-blind, parallel-group, placebo-controlled, multi-center trial will assess the efficacy and safety of SFQX in the treatment of CHF. 352 patients with CHF (heart-kidney Yang deficiency syndrome) from 22 hospitals in China will be enrolled. Besides their standardized western medicine, patients will be randomized to receive treatment of either SFQX or placebo for 12 weeks. The primary outcome is the plasma N-terminal pro-B-type natriuretic peptide levels, which will be measured uniformly by the central laboratory. The secondary outcomes include composite endpoint events (hospitalization due to worsening HF, all-cause mortality, other serious cardiovascular events), echocardiography indicators, grades of the New York Heart Association (NYHA) functional classification, the 6-minute walk test (6MWT) results, Minnesota Living With Heart Failure Questionnaire and TCM syndrome scores. DISCUSSION: The integrated TCM and western medicine therapy has developed into a treatment model in China. The rigorous design of the trial will assure an objective and scientific assessment of the efficacy and safety of SFQX in the treatment of CHF. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000028777 (registered on January 3, 2020).

Benefits of Tai Chi Exercise Among Adults With Chronic Heart Failure: A Systematic Review and Meta-Analysis.

BACKGROUND: Exercise-based cardiac rehabilitation is safe and effective for adults with chronic heart failure (CHF), yet services are greatly underutilized. However, tai chi is a popular and safe form of exercise among older adults with chronic health conditions. OBJECTIVE: A systematic review and meta-analysis was conducted to examine the benefits of tai chi exercise among persons with CHF. METHODS: An electronic literature search of 10 databases (Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature, Embase, OpenGrey, PsycARTICLES, PsycINFO, PubMed, Scopus, SPORTDiscus, and Web of Science) was conducted from January 1, 2004, to August 1, 2019. Clinical trials that examined tai chi exercise, were published in English or German languages, and conducted among participants with CHF were included. Comprehensive Meta-Analysis version 2.0 software (Biostat, Inc) was used to calculate effect sizes (ie, Hedges g) and 95% confidence intervals using random effects models. RESULTS: A total of 6 studies met the inclusion criteria, enrolling 229 participants (mean age, 68 years; 28% women; mean ejection fraction = 37%). At least 3 studies reported outcomes for exercise capacity (n = 5 studies), quality of life (n = 5 studies), depression (n = 4 studies), and b-type natriuretic peptide (n = 4 studies), allowing for meta-analysis. Compared with controls, tai chi participants had significantly better exercise capacity (g = 0.353; P = .026, I = 32.72%), improved quality of life (g = 0.617; P = .000, I = 0%), with less depression (g = 0.627; P = .000, I = 0%), and decreased b-type natriuretic peptide expression (g = 0.333; P = .016, I = 0%). CONCLUSION: Tai chi can be easily integrated into existing cardiac rehabilitation programs. Further research is needed with rigorous study designs and larger samples before widespread recommendations can be made.

Intervention Treatment for Myocardial Infarction With Tai Chi: A Systematic Review and Meta-analysis.

OBJECTIVE: To assess the efficacy of Tai Chi (TC) in patients with myocardial infarction and provide up-to-date evidence for its application. DATA SOURCES: Three English databases (PubMed, Embase, and Cochrane Central Register of Controlled Trials) and 3 Chinese databases (China Knowledge Resource Integrated, Wanfang, Weipu) were screened for the time period between January 1, 1976 and May 31, 2019. STUDY SELECTION: Seven randomized and controlled experiments were included. DATA EXTRACTION: Two independent researchers under 2 independent advisors extracted and classified the data from all relevant studies based on the prespecified inclusion criteria and rules for data extraction. DATA SYNTHESIS: A total of 615 patients were included in this study. The TC group was comprised of 294 patients, and the control group included 261 patients. The results revealed that TC has significant effects on the outcomes of the 6-minute walk (standardized mean difference, 1.30; 95% confidence interval, 0.50-2.11) and left ventricular ejection fraction (standardized mean difference, 1; 95% confidence interval, 0.43-1.57) compared with no or low-density exercise. Also, TC positively affected the quality of life, pro-B type natriuretic peptide, and short form-36. However, TC did not significantly affect activities of daily living (P=.060), sense of coherence-13 (P=.057) and N-terminal-pro-brain natriuretic peptide (P=.081). A moderate to high heterogeneity was observed across all comparisons. CONCLUSIONS: Compared with no exercise or other types of low-intensity physical activities, TC improved the outcome of the 6-minute walk, left ventricular ejection fraction, quality of life, and short form-36 scores, but reduced the outcome of pro-B type natriuretic peptide in patients with myocardial infarction. Therefore, TC could be an effective exercise option for cardiac rehabilitation. More research should be done to identify the effects of TC on academic functioning and to determine ways of motivating patients to use preventive TC interventions.

Effects of different doses of atorvastatin, rosuvastatin, and simvastatin on elderly patients with ST-elevation acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI).

OBJECTIVE: To conduct a randomized double-blind prospective study to investigate effect of different doses of atorvastatin, rosuvastatin, and simvastatin on elderly patients with ST-elevation AMI after PCI. METHODS: One hundred and ninety-two AMI patients over 60 years old who underwent PCI were randomly divided into six groups: the low atorvastatin group, high atorvastatin group; low rosuvastatin group; high rosuvastatin group; low simvastatin group; high simvastatin group. Demographic data and clinical information as well as coronary angiography parameters were recorded. Plasma levels of CK-MB, BNP, ALT, and TnI were measured at 12 hr, 24 hr, and 1 week after PCI. Major cardiovascular events (MACE) were recorded and analyzed using Kaplan-Meier (K-M) curve. RESULTS: No significant differences were observed in angiographic and procedural characteristics. In all high dose groups, all levels of CK-MB, BNP, ALT, and TnI were significantly lower. However, after 1 week of PCI, only CK-MB, BNP, and TnI showed significant difference between high and low dose groups. Patients in high dose groups had significantly lower rates for surgical or percutaneous intervention, recurrence of angina, and rehospitalization. K-M curve analysis also showed cumulative incidence freedom time of overall MACE in high dose groups was significantly longer. No significant differences were found among different drugs with the same doses. CONCLUSION: Patients with higher doses had lower level of CK-MB, BNP, ALT, and TnI and lower occurrence of MACE after PCI.

Genetic Variability of Antioxidative Mechanisms and Cardiotoxicity after Adjuvant Radiotherapy in HER2-Positive Breast Cancer Patients.

BACKGROUND: Breast cancer treatment is associated with the occurrence of various cardiac adverse events. One of the mechanisms associated with cardiotoxicity is oxidative stress, against which cells are protected by antioxidative enzymes. Genetic variability of antioxidative enzymes can affect enzyme activity or expression, which modifies the ability of cells to defend themselves against oxidative stress and could consequently contribute to the occurrence of treatment-related cardiotoxicity. Our aim was to evaluate the association of common polymorphisms in antioxidative genes with cardiotoxicity after adjuvant radiotherapy (RT) in HER2-positive breast cancer patients. METHODS: Our retrospective study included 101 HER2-positive early breast cancer patients who received trastuzumab and adjuvant RT. We isolated DNA from buccal swabs and used competitive allele-specific PCR for genotyping of PON1 rs854560 and rs662, GSTP1 rs1138272 and rs1695, SOD2 rs4880, CAT rs1001179, and HIF1 rs1154965 polymorphisms. N-terminal pro B-type natriuretic peptide (NT-proBNP), left ventricular ejection fraction, and NYHA class were used as markers of cardiotoxicity. We used logistic regression to evaluate the association of genetic factors with markers of cardiotoxicity. RESULTS: Carriers of at least one polymorphic PON1 rs854560 allele were less likely to have increased NT-proBNP (OR = 0.34; 95% CI = 0.15-0.79; P = 0.012), even after adjustment for age (OR = 0.35; 95% CI = 0.15-0.83; P = 0.017). Carriers of at least one polymorphic PON1 rs662 allele were more likely to have increased NT-proBNP (OR = 4.44; 95% CI = 1.85-10.66; P = 0.001), even after adjustment for age (OR = 5.41; 95% CI = 2.12-13.78; P < 0.001). GSTP1 rs1695 was also associated with decreased NT-proBNP in the multivariable analysis (P = 0.026), while CAT rs1001179 was associated with NYHA class in the univariable (P = 0.012) and multivariable analysis (P = 0.023). CONCLUSION: In our study, polymorphisms PON1 rs662 and rs854560, CAT rs1001179, and GSTP1 rs1695 were significantly associated with the occurrence of cardiac adverse events after adjuvant RT and could serve as biomarkers contributing to treatment personalization.

The influence of post-infarct heart failure and high fat diet on the expression of apelin APJ and vasopressin V1a and V1b receptors.

Vasopressin and apelin are reciprocally regulated hormones which are implicated in the pathophysiology of heart failure and the regulation of metabolism; however, little is known about their interactions under pathological conditions. In this study, we determined how post-infarct heart failure (HF) and a high fat diet (HFD) affect expression of the apelin APJ receptor (APJR) and the V1a (V1aR) and V1b (V1bR) vasopressin receptors in the hypothalamus, the heart, and the retroperitoneal adipose tissue. We performed experiments in male 4-week-old Sprague Dawley rats. The animals received either a normal fat diet (NFD) or a HFD for 8 weeks, then they underwent left coronary artery ligation to induce HF or sham surgery (SO), followed by 4 weeks of NFD or HFD. The HF rats showed higher plasma concentration of NT-proBNP and copeptin. The HF reduced the APJR mRNA expression in the hypothalamus. The APJR and V1aR protein levels in the hypothalamus were regulated both by HF and HFD, while the V1bR protein level in the hypothalamus was mainly influenced by HF. APJR mRNA expression in the heart was significantly higher in rats on HFD, and HFD affected the reduction of the APJR protein level in the right ventricle. The regulation of APJR, V1aR and V1bR expression in the heart and the retroperitoneal adipose tissue were affected by both HF and HFD. Our study demonstrates that HF and HFD cause significant changes in the expression of APJR, V1aR and V1bR, which may have an important influence on the cardiovascular system and metabolism.

Amyloid cardiomyopathy in a large integrated health care system.

BACKGROUND: Light Chain (AL) and transthyretin (ATTR) amyloidosis are the most common forms of amyloid cardiomyopathy. Population based studies describing the epidemiology and clinical features of amyloid cardiomyopathy are often based in tertiary medical centers and thus may be limited by referral bias. METHODS AND RESULTS: We performed a cohort study of 198 patients diagnosed and treated in the Kaiser Permanente Northern California health care system who had a confirmed diagnosis of cardiac amyloidosis between 2001 and 2016. Associations between demographic, clinical, laboratory and imaging data and patient outcomes were quantified using multivariable Cox proportional hazard models for both the AL and ATTR groups. The average length of follow up was 2.8 years (SD 2.9 years) and overall survival was 69.1 percent at one year and 35.4 percent at five years. In the AL group, lower left ventricular ejection fraction (HR 1.33 per 5-point decrease, P < .001), coronary artery disease (HR 3.56, P < .001), and diabetes mellitus (HR 3.19, P < .001) were associated with all-cause mortality. Increasing age at the time of diagnosis with associated with higher all-cause mortality in both the AL and ATTR groups. Higher levels of B-type natriuretic peptide were associated with all-cause mortality in both groups: Top quartile BNP HR 6.17, P < .001 for AL and HR 8.16, P = .002 for ATTR. CONCLUSIONS: This study describes a large cohort of patients with amyloid cardiomyopathy derived from a community based, integrated healthcare system and describes demographic, clinical, and laboratory characteristics associated with mortality and heart failure hospitalization. In this population, coronary artery disease, diabetes mellitus, and high BNP levels were strongly associated with mortality.

The Efficacy and Safety of Xinmailong Injection in Patients with Chronic Heart Failure: A Multicenter Randomized Double-Blind Placebo-Controlled Trial.

Objectives: Chronic heart failure (CHF) is a chronic and progressive disease with high incidence. The aim of this study was to evaluate the effectiveness and safety of Xinmailong injection (XI) on CHF patients with B-type natriuretic peptide (BNP) ≥200 ng/mL and left ventricular ejection fraction (LVEF) of ≤45%. Trial design: This is a randomized double-blind placebo-controlled trial. Settings: Hospitals. Subjects: One hundred patients with CHF were randomly divided into XI (n = 50) and control groups (n = 50). Intervention: The XI group was treated with standard treatment plus XI (100 mg/2 mL, intravenous drip infusion). The control group was treated with standard treatment plus equal amounts of XI placebo. The course of treatment was 5 days. Outcome measures: New York Heart Association (NYHA) functional class, LVEF, BNP, and 6-min walking distance were assessed for therapeutic effect. Results: NYHA functional classes and LVEF were better in the XI group than in the control (p < 0.01). BNP was significantly different after the treatments in both groups (p < 0.01), and compared with the control, BNP was reduced after XI treatment (p < 0.01). No deaths occurred in the course of this study. The number of adverse events between the two groups was not statistically different (p > 0.05). Conclusions: XI can alleviate the symptoms, improve heart function, and exercise tolerance in patients with CHF and is safe to use.