Clinical Outcomes of Cardiac Shockwave Therapy in Severe Coronary Artery Disease Patients after Coronary Artery Bypass Grafting.

Cardiac shockwave therapy (CSWT) is a noninvasive treatment for patients with refractory angina or myocardial ischemia. This study aims to evaluate the potential beneficial effect and safety of CSWT in patients with severe coronary artery disease (CAD) who have undergone coronary artery bypass grafting (CABG).This was a single-arm prospective cohort study. A total of 30 patients with severe CAD who were not suitable for coronary revascularization and who had undergone CABG were enrolled. All patients received CSWT for nine sessions. Evaluation was performed before and after CSWT, including the Canadian Cardiovascular Society (CCS) classification, New York Heart Association (NYHA) classification, 6-minute walk test (6MWT), Seattle Angina Questionnaire (SAQ) score, nitroglycerin dosage, echocardiography, myocardial perfusion imaging (MPI), and safety parameters. All patients were followed up at both 1 month and 9 months after CSWT.After treatment, CSWT significantly improved CCS classification (P < 0.05), NYHA classification (P < 0.05), nitroglycerin dosage (P < 0.001), and 6MWT (P < 0.05) at 1 month and 9 months after CSWT. SAQ score (P < 0.05) and left ventricular ejection fraction (LVEF; P = 0.037) by echocardiography significantly improved at 1 month after CSWT. Significant decreases in summed stress score (SSS), summed difference score (SDS), ischemic area stress, and ischemic area difference by MPI were observed at 1 month and 9 months after CSWT (P < 0.01). There were no changes in safety parameters before and after CSWT.CSWT may have a beneficial effect on improving myocardial perfusion, clinical symptoms, exertional capacity, and quality of life and is a safe alternative treatment for patients with severe CAD who have undergone CABG.

Efficacy and safety of cardiac shock wave therapy for patients with severe coronary artery disease: A randomized, double-blind control study.

BACKGROUND: Previous studies proved the efficacy of cardiac shock wave therapy (CSWT) for coronary artery disease (CAD) patients who are not candidate for reperfusion therapy. Randomized control trials are limited. We try to explore the efficacy and safety of CSWT for patients with severe CAD. METHODS: Thirty patients with severe CAD who had obvious ischemia on myocardial perfusion imaging (MPI) were enrolled and randomly assigned to the CSWT group or the control group. They had received optimal medication treatment for at least three months. Nine sessions of shock wave therapy were conducted over 3 months. CSWT group received the real treatment, while the control group received the pseudo-treatment. Clinical symptom, imaging outcomes and safety parameters were compared between two groups. RESULTS: After treatment, regional stress score (P = .023), improvement rate (IR) of ischemic area (IA) stress (P < .001) and IR of IA difference (P < .001) were significantly favor CSWT group. The interaction of summed rest score (P < .001), summed stress score (P = .004), summed difference score (P = .036) were significantly improved in the CSWT group compared to the control group. Seattle angina questionnaire, quality of life (QOL) and the distance of six-minute walking test (6MWT) were improved in both groups without significant difference between them. Hemodynamic parameters were stable during procedure. Myocardial injury markers showed no changes in two groups. CONCLUSIONS: Our study demonstrated CSWT could effectively and safely improve myocardial perfusion in patients with severe CAD. Clinical symptom, QOL and 6MWT were all improved after treatment, but no significant difference between two groups.

Clopidogrel-induced neutropenia in an 80-year-old patient with chronic kidney disease who underwent percutaneous coronary intervention: a case report and literature review.

BACKGROUND: Clopidogrel is a widely-used antiplatelet and acts as an adenosine diphosphate receptor inhibitor. Neutropenia is a rare but serious adverse effect of clopidogrel. It is unknown whether this adverse effect has any association with impaired kidney function. CASE PRESENTATION: An 80-year-old male with chronic kidney disease was diagnosed with non-ST elevation myocardial infarction and underwent percutaneous coronary intervention. During hospitalization, the patient was diagnosed with contrast-induced nephropathy, treated symptomatically, and discharged with a back-to-baseline creatinine level. Two weeks later, the patient presented to the emergency department with fever and chills. Complete blood count showed leukopenia (0.84 × 103/mm3) and severe neutropenia (0.13 × 103/mm3). Blood cultures were positive for Pseudomonas aeruginosa. Clopidogrel was stopped immediately and switched into ticagrelor. Imipenem and granulocyte colony-stimulating factor were administered to the patient. The patient's white blood cell and absolute neutrophil count were within the normal range after four days of treatment. The patient was discharged after a 10-day hospitalization, and his complete blood counts were normal during further follow-ups. CONCLUSIONS: Clopidogrel was the most likely primary cause of neutropenia in our case. The incidence of clopidogrel-induced neutropenia is low and the exact mechanism is not fully explained. We provide suggestions on the management of clopidogrel-associated neutropenia, and summarize all five cases of clopidogrel-induced neutropenia in patients with impaired kidney function.

Fractional esterification rate of cholesterol in high-density lipoprotein associates with risk of coronary heart disease.

BACKGROUND: Fractional esterification rate of cholesterol in high-density lipoprotein (FERHDL) has been found to be closely correlated with atherosclerotic dyslipidemia, especially lipoprotein distributions, and is a potentially useful predictor for coronary heart disease (CHD). The associations of FERHDL, measured by the simple and precise HPLC method, with angiographically defined CHD and its related risk factors in Chinese patients were evaluated. METHODS: Two hundred and fifty eight Chinese patients who had indications for angiography were enrolled in this study. Coronary angiograms were obtained by the standard techniques. FERHDL was determined by the HPLC method. Cholesterol levels in serum HDL, LDL and subfractions were measured by ultracentrifugation/HPLC method. Associations between FERHDL and CHD and CHD risk factors were analyzed. RESULTS: FERHDL was correlated with almost all the CHD risk factors. Compared with the non-CHD group, the CHD patients had higher values of FERHDL (20.9 ± 7.9%/h vs 17.7 ± 7.1%/h, p = 0.001). FERHDL was found to be independently and positively correlated with log TG (ß = 0.386, P < 0.001) and log (LDLb-C) (ß = 0.165, P = 0.020), respectively, and negatively correlated with log (HDL2-C)(ß = -0.351, P < 0.001). Logistic regression analysis demonstrated that age, diabetes mellitus, smoking and FERHDL (OR = 1.056-1.080, p < 0.05) were independent risk factors for CHD. CONCLUSION: FERHDL significantly correlated with both HDL2-C and LDLb-C, and therefore, is the predictor of lipoprotein distributions. In addition, after correcting for the presence of classic risk factors, FERHDL was independently associated with the presence of angiographically defined CHD.

Shock Wave Therapy Alleviates Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury by Inhibiting Both Apoptosis and Ferroptosis.

Shock wave therapy (SWT) is a new alternative therapy for patients with severe coronary artery disease that improves myocardial ischemic symptoms by delivering low-energy shock wave stimulation to ischaemic myocardium with low-energy pulsed waves. However, the specific mechanism of its protective effect is not fully understood, especially for the protective mechanism in cardiomyocytes after hypoxia/reoxygenation (H/R). We selected a rat H9c2 cardiomyocyte cell line to establish a stable H/R cardiomyocyte injury model by hypoxia/reoxygenation, and then used SWT for therapeutic intervention to explore its cardiomyocyte protective mechanisms. The results showed that SWT significantly increased cell viability and GSH levels while decreasing LDH levels, ROS levels, and MDA levels. SWT also improved mitochondrial morphology and function of cells after H/R. Meanwhile, we found that SWT could increase the expression of GPX4, xCT, and Bcl-2, while decreasing the expression of Bax and cleaved caspase-3, and inhibiting cardiomyocyte apoptosis and ferroptosis. Moreover, this protective effect of SWT on cardiomyocytes could be significantly reversed by knockdown of xCT, a key regulator protein of ferroptosis. In conclusion, our study shows that SWT can attenuate hypoxia-reoxygenation-induced myocardial injury and protect cardiomyocyte function by inhibiting H/R-induced apoptosis and ferroptosis, and this therapy may have important applications in the treatment of clinical myocardial ischemic diseases.

DEAD-box helicase 17 (DDX17) protects cardiac function by promoting mitochondrial homeostasis in heart failure.

DEAD-box helicase 17 (DDX17) is a typical member of the DEAD-box family with transcriptional cofactor activity. Although DDX17 is abundantly expressed in the myocardium, its role in heart is not fully understood. We generated cardiomyocyte-specific Ddx17-knockout mice (Ddx17-cKO), cardiomyocyte-specific Ddx17 transgenic mice (Ddx17-Tg), and various models of cardiomyocyte injury and heart failure (HF). DDX17 is downregulated in the myocardium of mouse models of heart failure and cardiomyocyte injury. Cardiomyocyte-specific knockout of Ddx17 promotes autophagic flux blockage and cardiomyocyte apoptosis, leading to progressive cardiac dysfunction, maladaptive remodeling and progression to heart failure. Restoration of DDX17 expression in cardiomyocytes protects cardiac function under pathological conditions. Further studies showed that DDX17 can bind to the transcriptional repressor B-cell lymphoma 6 (BCL6) and inhibit the expression of dynamin-related protein 1 (DRP1). When DDX17 expression is reduced, transcriptional repression of BCL6 is attenuated, leading to increased DRP1 expression and mitochondrial fission, which in turn leads to impaired mitochondrial homeostasis and heart failure. We also investigated the correlation of DDX17 expression with cardiac function and DRP1 expression in myocardial biopsy samples from patients with heart failure. These findings suggest that DDX17 protects cardiac function by promoting mitochondrial homeostasis through the BCL6-DRP1 pathway in heart failure.

Analysis of the status of social frailty in Chinese older adults with cardiovascular and cerebrovascular diseases: a national cross-sectional study.

Background: Social frailty is one type of frailty. Physical frailty with cardiovascular and cerebrovascular diseases (CCVD) have been studied a lot, but less research on social frailty. Objectives: To study the prevalence, related risk factors and regional differences of social frailty with CCVD in Chinese older adults. Methods: SSAPUR was a national cross-sectional survey. Participants aged 60 years or older were recruited in August 2015. Demographic data and information regarding family, health and medical conditions, living environment conditions, social participation, spiritual and cultural life, and health condition were obtained. Social frailty was assessed in five areas (HALFE Social Frailty Index) including inability to help others, limited social participation, loneliness, financial difficulty, and living alone. The prevalence of CCVD with social frailty, related risk factors and regional differences in CCVD with social frailty were studied. Results: A total of 222,179 participants were enrolled. 28.4% of them had CCVD history. The prevalence of social frailty in the CCVD group was 16.03%. In CCVD participants, compared with the group without social frailty, there were significant differences in gender, age, urban-rural distribution, ethnicity, marital status, and education levels in the social frailty group. Significant differences were also found in physical exercise participation, health status, cataract, hypertension, diabetes mellitus, hospitalization within 1 year, self-assessed health status, crutch or wheelchair usage, urinary and fecal incontinence, need for care from others, fall history, housing satisfaction, and self-assessed happiness in the social frailty group. Women with CCVD had a higher prevalence of social frailty than men. By age in CCVD with social frailty, the highest prevalence was found in participants 75-79 years old. The prevalence of CCVD was significant difference between social frailty in urban and rural group. The prevalence of social frailty with CCVD was significantly different in different regions. The highest prevalence was 20.4% in southwest area, and the lowest prevalence was 12.5% in northeast with area. Conclusion: The prevalence of social frailty among the CCVD older adults is high. Factors such as gender, age, region, urban-rural residence, and the state of the disease may be associated with social frailty.

MicroRNA-21 mediates the protective effects of salidroside against hypoxia/reoxygenation-induced myocardial oxidative stress and inflammatory response.

Myocardial ischemia-reperfusion (I/R) injury is the oxidative stress and inflammatory response that occurs when a tissue is reperfused following a prolonged period of ischemic injury. Growing evidence has demonstrated that microRNAs (miRs) are essential in the development of myocardial I/R injury. Salidroside, a phenylpropanoid glycoside isolated from a traditional Chinese medicinal plant, Rhodiola rosea, possesses multiple pharmacological functions and protects against myocardial I/R injury in vitro and in vivo. However, the role of miRs in the cardioprotective effects of salidroside against myocardial I/R injury has not been studied, to the best of our knowledge. In the present study, the role of miR21 in the underlying mechanism of salidroside-induced protection against oxidative stress and inflammatory injuries in hypoxia/reoxygenation (H/R)-treated H9c2 cardiomyocytes was determined. The cell viability was assessed with an MTT assay. Lactate dehydrogenase (LDH) release, caspase-3 activity, malondialdehyde (MDA) level, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were determined by commercial kits. Cell apoptosis was measured by flow cytometry. Intracellular reactive oxygen species (ROS) generation was monitored by DCFH-DA. The miR-21 level was quantified by reverse transcription-quantitative (RT-q)PCR. The interleukin (IL)-6, IL-1ß and tumor necrosis factor (TNF)-α levels were measured by RT-qPCR and ELISA. The results showed that salidroside pretreatment significantly increased cell viability and decreased the release of LDH, accompanied by an increase in miR-21 expression in H/R-treated H9c2 cells and a miR-21 inhibitor reversed these effects. In addition, the miR-21 inhibitor also abrogated the inhibition of salidroside on H/R-induced increases in apoptosis and caspase-3 activity in H9c2 cells. Salidroside mitigated H/R-induced oxidative stress as illustrated by the downregulation of ROS generation and MDA level and increased the activities of the antioxidant enzymes, SOD and GSH-Px, all of which were abrogated in cells transfected with the miR-21 inhibitor. Salidroside induced a decrease in the expression and levels of the pro-inflammatory cytokines, IL-6, IL-1ß and TNF-α, which were prevented by the miR-21 inhibitor. Together, these results provide evidence of the beneficial effects of salidroside against myocardial I/R injury by reducing myocardial oxidative stress and inflammation which are enhanced by increasing miR-21 expression.

Downregulated microRNA­133a induces HUVECs injury: Potential role of the (pro) renin receptor in angiotensin II­dependent hypertension.

The renin­angiotensin system (RAS) serves an essential role in hypertension. MicroRNAs (miRs) have been reported to be important regulators in angiotensin (Ang) II­dependent hypertension. We aimed to explore the roles of Ang II and miR­133a in the mechanism underlying hypertension. Human umbilical vein endothelial cells (HUVECs) were identified by immunofluorescence staining. Cell viability and miR­133a expression under the inhibition of Ang II of various concentrations were determined by an MTT assay and reverse transcription­quantitative polymerase chain reaction (RT­qPCR), respectively. The effects of HUVECs transfected with miR­133a mimic or inhibitor on Ang II­induced apoptosis were measured using flow cytometry. The potential targeting of miR­133a to the 3' untranslated region of (pro) renin receptor (PRR) was assessed using TargetScan and a dual­luciferase assay. The effects of PRR interference using small interfering (si)RNA on PRR expression and the rate of apoptosis were determined by RT­qPCR, western blotting and flow cytometry, respectively. Ang II at a concentration of 10­5 M significantly inhibited the cell viability (P<0.05) and miR­133a expression (P<0.01); Downregulation of miR­133a suppressed cell viability. HUVECs transfected with miR­133a mimic reduced the rate of Ang II­induced apoptosis from 21.99 to 12.38%, but miR­133a inhibitor promoted Ang II­induced apoptosis (apoptosis rate, 28.9%). PRR was predicted to be a target gene of miR­133a. Transfection with siPRR decreased the apoptotic rate in Ang II + negative control and Ang II + miR­133a inhibitor group to 11.39 and 12.94%, respectively. Our findings also suggested that Ang II promoted PRR expression to enhance the apoptotic rate of HUVECs via the suppression of miR­133a. Furthermore, siPRR efficiently decreased the Ang II­induced apoptosis.