Dapagliflozin ameliorates myocardial infarction injury through AMPKα-dependent regulation of oxidative stress and apoptosis.

Dapagliflozin (DAPA) has been demonstrated to reduce cardiovascular mortality and heart failure hospitalization rates in diabetic patients. However, the mechanism underlying its cardio-protective effect in non-diabetic patients remains unclear. Our study aimed to explore the cardio-protective impact of DAPA on myocardial infarction in non-diabetic mice. We induced myocardial infarction in C57BL/6 mice by ligating the descending branch of the left coronary artery. After surgery, the animals were randomly treated with either saline or DAPA. We employed echocardiography, Western blot analysis, and tissue staining to assess post-infarction myocardial injury. Additionally, we investigated the mechanism of action through cell experiments. Compared to the myocardial infarction group, DAPA treatment significantly attenuated ventricular remodeling and improved cardiac function. By mitigating myocardial oxidative stress and apoptosis, DAPA may activate the AMPKα signaling pathway, thereby exerting a protective effect. These findings suggest that DAPA could serve as a novel therapeutic approach for patients with cardiac infarction.

Chest pain in a patient with transthyretin cardiac amyloidosis: A case report.

Key Clinical Message: Patients with transthyretin cardiac amyloidosis (ATTR-CM) commonly present with dyspnea, fatigue, and edema. In our case, the main presentation was exertional angina, which was atypical in patients with ATTR-CM and should be paid more attention to. Abstract: A 54-year-old woman was admitted with a complaint of exertional chest pain, and she had a history of hypertension. The results of the electrocardiogram and echocardiography revealed the clues of cardiac amyloidosis, and the patient was finally diagnosed with transthyretin cardiac amyloidosis, then she received tafamidis, and the symptoms improved significantly.

Efficacy and safety of a single-pill versus free combination of perindopril/indapamide/amlodipine: a multicenter, randomized, double-blind study in Chinese patients with hypertension.

BACKGROUND: In China, the prevalence of hypertension is high and the use of combination antihypertensive therapy is low, which contributes to inadequate blood pressure (BP) control. The availability of simplified treatments combining complementary BP-lowering agents may help more patients achieve their goals. METHODS: This Phase III, multicenter, randomized, double-blind, noninferiority study included Chinese adults with mild-to-moderate hypertension. Following a 1-month run-in on perindopril/indapamide bi-therapy, patients with uncontrolled systolic/diastolic BP (≥140/90 mmHg) were randomized to perindopril 5 mg/indapamide 1.25 mg/amlodipine 5 mg (Per/Ind/Aml) single-pill combination (SPC) or perindopril 4 mg/indapamide 1.25 mg plus amlodipine 5 mg (Per/Ind + Aml) for 6 months. Uptitration was permitted from month 2 onwards. The primary efficacy objective was the noninferiority of Per/Ind/Aml in lowering office systolic BP at 2 months. The secondary objectives included the effectiveness of SPC on diastolic BP, uptitration efficacy, and office BP control (systolic/diastolic <140/90 mmHg). A subgroup of patients participated in 24-h ambulatory BP monitoring (ABPM). RESULTS: A total of 532 patients were randomized: Per/Ind/Aml (n = 262) and Per/Ind + Aml (n = 269). Overall, the mean (±SD) age was 55.7 ±â€Š8.8 years, 60.7% were male, and the mean office systolic/diastolic BP at baseline on Per/Ind was 150.4/97.2 mmHg. Systolic BP decreased in both groups at 2 months from baseline: -14.99 ±â€Š14.46 mmHg Per/Ind/Aml versus -14.49 ±â€Š12.87 mmHg Per/Ind +Aml. A predefined noninferiority margin of 4 mmHg was observed (P < 0.001). The effectiveness of the Per/Ind/Aml SPC was also demonstrated for all secondary endpoints. ABPM demonstrated sustained BP control over 24 h. Both treatments were well tolerated. CONCLUSIONS: Per/Ind/Aml is an effective substitute for Per/Ind + Aml, providing at least equivalent BP control over 24 h in a single pill, with comparable safety.

Prognostic value of red cell distribution width in non-ST elevation myocardial infarction: A cohort study.

Non-ST elevation myocardial infarction (NSTEMI) has a higher risk of long-term mortality than ST-elevation myocardial infarction; thus, identifying such high-risk patients is essential. Red cell distribution width (RDW) recently emerged as a strong predictor of mortality in several cardiovascular diseases, however, it is scarcely known whether RDW has a prognostic value in NSTEMI patients, therefore, this study aims to elucidate this issue. 421 consecutive patients with NSTEMI between January 2020 and June 2022 were prospectively enrolled. Patients were divided into 2 groups by the optimal cutoff value of RDW using time-dependent receiver operating characteristic curves. The optimal cutoff value of RDW for predicting all-cause mortality was 13.4 and the study population was divided into low RDW (≤13.4) and high RDW (>13.4). The primary endpoint of this study was long-term all-cause mortality. The secondary endpoint was the association between RDW and long-term adverse events, including heart failure, gastrointestinal hemorrhage, stroke events, re-infarction rate, cardiovascular mortality, and major adverse cardiovascular events. The association of RDW with the outcome was analyzed by Cox regression analysis. Patients with high RDW tended to be older, had a higher history of previous MI, a higher history of percutaneous coronary intervention, a higher level of neutrophil, high-sensitivity C-reactive protein, a lower level of albumin, and a lower level of ejection fraction (all P < .05). During a median follow-up of 720 days (IQR, 534-913 days), the all-cause mortality was significantly higher in the high RDW group than in the low RDW group (24.8% vs 6.3%, P < .001). In the multivariate Cox proportional hazard analysis, RDW > 13.4 was an independent predictor for long-term all-cause mortality [hazard ratio 3.008; 95% confidence interval 1.005, 9.003, P = .049]. Admission RDW could be used as a new biomarker for predicting long-term mortality in patients with NSTEMI, and high RDW was associated with an increased risk of all-cause mortality.

Impact of renal denervation on cardiac remodeling in resistant hypertension: A meta-analysis.

Twelve studies involving 433 patients were included. After RDN treatment, LVMI decreased by 13.08 g/m2 (95% confidence interval [CI]: -18.38, -7.78; p < .00001), PWTd decreased by 0.60 mm (95% CI: -0.87, -0.34; p < .00001), IVSTd decreased by 0.78 mm (95% CI: -1.06, -0.49; p < .00001), and LVEF increased by 1.80% (95% CI: 0.71, 2.90; p = .001). However, there were no statistically significant improvements in LVIDd (95% CI: -1.40, 0.24; p = .17) and diastolic function (E/A) (95% CI: -0.04, 0.14; p = .28). Drug treatment for resistant hypertension (RH) is challenging. Renal denervation (RDN) is one of the most promising treatments for RH. Although studies have shown RDN can control blood pressure, the impacts of RDN on cardiac remodeling and cardiac function are unclear. This meta-analysis evaluated the effect of RDN on cardiac structure and function in patients with RH. PubMed, Embase, and Cochrane were used to conduct a systematic search. The main inclusion criteria were studies on patients with RH who received RDN and reported the changes in echocardiographic parameters before and after RDN. Echocardiographic parameters included left ventricular mass index (LVMI), end-diastolic left ventricular internal dimension (LVIDd), left ventricular end-diastolic posterior wall thickness (PWTd), end-diastolic interventricular septum thickness (IVSTd), E/A, and left ventricular ejection fraction (LVEF). Data was analyzed using RevMan. Twelve studies involving 433 patients were included. After RDN treatment, LVMI decreased by 13.08g/m2 (95%confidence interval [CI]: -18.38, -7.78, p < .00001), PWTd decreased by 0.60mm (95% CI: -0.87, -0.34, p < 0.00001), IVSTd decreased by 0.78mm (95% CI: -1.06, -0.49, p < .00001), and LVEF increased by 1.80% (95% CI: 0.71, 2.90, p = .001). However, there were no statistically significant improvements in LVIDd (95% CI: -1.40, 0.24, p = .17) and diastolic function (E/A) (95% CI: -0.04, 0.14, p =.28). This meta-analysis finds that RDN can improve left ventricular hypertrophy and ejection fraction in patients with RH but has no significant effect on LVIDd and diastolic function. However, more studies are warranted due to the lack of a strict control group, a limited sample size, and research heterogeneity.

Edema Index Predicts Mortality in Patients with Chronic Heart Failure: A Prospective, Observational Study.

Introduction: Chronic fluid accumulation or congestion is considered an important pathophysiologic mechanism in heart failure, leading to cardinal symptoms such as dyspnea, pulmonary congestion, and pitting edema. Edema index (EI) recently emerged as a surrogate for extracellular volume status and has been proven to be able to reflect one's congestion status. In this study, we aimed to evaluate the prognostic value of EI in patients with chronic heart failure (CHF). Methods: A total of 401 consecutive patients with CHF between August 2019 and October 2021 were prospectively enrolled. EI was obtained by InBody S10. The primary endpoint was long-term all-cause and cardiovascular mortality. Results: Patients with high EI (>0.397) tended to be older, presented with atrial fibrillation, have higher N-terminal brain natriuretic peptide, and have higher creatinine (all p < 0.05). During a median follow-up of 1200 days, the all-cause and cardiovascular mortality rate was significantly higher in the high EI group compared to the low EI group (all-cause mortality rate 43.8% vs. 30.3%, p < 0.001, and cardiovascular mortality rate 17.5% vs. 13.0%, p < 0.001, respectively). In the multivariate Cox proportional hazard analysis, EI > 0.397 was an independent predictor for both all-cause mortality (HR 1.959; 95% CI 1.304, 2.944; p = 0.001) and cardiovascular mortality (HR 2.051; 95% CI 1.276, 3.296; p = 0.003). Conclusions: Admission EI could be used as a marker for predicting long-term mortality in patients with CHF, and higher EI was associated with an increased risk of all-cause and cardiovascular mortality. Furthermore, EI-guided management could be a promising therapy in patients with CHF.

The lncRNA GAS5 upregulates ANXA2 to mediate the macrophage inflammatory response during atherosclerosis development.

Inflammatory macrophages play a crucial role in atherosclerosis development. The long non-coding RNA growth arrest-specific 5 (GAS5) regulates THP-1 macrophage inflammation by sponging microRNAs. The purpose of this study was to investigate the regulatory mechanism of GAS5 in atherosclerosis development. GSE40231, GSE21545, and GSE28829 datasets from the Gene Expression Omnibus database were integrated after adjusting for batch effect. Differential analysis was performed on the integrated dataset and validated using the Genotype-Tissue Expression and GSE57691 datasets. Potential biological functions of GAS5 and annexin A2 (ANXA2) were identified using gene set enrichment analysis (GSEA). ssGSEA, CIBERSORTx, and ImmuCellAI algorithms were used to identify immune infiltration in plaque samples. GAS5 and ANXA2 expression levels in RAW264.7 cells treated with oxidized low-density lipoprotein (ox-LDL) were measured by qRT-PCR and Western blot. Small interfering and short hairpin RNA were used to silence GAS5 expression. Plasmids of ANXA2 were used to establish ANXA2 overexpression. Apoptosis and inflammatory markers in macrophages were detected by Western blot. Aortic samples from APOE-/- mice were collected to validate the expression of GAS5 and ANXA2. GAS5 expression was significantly increased during atherosclerosis. GAS5 expression was positively correlated with macrophage activation and ANXA2 expression in plaques. Furthermore, ANXA2 upregulation was also related to the activation of macrophage. GSEA indicated similar biological functions for GAS5 and ANXA2 in plaques. Moreover, in vitro experiments showed that both GAS5 and ANXA2 contributed to macrophage apoptosis and inflammation. Rescue assays revealed that the inflammatory effects of GAS5 on macrophages were ANXA2-dependent. In vivo experiments confirmed the highly expression of Gas5 and Anxa2 in the plaque group. We identified the atherogenic roles of GAS5 and ANXA2 in the inflammatory response of macrophages. The inflammatory response in ox-LDL-treated macrophages was found to be mediated by GAS5-ANXA2 regulation, opening new avenues for atherosclerosis therapy.

LncRNA GAS5 downregulates NLRP3 inflammasome activation-mediated pyroptosis in sepsis-induced myocardial injury by targeting SIRT3/AMPKα.

An increasing body of studies has demonstrated the significance of long non-coding RNA (lncRNA) growth arrest specific 5 (GAS5) in inflammation and myocardial injury in septic shock. This research aims to determine whether GAS5 contributes to the pathological development of sepsis-induced cardiac damage and NLRP3 inflammasome-mediated myocardial cell pyroptosis. Cecal ligation and puncture (CLP) surgery was used to cause septic shock in C57BL/6 wild-type mice. After CLP, inflammatory, pyroptosis parameters of myocardial tissue, survival rate, and Murine Sepsis Score (MSS) were assessed to evaluate the involvement of GAS5 in the mouse myocardial depression. To investigate GAS5's function in lipopolysaccharide (LPS) induced myocardial cell pyroptosis, gain- and loss-of-function experiments were conducted in vitro on HL-1 cells. Our findings indicated that CLP dramatically reduced survival rates, MSS, SIRT3 and p-AMPK expression, and activated the Nuclear factor-κB (NF-κB) pathway and NLRP3 inflammasome-mediated pyroptosis. The NF-κB and pyroptosis pathways were greatly elevated while SIRT3/p-AMPKα was dramatically decreased as a result of GAS5 being downregulated. Meanwhile, the regulatory effect could be suppressed by SIRT3 and AMPKα activator. Our observations supported the idea that GAS5 has a crucial protective impact against myocardial inflammation and pyroptosis in sepsis.

Case Report: SCN5A mutations in three young patients with sick sinus syndrome.

Background: Sick Sinus Syndrome (SSS) is generally regarded as a degenerative disease with aging; however, genetic mutations have been confirmed to be associated with SSS. Among them, mutations in SCN5A are common in patients with SSS. We report three young SSS patients with SCN5A mutations at different sites that have not been previously reported in Asian patients. Case presentation: The three patients were all young females who presented with symptoms of severe bradycardia and paroxysmal atrial flutter, for which two patients received ablation therapy. However, after ablation, Holter monitoring indicated a significant long cardiac arrest; therefore, the patients received pacemaker implantation. The three patients had familial SSS, and genetic testing was performed. Mutations were found in SCN5A at different sites in the three families. All three patients received pacemaker implantation, resulting in the symptoms of severe bradycardia disappearing. Conclusion: SCN5A heterozygous mutations are common among patients clinically affected by SSS. Their causative role is confirmed by our data and by the co-occurrence of genetic arrhythmias among our patients. Genetic testing for SSS cannot be performed as a single gene panel because of feasible literature results, but in presence of familial and personal history of SSS in association with arrhythmias can provide clinically useful information.

[Effects of virtual reality in phase I cardiac rehabilitation training for elderly coronary heart disease patients after percutaneous coronary intervention].

The study aimed to examine the effects of virtual reality (VR) technology-based phase I cardiac rehabilitation (CR) program in elderly coronary heart disease (CHD) patients after percutaneous coronary intervention (PCI). Thirty-six cases of elderly CHD patients who underwent PCI in the First Affiliated Hospital of Chongqing Medical University from June 2022 to April 2023 were recruited by convenience sampling method. The patients were randomly assigned by means of random digital table method to two study groups: control group (n = 18), which received conventional nursing intervention after PCI, and experimental group (n = 18), which received a combined program of conventional nursing intervention together with CR program based on VR technology. The 6 min walk test (6MWT), Simple Physical Performance Battery (SPPB), SF-36 scale, Hospital Anxiety and Depression Scale (HADS) and Impact of Events Scale-Revised (IES-R) were tested before and after rehabilitation. Moreover, the incidence of major adverse cardiovascular events (MACE) was recorded at 3 months after PCI. After VR-based CR, the 6MWT distance and SPPB scores of patients in the experimental group were higher than those in control group (P < 0.05). The HADS scores and IES-R scores of the patients in the experimental group were lower than those in control group (P < 0.01), and the difference in SF-36 scale scores was not statistically significant between two groups (P > 0.05). The incidence of MACE was not significantly different at 3 months after PCI (P > 0.05). These results suggest that VR-based phase I CR program mitigates the degree of PCI postoperative stress, anxiety, and depression in elderly CHD patients, however, enhances the resistance to fatigue and does not increase the risk of adverse cardiac events, suggesting it is a safe intervention.

Deficiency of S100A8/A9 attenuates pulmonary microvascular leakage in septic mice.

BACKGROUND: We have reported a positive correlation between S100 calcium-binding protein (S100) A8/S100A9 and sepsis-induced lung damage before. However, limited knowledge exists concerning the biological role of S100A8/A9 in pulmonary vascular endothelial barrier dysfunction, as well as the diagnostic value of S100A8/A9 in sepsis. METHODS: Sepsis was induced in C57BL/6J mice and S100A9-knockout (KO) mice through the cecal ligation and puncture (CLP). Pulmonary vascular leakage was determined by measuring extravasated Evans blue (EB). Reverse transcription polymerase chain reaction and the histological score were used to evaluate inflammation and lung injury, respectively. Recombinant S100A8/A9 (rhS100A8/A9) was used to identify the effects of S100A8/A9 on endothelial barrier dysfunction in human umbilical vein endothelial cells (HUVECs). Additionally, the diagnostic value of S100A8/A9 in sepsis was assessed using receiver operating characteristic. RESULTS: S100A8/A9 expression was up-regulated in the lungs of CLP-operated mice. S100A9 KO significantly reversed CLP-induced hypothermia and hypotension, resulting in an improved survival rate. S100A9 KO also decreased the inflammatory response, EB leakage, and histological scores in the lungs of CLP-operated mice. Occludin and VE-cadherin expressions were decreased in the lungs of CLP-operated mice; However, S100A9 KO attenuated this decrease. Moreover, CLP-induced signal transducer and activator of transcription 3 (STAT3) and p38/extracellular signal-regulated kinase (ERK) signalling activation and apoptosis were mitigated by S100A9 KO in lungs. In addition, rhS100A8/A9 administration significantly decreased occludin and VE-cadherin expressions, increased the phosphorylated (p)-ERK/ERK, p-p38/p38, and B-cell leukaemia/lymphoma 2 protein (Bcl-2)-associated X protein/Bcl-2 ratios in HUVECs. CONCLUSION: The present study demonstrated S100A8/A9 aggravated sepsis-induced pulmonary inflammation, vascular permeability, and lung injury. This was achieved, at least partially, by activating the P38/STAT3/ERK signalling pathways. Moreover, S100A8/A9 showed the potential as a biomarker for sepsis diagnosis.

Electrocardiographic semi-spiked helmet sign in critically Ill patients: A case series.

RATIONALE: ST-segment elevation on electrocardiogram (ECG) is an alarming sign. Although acute myocardial infarction (AMI) is the most common cause of ST-segment elevation, many non-ischemic conditions may produce pseudo-ST segment elevation. Spiked Helmet (SH) sign is one of the pseudo-ST segment elevations that is associated with critical illness and high risk of death. SH sign was characterized by an upward shift starting before the onset of the QRS complex; however, we found some patients presented with a peculiar characteristic on ECG with an upward convex ST-segment elevation after the QRS wave but without elevation before the QRS wave, therefore called Semi-SH sign. Also, this electrocardiographic feature exists in patients with critical disease and is related to poor prognosis. The purpose of this case series is to describe the electrocardiographic Semi-SH sign and enhance the awareness of such electrocardiographic manifestation for clinicians. PATIENTS CONCERNS: This case series explores the possibility of severe infection induced electrocardiographic changes resembling spiked-helmet sign. DIAGNOSES: Sepsis-induced secondary myocardial injury or coronary vasospasm. INTERVENTIONS: Gastric decompression, antibiotics, diuretics, advanced life support. OUTCOMES: The outcome of this case series is the association of the electrocardiographic Semi-SH sign with the prognosis. All 3 patients died several days post manifestation of electrocardiographic Semi-SH sign. LESSON: Like SH sign, electrocardiographic Semi-SH sign is a life-threatening or deadly ECG sign, and therefore early recognition and aggressive treatment are important.

ATF3 regulates SPHK1 in cardiomyocyte injury via endoplasmic reticulum stress.

AIM: Endoplasmic reticulum (ER) stress is common in different human pathologies, including cardiac diseases. Sphingosine kinase-1 (SPHK1) represents an important player in cardiac growth and function. Nevertheless, its function in cardiomyocyte ER stress remains vague. This study sought to evaluate the mechanism through which SPHK1 might influence ER stress during myocardial infarction (MI). METHODS: MI-related GEO data sets were queried to screen differentially expressed genes. Murine HL-1 cells exposed to oxygen-glucose deprivation (OGD) and mice with MI were induced, followed by gene expression manipulation using short hairpin RNAs and overexpression vectors. The activating transcription factor 3 (ATF3) and SPHK1 expression was examined in cells and tissues. Cell counting kit-8, TUNEL, DHE, HE, and Masson's staining were conducted in vitro and in vivo. The inflammatory factor concentrations in mouse serum were measured using ELISA. Finally, the transcriptional regulation of SPHK1 by ATF3 was validated. RESULTS: ATF3 and SPHK1 were upregulated in vivo and in vitro. ATF3 downregulation reduced the SPHK1 transcription. ATF3 and SPHK1 downregulation increased the viability of OGD-treated HL-1 cells and decreased apoptosis, oxidative stress, and ER stress. ATF3 and SPHK1 downregulation narrowed the infarction area and attenuated myocardial fibrosis in mice, along with reduced inflammation in the serum and ER stress in the myocardium. In contrast, SPHK1 reduced the protective effect of ATF3 downregulation in vitro and in vivo. CONCLUSIONS: ATF3 downregulation reduced SPHK1 expression to attenuate cardiomyocyte injury in MI.

Association between serum copper level and reproductive health of Women in the United States: a cross-sectional study.

Copper is an indispensable trace element in metabolism. This study aimed to investigate the relationship between copper and reproductive health, and possibly provide new insights for diagnosis and treatment. This study was based on data extracted from the NHANES database (2013-2014 and 2015-2016). The t-test, ANOVA, Chi-square test, multiple linear regression, and restricted cubic spline analysis were used. Serum copper levels were significantly higher in women with gestational diabetes than in those without gestational diabetes (P = 0.0150). Women with higher copper levels and smoking habits tended to deliver overweight babies (P = 0.028). Women with diabetes had higher serum copper and were prone to deliver overweight babies (P = 0.024). Serum copper levels showed a positive relationship with sex hormone-binding globulin (SHBG) levels (P < 0.0001). In this study, serum copper levels were found to be associated with reproductive health in women. Further studies are required to draw causal inferences.

iNOS aggravates pressure overload-induced cardiac dysfunction via activation of the cytosolic-mtDNA-mediated cGAS-STING pathway.

Background: Sterile inflammation contributes to the pathogenesis of cardiac dysfunction caused by various conditions including pressure overload in hypertension. Mitochondrial DNA (mtDNA) released from damaged mitochondria has been implicated in cardiac inflammation. However, the upstream mechanisms governing mtDNA release and how mtDNA activates sterile inflammation in pressure-overloaded hearts remain largely unknown. Here, we investigated the role of inducible NO synthase (iNOS) on pressure overload-induced cytosolic accumulation of mtDNA and whether mtDNA activated inflammation through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. Methods: To investigate whether the cGAS-STING cascade was involved in sterile inflammation and cardiac dysfunction upon pressure overload, cardiomyocyte-specific STING depletion mice and mice injected with adeno-associated virus-9 (AAV-9) to suppress the cGAS-STING cascade in the heart were subjected to transverse aortic constriction (TAC). iNOS null mice were used to determine the role of iNOS in cGAS-STING pathway activation in pressure-stressed hearts. Results: iNOS knockout abrogated mtDNA release and alleviated cardiac sterile inflammation resulting in improved cardiac function. Conversely, activating the cGAS-STING pathway blunted the protective effects of iNOS knockout. Moreover, iNOS activated the cGAS-STING pathway in isolated myocytes and this was prevented by depleting cytosolic mtDNA. In addition, disruption of the cGAS-STING pathway suppressed inflammatory cytokine transcription and modulated M1/M2 macrophage polarization, and thus mitigated cardiac remodeling and improved heart function. Finally, increased iNOS expression along with cytosolic mtDNA accumulation and cGAS-STING activation were also seen in human hypertensive hearts. Conclusion: Our findings demonstrate that mtDNA is released into the cytosol and triggers sterile inflammation through the cGAS-STING pathway leading to cardiac dysfunction after pressure overload. iNOS controls mtDNA release and subsequent cGAS activation in pressure-stressed hearts.

Presence and impact of anemia in patients supported with left ventricular assist devices.

BACKGROUND: Data on anemia and its effects on patients supported with continuous-flow left ventricular assist devices (LVADs) are lacking. OBJECTIVES: This study sought to describe the presence of anemia over time and investigate its association with mortality, quality of life, exercise capacity, and adverse events in LVAD patients. METHODS: Adults receiving durable LVADs between 2008 and 2017 were identified from the INTERMACS database. The full cohort was stratified according to anemia severity (no anemia, mild, and moderate-severe). RESULTS: The analysis of 19,509 patients (females: 21.2%, age: 56.9 ± 12.9 years) showed that moderate-severe anemia affected 45.2% of patients at baseline, 33.5% of them at 6 months, and 32.3% in the fourth year after implantation. The presence of normal hemoglobin was 24.4% before surgery, 32.5% at 6 months, and 36.6% at 4 years after implantation. Multivariable linear mixed-effect regression revealed that the average hemoglobin over time was significantly lower (ß, -0.233, 95% confidence interval (CI): -0.282 to -0.185), and the reduction of hemoglobin over time was bigger (ß, -0.032 95% CI: -0.035 to -0.028) for LVAD nonsurvivors compared with LVAD survivors. Adjusted Cox regression showed that the severity of preimplant anemia was associated with higher mortality (HR, mild: 1.19; 95% CI: 1.05-1.35 and moderate-severe: 1.44; 95% CI: 1.28-1.62), with similar results in competing risk regression. Anemia progression during follow-up was associated with decreased Kansas City Cardiomyopathy Questionnaire scores and shorter 6-minute walk distances. CONCLUSIONS: In patients supported with LVADs, anemia is a frequent comorbidity, and deterioration over time is associated with poor prognosis.

Ivabradine in patients with acute ST-elevation myocardial infarction: a meta-analysis of randomized controlled trials.

BACKGROUND: Elevated resting heart rate (HR) predicts poor outcomes in patients with coronary artery disease. Ivabradine has been recommended as a second-line anti-anginal agent in chronic coronary syndrome, while there are no clear indications for acute ST-elevation myocardial infarction (STEMI). RESULTS: We systematically searched PubMed, Medline, EMBASE, Clinical Trials.gov, and the Cochrane Central Register of Controlled Trials with search terms Ivabradine and Acute myocardial infarction. There are two study outcomes from this study: therapeutic and safety effects. Therapeutic effects include the efficacy of Ivabradine on HR, all-cause mortality, heart failure incidence, left ventricular function and remodeling. Safety effects include troponin levels and ischemic events (recurrent angina pectoris). A total of 6 RCTs was included and showed that Ivabradine was associated with greater resting HR reduction [MD - 5.40; 95%CI - 8.60, - 2.20], improvement of left ventricular ejection fraction [MD 2.98; 95%CI 0.44, 5.51], and left ventricular end systolic volume [MD - 3.81; 95%CI - 6.88, - 0.75]. However, Ivabradine had no impact on all-cause mortality [OR 0.76; 95%CI 0.35, 1.67], heart failure incidence [OR 0.61; 95%CI 0.21, 1.80], and recurrent angina pectoris [OR 0.71; 95%CI 0.50, 1.00]. CONCLUSIONS: Ivabradine is safe and effective for resting HR reduction in patients with STEMI; however, it has no significant influence on mortality. These results suggest that an elevated HR is only a marker of risk but not a modifiable determinant of outcomes in patients who have suffered an acute myocardial infarction.

Takotsubo cardiomyopathy induced by pheochromocytoma: a case report.

Pheochromocytoma presents various clinical manifestations and imprecise signs and symptoms. Along with other diseases, it is considered to be 'the great mimic'. This is the case of a 61-year-old man who on arrival presented with extreme chest pain accompanied by palpitations, and with a blood pressure of 91/65 mmHg. An echocardiogram showed an ST-segment elevation in the anterior leads. The cardiac troponin was 1.62 ng/ml, 50 times the upper limit of normal. Bedside, echocardiography revealed global hypokinesia of the left ventricle, with an ejection fraction of 37%. Because ST-segment elevation myocardial infarction-complicated cardiogenic shock was suspected, an emergency coronary angiography was performed. It showed no significant coronary artery stenosis, while left ventriculography demonstrated left ventricular hypokinesia. Sixteen days after admission, the patient suddenly presented with palpitations, headache and hypertension. A contrast-enhanced abdominal CT showed a mass in the left adrenal area. Pheochromocytoma-induced takotsubo cardiomyopathy was suspected.

Ventricular septal rupture after acute myocardial infarction in a patient with venous thromboembolism complicated by thrombocytopenia: A case report.

A woman that suffered burns previously presented with leg swelling and was diagnosed with venous thromboembolism. Heparin was given until she suddenly developed myocardial infarction. Ventricular septal rupture was detected and managed by transcatheter closure. She developed massive bleeding and extensive thrombosis that made treatment paradoxical and eventually died.

Aerobic exercise inhibits renal EMT by promoting irisin expression in SHR.

To determine the effect of aerobic exercise in different intensities on renal injury and epithelial-mesenchymal transformation (EMT) in the kidney of spontaneously hypertensive rats (SHR) and explore possible mechanisms, we subjected SHR to different levels of 14-week aerobic treadmill training. We tested the effects of aerobic exercise on irisin level, renal function, and EMT modulators in the kidney. We also treated angiotensin II-induced HK-2 cells with irisin and tested the changes in EMT levels. The data showed low and moderate aerobic exercise improved renal function and inhibited EMT through promoting irisin expression in SHR. However, high-intensity exercise training had no effect on renal injury and EMT in SHR but did significantly activate STAT3 phosphorylation in the kidney. These results clarify the mechanisms of exercise in improving hypertension-related renal injury and suggest that irisin might be a therapeutic target for patients with kidney injury.