UNASSIGNED: Implantable cardioverter-defibrillator (ICD) implantation to prevent sudden cardiac death (SCD) in post-myocardial infarction (MI) patients varies by geography but remains low in many regions despite guideline recommendations.
UNASSIGNED: This study aimed to characterize the care pathway of post-MI patients and understand barriers to referral for further SCD risk stratification and management in patients meeting referral criteria.
UNASSIGNED: This prospective, nonrandomized, multi-nation study included patients ≥18 years of age, with an acute MI ≤30 days and left ventricular ejection fraction <50% ≤14 days post-MI. The primary endpoint was defined as the physician\'s decision to refer a patient for SCD stratification and management.
UNASSIGNED: In total, 1,491 post-MI patients were enrolled (60.2 ± 12.0 years of age, 82.4% male). During the study, 26.7% (n = 398) of patients met criteria for further SCD risk stratification; however, only 59.3% of those meeting criteria (n = 236; 95% CI: 54.4%-64.0%) were referred for a visit. Of patients referred for SCD risk stratification and management, 94.9% (n = 224) attended the visit of which 56.7% (n =127; 95% CI: 50.1%-63.0%) met ICD indication criteria. Of patients who met ICD indication criteria, 14.2% (n = 18) were implanted.
UNASSIGNED: We found that ∼40% of patients meeting criteria were not referred for further SCD risk stratification and management and ∼85% of patients who met ICD indications did not receive a guideline-directed ICD. Physician and patient reasons for refusing referral to SCD risk stratification and management or ICD implant varied by geography suggesting that improvement will require both physician- and patient-focused approaches. (Improve Sudden Cardiac Arrest [SCA] Bridge Study; NCT03715790).

Cardiorenal syndrome type 2 (CRS2) is defined as a chronic cardiovascular disease, usually chronic heart failure (CHF), resulting in chronic kidney disease. We hypothesized that the cardiac spinal afferent reflex (CSAR) plays a critical role in the development of CRS2. Our data suggest that cardiac afferent ablation by resiniferatoxin not only improves cardiac function but also benefits the kidneys and increases long-term survival in the myocardial infarction model of CHF. We also found that renal denervation has a similar reno-protective effect in CHF rats. We believe this novel work contributes to the development of a unique neuromodulation therapy to treat CHF patients.

UNASSIGNED: There were no reports on the associations of aortic arch calcification (AAC) measured by chest X-ray with all-cause mortality and cardiovascular disease (CVD) in older general population. Moreover, previous studies of hemodialysis patients showed that AAC was correlated with left ventricular hypertrophy (LVH) and predicted CVD jointly. Whether the effects remained in the general population is unknown. We examined the associations of AAC with all-cause mortality and CVD in general population and the risk associated with the coexistence of AAC and LVH.
UNASSIGNED: Presence and severity (grades 0-2) of AAC were measured by chest X-ray, and LVH was identified by 12-lead electrocardiogram in 27,166 Chinese aged 50+ years free of CVD from Guangzhou Biobank Cohort Study. Multivariate Cox regressions were used to examine associations of AAC and LVH with outcomes.
UNASSIGNED: During an average follow-up of 14·3 years, 5,350 deaths and 4,012 CVD occurred. Compared to those without AAC at baseline, those with AAC had higher risks of all-cause mortality (HR 1·24, 95% CI 1·17-1·31) and CVD (HR 1·22, 95% CI 1·14-1·30), with dose-response relationship (P ≤ 0·001). Furthermore, those with coexistence of AAC and LVH had higher risks of all-cause mortality (HR 1·72, 95% CI 1·37-2·15) and CVD (HR 1·80, 95% CI 1·40-2·32) than those without AAC and LVH.
UNASSIGNED: As chest X-ray has been performed commonly for health screening and in hospital patients when first admitted, AAC measured by chest X-ray can be further applied to assist cardiovascular risk stratification in the community and clinical settings.
UNASSIGNED: The Natural Science Foundation of China (No. 81941019).

Umbilical cord mesenchymal stem cells (UCMSCs) transplantation has been proposed as a promising treatment modality for myocardial infarction (MI), but the low retention rate remains a considerable challenge. Injectable natural polymer hydrogels with conductivity ability are highly desirable as cell delivery vehicles to repair infarct myocardium and restore the cardiac function. In this work, we developed a hydrogel system based on gelatin methacrylate (GelMA) and oxidized dextran (ODEX) as cell delivery vehicles for MI. And dopamine could be used as a reductant of graphene oxide (GO) to form reductive GO (rGO). By adjusting the amount of rGO, the conductivity of hydrogels with 0.5 mg/mL rGO concentration (≈10-4 S/cm) was similar to that of natural heart tissue. In vitro cell experiments showed that the prepared hydrogels had excellent biocompatibility and cell delivery ability of UCMSCs. More importantly, GelMA-O5/rGO hydrogel could promote UCMSCs growth and proliferation, improve the myocardial differentiation ability of UCMSCs, and up-regulate the expression of cTnI and Cx43. Further in vivo experiments demonstrated that GelMA-O5/rGO/UCMSCs Hydrogel could significantly improve the ejection fraction (EF) of rats and significantly reduce myocardial infarct area compared to PBS group, promote the survival of UCMSCs, enhance the expression level of cTnI and Cx43, and decrease the expression level of caspase-3. The findings of this study suggested that the injectable conductive GelMA-O5/rGO hydrogel encapsulating UCMSCs could improve damaged myocardial tissue and reconstruct myocardial function, which will be a promising therapeutic strategy for cardiac repair.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling exert essential regulatory function in microbial-and onco-immunology through the induction of cytokines, primarily type I interferons. Recently, the aberrant and deranged signaling of the cGAS-STING axis is closely implicated in multiple sterile inflammatory diseases, including heart failure, myocardial infarction, cardiac hypertrophy, nonalcoholic fatty liver diseases, aortic aneurysm and dissection, obesity, etc. This is because of the massive loads of damage-associated molecular patterns (mitochondrial DNA, DNA in extracellular vesicles) liberated from recurrent injury to metabolic cellular organelles and tissues, which are sensed by the pathway. Also, the cGAS-STING pathway crosstalk with essential intracellular homeostasis processes like apoptosis, autophagy, and regulate cellular metabolism. Targeting derailed STING signaling has become necessary for chronic inflammatory diseases. Meanwhile, excessive type I interferons signaling impact on cardiovascular and metabolic health remain entirely elusive. In this review, we summarize the intimate connection between the cGAS-STING pathway and cardiovascular and metabolic disorders. We also discuss some potential small molecule inhibitors for the pathway. This review provides insight to stimulate interest in and support future research into understanding this signaling axis in cardiovascular and metabolic tissues and diseases.

Cardiovascular diseases such as myocardial infarction (MI) are among the major causes of death worldwide. Although intramyocardial injection of hydrogels can effectively enhance the ventricular wall, this approach is limited because of its restriction to the poor vascularization in the infarcted myocardium. Here, we reported a new type of hydrogel composed of alginate (ALG) and hyaluronic acid (HA) with lyophilized platelet-rich fibrin (Ly-PRF) for releasing abundant growth factors to realize their respective functions. The results of in vitro studies demonstrated favorable mechanical property and release ability of ALG-HA with Ly-PRF. When injected into the infarcted myocardium, this composite hydrogel preserved heart function and the Ly-PRF within the hydrogel promoted angiogenesis and increased vascular density in both infarcted and border zone, which rescued the ischemic myocardium. These beneficial effects were also accompanied by macrophage polarization and regulation of myocardial fibrosis. Moreover, the autologous origin of Ly-PRF with ALG-HA hydrogel offers myriad advantages including safety profile, easiness to obtain and cost-effectiveness. Overall, this study demonstrated the versatile therapeutic effects of a novel composite hydrogel ALG-HA with Ly-PRF, which optimizes a promising vascularized substitution strategy for improving cardiac function after MI.

BACKGROUND: The optimal antithrombotic strategy, especially regarding oral anticoagulants (OACs) for atrial fibrillation (AF) patients with bleeding and thrombosis risk after percutaneous coronary intervention (PCI), remains unknown. This study explored the optimal oral anticoagulants for AF patients after PCI using a meta-analysis.
METHODS: Randomised controlled trials were identified from PubMed, Embase, and the Cochrane Library through December 2020. Risk ratios, 95% confidence intervals, and random-effects models were used to compare different antithrombotic strategies through network meta-analysis, and the combination of antithrombotic agents was ranked according to the surface under the cumulative ranking curve and rankograms. Interval plots were drawn to observe pairwise comparisons between the different strategies.
RESULTS: Five studies of 11,532 patients were included. Factor IIa inhibitor 110 mg bid plus a P2Y12 inhibitor had the greatest advantage for reducing Thrombolysis In Myocardial Infarction (TIMI) major or minor bleeding; Factor Xa inhibitor plus a P2Y12 inhibitor had the greatest advantage for reducing International Society on Thrombosis and Hemostasis major bleeding. For patients at risk of stroke plus all-cause death, factor IIa inhibitor 150 mg bid plus a P2Y12 inhibitor should be prioritised, and for those at risk of myocardial infarction and stent thrombosis, vitamin K antagonists plus a P2Y12 inhibitor were preferred.
CONCLUSIONS: Factor IIa inhibitor 110 mg, factor IIa inhibitor 150 mg, factor Xa inhibitor and vitamin K antagonists should be selected in different situations.

UNASSIGNED: To carry out a systematic review of the effect of cardiac rehabilitation (CR) and its components on cardiovascular outcomes in patients with stable angina.
UNASSIGNED: We searched the databases including Ovid MEDLINE, Ovid Embase, Scopus, Web of Science, Google Scholar, and EBSCO CINAHL from their inception up to November 1, 2017. The search was not restricted to time or publication status but was limited to the English language. Two independent investigators screened the identified studies and extracted the data in duplicate. We reviewed the included studies and, where possible, pooled their results and conducted meta-analyses. Risk of bias was assessed using Cochrane Collaboration tools.
UNASSIGNED: The search identified 7508 studies. Ten randomized trials including 4005 participants with the mean (SD) age of 59.6 (5.7) years were considered eligible for inclusion in our analyses. The results of meta-analyses of exercise-based CR for patients with stable angina revealed that CR improved exercise capacity (the difference between baseline and follow-up was 0.76 watt [0.49 to 1.02] higher in the CR group vs the non-CR group) and decreased angina frequency (standard mean difference, -0.27 [CI, -0.43 to 0.11]). No significant differences were noted in other outcomes, including quality of life. Mortality could not be adequately assessed because it was analyzed in only 1 exercise-based CR study.
UNASSIGNED: Our systematic review, involving a relatively small number of studies with low to moderate risk of bias and with considerable heterogeneity, found a significant decrease in angina frequency and increase in exercise capacity in patients with stable angina who participated in an exercise-based CR program. Studies involving the impact of components of CR are limited and generally report beneficial outcomes. Additional studies are needed to clarify the possible role of CR in the management of patients with stable angina.

As an effective anticancer drug, the clinical limitation of doxorubicin (Dox) is the time- and dose-dependent cardiotoxicity. Yes-associated protein 1 (YAP1) interacts with transcription factor TEA domain 1 (TEAD1) and plays an important role in cell proliferation and survival. However, the role of YAP1 in Dox-induced cardiomyopathy has not been reported. In this study, the expression of YAP1 was reduced in clinical human failing hearts with dilated cardiomyopathy and Dox-induced in vivo and in vitro cardiotoxic model. Ectopic expression of Yap1 significantly blocked Dox-induced cardiomyocytes apoptosis in TEAD1 dependent manner. Isorhapontigenin (Isor) is a new derivative of stilbene and responsible for a wide range of biological processes. Here, we found that Isor effectively relieved Dox-induced cardiomyocytes apoptosis in a dose-dependent manner in vitro. Administration with Isor (30 mg/kg/day, intraperitoneally, 3 weeks) significantly protected against Dox-induced cardiotoxicity in mice. Interestingly, Isor increased Dox-caused repression in YAP1 and the expression of its target genes in vivo and in vitro. Knockout or inhibition of Yap1 blocked the protective effects of Isor on Dox-induced cardiotoxicity. In conclusion, YAP1 may be a novel target for Dox-induced cardiotoxicity and Isor might be a new compound to fight against Dox-induced cardiotoxicity by increasing YAP1 expression.

Mice were treated with a fully human monoclonal glucagon receptor antagonistic antibody REMD2.59 following myocardial infarction or pressure overload. REMD2.59 treatment blunted cardiac hypertrophy and fibrotic remodeling, and attenuated contractile dysfunction at 4 weeks after myocardial infarction. In addition, REMD2.59 treatment at the onset of pressure overload significantly suppressed cardiac hypertrophy and chamber dilation with marked preservation of cardiac systolic and diastolic function. Initiation of REMD2.59 treatment 2 weeks after pressure overload significantly blunted the progression of cardiac pathology. These results provide the first in vivo proof-of-concept evidence that glucagon receptor antagonism is a potentially efficacious therapy to ameliorate both onset and progression of heart failure.