Novel application of drug-coated balloons in coronary heart disease: A narrative review.

The incidence of coronary heart disease (CAD) has soared over the years, and coronary intervention has become an increasingly important therapeutic approach. The past decade has witnessed unprecedented developments in therapeutic medical instruments. Given that drug-coated balloons bring many benefits, they are indicated for an increasing number of conditions. In this article, we review the results of current clinical trials about drug-coated balloons and summarize their safety and clinical progression in different coronary artery diseases, laying the groundwork for basic research, and clinical therapeutics of this patient population.

Novel predictors of stent under-expansion regarding calcified coronary lesions assessed by optical coherence tomography.

A previous calcium scoring system using circumferential angle, thickness, and length of coronary calcium by OCT could assist in predicting stent under-expansion. However, this scoring system only reflects the calcification distribution within a single cross-section and fails to consider the lumen's original size. The current study aims to investigate whether novel parameters to quantify calcium lesions, including calcium burden, area, and volume assessed by optical coherence tomography (OCT), could predict stent under-expansion related to calcium lesions. Consecutive patients admitted between March 10th to October 19th 2021 with calcified coronary lesions undergoing percutaneous coronary intervention (PCI) with OCT guidance were screened for inclusion. The calcium burden, area, and volume of the target lesions were measured using OCT at pre-PCI. After successful stent implantation, stent expansion at the corresponding lesions was also measured by OCT. A total of 125 patients who underwent OCT-guided PCI were included in this study. While the calcium grades by angiography failed to show a significant correlation with stent expansion, maximum and average calcium burden, maximum calcium area, and calcium volume exhibited a moderate correlation with stent expansion. According to the receiver operating characteristic curves, the optimal cutoffs of calcium volume and area for predicting stent under-expansion were 4.37 mm3 and 2.48 mm2 , respectively. Calcium burden, area, and volume by OCT are more favorable predictors of stent under-expansion given its better performance than calcium grades by angiography. Using cutoffs of calcium area and volume could identify high-risk patients of under-expansion and might guide future clinical practice.

Pathogenetic mechanisms of septic cardiomyopathy.

Sepsis is a serious complication after infection, whose further development may lead to multiple organ dysfunction syndrome and so on. It is an important cause of death in critically ill patients who suffered an infection. Sepsis cardiomyopathy is a common complication that exacerbates the prognosis of patients. At present, though the pathogenesis of sepsis cardiomyopathy is not completely clear, in-depth study of the pathogenesis of sepsis cardiomyopathy and the discovery of its potential therapeutic targets may decrease the mortality of sepsis patients and bring clinical benefits. This article reviews mitochondrial dysfunction, mitophagy, oxidation stress, and other mechanisms in sepsis cardiomyopathy.

Effects of sacubitril/valsartan on cardiac reverse remodeling and cardiac resynchronization in patients with acute myocardial infarction.

Introduction: In 2014, the PARADIGM-HF trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) has shown that sacubitril/valsartan can reduce the risk of hospitalization and death from cardiovascular causes more effectively than enalapril (an ACEI) in heart failure patients with reduced ejection fraction (HFrEF). Similarly, the PARADIGM-HF trial (Comparison of Sacubitril-Valsartan vs. Enalapril on Effect on NT-proBNP in Patients Stabilized from an Acute Heart Failure Episode) came to similar conclusions and extended the PARADIGM-HF trial results in 2019. Since then, numerous new studies have provided further insight in HFrEF, sacubitril/valsartan can reduce N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, increase left ventricular ejection fraction (LVEF), reverse ventricular remodeling, and reduce other non-fatal manifestations of clinical deterioration as compared to ACEI/ARB. However, few trials have compared the effects of these drugs in patients shortly after AMI. Therefore, it is necessary to further explore the clinical efficacy and safety of sacubitril/valsartan vs. valsartan in patients with AMI. Methods: We conducted an open-label, prospective, randomized controlled trial to determine the superiority in ameliorating ventricular remodeling and preventing of heart failure in patients with AMI after percutaneous coronary intervention (PCI), 148 patients were randomly assigned (85 to sacubitril/valsartan and 63 to valsartan). Results: LAV, LVDV, and LVSV were all decreased in the sacubitril/valsartan group when compared with before treatment, but there was no difference between the sacubitril/valsartan group and the valsartan group. In addition, compared with before treatment in the sacubitril/valsartan group, the heart global work index (GWI) and the global work efficiency (GWE) increased, while the heart global wasted work (GWW) decreased. Patients in the sacubitril/valsartan group have similar MACE and adverse side effects to those in the valsartan group. Conclusion: Sacubitril/valsartan has the same performance as valsartan in inhibiting ventricular remodeling and preventing heart failure after PCI in patients with AMI, and its clinical application is safe. It provides a clinical foundation for the application of sacubitril/valsartan in patients with AMI.

Ube2s-stabilized ß-catenin protects against myocardial ischemia/reperfusion injury by activating HIF-1α signaling.

The activation of hypoxia-inducible factor (HIF) is an important event for mediating the adaptive response to myocardial ischemia/reperfusion (MI/R) injury. The ubiquitin-conjugating enzyme E2S (Ube2s) catalyzes ubiquitin conjugation to target proteins. Here, we report the positive regulation of HIF-1α signaling by Ube2s via stabilizing ß-catenin, by which Ube2s acts to protect against MI/R injury. We show that Ube2s expression is upregulated in the hearts of mice subjected to MI/R injury. Functionally, Ube2s depletion exacerbates and its overexpression ameliorates MI/R injury. In addition, Ube2s augments the activation of HIF-1α and reduces myocardial apoptosis. Moreover, Ube2s induces the accumulation of ß-Catenin through increasing its stabilization. Importantly, ß-Catenin knockdown abrogates Ube2s-augmented HIF-1α activation, and meanwhile, diminishes the protective effect of Ube2s on MI/R injury, thus establishing a causal link between Ube2s-stabilized ß-catenin and HIF-1α-mediated myocardial protection. Altogether, this study identifies the Ube2s/ß-catenin/HIF-1α axis as a novel protective regulator involved in MI/R injury, and also implies that it might represent a potential therapeutic target for ameliorating MI/R injury.

Irisin attenuates angiotensin II-induced cardiac fibrosis via Nrf2 mediated inhibition of ROS/ TGFß1/Smad2/3 signaling axis.

Angiotensin II-related cardiac fibrosis is one of the key pathological changes of the hypertrophied left ventricle in various heart disease. Irisin was recently reported to confer cardio-protective and anti-oxidative effects, while whether it can reverse the renin-angiotensin-aldosterone system(RAAS) activation related(angiotensin II-induced) cardiac fibrosis is unknown. In this study, we found that angiotensin II-induced cardiac dysfunction and fibrotic responses were dampened by irisin treatment in mice. Mechanistically, angiotensin II induced robust ROS generation, which in turn triggered activation of pro-fibrotic TGFß1-Smad2/3 signaling and subsequent collagen synthesis and fibroblast-myofibroblast transformation in cardiac fibroblasts. In contrast, Irisin treatment suppressed angiotensin II-induced ROS generation, TGFß1 activation, collagen synthesis and fibroblast-myofibroblast transformation, the effects of which was accompanied by Nrf2 activation and also abolished by a Nrf2 targeted siRNA. Taken together, we here identified irisin as a promising anti-fibrotic therapeutic for angiotensin II-related cardiac fibrosis.