Aims Non-invasive myocardial work offers a promising echocardiographic method to evaluate left ventricular (LV) function as it integrates myocardial deformation and afterload. The study sought to investigate the association of myocardial work indices with post-operative LV dysfunction in patients with chronic severe aortic regurgitation (AR). Methods and results Pre-operative LV ejection fraction (LVEF), LV global work index (LV GWI), LV global constructive work (LV GCW), LV global wasted work (LV GWW), and LV global work efficiency (LV GWE) were measured. Post-operative LV dysfunction was defined as LVEF < 50% at 12 months after surgery. One hundred and forty-one patients with chronic severe AR and preserved LVEF (52 (42-58) years; 74.5% men) who underwent aortic valve surgery were studied. Twenty-six patients (18%) developed post-operative LV dysfunction. Patients with post-operative LV dysfunction had lower LV GWI, LV GCW, and LV GWE compared with those without (all P < 0.05). In multivariate analysis, LV GWI (adjusted odds ratio (OR): 0.99; 95% CI: 0.98-1.00; P < 0.001), and LV GCW (adjusted OR: 0.99; 95% CI: 0.99-1.00; P < 0.001) were associated with post-operative LV dysfunction. Moreover, a multivariate logistic regression model with LV GWI (Akaike information criterion = 108.023, Bayesian information criterion = 119.818, C-statistics = 0.836) showed the best capability in predicting post-operative LV dysfunction. The comparative analysis of C-statistics across the three models-LV GWI, LV GCW, and LV GLS-did not reveal statistically significant differences (all P > 0.05). Conclusion In patients with chronic severe AR and preserved LVEF, impaired myocardial work indices are associated with post-operative LV dysfunction. Myocardial work has potential value for risk stratification and surgical decision-making in such a population.

PurposeThe impact of aortic stenosis (AS) severity on multidirectional myocardial function in patients with bicuspid aortic valve (BAV) remains unclear, despite the recognized presence of early left ventricular longitudinal myocardial dysfunction in BAV patients with normal valve function. The aim of the study was to evaluate the multidirectional myocardial functions of BAV patients.MethodsA total of 86 BAV patients (age 46.71 ± 13.62 years, 69.4% men) with normally functioning (BAV-nf), mild AS, moderate AS, and severe AS with preserved left ventricular ejection fraction (LVEF ≥ 52%) were included. 30 healthy volunteers were recruited as the control group. Multidirectional strain and volume analysis were performed by three-dimensional speckle tracking echocardiography(3D-STE).ResultsGlobal longitudinal strain (GLS), and global radial strain (GRS) were reduced in BAV-nf patients compared with the controls. With each categorical of AS severity from BAV-nf to severe AS, there was an associated progressive impairment of GLS and GRS (all P < 0.001). Global circumferential strain (GCS) did not show a significant decrease from BAV-nf to mild AS but began to decrease from moderate AS. Multiple linear regressions indicated that indexed aortic valve area (AVA/BSA), as a measure of AS severity, was an independent determinant of GLS, GCS and GRS.ConclusionsLeft ventricular longitudinal myocardial reduction is observed even in patients with well-functioning bicuspid aortic valves. With each categorical increase in the grade of AS severity from normally functioning to severe aortic stenosis, there was an associated progressive impairment of longitudinal myocardial function. Furthermore, circumferential myocardial function was starting damaged from moderate AS. AVA/BSA was independently associated with multidirectional myocardial function injuries.

Sepsis-associated encephalopathy (SAE) is a collection of clinical syndromes resulting from sepsis and characterized by widespread brain dysfunction. The high prevalence of SAE has adverse outcomes on the clinical management and prognosis of sepsis patients. However, currently, there are no effective treatments to ameliorate SAE. The pathogenesis of SAE is complex, including neuroinflammation and microglia activation, destruction of the blood-brain barrier (BBB), neurotransmitter dysfunction, cerebral metabolism and mitochondrial impairment, accumulation of amyloid beta and tauopathy, complement activation, among others. Furthermore, these mechanisms intertwine with each other, further complicating the comprehension of SAE. Among them, neuroinflammation mediated by hyperactivated microglia is considered the primary etiology of SAE. This instigates a detrimental cycle wherein BBB permeability escalates, facilitating direct damage to the central nervous system (CNS) by various neurotoxic substances. Activation of the NLRP3 inflammasome, situated within microglia, can be triggered by diverse danger signals, leading to cell pyroptosis, apoptosis, and tauopathy. These complex processes intricately regulate the onset and progression of neuroinflammation. In this review, we focus on elucidating the inhibitory regulatory mechanism of the NLRP3 inflammasome in microglia, which ultimately manifests as suppression of the inflammatory response. Our ultimate objective is to augment comprehension regarding the role of microglial NLRP3 inflammasome as we explore potential targets for therapeutic interventions against SAE.

BACKGROUND:Right ventricular (RV) involvement has been reported in type 2 diabetes mellitus (T2DM). The relationship between glycemic control and RV function remains unknown. We aimed to investigate the association between glycemic control and RV function assessed by two-dimensional speckle-tracking echocardiography and three-dimensional echocardiography in T2DM individuals. METHODS:This study prospectively enrolled 207 patients with T2DM and 84 individuals with normal glucose metabolism. The T2DM patients were divided into 2 subgroups according to glycated hemoglobin (HbA1c) level: controlled (HbA1c < 7.0%, n = 91) and uncontrolled subgroup (HbA1c ≥ 7.0%, n = 116). Right venticular free wall longitudinal strain (RVFWLS) was acquired by two-dimensional speckle-tracking echocardiography, and RV volumes and RV ejection fraction (RVEF) were assessed using three-dimensional echocardiography . Right ventricular coupling to pulmonary circulation was defined as the ratio of RVFWLS/pulmonary artery systolic pressure (PASP). RESULTS:Controlled and uncontrolled T2DM subgroups had impaired RV function as reflected by reduced RVFWLS and RVEF compared to the normal glucose metabolism group. The reduction in RVFWLS was more pronounced in the uncontrolled subgroup than in the controlled subgroup (P < .001), whereas no significant difference was found in RVEF between these 2 T2DM subgroups. Higher PASP and lower RVFWLS/PASP ratio were also noted in uncontrolled T2DM patients. Additionally, the incidence of RV dysfunction was significantly higher in the uncontrolled T2DM patients than in the controlled subgroup (43.1% vs 17.6%, P < .001). After adjustment for potential clinical confounders, PASP, and left ventricular parameters, HbA1c level was independently associated with RVFWLS (β = 0.290, P = .003) and RVFWLS/PASP ratio (β = 0.028, P = .006). CONCLUSIONS:Subclinical RV myocardial dysfunction is present in T2DM patients and is more pronounced in patients with uncontrolled blood glucose. HbA1c level is independently associated with subclinical RV myocardial dysfunction, providing further insight into a possible link between poor glycemic control and diabetic cardiomyopathy.

Background Left atrial reservoir strain (LARS) is a novel imaging biomarker of left ventricular diastolic dysfunction. This study aimed to examine the prognostic implications of LARS in patients with bicuspid aortic valve and significant (moderate‐severe to severe) aortic regurgitation. Methods and Results A total of 220 patients with bicuspid aortic valve and significant aortic regurgitation were prospectively enrolled in our study. LARS and left ventricular global longitudinal strain were derived from speckle‐tracking echocardiography. The end point was a composite of all‐cause mortality, heart failure hospitalization, and aortic valve repair or replacement. The threshold value of LARS <24% was used to identify impaired left atrial mechanics based on prior results. During a median follow‐up of 364 (interquartile range, 294–752) days, 46 patients (20.9%) reached the composite end points. On multivariable Cox analysis, impaired LARS (adjusted hazard ratio, 2.08 [95% CI, 1.05–4.11]; P =0.036) was a statistically significant predictor of composite end points after adjustment for other statistically significant predictors. Finally, adding impaired LARS to other statistically significant predictors (New York Heart Association functional class and left ventricular global longitudinal strain) significantly improved the global χ 2 (from 32.19 to 36.56; P =0.037) and reclassification (continuous net reclassification index=0.55; P <0.001) of the prediction model. Conclusions In patients with bicuspid aortic valve and significant aortic regurgitation, the impairment of LARS is a strong independent prognostic predictor and confers incremental prognostic utility over clinical and other echocardiographic parameters. These findings suggest that LARS could be considered in risk stratification for such populations.

Interfacial nanobubbles on a superhydrophobic surface can serve as ultrasound cavitation nuclei for continuously promoting sonodynamic therapy, but their poor dispersibility in blood has limited their biomedical application. In this study, we proposed ultrasound-responsive biomimetic superhydrophobic mesoporous silica nanoparticles, modified with red blood cell membrane and loaded with doxorubicin (DOX) (F-MSN-DOX@RBC), for RM-1 tumor sonodynamic therapy. Their mean size and zeta potentials were 232 ± 78.8 nm and −35.57 ± 0.74 mV, respectively. The F-MSN-DOX@RBC accumulation in a tumor was significantly higher than in the control group, and the spleen uptake of F-MSN-DOX@RBC was significantly reduced in comparison to that of the F-MSN-DOX group. Moreover, the cavitation caused by a single dose of F-MSN-DOX@RBC combined with multiple ultrasounds provided continuous sonodynamic therapy. The tumor inhibition rates in the experimental group were 71.5 8 ± 9.54%, which is significantly better than the control group. DHE and CD31 fluorescence staining was used to assess the reactive oxygen species (ROS) generated and the broken tumor vascular system induced by ultrasound. Finally, we can conclude that the combination of anti-vascular therapy, sonodynamic therapy by ROS, and chemotherapy promoted tumor treatment efficacy. The use of red blood cell membrane-modified superhydrophobic silica nanoparticles is a promising strategy in designing ultrasound-responsive nanoparticles to promote drug-release.

Background: Noninvasive left ventricular pressure-strain myocardial work (MW) is a novel method for evaluating left ventricular function that integrates myocardial deformation and afterload and has certain advantages over global longitudinal strain (GLS). The study aimed to analyze MW in patients with well-functioning bicuspid aortic valve (BAV) and explore the influences of aortic dilation and arterial stiffness on left ventricular function.Methods: A total of 104 patients with well-functioning BAVs and 50 controls were enrolled in our study. Global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE), GLS, and aortic stiffness index were measured. Based on the ascending aortic diameter, patients with BAV were divided into 3 subgroups (nondilated, mildly dilated, and moderately dilated).Results: GWI, GCW, GWW, and aortic stiffness index were significantly increased (P<0.001, P=0.023, P<0.001, and P<0.001, respectively), while GWE and GLS were significantly decreased among patients with BAV compared with controls (all P values <0.001). Patients with BAV and mildly and moderately dilated aortas had an increased GWW and aortic stiffness index but a decreased GWE compared with patients with BAV and nondilated aortas (all P values <0.05); meanwhile, GCW and GLS did not differ among the BAV subgroups (all P values >0.05). GWI was elevated in patients with BAV and moderately dilated aortas compared with patients with BAV and nondilated aortas (P<0.05). On multivariable analysis, the aortic stiffness index was an independent influencer of GWI, GCW, GWW, and GWE (P=0.025, P=0.049, P<0.001, and P=0.001, respectively). The aortic diameter was highly correlated with the aortic stiffness index (r=0.863; P<0.001).Conclusions: MW could assess early myocardial impairment in patients with well-functioning BAV. MW may help to differentiate the detrimental effect of aortic dilation on left ventricular function, whereas GLS may not.

BACKGROUND:Left atrial reservoir strain (LARS) is an early sensor of left ventricular (LV) diastolic dysfunction. Still, the clinical implications of LARS in patients with well-functioning bicuspid aortic valve (BAV) remain unknown.MATERIALS:The study recruited 103 patients with well-functioning BAV and 50 controls with tricuspid aortic valves. LARS, LV global longitudinal strain (LVGLS) and aortic elasticity indices (aortic strain, aortic distensibility and stiffness index) were acquired. This study aimed to analyze the changes of LARS and further explore the influential factors of LARS in patients with well-functioning BAV.RESULTS:Patients with BAV had lower LARS (34.17 ± 4.85 vs. 44.72 ± 6.06 %, P < .001) and LVGLS (20.53 ± 1.28 vs. 22.30 ± .62 %, P < .001), and abnormal aortic elasticity indices (aortic strain:7.14 ± 1.57 vs. 10.99 ± 1.03 %, aortic distensibility: 5.82 ± 1.50 vs. 8.98 ± 2.42 (10-6 cm2 dyne-1 ), and stiffness index: 6.30 ± 2.30 vs. 3.92 ± .98, all P < .05) compared with controls. LARS was associated with LVGLS (r = .799), interventricular septum index (r = -.232), lateral e' (r = .290), septal e' (r = .308), E/e' ratio (r = -.392), aortic strain (r = .829), aortic distensibility (r = .361), and stiffness index (r = -.724) (all P < .05). LVGLS, aortic strain and E/e' ratio were independent influencers of LARS in the multifactorial analysis model (all P < .05).CONCLUSION:In patients with well-functioning BAV, decreased LARS may provide evidence of subclinical LV diastolic function impairment. LARS may be helpful for clinical risk stratification in such a population.

二叶式主动脉瓣(BAV)是最常见的先天性心脏疾病,BAV主动脉扩张与主动脉不良事件如主动脉瘤、主动脉夹层及破裂的风险增加密切相关,是一种潜在的致命性疾病.BAV主动脉疾病是遗传因素和血流动力学因素不同模式相互作用的结果,机制较为复杂.本文根据近年来BAV在基因遗传学、分子标记物、血流动力学影像标记物方面的研究进展,对其引起主动脉扩张的相关机制进行简要综述.

Background: Oxidative stress is crucial in experimental autoimmune myocarditis (EAM)-induced inflammatory myocardial injury. Ursolic acid (UA) is an antioxidant-enriched traditional Chinese medicine formula. The present study aimed to investigate whether UA could alleviate inflammatory cardiac injury and determine the underlying mechanisms. Methods: Six-week-old male BALB/c mice were randomly assigned to one of the three groups: Sham, EAM group, or UA intervention group (UA group) by gavage for 2 weeks. An EAM model was developed by subcutaneous injection of α-myosin heavy chain derived polypeptide (α-MyHC peptide) into lymph nodes on days 0 and 7. Echocardiography was used to assess cardiac function on day 21. The inflammation level in the myocardial tissue of each group was compared using hematoxylin and eosin staining (HE) of heart sections and Interleukin-6 (IL-6) immunohistochemical staining. Masson staining revealed the degree of cardiac fibrosis. Furthermore, Dihydroethidium staining, Western blot, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) were used to determine the mechanism of cardioprotective effects of UA on EAM-induced cardiac injury, and the level of IL-6, Nrf2, and HO-1. Results: In EAM mice, UA intervention significantly reduced the degree of inflammatory infiltration and myocardial fibrosis while improving cardiac function. Mechanistically, UA reduced myocardial injury by inhibiting oxidative stress (as demonstrated by a decrease of superoxide and normalization of pro- and antioxidant enzyme levels). Interestingly, UA intervention upregulated the expression of antioxidant factors such as Nrf2 and HO-1. In vitro experiments, specific Nrf2 inhibitors reversed the antioxidant and antiapoptotic effects of ursolic acid, which further suggested that the amelioration of EAM by UA was in a Nrf2/HO-1 pathway-dependent manner. Conclusion: These findings indicate that UA is a cardioprotective traditional Chinese medicine formula that reduces EAM-induced cardiac injury by up-regulating Nrf2/HO-1 expression and suppressing oxidative stress, making it a promising therapeutic strategy for the treatment of EAM.

BackgroundThe relationship between acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) and cardiac function is not well established. This study aimed to evaluate whether AML patients exist early myocardial damages prior to chemotherapy and to investigate its association with cardiovascular biomarkers.MethodsConventional echocardiography and three-dimensional speckle-tracking strain analysis were performed prospectively in 72 acute leukemia (AL) patients before any chemotherapy therapy (of whom 44 were AML patients, 28 ALL patients). The results were compared with those from 58 control group matched for age and gender.ResultsThere were no significant differences in conventional biventricular systolic function parameters between AL patients and controls. The left ventricular global longitudinal strain (LVGLS) and right ventricular free wall longitudinal strain (RVFWLS) were significantly lower in AL patients (−23.0 ± 1.4% vs. −24.1 ± 1.3% and −27.9 ± 7.1% vs. −33.0 ± 4.6%, respectively, P < 0.001 for all). Compared with ALL patients, AML patients had lower LVGLS and RVFWLS (−22.7 ± 1.3% vs. −23.5 ± 1.6% and −26.2 ± 7.6% vs. −30.4 ± 5.5%, respectively, P < 0.05 for all). LVGLS was lower in ALL patients compared with controls (−23.5 ± 1.6% vs. −24.7 ± 1.4%, P < 0.05), however, there was no difference in right ventricular systolic function parameters between the two groups. LVGLS in AL patients was independently correlated with left ventricular ejection fraction (LVEF) and the absolute number of circulating lymphocytes.ConclusionsOur findings suggest that baseline myocardial systolic function is lower in AL patients than controls. AML patients had lower baseline LVGLS and RVFWLS than controls and ALL patients. The decreased LVGLS is correlated with LVEF and the absolute number of circulating lymphocytes.

The cholinergic anti-inflammatory pathway (CAP) has been widely studied to modulate the immune response. Current stimulating strategies are invasive or imprecise. Noninvasive low-intensity pulsed ultrasound (LIPUS) has become increasingly appreciated for targeted neuronal modulation. However, its mechanisms and physiological role on myocarditis remain poorly defined. The mouse model of experimental autoimmune myocarditis was established. Low-intensity pulsed ultrasound was targeted at the spleen to stimulate the spleen nerve. Under different ultrasound parameters, histological tests and molecular biology were performed to observe inflammatory lesions and changes in immune cell subsets in the spleen and heart. In addition, we evaluated the dependence of the spleen nerve and cholinergic anti-inflammatory pathway of low-intensity pulsed ultrasound in treating autoimmune myocarditis in mice through different control groups. The echocardiography and flow cytometry of splenic or heart infiltrating immune cells revealed that splenic ultrasound could alleviate the immune response, regulate the proportion and function of CD4+ Treg and macrophages by activating cholinergic anti-inflammatory pathway, and finally reduce heart inflammatory injury and improve cardiac remodeling, which is as effective as an acetylcholine receptor agonists GTS-21. Transcriptome sequencing showed significant differential expressed genes due to ultrasound modulation. It is worth noting that the ultrasound therapeutic efficacy depends greatly on acoustic pressure and exposure duration, and the effective targeting organ was the spleen but not the heart. This study provides novel insight into the therapeutic potentials of LIPUS, which are essential for its future application.

二叶式主动脉瓣(bicuspid aortic valve,BAV)是临床最常见的先天性心脏瓣膜病.近年来,其发病率呈增加趋势.BAV患者早期常无明显症状,难以准确诊断和及时干预,晚期易伴发瓣膜功能障碍及主动脉瘤、主动脉夹层等严重并发症.因此,早期准确评估BAV形态及功能从而对其进行及时有效干预是临床诊治BAV疾病的重点.近年来,多模态影像技术在BAV患者的早期诊断、临床治疗指导和预后评估等方面发挥重要作用.该文将重点论述超声心动图、计算机断层扫描和心脏磁共振技术在BAV瓣膜形态学及功能评价中的应用.

Significant advances in application of therapeutic ultrasound have been reported in the past decades. Therapeutic ultrasound is an emerging non-invasive stimulation technique. This approach has shown high potential for treatment of various disease including cardiovascular disease. In this review, application principle and significance of the basic parameters of therapeutic ultrasound are summarized. The effects of therapeutic ultrasound in myocardial ischemia, heart failure, myocarditis, arrhythmias, and hypertension are explored, with key focus on the underlying mechanism. Further, the limitations and challenges of ultrasound therapy on clinical translation are evaluated to promote application of the novel strategy in cardiovascular diseases.

急性心肌炎(AM)临床表现多变,早期明确诊断对临床决策与预后评估具有重要意义.作为无创诊断AM的主要工具,超声心动图、MRI及PET可从形态、功能及分子水平显示心肌损伤,在其风险分层和临床管理中发挥关键作用.本文就多模态影像学用于诊断与治疗AM进展进行综述.

暴发性心肌炎(fulminant myocarditis，FM)起病急骤、进展迅速、死亡率高。因缺乏特异性的诊断方法，FM易被忽视和误诊。早期评估心脏形态和功能改变能够为临床治疗和随访提供可靠依据。超声心动图作为一种无创、安全和便携的影像学诊断工具，在FM诊断和治疗中的作用不可替代。本文就超声心动图在FM诊断中的应用现状、预后评估和未来发展进行综述。

Atherosclerosis is regarded as chronic inflammatory disease. The IL-6/STAT3 pathway plays an important role in inflammation. We previously described a small-molecule compound, Bazedoxifene, which target IL-6/STAT3 pathway and has been approved for clinical use for osteoporosis in postmenopausal women. The aim of this study is to evaluate the effect of Bazedoxifene in the progression of atherosclerosis in apolipoprotein E-deficient (ApoE-/-) mice. Five-week-old male ApoE-/- mice were fed with High-fat diet (HFD) containing 5 mg/kg Bazedoxifene or a matching control for 12 weeks. Oil red O (ORO) staining was used to detect plaque size; immunohistochemical staining was used to detect the presence of endothelial cells, vascular muscle cells and phosphorylated STAT3 (PSTAT3) in localized plaques. The potential underlying mechanisms in human umbilical vein endothelial cells (HUVECs) and vascular muscle cells (VSMCs) was detected by Western blot analysis, Wound healing assay and Elisa assay. In the ApoE-/- mice fed with HFD, daily Bazedoxifene administration effectively attenuated atherosclerotic plaque area (P < 0.01), down-regulated IL-6 levels (P < 0.01), decreased STAT3 phosphorylation, reduced VSMCs proliferation and increased endothelial coverage in aortic vessels. Interestingly, we found HUVECs lack of membrane IL-6 receptor (IL-6R) compared to VSMCs (P < 0.01). Furthermore, we found that the soluble IL-6 receptor (sIL6R) participates in the activation of STAT3 induced by IL-6 or TNF-alpha in HUVECs and primary HUVECs. Bazedoxifene did not inhibit the growth of HUVECs while suppressing the proliferation of VSMCs. Bazedoxifene is an attractive novel therapeutic reagent for atherosclerosis diseases. This mechanism may be partially attributed to regulating IL-6/IL-6R/STAT3 signaling pathway.

Myocarditis is a type of inflammatory cardiomyopathy that has no specific treatment. Accumulating evidence suggests that Th17 cells play a prominent role in the pathogenesis of myocarditis. Interleukin-(IL)-6-mediated signal transducer and activation of transcription 3 (STAT3) signaling is essential for Th17 cell differentiation and secretion of inflammatory cytokines. Bazedoxifene inhibits IL-6/STAT3 signaling in cancer cells, but its effect on the Th17 immune response induced by myocarditis remains unknown. Here we explore the effect of Bazedoxifene on Th17 immune response and cardiac inflammation in a mouse model of experimental autoimmune myocarditis, which has been used to mimic human inflammatory heart disease. After eliciting an immune response, we found Bazedoxifene ameliorated cardiac inflammatory injury and dysfunction. Th17 cells and related inflammatory factors in splenic CD4+ T cells at day 14 and in the heart at day 21 were increased, which were reduced by Bazedoxifene. Furthermore, Bazedoxifene could regulate autophagy induction in polarized Th17 cells. In conclusion, Bazedoxifene affected STAT3 signaling and prevented cardiac inflammation deterioration, so may provide a promising therapeutic strategy for the treatment of experimental autoimmune myocarditis (EAM).

Antagomir-155 is an artificial inhibitor of miRNA-155, which is expected to be a promising therapeutic target to attenuate acute cardiac rejection (ACR). However, its vulnerability of being degraded by endogenous nuclease and potential off-target effect make the authors seek for a more suitable way to delivery it. In attribution of efficiency and safety, ultrasound targeted microbubbles destruction (UTMD) turns out to be an appropriate method to deliver gene to target tissues. Here, cationic microbubbles to deliver antagomir-155 downregulating miRNA-155 in murine allograft hearts triggered by UTMD are synthesized. The viability of this therapy is verified by fluorescent microscopy. The biodistribution of antagomir-155 is analyzed by optical imaging system. The results show antagomir-155 delivered by UTMD which significantly decreases the levels of miR-155. Also, this therapy downregulates the expression of cytokines and inflammation infiltration. And allograft survival time is significantly prolonged. Therefore, antagomir-loaded microbubbles trigged by UTMD may provide a novel platform for ACR target treatment.

Bicuspid aortic valve (BAV) is the most common congenital cardiac abnormality. BAV aortic dilatation is associated with an increased risk of adverse aortic events and represents a potentially lethal disease and hence a considerable medical burden. BAV with aortic dilatation warrants frequent monitoring, and elective surgical intervention is the only effective method to prevent dissection or rupture. The predictive value of the aortic diameter is known to be limited. The aortic diameter is presently still the main reference standard for surgical intervention owing to the lack of a comprehensive understanding of BAV aortopathy progression. This article provides a brief comprehensive review of the current knowledge on BAV aortopathy regarding clinical definitions, epidemiology, natural course, and pathophysiology, as well as hemodynamic and clinically significant aspects on the basis of the limited data available.