As an efficient genome-editing technology, Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-CRISPR-associated protein9 (Cas9) system is increasingly being recognized as a significant therapeutic strategy for brain diseases. In recent years, researchers have continuously tried to regulate the expression of genes related to the nervous system through CRISPR-Cas9 system, which provides a new and efficient strategy for the treatment of brain diseases. At the same time, various delivery vectors of CRISPR-Cas9 system have been reported. Although some delivery vectors have not been applied to the research of brain diseases, they still provide valuable ideas for the brain delivery of CRISPR-Cas9 system. In this review, we summarized the principle of CRISPR-Cas9 system and its application in the nervous system, discussed the barrier of blood-brain barrier (BBB) to the treatment of brain diseases, overviewed various delivery vectors of CRISPR-Cas9 system and their applications, and highlighted advanced of CRISPR-Cas9 system applied to various brain diseases. Furthermore, we also discussed the existing obstacles and promising avenues for future investigation regarding CRISPR-Cas9-based therapeutic approaches. This article, through retrieving keyword combinations[PubMed,from Jan. 2018 to Dec. 2025], aims to elucidate the CRISPR-Cas9 system's potential for extensive future research and application as a therapeutic strategy for brain disorders.

BackgroundAtherosclerosis is a public health problem with high morbidity and mortality,Gut microbiota dysbiosis disrupts bile acid metabolism, impedes cholesterol excretion, promotes arterial lipid deposition, and accelerates atherosclerosis. Jiangzhi ruanmai recipe (JZRM) is a Chinese herbal medicine prescribed for the treatment of hyperlipidemia and atherosclerosis. However, the mechanism is unclear.PurposeThis study aims to investigate the effects and mechanisms of JZRM on Atherosclerosis.MethodsLC-MS analysis was first performed to characterize the chemical composition of JZRM. Next, an atherosclerosis model was established in ApoE−/− mice fed a high-fat diet for 16 weeks, and the therapeutic effects of JZRM were evaluated based on serum lipids, glucose, bile acids, and aortic plaque area. Fecal bile acid levels were subsequently measured, and 16S rRNA sequencing was employed to assess the abundance, diversity, and compositional changes of gut microbial communities. Finally, hepatic expression of genes and proteins involved in reverse cholesterol transport and bile acid synthesis was determined by qPCR and Western blot.ResultsJZRM significantly reduced the lipid, glucose, and inflammation levels in mice; decreased the TBA levels of liver, intestine and faeces, and reduced the aortic plaque area; Second, JZRM increased the abundance and diversity of intestinal flora, significantly enhanced the level of intestinal bacteria that promote bile acid decomposition and excretion.Finally, JZRM significantly upregulated the protein expression of ABCA1, ABCG1, PPARγ, and LXRα, as well as the mRNA expression of Abca1, Abcg1, Pparg, and Nr1h3.; In terms of bile acid metabolism, JZRM significantly regulates effective endogenous agonists chenodeoxycholic acid (CDCA) and lithocholic acid (LCA), as well as the FXR/CYP7A1 pathway to promote bile acid synthesis.ConclusionJZRM regulates gut microbiota-liver-cholesterol axis, promotes cholesterol synthesis and metabolism to alleviate atherosclerosis.

Hypertension caused cardiomyocyte apoptosis and remodeling, leading to heart failure. Wogonoside (WOG), a flavonoid from Qingda granules, was evaluated for cardioprotective effects and mechanisms. Spontaneously hypertensive rats (SHRs) received WOG (0.075, 0.75, or 7.5 mg/kg/d) or valsartan (7.5 mg/kg/d) for 10 weeks. Blood pressure, cardiac function, histology, fibrosis, cardiomyocyte size, and apoptosis were assessed using echocardiography, hematoxylin and eosin, Masson, TUNEL and wheat germ agglutinin staining. Network pharmacology and Kyoto Encyclopedia of Genes and Genomes analyses identified targets and pathways. In vitro, Annexin V/propidium iodide staining, JC-1 staining, and Western blotting were adopted for the assessment of apoptosis and mitochondrial function in H9C2 cells stimulated by angiotensin II (Ang II). WOG treatment reduced elevated blood pressure and increased left ventricular ejection fraction and left ventricular fractional shortening in SHRs. Network pharmacology analysis revealed 74 overlapping targets enriched in apoptosis and MAPK pathways. WOG reduced myocardial hypertrophy, fibrosis, and apoptosis in SHRs, as evidenced by decreased expression of cleaved caspase-3 and Bax, and increased expression of Bcl-2. WOG treatment reduced cell apoptosis and mitochondrial depolarization, downregulated Bax and Cleaved caspase 3, and upregulated Bcl-2. Mechanistically, WOG treatment suppressed the phosphorylation levels of ERK, p38MAPK, and JNK in Ang II-stimulated H9C2 cells, as evidenced by decreased ratios of p-ERK/ERK, p-p38MAPK/p38MAPK, and p-JNK/JNK, in Ang II-stimulated H9c2 cells. WOG relieves cardiac injury and cardiomyocyte apoptosis induced by hypertension, likely by suppressing multiple signaling pathways including the MAPK signaling pathway.

Early identification of individuals vulnerable to acute mountain sickness (AMS) is clinically challenging. We hypothesized that exercise stress echocardiography (ESE), conducted within 6 h of arrival at 3,600 m following a staged ascent, could reveal distinctive right ventricular (RV) and pulmonary vascular responses predictive of AMS development. Fifty healthy lowland residents completed a staged bus ascent to 3,600 m and underwent ESE within 6 h of arrival. Key measures included systolic pulmonary artery pressure (SPAP), pulmonary vascular resistance (PVR), tricuspid annular peak systolic velocity (TV s′), RV fractional area change (FAC), inferior vena cava (IVC) diameter, and mean PAP/cardiac output (CO) slope. AMS was assessed the next morning using the Lake Louise Score. Of the participants, 23 (46

PURPOSE:Accurate evaluation of left ventricular (LV) dysfunction and infarct localization in acute myocardial infarction (AMI) remains challenging due to subjective variability in conventional echocardiographic analysis. This study validates an artificial intelligence (AI)-driven automated strain framework for standardized quantification of myocardial deformation and its correlation with clinical biomarkers. METHODS:A retrospective cohort of 102 first-onset ST-elevation AMI patients and 90 age-/sex-matched controls underwent 2D speckle-tracking echocardiography. A modified ResNet-18 architecture processed standardized apical views (112 × 112 pixels, 25-frame cycles) through dual-task learning: global/regional longitudinal strain (LPSS) quantification and infarct localization. Training employed a two-phase optimization-myocardial tracking followed by strain regression and infarct classification. Real-time augmentation included speckle noise and cardiac-phase variations. Statistical analyses assessed correlations between strain parameters, LV ejection fraction (LVEF), cardiac troponin T (cTnT), and ST-segment elevation. RESULTS:AI-derived global LPSS strongly correlated with LVEF (r = -0.609; p < 0.001), outperforming the wall motion score index (r = 0.291). Infarct-zone LPSS demonstrated the strongest associations with cTnT (r = 0.671; p < 0.001) and ST elevation (r = 0.321; p = 0.001). Remote myocardium exhibited compensatory hyperkinesis (LPSS = -17.93%). Bland-Altman analysis confirmed reproducibility (intra-observer bias: 0.7% ± 1.2%; interobserver: 1.1% ± 3.1%). CONCLUSIONS:AI-driven strain analysis standardized LV functional assessment in AMI, providing quantitative correlations with enzymatic and electrophysiological injury markers. Its ability to localize infarcts and detect compensatory mechanisms supports clinical decision-making, bridging gaps between echocardiography and advanced imaging.

Stress echocardiography (SE) has evolved beyond its traditional role of detecting coronary artery disease (CAD) through a single marker-regional wall motion abnormality (RWMA). This conventional approach, while guideline-embedded, faces a declining positivity rate and reduced prognostic power in today's diverse patient population. In response, SE has undergone a conceptual transformation into a multi-marker, comprehensive functional assessment of patient vulnerability. The modern multi-marker protocol, known as the ABCDE-SE, integrates five steps during a single stress test: Step A assesses RWMA for ischemia; Step B quantifies pulmonary congestion via B-lines and E/e'; Step C evaluates left ventricular volume response; Step D measures coronary flow velocity reserve for microvascular function; and Step E determines heart rate reserve for autonomic function. Each step identifies distinct pathophysiological mechanisms and actionable therapeutic targets, significantly refining risk stratification.Developed and validated over the past decade with the SE 2030 study (2016-2030), the flagship project of SIECVI, Italian Society of Echocardiography and Cardiovascular Imaging, and adopted by 50 laboratories from 20 countries, the ABCDE protocol represents a universal and widely accessible platform, applicable to all patients with suspected cardiac disease. It paves the way for personalized medicine by enabling tailored therapies targeted to the specific vulnerabilities.

Piperine is a common anti-ischemic compound and an active ingredient of herbal medicine for various ailments. It is widely sourced and affordable. However, its bioactivity and anti-ischemic effects on retinal ischemic injury are unknown. The chemical-gene interactions of piperine were analyzed using data from "SwissTargetPrediction," "Binding DB", and "TargetNet" databases. Gene expression data from GSE43671 dataset and the Kyoto encyclopedia of genes and genomes (KEGG) were used for differential gene and ontology analyses. To evaluate the activation of disease pathways, by analyzing gene sets and applying weighted gene co-expression networks to differential gene interaction data. Additionally, molecular complex detection analyses of retinal ischemia and control samples were performed to determine which genes are affected by piperine, to compare gene expression differences, and to map receiver operator characteristic data. Utilizing network pharmacology and transcriptome sequencing, this study elucidates the targets and pathways affected by pharmacological interventions involving piperine in retinal ischemia injury. 176 target genes connected to piperine were identified and retrieved. Screening of 8 hub genes using machine learning. Through screening, we detected disease-associated genes, differential genes, and drug targets, and pinpointed two biomarker genes, Aoc3 and Gabra3. We found that piperine may have a protective effect on retinal ischemic injury. Consequently, piperine may modulate retinal ischemic injury through specifically targeting Aoc3 and Gabra3 for retinal protection.

BACKGROUND Early identification of individuals vulnerable to acute mountain sickness (AMS) is clinically challenging. We hypothesized that exercise stress echocardiography (ESE), conducted shortly after high-altitude arrival, could reveal distinctive right ventricular (RV) and pulmonary vascular responses predictive of AMS development. METHODS Within 6 hours of arrival, 50 healthy lowland residents underwent ESE. Key measures included systolic pulmonary artery pressure (SPAP), pulmonary vascular resistance (PVR), tricuspid annular peak systolic velocity (TV s′), RV fractional area change (FAC), inferior vena cava (IVC) diameter, and mean PAP/cardiac output (CO) slope. AMS was assessed the next morning using the Lake Louise Score. RESULTS Of the participants, 23 (46%) developed AMS and 27 (54%) did not (non-AMS group). At peak exercise, the AMS group exhibited significantly higher SPAP (54.88 ± 7.89 vs. 46.71 ± 8.48 mmHg, p < 0.001) and PVR (2.24 ± 0.26 vs. 2.03 ± 0.17 WU, p = 0.001), accompanied by greater increases from rest (denoted as Δ) in SPAP (20.42 ± 8.13 vs. 13.21 ± 6.22 mmHg, p = 0.015) and PVR (0.40 ± 0.19 vs. 0.30 ± 0.17 WU, p = 0.010). Conversely, the AMS group demonstrated impaired RV contractile reserve, reflected by smaller in ΔTV s′ (0.05 ± 0.04 vs. 0.08 ± 0.03 m/s, p = 0.006) and ΔFAC (8.26 ± 3.89 vs. 12.22 ± 5.35%, p = 0.033). IVC diameter was larger in the AMS group both at rest and during peak exercise (p = 0.047 and p = 0.018). A nomogram incorporating peak IVC diameter, ΔPVR, and ΔTV s′ predicted AMS with an area under the curve (AUC) of 0.865 and an accuracy of 84.0%. CONCLUSION ESE detects early alterations in RV function, IVC dynamics, and pulmonary circulation in individuals susceptible to AMS within hours of high-altitude exposure. A model based on IVC, ΔPVR, and ΔTV s′ offers a practical tool for early AMS risk stratification. Clinical trial number: not applicable

Current experimental models of heart failure with preserved ejection fraction (HFpEF) lack standardized approaches for evaluating left atrial (LA) remodelling and atrioventricular (AV) coupling, leaving a critical gap in mechanistic understanding and phenotypic characterization. This study aimed to explore LA function and AV coupling status in a rat model of hypertension-related HFpEF, thereby providing support for phenotype-specific therapeutic strategies. We established two experimental rat models: A dual-hit model (high-fat diet combined with Nω-nitro-l-arginine methyl ester; HD + NAME) and a high-salt-sensitive model (Dahl salt-sensitive; Dahl/SS). LA function and AV coupling were quantified using speckle-tracking echocardiography (STE) with a modified LA imaging protocol and dedicated strain analysis software. Key parameters included phasic LA function, circumferential strain rates, LA stiffness index (LASI), and LA reservoir strain (LASr). Correlations with histopathological alterations were also examined. Both HFpEF groups exhibited significant left ventricular remodelling, diastolic dysfunction and reduced LASr compared with control (Control: 25.5 ± 3.4%, Dahl/SS: 17.8 ± 2.6%, and HD + NAME: 15.6 ± 2.9%; all P < 0.001 vs. Control). The HD + NAME model demonstrated higher LASI and E/early diastolic circumferential strain rate, indicating impaired AV coupling. Histological analysis revealed LA cardiomyocyte hypertrophy and interstitial fibrosis (fibrotic area: Control: 1.1 ± 0.5%; HD + NAME: 4.9 ± 1.7%, Dahl/SS: 6.7 ± 1.9%; all P < 0.001 vs. Control). Importantly, LASI correlated strongly with cardiomyocyte hypertrophy (r = 0.0.635) and fibrosis (r = 0.733; all P < 0.001). Standardized STE enables high-resolution quantification of LA function and AV coupling in preclinical HFpEF models. Comparative evaluation of dual-hit and salt-sensitive hypertension models provides phenotypic stratification and yields novel mechanistic insights into atrioventricular decoupling in HFpEF.

BackgroundNon-invasive myocardial work (MW) is a more precise parameter for evaluating left ventricular (LV) systolic function. However, studies examining sex-based differences in MW during exercise stress echocardiography (SE) in healthy individuals are scarce. Previous research has shown that global work efficiency (GWE) decreases following exercise.ObjectivesTo characterize sex-based differences in MW during exercise SE in healthy adults and to explore the factors influencing the decline in GWE post-exercise.MethodsThe study enrolled 200 healthy adults, all of whom underwent echocardiographic assessments both at rest and immediately after completing a symptom-limited treadmill stress test. We measured LV volume, ejection fraction (EF), force, peak positive strain (PPS), global work index (GWI), global constructive work (GCW), global wasted work (GWW), and GWE at rest and post-exercise.ResultsGWI, GCW, and GWW increased, while GWE decreased after exercise. There were no significant differences in any of the global MW parameters between sexes at rest (all p > 0.05). The change in △GWE was greater in women (p < 0.05), but no significant differences were found in other MW reserve parameters between sexes. The multivariable linear regression analysis revealed that GWW was independently associated with PPS (β = 0.842, p < 0.0001) and force (β = 0.306, p = 0.023). Furthermore, the multivariable linear regression analysis showed that GWE was independently associated with PPS (β = −0.395, p = 0.018) and EF (β = −0.236, p < 0.001).ConclusionSex had a minimal effect on MW-based LV systolic function in healthy adults. GWE decreased post-exercise, and both PPS and force were independently associated with GWW. These findings suggest that higher contractility is achieved at the cost of increased wasted work, which subsequently leads to a decrease in mechanical efficiency.

Small nucleolar RNAs (snoRNAs) are a class of small RNA molecules that play a pivotal role in diverse cellular processes and are extensively implicated in the pathophysiology of various diseases. Here, we provide a comprehensive overview of snoRNAs, encompassing their classification, biogenesis, and both canonical and noncanonical functions. Canonical roles include guiding RNA modifications such as 2'-O-methylation, pseudouridylation, and N4-acetylcytidine modification in targeted RNA molecules, as well as facilitating ribosome biogenesis. Noncanonical roles involve regulating mRNA processing, modulating alternative splicing, generating snoRNA-derived small RNAs, and interacting with long noncoding RNAs. Dysregulation of snoRNAs has been implicated in various human diseases, such as cancer, neurodegenerative disorders, cardiovascular diseases, immunity- and inflammation-related conditions, and aging, highlighting their potential as diagnostic and prognostic biomarkers. Advances in high-throughput sequencing, structural biology, and bioinformatics tools have significantly contributed to the detection, screening, and exploration of the intricate biofunctions of snoRNAs. However, despite these technological advancements, challenges remain in unraveling the biological complexity of snoRNAs and translating these findings into clinical applications. This review discusses the current state of snoRNA research, recent technological breakthroughs, and future directions, emphasizing their emerging roles in health and disease.

BACKGROUND:Weichang'an pill (WCA) possesses potential advantages in promoting gastrointestinal motility and treating constipation. Ethanol extract (EE) and aqueous extract (AE) of WCA were used to investigate its efficacy in treating slow transit constipation (STC) and the material basis for exerting this effect. METHODS:The STC model was established in vivo by gavage of loperamide (Lop) in Sprague-Dawley rats, followed by gavage of WCA, EE, and AE. In vitro, norepinephrine (NE) was used to stimulate isolated ileal smooth muscle of rats to imitate the state of insufficient gastrointestinal motility during STC, and a model of excessive relaxation of isolated ileal smooth muscle was established. This model was used to observe and record the changes in contraction tension, amplitude, and frequency of ileal smooth muscle after treatment with WCA, EE, AE, and the active ingredients of WCA. KEY RESULTS:In vivo, WCA, EE, and AE treatment increased fecal parameters, improved gastrointestinal transit time, and alleviated pathological damage to the colon in STC rats. Its mechanism might be closely related to c-kit/SCF, RhoA/ROCK/MYPT1/MLC signaling pathways. In vitro, WCA, EE, AE, and the active ingredients of WCA, including costunolide (Cos), dehydrocostus lactone (Deh), agarotetrol (Aga), muscone (Mus), gallic acid (GA), oleic acid (Oleic), linoleic acid (Lin), umbelliferone (Umb), synephrine (Syn), ferulic acid (FA), chlorogenic acid (ChA), betaine (Bet), and riboflavin (Rib), significantly inhibited the NE-induced excessive relaxation of ileal smooth muscles. CONCLUSIONS:WCA, EE, and AE significantly improved constipation in STC rats. Moreover, the active ingredients in WCA, including Cos, Deh, Aga, Mus, GA, Oleic, Lin, Umb, Syn, FA, ChA, Bet, and Rib, might be the material basis for promoting intestinal motility.

This review examines the mechanisms of left ventricular dysfunction, focusing on the interplay between ventricular remodeling, autophagy, and mitochondrial dysfunction following myocardial infarction. Left ventricular dysfunction directly affects the heart’s pumping efficiency and can lead to severe clinical outcomes, including heart failure. After myocardial infarction, the left ventricle may suffer from weakened contractility, diastolic dysfunction, and cardiac remodeling, progressing to heart failure. Thus, this article discusses the pathophysiological processes involved in ventricular remodeling, including the injury and repair of infarcted and non-infarcted myocardia, adaptive changes, and specific changes in left ventricular systolic and diastolic functions. Furthermore, the role of autophagy in maintaining cellular energy homeostasis, clearing dysfunctional mitochondria, and the key role of mitochondrial dysfunction in heart failure is addressed. Finally, this article discusses therapeutic strategies targeting mitochondrial dysfunction and enhancing mitophagy, providing clinicians and researchers with the latest insights and future research directions.

Background:Hypertrophic obstructive cardiomyopathy (HOCM) is characterized by asymmetric septal hypertrophy, diastolic dysfunction, and dynamic left ventricular outflow tract (LVOT) obstruction, and is often associated with systolic anterior motion (SAM) of the mitral valve and secondary mitral regurgitation (MR). Established treatments of HOCM include beta-blockers, calcium channel blockers, surgical myectomy, and alcohol septal ablation (ASA); however, elderly patients with a high surgical risk or an unsuitable coronary anatomy have limited therapeutic options. Transcatheter edge-to-edge repair (TEER) has been widely adopted in the treatment of MR, and emerging evidence suggests it could alleviate SAM-related LVOT obstruction. However, clinical research on octogenarians with HOCM is limited. Case Description:We report the case of an 83-year-old woman with a history of HOCM, hypertension, and chronic obstructive pulmonary disease, who presented with progressive dyspnea and chest tightness despite optimal medical therapy. Echocardiography revealed severe asymmetric septal hypertrophy, significant SAM, dynamic LVOT obstruction with a peak gradient of 233 mmHg during the Valsalva maneuver, and severe MR originating from the A2-P2 segment. Surgical risk assessment revealed a EuroSCORE II of 9.5% and a Society of Thoracic Surgeons score of 10.2%. Given the absence of suitable septal perforator arteries for ASA and the prohibitive surgical risk, the heart team performed TEER with the MitraClip™ system. A single narrow translational range (NTR) clip was deployed at the A2-P2 position under three-dimensional transesophageal echocardiography guidance, resulting in immediate MR reduction (from severe to mild), SAM resolution, and a decreased resting LVOT gradient to 81 mmHg. Her hemodynamics improved markedly, with left atrial pressure dropping from 55 to 25 mmHg. The patient was discharged with a New York Heart Association classification of I-II. At the 8-month follow-up, she remained asymptomatic, MR was mild, and her LVOT gradient had further decreased to 20 mmHg. Conclusions:TEER is a safe and effective therapeutic alternative for elderly HOCM patients with severe MR and SAM-related LVOT obstruction in whom surgical myectomy or ASA is unsuitable. This case showed sustained symptomatic and hemodynamic improvement at the mid-term follow-up, supporting further research on the use of TEER in this high-risk population.

The seed of fenugreek (FS) was traditionally used in diets and as a spice in India, as well as medicine in China. It had anti-diabetic and anti-hypolipidemic effects. According to the theory of traditional Chinese medicine, the effects of FS were enhanced after salt processing. But the enhanced effect of salt-processed fenugreek seed (SFS) on anti-hyperlipidemia was not yet fully understood. By UPLC-QTOF-MS analysis, five flavonoids and six saponins were tentatively identified in SFS. Salt processing increased the dissolution of polysaccharides and trigonelline. FS and SFS significantly improved the serum biochemical indexes, including total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) of hyperlipidemic rats, promoted the excretion of TC and total bile acid (TBA), and downregulated aspartate aminotransferase (AST). According to the results of factor analysis, FS and SFS restored the severity of hyperlipidemia to a similar extent, and SFS enhanced the excretion of cholesterol more significantly. FS and SFS reduced the ratio of Firmicutes/Bacteroidetes (F/B), which was upregulated in HFD group. Additionally, SFS significantly increased the abundance of Ruminococcus_1, which was negatively correlated with blood lipid levels. Thus, to regulate gut microbiota and promote the excretion of cholesterol were the mechanisms of the effects of SFS on hyperlipidemia. The higher amounts of total polysaccharides and trigonelline in SFS than in FS led to their different effects.

Background: Exposure to high altitude may unpredictably lead to acute mountain sickness (AMS). The purpose of this study was to identify the predictors of AMS at low altitude using exercise stress echocardiography (ESE). Methods: A total of 40 healthy adults were enrolled and underwent comprehensive supine bicycle ESE at low altitude, including pulmonary vascular resistance (PVR), right ventricular area index at the end of diastole, Blines, and inferior vena cava (IVC) diameter. All subjects ascended to 3,600 m within 24 hours. The risk factors for AMS were screened using least absolute shrinkage and selection operator regression analysis. A novel nomogram model was then established using multivariable logistic regression analysis, and a clinical impact curve was constructed. Results: At the altitude of 3,600 m, 20 of 40 subjects had AMS (AMS group). On least absolute shrinkage and selection operator regression analyses, PVR, IVC, and B-lines at peak exercise were all independent factors influencing AMS. The nomogram built on the basis of these factors predicted AMS with sensitivity of 0.950 and specificity of 0.804, which outperformed the individual predictive C indexes of each indicator (nomogram: cutoff, 59.3; area under the curve [AUC], 0.90 [95% CI, 0.80-1.00]; PVR at peak exercise: cutoff, 1.55; AUC, 0.81 [95% CI, 0.70-0.91]; B-lines at peak exercise: cutoff, 1; AUC, 0.78 [95% CI, 0.69-0.92]; IVC at peak exercise: cutoff, 13.8; AUC, 0.74 [95% CI, 0.65-0.87]). The established model was validated by plotting the clinical decision curve analysis and clinical impact curve. Conclusions: Supine bicycle ESE is a useful technique to identify subjects susceptible to AMS. This study established a nomogram to predict the development to AMS with high discrimination and accuracy. (J Am Soc Echocardiogr 2025;38:262-72.)

BackgroundThe arcade-like mitral apparatus is a rare congenital anomaly characterized by complex subvalvular pathology, often resulting in mitral dysfunction. These anatomical complexities make conventional surgical interventions particularly challenging, especially for elderly high-risk patients. For these patients, less invasive options like Transcatheter Edge-to-Edge Repair (TEER) present a promising alternative, addressing both anatomical challenges and procedural risks.AimsTo assess the feasibility, procedural success, safety, and clinical outcomes of TEER in patients with isolated severe MR due to arcade-like mitral apparatus.MethodsThis case series involved four high-risk patients with isolated severe mitral regurgitation (MR) secondary to arcade-like mitral apparatus treated with TEER between August 2022 and August 2023. Each patient was evaluated by a multidisciplinary Heart Team to ensure optimal selection and procedural planning. Detailed anatomical assessment using advanced imaging techniques, was performed to customize the approach and ensure procedural success. The MitraClip XTR device was employed in all cases, with careful attention to patient-specific anatomical challenges.ResultsTEER was successfully performed in all patients, with immediate and sustained reductions in MR severity. At the one-year follow-up, all patients demonstrated improved cardiac function, an increase in New York Heart Association (NYHA) functional class, and a reduction in Borg dyspnea scores. Significant improvements in myocardial mechanics and work parameters were observed. Global Longitudinal Strain (GLS) improved significantly compared to baseline. The Global Work Index (GWI), Global Constructive Work (GCW), Global Pressure-Volume Work (GPW), Global Systolic Constructive Work (GSCW) and Global Work Efficiency (GWE) also showed a marked increase.ConclusionTEER represents a promising, minimally invasive option for managing severe MR due to arcade-like mitral apparatus in high-risk patients. This case series underscores TEER's potential to offer significant symptom relief and improved hemodynamics, presenting a new therapeutic perspective for treating isolated MR in this anatomically challenging condition. Further large-scale studies are warranted to validate these findings and establish TEER's role in broader clinical practice.