IRF5 governs macrophage adventitial infiltration to fuel abdominal aortic aneurysm formation.

Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease characterized by the expansion of the aortic wall. One of the most significant features is the infiltration of macrophages in the adventitia, which drives vasculature remodeling. The role of macrophage-derived interferon regulatory factor 5 (IRF5) in macrophage infiltration and AAA formation remains unknown. RNA sequencing of AAA adventitia identified Irf5 as the top significantly increased transcription factor that is predominantly expressed in macrophages. Global and myeloid cell-specific deficiency of Irf5 reduced AAA progression, with a marked reduction in macrophage infiltration. Further cellular investigations indicated that IRF5 promotes macrophage migration by direct regulation of downstream phosphoinositide 3-kinase γ (PI3Kγ, Pik3cg). Pik3cg ablation hindered AAA progression, and myeloid cell-specific salvage of Pik3cg restored AAA progression and macrophage infiltration derived from Irf5 deficiency. Finally, we found that IRF5 and PI3Kγ expression in the adventitia is significantly increased in patients with AAA. These findings reveal that the IRF5-dependent regulation of PI3Kγ is essential for AAA formation.

First-phase ejection fraction to predict adverse outcomes in patients with heart failure.

BACKGROUND: First-phase ejection fraction (EF1) is a novel measurement of early left ventricular systolic dysfunction. We investigate its prognostic value in patients with heart failure (HF). METHODS AND RESULTS: Patients with HF were prospectively enrolled from July 2019 to September 2021. A total of 228 patients were included in the final analysis. The primary endpoint was the composite of all-cause mortality or rehospitalization for HF, which occurred in 74 patients (32.46%). EF1 as well as other parameters for left ventricular function were measured in echocardiography. Time-dependent ROC showed the cutoff value of EF1 was 18.55%. Kaplan-Meier analysis indicated a higher rate of adverse events in the lower EF1 group (EF1 ≤ 18.55%) (Log-rank test P < 0.001). Cox regression analyses showed EF1 was an independent predictor with adverse events as a continuous variable (Cox model 1: per 1% change in EF1: HR = 0.92, 95%CI: 0.87-0.97, P < 0.001), as well as a categorical variable (Cox model 2: EF1 > 18.55%: HR = 0.21, 95%CI: 0.08-0.53, P < 0.001) after adjustment for hypertension, coronary artery disease (CAD), Log10 (NT-proBNP), eGFR, E/e' and loop diuretics. Restricted cubic splines revealed a linear association between EF1 levels and the incidence of adverse events (P for non-linearity = 0.145). The subgroup analyses showed the predictive ability of elevated EF1 on the decreased risk of adverse events did not change substantially stratified by HF classification, age, CAD and hypertension. CONCLUSION: EF1, as a novel measurement of early systolic function, is a promising predictor of adverse events among HF patients. EF1 might be considered a new measurement for risk stratification of HF.

Mending a broken heart-targeting cardiomyocyte regeneration: a literature review.

Background and Objectives: Cardiovascular diseases have been the leading cause of death globally for decades. Pharmacological advances targeting the sympathetic nervous system, renin-angiotensin-aldosterone system, and fibrosis slow the progression of diverse cardiovascular diseases. However, ongoing cardiomyocyte loss is inevitable in divergent cardiovascular diseases, eventually leading to heart failure as the end stage. In this review, we focused on the key biomedical findings and underlying principles of cardiomyocyte regeneration. Methods: Literature regarding the key findings in cardiomyocyte regeneration research, including controversies on the origins of newly formed cardiomyocytes, potential barriers and strategies to heart regeneration, and the key animals, models, and methods applied in the study of heart regeneration, were broadly researched using the PubMed and Web of Science databases. Key Content and Findings: In the mammalian heart, cardiomyocytes proliferate during the embryonic and early postnatal stages, while the capability of proliferation disappears in the adult stage. An increasing amount of evidence suggests that cardiomyocytes self-renew at a very limited level and that most newly formed cardiomyocytes originate from pre-existing cardiomyocytes and not cardiac progenitor cells (CPCs). Several potential barriers to heart regeneration have been addressed, including metabolic switch, a large increase in multinucleated and polyploid cardiomyocytes, and alteration in the epigenome and transcriptome. In addition, immune system evolution is also associated with the loss of regenerative capacity. However, the activation of resident cardiomyocytes, somatic cell reprogramming, and direct reprogramming, in addition to the promotion of neovascularization and immune modulation, constitute the new insights into those strategies that can boost cardiac regeneration. Conclusions: Heart regeneration is one of the most popular fields in cardiovascular research and represents a promising avenue of therapeutics for mending a broken heart. Despite the controversies and challenges, a clearer picture of adult mammalian cardiac regeneration is emerging.

Clinical characteristics and prognosis of patients with left ventricular thrombus in East China.

Background: Left ventricular thrombus (LVT) is a serious complication in patients with left ventricular dysfunction. However, there is still a paucity of data on treatments and prognosis of patients with LVT. This study aims to evaluate the clinical characteristics of patients with LVT and to determine the impact of LVT on the incidence of major adverse cardiovascular events (MACEs) and all-cause mortality. Methods: From January 2010 to January 2020, 237 patients diagnosed with LVT at The Second Affiliated Hospital Zhejiang University School of Medicine in East China were retrospectively included. Clinical characteristics, treatments, MACEs, and bleeding events [thrombolysis in myocardial infarction (TIMI) I and II] were collected. MACE is determined as the composite of all-cause mortality, ischemic stroke, acute myocardial infarction (MI), and acute peripheral artery emboli. Results: The all-cause mortality rate was 28.3% (89.6% due to cardiovascular death), ischemic stroke 8.4%, MI 3%, peripheral artery emboli 1.7%, and bleeding events (TIMI I and II) 7.6% were found during a median follow-up of 736 days. Total LVT regression occurred in 152 patients (64.1%). Atrial fibrillation [hazard ratio (HR), 3.049; 95% confidence interval (95% CI) 1.264-7.355; p = 0.013], moderate and severe renal function injuries (HR, 2.097; 95% CI, 1.027-4.281; p = 0.042), and left ventricular ejection fraction (LVEF) ≤ 50% (HR, 2.243; 95% CI 1.090-4.615; p = 0.028) were independent risk factors for MACE, whereas the use of ß-blocker (HR, 0.397; 95% CI 0.210-0.753; p = 0.005) was its protective factor. Age (HR, 1.021; 95% CI 1.002-1.040; p = 0.031), previous caronary artery bypass grafting (CABG; HR, 4.634; 95% CI 2.042-10.517; p < 0.001), LVEF ≤ 50% (HR, 3.714; 95% CI 1.664-8.290; p = 0.001), and large thrombus area (HR, 1.071; 95% CI 1.019-1.126; p = 0.007) were independent risk factors for increasing all-cause mortality, whereas the use of ß-blocker (HR, 0.410; 95% CI 0.237-0.708; p = 0.001) was protective factor. Conclusion: This study showed that atrial fibrillation, moderate and severe renal dysfunction, and LVEF ≤ 50% were independent risk factors for MACE; age, previous CABG, LVEF ≤ 50%, and large thrombus area were independent risk factors for all-cause mortality. It was found that the use of ß-blockers could improve the prognosis of patient with LVT for the first time. It is recommended that clinicians could be more active in applying patient with LVT with anticoagulants.

Distinct Characteristics Between Perivascular and Subcutaneous Adipose-Derived Stem Cells.

Adipose-derived stem cells (ADSCs) can differentiate into vascular lineages and participate in vascular remodeling. Perivascular ADSCs (PV-ADSCs) draw attention because of their unique location. The heterogeneity of subcutaneous (SUB) and abdominal ADSCs were well addressed, but PV-ADSCs' heterogeneity has not been investigated. In this study, we applied single-cell analysis to compare SUB-ADSCs and PV-ADSCs regarding their subpopulations, functions, and cell fates. We uncovered four subpopulations of PV-ADSCs (Dpp4+, Col4a2+/Icam1+, Clec11a+/Cpe+, and Sult1e1+ cells), among which the Clec11a+ subpopulation potentially participated in and regulated PV-ADSC differentiation toward a smooth muscle cell (SMC) phenotype. Distinct characteristics between PV-ADSCs and SUB-ADSCs were revealed.

The efficacy of trimetazidine in non-ischemic heart failure patients: a meta-analysis of randomized controlled trials.

Trimetazidine has been reported to benefit patients with heart failure (HF) and angina. The impact of trimetazidine on non-ischemic HF remains unclear. We reviewed clinical trials to investigate whether trimetazidine could improve exercise endurance, life quality, and heart function in non-ischemic HF patients. We searched the Cochrane Central Register of Controlled Trials, EMBASE, PubMed, and Web of science for randomized clinical trials published before April 30th, 2020; Studies limited to patients with non-ischemic HF, aged ≥18 years, comparing trimetazidine with conventional therapy with/without placebo. Outcome measurements included primary outcomes (6 minutes walking test (6-MWT)) and secondary outcomes (life quality scores, echocardiography parameters, biomarker, peak oxygen consumption). The follow-up period was longer than three months. This study was registered with international prospective register of systematic reviews (PROSPERO) (CRD42020182982). Six studies with 310 cases were included in this research. Trimetazidine significantly improved 6-MWT (weighted mean difference (WMD) = 48.51 m, 95% confidence interval (CI) [29.41, 67.61], p < 0.0001, I2 = 0%), left ventricle ejection fraction (LVEF) (WMD = 3.09%, 95% CI [1.09, 5.01], p = 0.002, I2 = 0%) at 3 months, and LVEF (WMD = 6.09%, 95% CI [3.76, 8.42], p < 0.0001, I2 = 12%) at 6 months. Furthermore, it reduced peak oxygen consumption (WMD = -2.24 mL/kg per minute, 95% CI [-4.09, -0.93], p = 0.02). This meta-analysis suggested that trimetazidine might be an effective strategy for improving exercise endurance and cardiac function in patients with non-ischemic HF.

The association of reduced left ventricular strains with increased extracellular volume and their collective impact on clinical outcomes.

BACKGROUND: Myocardial fibrosis and left ventricular (LV) longitudinal strain are independently associated with adverse clinical outcomes. However, the relationship between tissue properties and strain indices as well as their collective impact on outcomes are yet to be fully elucidated. We aim to investigate the relationship between LV global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS) with extracellular volume (ECV) and their collective impact. METHODS: Consecutive patients referred for clinical cardiovascular magnetic resonance (CMR) due to cardiomyopathy were prospectively enrolled. All patients underwent CMR with T1 mapping. ECV was calculated incorporating native and post-contrast T1 as well as hematocrit. LV GLS, GCS, and GRS were assessed by feature tracking. Hazard ratios and Kaplan-Meier curves were produced to assess the association between strains and T1 mapping indices with a composite outcome of all-cause mortality and hospitalized heart failure. RESULTS: The study consisted of 259 patients with mixed referring diagnoses of non-ischemic/ischemic cardiomyopathy and 21 normal controls. Decreased GLS, GCS and GRS were associated with increased ECV, increased native T1, and reduced post-contrast T1 in a dose dependent manner when T1 or ECV was in the abnormal range. After a mean follow-up of 31 ± 23 months, 41 events occurred including 37 heart failure admissions and 4 deaths. Kaplan-Meier plots demonstrated that reduced strains were associated with reduced event-free survival predominantly in patients with increased ECV (≥ 28.3%). The worst outcome was among those with both reduced strains and increased ECV. In the multivariable models, increased ECV, reduced post-contrast T1 and reduced strains in all 3 directions remained predictors of outcome risk, respectively. CONCLUSION: Our findings highlight the intrinsic link between altered CMR tissue properties and impaired myocardial mechanical performance and additionally demonstrate improved risk stratification by characterizing tissue property among patients with reduced strain.

Serum Free Fatty Acids Independently Predict Adverse Outcomes in Acute Heart Failure Patients.

Background: Perturbation of energy metabolism exacerbates cardiac dysfunction, serving as a potential therapeutic target in congestive heart failure. Although circulating free fatty acids (FFAs) are linked to insulin resistance and risk of coronary heart disease, it still remains unclear whether circulating FFAs are associated with the prognosis of patients with acute heart failure (AHF). Methods: This single-center, observational cohort study enrolled 183 AHF patients (de novo heart failure or decompensated chronic heart failure) in the Second Affiliated Hospital, Zhejiang University School of Medicine. All-cause mortality and heart failure (HF) rehospitalization within 1 year after discharge were investigated. Serum FFAs were modeled as quartiles as well as a continuous variable (per SD of FFAs). The restricted cubic splines and cox proportional hazards models were applied to evaluate the association between the serum FFAs level and all-cause mortality or HF rehospitalization. Results: During a 1-year follow-up, a total of 71 (38.8%) patients had all-cause mortality or HF rehospitalization. The levels of serum FFAs positively contributed to the risk of death or HF rehospitalization, which was not associated with the status of insulin resistance. When modeled with restricted cubic splines, the serum FFAs increased linearly for the incidence of death or HF rehospitalization. In a multivariable analysis adjusting for sex, age, body-mass index, coronary artery disease, diabetes mellitus, hypertension, left ventricular ejection fraction and N-terminal pro-brain natriuretic peptid, each SD (303.07 µmol/L) higher FFAs were associated with 26% higher risk of death or HF rehospitalization (95% confidence interval, 2-55%). Each increasing quartile of FFAs was associated with differentially elevated hazard ratios for death or HF rehospitalization of 1 (reference), 1.71 (95% confidence interval, [0.81, 3.62]), 1.41 (95% confidence interval, [0.64, 3.09]), and 3.18 (95% confidence interval, [1.53, 6.63]), respectively. Conclusion: Serum FFA levels at admission among patients with AHF were associated with an increased risk of adverse outcomes. Additional studies are needed to determine the causal-effect relationship between FFAs and acute cardiac dysfunction and whether FFAs could be a potential target for AHF management.

LCZ696 and preservation of renal function in heart failure: A meta-analysis of 6 randomized trials.

Patients with heart failure (HF) are prone to combine with renal insufficiency. Recently, LCZ696 has been used in the treatment of HF, but whether LCZ696 is better than angiotensin converting enzyme inhibitors/angiotensin receptor antagonists (ACEI/ARB) in renal protection for HF patients has not been investigated. Therefore, we conducted a meta-analysis focusing on LCZ696 and its role in preservation of renal function in HF patients. Embase, PubMed, the Cochrane Library and ClinicalTrials.gov databases were electronically searched for available randomized controlled trials (RCTs). HF patients taking LCZ696 or ACEI/ARB were assessed for renal adverse events. The last search date was Sep 20, 2019. A total of 14959 patients from 6 trials were included in this meta-analysis. As compared to ACEI/ARB, LCZ696 significantly reduced the risk of renal function deterioration (odds ratio 0.77, 95% confidence interval 0.61-0.97, P = 0.02). In summary, LCZ696 may have superior renal protection in HF patients compared with ACEI/ARB.

Ultrasonographic assessment of right heart intracardiac mass in patients with hepatitis B virus infection.

OBJECTIVE: The characteristics of right heart intracardiac mass in hepatitis B virus infection patients are not well known. Our aim is to describe their ultrasonographic features and nature of such masses. METHODS: We retrospectively reviewed imaging reports of hepatitis B virus infection patients from January 2014 to December 2018. Patients with a confirmed finding of right heart intracardiac mass were included, whose pathology reports and contrast-enhanced images were analyzed. Various masses were compared to a general control group from a published study. RESULTS: Thirty-eight cases were finally included. Different types of masses presented with a variety of echocardiographic manifestations. Thirty-six cases had masses located in the right atrium, including five thrombus and 31 metastatic carcinoma. The later included one metastatic non-Hodgkin lymphoma and 30 metastatic hepatic carcinoma cases (27 of which had inferior vena cava tumor thrombus). Two cases presented with masses in the right ventricle that included one multiple myxoma and one tricuspid valve leaflet vegetation. Compared with the general population, no primary malignant tumor was found in our study (65% vs. 100%, P = 0.001), and hepatic metastasis was the most common type of malignant tumors (P < 0.001). CONCLUSION: The nature and ultrasonographic features of right heart intracardiac masses in hepatitis B virus infection patients are diverse, and the incidence of malignant tumors was similar to that seen in the general population. Hepatic metastasis, possibly extending via the inferior vena cava into the right atrium, was the most common type. Our study may improve understanding of the right heart intracardiac mass in hepatitis B virus infection patients.

Mitral Annular and Left Ventricular Dynamics in Atrial Functional Mitral Regurgitation: A Three-Dimensional and Speckle-Tracking Echocardiographic Study.

BACKGROUND: Patients with atrial fibrillation (AF) and left atrial (LA) enlargement may develop functional, normal leaflet motion mitral regurgitation (MR) without left ventricular (LV) remodeling. Mitral annular dynamics and LV mechanics are important for preserving normal mitral valve function. The aim of this study was to assess the annular and LV dynamics in patients with AF and functional MR. METHODS: Twenty-one patients with AF with moderate or more MR (AFMR+ group), 46 matched patients with AF with no or mild MR (AFMR- group), and 19 normal patients were retrospectively studied. Mitral annular dynamics were quantitatively assessed using three-dimensional echocardiography. Systolic LV global longitudinal strain (GLS), global circumferential strain, and LA strain were measured using two-dimensional speckle-tracking echocardiography. RESULTS: The normal annulus displayed presystolic followed by systolic contraction and increase in saddle shape (P < .01 for all). Presystolic annular dynamics were abolished in both groups of patients with AF (P > .05 vs normal). In contrast, systolic and total annular dynamics during the cardiac cycle were preserved in AFMR- patients (P > .10 vs normal) but impaired in AFMR+ patients (P < .05 vs normal and AFMR-). LV GLS (P < .0001) and LA strain (P = .02), but not LV global circumferential strain (P = .97), were impaired in AFMR+ compared with AFMR- patients despite comparable LA and LV volumes. MR severity correlated with systolic annular contraction (r = 0.64, P < .0001), saddle deepening (r = 0.53, P = .003), and LV GLS (r = 0.46, P < .0001). Multivariate analysis identified that impaired systolic contraction (odds ratio, 2.18; P = .001) and saddle deepening (odds ratio, 2.68; P = .04) were independently associated with MR. Excluding annular dynamics from the model, less negative LV GLS, but not LA strain, became associated with MR (odds ratio, 1.93; P < .0001). CONCLUSIONS: In patients with AF and absent LA contraction, the normal predominantly "atriogenic" annular dynamics become "ventriculogenic." Isolated LA enlargement is insufficient to cause important MR without coexisting abnormal LV mechanics and annular dynamics during systole. "Atrial" functional MR may not be purely an atrial disorder.

Association of serum ADAMTS7 levels and genetic variant rs1994016 with acute coronary syndrome in a Chinese population: A case control study.

BACKGROUND AND AIMS: Acute coronary syndrome (ACS) is commonly caused by rupture or erosion of coronary atherosclerotic plaques and secondary thrombus formation. Metalloproteinase ADAMTS7 was found to play an important role in atherogenesis. This study aimed to explore the association of serum ADAMTS7 levels and rs1994016 polymorphism at ADAMTS7 locus with ACS in a Chinese population. METHODS: 1881 patients who underwent coronary angiography were consecutively recruited. Among them, 426 patients were matched for case-controlled analysis. Serum ADAMTS7 levels were determined through enzyme-linked immunosorbent assay (ELISA) and rs1994016 polymorphism was detected by polymerase chain reaction (PCR). RESULTS: Serum ADAMTS7 levels in patients with unstable angina pectoris were much higher than in non-atherosclerotic patients, however, no difference was found among non-atherosclerotic patients, the coronary atherosclerosis subgroup and stable angina pectoris subgroup. A higher serum ADAMTS7 level was found in the ACS group than in the non-ACS group (0.61 ±â€¯0.04 vs. 0.47 ±â€¯0.02 ng/mL, p = 0.002) and serum ADAMTS7 level was found to be an independent risk factor for ACS after adjusting for major confounding factors (OR:2.81, 95% CI:1.33-5.93, p = 0.007). ADAMTS7 rs1994016 CT/TT polymorphism was negatively associated with the risk of ACS (OR:0.40, 95% CI:0.22-0.71, p = 0.002). Meanwhile, crossover analysis revealed that in CT/TT homozygotes, ACS risk was reduced nearly 80% in patients with serum ADAMTS7 levels <0.594 ng/mL (Interaction p = 0.002). CONCLUSIONS: Serum level of ADAMTS7 was positively associated and rs1994016 CT/TT genotype was negatively associated with the risk of ACS. Patients with lower serum ADAMTS7 level and rs1994016 CT/TT genotype are less likely to suffer from ACS in a Chinese population.

Functional Implication of Mitral Annular Disjunction in Mitral Valve Prolapse: A Quantitative Dynamic 3D Echocardiographic Study.

OBJECTIVES: This study aimed to assess the hypothesis that mitral annular disjunction (MAD) is associated with abnormal annular dynamics due to decoupling of annular-ventricular function. BACKGROUND: MAD, defined as a separation between the atrial wall-mitral valve (MV) junction and left ventricular (LV) attachment, is a structural abnormality occurring in MV prolapse (MVP). Few data exist on the 3-dimensional (3D) geometry of MAD and its functional implication. METHODS: A total of 156 subjects including 101 MVP patients (58 ± 11 years), 30 subjects with normal MV (57 ± 15 years), and 25 heart failure patients with functional mitral regurgitation (66 ± 10 years) were studied using real-time 3D transesophageal echocardiography. The spatial relation between atrial wall, MV, and LV attachment was examined for MAD. The 3D extent of MAD and annular dynamics were quantitatively assessed. The LV global longitudinal strain and basal circumferential strains were measured by speckle tracking echocardiography. RESULTS: MAD was evident in 42 MVP patients (42%), measuring 8.9 mm (6.3 to 10.7 mm), circumferentially spanning 87 ± 41°. Dynamically, normal and nondisjunctive annulus contracted and increased in a saddle shape during systole. In heart failure patients with functional mitral regurgitation, mitral annulus was dilated and relatively adynamic, probably related to poor LV function. In contrast, disjunctive annulus displayed paradoxical systolic expansion and flattening (p < 0.0001), despite preserved and comparable LV strains with normal patients. The 3D extent of MAD correlated significantly with abnormal annular dynamics and larger regurgitant orifice (p < 0.0001). In MVP patients without MAD, the LV global longitudinal strain correlated inversely with change in height (r = -0.61; p < 0.0001), whereas LV basal circumferential strain correlated with change in area (r = 0.61; p < 0.0001), but not in patients with MAD (p > 0.05). CONCLUSIONS: MAD is a common anatomic abnormality in MVP. The disjunctive annulus is decoupled functionally from the ventricle, leading to paradoxical annular dynamics with systolic expansion and flattening, and may thus require specific intervention.

Using Anatomic Intelligence to Localize Mitral Valve Prolapse on Three-Dimensional Echocardiography.

BACKGROUND: Accurate localization of mitral valve prolapse (MVP) is crucial for surgical planning. Despite improved visualization of the mitral valve by three-dimensional transesophageal echocardiography, image interpretation remains expertise dependent. Manual construction of mitral valve topographic maps improves diagnostic accuracy but is time-consuming and requires substantial manual input. A novel computer-learning technique called Anatomical Intelligence in ultrasound (AIUS) semiautomatically tracks the annulus and leaflet anatomy for parametric analysis. The aims of this study were to examine whether AIUS could improve accuracy and efficiency in localizing MVP among operators with different levels of experience. METHODS: Two experts and four intermediate-level echocardiographers (nonexperts) retrospectively performed analysis of three-dimensional transesophageal echocardiographic images to generate topographic mitral valve models in 90 patients with degenerative MVP. All echocardiographers performed both AIUS and manual segmentation in sequential weekly sessions. The results were compared with surgical findings. RESULTS: Manual segmentation by nonexperts had significantly lower sensitivity (60% vs 90%, P < .001), specificity (91% vs 97%, P = .001), and accuracy (83% vs 95%, P < .001) compared with experts. AIUS significantly improved the accuracy of nonexperts (from 83% to 89%, P = .003), particularly for lesions involving the A3 (from 81% to 94%, P = .006) and P1 (from 78% to 88%, P = .001) segments, presumably related to anatomic variants of the annulus that made tracking more challenging. AIUS required significantly less time for image analysis by both experts (1.9 ± 0.7 vs 9.9 ± 3.5 min, P < .0001) and nonexperts (5.0 ± 0.5 vs 13 ± 1.5 min, P < .0001), especially for complex lesions. CONCLUSIONS: Anatomic assessment of mitral valve pathology by three-dimensional transesophageal echocardiography is experience dependent. A semiautomated algorithm using AIUS improves accuracy and efficiency in localizing MVP by less experienced operators.

EphrinB2/EphB4 pathway in postnatal angiogenesis: a potential therapeutic target for ischemic cardiovascular disease.

Ischemic cardiovascular disease remains one of the leading causes of morbidity and mortality in the world. Proangiogenic therapy appears to be a promising and feasible strategy for the patients with ischemic cardiovascular disease, but the results of preclinical and clinical trials are limited due to the complicated mechanisms of angiogenesis. Facilitating the formation of functional vessels is important in rescuing the ischemic cardiomyocytes. EphrinB2/EphB4, a novel pathway in angiogenesis, plays a critical role in both microvascular growth and neovascular maturation. Hence, investigating the mechanisms of EphrinB2/EphB4 pathway in angiogenesis may contribute to the development of novel therapeutics for ischemic cardiovascular disease. Previous reviews mainly focused on the role of EphrinB2/EphB4 pathway in embryo vascular development, but their role in postnatal angiogenesis in ischemic heart disease has not been fully illustrated. Here, we summarized the current knowledge of EphrinB2/EphB4 in angiogenesis and their interaction with other angiogenic pathways in ischemic cardiovascular disease.

Automated quantification of mitral valve anatomy using anatomical intelligence in three-dimensional echocardiography.

BACKGROUND: Quantitative analysis of mitral valve morphology with three-dimensional (3D) transesophageal echocardiography (TEE) provides anatomic information that can assist clinical decision-making. However, routine use of mitral valve quantification has been hindered by tedious workflow and high operator-dependence. The purpose of this paper was to evaluate the feasibility, accuracy and efficiency of a novel computer-learning algorithm using anatomical intelligence in ultrasound (AIUS) to automatically detect and quantitatively assess the mitral valve anatomy. METHODS: A novice operator used AIUS to quantitatively assess mitral valve anatomy on the 3D TEE images of 55 patients (33 with mitral valve prolapse, 11 with functional mitral regurgitation, and 11 normal valves). The results were compared to that of manual mitral valve quantification by an experienced 3D echocardiographer and, in the 24 patients who underwent mitral valve repair, the surgical findings. Time consumption and reproducibility of AIUS were compared to the manual method. RESULTS: AIUS mitral valve quantification was feasible in 52 patients (95%). There were excellent agreements between AIUS and expert manual quantification for all mitral valve anatomic parameters (r=0.85-0.99, p<0.05). AIUS accurately classified surgically defined location of prolapse in 139 of 144 segments analyzed (97%). AIUS improved the intra- [intraclass-correlation coefficient (ICC)=0.91-0.99] and inter-observer (ICC=0.86-0.98) variability of novice users, surpassing the manual approach (intra-observer ICC=0.32-0.95; inter-observer ICC=0.45-0.93), yet requiring significantly less time (144±24s vs. 770±89s, p<0.0001). CONCLUSION: Anatomic intelligence in 3D TEE image can provide accurate, reproducible, and rapid quantification of the mitral valve anatomy.

Abnormal mitral-aortic intervalvular coupling in mitral valve diseases: a study using real-time three-dimensional transesophageal echocardiography.

BACKGROUND: Mitral and aortic valves are coupled via fibrous tissue. This coupling is considered to be important for cardiac function before and after mitral valve surgery. The relationship between mitral-aortic coupling and different types of mitral regurgitation (MR) is not completely understood. METHODS AND RESULTS: Real-time three-dimensional transesophageal echocardiography (RT3D-TEE) was performed in 133 subjects: 30 normal subjects, 15 patients with Carpentier type I MR (annular dilatation and congenital cleft), 40 type II (mitral valve prolapse), 20 type IIIa (rheumatic) and 28 type IIIb (ischemic mitral regurgitation). Custom software was used to track mitral (MA) and aortic annuli (AoA) in 3D space throughout cardiac cycle, allowing measurement of changes in mitral and aortic valve morphology. Normal mitral-aortic coupling is characterized by reciprocal changes in the annular areas throughout cardiac cycle, with systolic reduction of the angle between the two annular planes. In Carpentier type II patients, not only MA but also AoA areas were increased (P < 0.05 vs normal), but the reciprocal pattern of mitral-aortic coupling was preserved. In both type I IMR and IIIb patients, MA and AoA areas were both increased (P < 0.05 vs normal) and the reciprocal behavior of mitral-aortic coupling was lost. Only MA area was increased in type IIIa patients. The extent of mitral-aortic angle reduction during systole was diminished in all 4 Carpentier groups (P < 0.05 vs normal). CONCLUSIONS: Mitral valve diseases may affect normal mitral-aortic coupling and aortic valve function. Different patterns of abnormal mitral-aortic coupling are associated with different Carpentier types of MR.

The prevalence and prognosis of resistant hypertension in patients with heart failure.

BACKGROUND: Resistant hypertension is associated with adverse clinical outcome in hypertensive patients. However, the prognostic significance of resistant hypertension in patients with heart failure remains uncertain. METHODS AND RESULTS: The 1 year survival and heart failure re-hospitalization rate of 1288 consecutive patients admitted to a university hospital for either newly diagnosed heart failure or an exacerbation of prior chronic heart failure was analyzed. Resistant hypertension was defined as uncontrolled blood pressure (> 140/90 mmHg) despite being compliant with an antihypertensive regimen that includes 3 or more drugs (including a diuretic). A total of 176 (13.7%) heart failure patients had resistant hypertension. There was no difference in all cause mortality, cardiovascular mortality, and heart failure related re-hospitalization between patients with versus without resistant hypertension. Diabetes [hazard ratio = 1.62, 95% confidence interval = 1.13-2.34; P = 0.010] and serum sodium > 139 mmol/L (hazard ratio = 1.54, 95% confidence interval = 1.06-2.23; P = 0.024) were independently associated with resistant hypertension. Patients with resistant hypertension had a relatively higher survival rate (86.9% vs. 83.8%), although the difference was not significant (log-rank x2 = 1.00, P = 0.317). In patients with reduced ejection fraction, heart failure related re-hospitalization was significantly lower in patients with resistant hypertension (45.8% vs. 59.1%, P = 0.050). CONCLUSIONS: Resistant hypertension appears to be not associated with adverse clinical outcome in patients with heart failure, in fact may be a protective factor for reduced heart failure related re-hospitalization in patients with reduced ejection fraction.