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BACKGROUND: Aging-associated left ventricular dysfunction promotes cardiopulmonary fibrogenic remodeling, Group 2 pulmonary hypertension (PH), and right ventricular failure. At the time of diagnosis, cardiac function has declined, and cardiopulmonary fibrosis has often developed. Here, we sought to develop a molecular positron emission tomography (PET)-magnetic resonance imaging (MRI) protocol to detect both cardiopulmonary fibrosis and fibrotic disease activity in a left ventricular dysfunction model. METHODS AND RESULTS: Left ventricular dysfunction was induced by transverse aortic constriction (TAC) in 6-month-old senescence-accelerated prone mice, a subset of mice that received sham surgery. Three weeks after surgery, mice underwent simultaneous PET-MRI at 4.7 T. Collagen-targeted PET and fibrogenesis magnetic resonance (MR) probes were intravenously administered. PET signal was computed as myocardium- or lung-to-muscle ratio. Percent signal intensity increase and Δ lung-to-muscle ratio were computed from the pre-/postinjection magnetic resonance images. Elevated allysine in the heart (P=0.02) and lungs (P=0.17) of TAC mice corresponded to an increase in myocardial magnetic resonance imaging percent signal intensity increase (P

BackgroundRecently shown to regulate cardiac development, the secreted axon guidance molecule SLIT3 maintains its expression in the postnatal heart. Despite its known expression in the cardiovascular system after birth, SLIT3's relevance to cardiovascular function in the postnatal state remains unknown. As such, the objectives of this study were to determine the postnatal myocardial sources of SLIT3 and to evaluate its functional role in regulating the cardiac response to pressure overload stress.MethodsWe performed in vitro studies on cardiomyocytes and myocardial tissue samples from patients and performed in vivo investigation with SLIT3 and ROBO1 (roundabout homolog 1) mutant mice undergoing transverse aortic constriction to establish the role of SLIT3-ROBO1 in adverse cardiac remodeling.ResultsWe first found that SLIT3 transcription was increased in myocardial tissue obtained from patients with congenital heart defects that caused ventricular pressure overload. Immunostaining of hearts from WT (wild-type) and reporter mice revealed that SLIT3 is secreted by cardiac stromal cells, namely fibroblasts and vascular mural cells, within the heart. Conditioned media from cardiac fibroblasts and vascular mural cells both stimulated cardiomyocyte hypertrophy in vitro, an effect that was partially inhibited by an anti-SLIT3 antibody. Also, the N-terminal, but not the C-terminal, fragment of SLIT3 and the forced overexpression of SLIT3 stimulated cardiomyocyte hypertrophy and the transcription of hypertrophy-related genes. We next determined that ROBO1 was the most highly expressed roundabout receptor in cardiomyocytes and that ROBO1 mediated SLIT3's hypertrophic effects in vitro. In vivo, Tcf21+ fibroblast and Tbx18+ vascular mural cell-specific knockout of SLIT3 in mice resulted in decreased left ventricular hypertrophy and cardiac fibrosis after transverse aortic constriction. Furthermore, α-MHC+ cardiomyocyte-specific deletion of ROBO1 also preserved left ventricular function and abrogated hypertrophy, but not fibrosis, after transverse aortic constriction.ConclusionsCollectively, these results indicate a novel role for the SLIT3-ROBO1-signaling axis in regulating postnatal cardiomyocyte hypertrophy induced by pressure overload.

The effect of electronic cigarette (E-cig) vaping on cardiac and vascular function during the healing phase of myocardial infarction (MI), and post-MI remodeling was investigated. Sprague Dawley rats were subjected to left coronary artery ligation to induce MI. One week later, rats were randomized to receive either 12 weeks of exposure to purified air (n = 37) or E-cig vapor (15 mg/ml of nicotine) (n = 32). At 12 weeks, cardiac and vascular function, and post-MI remodeling were assessed. Baseline blood flow in the femoral artery did not differ between groups, but peak reperfusion blood flow was blunted in the E-cig group (1.59 ± 0.15 ml/min) vs. the air group (2.11 ± 0.18 ml/min; p = 0.034). Femoral artery diameter after reperfusion was narrower in the E-cig group (0.54 ± 0.02 mm) compared to the air group (0.60 ± 0.02 mm; p = 0.023). Postmortem left ventricular (LV) volumes were similar in the E-cig (0.69 ± 0.04 ml) and air groups (0.73 ± 0.04 ml; p = NS); and myocardial infarct expansion index did not differ between groups (1.4 ± 0.1 in E-cig group versus 1.3 ± 0.1 in air group; p = NS). LV fractional shortening by echo did not differ between groups at 12 weeks (E-cig at 29 ± 2% and air at 27 ± 1%; p = NS). Exposure to E-cig during the healing phase of MI was associated with altered vascular function with reduced femoral artery blood flow and diameter at reperfusion, but not with worsened LV dilation or worsened cardiac function.

Li, Xiaoxu, Zhijun Pu, Gang Xu, Yidong Yang, Yu Cui, Xiaoying Zhou, Chenyuan Wang, Zhifeng Zhong, Simin Zhou, Jun Yin, Fabo Shan, Chengzhong Yang, Li Jiao, Dewei Chen, and Jian Huang. Hypoxia-induced myocardial hypertrophy companies with apoptosis enhancement and p38-MAPK pathway activation. High Alt Med Biol. 25:186–196, 2024. Background: Right ventricular function and remodeling are closely associated with symptom severity and patient survival in hypoxic pulmonary hypertension. However, the detailed molecular mechanisms underlying hypoxia-induced myocardial hypertrophy remain unclear. Methods: In Sprague–Dawley rats, hemodynamics were assessed under both normoxia and hypobaric hypoxia at intervals of 7 (H7), 14 (H14), and 28 (H28) days. Morphological changes in myocardial tissue were examined using hematoxylin and eosin (HE) staining, while myocardial hypertrophy was evaluated with wheat germ agglutinin (WGA) staining. Apoptosis was determined through TUNEL assays. To further understand the mechanism of myocardial hypertrophy, RNA sequencing was conducted, with findings validated via Western blot analysis. Results: The study demonstrated increased hypoxic pulmonary hypertension and improved right ventricular diastolic and systolic function in the rat models. Significant elevations in pulmonary arterial systolic pressure (PASP), mean pulmonary arterial pressure (mPAP), right ventricular mean pressure (RVMP), and the absolute value of +dp/dtmax were observed in the H14 and H28 groups compared with controls. In addition, right ventricular systolic pressure (RVSP), −dp/dtmax, and the mean dp/dt during isovolumetric relaxation period were notably higher in the H28 group. Heart rate increased in the H14 group, whereas the time constant of right ventricular isovolumic relaxation (tau) was reduced in both H14 and H28 groups. Both the right heart hypertrophy index and the heart weight/body weight ratio (HW/BW) were elevated in the H14 and H28 groups. Myocardial cell cross-sectional area also increased, as shown by HE and WGA staining. Western blot results revealed upregulated HIF-1α levels and enhanced HIF-2α expression in the H7 group. In addition, phosphorylation of p38 and c-fos was augmented in the H28 group. The H28 group showed elevated levels of Cytochrome C (Cyto C), whereas the H14 and H28 groups exhibited increased levels of Cleaved Caspase-3 and the Bax/Bcl-2 ratio. TUNEL analysis revealed a rise in apoptosis with the extension of hypoxia duration in the right ventricle. Conclusions: The study established a link between apoptosis and p38-MAPK pathway activation in hypoxia-induced myocardial hypertrophy, suggesting their significant roles in this pathological process. [ABSTRACT FROM AUTHOR]

Objectives: Women with a hypertensive disorder of pregnancy (HDP) are at increased risk of developing hypertension and cardiovascular disease later in life. However, from previous studies, it is difficult to define whether this association reflects pre‐existing maternal cardiovascular risk or a potentially causal relationship between HDP and later cardiovascular risk. In this study, we performed detailed cardiovascular assessment in women in midgestation, prior to development of HDP, and at 2 years postpartum, aiming to identify cardiovascular changes prior to development of HDP and to assess persistent cardiovascular alterations long after the HDP event. Methods: This was a prospective observational study in which we performed detailed cardiovascular assessment in midgestation and at a median of 2.3 (interquartile range, 2.1–2.4) years postpartum. We examined 112 women who developed HDP and 451 women whose pregnancy was not complicated by hypertension. We used conventional and more advanced (i.e. speckle tracking) echocardiographic techniques to determine accurately left ventricular systolic and diastolic function. We used M‐mode measurements to determine left ventricular remodeling and estimate left ventricular mass. Maternal vascular status was assessed using ophthalmic artery Doppler and by calculating peak systolic velocity (PSV) ratio, as a marker of peripheral vascular resistance. Results: In midgestation, women who subsequently developed HDP had increased ophthalmic artery PSV ratio. These women also had mild cardiac functional and morphological alterations, which were accounted for mostly by maternal cardiovascular risk factors. At 2 years postpartum, women who had experienced HDP, compared to those who did not, had cardiovascular abnormalities with reduction in left ventricular systolic and diastolic function, which remained after multivariable analysis. Longitudinal analysis demonstrated that the evolution of cardiovascular changes in the HDP and non‐HDP groups was similar. Conclusions: Mild cardiac functional and morphological alterations precede the development of HDP and such changes persist for at least 2 years postpartum. The cardiac changes are likely to be the consequence of pre‐existing maternal cardiovascular risk factors rather than an adverse consequence of HDP. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Aims This study aims to explore the presence of left ventricular (LV) and left atrial (LA) morphological and functional abnormalities in patients with Barlow's disease (BD) without significant mitral regurgitation (MR) and to investigate whether these abnormalities may predict MR progression. Methods and results Consecutive patients with BD were retrospectively identified from two tertiary centres; those with MR graded from trivial to mild-to-moderate were selected and matched with healthy controls in a 1:1 ratio. Conventional and speckle-tracking echocardiographic data were collected. The development of moderate-to-severe or greater MR was evaluated on follow-up echocardiograms. Patients with BD (n = 231) showed increased LV dimensions and indexed LV mass (LVMi) in comparison with controls (P < 0.001); LV remodelling worsened with higher MR severity and was accompanied by an increased prevalence of eccentric LV hypertrophy (eLVH). Moreover, BD patients had larger LA volumes and more impaired LA reservoir strain vs. controls (P < 0.001), while LV strain was similar between the two groups. Multivariable linear regression analyses in the overall population identified BD and MR grade as independent predictors of remodelling markers (LV dimensions, LVMi, and LA volume) and BD as independent correlate of LA strain. MR progression was observed in 51 BD subjects (out of 170 patients with available follow-up). On Cox regression analysis, age, eLVH, mild-to-moderate MR, and mitral annular disjunction (MAD) emerged as independent predictors of MR progression. Conclusion BD patients without significant MR show early LV and LA remodelling, together with reduced LA strain. MR progression was associated with eccentric LV remodelling, MAD, and MR severity. [ABSTRACT FROM AUTHOR]

Pathologic left ventricular remodeling and valvular heart disease may contribute to the clinical presentation and outcomes of patients presenting with heart failure, and limit the effectiveness of guideline-directed medical therapy. Although surgical interventions including surgical ventricular restoration techniques and valve repair or replacement are effective therapies, there is growing evidence that transcatheter interventions may be options for patients with persistent symptoms of heart failure despite optimal medical therapy, where surgical options may be limited. This scientific statement will review the current available and investigational percutaneous strategies for the management of structural contributors to heart failure: dilated left ventricular cardiomyopathies and valvular heart disease. • Structural cardiac abnormalities limit the effectiveness of GDMT for HF. • Transcatheter interventions to address structural abnormalities are potential alternatives to high-risk surgery in patients with HF. • Better data are needed to confirm the safety and efficacy of transcatheter treatment of refractory HF. [ABSTRACT FROM AUTHOR]

Under the long‐term pressure overload stimulation, the heart experiences embryonic gene activation, leading to myocardial hypertrophy and ventricular remodelling, which can ultimately result in the development of heart failure. Identifying effective therapeutic targets is crucial for the prevention and treatment of myocardial hypertrophy. Histone lysine lactylation (HKla) is a novel post‐translational modification that connects cellular metabolism with epigenetic regulation. However, the specific role of HKla in pathological cardiac hypertrophy remains unclear. Our study aims to investigate whether HKla modification plays a pathogenic role in the development of cardiac hypertrophy. The results demonstrate significant expression of HKla in cardiomyocytes derived from an animal model of cardiac hypertrophy induced by transverse aortic constriction surgery, and in neonatal mouse cardiomyocytes stimulated by Ang II. Furthermore, research indicates that HKla is influenced by glucose metabolism and lactate generation, exhibiting significant phenotypic variability in response to various environmental stimuli. In vitro experiments reveal that exogenous lactate and glucose can upregulate the expression of HKla and promote cardiac hypertrophy. Conversely, inhibition of lactate production using glycolysis inhibitor (2‐DG), LDH inhibitor (oxamate) and LDHA inhibitor (GNE‐140) reduces HKla levels and inhibits the development of cardiac hypertrophy. Collectively, these findings establish a pivotal role for H3K18la in pathological cardiac hypertrophy, offering a novel target for the treatment of this condition. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of PCSK9 inhibitors on the level of inflammation and ventricular remodeling after PCI in ST-elevation acute myocardial infarction. Methods A total of 220 patients with acute ST-segment elevation myocardial infarction who received percutaneous coronary artery intervention in the Emergency Center of Qingdao Central Hospital from April 2021 to July 2023 were randomly divided into two groups, 110 patients in the control group were treated with conventional treatment, and 110 patients in the PCSK9i group were treated with PCSK9 inhibitors on the basis of conventional treatment. Compared before and after treatment left ventricular endsystolic diameter (LVESD) and left ventricular ejection fraction (LVEF) and triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC). C-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor α (TNF- α). The incidence of major adverse cardiovascular events (MACE) (including myocardial infarction, recurrence of heart failure, malignant arrhythmia, and cardiovascular death) was compared. Results After 6 months of treatment and follow-up, LVEDD (mm), LVESD(mm), TG(mmol/L), TC(mmol/L), LDL-C(mmol/L), CRP(mg/L), TNF-α(pg/mL) and JL-6 (ng/mL) after PCSK9i treatment were significantly lower than those in the control group, and the difference was statistically significant [(51.32 ± 5.84) vs. (54.43 ± 2.91);(34.88 ± 2.69) vs. (36.96 ± 3.19);(1.41 ± 0.61) vs. (2.13 ± 1.26);(3.53 ± 1.06) vs. (3.98 ± 0.93);(0.95 ± 0.36) vs. (1.79 ± 0.27);(5.18 ± 1.92) vs. (7.69 ± 2.61);(36.43 ± 9.41) vs. (57.79 ± 14.43);(17.4 ± 0.68) vs. (28.55 ± 8.92),All P < 0.01], and the LVEF (%)and HDL-C(mmol/L)in the PCSK9i group were higher than patients in the control group, and the difference was statistically significant [(46.69 ± 3.63) vs. (41.34 ± 3.42),P < 0.05,(1.35 ± 0.29) vs. (1.29 ± 0.27),P < 0.01]. The incidence of MACE events in the PCSK9i group was obviously lower than patients in the control group (5.2% vs. 13.6%, P < 0.05). Conclusion The application of PCSK9 inhibitors after PCI in patients with ST-segment elevation acute myocardial infarction can better reduce blood lipids, stabilize coronary plaque, reduce local and circulatory inflammatory responses after myocardial infarction, improve ventricular adverse remodeling after myocardial infarction, inhibit ventricular remodeling, and reduce the total incidence of MACE, worthing promoting use. [ABSTRACT FROM AUTHOR]

Aim Materials and Methods Results Conclusions To investigate the association between metabolically healthy obesity (MHO) and left ventricular geometric remodelling in Chinese children.This cross‐sectional study used data from two population‐based samples in China, including 2871 children aged 6–11 years. Weight status was defined based on body mass index according to the World Health Organization growth chart. Metabolic status was defined based on the 2018 consensus‐based criteria proposed by Damanhoury et al. Obes Rev 2018;19:1476–1491 (blood pressure, lipids and glucose). Left ventricular geometric remodelling was determined as concentric remodelling, eccentric hypertrophy, and concentric hypertrophy. Multinomial logistic regression analysis was used to determine odds ratios (ORs) and 95% confidence intervals (CIs) for the association between categories of weight and metabolic status and left ventricular geometric remodelling.Compared with children with metabolically healthy normal weight, those with MHO had higher odds of left ventricular geometric remodelling, with adjusted ORs (95% CIs) of 2.01 (1.23–3.28) for concentric remodelling, 6.36 (4.03–10.04) for eccentric hypertrophy, and 17.07 (7.97–36.58) for concentric hypertrophy. Corresponding ORs (95% CIs) were 2.35 (1.47–3.75), 10.85 (7.11–16.55), and 18.56 (8.63–39.94), respectively, for children with metabolically unhealthy obesity. In contrast, metabolically unhealthy normal weight was not associated with higher odds of left ventricular geometric remodelling. Findings were consistent in sensitivity analyses that used different definitions of weight and metabolic status and left ventricular geometric remodelling.Children with MHO had higher odds of left ventricular geometric remodelling than their metabolically healthy normal weight counterparts. Our findings suggest MHO may not be a benign condition for cardiac health in children. [ABSTRACT FROM AUTHOR]

Aim To investigate the inhibition role and mechanism of adipose derived mesenchymal stem cell (ADMSC) exosomes (Exo) on adverse ventricular remodeling after myocardial infarction (MI). Methods The changes of autophagy and inflammasomes phenotype of cardiac fibroblasts after H2O2 treatment were observed. MI rats were injected with an equal volume of normal saline, adipose derived mesenchymal stem cell exosomes (MSC-Exo) or fibroblast exosomes (MEF-Exo) via a tail vein. The expression of autophagy related 16 like protein 1 (ATG16L1), autophagy related protein 7 (ATG7) and NOD-like receptor protein 3 (NLRP3), inflammatory response, the degree of myocardial fibrosis, and the cardiac function were observed in different groups. Results After treatment with H2O2 on cardiac fibroblasts, the expressions of ATG16L1 and ATG7 were significantly decreased (P<0. 001), NLRP3 was significantly increased ( P < 0. 001 ), and the levels of inflammatory cytokines interleukin-1β ( IL-1β) and IL-18 were significantly elevated (P < 0. 001 ). After MI rats were intervened with MSC-Exo, the expressions of autophagy related proteins ATG16L1 and ATG7 were significantly up-regulated (P<0. 001), NLRP3 was significantly down-regulated (P<0. 001), serum IL-1β and IL-18 levels were significantly decreased (P<0. 001), fibrosis-related proteins collagen Ⅰ and Ⅲ were significantly reduced (P<0. 001), myocardial fibrosis was significantly relieved (P<0. 001), and cardiac function was significantly improved (P<0. 001). Conclusion Adipose derived MSC-Exo play a role in inhibiting adverse ventricular remodeling after MI by regulating the balance of autophagy and NLRP3 inflammasomes. [ABSTRACT FROM AUTHOR]

Background: Previous studies have initially reported accompanying elevated 2-deoxy-2[18F]fluoro-D-glucose ([18F]F-FDG) inflammatory activity in the remote area and its prognostic value after acute myocardial infarction (AMI). Non-invasive characterization of the accompanying inflammation in the remote myocardium may be of potency in guiding future targeted theranostics. [68Ga]Ga-Pentixafor targeting chemokine receptor 4 (CXCR4) on the surface of inflammatory cells is currently one of the promising inflammatory imaging agents. In this study, we sought to focus on the longitudinal evolution of [68Ga]Ga-Pentixafor activities in the remote myocardium following AMI and its association with cardiac function. Methods: Twelve AMI rats and six Sham rats serially underwent [68Ga]Ga-Pentixafor imaging at pre-operation, and 5, 7, 14 days post-operation. Maximum and mean standard uptake value (SUV) and target-to-background ratio (TBR) were assessed to indicate the uptake intensity. Gated [18F]F-FDG imaging and immunofluorescent staining were performed to obtain cardiac function and responses of pro-inflammatory and reparative macrophages, respectively. Results: The uptake of [68Ga]Ga-Pentixafor in the infarcted myocardium peaked at day 5 (all P = 0.003), retained at day 7 (all P = 0.011), and recovered at day 14 after AMI (P > 0.05), paralleling with the rise-fall pro-inflammatory M1 macrophages (P < 0.05). Correlated with the peak activity in the infarct territory, [68Ga]Ga-Pentixafor uptake in the remote myocardium on day 5 early after AMI significantly increased (AMI vs. Sham: SUVmean, SUVmax, and TBRmean: all P < 0.05), and strongly correlated with contemporaneous EDV and/or ESV (SUVmean and TBRmean: both P < 0.05). The transitory remote activity recovered as of day 7 post-AMI (AMI vs. Sham: P > 0.05). Conclusions: Corresponding with the peaked [68Ga]Ga-Pentixafor activity in the infarcted myocardium, the activity in the remote region elevated accordingly and led to contemporaneous left ventricular remodelling early after AMI. Further studies are warranted to clarify its clinical application potential. [ABSTRACT FROM AUTHOR]

Mitral valve prolapse is a common valve disorder that usually has a benign prognosis unless there is significant regurgitation or LV impairment. However, a subset of patients are at an increased risk of ventricular arrhythmias and sudden cardiac death, which has led to the recognition of "arrhythmic mitral valve prolapse" as a clinical entity. Emerging risk factors include mitral annular disjunction and myocardial fibrosis. While echocardiography remains the primary method of evaluation, cardiac magnetic resonance has become crucial in managing this condition. Cine magnetic resonance sequences provide accurate characterization of prolapse and annular disjunction, assessment of ventricular volumes and function, identification of early dysfunction and remodeling, and quantitative assessment of mitral regurgitation when integrated with flow imaging. However, the unique strength of magnetic resonance lies in its ability to identify tissue changes. T1 mapping sequences identify diffuse fibrosis, in turn related to early ventricular dysfunction and remodeling. Late gadolinium enhancement sequences detect replacement fibrosis, an independent risk factor for ventricular arrhythmias and sudden cardiac death. There are consensus documents and reviews on the use of cardiac magnetic resonance specifically in arrhythmic mitral valve prolapse. However, in this article, we propose an algorithm for the broader use of cardiac magnetic resonance in managing this condition in various scenarios. Future advancements may involve implementing techniques for tissue characterization and flow analysis, such as 4D flow imaging, to identify patients with ventricular dysfunction and remodeling, increased arrhythmic risk, and more accurate grading of mitral regurgitation, ultimately benefiting patient selection for surgical therapy. [ABSTRACT FROM AUTHOR]

Introduction: The association between paced LVAT and cardiac structure and function at baseline, as well as whether longer LVAT is associated with worse cardiac reverse remodeling in patients with heart failure (HF) and left bundle branch block (LBBB) has not been well investigated. The purpose of this study is to investigate the association between paced LVAT and baseline echocardiographic parameters and cardiac reverse remodeling at follow‐up. Methods: Patients with HF and LBBB receiving successful left bundle branch pacing (LBBP) from June 2018 to April 2023 were enrolled and grouped based on paced LVAT. NT‐proBNP and echocardiographic parameters were recorded during routine follow‐up. The relationships between paced LVAT and echocardiographic parameters at baseline and follow‐up were analyzed. Results: Eighty‐three patients were enrolled (48 males, aged 65 ± 9.8, mean LVEF 32.1 ± 7.5%, mean LVEDD 63.0 ± 8.5 mm, median NT‐proBNP 1057[513–3158] pg/mL). The paced QRSd was significantly decreased (177 ± 17.9 vs. 134 ± 18.5, p <.001) and median paced LVAT was 80[72–88] ms. After a median follow‐up of 12[9–29] months, LVEF increased to 52.1 ± 11.2%, LVEDD decreased to 52.6 ± 8.8 mm, and NT‐proBNP decreased to 215[73–532]pg/mL. Patients were grouped based on paced LVAT: LVAT < 80 ms (n = 39); 80 ≤ LVAT < 90 ms (n = 24); LVAT ≥ 90 ms (n = 20). Patients with longer LVAT had larger LVEDD and lower LVEF (LVEDDbaseline: p <.001; LVEFbaseline: p =.001). The difference in LVEF6M was statistically significant among groups (p <.001) and patients with longer LVAT had lower LVEF6M, while the difference in LVEF1Y was not seen (p =.090). There was no significant correlation between ΔLVEF6M‐baseline, ΔLVEF1Y‐6M and LVAT respectively (ΔLVEF6M‐baseline: p =.261, r = −.126; ΔLVEF1Y‐6M: p =.085, r =.218). Conclusion: Long paced LVAT was associated with worse echocardiographic parameters at baseline, but did not affect the cardiac reverse remodeling in patients with HF and LBBB. Those with longer LVAT required longer time to recover. [ABSTRACT FROM AUTHOR]

Effects of angiotensin receptor/neprilysin inhibitors (ARNI) on ventricular remodeling in patients with heart failure, especially heart failure with reduced ejection fraction (HFrEF), are better than those of angiotensin-converting enzyme inhibitors (ACEI). Acute myocardial infarction (AMI) complicated by mitral regurgitation exacerbates ventricular remodeling and increases the risk of heart failure. There is limited evidence on the effects of early administration of ARNI in patients with AMI complicated by mitral regurgitation. The aim of this trial was to examine the effectiveness and the safety of early administration of sacubitril/valsartan after coronary artery revascularization in patients with AMI complicated by moderate-to-severe mitral regurgitation. This was a randomized, single-blind, parallel-group, controlled trial. From June 2021 to June 2022, we enrolled 142 consecutive patients with AMI complicated by moderate-to-severe mitral regurgitation and followed them for 12 months. The patients received standard treatment for AMI and were randomly assigned to receive ARNI or benazepril. The primary efficacy end points were the differences in mitral regurgitant jet area (MRJA), mitral regurgitant volume (MRV), concentration of n-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), and left ventricular end-diastolic volume and end-systolic volume (LVEDV and LVESV) between groups and within groups at baseline, 1, 3, 6, and 12 months. Secondary end points included the rates of heart failure hospitalization, all-cause mortality, refractory angina, malignant arrhythmias, recurrent myocardial infarction, and stroke. Safety end points included the rates of hyperkalemia, renal dysfunction, hypotension, angioedema, and cough. The ARNI group had significantly lower NT-proBNP levels than the benazepril group at 1 month and later (P < 0.001). MRJA and MRV significantly improved in the ARNI group compared with the benazepril group at 12 months (MRJA: − 3.21 ± 2.18 cm2 vs. − 1.83 ± 2.81 cm2, P < 0.05; MRV: − 27.22 ± 15.22 mL vs. − 13.67 ± 21.02 mL, P < 0.001). The ARNI group also showed significant reductions in LVEDV and LVESV (P < 0.05) and improvement in LVEF (P < 0.05). Secondary end point analysis showed a significantly higher rate of heart failure hospitalization in the benazepril group compared with the ARNI group (HR = 2.03, 95% CI 1.12–3.68, P = 0.021). Safety end point analysis showed a higher rate of hypotension in the ARNI group (P < 0.05). Early use of sacubitril/valsartan after coronary artery revascularization in patients with AMI complicated by moderate-to-severe mitral regurgitation can significantly reduce mitral regurgitation, improve ventricular remodeling, and decrease heart failure hospitalization. Nevertheless, caution is needed to avoid hypotension. Chinese Clinical Trial Registry (ChiCTR2100054255) registered on December 11, 2021. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction is an important cardiovascular disease worldwide. Although the mortality rate of myocardial infarction (MI) has improved dramatically in recent years due to timely treatment, adverse remodeling of the left ventricle continues to affect cardiac function. Various immune cells are involved in this process to induce inflammation and amplification. The infiltration of inflammatory cells in the infarcted myocardium is induced by various cytokines and chemokines, and the recruitment of leukocytes further amplifies the inflammatory response. As an increasing number of clinical anti-inflammatory therapies have achieved significant success in recent years, treating myocardial infarction by targeting inflammation may become a novel therapeutic option. In particular, successful clinical trials of canakinumab have demonstrated the important role of the inflammatory factor interleukin-1 (IL-1) in atherosclerosis. Targeted IL-1 therapy may decrease inflammation levels and improve cardiac function in patients after myocardial infarction. This article reviews the complex series of responses after myocardial infarction, including the involvement of inflammatory cells and the role of cytokines and chemokines, focusing on the progression of the IL-1 family in myocardial infarction as well as the performance of current targeted therapy drugs in experiments. [ABSTRACT FROM AUTHOR]

Altered ankyrin-R (AnkR; encoded by ANK1) expression is associated with diastolic function, left ventricular remodeling, and heart failure with preserved ejection fraction (HFpEF). First identified in erythrocytes, the role of AnkR in other tissues, particularly the heart, is less studied. Here, we identified the expression of both canonical and small isoforms of AnkR in the mouse myocardium. We demonstrate that cardiac myocytes primarily express small AnkR (sAnkR), whereas cardiac fibroblasts predominantly express canonical AnkR. As canonical AnkR expression in cardiac fibroblasts is unstudied, we focused on expression and localization in these cells. AnkR is expressed in both the perinuclear and cytoplasmic regions of fibroblasts with considerable overlap with the trans-Golgi network protein 38, TGN38, suggesting a potential role in trafficking. To study the role of AnkR in fibroblasts, we generated mice lacking AnkR in activated fibroblasts (Ank1-ifKO mice). Notably, Ank1-ifKO mice fibroblasts displayed reduced collagen compaction, supportive of a novel role of AnkR in normal fibroblast function. At the whole animal level, in response to a heart failure model, Ank1-ifKO mice displayed an increase in fibrosis and T-wave inversion compared with littermate controls, while preserving cardiac ejection fraction. Collagen type I fibers were decreased in the Ank1-ifKO mice, suggesting a novel function of AnkR in the maturation of collagen fibers. In summary, our findings illustrate the novel expression of AnkR in cardiac fibroblasts and a potential role in cardiac function in response to stress. [ABSTRACT FROM AUTHOR]

Right ventricular (RV) function is an important prognostic indicator for pulmonary arterial hypertension (PAH), a vasculopathy that primarily and disproportionally affects women with distinct pre- and postmenopausal clinical outcomes. However, most animal studies have overlooked the impact of sex and ovarian hormones on RV remodeling in PAH. Here, we combined invasive measurements of RV hemodynamics and morphology with computational models of RV biomechanics in sugen-hypoxia (SuHx)-treated male, ovary-intact female, and ovariectomized female rats. Despite similar pressure overload levels, SuHx induced increases in end-diastolic elastance and passive myocardial stiffening, notably in male SuHx animals, corresponding to elevated diastolic intracellular calcium. Increases in end-systolic chamber elastance were largely explained by myocardial hypertrophy in male and ovary-intact female rats, whereas ovariectomized females exhibited contractility recruitment via calcium transient augmentation. Ovary-intact female rats primarily responded with hypertrophy, showing fewer myocardial mechanical alterations and less stiffening. These findings highlight sex-related RV remodeling differences in rats, affecting systolic and diastolic RV function in PAH. NEW & NOTEWORTHY: Combining hemodynamic and morphological measurements from male, female, and ovariectomized female pulmonary arterial hypertension (PAH) rats revealed distinct adaptation mechanisms despite similar pressure overload. Males showed the most diastolic stiffening. Ovariectomized females had enhanced myocyte contractility and calcium transient upregulation. Ovary-intact females primarily responded with hypertrophy, experiencing milder passive myocardial stiffening and no changes in myocyte shortening. These findings suggest potential sex-specific pathways in right ventricular (RV) adaptation to PAH, with implications for targeted interventions. [ABSTRACT FROM AUTHOR]

Background: Alcohol‐associated cardiomyopathy (ACM) is a cardiac muscle disease characterized by inflammation and oxidative stress. Thromboxane‐prostanoid receptor (TP‐R) plays an important role in the pathogenesis of cardiovascular disease. Herein, we hypothesize that TP‐R mediates alcohol‐induced early cardiac injury. Methods: Eight‐week‐old male C57BL/6 wild‐type mice were fed a chronic ethanol (ET) or control diet (CON) for 10 days followed by a single binge of ethanol or maltose‐dextrin through oral gavage. A cohort of ethanol‐fed mice received SQ 29,548 (SQ), a TP‐R antagonist. RNA sequencing, real‐time PCR, and western blot analysis were performed on left ventricle to investigate alterations in genes and/or proteins mediating oxidative stress, inflammation, and cardiac remodeling. Sirius Red staining was performed to measure myocardial fibrosis. Results: RNA‐sequencing analysis of myocardium from CON and ET groups identified 142 genes that were significantly altered between the two groups. In particular, the gene expression of thioredoxin‐interacting protein (TXNIP), a component of NLR family pyrin domain containing 3 (NLRP3) signaling, which mediates oxidative stress and inflammatory response, was upregulated in response to ethanol exposure. The myocardial protein levels of TP‐R and thromboxane A2 synthase were increased upon alcohol exposure. Ethanol increased the levels of 4‐hydroxynonenal, a marker of oxidative stress, with a concomitant increase in the protein levels of TXNIP and NLRP3, and administration of SQ attenuated these effects. Additionally, ethanol increased the protein levels of pro‐inflammatory mediators, including tumor necrosis factor alpha and the NLRP3 downstream product, secretory interleukin 1 beta, and SQ blunted these effects. Finally, the Sirius red staining of the myocardium revealed an increase in collagen deposition in ethanol‐fed mice which was attenuated by TP‐R antagonism. Conclusion: This study demonstrates that ethanol promotes the NLRP3 signaling pathway within the myocardium, leading to a pro‐inflammatory milieu that potentially initiates early myocardial remodeling, and TP‐R antagonism attenuates this effect. [ABSTRACT FROM AUTHOR]

Background Systemic sclerosis presents with a variety of cardiac manifestations, while myocarditis is usually a rare finding. Furthermore, there are no reports on the use of mitral transcatheter edge-to-edge repair (M-TEER) for the treatment of severe ventricular functional mitral regurgitation (vFMR) secondary to scleroderma myocarditis. Case summary A-79-year-old male was admitted to our hospital because of fever and fatigue. His physical examination revealed thickening of the fingertips' skin, Raynaud phenomenon, and mild pedal oedema. Positive anti-centromere antibodies indicated a diagnosis of a limited cutaneous systemic sclerosis. He presented with symptoms of heart failure, and moderate to severe lymphocytic infiltration was evident in his endomyocardial biopsy. He responded well to medical therapy and was discharged. However, one month after hospital discharge, he was readmitted to our institution because of worsening heart failure. Transthoracic echocardiography showed a decrease in left ventricular systolic function and progression of left ventricular remodelling, which caused severe vFMR. Endomyocardial biopsy revealed decreased lymphocytic infiltration and mild myocardial interstitial fibrosis, indicative of scleroderma myocarditis. As he was unable to be weaned off inotropes, we performed M-TEER for severe vFMR, which led to a significant reduction in MR volume and improvement of heart failure symptoms. A week after procedure, immunosuppressive therapy was initiated and the patient was discharged home in stable condition. Discussion Scleroderma myocarditis may manifest as heart failure with reduced ejection fraction with severe vFMR. Mitral transcatheter edge-to-edge repair for severe vFMR in the context of myocarditis can be one of the therapeutic options for haemodynamic stabilization. [ABSTRACT FROM AUTHOR]

Ventricular pump function, which is determined by myocyte contractility, preload and afterload, and, additionally, also significantly influenced by heart rhythm, synchrony of intraventricular contraction and ventricular interdependence, explains the difficulties in establishing the contribution of myocardial contractile dysfunction to the development and progression of heart failure. Estimating myocardial contractility is one of the most difficult challenges because the most commonly used clinical measurements of cardiac performance cannot differentiate contractility changes from alterations in ventricular loading conditions. Under both physiological and pathological conditions, there is also a permanent complex interaction between myocardial contractility, ventricular anatomy and hemodynamic loading conditions. All this explains why no single parameter can alone reveal the real picture of ventricular dysfunction. Over time there has been increasing recognition that a load-independent contractility parameter cannot truly exist, because loading itself changes the myofilament force-generating capacity. Because the use of a single parameter is inadequate, it is necessary to perform multiparametric evaluations and also apply integrative approaches using parameter combinations which include details about ventricular loading conditions. This is particularly important for evaluating the highly afterload-sensitive right ventricular function. In this regard, the existence of certain reluctance particularly to the implementation of non-invasively obtainable parameter combinations in the routine clinical praxis should be reconsidered in the future. Among the non-invasive approaches used to evaluate ventricular function in connection with its current loading conditions, assessment of the relationship between ventricular contraction (e.g., myocardial displacement or deformation) and pressure overload, or the relationship between ejection volume (or ejection velocity) and pressure overload, as well as the relationship between ventricular dilation and pressure overload, were found useful for therapeutic decision-making. In the future, it will be unavoidable to take the load dependency of ventricular function much more into consideration. A solid basis for achieving this goal will be obtainable by intensifying the clinical research necessary to provide more evidence for the practical importance of this largely unsolved problem. [ABSTRACT FROM AUTHOR]

Background: The timing of treatment for chronic aortic valve regurgitation (AR), especially in asymptomatic patients, is gaining attention since less invasive strategies have become available. The aim of the present study was to evaluate left ventricular reverse remodeling after aortic valve replacement (AVR) for severe AR. Methods: Patients (n = 25) who underwent surgical AVR for severe AR with left ventricular ejection fraction (LVEF) less than 55% were included in this study. Preprocedural and follow-up clinical and echocardiographic measurements of LVEF and left ventricular (LV) diameters were retrospectively analyzed. Results: Mean LVEF increased significantly following surgical AVR (p < 0.0001). LV diameters showed a clear regression (p = 0.0088). Younger patients and those receiving a mechanical valve tended to have less improved LVEF on follow-up than patients over 60 years or the ones who were implanted with a biological prosthesis (p = 0.0239 and p = 0.069, respectively). Gender had no effect on the degree of LVEF improvement (p = 0.4908). Conclusions: We demonstrated significant LV reverse remodeling following AVR for AR. However, more data are needed on LV functional and geometrical improvement comparing the different types of valve prostheses to provide an optimal treatment strategy. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) is a progressive disease marked by pulmonary vascular remodeling and right ventricular failure. Inflammation and oxidative stress are critical in PH pathogenesis, with early pulmonary vascular inflammation preceding vascular remodeling. Extracellular superoxide dismutase (EC-SOD), a key vascular antioxidant enzyme, mitigates oxidative stress and protects against inflammation and fibrosis in diverse lung and vascular disease models. This study utilizes a murine hypobaric hypoxia model to investigate the role of lung EC-SOD on hypoxia-induced platelet activation and platelet lung accumulation, a critical factor in PH-related inflammation. We found that lung EC-SOD overexpression blocked hypoxia-induced platelet activation and platelet accumulation in the lung. Though lung EC-SOD overexpression increased lung EC-SOD content, it did not impact plasma extracellular SOD activity. However, ex vivo, exogenous extracellular SOD treatment specifically blunted convulxin-induced platelet activation but did not blunt platelet activation with thrombin or ADP. Our data identify platelets as a novel target of EC-SOD in response to hypoxia, providing a foundation to advance the understanding of dysregulated redox signaling and platelet activation in PH and other chronic hypoxic lung diseases. [ABSTRACT FROM AUTHOR]

Aims: Recent years, several studies have suggested that abnormal baseline left ventricular (LV) function and structure are associated with left ventricular thrombus (LVT) formation. Despite this, most studies have given less attention to the potential role of left ventricular reverse remodelling (LVRR), that is, the improvement of LV function and structure, in resolving LVT. In this study, we aim to investigate the clinical characteristics, prognosis, and LVT resolution in patients with LVRR. Methods and results: This is a retrospective study conducted at The First Affiliated Hospital of Dalian Medical University. Our cohort consists of patients diagnosed with LVT between 1 November 2015 and 31 May 2020. Enrolled patients were categorized into two groups: LVRR and Failure of LVRR. The primary endpoints included LVT resolution and embolic events. A total of 84 patients were included in the study, with 59 patients in the LVRR group and 25 patients in the Failure of LVRR group. In our study, patients in the LVRR group experienced higher incidence of LVT resolution and a lower risk of embolic events. Multivariate logistic analysis revealed that Failure of LVRR was the only independent negative predictor for LVT resolution and positive predictor for embolic events. Conclusions: Patients with LVRR experience higher incidence of LVT resolution and have lower risk of embolic events, highlighting the significance of identifying and mitigating risk factors that contribute to abnormal LV function and structure in management of patients with LVT. [ABSTRACT FROM AUTHOR]

Hypoglycemic medications are widely used in managing diabetes mellitus, with emerging evidence suggesting their role in cardiac reverse remodeling. This systematic review aims to quantitatively synthesize data regarding the impact of these medications on left ventricular end-diastolic diameter (LVEDD) and end-systolic diameter (LVESD), and to evaluate the clinical relevance of these changes in promoting favorable cardiac outcomes. We conducted a comprehensive search across PubMed, Scopus, and the Web of Science up to 22 April 2024, selecting studies based on inclusion criteria that focused on the impact of hypoglycemic medications on LVEDD and LVESD in patients with diabetes. Studies were selected through a rigorous process, adhering to PRISMA guidelines, and involving various designs including randomized controlled trials and observational studies. The main outcomes were changes in LVEDD and LVESD measured by validated cardiac imaging techniques. A total of ten studies met the inclusion criteria, involving a total of 1180 patients. Treatment durations ranged from 3 to 24 months. Significant improvements in cardiac dimensions were noted with some medications. For instance, Liraglutide treatment over three months significantly improved LVEF from 47.2% to 57.2% and reduced LVEDD and LVESD from 46.5 mm to 45.2 mm and 35.2 mm to 32.7 mm, respectively. In contrast, other medications like Sitagliptin showed minimal impact over 24 months. On average, hypoglycemic medications reduced LVEDD from 58.2 mm to 55.0 mm and LVESD from 48.3 mm to 44.3 mm, with a mean improvement in LVEF from 38.9% to 43.8%. Hypoglycemic medications contribute variably to cardiac reverse remodeling. Medications such as Liraglutide and Dapagliflozin demonstrate significant potential in improving cardiac dimensions and function, indicating their utility beyond glycemic control. This review highlights the need for tailored treatment approaches to maximize cardiac outcomes in patients with diabetes, suggesting a broader therapeutic role for these agents. [ABSTRACT FROM AUTHOR]

BACKGROUND: Pulmonary arterial hypertension (PAH) is high blood pressure in the lungs that originates from structural changes in small resistance arteries. A defining feature of PAH is the inappropriate remodeling of pulmonary arteries (PA) leading to right ventricle failure and death. Although treatment of PAH has improved, the long-term prognosis for patients remains poor, and more effective targets are needed. METHODS: Gene expression was analyzed by microarray, RNA sequencing, quantitative polymerase chain reaction, Western blotting, and immunostaining of lung and isolated PA in multiple mouse and rat models of pulmonary hypertension (PH) and human PAH. PH was assessed by digital ultrasound, hemodynamic measurements, and morphometry. RESULTS: Microarray analysis of the transcriptome of hypertensive rat PA identified a novel candidate, PBK (PDZ-binding kinase), that was upregulated in multiple models and species including humans. PBK is a serine/threonine kinase with important roles in cell proliferation that is minimally expressed in normal tissues but significantly increased in highly proliferative tissues. PBK was robustly upregulated in the medial layer of PA, where it overlaps with markers of smooth muscle cells. Gain-of-function approaches show that active forms of PBK increase PA smooth muscle cell proliferation, whereas silencing PBK, dominant negative PBK, and pharmacological inhibitors of PBK all reduce proliferation. Pharmacological inhibitors of PBK were effective in PH reversal strategies in both mouse and rat models, providing translational significance. In a complementary genetic approach, PBK was knocked out in rats using CRISPR/Cas9 editing, and loss of PBK prevented the development of PH. We found that PBK bound to PRC1 (protein regulator of cytokinesis 1) in PA smooth muscle cells and that multiple genes involved in cytokinesis were upregulated in experimental models of PH and human PAH. Active PBK increased PRC1 phosphorylation and supported cytokinesis in PA smooth muscle cells, whereas silencing or dominant negative PBK reduced cytokinesis and the number of cells in the G2/M phase of the cell cycle. CONCLUSIONS: PBK is a newly described target for PAH that is upregulated in proliferating PA smooth muscle cells, where it contributes to proliferation through changes in cytokinesis and cell cycle dynamics to promote medial thickening, fibrosis, increased PA resistance, elevated right ventricular systolic pressure, right ventricular remodeling, and PH. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusions Reverse ventricular remodelling, defined as a decrease in left ventricular end‐systolic volume indexed to body surface area (LVESVI) or an increase in left ventricular ejection fraction (LVEF), is associated with improved clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, the underlying pathophysiological mechanisms remain unclear.We evaluated paired core‐lab assessed echocardiograms and measurements of 92 biomarkers at baseline and 8 months thereafter in 419 participants with HFrEF. Reverse ventricular remodelling was defined as a >5% LVEF increase or >15% LVESVI relative decrease between baseline and 8 months. We evaluated the association between baseline biomarkers and their changes with reverse ventricular remodelling in the prospectively randomized controlled VICTORIA (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction) trial. Of 419 patients (median age 66 [interquartile range 57–74] years, 27.4% women), 206 (49.2%) had reverse ventricular remodelling (either a 5% LVEF increase or a 15% LVESVI decrease). There were no differences in baseline biomarker concentrations between patients with versus those without reverse ventricular remodelling on follow‐up. However, in patients with reverse ventricular remodelling there were significant decreases in biomarkers relating to inflammation and cardiac metabolism; particularly the tumour necrosis factor superfamily member 13B (ratio 0.82, 95% confidence interval [CI] 0.77–0.88), growth differentiation factor‐15 (ratio 0.74, 95% CI 0.66–0.84), and insulin‐like growth factor binding protein 7 (ratio 0.80, 95% CI 0.73–0.88).Reverse ventricular remodelling in patients with HFrEF is associated with a decrease of biomarkers related to inflammation and cardiac metabolism. [ABSTRACT FROM AUTHOR]

Background: Heart failure with reduced ejection fraction (HFrEF) is associated with a high rate of mortality and morbidity. Evidence has shown that sex differences may be an important contributor to phenotypic heterogeneity in patients with HFrEF. Although diabetes mellitus (DM) frequently coexists with HFrEF and results in a worse prognosis, there remains a need to identify sex-related differences in the characteristics and outcomes of this population. In this study, we aimed to investigate the between-sex differences in clinical profile, left ventricular (LV) remodeling, and cardiovascular risk factors and outcomes in patients with HFrEF concomitant with DM. Methods: A total of 273 patients with HFrEF concomitant with DM who underwent cardiac MRI were included in this study. Clinical characteristics, LV remodeling as assessed by cardiac MRI, and cardiovascular risk factors and outcomes were compared between sexes. Results: Women were older, leaner and prone to have anemia and hypoproteinemia but less likely to have ischemic etiology. Cardiac MRI revealed that despite similar LVEFs between the sexes, there was more LV concentric remodeling, less impaired global systolic peak strain in longitudinal and circumferential components and a decreased likelihood of late gadolinium enhancement presence in women than in men. During a median follow-up time of 34.6 months, women exhibited better overall survival than men did (log-rank P = 0.042). Multivariable Cox proportional hazards analysis indicated different risk factors for predicting outcomes between sexes, with hypertension [hazard ratio (HR) = 2.05, 95% confidence interval (CI) 1.05 to 4.85, P = 0.041] and hypoproteinemia (HR = 2.27, 95% CI 1.06 to 4.37, P = 0.039) serving as independent determinants of outcomes in women, whereas ischemic etiology (HR = 1.96, 95% CI 1.11 to 3.48, P = 0.021) and atrial fibrillation (HR = 1.86, 95% CI 1.02 to 3.41, P = 0.044) served as independent determinants of outcomes in men. Conclusions: Among patients with HFrEF concomitant with DM, women displayed different LV remodeling and risk factors and had better survival than men did. Sex-based phenotypic heterogeneity in patients with HFrEF in the context of DM should be addressed in clinical practice. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusions The primary aim was to evaluate the effect of dapagliflozin according to QRS duration across the spectrum of left ventricular ejection fraction (LVEF), given that prolongation of QRS duration is associated with less favourable ventricular remodelling with pharmacological therapy and worse outcomes.A pooled analysis of the DAPA‐HF and DELIVER trials, excluding patients with a paced rhythm and cardiac resynchronization therapy. Overall, 4008 patients had heart failure (HF) with reduced ejection fraction (HFrEF), and 5816 had HF with mildly reduced/preserved ejection fraction (HFmrEF/HFpEF). QRS duration was <120 ms in 7039 patients (71.7%), 120–149 ms in 1725 (17.6%), and ≥150 ms in 1060 patients (10.8%). The median follow‐up time was 23 months. The rate of the primary composite outcome of cardiovascular death or worsening HF was 9.2 (95% confidence interval [CI] 8.7–9.7), 14.3 (13.0–15.7), and 15.9 (14.1–17.9) per 100 patient‐years in the <120, 120–149, and ≥150 ms groups, respectively. This gradient in event rates was observed both in HFrEF and HFmrEF/HFpEF. Dapagliflozin, compared with placebo, reduced the risk of the primary outcome consistently across the QRS duration subgroups (hazard ratio [95% CI] 0.75 [0.67–0.85], 0.79 [0.65–0.96], and 0.89 [0.70–1.13] in the <120, 120–149, and ≥150 ms groups, respectively; p for interaction = 0.28). The effect of dapagliflozin on the primary outcome was consistent across the QRS duration regardless of HF phenotype that is, HFrEF or HFmrEF/HFpEF.Prolongation of QRS duration is associated with worse outcomes irrespective of HF phenotype. Dapagliflozin reduced the risk of the primary outcome, regardless of QRS duration, in DAPA‐HF and DELIVER. [ABSTRACT FROM AUTHOR]

Heart failure (HF) remains prevalent in patients who survived myocardial infarction (MI). Despite the accessibility of the primary percutaneous coronary intervention and medications that alleviate ventricular remodeling with functional improvement, there is an urgent need for clinicians and basic scientists to further reveal the mechanisms behind post‐MI HF as well as investigate earlier and more efficient treatment after MI. Growing numbers of studies have highlighted the crucial role of macrophages in cardiac repair and remodeling following MI, and timely intervention targeting the immune response via macrophages may represent a promising therapeutic avenue. Recently, technology such as single‐cell sequencing has provided us with an updated and in‐depth understanding of the role of macrophages in MI. Meanwhile, the development of biomaterials has made it possible for macrophage‐targeted therapy. Thus, an overall and thorough understanding of the role of macrophages in post‐MI HF and the current development status of macrophage‐based therapy will assist in the further study and development of macrophage‐targeted treatment for post‐infarction cardiac remodeling. This review synthesizes the spatiotemporal dynamics, function, mechanism and signaling of macrophages in the process of HF after MI, as well as discusses the emerging bio‐materials and possible therapeutic agents targeting macrophages for post‐MI HF. [ABSTRACT FROM AUTHOR]

The IKZF1 gene encodes a transcription factor that belongs to the family of zincfinger DNA-binding proteins associated with chromatin remodeling. The protein product, IKAROS, had been proved to regulate lymphopoiesis. Subsequent mouse model studies have further confirmed its regulating role in lymphopoiesis as well as in hematopoiesis; besides, it associates with immune function, certain immune disorders like common variable immunodeficiency and dysgammaglobulinemia have been proved to be associated with germline IKZF1 mutations. Dysfunction of IKAROS also bears paramount significance in leukemic transformation and alterations of IKZF1 gene predicts a poor prognosis in hematological malignancies. As an independent prognostic marker, IKZF1 has been incorporated in the risk stratification of BCP-ALL and stratification-guided therapy has also been generated. In this review, we provide a concise and comprehensive overview on the multifaceted roles of IKZF1 gene. [ABSTRACT FROM AUTHOR]

Current understanding of iron-deficient heart failure is based on blood tests that are thought to reflect systemic iron stores, but the available evidence suggests greater complexity. The entry and egress of circulating iron is controlled by erythroblasts, which (in severe iron deficiency) will sacrifice erythropoiesis to supply iron to other organs, e.g. the heart. Marked hypoferraemia (typically with anaemia) can drive the depletion of cardiomyocyte iron, impairing contractile performance and explaining why a transferrin saturation < ≈15%–16% predicts the ability of intravenous iron to reduce the risk of major heart failure events in long-term trials (Type 1 iron-deficient heart failure). However, heart failure may be accompanied by intracellular iron depletion within skeletal muscle and cardiomyocytes, which is disproportionate to the findings of systemic iron biomarkers. Inflammation- and deconditioning-mediated skeletal muscle dysfunction—a primary cause of dyspnoea and exercise intolerance in patients with heart failure—is accompanied by intracellular skeletal myocyte iron depletion, which can be exacerbated by even mild hypoferraemia, explaining why symptoms and functional capacity improve following intravenous iron, regardless of baseline haemoglobin or changes in haemoglobin (Type 2 iron-deficient heart failure). Additionally, patients with advanced heart failure show myocardial iron depletion due to both diminished entry into and enhanced egress of iron from the myocardium; the changes in iron proteins in the cardiomyocytes of these patients are opposite to those expected from systemic iron deficiency. Nevertheless, iron supplementation can prevent ventricular remodelling and cardiomyopathy produced by experimental injury in the absence of systemic iron deficiency (Type 3 iron-deficient heart failure). These observations, taken collectively, support the possibility of three different mechanistic pathways for the development of iron-deficient heart failure: one that is driven through systemic iron depletion and impaired erythropoiesis and two that are characterized by disproportionate depletion of intracellular iron in skeletal and cardiac muscle. These mechanisms are not mutually exclusive, and all pathways may be operative at the same time or may occur sequentially in the same patients. [ABSTRACT FROM AUTHOR]

Introduction: We sought to examine midterm results and remodeling effect of false-lumen occlusion treatment using AFX VELA in case of chronic dissection repair. Material and Methods: From June 2019 to May 2022, we performed false lumen occlusion treatment using a modified Candy-Plug technique with AFX VELA on 8 chronic aortic dissection patients with a patent false lumen. We collected operative data, short-term clinical outcomes, mid-term clinical outcomes and imaging test results. We conducted follow-up examinations at postoperative, 6-month and 1-, 2- and 3-year intervals, including contrast-enhanced computed tomography to evaluate the diameter, false lumen thrombosis and any events. Results: The average time from the symptom onset to the thoracic endovascular repair was 81.5 (35-155) months. The aorta showed aneurysmal dilation with an average maximum short-axis diameter of 58.9 (41-91) mm. Two cases needed emergency surgery due to rupture and impending rupture. There were no postoperative deaths. Complete thrombosis within the false lumen was achieved in 6 cases (75%), but 2 cases had incomplete thrombosis, requiring additional treatment. The mean maximum diameter showed a significant decrease at 6 months, 1 year and 2 years postoperatively compared to preoperative measurements (P <.05). Conclusion: We showed the results of false lumen occlusion treatment using the AFX VELA cuff. We observed favorable clinical outcomes and remodeling effects. While the long-term durability and efficacy of this technique in aortic remodeling will need to be monitored with further observation, the use of this cuff is considered a reliable approach to false lumen occlusion treatment. [ABSTRACT FROM AUTHOR]

Background: Obesity is a significant risk factor for heart failure with preserved ejection fraction (HFpEF). In this study, we explore the relationships between body mass index (BMI) and adipose tissue compartments such as visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and epicardial adipose tissue (EAT), with respect to left ventricular (LV) structure and function in subjects with preserved LV systolic function. Methods: Between January and December 2020, this retrospective study included 749 participants who exhibited preserved LV systolic function and underwent transthoracic echocardiography along with abdominal computed tomography. LV structural and functional variables as well as EAT, VAT, and SAT thickness were evaluated using echocardiography and computed tomography. Results: SAT decreased, while VAT and EAT progressively increased with age. There were significant correlations between BMI and various adipose tissues, with the strongest correlation observed with SAT (r =.491, p <.001) compared to VAT (r =.371, p <.001) or EAT (r =.135, p <.001). However, EAT demonstrated the most substantial association with decreased LV end‐diastolic dimension, LV end‐systolic dimension, and septal mitral annular velocity and increased relative wall thickness (all p <.05), while VAT and SAT did not show significant associations with LV remodeling and functional parameters after adjusting for clinical variables. Conclusion: EAT is the most critical adipose tissue influencing LV geometric and functional changes, compared with VAT or SAT. Thick EAT is associated small LV chamber size, concentric remodeling, and relaxation abnormalities. [ABSTRACT FROM AUTHOR]

Background: Moderate/severe aortic regurgitation (AR) with concomitant mitral regurgitation (MR) is a common multiple valve disease for which treatment strategies are controversial. The current study explored long-term outcomes of concomitant MR after AR surgery and the effect of combined mitral valvuloplasty. Methods: A total of 506 patients with moderate/severe AR and concomitant MR undergoing aortic valve surgery between January 2013 and December 2021 in our cardiac center were enrolled. Risk factors for early mortality, late mortality and persistent MR were identified by logistic regression and generalized linear mixed model. Results: At least one follow-up record was available for 96.3% patients up to May 2022 and 264 (66.8%) patients had no or trivial MR, 112 (28.4%) had mild MR, 16 (4.1%) had moderate MR and 3 (0.8%) patients had severe MR. Persistent MR was recorded for 92 (23.3%) patients during follow-up. Combined mitral valvuloplasty (odds ratio: 0.23; 95% confidential interval: 0.08–0.64; p = 0.005) and better left ventricular reverse remodeling (odds ratio: 0.99; 95% confidential interval: 0.986–0.996); p < 0.001) were found likely to reduce the possibility of persistent MR during follow-up. Conclusions: Most patients with moderate/severe AR and concomitant MR had a good long-term post-surgical outcome for MR. However, a few had persistent MR during follow-up. Combined mitral valvuloplasty and better left ventricular reverse remodeling reduced the possibility of long-term persistent MR. [ABSTRACT FROM AUTHOR]

Background: Cardiac magnetic resonance (cMRI) is often used to diagnose acute myocarditis (AM). It is also performed after 6 months to monitor myocardial involvement. However, the clinical and predictive relevance of the 6-month cMRI is uncertain. Objective: We used cMRI to assess the morphology and heart function of patients with AM, the correlation between left ventricular remodeling and biomarkers of heart dysfunction and myocardial fibrosis, and the involvement of myocardial fibrosis initially and 6 months after the acute episode. Materials and methods: We conducted a prospective study of 90 patients with the clinical suspicion of AM, where cMRI was performed within the first week after symptom onset and repeated after 6 months. Results: Non-ischemic late gadolinium enhancement (LGE) was present in 88 (97.7%) patients and mainly involved the septum and inferior wall. cMRI at 6 months was associated with significantly reduced abnormalities of segmental kinetics (p < 0.001), myocardial edema (p < 0.001), presence of LGE (p < 0.05) and LGE mass (p < 0.01), native T1 mapping (p < 0.001), and presence of pericardial collection (p ≤ 0.001). At 6 months, signs of myocardial edema appeared in 34.4% of patients, and a complete cure (absence of edema and LGE) was found in 8.8% of patients. LGE disappeared in 15.2% of patients, and the mean number of myocardial segments involved decreased from 46% to 30%, remaining unchanged in 13% of patients. Patients with LGE without edema had a more severe prognostic condition than those with persistent edema. Patients with increased LGE extension on the control cMRI had a worse prognosis than those with modified or low LGE. The most significant independent predictive parameters for major cardiovascular events (MACEs) were LGE mass (adjusted OR = 1.27 [1.11–1.99], p < 0.001), myocardial edema (OR = 1.70 [1.14–209.3], p < 0.001), and prolonged native T1 (OR = 0.97 [0.88–3.06], p < 0.001). The mid-wall model of LGE and the presence of edema-free LGE were MACE-independent predictors. Conclusions: LGE, myocardial edema, and prolonged native T1 were predictors of MACEs. LGE does not necessarily mean constituted fibrosis in the presence of edema and may disappear over time. LGE without edema could represent fibrosis, whereas the persistence of edema represents active inflammation and could be associated with the residual chance of complete recovery. cMRI should be performed in all patients with AM at 6 months to evaluate progress and prognosis. [ABSTRACT FROM AUTHOR]