Arrhythmogenic Manifestations of Chagas Disease: Perspectives From the Bench to Bedside.

Chagas cardiomyopathy caused by infection with the intracellular parasite Trypanosoma cruzi is the most common and severe expression of human Chagas disease. Heart failure, systemic and pulmonary thromboembolism, arrhythmia, and sudden cardiac death are the principal clinical manifestations of Chagas cardiomyopathy. Ventricular arrhythmias contribute significantly to morbidity and mortality and are the major cause of sudden cardiac death. Significant gaps still exist in the understanding of the pathogenesis mechanisms underlying the arrhythmogenic manifestations of Chagas cardiomyopathy. This article will review the data from experimental studies and translate those findings to draw hypotheses about clinical observations. Human- and animal-based studies at molecular, cellular, tissue, and organ levels suggest 5 main pillars of remodeling caused by the interaction of host and parasite: immunologic, electrical, autonomic, microvascular, and contractile. Integrating these 5 remodeling processes will bring insights into the current knowledge in the field, highlighting some key features for future management of this arrhythmogenic disease.

Increased Expression of Inactive Rhomboid Protein 2 in Circulating Monocytes after Acute Myocardial Infarction.

Increased TNF-α levels following acute myocardial infarction (AMI) contribute to impaired recovery of myocardial function. Interaction of inactive rhomboid protein 2 (iRhom2) with TNF-α converting enzyme (TACE) is required for TNF-α shedding from immune cells. We hypothesized that iRhom2 expression increases in circulating monocytes following AMI. Transcript levels of iRhom2, TACE and TNF-α were evaluated by quantitative real-time PCR in isolated monocytes of 50 AMI patients at admission (d1) and 3 days (d3) after. We observed a significant increase in levels of iRhom2 mRNA expression in monocytes between d1-3, while TNF-α and TACE mRNA expression remained unchanged. At d3, iRhom2 mRNA expression positively correlated with levels of intermediate monocytes or serum TNF-α, and negatively with LV systolic function. iRhom2 may contribute to regulation of post-infarction inflammation and is associated with LV dysfunction following AMI. iRhom2 modulation should be evaluated as a potential therapeutic strategy to attenuate cardiac remodeling following AMI.

Normative Values of Echocardiographic Chamber Size and Function in Older Healthy Adults: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Echocardiographic (2-dimensional echocardiography) thresholds indicating disease or impaired functional status compared with normal physiological aging in individuals aged ≥65 years are not clearly defined. In the present study, we sought to establish standard values for 2-dimensional echocardiography parameters related to chamber size and function in older adults without cardiopulmonary or cardiometabolic conditions. METHODS: In this cross-sectional study of 3032 individuals who underwent 2-dimensional echocardiography at exam 6 in the MESA (Multi-Ethnic Study of Atherosclerosis), 608 participants fulfilled our inclusion criteria of healthy aging, with normative values defined as the mean ± 1.96 standard deviation and compared across sex and race and ethnicity. Functional status measures included NT-proBNP (N-terminal pro-B-type natriuretic peptide), 6-minute walk distance, and Kansas City Cardiomyopathy Questionnaire. Prognostic performance using MESA cutoffs was compared with established guideline cutoffs using time-to-event analysis. RESULTS: The normative aging cohort (69.5±7.0 years, 46.2% male, 47.5% White) had lower NT-proBNP, higher 6-minute walk distance, and higher (better) Kansas City Cardiomyopathy Questionnaire summary values. Women had significantly smaller chamber sizes and better biventricular systolic function. White participants had the largest chamber dimensions, whereas Chinese participants had the smallest, even after adjustment for body size. Current guidelines identified 81.6% of healthy older adults in MESA as having cardiac abnormalities. CONCLUSIONS: Among a large, diverse group of healthy older adults, we found significant differences in cardiac structure and function by sex and race/ethnicity, which may signal sex-specific cardiac remodeling with advancing age. It is crucial for existing guidelines to consider the observed and clinically significant differences in cardiac structure and function associated with healthy aging. Our study highlights that existing guidelines, which grade abnormalities in echocardiographic cardiac chamber size and function based on younger individuals, may not adequately address the anticipated changes associated with normal aging.

Association of Hypertensive Disorders of Pregnancy With Coronary Microvascular Dysfunction 8 to 10 Years After Delivery.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with subsequent adverse cardiac remodeling and cardiovascular disease. The role of myocardial microvascular disease among individuals with HDP and left ventricular (LV) remodeling as a potential link to cardiovascular disease is unknown. We aimed to determine whether individuals with HDP history have coronary microvascular dysfunction measured by coronary flow reserve 8 to 10 years after delivery and whether microvascular dysfunction correlates with LV remodeling. METHODS: Individuals with pregnancies delivered from 2008 to 2010 underwent burst-replenishment myocardial contrast echocardiography (2017-2020) to quantify myocardial perfusion at rest and during dobutamine stress. Video intensity versus time data were used to derive ß, the rate of rise of video intensity, a correlate for myocardial blood flow. Coronary flow reserve was calculated as the ratio of ß at peak stress to ß at rest, averaged across LV myocardial regions of interest. RESULTS: We studied 91 individuals (aged 38±6 and 9.1±0.9 years postdelivery) and 19 with a history of HDP. Individuals with coronary microvascular dysfunction (coronary flow reserve <2.0; n=13) had a higher proportion of HDP (46.2% versus 16.7%; P=0.026) and higher prepregnancy body mass index, baseline heart rate, and hemoglobin A1c compared with those without microvascular dysfunction. The association of coronary flow reserve and HDP was attenuated after adjusting for cardiometabolic factors (P=0.133). In exploratory subgroup analyses, individuals with both LV remodeling (relative wall thickness >0.42) and HDP (n=12) had the highest proportion of microvascular dysfunction (41.7% versus +HDP-LV remodeling [n=7] 14.3%; -HDP+LV remodeling [n=26] 7.7%; P=0.0498). CONCLUSIONS: In this small study, HDP history is associated with coronary microvascular dysfunction 1 decade after delivery, findings that may, in part, be driven by metabolic factors including obesity and diabetes. Microvascular dysfunction may contribute to cardiovascular disease among individuals with a history of HDP.

Mild renal dysfunction causes aggravated cardiac damage in type 2 diabetic patients: a comprehensive echocardiography study.

PURPOSE: We sought to detect left ventricular (LV) adverse alterations in structure and function in type 2 diabetes mellitus (T2DM) patients with or without mild renal dysfunction (MRD) using comprehensive echocardiography techniques and to explore the independent risk factors for LV remodeling (LVR) and dysfunction in these patients. METHODS: The study included 82 T2DM patients with normal LV ejection fraction (presence (n = 42)/absence (n = 40) of MRD). Age- and gender-matched controls (n = 40) were also recruited. LV structure and function were evaluated using conventional echocardiography and three-dimensional speckle tracking echocardiography (3DSTE). Global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS) were all measured using 3DSTE. RESULTS: Compared with the controls with absolute advantage of LV normal geometry, LVR was more frequently present in the two T2DM groups, with the largest proportion in those with T2DM and MRD (P < 0.001). Fasting plasma glucose (FPG) and MRD were both significant risk factors for LVR in T2DM patients. The detection rates of LV diastolic dysfunction and subclinical systolic dysfunction were significantly higher in the T2DM groups than in the controls (P = 0.000). Moreover, the two case groups also showed significantly lower strain values in multiple directions than the controls (all P < 0.05). FPG was significantly associated with LV diastolic dysfunction, whereas FPG and MRD were both significantly associated with subclinical LV systolic dysfunction in T2DM patients. CONCLUSIONS: The combined use of conventional echocardiography and 3DSTE allowed the timely detection of early cardiac damage in T2DM patients with or without MRD.

HLA-B and TIMP1 as hub genes of the ventricular remodeling caused by hypertension.

RATIONALE: Myocardial fibrosis is an important pathological change that occurs during ventricular remodeling in patients with hypertension and is an important pathophysiological basis of cardiovascular disease. However, the molecular mechanism underlying this ventricular remodeling is unclear. METHODS: Bioinformatics analysis identified HLA-B and TIMP1 as hub genes in the process of myocardial fibrosis. Expression and correlation analyses of significant hub genes with ventricular remodeling were performed. Weighted gene co-expression network analysis (WGCNA) was performed to verify the role of HLA-B. ceRNA network was constructed to identify the candidate molecule drugs. Receiver operating characteristic (ROC) curves were analyzed. RESULTS: RT-qPCR was performed to verify the roles of HLA-B and TIMP1 in seven control individuals with hypertension and seven patients with hypertension and ventricular remodeling. The WGCNA showed that HLA-B was in the brown module and the correlation coefficient between HLA-B and ventricular remodeling was 0.67. Based on univariate logistic proportional regression analysis, HLA-B influences ventricular remodeling (P<0.05). RT-qPCR showed that the relative expression levels of HLA-B and TIMP1 were significantly higher in HLVR samples compared with their expression in the control group. CONCLUSIONS: HLA-B and TIMP1 might provide novel research targets for the diagnosis and treatment of HLVR.

Kidney-tonifying blood-activating decoction delays ventricular remodeling in rats with chronic heart failure by regulating gut microbiota and metabolites and p38 mitogen-activated protein kinase/p65 nuclear factor kappa-B/aquaporin-4 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Myocardial infarction has likely contributed to the increased prevalence of heart failure(HF).As a result of ventricular remodeling and reduced cardiac function, colonic blood flow decreases, causing mucosal ischemia and hypoxia of the villous structure of the intestinal wall.This damage in gut barrier function increases bowel wall permeability, leading to fluid metabolism disorder,gut microbial dysbiosis, increased gut bacteria translocation into the circulatory system and increased circulating endotoxins, thus promoting a typical inflammatory state.Traditional Chinese Medicine plays a key role in the prevention and treatment of HF.Kidney-tonifying Blood-activating(KTBA) decoction has been proved for clinical treatment of chronic HF.However,the mechanism of KTBA decoction on chronic HF is still unclear. AIMS OF THE STUDY: The effect of KTBA decoction on gut microbiota and metabolites and p38MAPK/p65NF-κB/AQP4 signaling in rat colon was studied to investigate the mechanism that KTBA decoction delays ventricular remodeling and regulates water metabolism disorder in rats with HF after myocardial infarction based on the theory of "Kidney Storing Essence and Conducting Water". MATERIAL AND METHODS: In vivo,a rat model of HF after myocardial infarction was prepared by ligating the left anterior descending coronary artery combined with exhaustive swimming and starvation.The successful modeling rats were randomly divided into five groups:model group, tolvaptan group(gavaged 1.35mg/(kg•D) tolvaptan),KTBA decoction group(gavaged 15.75g/(kg•D) of KTBA decoction),KTBA decoction combined with SB203580(p38MAPK inhibitor) group(gavaged 15.75g/(kg•D) of KTBA decoction and intraperitoneally injected 1.5mg/(kg•D) of SB203580),and KTBA decoction combined with PDTC(p65NF-kB inhibitor) group(gavaged 15.75g/(kg•D) of KTBA decoction and intraperitoneally injected 120mg/(kg•D) of PDTC).The sham-operation group and model group were gavaged equal volume of normal saline.After 4 weeks of intervention with KTBA decoction,the effect of KTBA decoction on the cardiac structure and function of chronic HF model rats was observed by ultrasonic cardiogram.General state and cardiac index in rats were evaluated.Enzyme linked immunosorbent assay(ELISA) was used to measure N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration in rat serum.Hematoxylin and eosin(H&E) staining,and transmission electron microscope(TEM) were used to observe the morphology and ultrastructure of myocardial and colonic tissue,and myocardial fibrosis was measured by Masson's staining.Cardiac E-cadherin level was detected by Western blot.The mRNA expression and protein expression levels of p38MAPK,I-κBα, p65NF-κB,AQP4,Occludin and ZO-1 in colonic tissue were detected by reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR) and immunohistochemistry. Protein expression of p38MAPK, p-p38MAPK,I-κBα,p-I-κBα,p65NF-κB, p-p65NF-κB,AQP4,Occludin and ZO-1 in rat colon was detected using Western blot.Colonic microbiota and serum metabolites were respectively analyzed by amplicon sequencing and liquid chromatography-mass spectrometry.In vitro, CCD-841CoN cell was placed in the ischemic solution under hypoxic conditions (94%N2,5%CO2,and 1%O2) in a 37 °C incubator to establish an ischemia and hypoxia model.The CCD-841CoN cells were divided into 7 groups, namely blank group and model group with normal rat serum plus control siRNA, tolvaptan group with rat serum containing tolvaptan plus control siRNA, KTBA group with rat serum containing KTBA plus control siRNA, KTBA plus p38MAPK siRNA group, KTBA plus p65NF-κB siRNA group,and KTBA plus AQP4siRNA group.After 24h and 48h of intervention with KTBA decoction,RT-qPCR,immunofluorescence and Western blot was used to detect the mRNA expression and protein expression levels of p38MAPK,I-κBα,p65NF-κB,AQP4, Occludin and ZO-1 in CCD-841CoN cells. RESULTS: Compared with the model, KTBA decoction improved the general state, decraesed the serum NT-proBNP level,HW/BW ratio, LVIDd and LVIDs, increased E-cadherin level,EF and FS,reduced number of collagen fibers deposited in the myocardial interstitium,and recovered irregular arrangement of myofibril and swollen or vacuolated mitochondria with broken crista in myocardium.Moreover, KTBA decoction inhibited the expression of p38MAPK,I-κBα,and p65NF-κB and upregulated AQP4, Occludin and ZO-1 in colon tissues and CCD-841CoN cells.Additionally,p38siRNA or SB203580, p65siRNA or PDTC, and AQP4siRNA partially weakened the protective effects of KTBA in vitro and vivo.Notably,The LEfSe analysis results showed that there were six gut biomaker bacteria in model group, including Allobaculum, Bacillales,Turicibacter, Turicibacterales,Turicibacteraceae,and Bacilli. Besides, three gut biomaker bacteria containing Deltaproteobacteria, Desulfovibrionaceae,and Desulfovibrionales were enriched by KTBA treatment in chronic HF model.There were five differential metabolites, including L-Leucine,Pelargonic acid, Capsidiol,beta-Carotene,and L- Erythrulose, which can be regulated back in the same changed metabolic routes by the intervention of KTBA.L-Leucine had the positive correlation with Bacillales, Turicibacterales,Turicibacteraceae,and Turicibacter.L-Leucine significantly impacts Protein digestion and absorption, Mineral absorption,and Central carbon metabolism in cancer regulated by KTBA, which is involved in the expression of MAPK and tight junction in intestinal epithelial cells. CONCLUSIONS: KTBA decoction manipulates the expression of several key proteins in the p38MAPK/p65NF-κB/AQP4 signaling pathway, modulates gut microbiota and metabolites toward a more favorable profile, improves gut barrier function, delays cardiomyocyte hypertrophy and fibrosis,and improves cardiac function.

Prognostic value of triglyceride-glucose index for left ventricular remodeling in nondiabetic ST-elevation myocardial infarction patients.

Background: The triglyceride-glucose (TyG) index is a marker of insulin resistance and is associated with cardiovascular mortality and morbidity. Left ventricular remodeling (LVR) after myocardial infarction (STEMI) is associated with poor prognosis. Methods: This retrospective study included 293 STEMI patients. Echocardiography was performed before discharge and 3 months after MI. Results: Compared with the non-LVR group, TyG index value was found to be higher in the LVR group (p < 0.001). Logistic regression analysis showed that higher maximal troponin I value, higher calculated TyG index value, higher N-terminal prohormone of brain natriuretic peptide level and the presence of anterior MI were independently associated with the development of LVR. Conclusion: A high TyG index level may contribute to the prediction of LVR in nondiabetic STEMI patients undergoing successful primary percutaneous coronary intervention.

[Predictive value of cardiac magnetic resonance imaging for adverse left ventricular remodeling after acute ST-segment elevation myocardial infarction].

OBJECTIVE: To assess the value of cardiac magnetic resonance (CMR) imaging for predicting adverse left ventricular remodeling in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: We retrospectively analyzed the clinical data and serial CMR (cine and LGE sequences) images of 86 STEMI patients within 1 week and 5 months after percutaneous coronary intervention (PCI), including 25 patients with adverse LV remodeling and 61 without adverse LV remodeling, defined as an increase of left ventricular end-systolic volume (LVESV) over 15% at the second CMR compared to the initial CMR. The CMR images were analyzed for LV volume, infarct characteristics, and global and infarct zone myocardial function. The independent predictors of adverse LV remodeling following STEMI were analyzed using univariate and multivariate Logistic regression methods. RESULTS: The initial CMR showed no significant differences in LV volume or LV ejection fraction (LVEF) between the two groups, but the infarct mass and microvascular obstructive (MVO) mass were significantly greater in adverse LV remodeling group (P < 0.05). Myocardial injury and cardiac function of the patients recovered over time in both groups. At the second CMR, the patients with adverse LV remodeling showed a significantly lower LVEF, a larger left ventricular end-systolic volume index (LVESVI) and a greater extent of infarct mass (P < 0.001) with lower global peak strains and strain rates in the radial, circumferential, and longitudinal directions (P < 0.05), infarct zone peak strains in the 3 directions, and infarct zone peak radial and circumferential strain rates (P < 0.05). The independent predictors for adverse LV remodeling following STEMI included the extent of infarct mass (AUC=0.793, 95% CI: 0.693-0.873; cut-off value: 30.67%), radial diastolic peak strain rate (AUC=0.645, 95% CI: 0.534-0.745; cut-off value: 0.58%), and RAAS inhibitor (AUC= 0.699, 95% CI: 0.590-0.793). CONCLUSION: The extent of infarct mass, peak radial diastolic strain rate, and RAAS inhibitor are independent predictors of adverse LV remodeling following STEMI.

Myocardial Matrix Hydrogels Mitigate Negative Remodeling and Improve Function in Right Heart Failure Model.

This study evaluates the effectiveness of myocardial matrix (MM) hydrogels in mitigating negative right ventricular (RV) remodeling in a rat model of RV heart failure. The goal was to assess whether a hydrogel derived from either the right or left ventricle could promote cardiac repair. Injured rat right ventricles were injected with either RV-or left ventricular-derived MM hydrogels. Both hydrogels improved RV function and morphology and reduced negative remodeling. This study supports the potential of injectable biomaterial therapies for treating RV heart failure.

Left ventricular concentric remodeling in COPD patients: A cross-sectional observational study.

OBJECTIVE: To investigate the association between left ventricular structure and disease severity in COPD patients. METHODS: Twenty-eight COPD patients were stratified according to the disease severity, using the BODE index, into Lower (n=17) and Higher (n=11) groups, composed of patients with lower severity (BODE <5) and higher severity (BODE ≥5), respectively. Left ventricle (LV) was assessed by 2D-echocardiography. BODE index was calculated using body mass index (BMI); forced expiratory volume in the first second (FEV1, %); modified Medical Research Council (mMRC) and distance walked during 6-minute walk test (6MWD). RESULTS: Patients in the Higher group showed lower oxygen arterial saturation (p=0.02), FEV1 (p<0.01) and 6MWD (p=0.02) and higher value of relative posterior wall thickness (RWT) compared to Lower group (p=0.02). There were significant associations between LV end-systolic diameter (LVESD) and BODE index (r=-0.38, p=0.04), LV end-diastolic diameter (LVEDD) and FEV1 (r=0.44, p=0.02), LVEDD and BMI (r=0.45, p=0.02), LVESD and BMI (r=0.54, p=0.003) and interventricular septal thickness and 6MWD (r=-0.39, p=0.04). CONCLUSIONS: More severe COPD patients, BODE score ≥5, may have higher RWT, featuring a possible higher concentric remodeling of LV in this group. Besides that, a greater disease severity may be related to LV chamber size reduction.

Effects of right ventricular remodeling in chronic thromboembolic pulmonary hypertension on the outcomes of balloon pulmonary angioplasty: a 2D-speckle tracking echocardiography study.

BACKGROUND: Balloon pulmonary angioplasty (BPA) improves the prognosis of chronic thromboembolic pulmonary hypertension (CTEPH). Right ventricle (RV) is an important predictor of prognosis in CTEPH patients. 2D-speckle tracking echocardiography (2D-STE) can evaluate RV function. This study aimed to evaluate the effectiveness of BPA in CTEPH patients and to assess the value of 2D-STE in predicting outcomes of BPA. METHODS: A total of 76 patients with CTEPH underwent 354 BPA sessions from January 2017 to October 2022. Responders were defined as those with mean pulmonary artery pressure (mPAP) ≤ 30 mmHg or those showing ≥ 30% decrease in pulmonary vascular resistance (PVR) after the last BPA session, compared to baseline. Logistic regression analysis was performed to identify predictors of BPA efficacy. RESULTS: BPA resulted in a significant decrease in mPAP (from 50.8 ± 10.4 mmHg to 35.5 ± 11.9 mmHg, p < 0.001), PVR (from 888.7 ± 363.5 dyn·s·cm-5 to 545.5 ± 383.8 dyn·s·cm-5, p < 0.001), and eccentricity index (from 1.3 to 1.1, p < 0.001), and a significant increase in RV free wall longitudinal strain (RVFWLS: from 15.7% to 21.0%, p < 0.001). Significant improvement was also observed in the 6-min walking distance (from 385.5 m to 454.5 m, p < 0.001). After adjusting for confounders, multivariate analysis showed that RVFWLS was the only independent predictor of BPA efficacy. The optimal RVFWLS cutoff value for predicting BPA responders was 12%. CONCLUSIONS: BPA was found to reduce pulmonary artery pressure, reverse RV remodeling, and improve exercise capacity. RVFWLS obtained by 2D-STE was an independent predictor of BPA outcomes. Our study may provide a meaningful reference for interventional therapy of CTEPH.

Efficacy of early administration of sacubitril/valsartan after coronary artery revascularization in patients with acute myocardial infarction complicated by moderate-to-severe mitral regurgitation: a randomized controlled trial.

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.

Xinmailong injection on left ventricular remodeling and inflammatory mediators in patients with CHF: a systematic review and meta-analysis.

Background: Chronic heart failure (CHF) is a prevalent and highly challenging cardiovascular disease associated with high mortality rates. The occurrence and progression of CHF are closely linked to left ventricular remodeling (LVR) and inflammation. Addressing LVR and reducing inflammation can significantly slow down the progression of CHF and improve patient prognosis. Objective: To evaluate the effects of Xinmailong injection (XMLI) on LVR and inflammatory mediators in CHF patients. Method: The randomized controlled trials investigating the effectiveness of XMLI treatment for CHF were retrieved from eight databases up until 31 December 2023. To evaluate the methodological quality of included studies, the Cochrane bias risk tool was employed. Furthermore, statistical analysis, sensitivity analysis, and publication bias assessment were conducted using Stata 17.0 software. Result: Compared with conventional treatment (CT), the combination therapy of XMLI and CT significantly improved LVR and reduced inflammatory mediators, mainly manifested by an increase in LVEF (MD = 6.40, 95% CI: 5.25 to 7.55, p = 0.000), a decrease in LVEDD (MD = -4.63, 95% CI: -5.69 to -3.57, p = 0.000) and LVESD (MD = -4.00, 95% CI: -5.50 to -2.50, p = 0.000), as well as a decrease in TNF-α (MD = -7.93, 95% CI: -9.86 to -6.00, p = 0.000), IL-6 (MD = -5.25, 95% CI: -6.59 to -3.92, p = 0.000), IL-18 (MD = -36.07, 95% CI: -46.76 to -25.38, p = 0.000), CRP (MD = -4.41, 95% CI: -6.40 to -2.42, p = 0.000), hs-CRP (MD = -4.90, 95% CI: -5.71 to -4.08, p = 0.000), and an increase in IL-10 (MD = 20.19, 95% CI: 10.42 to 29.97, p = 0.000). In addition, the combination therapy showed enhanced clinical efficacy (OR = 4.08, 95% CI: 3.10 to 5.37, p = 0.000), decreased expression levels of BNP (MD = -138.48, 95% CI: -155.48 to -121.48, p = 0.000), and NT-pro BNP (MD = -315.63, 95% CI: -359.25 to -272.00, p = 0.000), and increased the 6-MWD (MD = 71.02, 95% CI: 57.23 to 84.81, p = 0.000). It is noteworthy that the combination therapy did not lead to an increase in the incidence of adverse reactions (OR = 1.01, 95% CI: 0.68 to 1.50, p = 0.97). Conclusion: This systematic review and meta-analysis demonstrated the superiority of combining XMLI and CT therapies over CT alone in improving LVR and reducing inflammatory mediators in patients with CHF. Importantly, this combination therapy does not increase adverse reactions. However, it is crucial to exercise caution while interpreting the survey results due to the limited quality of the included studies.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=492715, Identifier CRD42023492715.

Ethnicity Differences in Geometric Remodeling and Myocardial Composition in Hypertension unveiled by Cardiovascular Magnetic Resonance.

AIMS: Hypertensive patients of African-ancestry (Afr-a) have higher incidences of heart failure and worse clinical outcomes than hypertensive patients of European-ancestry (Eu-a), yet the underlying mechanisms remain misunderstood. This study investigated right (RV) and left (LV) ventricular remodeling alongside myocardial tissue derangements between Afr-a and Eu-a hypertensives. METHODS AND RESULTS: Sixty-three Afr-a and forty-seven Eu-a hypertensives underwent multi-parametric cardiovascular-magnetic-resonance. Biventricular volumes, mass, function, mass/end-diastolic volume (M/V) ratios, T2- and pre/post-contrast T1-relaxation-times, synthetic-extracellular-volume (s-ECV) and myocardial fibrosis (MF) were measured. Three-dimensional shape modeling was implemented to delineate ventricular geometry.LV and RV-mass (indexed to body-surface-area) and M/V ratios were significantly greater in Afr-a than Eu-a hypertensives (67.1±21.7 vs. 58.3±16.7g/m2, 12.6±3.48 vs. 10.7±2.71g/m2, 0.79±0.21 vs. 0.70±0.14g/ml, 0.16±0.04 vs. 0.13±0.03g/ml, respectively; P<0.03) mirroring LV remodeling. Afr-a patients showed greater basal-interventricular-septum thickness than Eu-a patients, which may influence LV hypertrophy and RV cavity changes. This biventricular remodeling was associated with prolonged T2-relaxation-time (47.0±2.2 vs. 45.7±2.2ms, P=0.005) and higher prevalence (23% vs. 4%, P=0.001) and extent of MF (2.3[0.6-14.3] vs. 1.6[0.9-2.5] % of LV-mass, P=0.008) in Afr-a patients. Multivariable linear regression showed modifiable cardiovascular risk-factors and greater end-diastolic volume were independently associated with greater LV or RV-mass. Furthermore, ethnicity was independently associated with greater RV-mass, supporting our hypothesis of ethnic-specific hypertensive remodeling. CONCLUSIONS: Afr-a hypertensives had distinctive biventricular remodeling, including increased RV-mass and septal thickening, and subtle myocardial tissue abnormalities compared to Eu-a hypertensives. From this study, modifiable cardiovascular risk-factors, and ventricular geometry, but not ethnicity, were independently associated with higher LV mass.

A review of therapeutic approaches for post-infarction left ventricular remodeling.

Left ventricular remodeling is an adaptive process initially developed in response to acute myocardial infarction (AMI), but it ends up with negative adverse outcomes such as infarcted wall thinning, ventricular dilation, and cardiac dysfunction. A prolonged excessive inflammatory reaction to cardiomyocytes death and necrosis plays the crucial role in the pathophysiological mechanisms. The pharmacological treatment includes nitroglycerine, ß-blockers, ACEi/ARBs, SGLT2i, mineralocorticoid receptor antagonists, and some miscellaneous aspects. Stem cells therapy, CD34+ cells transplantation and gene therapy constitute the promissing therapeutic approaches for post AMI cardiac remodeling, thereby enhancing angiogenesis, cardiomyocytes differenciation and left ventricular function on top of inhibiting apoptosis, inflammation, and collagen deposition. All these lead to reduce infarct size, scar formation and myocardial fibrosis.

Sacubitril/valsartan reversal of left ventricular remodeling is associated with improved hemodynamics in resistant hypertension.

BACKGROUND: Sacubitril/valsartan (S/V) has been shown to be an effective antihypertensive drug combination. However, its therapeutic effects on blood pressure (BP), hemodynamics, and left ventricular (LV) remodeling in resistant hypertension (RHTN) remain unclear. METHODS: Eighty-six patients completed this self-control study, during which olmesartan was administered within the first 8 weeks (phase 1), followed by S/V within the second 8 weeks (phase 2), with nifedipine and hydrochlorothiazide taken as background medications. Office BP, echocardiography, and hemodynamics assessment using impedance cardiography were performed at baseline and at the eighth and sixteenth weeks. RESULTS: The reduction in office BP was larger in phase 2 than in phase 1 (19.59/11.66 mmHg vs. 2.88/1.15 mmHg). Furthermore, the treatment in phase 2 provided greater reductions in systemic vascular resistance index (SVRI) and thoracic blood saturation ratio (TBR), with differences between the two phases of -226.59 (-1212.80 to 509.55) dyn·s/cm5/m2 and -0.02 (-0.04 to 0.02). Switching from olmesartan to S/V also significantly reduced E/E', LV mass index, LV end-diastolic volume index, and LV end-systolic volume index (all P < 0.05). Decreases in arterial stiffness, SVRI, and TBR were correlated with changes in indicators of LV remodeling (all P < 0.05). This correlation persisted even after adjusting for confounders including changes in BP. CONCLUSIONS: Switching from olmesartan to S/V effectively lowered BP and reversed ventricular remodeling in RHTN. In addition, hemodynamic improvement was also observed. Changes in hemodynamics played an important role in reversing LV remodeling of S/V, and were independent of its antihypertensive effect.

Left Ventricular Remodelling Associated with the Transient Elevated [68Ga]Ga-Pentixafor Activity in the Remote Myocardium Following Acute Myocardial Infarction.

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.

The Role of Epicardial Adipose Tissue in Acute Coronary Syndromes, Post-Infarct Remodeling and Cardiac Regeneration.

Epicardial adipose tissue (EAT) is a fat deposit surrounding the heart and located under the visceral layer of the pericardium. Due to its unique features, the contribution of EAT to the pathogenesis of cardiovascular and metabolic disorders is extensively studied. Especially, EAT can be associated with the onset and development of coronary artery disease, myocardial infarction and post-infarct heart failure which all are significant problems for public health. In this article, we focus on the mechanisms of how EAT impacts acute coronary syndromes. Particular emphasis was placed on the role of inflammation and adipokines secreted by EAT. Moreover, we present how EAT affects the remodeling of the heart following myocardial infarction. We further review the role of EAT as a source of stem cells for cardiac regeneration. In addition, we describe the imaging assessment of EAT, its prognostic value, and its correlation with the clinical characteristics of patients.

Histologically Validated Myocardial Fibrosis in Relation to Left Ventricular Geometry and Its Function in Aortic Stenosis.

Background and Objectives: The combination of aortic valve stenosis (AS) and ischemic heart disease (IHD) is quite common and is associated with myocardial fibrosis (MF). The purpose of this study was to evaluate the association between the histologically verified left ventricular (LV) MF and its geometry and function in isolated AS and AS within IHD groups. Materials and Methods: In a single-center, prospective trial, 116 patients underwent aortic valve replacement (AVR) with/without concomitant surgery. The study population was divided into groups of isolated AS with/without IHD. Echocardiography was used, and LV measurements and aortic valve parameters were obtained from all patients. Myocardial tissue was procured from all study patients undergoing elective surgery. Results: There were no statistical differences between isolated AS and AS+IHD groups in LV parameters or systolic and diastolic functions during the study periods. The collagen volume fraction was significantly different between the isolated AS and AS+IHD groups and was 7.3 ± 5.6 and 8.3 ± 6.4, respectively. Correlations between MF and left ventricular end-diastolic diameter (LVEDD) (r = 0.59, p = < 0.001), left ventricular mass (LVM) (r = 0.42, p = 0.011), left ventricular ejection fraction (LVEF) (r = -0.67, p < 0.001) and an efficient orifice area (EOA) (r = 0.371, p = 0.028) were detected in isolated AS during the preoperative period; the same was observed for LVEDD (r = 0.45, p = 0.002), LVM (r = 0.36, p = 0.026), LVEF (r = -0.35, p = 0.026) and aortic annulus (r = 0.43, p = 0.018) in the early postoperative period; and LVEDD (r = 0.35, p ≤ 0.05), LVM (r = 0.43, p = 0.007) and EOA (r = 0.496, p = 0.003) in the follow-up period. In the group of AS and IHD, correlations were found only with LV posterior wall thickness (r = 0.322, p = 0.022) in the follow-up period. Conclusions: Histological MF in AS was correlated with LVM and LVEDD in all study periods. No correlations between MF and LV parameters were found in aortic stenosis in the ischemic heart disease group across all study periods.