Empagliflozin and Left Ventricular Remodeling in People Without Diabetes: Primary Results of the EMPA-HEART 2 CardioLink-7 Randomized Clinical Trial.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors have been demonstrated to promote reverse cardiac remodeling in people with diabetes or heart failure. Although it has been theorized that sodium-glucose cotransporter 2 inhibitors might afford similar benefits in people without diabetes or prevalent heart failure, this has not been evaluated. We sought to determine whether sodium-glucose cotransporter 2 inhibition with empagliflozin leads to a decrease in left ventricular (LV) mass in people without type 2 diabetes or significant heart failure. METHODS: Between April 2021 and January 2022, 169 individuals, 40 to 80 years of age, without diabetes but with risk factors for adverse cardiac remodeling were randomly assigned to empagliflozin (10 mg/d; n=85) or placebo (n=84) for 6 months. The primary outcome was the 6-month change in LV mass indexed (LVMi) to baseline body surface area as measured by cardiac magnetic resonance imaging. Other measures included 6-month changes in LV end-diastolic and LV end-systolic volumes indexed to baseline body surface area and LV ejection fraction. RESULTS: Among the 169 participants (141 men [83%]; mean age, 59.3±10.5 years), baseline LVMi was 63.2±17.9 g/m2 and 63.8±14.0 g/m2 for the empagliflozin- and placebo-assigned groups, respectively. The difference (95% CI) in LVMi at 6 months in the empagliflozin group versus placebo group adjusted for baseline LVMi was -0.30 g/m2 (-2.1 to 1.5 g/m2; P=0.74). Median baseline (interquartile range) NT-proBNP (N-terminal-pro B-type natriuretic peptide) was 51 pg/mL (20-105 pg/mL) and 55 pg/mL (21-132 pg/mL) for the empagliflozin- and placebo-assigned groups, respectively. The 6-month treatment effect of empagliflozin versus placebo (95% CI) on blood pressure and NT-proBNP (adjusted for baseline values) were -1.3 mm Hg (-5.2 to 2.6 mm Hg; P=0.52), 0.69 mm Hg (-1.9 to 3.3 mm Hg; P=0.60), and -6.1 pg/mL (-37.0 to 24.8 pg/mL; P=0.70) for systolic blood pressure, diastolic blood pressure, and NT-proBNP, respectively. No clinically meaningful between-group differences in LV volumes (diastolic and systolic indexed to baseline body surface area) or ejection fraction were observed. No difference in adverse events was noted between the groups. CONCLUSIONS: Among people with neither diabetes nor significant heart failure but with risk factors for adverse cardiac remodeling, sodium-glucose cotransporter 2 inhibition with empagliflozin did not result in a meaningful reduction in LVMi after 6 months. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04461041.

Deficiency of the sphingosine-1-phosphate (S1P) transporter Mfsd2b protects the heart against hypertension-induced cardiac remodeling by suppressing the L-type-Ca2+ channel.

The erythrocyte S1P transporter Mfsd2b is also expressed in the heart. We hypothesized that S1P transport by Mfsd2b is involved in cardiac function. Hypertension-induced cardiac remodeling was induced by 4-weeks Angiotensin II (AngII) administration and assessed by echocardiography. Ca2+ transients and sarcomere shortening were examined in adult cardiomyocytes (ACM) from Mfsd2b+/+ and Mfsd2b-/- mice. Tension and force development were measured in skinned cardiac fibers. Myocardial gene expression was determined by real-time PCR, Protein Phosphatase 2A (PP2A) by enzymatic assay, and S1P by LC/MS, respectively. Msfd2b was expressed in the murine and human heart, and its deficiency led to higher cardiac S1P. Mfsd2b-/- mice had regular basal cardiac function but were protected against AngII-induced deterioration of left-ventricular function as evidenced by ~ 30% better stroke volume and cardiac index, and preserved ejection fraction despite similar increases in blood pressure. Mfsd2b-/- ACM exhibited attenuated Ca2+ mobilization in response to isoprenaline whereas contractility was unchanged. Mfsd2b-/- ACM showed no changes in proteins responsible for Ca2+ homeostasis, and skinned cardiac fibers exhibited reduced passive tension generation with preserved contractility. Verapamil abolished the differences in Ca2+ mobilization between Mfsd2b+/+ and Mfsd2b-/- ACM suggesting that S1P inhibits L-type-Ca2+ channels (LTCC). In agreement, intracellular S1P activated the inhibitory LTCC phosphatase PP2A in ACM and PP2A activity was increased in Mfsd2b-/- hearts. We suggest that myocardial S1P protects from hypertension-induced left-ventricular remodeling by inhibiting LTCC through PP2A activation. Pharmacologic inhibition of Mfsd2b may thus offer a novel approach to heart failure.

Increased Secreted Frizzled-Related Protein 2 in Hypertension-Induced Left Ventricular Remodeling.

Background: Secreted frizzled-related protein 2 (sFRP2) is involved in various cardiovascular diseases. However, its relevance in left ventricular (LV) remodeling in patients with hypertension (HTN) is obscure. Methods: In this study, 196 patients with HTN were included, 59 with echocardiographic LV remodeling. A total of 100 healthy subjects served as normal controls. The serum-sFRP2 level was measured by enzyme-linked immunosorbent assay (ELISA). Data were collected from medical records for baseline characteristics, biochemistry tests, and echocardiography. Receiver operating characteristic (ROC) curves were used to assess the distinguishing value of sFRP2 for LV remodeling in patients with HTN. Spearman rank correlation analysis was utilized to identify factors correlated with sFRP2. Cardiac sFRP2 was determined by Western blot and quantitative polymerase chain reaction (qPCR). Results: The level of serum-sFRP2 was higher in HTN patients with echocardiographic LV remodeling than their non-remodeling counterparts. ROC analysis showed that the area under the curve (AUC) for sFRP2 in distinguishing echocardiographic LV remodeling in HTN patients was 0.791 (95% confidence interval (CI): 0.714-0.869). The sFRP2 was negatively correlated with LV dimension and positively correlated with relative wall thickness (RWT). The expression of sFRP2 was higher in hypertrophic hearts, which could be reversed by myricetin. Conclusions: The serum level and cardiac sFRP2 increased in the setting of LV remodeling and decreased by myricetin. Serum sFRP2 may be a promising distinguishing factor for LV remodeling in HTN patients.

99mTc-HFAPi SPECT imaging predicts left ventricular remodeling after acute myocardial infarction.

BACKGROUND: Despite improved treatments for acute myocardial infarction (AMI), myocardial fibrosis remains a key driver of adverse left ventricular (LV) remodeling and increased mortality. Fibroblast activation and proliferation significantly contribute to this process by enhancing cardiac fibrosis, which can lead to detrimental changes in LV structure. This study evaluates the effectiveness of 99mTc-labeled fibroblast activation protein inhibitor (99mTc-HFAPi) SPECT imaging in predicting LV remodeling over 12 months in post-AMI patients. METHODS: A cohort of 58 AMI patients (46 males, median age 61 [53, 67] years) underwent baseline 99mTc-HFAPi imaging (5 ± 2 days post-MI), perfusion imaging (6 ± 2 days post-MI), and echocardiography (2 ± 2 days post-MI). Additionally, 15 patients had follow-up 99mTc-HFAPi and perfusion imaging, while 30 patients had follow-up echocardiography. Myocardial 99mTc-HFAPi activity was assessed at the patient level. LV remodeling was defined as a ≥10% increase in LV end-diastolic diameter (LVEDD) or LV end-systolic diameter (LVESD) from baseline to follow-up echocardiography. RESULTS: AMI patients displayed localized but non-uniform 99mTc-HFAPi uptake, exceeding perfusion defects. Baseline 99mTc-HFAPi activity exhibited significant correlations with BNPmax, LDHmax, cTNImax, and WBCmax, inversely correlating with LVEF. After 12 months, 11 patients (36.66%) experienced LV remodeling. Univariate regression analysis demonstrated an association between baseline 99mTc-HFAPi uptake extent and LV remodeling (OR = 2.14, 95%CI, 1.04, 4.39, P = 0.038). CONCLUSIONS: 99mTc-HFAPi SPECT imaging holds promise in predicting LV remodeling post-MI, providing valuable insights for patient management and prognosis.

Routine first-trimester pre-eclampsia screening and maternal left ventricular geometry.

OBJECTIVE: Pre-eclampsia (PE) is a pregnancy complication associated with premature cardiovascular disease morbidity and mortality (i.e. before 60 years of age or in the first year postpartum). PE is associated with adverse left ventricular (LV) remodeling in the peri- and postpartum periods, an independent risk factor for cardiovascular disease. This study aimed to compare LV geometry by LV mass (LVM) and LVM index (LVMI) between participants with a high vs low screening risk for preterm PE in the first trimester. METHODS: This was a prospective cohort study of singleton pregnancies between 11 + 0 and 13 + 6 weeks' gestation that underwent screening for preterm PE as part of their routine first-trimester ultrasound assessment at a tertiary center in London, UK, from February 2019 until March 2020. Screening for preterm PE was performed using the Fetal Medicine Foundation algorithm. Participants with a screening risk of ≥ 1 in 50 for preterm PE were classified as high risk and those with a screening risk of ≤ 1 in 500 were classified as low risk. All participants underwent two-dimensional and M-mode transthoracic echocardiography. RESULTS: A total of 128 participants in the first trimester of pregnancy were included in the analysis, with 57 (44.5%) participants screened as low risk and 71 (55.5%) participants as high risk for PE. The risk groups did not vary in maternal age and gestational age at assessment. Maternal body surface area and body mass index were significantly higher in the high-risk group (all P < 0.05). The high-risk participants were significantly more likely to be Afro-Caribbean, nulliparous and have a family history of hypertensive disease in pregnancy as well as other cardiovascular disease (all P < 0.05). In addition, mean arterial blood pressure (P < 0.001), mean heart rate (P < 0.001), median LVM (130.06 (interquartile range, 113.62-150.50) g vs 97.44 (81.68-114.16) g; P < 0.001) and mean LVMI (72.87 ± 12.2 g/m2 vs 57.54 ± 12.72 g/m2 ; P < 0.001) were significantly higher in the high-risk group. Consequently, those in the high-risk group were more likely to have abnormal LV geometry (37.1% vs 7.0%; P < 0.001). CONCLUSIONS: Early echocardiographic assessment in participants at high risk of preterm PE may unmask clinically healthy individuals who are at increased risk for future cardiovascular disease. Adverse cardiac remodeling in the first trimester of pregnancy may be an indicator of decreased cardiovascular reserve and subsequent dysfunctional cardiovascular adaptation in pregnancy. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Circulating microRNA-409-5p and USP7 are associated with left ventricular remodeling in patients with acute myocardial infarction.

BACKGROUND: Our previous study demonstrated that microRNA-409-5p (miR-409-5p) and its target ubiquitin-specific protease 7 (USP7) were involved in hypoxia-induced cardiomyocyte injury and ischemic left ventricular remodeling (LVR) in rats. This study aimed to probe into the relationship between plasma miR-409-5p and USP7 levels and LVR and dysfunction in patients with acute myocardial infarction (AMI). METHODS: Sixty patients with acute myocardial infarction (AMI) and 60 cases with chronic coronary syndrome (CCS) were enrolled. The clinical characteristics, echocardiographic/serum parameters of LVR, and circulating miR-409-5p and USP7 mRNA levels between the two groups and between admission and 6 weeks after discharge were compared. The correlations between circulating miR-409-5p/USP7 levels and serum/echocardiographic parameters were analyzed. RESULTS: The demographic characteristics of the AMI group and CCS group were comparable. Patients with AMI admitted to the study displayed significantly higher levels of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) and growth stimulation expressed gene 2 (ST2), along with a greater left ventricular end-systolic volume (LVESV). Conversely, their left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), and global radial strain (GRS) were significantly lower compared to patients with CCS. These changes were normalized 6 weeks after discharge. Circulating miR-409-5p levels at admission were significantly decreased while circulating USP7 mRNA expression levels were significantly increased in patients with AMI compared with those with CCS (both P < 0.01). However, these changes were restored 6 weeks after discharge (both P < 0.01). Moreover, circulating miR-409-5p and USP7 mRNA levels showed varying correlations with GLS, GRS, LVESV, LVEF, and NT-proBNP in patients with AMI but not in those with CCS. Additionally, circulating miR-409-5p and USP7 levels predicted the incidence of LVR and major adverse cardiovascular events (MACE) after AMI. CONCLUSION: Serum miR-409-5p and USP7 may influence the occurrence and evolution of LVR and left ventricular dysfunction after AMI.

Early Famine Exposure Results in Left Ventricular Remodeled, Diastolic Dysfunction and Systolic Function Preserved in Adults.

INTRODUCTION: Malnutrition during a critical window of development in a fetus or infant can result in abnormal cardiac remodeling and function. It is uncertain whether the contribution of these effects continues to impact the cardiac remodeling and function of adults over the course of several decades of growth. Our study examined the impact of early Chinese famine exposure on cardiac remodeling, left ventricular (LV) diastolic function, and LV systolic function in adults. METHODS: Participants at high risk of cardiovascular disease from the China Patient-Centered Evaluative Assessment of Cardiac Events Million Persons Project (PEACE MPP) were enrolled. The famine in China lasted from 1959 to 1962. A total of three groups were formed based on the participants' birth dates: pre-famine group, famine exposure group, and post-famine group. Logistic regression and linear mixed models were used to explore the association between famine exposure and cardiac remodeling, LV diastolic function and LV systolic function in adults. RESULTS: The study included 2,758 participants, the mean age was 57.05 years, 62.8% were female, 26.4% had LV hypertrophy (LVH), 59.6% had LV diastolic dysfunction (LVDD), and 10.5% had reduced global longitudinal strain (GLS). Compared to post-famine exposure, participants had independently increased risk of LVH in the famine exposure group (OR: 2.02, 95% CI: 1.60-2.56) and pre-famine exposure (OR: 1.36, 95% CI: 1.06-1.76). Compared to post-famine exposure, the risk of LVDD remarkably increased in the famine exposure group (OR: 3.04, 95% CI: 2.49-3.71) and pre-famine exposure group (OR: 1.87, 95% CI: 1.52-2.31). Famine exposure had no significant impact on GLS but was associated with a significant increase in LV ejection fraction (LVEF) and LV end-diastolic diameter (LVEDD). Significant interactions were observed between the effects of famine exposure and other clinical/sociodemographic variables (gender, systolic blood pressure [SBP] ≥140 mm Hg or not, high school or above or not, and annual income <50,000 RMB or not) on these outcomes. CONCLUSION: Exposure to famine, particularly during fetal and infant stages, increases the risk of LVH and LVDD in adults. However, the LV systolic function remains preserved. These impacts are more pronounced in females, individuals with SBP ≥140 mm Hg, those with low income, or those with high educational status.

Left ventricular remodeling and long-term outcomes of aortic stenosis patients receiving 19 mm Mosaic.

Mosaic valve shows higher pressure gradient after aortic valve replacement compared to other same size labeled prostheses in postoperative echocardiogram. The purpose of this study was to evaluate the mid-term echocardiogram findings and long-term clinical outcomes of patients receiving a 19 mm Mosaic. Forty-six aortic stenosis patients receiving 19 mm Mosaic and 112 patients receiving either 19 mm Magna or Inspiris, who underwent mid-term follow-up echocardiogram were included in the study. Mid-term hemodynamic measurements evaluated by trans-thoracic echocardiogram and long-term outcomes were compared. Patients receiving Mosaic were significantly older (Mosaic: 76 ± 5.1 years vs. Magna/Inspiris: 74 ± 5.5 years, p = 0.046) and had smaller body surface area (Mosaic: 1.40 ± 0.114m2 vs. Magna/Inspiris: 1.48 ± 0.143m2, p < 0.001). There were no significant differences in comorbidities and medications. Post-operative echocardiogram performed at 1 week after the surgery showed higher maximum pressure gradient in patients receiving Mosaic (Mosaic: 38 ± 13.5 mmHg vs. Magna/Inspiris: 31 ± 10.7 mmHg, p = 0.002). Furthermore, mid-term echocardiogram follow-up performed at median duration of 53 ± 14.9 months after the surgery continuously showed higher maximum pressure gradient in patients receiving Mosaic (Mosaic: 45 ± 15.6 mmHg vs. Magna/Inspiris: 32 ± 13.0 mmHg, p < 0.001). However, there were no significant difference in changes in left ventricular mass from baseline in both groups. Kaplan-Meyer curve also showed no difference in long-term mortality and major adverse cardiac and cerebrovascular event between the two groups. Although the pressure gradient across the valve evaluated by echocardiogram was higher in 19 mm Mosaic compared to 19 mm Magna/Inspiris, there were no significant differences in left ventricular remodeling and long-term outcomes between the two groups.

Left ventricular remodeling and its association with mineral and bone disorder in kidney transplant recipients.

BACKGROUND: The assessment of left ventricular (LV) remodeling and its association with mineral and bone disorder (MBD) in kidney transplant recipients (KTRs) have not been systematically studied. We aimed to evaluate LV remodeling changes one year after kidney transplantation (KT) and identify their influencing factors. METHODS: Ninety-five KTRs (68 males; ages 40.2 ± 10.8 years) were followed before and one year after KT. Traditional risk factors and bone metabolism indicators were assessed. Left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF) and left ventricular diastolic dysfunction (LVDD) were measured using two-dimensional transthoracic echocardiography. The relationship between MBD and LV remodeling and the factors influencing LV remodeling were analyzed. RESULTS: One year after KT, MBD was partially improved, mainly characterized by hypercalcemia, hypophosphatemia, hyperparathyroidism, 25-(OH) vitamin D deficiency, elevated bone turnover markers, and bone loss. LVMI, the prevalence of left ventricular hypertrophy (LVH), and the prevalence of LVDD decreased, while LVEF increased. LVH was positively associated with postoperative intact parathyroid hormone (iPTH) and iPTH nonnormalization. △LVMI was positively associated with preoperative type-I collagen N-terminal peptide and postoperative iPTH. LVEF was negatively associated with postoperative phosphorous. △LVEF was negatively associated with postoperative iPTH. LVDD was positively associated with postoperative lumbar spine osteoporosis. Preoperative LVMI was negatively associated with △LVMI and positively associated with △LVEF. Advanced age, increased BMI, diabetes, longer dialysis time, lower albumin level, and higher total cholesterol and low-density lipoprotein levels were associated with LV remodeling. CONCLUSIONS: LV remodeling partially improved after KT, showing a close relationship with MBD.

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.

Association of insulin use with LV remodeling and clinical outcomes in diabetic patients with heart failure and reduced ejection fraction: assessed by cardiac MRI.

BACKGROUND: Insulin is commonly used in type 2 diabetes mellitus (T2DM) to achieve glycemic control. However, recent evidence showed that insulin use is associated with poor outcomes in the context of heart failure (HF). Since heart failure with reduced ejection fraction (HFrEF) accounts for approximately 50% of cases in the general HF population, we aimed to evaluate the effect of insulin treatment on left ventricular (LV) remodeling and contractility abnormalities in a HFrEF cohort and assess whether insulin was a predictor of adverse outcomes in this entity. METHODS: A total of 377 HFrEF patients who underwent cardiac MRI were included and divided according to diabetes status and the need for insulin treatment. LV structural and functional indices, as well as systolic strains, were measured. The determinants of impaired myocardial strains were assessed using linear regression analysis. The associated endpoints were determined using a multivariable Cox proportional hazards model. RESULTS: T2DM patients on insulin displayed a higher indexed LV end-diastolic volume and LV mass than those with T2DM not on insulin or those without T2DM, despite similar LV ejection fractions, accompanied by a higher three-dimensional spherical index (P < 0.01). Worse longitudinal and circumferential peak systolic strain was shown to occur in T2DM patients on insulin (P < 0.01). Insulin treatment was independently associated with impaired magnitudes of systolic strain. The median follow-up duration was 32.4 months (IQR, 15.6-43.2 months). Insulin treatment remained consistently associated with poor outcomes after adjustment for established confounders, with an adjusted hazard ratio of 3.11; (95% CI, 1.45-6.87; P = 0.009) in the overall cohort and 2.16 (95% CI, 1.08-4.59; P = 0.030) in the diabetes cohort. CONCLUSIONS: Insulin may further lead to adverse LV remodeling and contractile dysfunction in the context of HFrEF with T2DM. Considerable care should be taken when treating HFrEF patients with insulin.

The inflammatory score and cardiovascular risk in young adults with overweight or obesity: The African-PREDICT study.

OBJECTIVES: A complex relationship of adipokines and cytokines with cardiovascular risk motivates the use of an integrated approach to identify early signs of adiposity-related inflammation. We compared the inflammatory profiles, including an integrated inflammatory score, and cardiovascular profiles of young adults who are living with overweight and/or obesity (OW/OB). DESIGN AND METHODS: This cross-sectional study included 1194 men and women with a median age of 24.5 ± 3.12 years from the African Prospective study on the Early Detection and Identification of Cardiovascular disease and Hypertension (African-PREDICT). Participants were divided into approximate quartiles based on adiposity measures (body mass index, waist circumference, and waist-to-height ratio). We compared an integrated inflammatory score (including leptin, adiponectin, interleukin-6, interleukin-8, interleukin-10, and tumour necrosis factor-α) as well as the individual inflammatory markers, between extreme quartiles. We also compared blood pressure measures, left ventricular mass index, carotid-femoral pulse wave velocity, and carotid intima-media thickness between these groups. RESULTS: Individuals in the top quartile had worse inflammatory- and cardiovascular profiles as the integrated inflammatory score, leptin, interleukin-6, blood pressure measures, and left ventricular mass index were higher, while adiponectin was lower (all p ≤ 0.003). Unexpectedly, carotid-femoral pulse wave velocity was also lower (p < 0.001) in the top quartile. Exclusively in the top quartile, all adiposity measures related positively with the integrated inflammatory score and central systolic blood pressure (both r ≥ 0.24; p < 0.001), and negatively with interleukin-10 (all r ≤ -0.13; p < 0.03). Of these relationships, the correlations with the integrated inflammatory score were the strongest (p < 0.001). The percentage difference of being in the top quartile of all adiposity measures were higher for the inflammatory score (all ≥ 263 %), leptin (all ≥ 175 %), interleukin-6 (all ≥ 134 %), and tumour necrosis factor-α (all ≥ 26 %), and lower for adiponectin (all ≥ 57 %), interleukin-10 (all ≥ 9 %), and interleukin-8 (all ≥ 15 %) compared to being in the bottom quartile. CONCLUSION: The inflammatory score, as a comprehensive marker of adiposity-related inflammation, is strongly related to adiposity and may be an indication of early cardiovascular risk in young adults; however, further work is required to establish the clinical use thereof.

[68Ga]Ga-DOTA-FAPI-04 PET/MR in patients with acute myocardial infarction: potential role of predicting left ventricular remodeling.

PURPOSE: To assess predictive value of 68Ga-labeled fibroblast activation protein inhibitor-04 ([68Ga]Ga-DOTA-FAPI-04) PET/MR for late left ventricular (LV) remodeling in patients with ST-segment elevated myocardial infarction (STEMI). METHODS: Twenty-six patients with STEMI were included in the study. [68Ga]Ga-DOTA-FAPI-04 PET/MR was performed at baseline and at average 12 months after STEMI. LV remodeling was defined as >10% increase in LV end-systolic volume (LVESV) from baseline to 12 months. RESULTS: The LV remodeling group demonstrated higher [68Ga]Ga-DOTA-FAPI-04 uptake volume (UV) at baseline than the non-LV remodeling group (p < 0.001). [68Ga]Ga-DOTA-FAPI-04 UV at baseline was a significant predictor (OR = 1.048, p = 0.011) for LV remodeling at 12 months after STEMI. Compared to clinical information, MR imaging and cardiac function parameters at baseline, [68Ga]Ga-DOTA-FAPI-04 UV demonstrated better predictive ability (AUC = 0.938, p < 0.001) for late LV remodeling, with sensitivity of 100.0% and specificity of 81.3%. CONCLUSIONS: [68Ga]Ga-DOTA-FAPI-04 PET/MR is an effective tool to non-invasively quantify myocardial fibroblasts activation, and baseline [68Ga]Ga-DOTA-FAPI-04 UV may have potential predictive value for late LV remodeling.

Association between systemic inflammatory response index and left ventricular remodeling and systolic dysfunction in atrial fibrillation patients.

BACKGROUND: Cardiac remodeling and dysfunction can be caused by atrial fibrillation (AF). The aim of this research is to investigate the relationship between the systemic inflammatory response index (SIRI) and left ventricular (LV) remodeling and systolic function in individuals with AF. METHODS: 416 patients with AF who were admitted to the Second Department of Cardiology in the East Ward of the Qingdao Municipal Hospital between January 2020 and May 2022 were included in the present retrospective research. The relationship between SIRI and various cardiac parameters was analyzed. The patients' left atrial (LA) enlargement and left ventricular (LV) hypertrophy and systolic dysfunction were evaluated. SIRI was calculated by the formula: neutrophil × monocyte/lymphocyte. RESULTS: SIRI significantly correlated with LV end-diastolic diameter (LVDd), LV posterior wall thickness at end-diastole (LVPWTd), interventricular septal thickness at end-diastole (IVSTd), LV mass index (LVMI), LV ejection fraction (LVEF), LA diameter (LAD), C-reactive protein (CRP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with AF. In multivariate linear regression analyses, SIRI was discovered to be significantly related to LVMI (ln-transformed) (p = 0.025), LVEF (ln-transformed) (p = 0.005), and LAD (ln-transformed) (p = 0.007). In multivariate logistic regression, the highest quartile of SIRI (SIRI > 1.62) was significantly associated with LV hypertrophy (p = 0.026), impaired LV systolic function (p = 0.002), and LA enlargement (p = 0.025). CONCLUSIONS: SIRI was significantly associated with LV remodeling and systolic function impairment in patients with AF. SIRI may serve as a reliable and convenient inflammatory biomarker for detecting impaired cardiac structure and systolic function in patients with AF.

Effect of SGLT-2 inhibitor, dapagliflozin, on left ventricular remodeling in patients with type 2 diabetes and HFrEF.

The current study evaluated the effect of SGLT-2 inhibitor, dapagliflozin, on left ventricular remodeling in patients with type 2 diabetes and HFrEF. 60 patients were randomized (1:1) to receive dapagliflozin 10 mg once daily, or placebo double blind for 1 year. Patients underwent transthoracic echocardiography and doppler evaluation prior to dapagliflozin initiation and at 1 year. At 1year, adjusted mean difference versus placebo in change from baseline in LVEF was 2.5% (95% CI: 1.00-4.06, P = 0.002). Adjusted mean difference versus placebo in change from baseline in LVED volume was - 6.0ml (95% CI: -8.07 --3.87, P<0.001). Adjusted mean difference versus placebo in change from baseline in LVES volume was - 8.1ml (95% CI: -11.07 --5.14, P<0.001). Similarly, adjusted mean difference versus placebo in change from baseline in LVED diameter was - 1.6 mm (95% CI: -2.67 --0.62, P = 0.002). Adjusted mean difference versus placebo in change from baseline in VTI was 0.20 cm (95% CI: 0.01-0.38, P = 0.036). Dapagliflozin was well tolerated. Dapagliflozin was associated with significant and clinically meaningful improvement in echocardiographic parameters versus placebo in patients with type 2 diabetes and HFrEF.Registration number and date: ChiCTR2300072707, 21/06/2023.

Reverse of left ventricular remodeling in heart failure patients with left bundle branch area pacing: Systematic review and meta-analysis.

BACKGROUND: Left bundle branch area pacing (LBBAP) has recently become a promising option for the near-natural restoration of electrical activation. However, the clinical relevance of therapeutic effects in individuals with heart failure with reduced ejection fraction (HFrEF) and dyssynchrony remains unknown. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched from inception until June 2022. Data from each study was combined using a random-effects model, the generic inverse variance method of DerSimonian and Laird, to calculate standard mean differences and pooled incidence ratio, with 95% confidence intervals (CIs). RESULTS: A total of 772 HFrEF patients were analyzed from 15 observational studies per protocol. The success rate of LBBAP implantation was 94.8% (95% CI 89.9-99.6, I2 = 79.4%), which was strongly correlated with shortening QRS duration after LBBAP implantation, with a mean difference of -48.10 ms (95% CI -60.16 to -36.05, I2 = 96.7%). Over a period of 6-12 months of follow-up, pacing parameters were stable over time. There were significant improvements in left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic diameter (LVEDD), and left ventricular end-diastolic volume (LVEDV) with mean difference of 16.38% (95% CI 13.13-19.63, I2 = 90.2%), -46.23 ml (95% CI -63.17 to -29.29, I2 = 86.82%), -7.21 mm (95% CI -9.71 to -4.71, I2 = 84.6%), and -44.52 ml (95% CI -64.40 to -24.64, I2 = 85.9%), respectively. CONCLUSIONS: LBBAP was associated with improvements in both cardiac function and electrical synchrony. The benefits of LBBAP in individuals with HFrEF and dyssynchrony should be further validated by randomized studies.

Impact of anemia treatment for left ventricular hypertrophy using long-acting erythropoietin-stimulating agents from the pre-dialysis to maintenance dialysis period in patients with chronic kidney disease, retrospective longitudinal cohort study.

BACKGROUND: Anemia in patients with chronic kidney disease (p-CKDs) may initiate or exacerbate left ventricular hypertrophy (LVH). This study aimed to determine whether treatment using long-acting erythropoietin-stimulating agents (L-ESAs) is independently associated with LVH during the pre-dialysis to maintenance dialysis period in p-CKDs. METHODS: Physical and laboratory examinations were performed 120 days before initiating dialysis in p-CKDs (baseline). To evaluate the left ventricular mass index (LVMI) after starting dialysis, the mean hemoglobin (Hb) was defined as the average at the start of dialysis and 6 months after starting dialysis. Changes in the LVMI were observed in three groups according to mean Hb levels (Hb < 10.1, 10.1 < Hb < 11.0, and Hb > 11.0 g/dL for Groups 1, 2, and 3, respectively). LVMI was evaluated using echocardiography at the pre-dialysis, initiation, and maintenance dialysis periods. RESULTS: A lower LVMI at dialysis initiation and an improvement in LVMI were detected in the highest tertile group of mean Hb (11.0 g/dl). Consequently, in the high Hb group (Hb level > 11.0 g/dl), LVMI remained low from dialysis initiation until after 6 months.The relationship between Hb and LVMI was not significant; however, a constant correlation with ß ≥ 0.4 in the absolute value was maintained. CONCLUSION: L-ESAs may correlate with Hb and LVMI after administration, independent of the baseline LVMI and Hb values. These findings have therapeutic implications in the treatment strategies for p-CKDs during the pre-dialysis to maintenance dialysis period.

Electrocardiographic prediction of left ventricular hypertrophy in women and men with left bundle branch block - Comparison of QRS duration, amplitude and voltage-time-integral.

BACKGROUND: Standard ECG criteria for left ventricular (LV) hypertrophy rely on QRS amplitudes. However, in the setting of left bundle branch block (LBBB), ECG correlates of LV hypertrophy are not well established. We sought to evaluate quantitative ECG predictors of LV hypertrophy in the presence of LBBB. METHODS: We included adult patients with typical LBBB having ECG and transthoracic echocardiogram performed within 3 months of each other in 2010-2020. Orthogonal X, Y, Z leads were reconstructed from digital 12­lead ECGs using Kors's matrix. In addition to QRS duration, we evaluated QRS amplitudes and voltage-time-integrals (VTIs) from all 12 leads, X, Y, Z leads and 3D (root-mean-squared) ECG. We used age, sex and BSA-adjusted linear regressions to predict echocardiographic LV calculations (mass, end-diastolic and end-systolic volumes, ejection fraction) from ECG, and separately generated ROC curves for predicting echocardiographic abnormalities. RESULTS: We included 413 patients (53% women, age 73 ± 12 years). All 4 echocardiographic LV calculations were most strongly correlated with QRS duration (all p < 0.00001). In women, QRS duration ≥ 150 ms had sensitivity/specificity 56.3%/64.4% for increased LV mass and 62.7%/67.8% for increased LV end-diastolic volume. In men, QRS duration ≥ 160 ms had a sensitivity/specificity 63.1%/72.1% for increased LV mass and 58.3%/74.5% for increased LV end-diastolic volume. QRS duration was best able to discriminate eccentric hypertrophy (area under ROC curve 0.701) and increased LV end-diastolic volume (0.681). CONCLUSIONS: In patients with LBBB, QRS duration (≥ 150 in women and ≥ 160 in men) is a superior predictor of LV remodeling esp. eccentric hypertrophy and dilation.

Streptozotocin-Induced Type 1 and 2 Diabetes Mellitus Mouse Models Show Different Functional, Cellular and Molecular Patterns of Diabetic Cardiomyopathy.

The main cause of morbidity and mortality in diabetes mellitus (DM) is cardiovascular complications. Diabetic cardiomyopathy (DCM) remains incompletely understood. Animal models have been crucial in exploring DCM pathophysiology while identifying potential therapeutic targets. Streptozotocin (STZ) has been widely used to produce experimental models of both type 1 and type 2 DM (T1DM and T2DM). Here, we compared these two models for their effects on cardiac structure, function and transcriptome. Different doses of STZ and diet chows were used to generate T1DM and T2DM in C57BL/6J mice. Normal euglycemic and nonobese sex- and age-matched mice served as controls (CTRL). Immunohistochemistry, RT-PCR and RNA-seq were employed to compare hearts from the three animal groups. STZ-induced T1DM and T2DM affected left ventricular function and myocardial performance differently. T1DM displayed exaggerated apoptotic cardiomyocyte (CM) death and reactive hypertrophy and fibrosis, along with increased cardiac oxidative stress, CM DNA damage and senescence, when compared to T2DM in mice. T1DM and T2DM affected the whole cardiac transcriptome differently. In conclusion, the STZ-induced T1DM and T2DM mouse models showed significant differences in cardiac remodeling, function and the whole transcriptome. These differences could be of key relevance when choosing an animal model to study specific features of DCM.