Adverse Left Ventricular Remodeling Research Articles

The kidney-skeletal muscle-heart axis in chronic kidney disease: implications for myokines.

Myokines are signalling moieties released by the skeletal muscle in response to acute and/or chronic exercise, which exert their beneficial or detrimental effects through paracrine and/or autocrine pathways on the own muscle and through endocrine pathways in many other organs (e.g. the heart). Interestingly, alterations in myokines have been described in patients with heart failure (HF) that are associated with adverse structural and functional left ventricular remodelling and poor cardiac outcomes. Recent experimental and clinical studies have shown that the muscle regulation of a number of myokines is altered in chronic kidney disease (CKD) thus representing a new molecular aspect of the pathophysiology of skeletal myopathy present in patients with CKD. Muscle dysregulation of myokines may contribute to a number of disorders in non-dialysis and dialysis patients with CKD, including the high risk of developing HF. This possibility would translate into a range of new diagnostic and therapeutic options. In fact, the measurement of circulating myokines opens their possible usefulness as biomarkers to personalize exercise training and pharmacological therapies for the prevetion and treatment of HF in patients with CKD and skeletal myopathy. This review will analyze information on some myokines that target the heart and are altered at the level of skeletal muscle and circulation in patients with CKD.

Prognostic Value of Resting Left Ventricular Sphericity Indexes in Coronary Artery Disease With Preserved Ejection Fraction.

Adverse left ventricular remodeling is a significant cardiovascular predictor for patients with coronary artery disease and preserved left ventricular ejection fraction (LVEF). However, the remodeling indexes reflecting left ventricular spherization by myocardial perfusion imaging are underexplored. 727 patients (mean age 59.8±13.5 years, 329 women) diagnosed or suspected coronary artery disease with preserved LVEF who underwent resting myocardial perfusion imaging were retrospectively enrolled. The myocardial perfusion imaging findings including the total perfusion deficit and sphericity indexes (shape index (SI) and eccentricity index (EI) obtained from gated (QGS) and non-gated (QPS) images) were collected. Major adverse cardiovascular events (MACE) were followed up for 45.1±22.0 months. All patients were divided into 4 subgroups based on total perfusion deficit at 10% and LVEF at 65%. Univariable comparative analyses were performed in 5 cohorts (all patients and 4 subgroups). Patients who experienced MACE displayed higher SI and/or lower EI (all P<0.05). Kaplan-Meier survival analyses suggested significant differences for SIQPS in all 5 cohorts, for EIQPS and EIQGS in 4 cohorts, and for end-systolic and end-diastolic SIQGS in 3 cohorts (allP<0.05). Multivariate Cox analysis showed that abnormal SI and EI remained statistically significant predictors for MACE after adjusting for total perfusion deficit, LVEF, and other confounding factors. For patients diagnosed or suspected of coronary artery disease with preserved or supra-normal LVEF, resting sphericity indexes by myocardial perfusion imaging displayed incremental long-term prognostic value. Among these indicators, SIQPS is particularly promising across different perfusion or preserved functional conditions.

Myocardial ischemia in patients with mild-to-moderate aortic stenosis: Interaction with cardiac remodeling and adverse events

BackgroundThe association between aortic valve stenosis (AVS) and myocardial perfusion abnormalities has been incompletely characterized. We sought to assess the predictors of myocardial ischemia in patients with mild-to-moderate AVS, and its relationship with long-term prognosis. MethodsEighty-nine patients with mild-to-moderate AVS (peak velocity between 2.6 and 4.0 m/second and aortic valve area > .6 cm2/m2), preserved left ventricular (LV) function, and either normal coronary arteries (28 patients) or non-obstructive coronary artery disease (<50% stenosis; 61 patients) were individuated. Myocardial perfusion imaging was performed using a cadmium–zinc–telluride camera, and the summed difference score (SDS) was computed. The presence of either LV hypertrophy (LVH) (LV mass index [LVMI] > 115 g/m2 [males] or 95 g/m2 [females]) or concentric LV remodeling (relative wall thickness: >.42) was determined at two-dimensional echocardiography. ResultsForty (45%) and 49 (55%) patients had mild and moderate AVS, respectively. Fifty (56%), 17 (19%), and 22 (25%) patients had normal LV geometry, concentric LV remodeling, and LVH, respectively. An interaction between LV remodeling and inducible ischemia was revealed with progressively higher values of SDS in patients with normal LV geometry (3 ± 3), concentric remodeling (4 ± 2), and LVH (7 ± 2) (P < .001).Accordingly, a moderate correlation existed between LVMI and SDS values (R: .67; P < .001). After a median follow-up of 84 ± 47 months, 27 adverse events were recorded, including 19 AV replacements and 8 deaths. On multivariable analysis, the presence of LVH (hazard ratio [HR]: 6.46; 95% confidence interval [CI]: 2.09–20.00; P = .001) and a higher SDS (HR: 1.41; 95% CI: 1.15–1.75; P = .001) were the two independent predictors of AE. ConclusionsIn patients with mild-to-moderate AVS, myocardial ischemia correlates with the severity of adverse LV remodeling. Patients with LVH and ischemia are at increased risk of AE.

The Pathobiology of Myocardial Recovery and Remission: From Animal Models to Clinical Observations in Heart Failure Patients.

Heart failure with reduced left ventricular (LV) ejection fraction (HFrEF) is a morbid and life-threatening disease, arising secondary to abnormalities of cardiac structure and function that lead to adverse LV remodeling. Implementation of medical and device therapies results in significant improvements in patient outcomes that are associated with reverse LV remodeling and improved LV ejection fraction. This review provides an overview of the pathobiology of reverse LV remodeling in animal models and in HFrEF patients. We emphasize the differences between myocardial recovery and remission as well as the fragile nature of maintaining a state of myocardial remission.

Cardiovascular magnetic resonance reveals myocardial involvement in patients with active stage of inflammatory bowel disease.

Active inflammatory bowel disease (A-IBD) but not remission (R-IBD) has been associated with an increased risk of cardiovascular death and hospitalization for heart failure. Using cardiovascular magnetic resonance (CMR), this study aims to assess adverse myocardial remodeling in patients with IBD in correlation with disease activity. Forty-four IBD patients without cardiovascular disease (24 female, median-age: 39.5years, 26 A-IBD, 18 R-IBD) and 44 matched healthy volunteers (HV) were prospectively enrolled. The disease stage was determined by endoscopic and patient-reported criteria. Participants underwent CMR for cardiac phenotyping: cine imaging and strain analysis were performed to assess ventricular function. T1 mapping, extracellular volume and late-gadolinium enhanced images were obtained to assess focal and diffuse myocardial fibrosis. Simultaneous T1 and T2 elevation (T1 > 1049.3ms, T2 > 54ms) was considered to indicate a myocardial segment was inflamed. 16/44 (16.4%) IBD patients described dyspnea on exertion and 10/44 (22.7%) reported chest pain. A-IBD patients showed impaired ventricular function, indicated by reduced global circumferential and radial strain despite preserved left-ventricular ejection fraction. 16% of all IBD patients had focal fibrosis in a non-ischemic pattern. A-IDB patients had increased markers of diffuse left ventricular fibrosis (T1-values: A-IBD: 1022.0 ± 34.83ms, R-IBD: 1010.10 ± 32.88ms, HV: 990.61 ± 29.35ms, p < .01). Significantly more participants with A-IDB (8/26, 30.8%) had at least one inflamed myocardial segment than patients in remission (0/18) and HV (1/44, 2.3%, p < .01). Markers of diffuse fibrosis correlated with disease activity. This study, using CMR, provides evidence of myocardial involvement and patterns of adverse left ventricular remodeling in patients with IBD. ISRCTN30941346.

Abstract Tu075: Cardiac macrophages expressing CD206 and IL-4Ra are required for adverse LV remodeling in HF

Cardiac macrophages significantly expand in chronic heart failure (HF). We tested the hypothesis that CD206 + macrophages expressing interleukin (IL)-4Ra in the failing heart are key drivers of left ventricular (LV) remodeling and ischemic cardiomyopathy. Cardiac macrophages were profiled using flow cytometry in adult male C57BL/6 (WT) mice following non-reperfused myocardial infarction (MI) to induce HF or sham operation. CD206 + macrophages progressively expanded in post-MI hearts during the progression of LV remodeling and comprised ~85% of macrophages at 8 w. These macrophages were exclusively proliferative and predominantly C-C motif chemokine receptor (CCR2) – and major histocompatibility complex (MHC)II hi in failing hearts, with the majority (92%) of CD206 + CCR2 – macrophages expressing LYVE-1, an embryonically-derived resident macrophage marker. Nearly half of cardiac CD206 + macrophages expressed IL-4Ra; the abundance of CD206 + IL-4Ra + directly correlated with LV dysfunction and fibrosis. Intramyocardial adoptive transfer of IL-4-polarized bone marrow derived CD206 + macrophages induced progressive LV dilation, dysfunction and fibrosis over 4 w in naïve recipient mice. To evaluate the role of CD206 + IL-4Ra + macrophages in LV remodeling, we used male and female LysM CreERT2 ;IL-4Ra F/F mice that allow for inducible myeloid-specific IL-4Ra gene deletion. Administration of tamoxifen from at 4 to 10 w post-MI (in established HF), effectively deleted IL-4Ra in cardiac macrophages and significantly reduced CD206 + macrophage abundance and proliferation in the remodeling heart. Myeloid-specific IL-4Ra deletion further prevented LV remodeling progression, improved fibrosis and neovascularization, and alleviated LV systolic dysfunction, while suppressing expansion of cardiac immune cells and blood Ly6C high monocytosis. We conclude that an expanded and proliferative population of CD206 + IL-4Ra + macrophages primarily derived from resident macrophages are key mediators of pathological LV remodeling and fibrosis. Inhibition of CD206 + macrophage IL-4Ra signaling may be a fruitful therapeutic approach to alleviate disease progression in HF.

Adulthood adiposity affects cardiac structure and function in later life.

Excess adiposity is associated with poorer cardiac function and adverse left ventricular (LV) remodelling. However, its importance over the adult life course on future cardiac structure and systolic and diastolic function is unknown. A total of 1690 participants in the National Survey of Health and Development birth cohort underwent repeated adiposity [body mass index (BMI)/waist-to-hip ratio (WHR)] measurements over adulthood and investigation, including echocardiography at age 60-64 years. The relationship between LV structure [LV mass (LVM), relative wall thickness, and LV internal diameter in diastole (LVIDd)] and function (diastolic: E/e', e', and left atrial volume indexed to body surface area; systolic: ejection fraction, S', and myocardial contraction fraction) was investigated using multivariable linear regression models. Increased BMI from age 20 years onwards was associated with greater LVM and LVIDd independent of confounders. Associations remained independent of current BMI for LVIDd and at age 26, 43, and 53 years for LVM. Increased BMI from 43 years onwards was associated with greater relative wall thickness, but not when BMI at age 60-64 years was accounted for. Increased BMI at age 26, 36, and 53 years and at 20 years onwards was associated with lower ejection fraction and myocardial contraction fraction, respectively, but not independently of BMI at 60-64 years. Higher BMI from 20 years onwards was associated with poorer diastolic function independent of confounders. Associations between BMI and left atrial volume indexed to body surface area persisted from 26 years onwards after adjustment for BMI at 60-64 years. Similar relationships were observed for WHR from age 43 years onwards. Higher adiposity (BMI/WHR) over adulthood is associated with evidence of adverse cardiac structure and function. Some of these associations are independent of adiposity in later life.

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

BackgroundDespite 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. MethodsA 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. ResultsAMI 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). Conclusions99mTc-HFAPi SPECT imaging holds promise in predicting LV remodeling post-MI, providing valuable insights for patient management and prognosis.

Simultaneous Positron Emission Tomography and Molecular Magnetic Resonance Imaging of Cardiopulmonary Fibrosis in a Mouse Model of Left Ventricular Dysfunction.

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. 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<0.0001) and Δlung-to-muscle ratio (P<0.0001). Hydroxyproline in the heart (P<0.0001) and lungs (P<0.01) were elevated in TAC mice, which corresponded to an increase in heart (myocardium-to-muscle ratio, P=0.02) and lung (lung-to-muscle ratio, P<0.001) PET measurements. Pressure-volume loop and echocardiography demonstrated adverse left ventricular remodeling, function, and increased right ventricular systolic pressure in TAC mice. Administration of collagen-targeted PET and allysine-targeted MR probes led to elevated PET-magnetic resonance imaging signals in the myocardium and lungs of TAC mice. The study demonstrates the potential to detect fibrosis and fibrogenesis in cardiopulmonary disease through a dual molecular PET-magnetic resonance imaging protocol.

Myocardial transcriptomic analysis of diabetic patients with aortic stenosis: key role for mitochondrial calcium signaling

BackgroundType 2 diabetes (T2D) is a frequent comorbidity encountered in patients with severe aortic stenosis (AS), leading to an adverse left ventricular (LV) remodeling and dysfunction. Metabolic alterations have been suggested as contributors of the deleterious effect of T2D on LV remodeling and function in patients with severe AS, but so far, the underlying mechanisms remain unclear. Mitochondria play a central role in the regulation of cardiac energy metabolism.ObjectivesWe aimed to explore the mitochondrial alterations associated with the deleterious effect of T2D on LV remodeling and function in patients with AS, preserved ejection fraction, and no additional heart disease.MethodsWe combined an in-depth clinical, biological and echocardiography phenotype of patients with severe AS, with (n = 34) or without (n = 50) T2D, referred for a valve replacement, with transcriptomic and histological analyses of an intra-operative myocardial LV biopsy.ResultsT2D patients had similar AS severity but displayed worse cardiac remodeling, systolic and diastolic function than non-diabetics. RNAseq analysis identified 1029 significantly differentially expressed genes. Functional enrichment analysis revealed several T2D-specific upregulated pathways despite comorbidity adjustment, gathering regulation of inflammation, extracellular matrix organization, endothelial function/angiogenesis, and adaptation to cardiac hypertrophy. Downregulated gene sets independently associated with T2D were related to mitochondrial respiratory chain organization/function and mitochondrial organization. Generation of causal networks suggested a reduced Ca2+ signaling up to the mitochondria, with the measured gene remodeling of the mitochondrial Ca2+ uniporter in favor of enhanced uptake. Histological analyses supported a greater cardiomyocyte hypertrophy and a decreased proximity between the mitochondrial VDAC porin and the reticular IP3-receptor in T2D.ConclusionsOur data support a crucial role for mitochondrial Ca2+ signaling in T2D-induced cardiac dysfunction in severe AS patients, from a structural reticulum-mitochondria Ca2+ uncoupling to a mitochondrial gene remodeling. Thus, our findings open a new therapeutic avenue to be tested in animal models and further human cardiac biopsies in order to propose new treatments for T2D patients suffering from AS.Trial registrationURL: https://www.clinicaltrials.gov; Unique Identifier: NCT01862237.Graphical abstract

Transcriptional regulation of macrophage inflammation in the heart failure with preserved ejection fraction

Abstract Funding Acknowledgements None. Introduction Heart failure with preserved ejection fraction (HFpEF) is a global public health problem with no effective treatment available. Pro-inflammatory cardiac macrophages are emerging as key determinants of adverse left ventricular remodeling; however, their role in HFpEF remains poorly understood. Mechanistically, the recruitment and activation of macrophages represent a key event in maladaptive myocardial remodeling in HFpEF patients. Evidence suggests that remodeling processes in HFpEF hearts are orchestrated and amplified by cardiac macrophages which regulate cardiomyocyte function, endothelial cell activation and fibroblast differentiation. Here we sought to determine the role of macrophage inflammation in experimental and human HFpEF. Methods Experiments were performed in rat cardiomyocytes (H9c2), human endothelial cells (HAECS), transgenic mice, and left ventricular (LV) myocardial samples from patients with HFpEF. H9c2 and HAECS treated with pro-inflammatory macrophage-like cells (RAW 264.7) conditional media in the presence or knockdown of a top-ranking activator of M1 type macrophages such as nuclear receptor corepressor 1 (NCOR1), were used to elucidate better the involvement of this gene in transcriptional regulation in vitro. The cardiac function of myeloid cell-specific NCOR1 knockout HFpEF mice undergoing a high-fat diet and L-NAME was investigated. LV myocardial samples were used to evaluate the pro-inflammatory activity of macrophages in human HFpEF tissues. Results Human and murine LV specimens showed upregulation of vascular adhesion molecules (ICAM1, ICAM2, E-selectin), recruitment of M1 macrophages to the myocardium, and decreased M2 macrophages. Notably, NCOR1 deletion in macrophages protected against diastolic dysfunction, exercise intolerance, and myocardial inflammation (TNF-a, IL6, IL-1b). Mechanistically, induction of metabolic stress by palmitic acid induced macrophage polarization, upregulation of NCOR1 and inflammatory genes in RAW cells. By contrast, Finally, NCOR1 depletion prevented pro-inflammatory transcriptional programs and secretion of TNF-a, IL6 and IL-1b in the macrophage secretome. Conclusion Targeting macrophage NCOR1 could represent a promising approach to blunt myocardial inflammation in HFpEF.

Effects of the Low-Dose Colchicine Regimen on Left Ventricular Adverse Remodeling and Systolic Function in Acute Myocardial Infarction Patients with Anterior ST-Segment Elevation Undergoing Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial

Background: Inflammation in reperfusion injury results in adverse ventricular remodeling and reduced systolic function. The anti-inflammatory effects of colchicine have shown beneficial effects in cardiovascular disease. Objective: To determine the effects of low-dose colchicine on left ventricular (LV) adverse remodeling and systolic function in acute myocardial infarction with anterior ST-segment elevation (anterior STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). Material and Methods: This prospective, randomized, double-blinded study randomly assigned anterior STEMI patients who underwent PPCI to receive either low-dose colchicine (1mg loading dose followed by 0.5mg daily) or a matching placebo for 30 days in addition to standard therapy. Outcomes included adverse LV remodeling and systolic function, determined by transthoracic echocardiography (TTE) in the first and third month. Result: Enrollment comprised 196 patients, with 92 patients in the colchicine group and 104 patients in the placebo group. Adverse LV remodeling and a decrease in systolic function were observed in both groups. No significant differences in LV remodeling were observed between the colchicine and placebo groups, as indicated by the change in LV end-systolic volume index (LVESVI) at the first month (16.5% vs. 18.25% [p=0.091]) and third month (19.5% vs. 21.5% [p=0.124]). Similar results were found in LV systolic function between the colchicine and placebo groups, with a reduction in LV ejection fraction (LVEF) observed in the first month (6.3% vs. 8.95% [p=0.083]) and third month (9.5% vs. 11.5% [p=0.163]). Diarrhea was the only reported side effect, occurring in 6.5% of patients in the colchicine group. Conclusion: Low-dose colchicine administration in anterior STEMI patients undergoing PPCI did not reduce LV adverse remodeling or systolic function. Keyword: Adverse Remodeling, Colchicine, Reperfusion Injury, STEMI, Systolic Function.

Long-Term Protective Effects of Succinate Dehydrogenase Inhibition during Reperfusion with Malonate on Post-Infarction Left Ventricular Scar and Remodeling in Mice.

Succinate dehydrogenase inhibition with malonate during initial reperfusion reduces myocardial infarct size in both isolated mouse hearts subjected to global ischemia and in in situ pig hearts subjected to transient coronary ligature. However, the long-term effects of acute malonate treatment are unknown. Here, we investigated whether the protective effects of succinate dehydrogenase inhibition extend to a reduction in scar size and adverse left ventricular remodeling 28 days after myocardial infarction. Initially, ten wild-type mice were subjected to 45 min of left anterior descending coronary artery (LAD) occlusion, followed by 24 h of reperfusion, and were infused during the first 15 min of reperfusion with saline with or without disodium malonate (10 mg/kg/min, 120 μL/kg/min). Malonate-treated mice depicted a significant reduction in infarct size (15.47 ± 3.40% of area at risk vs. 29.34 ± 4.44% in control animals, p < 0.05), assessed using triphenyltetrazolium chloride. Additional animals were then subjected to a 45 min LAD ligature, followed by 28 days of reperfusion. Treatment with a single dose of malonate during the first 15 min of reperfusion induced a significant reduction in scar area, measured using Picrosirius Red staining (11.94 ± 1.70% of left ventricular area (n = 5) vs. 23.25 ± 2.67% (n = 9), p < 0.05), an effect associated with improved ejection fraction 28 days after infarction, as determined using echocardiography, and an attenuated enhancement in expression of the pro-inflammatory and fibrotic markers NF-κB and Smad2/3 in remote myocardium. In conclusion, a reversible inhibition of succinate dehydrogenase with a single dose of malonate at the onset of reperfusion has long-term protective effects in mice subjected to transient coronary occlusion.

Left ventricular shape index and eccentricity index with ECG-gated Nitrogen-13 ammonia PET/CT in patients with myocardial infarction, ischemia, and normal perfusion

BackgroundLV geometry with shape index (SI) and eccentricity index (EI) measured by myocardial perfusion positron emission tomography/computed tomography (PET/CT) may allow the evaluation of left ventricular (LV) adverse remodeling. This first study aims to explore the relationship of SI and EI values acquired by Nitrogen-13 ammonia PET/CT in patients with normal perfusion, ischemia, and myocardial infarction. And evaluate the correlations between the variables of LV geometry, and with the variables of LV function. Methods and resultsOne hundred and forty patients who underwent an electrocardiogram (ECG)-gated PET/CT were selected and classified into 4 groups according to ischemia or infarction burden (normal perfusion, mild ischemia, moderate-severe ischemia, and infarction). The variables were automatically retrieved using dedicated software (QPS/QGS; Cedars-Sinai, Los Angeles, CA, USA). On multicomparison analysis (one-way ANOVA and Dunnett's Test), subjects in the infarction group had significant higher values of SI end-diastolic rest (P < 0.001), and stress (P = 0.003), SI end-systolic rest (P = 0.002) and stress (P < 0.001) as well as statistically significant lower values of EI rest (P < 0.001) and stress (P < 0.001) when compared with all other groups. Regarding Pearson correlation, in the infarcted group all the variables of SI and EI were significantly correlated (P < 0.001) with strong correlation coefficients (>0.60). SI end-systolic correlated significantly with the variables of LV function independently of the group of patients (P < 0.05). ConclusionsShape and eccentricity indices differ in patients with myocardial infarction as compared to patients with ischemia or normal perfusion. This encourage further research in their potential for detecting LV adverse remodeling.

Differential associations between abnormal cardiac left ventricular geometry types and cerebral white matter disease

ObjectivesReduced cardiac outflow due to left ventricular hypertrophy has been suggested as a potential risk factor for development of cerebral white matter disease. Our study aimed to examine the correlation between left ventricular geometry and white matter disease volume to establish a clearer understanding of their relationship, as it is currently not well-established. MethodsConsecutive patients from 2016 to 2021 who were ≥18 years and underwent echocardiography, cardiac MRI, and brain MRI within one year were included. Four categories of left ventricular geometry were defined based on left ventricular mass index and relative wall thickness on echocardiography. White matter disease volume was quantified using an automated algorithm applied to axial T2 FLAIR images and compared across left ventricular geometry categories. ResultsWe identified 112 patients of which 34.8 % had normal left ventricular geometry, 20.5 % had eccentric hypertrophy, 21.4 % had concentric remodeling, and 23.2 % had concentric hypertrophy. White matter disease volume was highest in patients with concentric hypertrophy and concentric remodeling, compared to eccentric hypertrophy and normal morphology with a trend-P value of 0.028. Patients with higher relative wall thickness had higher white matter disease volume (10.73 ± 10.29 cc vs 5.89 ± 6.46 cc, P = 0.003), compared to those with normal relative wall thickness. ConclusionOur results showed that abnormal left ventricular geometry is associated with higher white matter disease burden, particularly among those with abnormal relative wall thickness. Future studies are needed to explore causative relationships and potential therapeutic options that may mediate the adverse left ventricular remodeling and its effect in slowing white matter disease progression.

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

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). 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. 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). The extent of infarct mass, peak radial diastolic strain rate, and RAAS inhibitor are independent predictors of adverse LV remodeling following STEMI.

Do False Tendons Prevent Adverse Left Ventricular Remodeling After Anterior Wall Myocardial Infarction? An Echocardiographic Strain Imaging Study

The role of muscular left ventricular (LV) false tendons (FTs) is poorly understood. To gain insight into their pathophysiologic significance, we adapted echocardiographic LV strain imaging software to measure LVFT longitudinal strain in subjects with normal left ventricles and in patients who sustained previous anterior wall myocardial infarction (AWMI). GE EchoPAC software was used to measure longitudinal strain in LVFTs ≥0.3 cm in diameter. Tendinous strain was measured in 11 patients with LVFTs confined to the left anterior descending artery territory (connecting the anteroseptum or anterior wall to the apex) ≥6 months after AWMI (myocardial infarction [MI]+FT+ group) and in 25 patients with normal hearts containing LVFTs (MI-FT+ group). We also compared the indexed LV end-diastolic volumes in the MI+FT+ group to that of 25 patients with previous AWMI without LVFTs (MI+FT- group). The mean LVFT strain in MI+FT+ group was 5.5 ± 6.2% and -28.9 ± 4.7% in the MI-FT+ group (p <0.0001). The indexed LV end-diastolic volume in the MI+FT+ group did not differ from the MI+FT- group (88.4 ± 17.8 vs 87.9 ± 17 ml/m2, p = 0.90). In conclusion, the negative strain (contraction) developed by LVFTs in the MI-FT+ group may help maintain normal LV size and shape by generating inward restraining forces. The development of positive strain (stretch) in LVFTs in patients in the MI+FT+ group suggests they become infarcted after AWMI. This implies that they are incapable of generating inward restraining forces that might otherwise mitigate adverse remodeling. Of note, LV volumes after AWMI do not differ whether or not LVFTs are present.

Mast Cells in Cardiac Remodeling: Focus on the Right Ventricle.

In response to various stressors, cardiac chambers undergo structural remodeling. Long-term exposure of the right ventricle (RV) to pressure or volume overload leads to its maladaptive remodeling, associated with RV failure and increased mortality. While left ventricular adverse remodeling is well understood and therapeutic options are available or emerging, RV remodeling remains underexplored, and no specific therapies are currently available. Accumulating evidence implicates the role of mast cells in RV remodeling. Mast cells produce and release numerous inflammatory mediators, growth factors and proteases that can adversely affect cardiac cells, thus contributing to cardiac remodeling. Recent experimental findings suggest that mast cells might represent a potential therapeutic target. This review examines the role of mast cells in cardiac remodeling, with a specific focus on RV remodeling, and explores the potential efficacy of therapeutic interventions targeting mast cells to mitigate adverse RV remodeling.

Patterns of left ventricular remodeling post-myocardial infarction, determinants, and outcome.

Left ventricular remodeling (LVR) after myocardial infarction (MI) can lead to heart failure, arrhythmia, and death. We aim to describe adverse LVR patterns at 6 months post-MI and their relationships with subsequent outcomes and to determine baseline. A multicenter cohort of 410 patients (median age 57 years, 87% male) with reperfused MI and at least 3 akinetic LV segments on admission was analyzed. All patients had transthoracic echocardiography performed 4 days and 6 months post-MI, and 214 also had cardiac magnetic resonance imaging performed on day 4. To predict LVR, machine learning methods were employed in order to handle many variables, some of which may have complex interactions. Six months post-MI, echocardiographic increases in LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF) were 14.1% [interquartile range 0.0, 32.0], 5.0% [- 14.0, 25.8], and 8.7% [0.0, 19.4], respectively. At 6 months, ≥ 15% or 20% increases in LVEDV were observed in 49% and 42% of patients, respectively, and 37% had an LVEF < 50%. The rate of death or new-onset HF at the end of 5-year follow-up was 8.8%. Baseline variables associated with adverse LVR were determined best by random forest analysis and included stroke volume, stroke work, necrosis size, LVEDV, LVEF, and LV afterload, the latter assessed by Ea or Ea/Ees. In contrast, baseline clinical and biological characteristics were poorly predictive of LVR. After adjustment for predictive baseline variables, LV dilation > 20% and 6-month LVEF < 50% were significantly associated with the risk of death and/or heart failure: hazard ratio (HR) 2.12 (95% confidence interval (CI) 1.05-4.43; p = 0.04) and HR 2.68 (95% CI 1.20-6.00; p = 0.016) respectively. Despite early reperfusion and cardioprotective therapy, adverse LVR remains frequent after acute MI and is associated with a risk of death and HF. A machine learning approach identified and prioritized early variables that are associated with adverse LVR and which were mainly hemodynamic, combining LV volumes, estimates of systolic function, and afterload.

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

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. 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. 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). 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.