Development Of Adverse Left Ventricular Remodeling Research Articles

Practical use of the markers for prediction of adverse left ventricular remodeling after acute ST segment elevation myocardial infarction

Objective — to determine the most important markers for predicting of the development of prediction of adverse left ventricular (LV) remodeling in patients within 1 year after acute ST‑segment elevation myocardial infarction (STEMI).
 Materials and methods. The study involved 134 patients with acute STEMI, 95 (70.9 %) men and 39 (29.1 %) women, who satisfied inclusion criteria and had no exclusion criteria. All of them were hospitalized in the emergency department of L.T. Mala National Therapy Institute of NAMS of Ukraine from January 2018 to February 2021. All patients underwent myocardial revascularization by percutaneous coronary intervention (PCI) within 2 — 12 hours after the event in the V. T. Zaytsev Institute of General and Emergency Surgery. TIMI — 3 flow was restored in all 134 patients. Within 1 — 3 days after revascularization patients were transferred to the research center.
 Late adverse LV remodeling was defined as elevated LV end diastolic volume (LVEDV) > 10 % and/or LV end systolic volume (LVESV) > 10 % within 1 year after the index event. Serum soluble tumor suppressor‑2 (sST2) levels were determined by enzyme‑linked immunosorbent assay (Presage ST2 Assay, Critical Diagnostics, USA), N‑Terminal Pro‑Brain Natriuretic Peptide (NT‑proBNP) was detected by R&D Systems GmbH, Wiesbaden‑Nordenstadt, Germany), macrophage inhibitory factor (MIF) in blood serum serum was determined by enzyme‑linked immunosorbent assay RayBio®Human MIF ELISA KIT, USA). Statistical analysis was performed using Statistica 8.0 (Stat Soft Inc, USA).
 Results. Patients were divided into two groups: group 1 included 48 patients with adverse LV remodeling and group 2 consisted of 86 patients without LV remodeling. Uni‑ and multivariate log‑regression analysis demonstrated that LV ejection fraction (EF), MIF, number of damaged coronary vessels, sST2, longitudinal strain were independent predictors of adverse LV remodeling. Analysis of ROC curves showed that the cumulative value of markers such as MIF, ST2, longitudinal strain, number of damaged vessels, LV ejection fraction (AUC = 0.718; p < 0.0001, 95 %, CI 0.634 — 0.792) allows to identify patients with high risk of the development of adverse LV remodeling in patients within 1 year after acute STEMI. The formula with these markers was found out, that can be used to predict adverse LV remodeling: the prognosis of positive effect at Y ≥ 0.5, negative — at Y < 0.5.
 Conclusions. The study results demonstrated that LV ejection fraction, MIF, number of damaged coronary arteries, sST2, and global longitudinal strain can be used as predictors of adverse LV remodeling.

Oncostatin M is associated with adverse left ventricular remodeling in patients with ST-segment elevation myocardial infarction

Abstract Introduction The development of adverse left ventricular remodeling (LVR) after myocardial infarction (MI) remains a significant problem despite current achievements in invasive and pharmacological treatment. A large number of biomarkers are known that reflect various processes and pathophysiological mechanisms of the pathogenesis of MI and the development of adverse cardiovascular events in the post-infarction period. Oncostatin M (OSM) is a cytokine of the interleukin-6 family that is involved in the pathophysiology of cardiovascular diseases and takes part in processes of inflammation, tissue regeneration, cell development and growth. Purpose To assess the dynamics of serum levels of OSM and its association with the development of adverse left ventricular remodeling in the long-term post-infarction period in patients with acute primary myocardial infarction with ST-segment elevation (STEMI). Methods Subjects were 21 patients (59.2±8.1 y.o.) with STEMI, who underwent percutaneous coronary intervention during the first 24 h of the onset of MI. The serum level of OSM and echocardiography with 2D speckle tracking imaging were assessed at days 1 and 6 months after STEMI. The criterion of adverse LVR is an increased of end-diastolic (EDV) or/and end-systolic (ESV) volume more than 20% from admission to 6 month period. Results A significant increase of the serum levels of OSM during the first 24 hours of MI was detected [46.9 (18.9; 75.7)] pg/ml. A decrease of the OSM levels in 6 months after STEMI was revealed [13.1 (6.9; 19.6)] pg/ml (p<0.0005). Correlation analysis showed strong positive association between the values of OSM with Troponin I (R=0.797 p=0.0001) and Nt-proBNP (R=0,713 p=0.0013). The relationship between OSM and Troponin I persisted in the long-term post-infarction period (R=0.751, p=0.0005). An inverse correlation between the OSM, measured at admission to hospital and the left ventricular ejection fraction at day 7 after MI was found (R=−0.63, p=0.023). Logistic regression analysis showed that the values of OSM at day 1 of the MI were associated with development of adverse LVR in the long term after STEMI. OSM level of more than 18.4 pg/ml at a time of admission was associated with the increased of ESV in 6 months after STEMI by more than 20% (p<0.05). Conclusions Our study showed the serum levels of OSM statistically significantly decreased in 6 months after STEMI. The content of OSM was positive associated with Troponin I and Nt-proBNP. Elevated levels of OSM were associated with an increase of ESV in 6 months after STEMI. The serum levels of OSM can be used to predict of adverse remodeling in patients undergoing STEMI. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Science

Diffusion tensor cardiovascular magnetic resonance predicts adverse remodelling after myocardial infarction

Abstract Background Changes in myocardial microstructure that underlie post-myocardial infarction (MI) left ventricular (LV) remodelling may contribute to progressive deterioration in cardiac function and increased risk of adverse clinical events. Diffusion Tensor Cardiovascular Magnetic Resonance (DT-CMR) derived parameters provide in vivo measures of helix angle (HA) and sheetlet angle (SA), which allow non-invasive characterization of microstructural dynamics associated with cardiac contraction. Purpose To evaluate the relationship between DT-CMR metrics of myocardial microstructure with the development of adverse LV remodelling and to determine the relationship between DT-CMR and strain post- MI. Methods We performed a longitudinal pre-clinical CMR study whereby DT-CMR, cine imaging and strain were acquired pre-MI and 3 days and 16 weeks post- MI in a pig model. HA (E1A), SA (E2A), and sheetlet angle mobility (ΔE2A = E2Asystole– E2Adiastole), as well as circumferential (Ecc) and radial (Err) strain were calculated at each timepoint and related to change in left ventricular end-diastolic volume (ΔLVEDV) and change in left ventricular end-systolic volume (ΔLVESV) between 3 days post-MI and 16 weeks post-MI. The translational value of this preclinical study was further assessed in six patients with chronic MI. Results ΔE2A over the whole LV (global ΔE2A) at 3 days post-MI correlated significantly with ΔLVEDV (R2=0.89, p=0.0013, Fig.1A;) and ΔLVESV (R2=0.81, p=0.0055, Fig.1B). Global Ecc at 3 days post-MI also correlated with both ΔLVEDV (R2=0.75, p=0.012, Fig.1C) and ΔLVESV (R2=0.71, p=0.018, Fig.1D). Global Err at 3 days post-MI did not show significant correlation with either ΔLVEDV (R2=0.32, p=0.19, Fig.1E) or ΔLVESV (R2=0.35, p=0.17, Fig.1F). Global ΔE2A correlated strongly with global Ecc 3 days post-MI (R2=0.9, p=0.00099, Fig.1G) but less strongly with global Err 3 days post-MI (R2=0.57, p=0.049, Fig.1H). Global ΔE2A at the chronic stage correlated significantly with ejection Fraction (EF), in both clinical (R2=0.87, p=0.007) and preclinical data (R2=0.87, p=0.0024). Global ΔE2A correlated well with LVEDV (clinical: R2=0.72, p=0.033; preclinical: R2=0.8, p=0.0066) and LVESV (clinical: R2=0.78, p=0.020; preclinical: R2=0.89, p=0.0013). In vivo E1A maps at 16 weeks post-MI and ex vivo DT-CMR demonstrated reduced right-handed helix angles in the endocardium of the infarct region. Conclusion ΔE2A measured at 3 day post-reperfused MI is strongly correlated with the development of increased end-systolic and end-diastolic volumes, and may therefore serve as a novel CMR early predictor of adverse LV remodelling after reperfused MI. Strong correlations between ΔE2A, LV volumes and EF in a small cohort of stable patients with remodelled hearts after chronic MI confirm the feasibility of performing these measurements in patients and the plausibility of further evaluation of ΔE2A as a predictor of adverse remodelling after reperfused MI. Sheetlet mobility predicts volume change Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Institutes of Health by the Division of Intramural Research (NHLBI, NIH, DHHS); British Heart Foundation

Serum Levels of Bone Morphogenetic Proteins 2 and 4 in Patients with Acute Myocardial Infarction.

Background: Bone morphogenetic proteins-2 and -4 (BMPs) have been implicated in left ventricular remodeling (LVR) processes such as an inflammation and fibrogenesis. We hypothesized that this knowledge could be translated into clinics. Methods: We studied the dynamics of serum levels of BMPs, its correlation with markers of LVR and with parameters of echocardiography in patients (n = 31) during the six-month follow-up period after myocardial infarction (MI). Results: Elevated serum levels of BMPs decreased by the six-month follow-up period. BMP-2 decreased from the first day after MI, and BMP-4 decreased from the Day 14. The elevated level of BMP-2 at Day 1 was associated with a lower level of troponin I, reperfusion time and better left ventricular ejection fraction (LV EF) at the six-month follow-up. Elevated serum level of BMP-4 at Day 1 was associated with a lower level of a soluble isoform of suppression of tumorigenicity 2 (sST2), age and reperfusion time. An elevated level of BMP-2 at the six-month follow-up was associated with higher levels of BMP-4, high-sensitivity C-reactive protein (hCRP) and sST2. High serum level of BMP-2 correlated with high levels of hCRP and matrix metalloproteinase (MMP)-9 on Day 7. High serum level of BMP-4 correlated with low levels of hCRP, MMP-9 at Day 3, sST2 at Day 1 and with decreased LV EF on Day 7. The findings of multivariate analysis support the involvement of BMP-2 in the development of post-infarction LVR. Conclusions: Our research translates experimental data about the BMPs in the development of adverse LVR into the clinic. Elevated serum levels of BMPs decreased by the end of the six-month period after MI. BMP-2 decreased from the first day and BMP-4 decreased from Day 14. BMP-2 and BMP-4 were associated with the development of LVR. Their correlations with markers of inflammation, degradation of the extracellular matrix, hemodynamic stress and markers of myocardial damage further support our hypothesis. Diagnostic and predictive values of these BMPs at the development of post-infarction LVR in vivo should be investigated further.

Serum Soluble ST2 and Adverse Left Ventricular Remodeling in Patients With ST-Segment Elevation Myocardial Infarction.

Objective:To assess the dynamics of serum levels of soluble isoform of suppression of tumorigenicity 2 (sST2) and N-terminal pro-brain natriuretic peptide (NT-proBNP) and their correlations with the development of adverse left ventricular remodeling (LVR) through 6 months in patients with primary myocardial infarction with ST-segment elevation (STEMI).Methods:Subjects were 31 patients with STEMI (median age: 58 years), who underwent percutaneous coronary intervention (PCI) during the first 24 hours of the onset of myocardial infarction (MI). Blood samples and parameters of echocardiography were assessed at days 1, 3, 7, and 14 and 6 months after STEMI.Results:Serum levels of sST2 and NT-proBNP decreased during the 6-month period. Levels of sST2 decreased by 48% from admission to day 7, and levels of NT-proBNP decreased by 40% from day 7 to 6 months after STEMI. Serum levels of sST2 at day 1 (r = 0.5, P < .05) and day 3 (r = 0.4, P < .05) were associated with adverse LVR by 6 months after STEMI. Logistic regression analysis showed that a high concentration of sST2 at day 7 increased the risk of adverse LVR (95% confidence interval [CI], 0.5-0.9; areas under curve [AUC] = 0.8; P = .002), with 92% sensitivity and 70% specificity. A multivariate analysis model revealed that adverse LVR was associated with the level of sST2 (P = .003) and with complete revascularization (P = .01) at the admission.Conclusions:The dynamics of serum levels of sST2 and NT-proBNP were different. The level of sST2 normalized by the 7th day; NT-proBNP decreased only by the end of the 6-month period after MI. Increased serum levels of sST2 by the 7th day of MI were associated with the development of adverse LVR by the end of the 6-month period.

Failed Downregulation of Circulating MicroRNA-155 in the Early Phase after ST Elevation Myocardial Infarction Is Associated with Adverse Left Ventricular Remodeling

Background: MicroRNA are noncoding RNA that have a significant role in both inflammatory and cardiovascular diseases. Aims: We aimed to assess whether the inflammation-related microRNA-155 is associated with the development of adverse left ventricular (LV) remodeling following ST elevation myocardial infarction (STEMI). Methods: Peripheral blood samples were collected in the inflammatory (day 2), proliferative (day 5), and maturation phases (6 months) after STEMI (n = 20). Granulocytes, monocytes, and lymphocytes were enumerated with flow cytometry. The changes in LV volumes were assessed with 3-D echocardiography on day 1 and after 6 months. Adverse remodeling was defined as a >20% increase in end-diastolic volume. Healthy subjects were recruited as controls. Results: MicroRNA-155 measured on day 5 correlated positively with the relative change in end-diastolic volume (ρ = 0.490, p = 0.028). MicroRNA-155 (day 5) was significantly higher in patients with compared to patients without adverse LV remodeling. The expression level was similar in healthy subjects (n = 8) and in patients with LV remodeling. There was a positive correlation between microRNA-155 and the amount of monocytes (day 5, ρ = 0.463, p = 0.046). Conclusion: Impaired downregulation of microRNA-155 during the second phase of the post- STEMI inflammatory response is a determinant of the development of adverse LV remodeling.

Comparison of global myocardial strain assessed by cardiovascular magnetic resonance tagging and feature tracking to infarct size at predicting remodelling following STEMI

BackgroundTo determine if global strain parameters measured by cardiovascular magnetic resonance (CMR) acutely following ST-segment Elevation Myocardial Infarction (STEMI) predict adverse left ventricular (LV) remodelling independent of infarct size (IS).MethodsSixty-five patients with acute STEMI (mean age 60 ± 11 years) underwent CMR at 1–3 days post-reperfusion (baseline) and at 4 months. Global peak systolic circumferential strain (GCS), measured by tagging and Feature Tracking (FT), and global peak systolic longitudinal strain (GLS), measured by FT, were calculated at baseline, along with IS. On follow up scans, volumetric analysis was performed to determine the development of adverse remodelling – a composite score based on development of either end-diastolic volume index [EDVI] ≥20% or end-systolic volume index [ESVI] ≥15% at follow-up compared to baseline.ResultsThe magnitude of GCS was higher when measured using FT (−21.1 ± 6.3%) than with tagging (−12.1 ± 4.3; p < 0.001 for difference). There was good correlation of strain with baseline LVEF (r 0.64–to 0.71) and IS (ρ -0.62 to–0.72). Baseline strain parameters were unable to predict development of adverse LV remodelling. Only baseline IS predicted adverse remodelling – Odds Ratio 1.05 (95% CI 1.01–1.10, p = 0.03), area under the ROC curve 0.70 (95% CI 0.52–0.87, p = 0.04).ConclusionBaseline global strain by CMR does not predict the development of adverse LV remodelling following STEMI.

Global myocardial strain assessment by different imaging modalities to predict outcomes after ST-elevation myocardial infarction: A systematic review

To conduct a systematic review relating myocardial strain assessed by different imaging modalities for prognostication following ST-elevation myocardial infarction (STEMI). An online literature search was performed in PubMed and OVID(®) electronic databases to identify any studies that assessed global myocardial strain parameters using speckle-tracking echocardiography (STE) and/or cardiac magnetic resonance imaging (CMR) techniques [either myocardial tagging or feature tracking (FT) software] in an acute STEMI cohort (days 0-14 post-event) to predict prognosis [either development of major adverse cardiac events (MACE)] or adverse left ventricular (LV) remodelling at follow-up (≥ 6 mo for MACE, ≥ 3 mo for remodelling). Search was restricted to studies within the last 20 years. All studies that matched the pre-defined search criteria were reviewed and their results interpreted. Due to considerable heterogeneity between studies, meta-analysis was not performed. A total of seven studies (n = 7) were identified that matched the search criteria. All studies used STE to evaluate strain parameters - five (n = 5) assessed global longitudinal strain (GLS) (n = 5), one assessed GLS rate (GLS-R) (n = 1) and one assessed both (n = 1). Three studies showed that GLS independently predicted the development of adverse LV remodelling by multivariate analysis - odds ratio between 1.19 (CI: 1.04-1.37, P < 0.05) and 10 (CI: 6.7-14, P < 0.001) depending on the study. Four studies showed that GLS predicted the development of MACE - hazard ratio (HR) between 1.1 (CI: 1-1.1, P = 0.006) and 2.34 (1.10-4.97, P < 0.05). One paper found that GLS-R could significantly predict MACE - HR 18 (10-35, P < 0.001) - whilst another showed it did not. GLS < -10.85% had sensitivity/specificity of 89.7%/91% respectively for predicting the development of remodelling whilst GLS < -13% could predict the development of MACE with sensitivity/specificity of 100%/89% respectively. No suitable studies were identified that assessed global strain by CMR tagging or FT techniques. GLS measured acutely post-STEMI by STE is a predictor of poor prognosis. Further research is needed to show that this is true for CMR-based techniques.

Echocardiographic Speckle-Tracking Based Strain Imaging for Rapid Cardiovascular Phenotyping in Mice

High-sensitivity in vivo phenotyping of cardiac function is essential for evaluating genes of interest and novel therapies in small animal models of cardiovascular disease. Transthoracic echocardiography is the principal method currently used for assessing cardiac structure and function; however, standard echocardiographic techniques are relatively insensitive to early or subtle changes in cardiac performance, particularly in mice. To develop and validate an echocardiographic strain imaging methodology for sensitive and rapid cardiac phenotyping in small animal models. Herein, we describe a modified echocardiographic technique that uses speckle-tracking based strain analysis for the noninvasive evaluation of cardiac performance in adult mice. This method is found to be rapid, reproducible, and highly sensitive in assessing both regional and global left ventricular (LV) function. Compared with conventional echocardiographic measures of LV structure and function, peak longitudinal strain and strain rate were able to detect changes in adult mouse hearts at an earlier time point following myocardial infarction and predicted the later development of adverse LV remodeling. Moreover, speckle-tracking based strain analysis was able to clearly identify subtle improvement in LV function that occurred early in response to standard post-myocardial infarction cardiac therapy. Our results highlight the utility of speckle-tracking based strain imaging for detecting discrete functional alterations in mouse models of cardiovascular disease in an efficient and comprehensive manner. Echocardiography speckle-tracking based strain analysis represents a method for relatively high-throughput and sensitive cardiac phenotyping, particularly in evaluating emerging cardiac agents and therapies in mice.