Pathological Left Ventricular Remodeling Research Articles

The Use of Hematopoietic Stem Cells for Heart Failure: A Systematic Review.

The purpose of this review is to summarize the current understanding of the therapeutic effect of stem cell-based therapies, including hematopoietic stem cells, for the treatment of ischemic heart damage. Following PRISMA guidelines, we conducted electronic searches in MEDLINE, and EMBASE. We screened 592 studies, and included RCTs, observational studies, and cohort studies that examined the effect of hematopoietic stem cell therapy in adult patients with heart failure. Studies that involved pediatric patients, mesenchymal stem cell therapy, and non-heart failure (HF) studies were excluded from our review. Out of the 592 studies, 7 studies met our inclusion criteria. Overall, administration of hematopoietic stem cells (via intracoronary or myocardial infarct) led to positive cardiac outcomes such as improvements in pathological left-ventricular remodeling, perfusion following acute myocardial infarction, and NYHA symptom class. Additionally, combined death, rehospitalization for heart failure, and infarction were significantly lower in patients treated with bone marrow-derived hematopoietic stem cells. Our review demonstrates that hematopoietic stem cell administration can lead to positive cardiac outcomes for HF patients. Future studies should aim to increase female representation and non-ischemic HF patients.

Cardiomyocyte Specific MLK3 Deletion Opposes LV Dysfunction and Cardiac Fetal Gene Re-Expression

Study Objective: To determine the cardiac myocyte (CM) and blood pressure-independent effects of Mixed lineage kinase 3 (MLK3) in the regulation of left ventricular (LV) function at baseline and in response to pathological stress. Background: MLK3 functions as a direct substrate effector of cGMP-dependent protein kinase 1α (PKG1α). Whole-body MLK3 deletion in mice increases cardiac dysfunction and remodeling after pressure overload and prevents the therapeutic effect of cGMP augmentation on LV function. However, MLK3 deletion also causes hypertension, which may confound these findings. Hypothesis: MLK3 opposes LV dysfunction through a blood pressure-independent function in the cardiac myocyte (CM). Methods: We generated mice harboring LoxP sites flanking the MAP3K11 gene encoding MLK3 (MLK3fl/fl) and crossed them with αMHC-Cre transgenic mice, enabling constitutive postnatal cardiac myocyte-specific MLK3 deletion (CMKO). Male and female 3- and 6-month-old MLK3 CMKO and control MLK3 intact (MLK3fl/fl Cre-) littermates were studied in the basal state. We also performed transaortic constriction (TAC) or sham surgery for 4 weeks on 3-month-old male mice. We assessed LV structure and function by organ mass, echocardiography, pressure volume loop analysis, qPCR, and immunoblot. In basal and TAC studies, we used age-matched αMHC-Cre x MLK3+/+ (non-floxed) mice as additional controls. Results: MLK3 gene excision in CMs was confirmed by PCR. By 6 months of age, MLK3 CMKO mice displayed: progressive reduction in LV ejection fraction; increase in LV internal diameter; and LV hypertrophy, indicating LV dysfunction and pathological remodeling, compared with littermate controls or with αMHC-Cre x MLK3+/+ non-floxed mice. This effect was more prominent in females than in males. LV fetal gene expression did not differ between genotypes at 3 months. At 6 months of age, however, the fetal genes nppa, RCAN, and CTGF were significantly upregulated in both male and female MLK3 CMKO mice, compared with MLK3 intact, indicating pathological remodeling. After 4-week TAC, MLK3 CMKO LVs developed more severe reduction in LV systolic function compared with MLK3 intact littermates as assayed by echocardiographic measures of LV ejection fraction; and invasive hemodynamic indices of preload recruitable stroke work, maximum LV pressure and LV developed pressure. The MLK3 CMKO LVs also demonstrated a more eccentric remodeling phenotype in which LV mass/tibia length, LV end diastolic and end systolic diameters increased more severely in CMKO mice, with corresponding reduced LV wall thicknesses. Finally, lung mass/tibia length was elevated in the MLK3 CMKO TAC mice compared to MLK3 intact TAC littermates, indicating overt heart failure. Conclusion: (1) MLK3 functions as a tonic inhibitor of LV dysfunction and pathological remodeling through a role in the CM, possibly through sex-specific mechanisms. (2) Intact MLK3 is required for normal LV compensation and concentric remodeling in response to pressure overload. These findings have important clinical implications, as drugs which activate PKG1 in heart failure improve outcomes but are limited by excess hypotension. As a myocardial PKG1 substrate which opposes pathological LV remodeling through blood pressure-independent mechanisms, MLK3 may represent a candidate therapeutic target for heart failure. NIH 1R01HL162919. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Increased left ventricular remodelling index in paradoxical low-flow severe aortic stenosis with preserved left ventricular ejection fraction compared to normal-flow severe aortic stenosis.

Patients with paradoxical low-flow (LF) severe aortic stenosis (AS) despite preserved left ventricular ejection fraction (LVEF) appear distinct from normal-flow (NF) patients, showing worse prognosis, more concentric hypertrophy and smaller left ventricular (LV) cavities. The left ventricular remodelling index (LVRI) has been demonstrated to reliably discriminate between physiologically adapted athlete's heart and pathological LV remodelling. We studied patients with index echocardiographic diagnosis of severe AS (aortic valve area <1 cm2) with preserved LVEF (>50%). The LVRI was determined by the ratio of the LV mass to the end-diastolic volume, as previously reported, and was compared between patients with LF and NF AS. Patients were prospectively followed up for at least 3 years, and clinical outcomes were examined in association with LVRI. Of the 450 patients studied, 112 (24.9%) had LF AS. While there were no significant differences in baseline clinical profile between LF and NF patients, LVRI was significantly higher in the LF group. Patients with high LVRI (>1.56 g/mL) had increased all-cause mortality (log-rank 9.18, P = 0.002) and were more likely to be admitted for cardiac failure (log-rank 7.61, P = 0.006) or undergo aortic valve replacement (log-rank 18.4, P < 0.001). After adjusting for the effect of age, hypertension, aortic valve area and mean pressure gradient on multivariate Cox regression, high LVRI remained independently associated with poor clinical outcomes (hazard ratio 1.64, 95% confidence interval 1.19-2.25, P = 0.002). Pathological LV remodelling (increased LVRI) was more common in patients with LF AS, and increased LVRI independently predicts worse clinical outcomes.

Histological and functional assessment of a Takotsubo cardiomyopathy model established by immobilization stress.

Takotsubo cardiomyopathy (TTC), also known as stress-induced cardiomyopathy, resembles acute heart failure syndrome but lacks disease-specific diagnosis and treatment strategies. TTC accounts for approximately 5-6% of all suspected cases of acute coronary syndrome in women. At present, animal models of TTC are often created by large amounts of exogenous catecholamines such as isoproterenol. However, isoproterenol injection cannot fully simulate the onset of stress-induced cardiomyopathy in humans since stress is not an instantaneous event. Rats were immobilized for 6h per day for 1-14 days. To examine whether the TTC model was successful, echocardiography was employed; Elisa detected serum sympathetic activation markers; and the Open-Field test (OFT) was used to analyze behavioral changes in rats after stress. Western blot and histology were used to assess sympathetic remodeling, inflammation levels, and fibrosis; qRT-PCR was used to explore the levels of fibrosis and myocardial hypertrophy. The electrical stability of ventricular was determined by electrophysiological testing. The rats showed severe stress behavior and local sympathetic remodeling of the heart after only 1 day of stress. After 3 days of stress, the induction of ventricular tachyarrhythmia increased prominently. The highest incidence of TTC in rats was at 5 days of immobilization stress. The pathological left ventricular remodeling caused by immobilization (IMO) stress includes inflammatory infiltration, fibrosis, and myocardial hypertrophy. Our study confirms the hypothesis that IMO stress can mimic Takotsubo cardiomyopathy, and the various effects on the heart depending on the duration of IMO stress. We observed the highest incidence of TTC occurred after 5 days of stress. Furthermore, there is a gradual occurrence of electrical and structural remodeling as the stress duration prolongs.

Abstract 15649: Human Induced Pluripotent Stem Cell-Derived Cardiac Fibroblast Assembled Extracellular Matrix Rescues Cardiac Function in an Acute Myocardial Infarction Mouse Model

Background: Acute myocardial infarction (AMI) is the leading cause of heart failure (HF). Therapies to curb post-AMI pathological left ventricular remodeling could reduce the burden of HF. Human iPSC derived cardiac fibroblast assembled extracellular matrix (iCFX) is a novel acellular biomaterial that consists of a unique blend of extracellular matrix proteins with tissue reparative potential. We hypothesize that direct cardiac injection of iCFX into the peri-infarct border in a mouse AMI model will restore cardiac function and reduce pathological remodeling. Methods: Acute MI was induced by permanent ligation of the left anterior descending coronary artery in 10-week immunocompetent C57BL/6 mice. iCFX was supplied by Cellular Logistics Inc, Madison, WI. One day post-AMI, mice were randomly treated with a 50 microliter epicardial injection of either PBS control, 1 mg iCFX or 10 mg iCFX. Baseline and 28-day echo were performed. Results: At baseline, there were no differences in any echo parameter between treatment groups. By 28 days post treatment, mice treated with 10 mg iCFX had increased ejection fraction ((25.8+/-3.1% (n=8) vs. (13.9+/-1.8% (n=11) p=0.001), fractional shortening ((15.5+/-2.0% (n=8) vs. 6.9+/-1.3%) (n=11) p=0.003), and cardiac output (16.0+/-2.3 ml/min (n=8) vs. 9.7+/-1.2 ml/min (n=11) p=0.002) compared to placebo treated animals. The 1 mg dosing group showed non-significant improvements in contractility parameters. Reduced end systolic and end diastolic volumes in the 10 mg group was observed, but these were not statistically significant. Conclusions: Therapeutic administration of human iCFX was associated with significant improvements in left ventricular contractility following AMI in an immunocompetent mouse model. Furthermore, a clear dose response pattern was observed.

Subtle Changes in Myocardial Work Indices Assessed by 2D-Speckle Tracking Echocardiography Are Linked with Pathological LV Remodeling and MACEs Following an Acute Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention.

The goal of this study was to assess whether subtle changes in myocardial work indices may predict left ventricular (LV) remodeling and major cardiac events (MACEs) in patients with a first ST-elevation acute myocardial infarction (STEMI) and preserved LVEF after successful myocardial revascularization with PCI. Methods. Consecutive STEMI patients in sinus rhythm and with an LV ejection fraction ≥ 50% following a successful PCI were recruited. Conventional and two-dimensional speckle tracking echocardiography (2D-STE) was conducted within 36 h of the PCI and 3 months later. Patients having an increase of more than 20% in LV diastolic volume were included in the LV remodeling group. MACEs were noted throughout a four-year period of follow-up. Results: The study comprised 246 STEMI patients with a mean age of 66; 72% of whom were men. In 24% (58) of the patients, LV remodeling developed. These patients were older, more frequently hypertensive, and had a smoking history. They also exhibited significantly lower baseline and 3-month values for the myocardial global index (GWI), global constructive work (GCW), and global myocardial efficiency (GWE). The cut-off values of 1670 mmHg% for GWI and 83% for GWE were predictive of LV remodeling (p < 0.0001). During the four-year follow-up period, 19% of STEMI patients experienced a MACE, involving 15% from non-LV remodelers and 34% from LV remodelers (p = 0.01). The cut-off values for baseline GWI of 1680 mmHg% and baseline GWE of 84% had the best accuracy in predicting MACEs. In conclusion, non-invasive myocardial work indices offered a reproducible and accurate method to predict post-MI LV remodeling and MACEs.

Predictors of post-infarction left ventricular aneurysm

Post-infarction left ventricular aneurysm (LVA) is a complication of myocardial infarction (MI), which is of great clinical importance due to high mortality. Data on its incidence are contradictory. The aim of the review was to highlight the existing and novel predictors of post-infarction LVA, the identification of which will help in identifying high-risk patients in order to optimize their treatment and rehabilitation. Known predictors of post-infarction LVA include pain-to-balloon time, age, female sex, recurrent MI, coronary angiography parameters, echocardiography, and electrocardiography. Increased levels of leukocytes, C-reactive protein, growth differentiation factor, stimulating growth factor, interleukin-1β, interleukin-6, tumor necrosis factor-α, matrix metalloproteinases, proprotein convertase subtilisin-kexin type 9, N-terminal pro-brain natriuretic peptide &gt;400 pg/ml indicate the risk of pathological left ventricular remodeling and LVA. In this connection, there is a need to assess the incidence of post-infarction LVA and a comprehensive assessment of its predictors in patients with MI.

Developmental programming: adverse sexually dimorphic transcriptional programming of gestational testosterone excess in cardiac left ventricle of fetal sheep

Adverse in-utero insults during fetal life alters offspring’s developmental trajectory, including that of the cardiovascular system. Gestational hyperandrogenism is once such adverse in-utero insult. Gestational testosterone (T)-treatment, an environment of gestational hyperandrogenism, manifests as hypertension and pathological left ventricular (LV) remodeling in adult ovine offspring. Furthermore, sexual dimorphism is noted in cardiomyocyte number and morphology in fetal life and at birth. This study investigated transcriptional changes and potential biomarkers of prenatal T excess-induced adverse cardiac programming. Genome-wide coding and non-coding (nc) RNA expression were compared between prenatal T-treated (T propionate 100 mg intramuscular twice weekly from days 30 to 90 of gestation; Term: 147 days) and control ovine LV at day 90 fetus in both sexes. Prenatal T induced differential expression of mRNAs in the LV of female (2 down, 5 up) and male (3 down, 1 up) (FDR < 0.05, absolute log2 fold change > 0.5); pathways analysis demonstrated 205 pathways unique to the female, 382 unique to the male and 23 common pathways. In the male, analysis of ncRNA showed differential regulation of 15 lncRNAs (14 down, 1 up) and 27 snoRNAs (26 down and 1 up). These findings suggest sexual dimorphic modulation of cardiac coding and ncRNA with gestational T excess.

Myocardial strain parameters and autonomic balance in various variants of the postinfarction course in patients receiving high-dose atorvastatin therapy

Aim. To study parameters of left ventricular (LV) strain and heart rate variability (HRV) in patients with ST-segment elevation myocardial infarction (STEMI) in various variants of postinfarction receiving high-dose atorvastatin therapy.Material and methods. The study included 96 patients with STEMI. All patients underwent two-dimensional speckle tracking echocardiography and 24-hour electrocardiographic monitoring with HRV analysis. The included individuals were divided into groups without pathological LV remodeling (R (-), n=57) and with pathological post-infarction LV remodeling (R (+), n=39), the criterion for which was an increase in end-diastolic and/or end-systolic volume &gt;20% and &gt;15%, respectively. Further, depending on the achievement of target low-density lipoprotein cholesterol (LDL-C) (1,5 mmol/l and/or a decrease of more than 50%), the following subgroups were identified: 17 (43,6%) people, who reached target LDL-C levels (group 1), 22 (56,4%) patients, who did not reach target LDL-C levels (group 2). Similar subgroups were identified in the R (-) group as follows: 28 (49,1%) people, who reached target LDL-C levels (group 3) and 29 (50,9%) people, who did not reach target LDL-C levels (group 4).Results. Starting from the 12th week of follow-up, worsening of global longitudinal (GLS), circumferential (GCS), and radial (GRS) strain (p&lt;0,01) was registered in group 2. In group 1, worsening of these parameters was registered only by the 48th week (p&lt;0,01). In group 3, an increase in GLS was revealed by the 48th week (p=0,001), GCS and GRS — by the 12th week (p&lt;0,05). In group 4, favorable changes were observed only in GLS and GCS by the 48th week (p&lt;0,01). A significant change in HRV parameters was observed in group 3. By the 48th week, there was an increase in temporal indicators (SDNN, SDNNi, SDANN, RMSSD, pNN50) (p&lt;0,0001) and total spectrum power (p=0,0001) due to an increase in all frequency indicators (p&lt;0,001), while the index of autonomic balance L/H decreased by 33% (p=0,002). In group 4, only SDNN, SDANN and pNN50 (p&lt;0,05), as well as the total spectrum power (p=0,001) increased, but no change in frequencies. According to intergroup analysis in the acute period of STEMI, group 4 patients had higher HRV than in group 3 (p&lt;0,05).Conclusion. High-dose atorvastatin therapy improves LV strain characteristics and autonomic balance during the rehabilitation period after STEMI.

The cardiac computed tomography-derived extracellular volume fraction predicts patient outcomes and left ventricular mass reductions after transcatheter aortic valve implantation for aortic stenosis

BackgroundTranscatheter aortic valve implantation (TAVI) improved outcome of patients with severe aortic valve stenosis (AS). Myocardial fibrosis is associated with AS-related pathological left ventricular (LV) remodeling and predicts cardiovascular mortality after TAVI. The present study aimed to investigate the impact of preoperative extracellular volume (ECV) assessed by computed tomography (CT) on left ventricular mass (LVM) regression and clinical outcomes in severe AS patients after TAVI. MethodsWe examined 71 consecutive severe AS patients who underwent CT with ECV determination before TAVI. ECV was calculated as the ratio of the change in Hounsfield units in the myocardium and LV blood before and after contrast administration, multiplied by (1-hematocrit). Delayed scan was performed at 5 min after contrast injection. Echocardiography was performed before and 6 months after TAVI. The primary endpoint was heart failure (HF) hospitalization after TAVI. Patients were divided into two subgroups according to the median value of global ECV with 32 % (Low-ECV group: n = 35, and High-ECV group: n = 36). ResultsNo significant differences were observed in background characteristics between the 2 groups. However, the preoperative LV ejection fraction and LVM index were similar between the 2 groups, the Low-ECV group had greater LVM index reduction than the High-CV group after 6 months (p < 0.001). Kaplan-Meier curves demonstrated that the High-ECV group had significantly higher rate of HF hospitalization than the Low-ECV group (p = 0.016). In addition, multivariate analyses identified high global ECV as an independent predictor of HF hospitalization (HR 10.8, 95 % confidence interval 1.36 to 84.8, p = 0.024). ConclusionThe low preoperative ECV assessed by CT is associated with the greater LVM regression, and predict better outcome in AS patients after TAVI.

Qiliqiangxin Modulates the Gut Microbiota and NLRP3 Inflammasome to Protect Against Ventricular Remodeling in Heart Failure.

Aims: Pathological left ventricular (LV) remodeling induced by multiple causes often triggers fatal cardiac dysfunction, heart failure (HF), and even cardiac death. This study is aimed to investigate whether qiliqiangxin (QL) could improve LV remodeling and protect against HF via modulating gut microbiota and inhibiting nod-like receptor pyrin domain 3 (NLRP3) inflammasome activation. Methods: Rats were respectively treated with QL (100 mg/kg/day) or valsartan (1.6 mg/kg/day) by oral gavage after transverse aortic constriction or sham surgery for 13 weeks. Cardiac functions and myocardial fibrosis were assessed. In addition, gut microbial composition was assessed by 16S rDNA sequencing. Furthermore, rats’ hearts were harvested for histopathological and molecular analyses including immunohistochemistry, immunofluorescence, terminal-deoxynucleotidyl transferase-mediated 2’-deoxyuridine 5’-triphosphated nick end labeling, and Western blot. Key findings: QL treatment preserved cardiac functions including LV ejection fractions and fractional shortening and markedly improved the LV remodeling. Moreover, HF was related to the gut microbial community reorganization like a reduction in Lactobacillus, while QL reversed it. Additionally, the protein expression levels like IL-1β, TNF-α, NF-κB, and NLRP3 were decreased in the QL treatment group compared to the model one. Conclusion: QL ameliorates ventricular remodeling to some extent in rats with HF by modulating the gut microbiota and NLRP3 inflammasome, which indicates the potential therapeutic effects of QL on those who suffer from HF.

Early markers of pathological left ventricular remodeling in patients after ST-elevation myocardial infarction according to speckle-tracking echocardiography

Aim. To assess early predictors of pathological remodeling in patients after ST-elevation myocardial infarction (STEMI) using speckle-tracking echocardiography (STE).Material and methods. The study included 114 STEMI patients aged 52 (44; 58) years. A two-dimensional echocardiography was performed with the analysis of standard parameters and STE with an analysis of strain and rotational characteristics of the myocardium. In addition, brain natriuretic peptide and troponin-I concentration was determined. The development of pathological post-infarction remodeling within 12-month follow-up was assessed as an end point. Depending on the outcome, 2 groups were formed: group 1 — patients with pathological remodeling (PR), n=45 (39,5%), group 2 — patients without PR, n=69 (60,5%).Results. Early remodeling was detected in 24 (53,3%) people, mid-term — in 15 (33,4%), and late remodeling — in 6 (13,3%). In the PR group, heart failure (HF) was detected in 100% of patients, while in non-PR group, 23 (33,3%) patients had no signs of HF.In the early period of myocardial infarction, each of following indicators with high sensitivity and specificity predicts postinfarction pathological dilatation: global longitudinal strain (GLS) &lt;11,7%, global circular strain (GCS) &lt;12,4%, and a Twist decrease to 7,8o. A multivariate logistic regression model was created for the formation of pathological remodeling in patients with STEMI, which included GLS, global radial deformation (GRS), end-systolic volume index (ESVI), determined on days 7-9 of STEMI.Conclusion. GLS, GCS, and left ventricular Twist are independent highly sensitive and specific predictors of pathological remodeling. The following early predictors of postinfarction pathological dilatation have been established: reduced GLS in combination with higher GRS and left ventricular ESVI.

Using parameters of myocardial deformation as markers of pathological postinfarction remodeling

Abstract Funding Acknowledgements Type of funding sources: None. Objective to predict pathological left ventricular (LV) remodeling using global parameters of strain and twisting. Methods the study included 114 people with primary ST-segment elevation myocardial infarction (STEMI): 14 women and 100 males aged 32 to 67 years (52.3 ± 8.4). STEMI has been confirmed by ECG data, cardiospecific biomarkers (troponin T, CPK-MB) and coronary angiography - the presence of one infarct-related coronary artery in the absence of hemodynamically significant stenosis of other arteries. Echocardiography has been performed using a MyLab ultrasound scanner (Italy) on the 7th-9th day, 3rd, 6th and 12th months after the disease onset with the evaluation of standard parameters. On the 7th-9th days the parameters of global longitudinal (GLS,%), circumferential (GCS,%) strain, and LV twisting (Twist, °) have been analyzed using the X-Strain ™ software. The criterion for pathological LV remodeling has been considered to be an increase in EDVi ≥ 20% compared with the initial value. Prediction of pathological remodeling has been performed using ROC analysis by 3 criteria. To assess the quality of the model, the area under the curve (AUR –Area under ROC) has been determined with the calculation of 95% confidence intervals and the statistical significance of the point estimate of the area. Results Within 48 weeks pathological remodeling was developed in 45 (39.5%) patients. Three months after the index event, LV remodeling was detected in 24 (53.3%) patients of these 45; after 6 months - in another 15 (33.3%); after 12 months - in another 6 (13.4%). GLS - 11.7% with 96% sensitivity and 80% specificity, AUR 0.750 (95% CI 0.659 - 0.841), GCS - 12.4% with test sensitivity and specificity - 90% and 82%, respectively ((AUR 0.641 ( 95% CI 0.534 - 0.749)), Twist - 7.8 ° with a sensitivity of 93% and a specificity of 78%, AUR 0.657 (95% CI 0.558 - 0.757) predict the development of pathological postinfarction LV remodeling on the 7th-9th day. For all models the value of p ≤ 0.001. Conclusion Previously, LV remodeling has developed within 3 months after STEMI in 45 (39.5%) patients. The longitudinal strain, measured in the acute period of STEMI, has the greatest predictive ability in relation to the development of pathological postinfarction LV remodeling.

Early predictors of the development of pathological postinfarction left ventricular remodeling

Abstract Funding Acknowledgements Type of funding sources: None. Objective to assess the ability of standard echocardiography parameters and parameters of myocardial deformation on the 7th-9th day of the STEMI to predict the risk of pathological remodeling in the postinfarction period. Methods the study included 114 patients with ST-segment elevation myocardial infarction (STEMI) mean age was 52.3 ± 8.4 years, men prevailed 100 (88%). On the 7th-9th day, echocardiography has been performed using the MyLab device (Italy) with the determination of end-diastolic and systolic volume indices (EDVi, ESVi), left ventricular myocardial mass index (LVMI). Global longitudinal (GLS), circumferential (GCS) and radial (GRS) strain (-%) have been determined using X-Strain ™ software. The development of pathological left ventricular remodeling (an increase in EDVi of more than 20% and / or ESVi of more than 15% at any visit within 48 weeks) has been considered as the end point. Multivariate Cox regression analysis was performed by including significant variables from a one-dimensional model (p &amp;lt;0.05), taking into account the absence of correlations between them. Results within 48 weeks, 45 (39%) patients developed pathological postinfarction remodeling. The following strong and independent predictors of the pathological postinfarction remodeling were included in the multivariate predictive model: GLS - RR 0.799 (95% CI 0.735-0.868) (p = 0.001), GRS - 1.047 (95% CI 1.013-1.083) (p = 0.001), EDVi - RR 1.041 (95% CI 1.015-1.07) (p = 0.026). Chi-square model 30.02, p ˂ 0.0001. Maximum likelihood ratio 385. Conclusions a multivariate model including GLS, GRS, and EDVi parameters on the 7th-9th day of STEMI is able to predict the development of pathological remodeling in patients within 48 weeks of the postinfarction period.

Предикторна цінність ожиріння у хворих з інфарктом міокарда з елевацією сегмента ST

The aim – to determine predictors of pathological left ventricular (LV) remodeling in patients with ST-segment elevation myocardial infarction (STEMI) with obesity. Materials and methods. Retrospective cohort study was performed. 111 patients that were hospitalized in the intensive care unit from January 2018 to February 2021 were involved to the study. TIMI-3 flow was restored in all 111 patients. Early cardiac postinfarction pathological remodeling was defined as left ventricular ejection fraction (LVEF) &lt; 50 % and/or Е/е’ ≥ 13; LV diastolic dysfunction was defined as LVEF ≥ 50 % and/or Е/е’ &lt; 13 units. Echocardiography was performed during hospitalization. Also there were determine weight, fat content, visceral fat ratio, skeletal muscle content, daily metabolism, body mass index (BMI).Results and discussion. Patients were divided into two subgroups – 49 patients with obesity (BMI ≥ 30 kg/m2) and 62 – without obesity (BMI &lt; 30 kg/m2). The prognostic value of various factors for pathological remodeling of left ventricle (LV) was studied in patients with STEMI with and without obesity. Pathological remodeling was assessed as systolic – with reduced LFEF &lt; 50 %, and diastolic – with E/e’ &lt; 13. It was found that multivascular injury is more important for the deve­lopment of LV remodeling in patients with LVEF &lt; 50 % regardless of diastolic function. Visceral fat leads to LV remodeling due to diastolic dysfunction.Conclusion. The predictor value of visceral fat is important for predicting early remodeling associated with isolated diastolic dysfunction in patients with STEMI.

Myocardial Infarction by Percutaneous Embolization Coil Deployment in a Swine Model

Myocardial infarction (MI) is the leading cause of mortality worldwide. Despite the use of evidence-based treatments, including coronary revascularization and cardiovascular drugs, a significant proportion of patients develop pathological left-ventricular remodeling and progressive heart failure following MI. Therefore, new therapeutic options, such as cellular and gene therapies, among others, have been developed to repair and regenerate injured myocardium. In this context, animal models of MI are crucial in exploring the safety and efficacy of these experimental therapies before clinical translation. Large animal models such as swine are preferred over smaller ones due to the high similarity of swine and human hearts in terms of coronary artery anatomy, cardiac kinetics, and the post-MI healing process. Here, we aimed to describe an MI model in pig by permanent coil deployment. Briefly, it comprises a percutaneous selective coronary artery cannulation through retrograde femoral access. Following coronary angiography, the coil is deployed at the target branch under fluoroscopic guidance. Finally, complete occlusion is confirmed by repeated coronary angiography. This approach is feasible, highly reproducible, and emulates the pathogenesis of human non-revascularized MI, avoiding the traditional open-chest surgery and the subsequent postoperative inflammation. Depending on the time of follow-up, the technique is suitable for acute, sub-acute, or chronic MI models.

Contemporary Pillars of Heart Failure with Reduced Ejection Fraction Medical Therapy.

Heart failure with reduced ejection fraction (HFrEF) is a clinical condition associated with cardiac contractility impairment. HFrEF is a significant public health issue with a high morbidity and mortality burden. Pathological left ventricular (LV) remodeling and progressive dilatation are hallmarks of HFrEF pathogenesis, ultimately leading to adverse clinical outcomes. Therefore, cardiac remodeling attenuation has become a treatment goal and a standard of care over the last three decades. Guideline-directed medical therapy mainly targeting the sympathetic nervous system and the renin–angiotensin–aldosterone system (RAAS) has led to improved survival and a reduction in HF hospitalization in this population. More recently, novel pharmacological therapies targeting other pathways implicated in the pathophysiology of HFrEF have emerged at an exciting rate, with landmark clinical trials demonstrating additive clinical benefits in patients with HFrEF. Among these novel therapies, angiotensin receptor–neprilysin inhibitors (ARNI), sodium–glucose cotransporter-2 inhibitors (SGLT2i), vericiguat (a novel oral guanylate cyclase stimulator), and omecamtiv mecarbil (a selective cardiac myosin activator) have shown improved clinical benefit when added to the traditional standard-of-care medical therapy in HFrEF. These new comprehensive data have led to a remarkable change in the medical therapy paradigm in the setting of HFrEF. This article will review the pivotal studies involving these novel agents and present a suggestive paradigm of pharmacological therapy representing the 2021 European Society of Cardiology (ESC) guidelines for the treatment of chronic HFrEF.

Динамика ремоделирования левого желудочка у больных артериальной гипертензией с сахарным диабетом 2-го типа и ожирением под влиянием одногодичной комбинированной терапии

Актуальность. Патологическое ремоделирование левого желудочка (ЛЖ) у больных артериальной гипертензией (АГ) с сахарным диабетом (СД) 2-го типа и ожирением ассоциируется со значительным повышением сердечно-сосудистого риска и требует ранней и адекватной медикаментозной коррекции. Материалы и методы. В исследование включены 38 больных АГ 2-й степени с субкомпенсированным СД 2-го типа и абдоминальным ожирением (АО). Обследование проводили до и после одногодичной терапии блокатором рецепторов ангиотензина ІІ олмесартаном и антагонистом кальция лерканидипином в сочетании с аторвастатином и метформином. Результаты. У больных выявлена высокая частота патологических типов ремоделирования ЛЖ (концентрическая и эксцентрическая гипертрофия ЛЖ (ГЛЖ) (50 и 37 % соответственно) с развитием его диастолической дисфункции в 89 % случаев. Комбинированная терапия способствовала достоверному снижению выраженности ГЛЖ и частоты диастолической дисфункции. Выводы. Длительное применение олмесартана и лерканидипина в сочетании с аторвастатином и метформином у больных АГ с СД 2-го типа и АО является эффективным методом торможения прогрессирования патологического ремоделирования ЛЖ.

Replication Stress Response Modifies Sarcomeric Cardiomyopathy Remodeling.

BackgroundSarcomere gene mutations lead to cardiomyocyte hypertrophy and pathological myocardial remodeling. However, there is considerable phenotypic heterogeneity at both the cellular and the organ level, suggesting modifiers regulate the effects of these mutations. We hypothesized that sarcomere dysfunction leads to cardiomyocyte genotoxic stress, and this modifies pathological ventricular remodeling.Methods and ResultsUsing a murine model deficient in the sarcomere protein, Mybpc3−/− (cardiac myosin‐binding protein 3), we discovered that there was a surge in cardiomyocyte nuclear DNA damage during the earliest stages of cardiomyopathy. This was accompanied by a selective increase in ataxia telangiectasia and rad3‐related phosphorylation and increased p53 protein accumulation. The cause of the DNA damage and DNA damage pathway activation was dysregulated cardiomyocyte DNA synthesis, leading to replication stress. We discovered that selective inhibition of ataxia telangiectasia and rad3 related or cardiomyocyte deletion of p53 reduced pathological left ventricular remodeling and cardiomyocyte hypertrophy in Mybpc3−/− animals. Mice and humans harboring other types of sarcomere gene mutations also had evidence of activation of the replication stress response, and this was associated with cardiomyocyte aneuploidy in all models studied.ConclusionsCollectively, our results show that sarcomere mutations lead to activation of the cardiomyocyte replication stress response, which modifies pathological myocardial remodeling in sarcomeric cardiomyopathy.

Role of speckle tracking echocardiography in patients with myocardial infarction

All over the world cardiovascular diseases are one of the main reason of morbidity and mortality in the structure of non-communicable diseases, and myocardial infarction has a leading role. Markers of modern advanced ultrasound techniques, speckle tracking echocardiography, play significant role in the detection and assessment of cardiovascular disease. Deviation of them can detect myocardial ischemia, hypertrophy, dystrophy and infiltration, severe systemic diseases, cardiotoxicity of the drugs, etc. This technology significantly improves diagnostic capabilities of transthoracic echocardiography, it allows to assess myocardial function in all three planes (longitudinal, circumferential and radial), in which myocardium moves during cardiac cycle. Speckle tracking echocardiography can determine the volume of myocardial damage, differentiate subendocardial and transmural myocardial infarction, identify viable and fibrous areas of the myocardium, that is confirmed by the results of magnetic resonance imaging. Besides, this method helps to detect and assess mechanical dyssynchrony and also predict the risk of pathological left ventricular remodeling and life-threatening adverse cardiovascular events (arrhythmias, increasing of heart failure, recurrent myocardial infarction, stroke, death, etc.), that is important for patients with acute myocardial infarction to identify high-risk patients. The most studied markers of this technique are longitudinal, circumferential and radial strain, mechanical dispersion and postsystolic shortening. Markers of this ultrasound technique significantly complete other markers of transthoracic echocardiography, such as left ventricular ejection fraction, to assess risk stratification of cardiovascular complications. The value of speckle-tracking echocardiography markers has been demonstrated alone or in combination with other markers.