Cardiac Systolic Function Research Articles

Impaired cardiac structure and systolic function in athletes using supra-physiological doses of anabolic androgenic steroids

ObjectivesAthletes are increasingly using supra-physiological doses of anabolic androgenic steroids without weighing health side effects. This study aims to conjointly evaluate the effect of supraphysiological doses of anabolic androgenic steroids on global cardiovascular structure and functional capacity. DesignCross-sectional study. Methods92 males enrolled in the study, including 18 sedentary subjects, 26 anabolic androgenic steroid non-user athletes, and 48 anabolic androgenic steroid-user athletes. Two-dimensional echocardiography was done to evaluate the cardiovascular structure and function. ResultsAnabolic androgenic steroid-users presented increased cardiac remodeling of the left ventricle and left atrium compared to control groups (p < 0.001). Anabolic androgenic steroid-users showed increased left ventricular mass/body surface area versus control groups (p < 0.001), with 28 steroid-users (58.3 %) having cardiac remodeling, which is more than control groups (p < 0.001). Anabolic androgenic steroid-users presented lower diastolic function (E and E/A) compared to non-users (p = 0.003 and <0.001, respectively). Ejection fraction was decreased among anabolic androgenic steroid-users versus the sedentary group only (p = 0.020), while anabolic androgenic steroid-users presented reduced global longitudinal strain of 15.43 % compared to both control groups (p < 0.001). Moreover, anabolic androgenic steroid-users experienced more tricuspid valve regurgitation (p = 0.001). ConclusionsAnabolic androgenic steroid consumption is associated with global cardiac remodeling with increased dimensions of the left ventricle, and atrium. Anabolic androgenic steroid-users present left ventricular hypertrophy with reduced subclinical systolic function. Moreover, anabolic androgenic steroid consumption is correlated with valve regurgitation and dilation of the sino-tubular junction.

Prognosis value of EAS index in patients with obstructive coronary artery disease.

EAS index is reported to be an adjunctive tool for risk stratification in addition to left ventricular ejection fraction (LVEF). This study aimed to verify the predictive value of EAS index among coronary artery disease (CAD) patients with different cardiac systolic function levels. A total of 477 patients with obstructive CAD were included in the exploratory analysis of a prospective cohort between October 2017 and January 2018 at Guangdong Provincial People's Hospital. EAS index, e'/(a' × s'), is a novel parameter assessed by tissue Doppler imaging (TDI) indicating combined diastolic and systolic performance. Any occurrence of major adverse cardiovascular event (MACE) was recorded, including first onset of myocardial infarction, stroke, readmission for heart failure, coronary revascularization, or cardiovascular death that occurred within 6 months of the first admission. Kaplan-Meier survival and Cox regression analyses were applied to testify the predictive value of EAS index for cardiovascular outcome. A total of 415 patients (87.2%) completed the follow-up (median, 25.9 months) and experienced 101 (24.3%) MACEs, 17 (4.0%) deaths, and 139 (33.4%) composite events. Elevated EAS index was significantly associated with a higher incidence of MACE, even after adjustment for age, sex, body mass index, N-terminal pro brain natriuretic peptide, high-sensitivity troponin T, high-density lipoprotein, stenosis degree, and other TDI parameters [Model 3, hazard ratio: 1.81, 95% confidence interval (CI): 1.15-2.85]. For different levels of cardiac function, Kaplan-Meier survival analysis revealed that elevated EAS index was associated with higher MACE incidence only in patients with LVEF ≥50% (P<0.05). EAS index is an independent predictor of MACE in patients with obstructive CAD, which could be utilized as a tool for risk stratification in CAD patients or incorporated into a prediction model to improve efficacy.

The Impact of Dapagliflozin on Cardiac LV Systolic Function in Patients with ST Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention Who Developed Post MI LV Dysfunction

Abstract Aim and objectives To study the impact of dapagliflozin on LV systolic function in patients with ST Elevation Myocardial Infarction undergoing primary percutaneous Coronary Intervention who developed post MI LV dysfunction. Patients and Methods The study included 80 patient who presented with ST-segment elevation myocardial infarction and underwent primary PCI at the catheterization lab unit, Cardiology department, Ain Shams University. The patients were divided into 2 groups. The standard treatment was given to all patients according to the ESC guidelines including: ACEI or ARNi, a beta-blocker, and an MRA[1] uptitrated according to the clinical state of the patient. The study medication was 10 mg of dapagliflozin[1] given once daily in the morning to the case group and a placebo medication to the control group. LVEF was assessed in both groups post primary PCI and at follow-up after 3 months by the same Echo machine GE VIVED S5 after the procedure since first of June 2021 till end of January 2022. Results There were no statistically significant difference between both groups regarding gender distribution, mean age, and the incidence of different risk factors of CAD (smoking, Diabetes and hypertension). Regarding pain to door (PTD) time, there was no statistically significant difference between case and control groups (P-value = 0.695), and anterior STEMI was the most common presentation in both groups (90% in the case group and 77.5% in the control group in the control group). Subsequently, there was no statistically significant difference between case and control groups regarding TIMI flow, and post-MI EF with mean range 34.88% ± 3.55% in the case group and 34.58% ± 3.65% in the control group (P = 0.711). On the other hand, there was statistically significant improvement in follow-up EF in the case group which showed a mean range of 45.36% ± 7.13% in comparison with the control group which showed a mean range of 41.80% ± 6.93% (P = 0.027). Conclusion Dapagliflozin administration in the early phase after STEMI results in significant improvement in LV systolic function in comparison with the placebo. Abbreviations ACE-I: Angiotensin-converting enzyme inhibitor; ACS: Acute coronary syndrome; ARNI: Angiotensin receptor-neprilysin inhibitor; CBC: Complete blood picture; DM: Diabetes Mellitus; ECG: Electrocardiogram; FH: Family History; GLS: Global longitudinal strain; HF: Heart Failure; HFrEF: Heart Failure reduced Ejection Fraction; HTN: Hypertension IV: Intravenous; LV: Left ventricle; LVEF: Left ventricular ejection fraction; MI: Myocardial Infarction; MRA: Mineralocorticoid receptor antagonists; PCI: Primary percutaneous coronary intervention; SD: Standard deviation; SGLT-2: Sodium-glucose cotransporter-2 inhibitors; SPSS: Statistical Package for the Social Science; STEMI: ST-segment elevation myocardial infarction; T2D: Type 2 Diabetes Mellitus

Establishment and identification of cardiomyocyte arhGEF18 gene conditional knockout mice

AbstractLeft ventricular noncompaction (LVNC) is a heterogeneous disorder with unclear genetic causes. The arhGEF18 gene is a guanine nucleotide exchange factor related to the Rho pathway and a possible predisposing gene for LVNC. In this study, a mouse model of arhGEF18 gene conditional knockout (cKO) in cardiomyocytes was established using the Cre‐LoxP system to provide an animal model for the genetic study of LVNC. ArhGEF18 cKO mice were obtained by crossing arhGEF18f/+/myh6‐Cre+ and arhGEF18f/f mice. The mRNA and protein expression levels of arhGEF18 in different tissues were verified. The myocardial cytoskeleton and polar protein expression, the survival rate, cardiac function, and cardiac histology of model mice were determined. ArhGEF18 cKO mice were successfully established. ArhGEF18 was confirmed to be specifically knocked out in the myocardial tissue of arhGEF18f/f/myh6‐Cre+ mice at the mRNA and protein levels, and the knockout rate was approximately 75%. The relative expression levels of cytoskeleton and cell polarity proteins such as α/β‐tubulin, Scribble, Crb2, and PAR3 in the cKO group were significantly lower than those in the control group (p &lt; 0.05). During monitoring, the survival rate, cardiac systolic function, and myocardial structure of arhGEF18f/f/myh6‐Cre+ mice were not significantly different from those of control mice. A mouse model of cardiomyocyte arhGEF18 gene cKO was successfully established, and it was confirmed that knocking out arhGEF18 changed cytoskeleton and cell polar protein expression levels in the myocardium. However, there was no obvious LVNC phenotype in the constructed arhGEF18 cKO mice.

State-of-the-art methodologies used in preclinical studies to assess left ventricular diastolic and systolic function in mice, pitfalls and troubleshooting.

Cardiovascular diseases (CVD) are still the leading cause of death worldwide. The improved survival of patients with comorbidities such as type 2 diabetes, hypertension, obesity together with the extension of life expectancy contributes to raise the prevalence of CVD in the increasingly aged society. Therefore, a translational research platform that enables precise evaluation of cardiovascular function in healthy and disease condition and assess the efficacy of novel pharmacological treatments, could implement basic science and contribute to reduce CVD burden. Heart failure is a deadly syndrome characterized by the inability of the heart to meet the oxygen demands of the body (unless there is a compensatory increased of filling pressure) and can manifest either with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). The development and progression of HFrEF is mostly attributable to impaired contractile performance (systole), while in HFpEF the main problem resides in decreased ability of left ventricle to relax and allow the blood filling (diastole). Murine preclinical models have been broadly used in research to understand pathophysiologic mechanisms of heart failure and test the efficacy of novel therapies. Several methods have been employed to characterise cardiac systolic and diastolic function including Pressure Volume (PV) loop hemodynamic analysis, echocardiography and Magnetic Resonance Imaging (MRI). The choice of one methodology or another depends on many aspects including budget available, skills of the operator and design of the study. The aim of this review is to discuss the importance of several methodologies that are commonly used to characterise the cardiovascular phenotype of preclinical models of heart failure highlighting advantages and limitation of each procedure. Although it requires highly skilled operators for execution, PV loop analysis represents the "gold standard" methodology that enables the assessment of left ventricular performance also independently of vascular loading conditions and heart rate, which conferee a really high physiologic importance to this procedure.

Abstract P1055: Takotsubo Syndrome Model In Rats

Background: Takotsubo syndrome (TS) is an acute form of heart failure. The pathophysiology of the life-threatening syndrome is partially understood. A relevant animal model can aid in elucidating mechanisms behind TS. Current models of TS lack proper reproducibility, have high mortality, and fail to reflect the human condition adequately. This experimental study aimed to produce a human-like TS model. Methods: Rats were infused i.v. with a single dose of isoprenaline in varying doses (0.1-50 mg/kg) and infusion times (1-60 min). High-resolution speckle-tracking echo and 3D imaging was used to study heart function for up to 30 days. Results: Mechanical dyssynchrony preceded global contractile dysfunction and development of transient apical akinesia. Surviving rats showed normal behaviour, ECG and imaging at day 30. TS-like phenotype was achieved in 92.9% of survivors. Mortality at 30-day was 6.7%. The deceased animals developed complications like TS patients including heart failure, malignant arrhythmias, mural thrombus formation, cardiogenic shock. A dose-dependent relationship in incidence (p&lt;0.0001), extent of akinesia (p&lt;0.01), mortality (p&lt;0.01), and cardiac function was seen with stress hormone. Systolic cardiac function at first echo was a good predictor for mortality (Odds Ratio 0.73; 95% CI 0.57-0.85), while the extent of akinesia strongly correlated with time until recovery (Rho = 0.86). Conclusions: This study provides a highly reproducible TS model with low mortality and excellent translational potential. High-resolution imaging and the natural course demonstrate the presence of the most critical characteristics of TS-like phenotype as in humans.

Abstract P2051: Fibroblast-specific TGF-b Signaling Promotes Interstitial Fibrosis, Cardiomyocyte Hypertrophy And Cardiac Dysfunction In The Diabetic Heart Through Smad3 Activation

Objectives: Patients with diabetes exhibit a high prevalence of HFpEF associated with interstitial fibrosis and cardiomyocyte hypertrophy. However, the cellular and molecular mechanisms involved in diabetic heart disease remain poorly understood. TGF-bs are potent fibrogenic mediators that are activated in diabetic hearts, and act through a single type 2 receptor, TbRII. We hypothesized that fibroblast-specific actions of TGF-bs may mediate fibrosis and dysfunction in diabetic hearts. Methods and Results: To test the hypothesis, we developed lean and db/db type 2 diabetic TbRII KO mice (FTbRII2KO) using the Col1a2 CreER driver. Fibroblast-specific loss of TGF-b signaling attenuated hypertrophy in db/db mouse hearts. Speckle-tracking echocardiography with strain imaging showed that fibroblast-specific TbRII loss improved systolic and diastolic cardiac function in diabetic animals. In contrast, fibroblast TbRII disruption caused a worsening of both cardiac systolic and diastolic function in lean animals. Attenuated dysfunction in diabetic mice lacking fibroblast TGF-b signaling was associated with reduced collagen fiber thickness and with decreased cardiomyocyte size, suggesting paracrine effects of fibroblasts on cardiomyocytes. To study the downstream cascade responsible for the effects of TGF-b, we generated lean and diabetic mice with fibroblast-specific Smad3 loss. In db/db mice, fibroblast-specific Smad3 loss phenocopied the effects of fibroblast-specific TbRII disruption, suggesting that in diabetic cardiac fibroblasts TGF-b acts through Smad3 signaling. The bioinformatic analyses of transcriptomic profiles of cardiac fibroblasts identified thrombospondin 4 as a candidate mediator of Smad3-dependent diabetes-associated activation. Conclusions: Fibroblast-specific TGF-b actions in diabetes promote cardiac dysfunction through effects on collagen deposition and via paracrine actions on cardiomyocytes. The effects of TGF-b on diabetic cardiac fibroblasts are Smad3-dependent. In contrast to the deleterious effects of fibroblast TGFb/Smad3 signaling in diabetic hearts, TGF-b-activated Smad3-dependent signaling is important to maintain homeostatic function and geometry in normal lean animals.

Abstract P2072: Chronic Treatment With An Androgen Receptor Antagonist Promotes Maladaptive Structural And Functional Cardiac Remodeling In Aging Male Mice

Testosterone levels decrease with age in men, while the risk for cardiovascular diseases (CVD) increases dramatically. Indeed, low circulating testosterone levels in men are associated with diseases such as heart failure. Testosterone exerts its effects via androgen receptors, which are even present in the heart. In addition, androgen receptor antagonists are used to treat prostate cancer in older men who may also have CVD. We investigated the effects of the androgen receptor antagonist flutamide on cardiac structure and function in aged mice. Twenty-month-old male C57BL/6 mice were treated with flutamide for 90 days (slow-release pellet implant; ~20mg/kg/day). In-vivo heart structure/function was assessed using echocardiography and then hearts were Langendorff-perfused to assess load-independent ventricular function ex-vivo . Androgen receptor blockade via flutamide caused maladaptive ventricular remodeling. In-vivo studies showed that flutamide-treated mouse hearts had smaller left ventricular inner diameters when compared to vehicle-treated mice ( e.g. , diastolic: 4.7 ± 0.1 vs. 4.4 ± 0.1 mm; p=0.01; n=8,7). Flutamide also caused left ventricular (LV) atrophy with thinner posterior walls (0.91 ± 0.07 vs. 0.74 ± 0.04 mm; p=0.05) and reduced LV mass when compared to vehicle controls (140 ± 12 vs. 105 ± 6 mg; p=0.03). Ex-vivo functional assessment showed a marked reduction in LV developed pressure in the flutamide-treated mice (111 ± 11 vs. 71 ± 3 mmHg; p&lt;0.01). These mice also had significantly slower rates of LV pressure rise (+dP/dT=2219 ± 263 vs. 1406 ± 95 mmHg/s; p&lt;0.01) as well as LV pressure decay (-dP/dT=-1975 ± 263 vs. -1327 ± 132 mmHg/s; p=0.04). This indicates that flutamide-treated mice had defects in both systolic and diastolic cardiac function. These results demonstrate that suppressing the effects of testosterone by blocking androgen receptors promotes maladaptive structural remodeling of the left ventricle and promotes systolic and diastolic dysfunction in hearts from aged male mice. This study suggests that chronic treatment with androgen receptor antagonists may induce cardiac dysfunction in older men, which has implications for individuals taking these medications for prostate cancer treatment.

Ninety-day mortality of extremely elderly patients undergoing hip fracture surgery and its association with preoperative cardiac function: a single-center retrospective study.

We investigated the 90-day mortality rate in elderly patients who underwent hip fracture surgery and the association of preoperative cardiac function with mortality. We retrospectively enrolled 133 consecutive patients aged 80years or older who underwent hip fracture surgery. We obtained information for patient sex, age, comorbidities, medications, anesthesia method, left ventricular systolic and diastolic functions assessed by echocardiography, and preoperative brain natriuretic peptide (BNP) levels. Multivariate logistic regression analysis was performed. The 90-day mortality rate in patients with a mean age of 88.9years was 7.5% (10/133). More than half of the patients had diastolic dysfunction of the left ventricle. There were no significant differences in preoperative cardiac systolic and diastolic functions between the mortality group and non-mortality group. The preoperative BNP level in the mortality group was significantly higher than that in the non-mortality group (p = 0.038). Preoperative BNP level was not an independent risk factor for 90-day mortality (p = 0.081) in the primary multivariate logistic regression analysis but was an independent risk factor (p = 0.039) with an odds ratio of 1.004 (95% CI 1.000-1.008) in the sensitivity analysis with different explanatory variables. The 90-day mortality rate in patients over 80years old after hip fracture surgery was 7.5%. There were no significant differences in preoperative cardiac function assessed by echocardiography between the mortality and non-mortality groups. Our results suggest that there is no association or only a weak association of high BNP level with 90-day mortality in this age population.

Effect of Liraglutide on Cardiac Function in Individuals With Type 2 Diabetes: A Meta-Analysis.

The aim of this study was to determine the effect of liraglutide on cardiac function in individuals with type 2 diabetes. The present meta-analysis aimed to identify studies testing liraglutide in individuals with type 2 diabetes. We included observational and randomized controlled trials comparing liraglutide with placebo or any other drug alone or in combination with other drugs. A comprehensive search was carried out using online databases including PubMed, Google Scholar, and Cochrane Library to find relevant studies from inception to June 30, 2023, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Key terms used to search for relevant studies included "liraglutide," "cardiac function," and "type 2 diabetes," along with their synonyms and Medical Subject Heading (MeSH) terms. The outcomes assessed in the present meta-analysis included diastolic cardiac function and systolic cardiac function. For diastolic cardiac function, we assessed the E to A (E/A) ratio and the E to Ea (E/Ea) ratio. To assess the impact of liraglutide on systolic function, we assessed stroke volume in mL, left ventricular ejection fraction (LVEF) in %, cardiac output in L/min, and cardiac index in L/min/m². A total of seven studies were included, with a pooled sample size of 307 individuals (160 in the liraglutide group and 147 in the control group). The results indicated that liraglutide significantly reduced the E/A ratio (mean difference [MD]: -0.22, 95% CI: -0.38 to -0.06, p-value: 0.008) and E/Ea ratio (MD: -0.76, 95% confidence interval (CI): -1.39 to -0.12, p-value: 0.02, suggesting a potential clinical benefit on ventricular diastolic function. However, there was no significant impact on LVEF (MD: 0.46, 95% CI: -3.13 to 4.05, p-value: 0.80), cardiac output (MD: 0.05, 95% CI: -0.39 to 0.49), cardiac index (MD: 0.07, 95% CI: -0.18 to 0.32), and stroke volume (MD: -5.34, 95% CI: -14.81 to 4.12), indicating that liraglutide did not improve systolic function.

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

BackgroundCardiac remodeling and dysfunction can be caused by atrial fibrillation (AF). The aim of this research is to investigate the relationship between the systemic inflammatory response index (SIRI) and left ventricular (LV) remodeling and systolic function in individuals with AF.Methods416 patients with AF who were admitted to the Second Department of Cardiology in the East Ward of the Qingdao Municipal Hospital between January 2020 and May 2022 were included in the present retrospective research. The relationship between SIRI and various cardiac parameters was analyzed. The patients’ left atrial (LA) enlargement and left ventricular (LV) hypertrophy and systolic dysfunction were evaluated. SIRI was calculated by the formula: neutrophil × monocyte/lymphocyte.ResultsSIRI significantly correlated with LV end-diastolic diameter (LVDd), LV posterior wall thickness at end-diastole (LVPWTd), interventricular septal thickness at end-diastole (IVSTd), LV mass index (LVMI), LV ejection fraction (LVEF), LA diameter (LAD), C-reactive protein (CRP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with AF. In multivariate linear regression analyses, SIRI was discovered to be significantly related to LVMI (ln-transformed) (p = 0.025), LVEF (ln-transformed) (p = 0.005), and LAD (ln-transformed) (p = 0.007). In multivariate logistic regression, the highest quartile of SIRI (SIRI > 1.62) was significantly associated with LV hypertrophy (p = 0.026), impaired LV systolic function (p = 0.002), and LA enlargement (p = 0.025).ConclusionsSIRI was significantly associated with LV remodeling and systolic function impairment in patients with AF. SIRI may serve as a reliable and convenient inflammatory biomarker for detecting impaired cardiac structure and systolic function in patients with AF.

Hematopoietic cell transplantation for Mucopolysaccharidosis I in the presence of decreased cardiac function

BackgroundSevere mucopolysaccharidosis type I, (MPS IH) is a rare inherited lysosomal disorder resulting in progressive storage of proteoglycans (GAGs) in central nervous system and somatic tissues and, if left untreated, causing death within the first decade of life. Hematopoietic cell transplantation (HCT) arrests many of the features of MPS IH but carries a 10–15% risk of mortality. Decreased cardiac function can occur in MPS IH and increase the risk of HCT. MethodsRetrospective chart review was performed to determine the long-term outcome of individuals evaluated for HCT with MPS IH who had decreased cardiac function as measured by cardiac echocardiogram (echo) and ejection fraction (EF) of <50% at the time of initial evaluation. ResultsSix patients ranging in age from 1 week to 21 months (median: 4 months) had EFs ranging from 25 to 47% (median: 32%) at diagnosis and were initiated on enzyme replacement therapy (ERT) with improvement in EF in three patients by 5 months. The remaining three patients continued to have EFs <50% and continuous milrinone infusion was added in the pre-HCT period. On average, milrinone infusion was able to be discontinued post-HCT, prior to hospital discharge, within a mean of 37 days. Five patients survived HCT and are alive today with normal EFs. One patient receiving milrinone died of sepsis during HCT with a normal EF. ConclusionDecreased cardiac systolic function in infants with MPS IH that fails to normalize with ERT alone may benefit from the addition of continuous milrinone infusion during HCT.

Echocardiography and extravascular lung water during 3weeks of exposure to high altitude in otherwise healthy asthmatics.

Background: Asthma rehabilitation at high altitude is common. Little is known about the acute and subacute cardiopulmonary acclimatization to high altitude in middle-aged asthmatics without other comorbidities. Methods: In this prospective study in lowlander subjects with mostly mild asthma who revealed an asthma control questionnaire score >0.75 and participated in a three-week rehabilitation program, we assessed systolic pulmonary artery pressure (sPAP), cardiac function, and extravascular lung water (EVLW) at 760m (baseline) by Doppler-echocardiography and on the second (acute) and last day (subacute) at a high altitude clinic in Kyrgyzstan (3100m). Results: The study included 22 patients (eight male) with a mean age of 44.3 ± 12.4 years, body mass index of 25.8 ± 4.7kg/m2, a forced expiratory volume in 1s of 92% ± 19% predicted (post-bronchodilator), and partially uncontrolled asthma. sPAP increased from 21.8mmHg by mean difference by 7.5 [95% confidence interval 3.9 to 10.5] mmHg (p < 0.001) during acute exposure and by 4.8 [1.0 to 8.6] mmHg (p = 0.014) during subacute exposure. The right-ventricular-to-pulmonary-artery coupling expressed by TAPSE/sPAP decreased from 1.1 by -0.2 [-0.3 to -0.1] mm/mmHg (p < 0.001) during acute exposure and by -0.2 [-0.3 to -0.1] mm/mmHg (p = 0.002) during subacute exposure, accordingly. EVLW significantly increased from baseline (1.3 ± 1.8) to acute hypoxia (5.5 ± 3.5, p < 0.001) but showed no difference after 3weeks (2.0 ± 1.8). Conclusion: In otherwise healthy asthmatics, acute exposure to hypoxia at high altitude increases pulmonary artery pressure (PAP) and EVLW. During subacute exposure, PAP remains increased, but EVLW returns to baseline values, suggesting compensatory mechanisms that contribute to EVLW homeostasis during acclimatization.

An Experimental Model of Myocardial Infarction for Studying Cardiac Repair and Remodeling in Knockout Mice.

Cardiovascular disease is the most prevalent cause of death in Western countries, with acute myocardial infarction (MI) being the most prevalent form. This paper describes a protocol for studying the role of galectin 3 (Gal-3) in the temporal evolution of cardiac healing and remodeling in an experimental animal model of MI. The procedures described include an experimental model of MI with a permanent coronary ligature in male C57BL/6J (control) and Gal-3 knockout (KO) mice, an echocardiography procedure to study cardiac remodeling and systolic function in vivo, a histological evaluation of interstitial myocardial fibrosis with picrosirius red-stained and rhodamine-conjugated lectin-stained sections for studying myocyte hypertrophy by the cross-sectional area (MCSA), and the quantification of infarct size and cardiac remodeling (scar thinning, septum thickness, and expansion index) by planimetry in slices stained with Masson's trichrome and triphenyl tetrazolium chloride. Gal-3 KO mice with MI showed disrupted cardiac remodeling and an increase in the scar thinning ratio and the expansion index. At the onset of MI, myocardial function and cardiac remodeling were also severely affected. At 4 weeks post MI, the natural evolution of fibrosis in infarcted Gal-3 KO mice was also affected. In summary, the experimental model of MI is a suitable model for studying the temporal evolution of cardiac repair and remodeling in mice with the genetic deletion of Gal-3 and other animal models. The lack of Gal-3 affects the dynamics of cardiac repair and disrupts the evolution of cardiac remodeling and function after MI.

Dysregulated Calcium Handling in Cirrhotic Cardiomyopathy.

Cirrhotic cardiomyopathy is a syndrome of blunted cardiac systolic and diastolic function in patients with cirrhosis. However, the mechanisms remain incompletely known. Since contractility and relaxation depend on cardiomyocyte calcium transients, any factors that impact cardiac contractile and relaxation functions act eventually through calcium transients. In addition, calcium transients play an important role in cardiac arrhythmias. The present review summarizes the calcium handling system and its role in cardiac function in cirrhotic cardiomyopathy and its mechanisms. The calcium handling system includes calcium channels on the sarcolemmal plasma membrane of cardiomyocytes, the intracellular calcium-regulatory apparatus, and pertinent proteins in the cytosol. L-type calcium channels, the main calcium channel in the plasma membrane of cardiomyocytes, are decreased in the cirrhotic heart, and the calcium current is decreased during the action potential both at baseline and under stimulation of beta-adrenergic receptors, which reduces the signal to calcium-induced calcium release. The study of sarcomere length fluctuations and calcium transients demonstrated that calcium leakage exists in cirrhotic cardiomyocytes, which decreases the amount of calcium storage in the sarcoplasmic reticulum (SR). The decreased storage of calcium in the SR underlies the reduced calcium released from the SR, which results in decreased cardiac contractility. Based on studies of heart failure with non-cirrhotic cardiomyopathy, it is believed that the calcium leakage is due to the destabilization of interdomain interactions (dispersion) of ryanodine receptors (RyRs). A similar dispersion of RyRs may also play an important role in reduced contractility. Multiple defects in calcium handling thus contribute to the pathogenesis of cirrhotic cardiomyopathy.

Characterizing regional and global effects of epicardial adipose tissue on cardiac systolic and diastolic function.

The aim of this retrospective study was to determine whether regional epicardial adipose tissue (EAT) exerts localized effects on adjacent myocardial left ventricular (LV) function. Cardiac magnetic resonance imaging (MRI), echocardiography, dual-energy x-ray absorptiometry, and exercise testing were performed in 71 patients with obesity with elevated cardiac biomarkers and visceral fat. Total and regional (anterior, inferior, lateral, right ventricular) EAT was quantified by MRI. Diastolic function was quantified by echocardiography. MRI was used to quantify regional longitudinal LV strain. EAT was associated with visceral adiposity (r = 0.47, p < 0.0001) but not total fat mass. Total EAT was associated with markers of diastolic function (early tissue Doppler relaxation velocity [e'], mitral inflow velocity ratio [E/A], early mitral inflow/e' ratio [E/e']), but only E/A remained significant after adjustment for visceral adiposity (r = -0.30, p = 0.015). Right ventricular and LV EAT had similar associations with diastolic function. There was no evidence for localized effects of regional EAT deposition on adjacent regional longitudinal strain. There was no association between regional EAT deposition and corresponding regional LV segment function. Furthermore, the association between total EAT and diastolic function was attenuated after adjustment for visceral fat, indicating that systemic metabolic impairments contribute to diastolic dysfunction in high-risk middle-aged adults.

Effector T cell chemokine IP-10 predicts cardiac recovery and clinical outcomes post-myocardial infarction.

Preclinical data suggest that activation of the adaptive immune system is critical for myocardial repair processes in acute myocardial infarction. The aim of the present study was to determine the clinical value of baseline effector T cell chemokine IP-10 blood levels in the acute phase of ST-segment elevation myocardial infarction (STEMI) for the prediction of the left ventricular function changes and cardiovascular outcomes after STEMI. Serum IP-10 levels were retrospectively quantified in two independent cohorts of STEMI patients undergoing primary percutaneous coronary intervention. We report a biphasic response of the effector T cell trafficking chemokine IP-10 characterized by an initial increase of its serum levels in the acute phase of STEMI followed by a rapid reduction at 90min post reperfusion. Patients at the highest IP-10 tertile presented also with more CD4 effector memory T cells (CD4 TEM cells), but not other T cell subtypes, in blood. In the Newcastle cohort (n=47), patients in the highest IP-10 tertile or CD4 TEM cells at admission exhibited an improved cardiac systolic function 12 weeks after STEMI compared to patients in the lowest IP-10 tertile. In the Heidelberg cohort (n=331), STEMI patients were followed for a median of 540 days for major adverse cardiovascular events (MACE). Patients presenting with higher serum IP-10 levels at admission had a lower risk for MACE after adjustment for traditional risk factors, CRP and high-sensitivity troponin-T levels (highest vs. rest quarters: HR [95% CI]=0.420 [0.218-0.808]). Increased serum levels of IP-10 in the acute phase of STEMI predict a better recovery in cardiac systolic function and less adverse events in patients after STEMI.

Sudden cardiac death in myocarditis

According to statistics, myocarditis is one of the leading causes of sudden cardiac death (SCD) in children and young adults. The etiology of myocarditis includes infectious and non-infectious, including autoimmune diseases, as well as toxicities and hypersensitivity to various drugs or bites of insects, spiders, snakes, etc. The risk of myocarditis among patients with COVID-19 is 15.7-fold higher than that in the general population. The most common cause of death in myocarditis is heart arrhythmia, such as ventricular tachyarrhythmia, ventricular fibrillation, or severe bradycardia. Genetic predisposition, ion and metabolic disorders, mechanisms of autoimmune response, and direct cardiotoxic action in viral diseases play a role in the pathophysiology of inflammatory myocardial damage. While the majority of patients with myocarditis, who died suddenly, was asymptomatic or had few symptoms, a timely and accurate diagnosis of myocarditis seems to be an important challenge for prevention or minimization of SCD risk. Nonetheless, at present there is no convincing evidence of an association between laboratory and instrumental parameters and the SCD risk in such patients. Endomyocardial biopsy remains the "golden standard" in the diagnosis of myocarditis. Biomarkers (troponins or creatine phosphokinase) are not highly specific. The most common electrocardiographic findings in myocarditis are sinus tachycardia and nonspecific changes in the ST-T segment. The presence of Q wave, bundle branch block, Brugada syndrome, shortened or prolonged QT interval, and early ventricular repolarization are associated with an increased risk of SCD in myocarditis. Given the absence of specific echocardiographic signs of myocarditis, special attention is paid to the assessment of the size of the cardiac chambers, wall thicknesses, global and regional systolic and diastolic function of both the left and right ventricles, visualization of pericardial effusion and intracardiac thrombi. A combined cardiac magnetic resonance imaging using T2-weighted imaging and early and late gadolinium enhancement provides high diagnostic accuracy and seems to be a useful tool in the stratification of patients with suspected acute myocarditis. With the established etiology of myocarditis, specific therapy is necessary to eliminate the pathogen. It is necessary to take into account the likely arrhythmogenic effects of the drugs used in treatment. Non-steroidal anti-inflammatory drugs are generally not indicated in patients with myocarditis because they cause renal impairment and sodium retention, which can exacerbate left ventricular dysfunction and increase the risk of SCD. In the case of severe conduction disturbances and ventricular tachyarrhythmias, implantation of a pacemaker or cardioverter-defibrillator is necessary.

Improvement of left ventricular global longitudinal strain (LV GLS) after 6-months of GLP-1 RAs treatment in diabetes mellitus type 2

Abstract Funding Acknowledgements Type of funding sources: None. Background Glucagone Like Peptide-1 Receptor Agonists (GLP-1RAs) are incretine-based glucose-lowering drugs widely used in the treatment of Diabetes Mellitus type 2 (DM2). Several cardiovascular outcomes trials demonstrated that GLP-1RAs are capable to induce a reduction of major adverse cardiovascular events (MACE) in DM2 patients with atherosclerotic cardiovascular diseases (ASCVD) or with high/very high cardiovascular (CV) risk. However, the direct effect of GLP1-RAs on cardiac function needs to be further explored. Purpose The aim of this study was the investigation of the effects of GLP-1RAs semaglutide or dulaglutide on cardiac systolic function in patients with DM2 and ASCVD or high/very high CV risk. Methods We conducted a proof-of-concept, observational, perspective, monocentric study by the enrollment of 22 patients treated with semaglutide or dulaglutide from December 2019 to March 2020 coming from the outpatient diabetology clinic in our hospital. Each patient underwent a transthoracic echocardiographic evaluation before the drug initiation, and then reassessed after a mean follow-up of 6 months by two cardiologists with experience in echocardiography. The examination was focused on the detection of the left ventricular ejection fraction (LVEF) and the left ventricular global longitudinal strain (LV GLS) with speckle tracking echocardiography (STE) (figure 1). Results Mean age of the sample was 65 ± 10 years, with a small prevalence of male sex (64% of cases). A huge number of patients had arterial hypertension (100%), dyslipidaemia (95%), family history of CV disease (91%), obesity (86%), smoking habit (68%) and two patients had a previous myocardial infarction (MI). Chronic Obstructive Pulmonary Disease (COPD) was the most frequent comorbidity (32% of cases). A mild LV concentric hypertrophy was highly represented [median interventricular septum 12 (IQR 1) mm]. No one had valvular diseases, except for minimum/mild tricuspid and mitral regurgitation. No relevant alterations were seen in the right cardiac sections. The LVEF was normal in the majority of patients, with a median value of 59% (IQR 7%). The mean LV GLS was slightly under the normal range (−18,0% ± 1,8%). After 6-months of treatment with semaglutide or dulaglutide, was documented a clinical and statistically significant improvement of LV GLS (mean difference −1,4% ± 1,1%; p&amp;lt;0,001), with a mean value tending towards the normal range (19,5% ± 2,1%) (figure 2). No relevant changes were seen on the other echocardiographic parameters evaluated. Conclusions In this setting of patients, a subclinical LV dysfunction defined by a mild reduction of LV GLS is common and may evolve towards diabetic cardiomyopathy. Semaglutide or dulaglutide should be considered as antidiabetic drugs in order to improve the systolic function. Further studies with a larger sample size and longer follow-up are ongoing to confirm these preliminary results.

#5667 PULMONARY CONGESTION IN HEMODIALYSIS: PREVALENCE, DYNAMICS AND ASSOCIATED FACTORS

Abstract Background and Aims Lung ultrasound (LUS) helps detecting pulmonary congestion (PC) among haemodialysis (HD) patients. This study investigated the relation between PC, cardiac function parameters, volume status and ultrafiltration, as well as chronic inflammation in two consecutive HD sessions with different inter-dialytic intervals. Method Prospective observational study, where 18 HD patients underwent LUS to calculate the B Lines Score (BLS) using the 8 zone method, inferior vena cava (IVC) dimensions measurement, and echocardiography before and after their regular first (S1) and second (S2) HD sessions of the week. The cut-off for BLS was fixed as 0.54 line per zone. Total body volume using Bio-electrical Impedance Analysis (BIA) was measured before both HD sessions besides serum NT-pro BNP (N-Terminal Pro-Brain Natriuretic Peptide Type B) levels. Moreover, circulating markers of inflammation (soluble urokinase Plasminogen Activator Receptor [suPAR] and soluble Suppression of Tumorigenicity 2 [sST2]) were measured before each session. Results Interdialytic interval did not impact BLS, which was high before and after both sessions. There was no significant difference in BLS before and after S1, whereas the difference was significant in S2 (P: 0.03, ES: 0.54). BIA was correlated to PC only before S2 (R² = 0.374, P = 0.007). BLS and the systolic cardiac function represented by the ejection fraction were correlated only after S2. Nt-ProBNP levels and BLS were correlated before both sessions (R²: 0.421, P: 0.004; R² = 0.505, P = 0.001), respectively. Cardiac diastolic function was correlated with BLS before S1 (R² = 0.476, P = 0.002) and after S2 (R² = 0.193, P = 0.034). Mean levels (± SD, ng/ml) of suPAR (7.88 ± 3.07), (7.78 ± 3.02) remained significantly above the normal range (&amp;lt; 4 ng/ml), while sST2 levels reached 2-fold the upper normal value in some patients (27.4 ± 17.8). Conclusion PC is common in HD patients even after reaching their dry weight at the end of their two consecutive sessions. It is not only correlated to volume status and cardiac function. Chronic inflammation may be involved in PC pathophysiology. A better management strategy is thus needed to better reduce PC in HD patients.