Early Cardiac Dysfunction Research Articles

Effects of insulin and sitagliptin on early cardiac dysfunction in diabetic rats

AimsCardiac affection is common in diabetic patients. Although insulin exerts a cardioprotective role, it may not be enough to totally prevent this affection. The current study aimed to compare the cardioprotective effect of insulin alone or combined with sitagliptin in a rat model of type 1 diabetes mellitus. Materials and methodsDiabetes was induced by a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg). Diabetic rats were treated with insulin (3 IU), insulin (6 IU), or insulin (3 IU) + sitagliptin (10 mg/kg) for 42 days. Key findingsDiabetic rats exhibited significant systolic and diastolic cardiac affection with significant elevation of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and brain natriuretic peptide (BNP) levels. Treatment with insulin prevented the deterioration of diabetes-induced cardiac condition, an effect that was significantly potentiated by the combined use of sitagliptin. SignificanceThe combined use of sitagliptin and insulin significantly improved the cardioprotective effect of insulin and prevented the early cardiac dysfunction in STZ diabetic rats.

Contemporary non-invasive methods for the diagnosis of early cardiac dysfunction in young patients with beta-thalassemia major

Thalassemias are a group of inherited disorders, that require regular lifelong blood transfusions, which are vital for the normal development and life of the patients. With time, complications occur due to iron deposition in internal organs with subsequent chronic hemochromatosis development and predominantly affecting the heart, the liver and the endocrine glands. Despite the absence of clinical symptoms in young patients, enough data are supporting the fact that early myocardial iron deposition occurs. This necessitates the introduction of suffi ciently reliable methods and techniques for the detection and follow-up of early heart disorders before the onset of symptoms. Evaluation of myocardial iron deposition by the T2* MRI technique is established as a reliable, non-invasive method with good reproducibility and a low percentage of variability. Echocardiography as a method does not give information concerning the iron deposition in the heart but is easily applicable, safe and widespread for screening and follow up of patients. The use of new technique such as longitudinal strain makes the method almost comparable for the assessment of early subclinical myocardial damage. Although still in the fi eld of research, the identifi cation of specifi c miRNAs associated with cardiac stroke, fi brosis and remodeling is emerging as a new, potential biomarker for myocardial damage that could support the overall cardiovascular assessment of patients. This review will focus on current manifestations of cardiac complications in young patients with beta-thalassemia major, as well as the noninvasive methods for assessing cardiac function described above.  

Subclinical left ventricular dysfunction during systemic lupus erythematosus activity with follow-up after remission – A speckle tracking echocardiographic study

Aim of the workTo investigate the subclinical left ventricular (LV) dysfunction in patients with active systemic lupus erythematosus (SLE) using speckle tracking echocardiography (STE). The echocardiographic parameters were followed up when the disease activity was controlled. Patients and methodsThis prospective study included 63 patients with active SLE and LV ejection fraction (EF) ≥50%.Safety of Estrogens in Lupus Erythematosus: National Assessment – Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) was assessed and categorized as mild/moderate (≤12) or severe (>12). Fifty SLE patients continued follow-up after 3–6 months of the disease remission. Fifty age- and gender-matched healthy individuals acted as the control group. The measured STE parameters included LV deformation (global longitudinal strain [GLS] and global circumferential strain [GCS]) and rotational parameters (rotation, twist, and torsion). ResultsThe patients were 56 females and 7 males (F:M 8:1) and median age 26 years (IQR: 21–31 years) and a disease duration of 3 years (IQR 2–5 years. Active SLE patients showed worse strain parameters than controls (mean GLS −19.9%±2.1 vs −22.7%±1.3 and mean GCS −21.2 ± 2.5% vs −25.1 ± 1.7% respectively; p < 0.001 for both). Patients had lower LV rotational parameters (p < 0.001 for all). STE parameters were similar in patients with mild-moderate and severe activity and improved after remission in both groups. ConclusionActive SLE patients had modest LV dysfunction by STE despite having normal function by traditional echocardiography. Disease remission resulted in the improvement of STE parameters. STE is a simple tool to use in SLE activity scores to detect early cardiac dysfunction.

Analysis of the correlation between amino-terminal pro-brain natriuretic peptide levels and prognosis of patients with off-pump coronary artery bypass grafting

IntroductionThis study aims to investigate the correlation between the postoperative changes in serum amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels and the prognosis of patients with off-pump coronary artery bypass grafting. MethodsThe patients were divided into two groups according to the left ventricular ejection fraction (LVEF) value of their cardiac ultrasound 48 h after surgery: the study group, those with early postoperative cardiac dysfunction (LVEF ≤45%, 36 cases), and the control group, those without early postoperative cardiac dysfunction (LVEF >45%, 60 cases). The serum NT-proBNP levels at 24 h and 48 h after surgery and before discharge were measured in the two groups, and any major postoperative adverse events were observed to analyze the relationship between the NT-proBNP levels and early postoperative cardiac dysfunction and prognosis. ResultsThe serum NT-proBNP levels in the study group were significantly higher than in the control group at 24 h and 48 h after surgery (p < 0.05). However, there was no significant difference between the two groups in the serum NT-proBNP levels before discharge (p > 0.05). The main adverse events of the study group during hospitalization were significantly higher than in the control group (p < 0.05). The area under the curve of NT-proBNP in predicting early postoperative cardiac dysfunction was 0.850 (95% CI: 0.826–0.903) (p < 0.001). The best diagnostic value was 5653.95 pg/ml, the sensitivity was 87.8%, and the specificity was 83.6%. ConclusionThe postoperative NT-proBNP level is closely related to early cardiac dysfunction and major adverse events after off-pump coronary artery bypass grafting.

Evaluation of diastole by echocardiography for detecting early cardiac dysfunction: an outcome study.

AimsTimely detection of subclinical left ventricular diastolic dysfunction (LVDDF) is of importance for precise risk stratification of asymptomatic subjects. Here, we evaluated the prevalence of LVDDF and its prognostic significance in the general population using two grading approaches: the 2016 ASE/EACVI recommendations and population‐derived, age‐specific criteria.Methods and resultsWe randomly recruited 1407 community‐dwelling participants (mean age, 51.2 years; 51.1% women; 53.5% with cardiovascular risk factors). We measured left heart dimensions, strain, tricuspid regurgitation, transmitral blood flow, and mitral annular tissue velocities using conventional echocardiography and Doppler imaging. We utilized these measurements to grade of LVDDF according to the 2016 recommendations and population‐derived, age‐specific approach. According to the 2016 recommendations, 26 subjects (1.85%) were classified as having the advanced stage (Grade 2), whereas in 109 participants (7.75%) diastolic function was indeterminate. When applying the population‐derived criteria, the prevalence of advanced LVDDF was 17.9% (n = 252). During the follow‐up period (8.4 years), 100 participants experienced adverse cardiac events. After full adjustment, we did not observe any significant differences in the risk of events between subjects with indeterminate or any grade of LVDDF and subjects with normal diastolic function when classified according to the 2016 recommendation (P ≥ 0.25). In contrast, the adjusted risks of adverse cardiac events (HR = 1.28; P = 0.0045) were significantly elevated in participants with LVDDF when classified according to the population‐derived criteria.ConclusionsOur study underscored the importance of considering age‐ and population‐derived thresholds in LVDDF grading in subjects at high cardiovascular risk which led to a better risk stratification and outcome prediction.

Disruption of polycystin-1 cleavage leads to cardiac metabolic rewiring in mice

Cardiovascular manifestations account for marked morbi-mortality in autosomal dominant polycystic kidney disease (ADPKD). Pkd1- and Pkd2-deficient mice develop cardiac dysfunction, however the underlying mechanisms remain largely unclear. It is unknown whether impairment of polycystin-1 cleavage at the G-protein-coupled receptor proteolysis site, a significant ADPKD mutational mechanism, is involved in this process. We analyzed the impact of polycystin-1 cleavage on heart metabolism using Pkd1V/V mice, a model unable to cleave this protein and with early cardiac dysfunction. Pkd1V/V hearts showed lower levels of glucose and amino acids and higher lipid levels than wild-types, as well as downregulation of p-AMPK, p-ACCβ, CPT1B-Cpt1b, Ppara, Nppa and Acta1. These findings suggested decreased fatty acid β-oxidation, which was confirmed by lower oxygen consumption by Pkd1V/V isolated mitochondria using palmitoyl-CoA. Pkd1V/V hearts also presented increased oxygen consumption in response to glucose, suggesting that alternative substrates may be used to generate energy. Pkd1V/V hearts displayed a higher density of decreased-size mitochondria, a finding associated with lower MFN1, Parkin and BNIP3 expression. These derangements were correlated with increased apoptosis and inflammation but not hypertrophy. Notably, Pkd1V/V neonate cardiomyocytes also displayed shifts in oxygen consumption and p-AMPK downregulation, suggesting that, at least partially, the metabolic alterations are not induced by kidney dysfunction. Our findings reveal that disruption of polycystin-1 cleavage leads to cardiac metabolic rewiring in mice, expanding the understanding of heart dysfunction associated with Pkd1 deficiency and likely with human ADPKD.

Strain Imaging for the Early Detection of Cardiac Remodeling and Dysfunction in Primary Aldosteronism.

Speckle tracking echocardiography is a novel technique to quantify cardiac function and deformation. It has been applied in a series of cardiovascular diseases for the evaluation of early cardiac impairment. We recently used this technique to investigate cardiac structure and function in patients with primary aldosteronism. Cardiac damage usually occurs earlier in patients with primary aldosteronism than those with primary hypertension, probably because aldosterone hypersecretion is more commonly observed in the former than the latter patients. In this article, we will review the imaging studies, especially with speckle tracking echocardiography, for the detection of early cardiac dysfunction in primary aldosteronism as a disease model.

Early Detection of Cardiac Damage by Two-Dimensional Speckle Tracking Echocardiography After Thoracic Radiation Therapy: Study Protocol for a Prospective Cohort Study.

BackgroundAs one of the important treatment methods for cancer patients, radiotherapy may lead to incidental irradiation of the heart, resulting in radiotherapy-induced heart disease (RIHD) arising many years after radiotherapy. While, there are few studies on early subclinical cardiac damage, which may be essential for the protection of late RIHD. To detect and predict RIHD and early subclinical cardiac damage induced by thoracic radiation therapy, based on two-dimensional speckle tracking echocardiography (2D STE) combined with multiple circulating biomarkers and accurate heart dosimetry.Methods and AnalysisThis is a monocentric prospective cohort study in which 104 patients treated for malignant tumors and with cardiac radiation exposure will be included. All participants will be followed for 12 months after radiotherapy. Echocardiography, 2D STE, and blood samples will be underwent at 5-time points (baseline; after completion of RT; 2, 6, and 12 months after RT). Left ventricular ejection fraction (LVEF); global longitudinal, radial, and circumferential strain; diastolic function parameters; creatine kinase (CK); creatine kinase isoenzyme (CK-MB); cardiac troponin T (cTnT); N-terminal pro-B-type natriuretic peptide (NT-proBNP) and hypersensitive C-reactive protein (hs-CRP) will be measured at baseline and every follow-up time. The incidence of major adverse cardiovascular events will be recorded.DiscussionThis study details the protocol and presents the primary limits and advantages of this single-center project. The inclusion of patients began in 2021, and the results are expected to be published in 2023. This study will be allowed to enhance knowledge on detection and prediction of early subclinical cardiac dysfunction induced by thoracic radiation therapy, based on two-dimensional speckle tracking echocardiography (2D STE) combined with circulating biomarkers and accurate heart dosimetry. Furthermore, we will evaluate risk factors of subtle cardiac damage and identify high-risk groups for early heart damage.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT04443400.

Cardiac Dysfunction in Early Stages of Diabetic Kidney Disease- Fact or Fiction: A Case-control Study

Introduction: The occurrence of kidney dysfunction in diabetics promotes early cardiac dysfunction. The timing of Diabetic Kidney Disease (DKD) and the impact of the stage of DKD on cardiac dysfunction is far from elucidated in current literature. Aim: To evaluate the association between the early stages of DKD and cardiac dysfunction by echocardiography. Materials and Methods: The present descriptive, case-control study was conducted in the Pondicherry Institute of Medical Sciences (PIMS), Kalapet, Puducherry, India, from November 2018 to November 2020. All diabetic patients between 25- 60 years, who attended the medicine Outpatient Department (OPD) or were admitted into the medical wards, were screened, among which 280 subjects were selected for the study. Patients with Estimated Glomerular Filtration Rate (eGFR) of more than 45 mL/min/1.73m2 were characterised as cases and those with eGFR of more than 90 mL/min/1.73m2 were controls. Echocardiographic parameters were recorded. Chi-square test, Mann-Whitney U test, and unpaired t-test were used for statistical analysis. Multivariate logistic regression analysis was done using an odd’s ratio to assess the association between early DKD and cardiac dysfunction. Results: The number of diabetics with early kidney disease (cases) were 139 and without kidney disease (controls) were 141. The mean age of the cases was 54.63±4.84 years and the controls were 52.61±7.916 years. The number of males among the cases and controls were 68 (48.92%) out of 139 and 96 (68.1%) out of 141, respectively. The prevalence of systolic dysfunction among diabetic patients with early kidney disease was 12.23% (17/139) and diastolic dysfunction was prevalent in 99.29% (138/139). Systolic dysfunction was 9.68 times more common in cases (n=139) than in controls (n=141). Women had a 2.6 times higher likelihood, and hypertension had (an independent association which was) a 2.6 times higher likelihood of developing cardiac dysfunction in the early stages of DKD. Conclusion: Systolic cardiac dysfunction is significantly higher (9.68 times more common) in those with early DKD when compared to those without kidney disease; with female gender and systemic hypertension as independent and significant risk factors.

Abstract 8881: Comprehensive Assessment of Systemic Atherosclerosis in Relation to the Ocular Resistive Index in Acute Coronary Syndrome Patients

Introduction: It remains unclear how systemic atherosclerosis can affect ocular microvessels. The abnormality of the ocular microvasculatures can be non-invasively detected by measuring ocular arterial blood flow velocity using laser speckle flowgraphy (LSFG). Among the ocular blood flow parameters obtained by LFSG, the ocular blowout time (BOT) and the ocular resistivity index (RI) are used as the index of retinal vascular resistance. The purpose of this study was to investigate the relationship between ocular vascular resistance evaluated by LSFG and cardiac function evaluated by transthoracic echocardiography in patients with acute coronary syndrome (ACS). Methods: We evaluated 53 patients with ACS who were taken to Coronary Care Unit between April 2019 and September 2020. The mean blur rate (MBR), the ocular blowout time (BOT) and the ocular resistivity index (RI) were measured by LSFG. In addition, the age-matched normal subjects were also evaluated the measurement of LSFG in 20 healthy subjects with no ocular disease and no history of cardiovascular disease. Results: Among all ACS patients, there were significant positive correlations between ocular RI and systemic parameters, i.e., IMT(r = 0.34, P = 0.01), PWV(r = 0.41, P &lt; 0.01), BUN(r = 0.27, P = 0.047), cystatin C(r = 0.32, P = 0.020), urinary β2 microglobulin(r = 0.30, P = 0.029), L-FABP(r = 0.28, P = 0.046), and E/e’(r = 0.34, P = 0.013). There was also significant negative correlation between ocular BOT and PWV(r = -0.44, P &lt; 0.01). Age-matched comparing the selective ACS (n=20) with healthy group (n=20), the ocular RI was significantly higher in the ACS group (0.34 ± 0.04 vs 0.38 ± 0.07, P = 0.03). Conclusions: We found that the ocular resistivity index, which was non-invasively obtained by LSFG, was associated with systemic atherosclerosis, early renal dysfunction and cardiac diastolic dysfunction in ACS patients, suggesting that it might be useful index as an non-invasive comprehensive arteriosclerotic markers.

Advances in Biomarkers for Detecting Early Cancer Treatment-Related Cardiac Dysfunction.

With the gradual prolongation of the overall survival of cancer patients, the cardiovascular toxicity associated with oncology drug therapy and radiotherapy has attracted increasing attention. At present, the main methods to identify early cancer treatment-related cardiac dysfunction (CTRCD) include imaging examination and blood biomarkers. In this review, we will summarize the research progress of subclinical CTRCD-related blood biomarkers in detail. At present, common tumor therapies that cause CTRCD include: (1) Chemotherapy—The CTRCD induced by chemotherapy drugs represented by anthracycline showed a dose-dependent characteristic and most of the myocardial damage is irreversible. (2) Targeted therapy—Cardiovascular injury caused by molecular-targeted therapy drugs such as trastuzumab can be partially or completely alleviated via timely intervention. (3) Immunotherapy—Patients developed severe left ventricular dysfunction who received immune checkpoint inhibitors have been reported. (4) Radiotherapy—CTRCD induced by radiotherapy has been shown to be significantly associated with cardiac radiation dose and radiation volume. Numerous reports have shown that elevated troponin and B-type natriuretic peptide after cancer treatment are significantly associated with heart failure and asymptomatic left ventricular dysfunction. In recent years, a few emerging subclinical CTRCD potential biomarkers have attracted attention. C-reactive protein and ST2 have been shown to be associated with CTRCD after chemotherapy and radiation. Galectin-3, myeloperoxidas, placental growth factor, growth differentiation factor 15 and microRNAs have potential value in predicting CTRCD. In this review, we will summarize CTRCD caused by various tumor therapies from the perspective of cardio-oncology, and focus on the latest research progress of subclinical CTRCD biomarkers.

Global Longitudinal Myocardial Strain Correlates with Degree of Anemia in Sickle Cell Disease but Not Transfusion-Dependent Thalassemia

Cardiac failure is one of the leading causes of death in sickle cell disease (SCD) and transfusion-dependent thalassemia (TDT). For this reason, early detection of silent cardiac dysfunction is crucial for treatment and prevention of heart failure. Speckle-tracking echocardiography (STE) is an easily accessible tool for analyzing myocardial function and this modality has increased sensitivity in detecting asymptomatic disease. Attenuation in cardiac strain has been correlated to early systolic dysfunction among patients with cardiomyopathies. This technique has not been consistently evaluated in children with SCD and TDT. Due to the role of anemia and siderosis in the pathology of cardiac dysfunction, we hypothesized that early myocardial dysfunction correlates with the degree of anemia and hyperferritinemia in SCD. We analyzed the clinical, echocardiographic, STE and laboratory parameters in SCD and compared them to children with TDT and normal controls.We retrospectively analyzed date from consecutive patients with SCD and TDT who received treatment at our institution from 2008 to 2018. Echocardiographic data from children with benign murmurs served as normal controls (NC). Data was independently verified by a pediatric cardiologist. Descriptive and correlation analysis were used; a p-value < 0.05 was considered significant.Echocardiographic data were available for 77 SCD (HbSS and HbS/ ß 0 Thal), 25 TDT (ß 0/ ß 0 and ß +/ ß + Thal)and 138 NC. Mean hemoglobin (Hg) and ferritin values were 9.8 g/dl (6.8-14.6 g/dl); 392 ng/ml (19.3-8,3437.67 ng/ml), respectively for SCD patients and 9.3 g/dl (7-17.03 ng/dl); 2,960 ng/ml (13-13,831 ng/ml), respectively for TDT. Standard echocardiographic parameters left ventricular ejection fraction (LVEF), right VEF and LV shortening fraction (LVSF) were within the normal limits in SCD, TDT, and NC children. Significant differences were observed in the steady-state global circumferential strain (GCS) between the three groups SCD, TDT and NC [-26.5 (mean), 3.6 (SD); -27.6 (mean), 4.8(SD); -25.0 (mean), 3.6 (SD), respectively; p = 0.002] (Table 1). Subset analysis based on ferritin levels (> or < 1000 ng/ml), revealed no significant difference in GCS between the SCD or TDT groups (Table 2). However, global longitudinal strain (GLS) was significantly lower among SCD compared to TDT with ferritin levels greater than 1,000 ng/ml (Table 2). A positive correlation (r = 0.25, p = 0.046) was found between GLS and Hg in SCD patients (n=63) (Figure 1). No significant correlation was found between Hg and GLS in the TDT group (Figure 2). No significant correlation was found between GCS and Hg (r = 0.1, p = 0.42); GLS and GCS and ferritin in the SCD group. LVEF was found to be normal in patients with abnormal strain indices.Cardiac strain indices are abnormal in children with SCD and TDT compared to normal children. Significantly abnormal GLS was noted in hyperferritinemic SCD patients compared to TDT patients. A positive correlation between severity of anemia and GLS was observed in this study in SCD children. Based on these results, we speculate that therapies aimed at ameliorating anemia can potentially improve GLS and thus, early cardiac dysfunction in SCD patients. However, further studies are warranted to understand the contributory role of anemia and hyperferritinemia and its therapeutic implications on early myocardial dysfunction in SCD. [Display omitted] DisclosuresSathi: Vertex Pharmaceuticals: Consultancy.

Heart Failure in Breast Cancer Survivors: Focus on Early Detection and Novel Biomarkers.

Breast cancer survival rate has greatly improved in the last two decades due to the emergence of next-generation anti-cancer agents. However, cardiotoxicity remains a significant adverse effect arising from traditional and emerging chemotherapies as well as targeted therapies for breast cancer patients. In this review, we will discuss cardiotoxicities of both traditional and emerging therapies for breast cancer. We will discuss current practices to detect cardiotoxicity of these therapies with the focus on new and emerging biomarkers. We will then focus on 'omics approaches, especially the use of epigenetics to discover novel biomarkers and therapeutics to mitigate cardiotoxicity. Significant cardiotoxicities of conventional chemotherapies remain and new and unpredictable new forms of cardiac and/or vascular toxicity emerge with the surge in novel and targeted therapies. Yet, there is no clear guidance on detection of cardiotoxicity, except for significant left ventricular systolic dysfunction, and even then, there is no uniform definition of what constitutes cardiotoxicity. The gold standard for detection of cardiotoxicity involves a serial echocardiography in conjunction with blood-based biomarkers to detect early subclinical cardiac dysfunction. However, the ability of these tests to detect early disease remains limited and not all forms of toxicity are detectable with these modalities. There is an unprecedented need to discover novel biomarkers that are sensitive and specific for early detection of subclinical cardiotoxicity. In that space, novel echocardiographic techniques, such as strain, are becoming more common-place and new biomarkers, discovered by epigenetic approaches, seem to become promising alternatives or adjuncts to conventional non-specific cardiac biomarkers.

Abstract MP228: The Role Of Gut Microbiome Secreted Short Chain Fatty Acids In The Development Of Heart Failure With Preserved Ejection Fraction HFpEF

More than 50% of patients with heart failure are diagnosed with heart failure with preserved ejection fraction (HFpEF), and 80% of them are obese. It is a prominent disease with no available treatments. It is characterized by diastolic dysfunction that involves increase in left ventricle stiffness and decrease in its relaxation during diastole. To better understand the pathogenesis of obesity associated HFpEF, our studies focus on the early asymptomatic changes in cardiac mechanics that occurs before the increases in intracardiac pressure. Therefore, we have developed an obesity associated mouse model that we called pre-HFpEF where mice were fed either Normal Chow or Western Diet for 14 weeks. Our echocardiography measurements indicated the presence of early cardiac dysfunction consistent with obesity associated pre-HFpEF phenotype. Mice on WD had decrease in Global Longitudinal Strain (%GLS) and Longitudinal strain rate reverse (LSRr) indicating early signs of systolic and diastolic dysfunction, as well as increase in left ventricle anterior and posterior wall thickness during diastole (LVAWd, LVPWd). Obesity is also known to cause microbiome imbalance, which plays a significant role in the development of cardiovascular diseases through changes in short chains fatty acids, which are products of dietary fiber fermentation by the gut bacteria. In order to study the association between gut microbiome imbalance and HFpEF development, we treated our obese pre-HFpEF mice with fecal matter transplantation (FMT) from either lean or obese mice, and we found that FMT from lean mice led to significant improvements in systolic and diastolic dysfunction by increasing %GLS and LSRr and preventing hypertrophy by decreasing LVAWd and LVPWd. In addition, WD reduced butyrate producing bacteria, however circulating levels of butyrate were significantly increased with lean FMT treatment. Using an in-vitro approach to mimic WD we found butyrate treatment to inhibit the activation of NLRP3 inflammasome and NF-KB. Therefore, since FMT treatment improved cardiac dysfunction in obesity associated pre-HFpEF mice, and that butyrate is increased after FMT and can play a role in metabolic homeostasis, we predict that butyrate could be an important player in FMT improvements through cardiac metabolic regulation and cardiac inflammation suppression

Sirtuin 1, Visfatin and IL-27 Serum Levels of Type 1 Diabetic Females in Relation to Cardiovascular Parameters and Autoimmune Thyroid Disease.

The loss of cardioprotection observed in premenopausal, diabetic women may result from the interplay between epigenetic, metabolic, and immunological factors. The aim of this study was to evaluate the concentration of sirtuin 1, visfatin, and IL-27 in relation to cardiovascular parameters and Hashimoto’s disease (HD) in young, asymptomatic women with type 1 diabetes mellitus (T1DM). Thyroid ultrasound, carotid intima-media thickness (cIMT) measurement, electrocardiography, and echocardiography were performed in 50 euthyroid females with T1DM (28 with HD and 22 without concomitant diseases) and 30 controls. The concentrations of serum sirtuin 1, visfatin and IL-27 were assessed using ELISA. The T1DM and HD group had higher cIMT (p = 0.018) and lower left ventricular global longitudinal strain (p = 0.025) compared to females with T1DM exclusively. In women with a double diagnosis, the sirtuin 1 and IL-27 concentrations were non-significantly higher than in other groups and significantly positively correlated with each other (r = 0.445, p = 0.018) and thyroid volume (r = 0.511, p = 0.005; r = 0.482, p = 0.009, respectively) and negatively correlated with relative wall thickness (r = –0.451, p = 0.016; r = –0.387, p = 0.041, respectively). These relationships were not observed in the control group nor for the visfatin concentration. These results suggest that sirtuin 1 and IL-27 contribute to the pathogenesis of early cardiac dysfunction in women with T1DM and HD.

Skeletal Muscle Microvascular Dysfunction Manifests Early in Diabetic Cardiomyopathy.

Aim: To perform a deep cardiac phenotyping of type II diabetes in a rat model, with the goal of gaining new insight into the temporality of microvascular dysfunction, cardiac dysfunction, and exercise intolerance at different stages of diabetes.Methods and Results: Diabetes was reproduced using a non-obese, diet-based, low-dose streptozotocin model in male rats (29 diabetic, 11 control). Time-course monitoring over 10 months was performed using echocardiography, treadmill exercise, photoacoustic perfusion imaging in myocardial and leg skeletal muscle, flow-mediated dilation, blood panel, and histology. Diabetic rats maintained a normal weight throughout. At early times (4 months), a non-significant reduction (30%) emerged in skeletal muscle perfusion and in exercise tolerance. At the same time, diabetic rats had a normal, slightly lower ejection fraction (63 vs. 71% control, p < 0.01), grade 1 diastolic dysfunction (E/A = 1.1 vs. 1.5, isovolumetric relaxation time = 34 vs. 27 ms; p < 0.01), mild systolic dysfunction (ejection time = 69 vs. 57 ms, isovolumetric contraction time = 21 vs. 17 ms; p < 0.01), and slightly enlarged left ventricle (8.3 vs. 7.6 mm diastole; p < 0.01). Diastolic dysfunction entered grade 3 at Month 8 (E/A = 1.7 vs. 1.3, p < 0.05). Exercise tolerance remained low in diabetic rats, with running distance declining by 60%; in contrast, control rats ran 60% farther by Month 5 (p < 0.05) and always remained above baseline. Leg muscle perfusion remained low in diabetic rats, becoming significantly lower than control by Month 10 (33% SO2 vs. 57% SO2, p < 0.01). Myocardial perfusion remained normal throughout. Femoral arterial reactivity was normal, but baseline velocity was 25% lower than control (p < 0.05). High blood pressure appeared late in diabetes (8 months). Histology confirmed absence of interstitial fibrosis, cardiomyocyte hypertrophy, or microvascular rarefaction in the diabetic heart. Rarefaction was also absent in leg skeletal muscle.Conclusion: Reduced skeletal muscle perfusion from microvascular dysfunction emerged early in diabetic rats, but myocardial perfusion remained normal throughout the study. At the same time, diabetic rats exhibited exercise intolerance and early cardiac dysfunction, in which changes related to heart failure with preserved ejection fraction (HFpEF) were seen. Importantly, skeletal muscle microvascular constrictionadvanced significantly before the late appearance of hypertension. HFpEF phenotypes such as cardiac hypertrophy, fibrosis, and rarefaction, which are typically associated with hypertension, were absent over the 10 month time-course of diabetes-related heart failure.

Early Myocardial Dysfunction and Benefits of Cardiac Treatment in Young X-Linked Duchenne Muscular Dystrophy Mice.

Duchenne muscular dystrophy (DMD) is associated with a progressive alteration in cardiac function. The aim of this study was to detect early cardiac dysfunction using the high sensitive two-dimensional speckle-tracking echocardiography (2D strain) in mdx mouse model and to investigate the potential preventive effects of the S107 ryanodine receptor (RyR2) stabilizer on early onset of DMD-related cardiomyopathy. Conventional echocardiography and global and segmental left ventricle (LV) 2D strains were assessed in male mdx mice and control C57/BL10 mice from 2 to 12months of age. Up to 12months of age, mdx mice showed preserved myocardial function as assessed by conventional echocardiography. However, global longitudinal, radial, and circumferential LV 2D strains significantly declined in mdx mice compared to controls from the 9months of age. Segmental 2D strain analysis found a predominant alteration in posterior, inferior, and lateral LV segments, with a more marked impairment with aging. Then, mdx mice were treated with S107 in the drinking water at a dose of 250mg/L using two different protocols: earlier therapy from 2 to 6months of age and later therapy from 6 to 9months of age. The treatment with S107 was efficient only when administered earlier in very young animals (from 2 to 6months of age) and prevented the segmental alterations seen in non-treated mdx mice. This is the first animal study to evaluate the therapeutic effect of a drug targeting early onset of DMD-related cardiomyopathy, using 2D strain echocardiography. Speckle-tracking analyses revealed early alterations of LV posterior segments that could be prevented by 4months of RyR2 stabilization.

Triggers of Cardiovascular Diseases in Rheumatoid Arthritis.

The risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) is higher than that in patients without RA, and it is even higher than that in patients with diabetes. Autoimmune-mediated inflammation is observed in patients with RA, resulting in endothelial dysfunction, oxidative stress and activation, and vascular migration of white blood cells. Traditionally, RA-associated CVD was assumed to be mediated by disease-related inflammation, resulting in atherosclerosis (AS). However, this concept has been challenged because treatment with anti-rheumatic drugs, such as methotrexate or proinflammatory cytokine antagonists, such as tumor necrosis factor-alpha (TNF-α) inhibitors, did not reduce the risk of CVD in patients with RA. Current cardiovascular guidelines recommend screening and treatment of CVD risk factors in patients with RA but without clear biomarkers and treatment goals. There is no scientific basis for establishing therapeutic targets for cardiovascular risk factors in RA. Numerous studies have shown that the mechanism of early cardiac dysfunction in patients with RA may occur prior to AS. Therefore, it is crucial to explore the related mechanisms to prevent early cardiac dysfunction in patients with RA.

IN MILD HYPERTENSIVE PATIENTS 24-HOUR AVERAGE HEART RATE IS ASSOCIATED WITH EARLY CARDIAC DAMAGE AND ENDOTHELIAL DYSFUNCTION

Objective: To investigate the correlation of 24-hour average heart rate (HR) in untreated and recently diagnosed mild hypertensives, and evaluate their association with subclinical initial signs of cardiac target organ damage (TOD), and endothelial dysfunction. Design and method: A total of 400 outpatients with initial diagnosis of mild hypertension were recruited between December 2017 and November 2019. Ambulatory electrocardiogram and blood pressure (BP) were monitored in all patients. According to the 24-hour average HR, patients were divided into fast HR group (24-hour average HR &gt; 75 beats/minute, n = 220) and non-fast HR group (24-hour average HR less or equal to 75 beats/minute, n = 180) We evaluate endothelial dysfunction by flow mediated vasodilatation (FMD) at the level of brachial artery. We use echocardiography to determine the presence of initial signs of (TOD), (presence of signs of left ventricular hypertrophy left ventricular mass indexed for height (LVMi) &gt; 48 g/m2 for men and &gt; 44 g/m2 for women and/or increased left atrial volume 4-chamber indexed for body surface area (LAVi) &gt; 34 ml/m2). Results: Endothelial dysfunction, LVMi and LAVi, 24-hour average HR, night and day average HR, diastolic BP, and daytime systolic BP were higher, while nocturnal BP drop rate was lower in patients with fast HR group than those in non-fast HR group (all P &lt; 0.04). Twenty-four-hour HR, the degree of endothelial dysfunction and TOD increased significantly with increases of office BP (P &lt; 0.04). The 24-hour average HR and resting HR were correlated positively with the presence of TOD (r = 0.159, 0.262, respectively, both P &lt; 0.01), and degree of endothelial dysfunction (r = 0.155, 0.260, respectively, both P &lt; 0.01). Multivariate linear regression analysis showed that the level of BP (B = 17.420, 16.540), nocturnal BP drop rate (B = 1.652, 1,586), and 24-hour average HR (B = 0.558, 0.5442) were correlated with the presence of TOD and FMD cuantified endothelial dysfunction. Conclusions: In patients with initial diagnosis of mild hypertension, 24-hour average heart rate is associated with the early cardiac damage and endothelial dysfunction, confirming the participation of increased heart rate in initial cardiac and vascular changes in human hypertension.

Early-onset Cardiotoxicity assessment related to anthracycline in children with leukemia. A Prospective Study.

Background: Acute leukemias are the most frequent malignancies in children. Advances in treatment have improved the overall survival to 80%. Almost 10% of children with cancer develop clinical cardiac toxicity. Total anthracycline cumulative dose is a risk factor for early-onset cardiotoxicity.Objective: To describe the incidence of early-onset cardiotoxicity in children with acute leukemia treated with chemotherapy.Methods: A prospective descriptive study of patients >1 y and <18 years diagnosed with acute leukemia. Assessed with electrocardiograma, echocardiography, and blood biomarkers at diagnosis and during the follow-up.Results: 94 patients with acute lymphoblastic leukemia and 18 with acute myeloid leukemia were included. 20 patients (17.9%) developed early-onset cardiotoxicity. Statistically significant data was seen after anthracycline dose >150 mg/m2, between the first echocardiographic evaluation and posterior analyses in the left ventricular fraction ejection with Teicholz p 0.05, Simpson p 0.018 and GLS p 0.004. In this study, there was no relation between blood biomarkers and cardiotoxicity.Conclusions: Cancer therapeutic-related cardiac dysfunction is related to anthracycline cumulative dose. In this study, echocardiographic follow-up was useful to predict risk factors for early cardiac dysfunction.