Cardiac Structural Changes Research Articles

Metabolic Changes Precede Radiation-Induced Cardiac Remodeling in Beagles: Using Noninvasive 18F-FDG (18F-Fludeoxyglucose) and 13N-Ammonia Positron Emission Tomography/Computed Tomography Scans.

BackgroundThis study was performed to characterize the metabolic, functional, and structural cardiac changes in a canine model of radiation‐induced heart disease by serial in vivo imaging and ex vivo analyses.Methods and ResultsThirty‐six dogs were randomly assigned to control or irradiated groups at 3 time points (months 3, 6, and 12 after radiation; each group comprised 6 dogs). The left anterior myocardium of dogs in irradiated groups was irradiated locally with a single dose of 20‐Gy X‐ray. The irradiated myocardial regions showed increased myocardial uptake of 18F‐FDG (18F‐fludeoxyglucose) in the irradiated beagles, but the increased uptake area decreased at months 6 and 12 compared with month 3 after radiation. Abnormality of myocardial perfusion and cardiac function were detected at month 6 after radiation. Compared with the control groups, the protein expression of GLUT4 (glucose transporter 4) was upregulated in the irradiated groups, correlating with significantly decreased CPT1 (carnitine acyltransferase 1) expression. Mitochondria degeneration, swelling, and count reduction in the irradiated groups were observed. The difference in CD68 of macrophage markers and the inflammatory cytokines (IL‐6 [interleukin 6], TNF‐α [tumor necrosis factor α]) between the irradiation and control groups was not significant. Furthermore, the progressive aggravation of apoptosis and fibrosis was displayed.ConclusionsElevated 18F‐FDG uptake occurred after irradiation and subsequently led to ventricular perfusion defects and dysfunction. The process was associated with myocardial metabolic substrate remodeling, cardiac muscle cell apoptosis, and myocardial fibrosis rather than inflammation.

Exercise Regulates MicroRNAs to Preserve Coronary and Cardiac Function in the Diabetic Heart.

Diabetic heart disease (DHD) is a debilitating manifestation of type 2 diabetes mellitus. Exercise has been proposed as a potential therapy for DHD, although the effectiveness of exercise in preventing or reversing the progression of DHD remains controversial. Cardiac function is critically dependent on the preservation of coronary vascular function. We aimed to elucidate the effectiveness and mechanisms by which exercise facilitates coronary and cardiac-protection during the onset and progression of DHD. Diabetic db/db and nondiabetic mice, with or without underlying cardiac dysfunction (16 and 8 weeks old, respectively) were subjected to either moderate-intensity exercise or high-intensity exercise for 8 weeks. Subsequently, synchrotron microangiography, immunohistochemistry, Western blot, and real-time polymerase chain reaction were used to assess time-dependent changes in cardiac and coronary structure and function associated with diabetes mellitus and exercise and determine whether these changes reflect the observed changes in cardiac-enriched and vascular-enriched microRNAs (miRNAs). We show that, if exercise is initiated from 8 weeks of age, both moderate-intensity exercise and high-intensity exercise prevented the onset of coronary and cardiac dysfunction, apoptosis, fibrosis, microvascular rarefaction, and disruption of miRNA signaling, as seen in the nonexercised diabetic mice. Conversely, the cardiovascular benefits of moderate-intensity exercise were absent if the exercise was initiated after the diabetic mice had already established cardiac dysfunction (ie, from 16 weeks of age). The experimental silencing or upregulation of miRNA-126 activity suggests the mechanism underpinning the cardiovascular benefits of exercise were mediated, at least in part, through tissue-specific miRNAs. Our findings provide the first experimental evidence for the critical importance of early exercise intervention in ameliorating the onset and progression of DHD. Our results also suggest that the beneficial effects of exercise are mediated through the normalization of cardiovascular-enriched miRNAs, which are dysregulated in DHD.

Electrocardiographic Evaluation of Cardiac Rhythm: A Comparative Study of Apparently Healthy German Shepherd Dogs Versus Dogs with Cardiac Affections

Background: The objective of the present study was to define existence of age and body weight related cardiac structural and functional changes in both healthy GSD as well as those having structural or functional cardiac affections. Thus the present study was conducted to establish the reference values of various parameters of ECG based on age and body weight and further evaluation of clinical cases based on these reference values. Method: The present study was conducted on eight apparently healthy German shepherd dogs aged 36-72 months with body weight 22-33.2 kg free from cardio-thoracic diseases to establish the reference values of various electrocardiographic parameters (Group-I) and used to evaluate the cardiac rhythm in 3 GSD dogs having some cardiac diseases (Group-II) based on the reference values obtained from Group-I. Result: Heart rate showed negative correlation with age and body weight. Positive correlation of amplitude of S and T wave, QRS complex, duration of T wave, P-R interval and R-R interval with age and body weight; amplitude of Q wave, duration of P wave and Q-T interval with body weight was observed. Negative correlation of amplitude of P and R wave, S-T interval with age and body weight; amplitude of Q wave, duration of P wave and Q-T interval with age was observed.

Cardiovascular Changes in Patients With COVID-19 From Wuhan, China

Background: Coronavirus disease 2019 (COVID-19) is rapidly spreading and resulting in a significant loss of life around the world. However, specific information characterizing cardiovascular changes in COVID-19 is limited.Methods: In this single-centered, observational study, we enrolled 38 adult patients with COVID-19 from February 10 to March 13, 2020. Clinical records, laboratory findings, echocardiography, and electrocardiogram reports were collected and analyzed.Results: Of the 38 patients enrolled, the median age was 68 years [interquartile range (IQR), 55–74] with a slight female majority (21, 55.3%). Nineteen (50.0%) patients had hypertension. Seven (33.3%) had ST-T segment and T wave changes, and four (19%) had sinus tachycardia. Twenty (52.6%) had an increase in ascending aorta (AAO) diameter, 22 (57.9%) had an increase in left atrium (LA) size, and 28 (73.7%) presented with ventricular diastolic dysfunction. Correlation analysis showed that the AAO diameter was significantly associated with C-reactive protein (r = 0.4313) and creatine kinase-MB (r = 0.0414). LA enlargement was significantly associated with C-reactive protein (r = 0.4377), brain natriuretic peptide (r = 0.7612), creatine kinase-MB (r = 0.4940), and aspartate aminotransferase (r = 0.2947). Lymphocyte count was negatively associated with the AAO diameter (r = −0.5329) and LA enlargement (r = −0.3894).Conclusions: Hypertension was a common comorbidity among hospitalized patients with COVID-19, and cardiac injury was the most common complication. Changes in cardiac structure and function manifested mainly in the left heart and AAO in these patients. Abnormal AAO and LA size were found to be associated with severe inflammation and cardiac injury. Alternatively, ascending aortic dilation and LA enlargement might be present before infection but characterized the patient at risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Assessment of cardiac structure and function in kidney failure: understanding echocardiography and magnetic resonance imaging for the nephrologist.

Cardiovascular disease is the leading cause of death in patients with kidney failure or on chronic dialysis. Patients on chronic dialysis have a 10- to 50-fold increased risk of sudden cardiac death compared to patients with normal kidney function. Adverse changes in cardiac structure and function may not manifest with clinical symptoms in patients with kidney failure and, therefore, pose a challenge in identifying cardiac dysfunction early. Fortunately, there are multi-modality cardiac imaging techniques available, including echocardiography and cardiac magnetic resonance imaging, that can help our understanding of the pathophysiology of cardiac dysfunction in kidney failure. This review describes the benefits and limitations of these two commonly available cardiac imaging modalities to assess cardiac structure and function, thereby aiding nephrologists in choosing the most appropriate investigative tool based on individual clinical circumstances. For the purposes of this review, cardiac imaging for detection of coronary artery disease has been omitted.

Maladaptive Changes Associated With Cardiac Aging Are Sex-Specific and Graded by Frailty and Inflammation in C57BL/6 Mice

We investigated whether late-life changes in cardiac structure and function were related to high levels of frailty and inflammation in male and female mice. Frailty (frailty index), ventricular structure/function (echocardiography), and serum cytokines (multiplex immunoassay) were measured in 16- and 23-month-old mice. Left ventricular (LV) mass and septal wall thickness increased with age in both sexes. Ejection fraction increased with age in males (60.4 ± 1.4 vs 68.9 ± 1.8%; p < .05) but not females (58.8 ± 2.5 vs 62.6 ± 2.4%). E/A ratios declined with age in males (1.6 ± 0.1 vs 1.3 ± 0.1; p < .05) but not females (1.4 ± 0.1 vs 1.3 ± 0.1) and this was accompanied by increased ventricular collagen levels in males. These changes in ejection fraction (r = 0.52; p = .01), septal wall thickness (r = 0.59; p = .002), E/A ratios (r = −0.49; p = .04), and fibrosis (r = 0.82; p = .002) were closely graded by frailty scores in males. Only septal wall thickness and LV mass increased with frailty in females. Serum cytokines changed modestly with age in both sexes. Nonetheless, in males, E/A ratios, LV mass, LV posterior wall thickness, and septal wall thickness increased as serum cytokines increased (eg, IL-6, IL-3, IL-1α, IL-1β, tumor necrosis factor-α, eotaxin, and macrophage inflammatory protein-1α), while ejection fraction declined with increasing IL-3 and granulocyte-macrophage colony stimulating factor. Cardiac outcomes were not correlated with inflammatory cytokines in females. Thus, changes in cardiac structure and function in late life are closely graded by both frailty and markers of inflammation, but this occurs primarily in males. This suggests poor overall health and inflammation drive maladaptive changes in older male hearts, while older females may be resistant to these adverse effects of frailty.

Cardiac function in gestational diabetes mellitus: A longitudinal study from fetal life to infancy.

To determine whether cardiac functional and structural changes in fetuses of mothers with gestational diabetes mellitus (GDM) persist in the offspring beyond the neonatal period. Longitudinal study. Fetal Medicine Unit in a UK teaching hospital. 73 women with GDM and 73 women with uncomplicated pregnancy were recruited and fetal cardiac scans were performed at 35-36weeks' gestation. Repeat echocardiogram was performed in their offspring during infancy. Fetal and infant cardiac functional and structural changes. Fetuses of mothers with GDM, compared with controls, had more globular right ventricles (sphericity index 0.7, interquartile range [IQR] 0.6/0.7 versus 0.6, IQR 0.5/0.6, P<0.001) and reduced right global longitudinal systolic strain (-16.4, IQR -18.9/-15.3 versus -18.5, IQR -20.6/-16.8, P=0.001) and left global longitudinal systolic strain (-20.1, IQR -22.5/-16.9 versus -21.3, IQR -23.5/-19.5), P=0.021). In the GDM group, compared with controls, in infancy there was higher left ventricular E/e' (8.7, IQR 7.3/9.7 versus 7.9 IQR, 6.8/8.9 P=0.011) and lower left ventricular global longitudinal systolic strain (-21.0, IQR -22.5/-19.4 versus -22.3, IQR -23.5/-20.7, P=0.001) and tricuspid annular plane systolic excursion (13.8, IQR 12.7/16.1 versus 15.2, IQR 13.8/16.8, P=0.003). These differences remained following multivariable analysis. Gestational diabetes mellitus is associated with alterations in fetal cardiac function and structure compared with controls and persistent cardiac changes in infancy. Gestational diabetes mellitus, even when well controlled, is associated with fetal cardiac changes and these persist in infancy.

Impact of the Vulnerable Preterm Heart and Circulation on Adult Cardiovascular Disease Risk.

Preterm birth accounts for over 15 million global births per year. Perinatal interventions introduced since the early 1980s, such as antenatal glucocorticoids, surfactant, and invasive ventilation strategies, have dramatically improved survival of even the smallest, most vulnerable neonates. As a result, a new generation of preterm-born individuals has now reached early adulthood, and they are at increased risk of cardiovascular diseases. To better understand the sequelae of preterm birth, cardiovascular follow-up studies in adolescents and young adults born preterm have focused on characterizing changes in cardiac, vascular, and pulmonary structure and function. Being born preterm associates with a reduced cardiac reserve and smaller left and right ventricular volumes, as well as decreased vascularity, increased vascular stiffness, and higher pressure of both the pulmonary and systemic vasculature. The purpose of this review is to present major epidemiological evidence linking preterm birth with cardiovascular disease; to discuss findings from clinical studies showing a long-term impact of preterm birth on cardiac remodeling, as well as the systemic and pulmonary vascular systems; to discuss differences across gestational ages; and to consider possible driving mechanisms and therapeutic approaches for reducing cardiovascular burden in individuals born preterm.

Identification of potentially effective antiarrhythmic drugs to individualize premature ventricular contraction therapy in patients without structural cardiac changes

Identification of potentially effective antiarrhythmic drugs to individualize premature ventricular contraction therapy in patients without structural cardiac changes

Structural and functional myocardial abnormalities and arrhythmias in patients with type 1 diabetes complicated with ketoacidosis

Aim.To study the structural and functional cardiac changes and arrhythmias in patients with type 1 diabetes (T1D) complicated with ketoacidosis.Material and methods.We analyzed 24-hour Holter monitoring data in 112 patients with T1D complicated with diabetic ketoacidosis (DKA). To assess the left ventricular (LV) diastolic function, all patients underwent echocardiography.Results.In patients with T1D complicated with DKA, the following cardiac arrhythmias were recorded: supraventricular arrhythmias — 60,7%, premature ventricular contractions — 26,2%, premature ventricular and supraventricular contractions — 13,1%. In 30% of patients with T1D complicated with DKA, premature ventricular contractions were classified as class 4A, in 10% — class 4B. With severe DKA, 5% of patients had short runs of unstable ventricular tachycardia. As the severity of ketosis increases, myocardial remodeling and LV diastolic dysfunction are recorded, as well as the spectral and temporal parameters of heart rate variability decrease.Conclusion.In patients with T1D complicated with DKA, structural and functional LV abnormalities, the development of LV diastolic dysfunction and cardiac arrhythmias are more often recorded. The most pronounced changes were found in the group of patients with T1D with moderate and severe DKA.

Abstract LB-211: Synergistic anti-metastatic effect of pembrolizumab in combination with a novel mTORC1 inhibitor/AMPK agonist in a CAM metastatic triple negative breast cancer model

Abstract Triple negative breast cancer (TNBC) is highly aggressive and has higher rates of recurrence, resistance, and death than other breast cancers. Ten year survival rate is &amp;lt; 50%. Changes in the tumor stroma create an environment that provides support for tumor growth, progression, invasion and metastasis. The most prominent cell type in the tumor stroma is an activated form of fibroblasts, known as cancer associated fibroblasts (CAFs). In breast cancer, as much as 80% of stromal fibroblasts acquire the CAF phenotype secreting growth factors, hormones, and cytokines that act upon both the tumor and the stroma to promote the metastatic phenotype. NovoMedix has developed a novel mTORC1 inhibitor/AMPK agonist (NMIC9) that inhibits tumor cell proliferation, migration (98% decrease, p=0.0002), and invasion; and it prevents activation of the tumor stroma and formation of CAFs. NMIC9, a small molecule, has demonstrated oral efficacy as a single agent in mouse models of TNBC (93% reduction in tumor growth, p&amp;lt;0.005, with no significant tumor regrowth after treatment cessation) and safety in non-GLP toxicology studies in rats (NOAEL &amp;gt; 1000 mg/kg p.o.). Further, NMIC9 has no hERG effects, no CYP interactions, no mutagenicity in the AMES assay, and no kinase inhibition. Many TNBC therapies cause cardiomyopathy leading to heart failure. In primary mouse adult ventricular cardiomyocytes, addition of NMIC9 significantly reduces DOX-induced cardiomyocyte apoptosis and death (p&amp;lt;0.001) while increasing efficacy in TNBC cells. Further, daily treatment with NMIC9 at therapeutic levels for 8 weeks did not cause any changes in cardiac structure or function, indicating that there are no cardiac liabilities. Inhibition of metastases is particularly relevant for TNBC because it is the main cause of mortality. While immune checkpoint inhibitors have shown remarkable response rates in several types of cancer, the response rate in TNBC is only 5 – 30%. A drug that could increase efficacy of immune checkpoint inhibitors and decrease metastasis in TNBC could dramatically improve outcomes for these patients. Recent data in a chicken chorioallantoic membrane model with a highly aggressive TNBC cell line (MDA-MB-231) show that NMIC9 decreases tumor growth and metastasis alone and in combination with pembrolizumab. Tumor regression was 20% for pembrolizumab (ns), 30% for NMIC9 (p&amp;lt;0.05), and 64% for pembrolizumab + NMIC9 (p&amp;lt;0.005). Decrease in metastasis invasion was -0.08% (ns) for pembrolizumab, 49% (p&amp;lt;0.05) for NMIC9, and 64% (p&amp;lt;0.005) for pembrolizumab + NMIC9. Therefore, NMIC9 is a promising first in class drug, which when used in combination with pembrolizumab can significantly reduce tumor growth and metastasis and improve survival rates in TNBC. Citation Format: Leah Fung, Laura G. Corral, Robert W. Sullivan, Kyle W. Chan, Cathy A. Swindlehurst. Synergistic anti-metastatic effect of pembrolizumab in combination with a novel mTORC1 inhibitor/AMPK agonist in a CAM metastatic triple negative breast cancer model [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-211.

Identifying Cardiac Diseases using Cardiac Biomarkers in Rhesus Macaques (Macaca mulatta).

Cardiac biomarkers are an important tool for diagnosing cardiac diseases in both human and veterinary patients. Serum concentrations of N-terminal probrain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) have been used to indicate the presence of various cardiac diseases including hypertrophic cardiomyopathy (HCM) in various species including humans. However, these cardiac biomarkers have not been established as a diagnostic tool for detecting cardiac disease in rhesus macaques. In the rhesus macaque colony at the California National Primate Research Center, naturally occurring HCM and various other cardiac diseases have been identified. In this study, commercially available assays were used to measure serum cTnI and NT-proBNP concentrations to evaluate their utility as a diagnostic screening tool for cardiac diseases in rhesus macaques. This study revealed that the serum cTnI concentration was significantly higher in animals with echocardiographically apparent cardiac disease as compared with the animals that had no cardiac structural and functional changes (the control group). However, no significant differences were detected between animals with HCM and non-HCM cardiac disease. Because the area under the receiver operating characteristic curve was 0.81 when the serum cTnI was compared between the control and cardiac disease groups, serum cTnI was considered a moderately accurate test to predict the presence of cardiac disease. The optimal cut-off value of serum cTnI concentration for diagnosis of cardiac disease was 0.0085 ng/mL, with a sensitivity of 0.68 and specificity of 0.94. Significant but weak correlations were noted between the serum cTnI concentration and several echocardiographic parameters. Conversely, no significant differences in NT-proBNP concentrations were detected between animals with and without cardiac diseases. In conclusion, measurement of serum cTnI can be used to aid in diagnosing cardiac diseases in rhesus macaques. However, cTnI measurement does not replace echocardiographic evaluation to diagnose cardiac diseases in rhesus macaques due to the poor sensitivity of the assay and the weak correlation to with more established echocardiographic markers for cardiac disease.

Prognostic impacts of dynamic cardiac structural changes in heart failure patients with preserved left ventricular ejection fraction.

AimsWe aimed to examine temporal changes in left ventricular (LV) structures and their prognostic impacts in patients with heart failure (HF) and preserved ejection fraction (HFpEF).Methods and resultsIn the Chronic Heart Failure Analysis and Registry in the Tohoku District‐2 (CHART‐2) study (n = 10 219), we divided 2698 consecutive HFpEF patients (68.9 ± 12.2 years, 32.1% female) into three groups by LV hypertrophy (LVH) and enlargement (LVE) at baseline: (−)LVH/(−)LVE (n = 989), (+)LVH/(−)LVE (n = 1448), and (+)LVH/(+)LVE (n = 261). We examined temporal changes in LV structures and their prognostic impacts during a median 8.7‐year follow‐up. From (−)LVH/(−)LVE, (+)LVH/(−)LVE to (+)LVH/(+)LVE at baseline, the incidence of the primary outcome, a composite of cardiovascular death or HF admission, significantly increased. Among 1808 patients who underwent echocardiography at both baseline and 1 year, we noted substantial group transitions from baseline to 1 year; the transition rates from (−)LVH/(−)LVE to (+)LVH/(−)LVE, from (+)LVH/(−)LVE to (−)LVH/(−)LVE, from (+)LVH/(−)LVE to (+)LVH/(+)LVE, and from (+)LVH/(+)LVE to (+)LVH/(−)LVE were 27% (182/671), 22% (213/967), 6% (59/967), and 26% (44/170), respectively. In the univariable Cox proportional hazard model, patients who transitioned from (+)LVH/(−)LVE to (+)LVH/(+)LVE or remained in (+)LVH/(+)LVE had the worst subsequent prognosis [hazard ratio (HR) 4.65, 95% confidence interval (CI) 3.09–6.99, P < 0.001; HR 4.01, 95% CI 2.85–5.65, P < 0.001, respectively], as compared with those who remained in (−)LVH/(−)LVE. These results were unchanged after adjustment for the covariates including baseline LV ejection fraction (LVEF) and 1‐year LVEF change.ConclusionIn HFpEF patients, LV structures dynamically change over time with significant prognostic impacts, where patients who develop LVE with LVH have the worst prognosis.

Disruption of endothelial cell intraflagellar transport protein 88 exacerbates doxorubicin-induced cardiotoxicity

AimsDoxorubicin (DOX) is a potent anticancer drug with severe dose-dependent cardiotoxicity. To address this issue, previous research primarily focused on DOX-induced toxicity on cardiomyocytes. However, more recent research has looked into the endothelium as a therapeutic target due to the emerging role of endothelial cells in the support of cardiomyocyte survival and function. Main methodsWe investigated a novel role of endothelial cell (EC) primary cilia in the prevention of DOX-mediated cardiotoxicity. Mice lacking EC primary cilia, via the deletion of EC-specific intraflagellar protein 88 (IFT88) expression, were administered DOX (20 mg/kg i.p.), and assessed for survival, cardiac function, cardiac structure changes, and indices of cardiomyocyte injury. Key findingsDOX-treatment resulted in reduced survival and cardiac function (ejection fraction and fractional shortening) in EC-IFT88−/− mice vs. their similarly treated wild-type littermates. Cardiomyocyte vacuolization, cardiac fibrosis, and serum CK-MB levels were also increased in DOX-treated mice compared to saline-treated controls. However, these parameters were not significantly different when comparing WT and EC-IFT88−/− mice after DOX treatment. SignificanceThe loss of EC primary cilia accelerated DOX-mediated mortality and reduced cardiac function, suggesting pathways downstream of ciliary-mediated signal transduction as potential targets to promote EC support of cardiomyocyte function during DOX treatment.

Long-term atorvastatin or the combination of atorvastatin and nicotinamide ameliorate insulin resistance and left ventricular diastolic dysfunction in a murine model of obesity

Current studies aimed at investigating the association between atorvastatin therapy and insulin resistance (IR) appear to be controversial. IR is considered to be an important contributor to inducing cardiac dysfunction through multiple signals. The paradoxical cardiotoxicity of atorvastatin reported under different conditions suggests that the association between atorvastatin treatment, insulin resistance and cardiac function should be clarified further. In this study, C57BL/6 J male mice were fed a high-fat diet (HD) or standard chow diet (SD) for 12 weeks and subsequently randomly divided into four groups: the SD-Control (SD-C) and HD-Control (HD-C) groups treated with saline for 10 months and the HD-A and HD-A + N groups treated with atorvastatin (20 mg/kg/day) alone or atorvastatin combined with nicotinamide (NAM, 1 g/kg/day) for 10 months. Although no significant changes in systolic function and structure were observed between the four groups of mice at an age of 46 or 58 weeks, respectively, long-term treatment with atorvastatin alone or atorvastatin and NAM combination significantly retarded the HD-induced IR and diastolic dysfunction and attenuated both cardiac and hepatic fibrosis in obese mice possibly by regulating the cleavage of osteopontin and then controlling profibrotic activity. Changes in cardiac function and structure were similar between the HD-A and HD-A + N groups; however, mice in the HD-A + N group exhibited better glucose control and marked reduction in body weight and hepatic lipid accumulation. Thus, these results suggest that long-term treatment with atorvastatin or the combination of atorvastatin and nicotinamide may be alternative therapies due to their beneficial effects on IR and diastolic function.

Thyroid Hormones within the Normal Range and Cardiac Function in the General Population: The EPIPorto Study

Background: Hypothyroidism and hyperthyroidism are associated with marked changes in cardiac structure and function. However, the association of thyroid function within the normal range with cardiac structure and function in the general population remains uncertain. Methods: Eight hundred thirty-five subjects aged ≥45 years from the EPIPorto cohort (evaluation between 2006 and 2008) were cross-sectionally analyzed. We excluded participants with TSH, free T4 (FT4), or free T3 (FT3) outside of the reference range or with self-reported cardiovascular or thyroid disease. Cardiac structure and function were evaluated by echocardiography. We used linear regression models unadjusted and adjusted for sex and age (model 1), and sex, age, BMI, diabetes, hypertension, and smoking (model 2). Nonlinear associations were assessed using restricted cubic splines. Results: The mean age was 61.5 years (SD 10.5); 61.1% of the patients were women. In the adjusted model 2, heart rate was positively associated with FT3; diastolic blood pressure was positively associated with TSH; LV end-diastolic and end-systolic volumes were inversely associated with TSH, and ejection fraction was nonlinearly associated with FT3, with higher ejection fractions near the limits of the reference range. Left ventricle (LV) posterior wall thickness was nonlinearly associated with FT4 in the adjusted model 1, with a greater thickness near the limits of the reference range. Regarding diastolic function, no significant associations were observed in adjusted models. Conclusions: Thyroid function within the reference range was associated with heart rate, blood pressure, cardiac structure, and function. Increasing thyroid function (lower TSH, higher FT4, or higher FT3) was associated with a higher heart rate, a lower diastolic blood pressure, and larger LV volumes. LV wall thickness and ejection fraction had a U-shaped association with thyroid hormones.

Structural alterations and inflammation in the heart after multiple trauma followed by reamed versus non-reamed femoral nailing.

BackgroundApproximately 30,000 patients with blunt cardiac trauma are recorded each year in the United States. Blunt cardiac injuries after trauma are associated with a longer hospital stay and a poor overall outcome. Organ damage after trauma is linked to increased systemic release of pro-inflammatory cytokines and damage-associated molecular patterns. However, the interplay between polytrauma and local cardiac injury is unclear. Additionally, the impact of surgical intervention on this process is currently unknown. This study aimed to determine local cardiac immunological and structural alterations after multiple trauma. Furthermore, the impact of the chosen fracture stabilization strategy (reamed versus non-reamed femoral nailing) on cardiac alterations was studied.Experimental approach15 male pigs were either exposed to multiple trauma (blunt chest trauma, laparotomy, liver laceration, femur fracture and haemorrhagic shock) or sham conditions. Blood samples as well as cardiac tissue were analysed 4 h and 6 h after trauma. Additionally, murine HL-1 cells were exposed to a defined polytrauma-cocktail, mimicking the pro-inflammatory conditions after multiple trauma in vitro.ResultsAfter multiple trauma, cardiac structural changes were observed in the left ventricle. More specifically, alterations in the alpha-actinin and desmin protein expression were found. Cardiac structural alterations were accompanied by enhanced local nitrosative stress, increased local inflammation and elevated systemic levels of the high-mobility group box 1 protein. Furthermore, cardiac alterations were observed predominantly in pigs that were treated by non-reamed intramedullary reaming. The polytrauma-cocktail impaired the viability of HL-1 cells in vitro, which was accompanied by a release of troponin I and HFABP.DiscussionMultiple trauma induced cardiac structural alterations in vivo, which might contribute to the development of early myocardial damage (EMD). This study also revealed that reamed femoral nailing (reamed) is associated with more prominent immunological cardiac alterations compared to nailing without reaming (non-reamed). This suggests that the choice of the initial fracture treatment strategy might be crucial for the overall outcome as well as for any post-traumatic cardiac consequences.

Effects of body mass index and gender on left atrial size in Chinese hypertensive patients

ABSTRACT Background Left atrial enlargement (LAE) is a common cardiac structural change in patients with hypertension, and obesity could further promote LAE. However, little is known about the effect of overweight on left atrial size, and if there is a gender difference of the effect. The aim of this study was to analyze the effects of different body mass index (BMI) grades (normal weight, overweight, and obesity) on left atrial size in both male and female patients with hypertension. Methods A total of 710 patients with hypertension were divided into 3 study groups: normal weight group (BMI < 24 g/m2, n = 302), overweight group (24 kg/m2 ≤ BMI < 28 kg2, n = 318), and obesity group (BMI ≥28 kg/m2, n = 90). The clinical data, echocardiographic indexes and left atrial size were obtained from all the subjects. Pearson correlation analysis was used to analyze the correlation between clinical variables and left atrial diameter (LAD)/left atrial diameter index (LADI), and stepwise regression evaluation was used to study the relevant factors affecting LAD/LADI among all patients, male and female patients for possible gender difference. Results The significant difference in LADI was noted in the three study groups with obesity group of 23.96 ± 2.90 mm/m, overweight group of 22.50 ± 3.02 mm/m and normal weight group of 21.08 ± 2.80 mm/m, respectively (P < . 05). After adjusting for age and gender, there was still significant difference in LADI among the three groups (P < . 05). The correlation between BMI and LADI was higher than that between systolic blood pressure (SBP) and diastolic blood pressure (DBP) (r = 0.348 vs 0.092 and −0.068, respectively, P < .05). After adjusting for other influencing factors, there was still a significant correlation between BMI and LADI (β = 0.326, P < .001), but no correlation was found between SBP and DBP (P > .05). For each additional unit of BMI, LAD increased by 0.034 mm and LADI increased by 0.305 mm/m. Multiple linear regression analysis showed that BMI, left ventricular mass index (LVMI), age and female gender were independently correlated with LADI (P < .05). And BMI was the most significant influencing factor of LADI in male patients (β = 0.350, P < .001), followed by LVMI (β = 0.343, P < .001). While in female patients, LVMI was the most significant (β = 0.353, P < .001), followed by BMI (β = 0.302, P < .001). Conclusion Overweight and obesity were significantly associated with LAE in hypertensive patients, with obesity more significant than overweight. While BMI had the greatest correlation with LAE in male, LVMI was the most important determinant of LAE in female. Therefore, in addition to weight loss, more attention should be paid to early inhibition of left ventricular remodeling in female with hypertension.

Longitudinal Changes in Cardiac Structure and Function From Adolescence to Young Adulthood in Participants With Type 2 Diabetes Mellitus: The TODAY Follow-Up Study.

Heart failure is a prominent complication of type 2 diabetes mellitus (T2D). The goal of this study was to provide longitudinal data on cardiac structure and function (and cross-sectional comparison to normal-weight and obese controls without T2D) in individuals followed from adolescence with youth-onset T2D. In the TODAY study (Treatment Options for Type 2 Diabetes Mellitus in Adolescents and Youth), echocardiograms were performed at study years 4 to 5 and 9 to 10. Echocardiograms were also obtained at years 8 to 9 in a control population of age, race/ethnicity, and sex-matched normal-weight and obese individuals without diabetes mellitus. Study outcomes were measures of left ventricular structure and function. The cohort included 411 participants with T2D, 194 obese controls, and 51 normal-weight controls. At follow-up, mean participant age was 23 years, 65% women, 20% non-Hispanic white, 35% non-Hispanic black, and 39% Hispanic. Ejection fraction was <52% in 11.7% of male participants with T2D. Diastolic function declined during follow-up in participants with T2D (mitral valve lateral E/Em increased 0.72±0.12 in women and 0.50±0.17 in men; P<0.01) and was significantly higher than obese controls (women, 6.65±1.89 versus 5.66±1.37; men, 6.15±1.90 versus 5.26±1.31; P<0.0001). Predictors of adverse changes included hypertension, obesity, female sex, Hispanic and non-Hispanic black ethnicity, worse glycemic control, and elevated heart rate. Cardiac structural abnormalities, left ventricular hypertrophy, or concentric geometry, were highest in those with T2D (15.8% versus 5.7% obese versus 0% normal weight). Adverse changes in cardiac structure and function changed significantly from adolescence to early adulthood in participants with youth-onset T2D. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00081328.

Longitudinal Changes in Cardiac Structure and Function in Severe Obesity: 11-Year Follow-Up in the Utah Obesity Study.

BackgroundProgressive cardiac remodeling and worsening myocardial function over time have been proposed as potential mediators of heart failure in obesity.Methods and ResultsWe serially assessed cardiac structure and function in 254 subjects participating in a longitudinal study of obesity. Demographic, clinical, laboratory, and echocardiographic features were determined at baseline and 2‐, 6‐, and 11‐year follow‐up. We measured body mass index (BMI) exposure as the area under the curve of the BMI at each of the 4 visits. At enrollment, mean age of the subjects was 47 years, 79% were women, mean BMI was 44 kg/m2, 26% had diabetes mellitus, 48% had hypertension, and 53% had hyperlipidemia. Between baseline and 11 years, BMI increased by 1.1 and 0.3 kg/m2 in men and women, respectively. There were modest increases in left ventricular (LV) end‐diastolic volume, LV mass, and left atrial volume, and significant decreases in early/late mitral diastolic flow velocity ratio and E wave deceleration time. However, there were no significant changes in LV ejection fraction or ratio of early mitral diastolic flow velocity/early mitral annular velocity, whereas right ventricular fractional area change increased. Significant predictors of the change in LV mass were male sex, baseline BMI, BMI area under the curve, and change in LV stroke volume, but not smoking, hypertension, or diabetes mellitus.ConclusionsIn long‐standing, persistent severe obesity, there was evidence of cardiac remodeling over a period of 11 years, but no clear worsening of systolic or diastolic function. Measures of remodeling were most strongly related to BMI. The observed changes might predispose to heart failure with preserved ejection fraction, but are not classic for an evolving dilated cardiomyopathy.