Marker Of Cardiac Function Research Articles

Association of galectin-3 with markers of myocardial function, atherosclerosis, and vascular fibrosis in patients with rheumatoid arthritis.

Galectin-3 has emerged as a promising novel biomarker of cardiovascular fibrosis in patients with cardiovascular diseases. We investigated whether galectin-3 correlates with markers of vascular fibrosis, subclinical atherosclerosis, and cardiac function in patients with rheumatoid arthritis (RA), a disease accompanied by high cardiovascular risk. RA and non-RA individuals underwent applanation tonometry, carotid ultrasound, and impedance cardiography, to obtain markers of arterial stiffness, subclinical atherosclerosis, and myocardial function, respectively. Cardiovascular risk was estimated from the Framingham Heart Study. Serum levels of galectin-3 were determined by enzyme-linked immunosorbent assay. Galectin-3 was elevated in RA patients (n = 85) compared to controls (n = 39), but this difference was no longer significant after adjustment for the presence of cardiovascular comorbidities. In the univariate analysis, galectin-3 significantly correlated with markers of vascular stiffness (including pulse wave velocity, central blood pressure, central and peripheral pulse pressure, and total arterial compliance); atherosclerosis (carotid intima-media thickness); myocardial blood flow (cardiac output, stroke volume) and contractibility (acceleration and velocity index); systemic vascular resistance, and estimated cardiovascular risk. Multivariate analysis models revealed an independent association between galectin-3 and both cardiac output (β = -0.274, P = 0.039), as well as systemic vascular resistance (β = 0.266, P = 0.039). In a relatively well-controlled cohort of RA patients with low-grade systemic inflammation and long-standing disease, serum galectin-3 might be useful as a marker of cardiac function and cardiovascular fibrosis.

Doppler myocardial performance index combined with plasma B-type natriuretic peptide levels as a marker of cardiac function in patients with decompensated cirrhosis.

Background:In chronic liver diseases, cirrhosis ranks as the 14th highest death cause worldwide, developing into decompensated cirrhosis. A potential and feasible technique in assessing cardiac function is urgent. This study explores if the Doppler myocardial performance (Tei) index combined with the plasma B-type natriuretic peptide (BNP) levels can assess cardiac function in patients with decompensated cirrhosis.Methods:A total of 140 individuals were selected in the study and were classified into 3 groups: control group (n = 40, healthy individuals), compensated cirrhosis group (n = 50), and decompensated cirrhosis group (n = 50). Plasma BNP levels, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and albumin (ALB) were identified by an enzyme-linked immunosorbent assay (ELISA). The correlation of Tei index between left ventricle (LV) and right ventricle (RV) as well as plasma BNP levels with cardiac function was assessed using a Pearson test analysis. All patients were subjected to this experiment for 1 year to analyze the relationship between Tei index and plasma BNP levels in prognosis of decompensated cirrhosis patients.Results:Patients with decompensated cirrhosis showed significantly elevated levels of ALT, AST, and TBIL level in contrary to a reduced ALB level. Cirrhosis patients also showed a significantly reduced ejection fraction (ET) index, but an increase in isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT), Tei index, and plasma BNP levels in comparison to healthy individuals. ICT, IRT, Tei index, and plasma BNP levels were elevated in decompensated cirrhotic patients as opposed to compensated cirrhotic patients. These results indicate a positive correlation of both Tei index and plasma BNP levels with cirrhosis and its progression. Tei index and plasma BNP levels are positively associated with Child–Pugh classification and negatively correlated with both cardiac function and prognosis in patients suffering from decompensated cirrhosis.Conclusion:The study provided evidence supporting the correlation of Tei index and plasma BNP levels in decompensated cirrhotic patients with cardiac function, highlighting a potential value for evaluation.

Does right ventricle dysfunction represent cardiac frailty in critically ill trauma patients?

Introduction Cardiac function includes left ventricle ejection fraction, right ventricle function, diastolic function, and multiple markers of cardiac outflow. Markers of cardiac function associated with mortality are unknown. The purpose of this study was to determine markers of cardiac function associated with mortality in the elderly which represent cardiac frailty and the relative importance of these many measurements of cardiac function when compared with each other. Methods A retrospective review of patients who underwent focused rapid echocardiographic evaluations was performed from 2009 to 2014. Focused rapid echocardiographic evaluations are echocardiographic exams focusing on cardiac function rather than structure. Results Overall, 513 trauma patients received focused rapid echocardiographic evaluations. In elderly patients, mortality increase of 33.9% was seen with left ventricle ejection fraction less than 30% (p = 0.05), 28.5% with moderate right ventricle dysfunction (p = 0.03), and 18.5% with velocity time integral less than 18 cm (p = 0.02). Any level of diastolic dysfunction, cardiac output of less than 4 l/min, and cardiac index less than 2.5 l/min/m2 was not significantly associated with increased mortality in the elderly (not significant [NS] for all). In younger patients, a mortality increase of 68.1% was seen with grade 3–4 diastolic dysfunction (p<0.001) and 14.6% with velocity time integral less than 18 cm (p = 0.02), with right ventricle dysfunction, decreased left ventricle ejection fraction, cardiac output less than 4 l/min, and cardiac index less than 2.5 l/min/m2 not associated with mortality (NS for all). In logistic regression for elderly patients, only moderate right ventricle dysfunction was associated with mortality (odds ratio 4.321, 95% confidence interval 1.451–12.866, p = 0.009). Conclusions Markers of cardiac function associated with mortality vary with age. Right ventricle dysfunction may represent cardiac frailty, while diastolic dysfunction and left ventricle ejection fraction likely do not.

NT-proBNP Levels in Patients with Hereditary Transthyretin-mediated Amyloidosis Treated in the Phase 3 APOLLO Study Based on Diuretic Use

Hereditary transthyretin-mediated (hATTR) amyloidosis is a rare, multisystem, rapidly progressive, life-threatening disease caused by a mutation in the TTR gene, resulting in deposition of amyloid fibrils in multiple organs. Heterogeneous clinical presentation includes neuropathy and cardiomyopathy, resulting in significant morbidity and mortality. NT-proBNP, a marker of cardiac function, has been shown to be an independent predictor of survival in patients (pts) with hATTR amyloidosis. Patisiran, an investigational RNAi therapeutic, significantly reduced NT-proBNP compared with placebo (pbo) in pts with hATTR amyloidosis in the Phase 3 APOLLO study. Evaluate in a post-hoc analysis whether the patisiran treatment effect on NT-proBNP in APOLLO was impacted by concomitant diuretic use. APOLLO was a Phase 3, randomized (2:1), double-blind, pbo-controlled study of patisiran in patients with hATTR amyloidosis with polyneuropathy (NCT01960348). NT-proBNP was measured in a central laboratory at baseline, months 9 and 18 (or at early withdrawal). Of the 225 randomized pts, 94 (42%) were receiving concomitant diuretics at baseline or at any time during the study. A higher proportion pts in the pbo group (n=37, 48%) were receiving diuretics than in the patisiran group (n=57, 39%). Within the patisiran group, NT-proBNP was significantly lowered compared with pbo at month 18 in both pts receiving diuretics (43% relative reduction) and pts not receiving diuretics (58% relative reduction). In a pre-specified subpopulation of pts with echocardiographic evidence of cardiac involvement at study entry (n=126), patisiran significantly lowered NT-proBNP compared with pbo at month 18 and NT-proBNP lowering was similar in those receiving diuretics (56% relative reduction) and not receiving diuretics (55% relative reduction). Improvement in NT-proBNP occurred regardless of concomitant diuretic use. This finding, together with additional echocardiographic data showing impact of patisiran on cardiac structure and function, indicate that patisiran improved the underlying cardiomyopathy relative to placebo in patients with hATTR amyloidosis.

Morin attenuates doxorubicin-induced heart and brain damage by reducing oxidative stress, inflammation and apoptosis

Doxorubicin (DOX) is an effective antineoplastic agent of the anthracycline group. However, as with most anticancer drugs, they cause some toxic effects, including major cardiotoxicity and cognitive impairment. In this study, protective effects of morin against DOX-induced cardiotoxicity and neurotoxicity in rats were investigated. Morin was orally administered to rats at a dose of 50 and 100 mg/kg body weight for 10 days. DOX was administered 40 mg/kg body weight by single dose intraperitoneal injection on the 8th day of the study. Both the levels of glutathione (GSH) and malondialdehyde (MDA) were assessed and enzyme activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were assessed to determine the protective effect of morin against oxidative stress. To determine the anti-inflammatory effect, the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), nuclear factor kappa B (NF-κB) were assessed in the heart and brain tissues. Lactate dehydrogenase (LDH) and creatine kinase isoenzyme-MB (CKMB) activities, which are cardiac function markers, and cardiac troponin-I (cTn-I) levels were also determined. Anti-apoptotic effect was determined by anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) and pro-apoptotic protein cysteine aspartate specific protease-3 (caspase-3) changes. The regulatory role of morin in signal transduction in the brain tissue was assigned with the determination of amount of acetylcholinesterase (AChE), and its healing effect on the central nervous system was determined with imuinohistochemical detection of glial fibrillar acidic protein (GFAP) level. Histopathological evaluation of heart and brain tissues was performed in all groups.

Prognostic Effect of Renal Function in Ambulatory Patients With Heart Failure and Reduced Ejection Fraction: The Kidney Is a Marker of Cardiac Function

BackgroundChronic kidney disease is a frequent comorbidity in heart failure (HF), associated with increased mortality. The impact of temporal evolution of kidney function in HF prognosis is largely unknown. We evaluated the effect of renal function over time in all-cause mortality among ambulatory patients with HF. MethodsWe retrospectively analyzed data from 560 patients with HF with left ventricular systolic dysfunction followed for a median of 25.1 months at an outpatient clinic. Demographics and comorbidities were collected at baseline. Creatinine values were abstracted from records at each clinical visit. Kidney function was assessed by estimated glomerular filtration rate (eGFR) and was categorized into 3 classes. Extended Cox models were performed to study the association between time-varying eGFR and death. ResultsPatients’ mean age was 67.5 ± 13.9 years, 67.0% were men, 46.1% had ischemic etiology, the majority had moderate-to-severe left ventricular systolic dysfunction, and 45.9% had chronic kidney disease at baseline. The eGFR declined approximately 9.0 mL/min/1.73 m2 over 5 years. In crude analysis, time-varying eGFR had a significant dose-dependent association with death (hazard ratio [HR] = 1.34, 95% confidence interval [CI]: 1.03-1.75 for eGFR between 30 and 60 mL/min/1.73 m2; HR = 1.55, 95% CI: 1.11-2.17 for <30 mL/min/1.73 m2). The prognostic value of time-varying eGFR was totally explained by baseline comorbidities, indicators of HF severity and drugs (adjusted HR = 1.11, 95% CI: 0.83-1.48; HR = 1.19, 95% CI: 0.79-1.80, for eGFR 30-60 and <30 mL/min/m2, respectively). ConclusionsTime-varying kidney function is not independently related to poor prognosis in HF. Rather than directly affecting survival, renal impairment is probably a surrogate marker of HF severity.

Boost of vitamin E metabolism as a novel treatment strategy for myocardial infarction

Recently, highly anti-inflammatory metabolites (α-LCMs) of α-tocopherol (α-TOH) have shed new light on the mechanism of vitamin E. A central part of myocardial infarction (MI) is a massive pro-inflammatory response in the infarcted myocardium. Since a drop of antioxidant plasma concentration has been reported during MI, we hypothesized that application of α-TOH and α-LCMs as an actual treatment of patients suffering MI provides anti-oxidative and -inflammatory protection and preserves cardiac function. Effects of vitamin E compounds on MI have been tested using the model of cardiac ischemia reperfusion (I/R) injury in mice. Treatment with vitamin E restored ejection fraction, a marker for cardiac function, and ameliorated infarct size post-I/R via regulation of immune cell infiltration, such as neutrophils and monocytes. In addition, α-TOH and α-LCMs decreased gene and protein expression as well as production of respective signaling molecules of key pro-inflammatory pathways in vitro. Since, MI is a leading cause of death worldwide, new drugs for the treatment of I/R injury in patients with MI are highly sought-after. Our study provides a new perspective for vitamin E as a treatment and its potent metabolites as possible lead structures for the therapy of MI.

Cardiac Structural and Functional Consequences of Amyloid Deposition by Cardiac Magnetic Resonance and Echocardiography and Their Prognostic Roles

ObjectivesThis cross-sectional study aimed to describe the functional and structural cardiac abnormalities that occur across a spectrum of cardiac amyloidosis burden and to identify the strongest cardiac functional and structural prognostic predictors in amyloidosis using cardiac magnetic resonance (CMR) and echocardiography. BackgroundCardiac involvement in light chain and transthyretin amyloidosis is the main driver of prognosis and influences treatment strategies. Numerous measures of cardiac structure and function are assessed by multiple imaging modalities in amyloidosis. MethodsA total f 322 subjects (311 systemic amyloidosis and 11 transthyretin gene mutation carriers) underwent comprehensive CMR and transthoracic echocardiography. The probabilities of 11 commonly measured structural and functional cardiac parameters being abnormal with increasing cardiac amyloidosis burden were evaluated. Cardiac amyloidosis burden was quantified using CMR-derived extracellular volume. The prognostic capacities of these parameters to predict death in amyloidosis were assessed using Cox proportional hazards models. ResultsLeft ventricular mass and mitral annular plane systolic excursion by CMR along with strain and E/e’ by echocardiography have high probabilities of being abnormal at low cardiac amyloid burden. Reductions in biventricular ejection fractions and elevations in biatrial areas occur at high burdens of infiltration. The probabilities of indexed stroke volume, myocardial contraction fraction, and tricuspid annular plane systolic excursion (TAPSE) being abnormal occur more gradually with increasing extracellular volume. Ninety patients (28%) died during a median follow-up of 22 months (interquartile range: 10 to 38 months). Univariable analysis showed that all imaging markers studied significantly predicted outcome. Multivariable analysis showed that TAPSE (hazard ratio: 1.46; 95% confidence interval: 1.16 to 1.85; p < 0.01) and indexed stroke volume (hazard ratio: 1.24; 95% confidence interval: 1.04 to 1.48; p < 0.05) by CMR were the only independent predictors of mortality. ConclusionsSpecific functional and structural abnormalities characterize different burdens of cardiac amyloid deposition. In a multimodality imaging assessment of a large cohort of amyloidosis patients, CMR-derived TAPSE and indexed stroke volume are the strongest prognostic cardiac functional markers.

Longitudinal evaluation of ventricular ejection fraction and NT-proBNP across heart failure subgroups

Objectives: Left ventricular ejection fraction (EF) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are important surrogate markers of cardiac function and wall stress. Randomized trials of heart failure (HF) have shown improvements in survival in patients with reduced EF (<40%, HFrEF) but not with preserved EF (≥50%, HFpEF) or mid-range EF (40-49%, HFmrEF). Limited information is available on the trajectory of EF in contemporary heart failure management programs (HFMPs).Design: 201 HF patients consecutively enrolled 2010–2011 in the outpatient-based HFMP of Skåne University Hospital in Lund were included in the study. Probable etiology, EF, NT-proBNP and medications were assessed at baseline and 1 year after enrollment.Results: HFrEF was the most common heart failure subgroup (78.1% of patients) in this HFMP, followed by HFmrEF (14.9%) and HFpEF (7.0%). The most common etiology was ischemic heart disease (IHD, 40.8%).Complete recovery of EF (>50%) was rare (14.1% of patients with HFrEF and 26.7% with HFmrEF), some degree of improvement was observed in 57.7% and 46.7% of patients. LVEF improved on average 9.1% in patients with HFrEF (p < .001) and NT-proBNP decreased from 4,202 to 2,030 pg/ml (p < .001). A similar trend was noticed for the HFmrEF group but was not statistically significant. The improvement in LVEF was consistent across subgroups with HF attributable to IHD (6.2%), idiopathic dilated cardiomyopathy (7.1%) and tachycardia-induced HF (17.5%).Conclusions: This study provides estimates of the improvement in LVEF and NT-proBNP that can be expected with contemporary management across subgroups of HF and different etiologies in a contemporary HFMP.

Abstract MP05: N Terminal Pro B Type Natriuretic Peptide as a Stroke Risk Factor in the European Population: Results From the Biomarcare Consortium

Introduction: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a risk factor for atrial fibrillation and a marker of cardiac function used in detection of heart failure. Few studies evaluated the role of NT-proBNP as risk factor for stroke. Hypothesis: Given the link between cardiac dysfunction and stroke, NT-proBNP is a candidate marker of stroke risk. Our aim was to evaluate the association of NT-proBNP with stroke outcomes and to determine the predictive value beyond a panel of established risk factors for stroke. Methods: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE)-project we analysed data of 43,815 participants (48.3% men; mean age 52 yr) free of cardiovascular disease from 6 prospective population-based cohorts across Europe with a maximum follow-up of 22 years. All NT-proBNP measurements were performed on frozen samples in the central BiomarCaRE laboratory. The endpoints considered were validated fatal and non-fatal stroke. Results: We observed 565 stroke events (78 fatal) in men and 290 (54) in women. Growing quartiles of NT-proBNP were associated with increasing risk of stroke (Table; multivariable cox regression analysis adjusted for the base model: age, centre, smoking, BMI, diabetes, hypertension medication, systolic and diastolic blood pressure, total and HDL cholesterol), both in men (p for trend &lt;0.0001) and in women (P&lt;0.0001). Examining C-statistics for prediction of stroke we could observe only very small changes after the addition of NT-proBNP to the base model (delta AUC=0.0053 and 0.0048 in men and women, respectively). Conclusions: In European individuals free of cardiovascular disease, levels of NT-proBNP in the top quartile (&gt;87.7 pg/mL) are associated with a doubled risk of stroke. However, the addition of NT-proBNP to variables of established risk score poorly improves prediction of stroke disease.

Abstract MP02: N-Terminal Pro-B-type Natriuretic Peptide and Risk of Stroke in Those With and Without Cerebrovascular Disease: The REGARDS Cohort

Background: N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), a commonly used marker of cardiac function, is associated with presence of stroke symptoms and is a strong risk factor for future atrial fibrillation, stroke and mortality. Little data are available on the association between NT-pro-BNP levels and stroke recurrence. Objective: We studied the relationship between NT-proBNP with the risk of future ischemic stroke across a spectrum of pre-existing cerebrovascular conditions, ranging from history of stroke symptoms, to prior transient ischemic attack (TIA), to prior stroke. Methods: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort enrolled 30 239 black and white Americans age 45 years and older in 2003-14. Among a case-cohort study sample including 1109 stroke cases and a 4311-person cohort random sample, we calculated hazard ratios of future ischemic stroke by baseline NT-proBNP stratified by presence of prior cerebrovascular conditions. Results: In the cohort sample, there were 3056 participants without any history of cerebrovascular disease, 738 with prior stroke symptoms, 196 with history of TIA and 338 with history of prior stroke. In a fully adjusted model, elevated NT-proBNP was associated with risk of stroke in participants without a pre-existing cerebrovascular condition (HR 2.32, 95% CI 1.84, 2.94), and in participants with a history of stroke symptoms (HR 1.67 95% CI 1.01, 2.78) or TIA (HR 2.66, 95% CI 1.00, 7.04), but not among those with prior stroke (HR 1.26, 95% CI 0.71, 2.21). Conclusions: These findings further support the potential for NT-proBNP testing to identify patients who are at highest risk for future stroke, although not in those with prior stroke.

Analysis of volatile organic compounds: an innovative approach to heart failure characterization in older patients

Background: Analysis of exhaled volatile organic compounds (VOCs) may be applied for diagnostic purposes in some chronic diseases, but there are no data on their role for discriminating people with congestive heart failure (CHF), particularly in older patients where natriuretic peptides have lower accuracy. We evaluated whether VOCs analysis can discriminate patients with or without CHF, stratify CHF severity and predict the response to therapy of decompensated CHF. Methods and Results: We recruited 89 subjects admitted to an acute care ward with acutely decompensated CHF, 117 healthy controls and 103 chronic obstructive pulmonary disease (COPD) controls. CHF patients performed echocardiography. VOCs were collected using the Pneumopipe® and analyzed with the BIONOTE electronic nose. Partial least square analysis was used to evaluate the discriminative capacity of VOCs. Accuracy in discrimination of CHF versus healthy and COPD controls was 81% and 69%, respectively; accuracy did not decrease in a sensitivity analysis excluding subjects younger than 65 and older than 80 years. In CHF patients VOCs pattern could predict with fair precision ejection fraction and systolic pulmonary arterial pressure, but not changes in weight due to therapy. Conclusions: VOCs pattern is able to discriminate older CHF patients from healthy people and COPD patients and correlates with cardiac function markers.

Exploring kinetic energy as a new marker of cardiac function in the single ventricle circulation.

Ventricular volumetric ejection fraction (VV EF) is often normal in patients with single ventricle circulations despite them experiencing symptoms related to circulatory failure. We sought to determine if kinetic energy (KE) could be a better marker of ventricular performance. KE was prospectively quantified using four-dimensional flow MRI in 41 patients with a single ventricle circulation (aged 0.5-28 yr) and compared with 43 healthy volunteers (aged 1.5-62 yr) and 14 patients with left ventricular (LV) dysfunction (aged 28-79 yr). Intraventricular end-diastolic blood was tracked through systole and divided into ejected and residual blood components. Two ejection fraction (EF) metrics were devised based on the KE of the ejected component over the total of both the ejected and residual components using 1) instantaneous peak KE to assess KE EF or 2) summating individual peak particle energy (PE) to assess PE EF. KE EF and PE EF had a smaller range than VV EF in healthy subjects (97.9 ± 0.8 vs. 97.3 ± 0.8 vs. 60.1 ± 5.2%). LV dysfunction caused a fall in KE EF ( P = 0.01) and PE EF ( P = 0.0001). VV EF in healthy LVs and single ventricle hearts was equivalent; however, KE EF and PE EF were lower ( P < 0.001) with a wider range indicating a spectrum of severity. Those reporting the greatest symptomatic impairment (New York Heart Association II) had lower PE EF than asymptomatic subjects ( P = 0.0067). KE metrics are markers of healthy cardiac function. PE EF may be useful in grading dysfunction. NEW & NOTEWORTHY Kinetic energy (KE) represents the useful work of the heart in ejecting blood. This article details the utilization of KE indexes to assess cardiac function in health and a variety of pathophysiological conditions. KE ejection fraction and particle energy ejection fraction (PE EF) showed a narrow range in health and a lower wider range in disease representing a spectrum of severity. PE EF was altered by functional status potentially offering the opportunity to grade dysfunction.

Mediterranean Diet and Other Dietary Patterns in Primary Prevention of Heart Failure and Changes in Cardiac Function Markers: A Systematic Review

Background: Heart failure (HF) is a complex syndrome and is recognized as the ultimate pathway of cardiovascular disease (CVD). Studies using nutritional strategies based on dietary patterns have proved to be effective for the prevention and treatment of CVD. Although there are studies that support the protective effect of these diets, their effects on the prevention of HF are not clear yet. Methods: We searched the Medline, Embase, and Cochrane databases for studies that examined dietary patterns, such as dietary approaches to stop hypertension (DASH diet), paleolithic, vegetarian, low-carb and low-fat diets and prevention of HF. No limitations were used during the search in the databases. Results: A total of 1119 studies were identified, 14 met the inclusion criteria. Studies regarding the Mediterranean, DASH, vegetarian, and Paleolithic diets were found. The Mediterranean and DASH diets showed a protective effect on the incidence of HF and/or worsening of cardiac function parameters, with a significant difference in relation to patients who did not adhere to these dietary patterns. Conclusions: It is observed that the adoption of Mediterranean or DASH-type dietary patterns may contribute to the prevention of HF, but these results need to be analyzed with caution due to the low quality of evidence.

Protective effect of the hydroalcoholic extract of Tripodanthus acutifolius in hypercholesterolemic Wistar rats

Cardiovascular disease (CVD) are a major public health problem, as they are among the leading causes of mortality worldwide. Tripodanthus acutifolius (TA) is a hemiparasite plant used for medicinal purposes with great antioxidant capacity. However, little is known about its hypolipemic effect. Thus, the aim of this study was to evaluate the effects of the hydroalcoholic extract of Tripodanthus acutifolius leaves in hypercholesterolemic Wistar rats. The animals were divided into: (1) NC (Normocaloric Control); (2) HC (Hypercaloric Control); (3) Oral Simvastatin Suspension 10mg/kg (SIM); (4) TA extract 50mg/kg (TA 50mg/kg) and (5) TA 100mg/kg. The in vitro antioxidant activity assay demonstrated that TA shows high antioxidant capacity. The in vivo findings demonstrated that TA supplementation resulted in significant decreases (p<0.05) in Total Cholesterol (TC), Triglycerides (TG) and Low density lipoprotein (LDL) levels, whereas High density lipoprotein (HDL) levels increased significantly in all TA-supplemented groups in relation to the HC group. Hepatic, renal and cardiac function markers improved during supplementation. Serum adiponectin levels increased significantly, whereas C-reactive protein (PCRus) levels decreased in the TA-supplemented in relation to the HC group. Catalase (CAT), superoxide dismutase (SOD) and gluthatione peroxidase (GPx) activities, as well as polyphenols, vitamin C (VitC) and total gluthatione (GSH), increased significantly in the TA-supplemented groups treated when compared to the HC group. Concerning oxidative damage to biomolecules, TA showed a protective effect on lipids, proteins and DNA. Regarding the histological analysis of the aortic artery, TA treatment was able to decrease aortic vasculature. Therefore, TA is rich in antioxidant compounds and may be an alternative for the treatment of hypercholesterolemia.

Concomitant diastolic dysfunction further interferes with cognitive performance in moderate to severe systolic heart failure.

BackgroundStudies of the relevance of cardiac functional markers to cognitive performance in heart failure (HF) have primarily focused on systolic markers. In this study, we examine whether concomitant diastolic dysfunction further interferes with cognitive performance in memory, attention, and executive function in patients with HF.Methods and resultsIn this cross-sectional correlational study, 82 patients completed face-to-face interviews for neuropsychological testing for cognitive evaluation. Echocardiographic data were obtained from a review of medical records. Mild to moderate (ejection fraction [EF] ≥ 30%) and severe (EF < 30%) systolic dysfunction were present in 55 (67.1%) and 27 (32.9%) patients, respectively, while 21 (26.3%) had diastolic dysfunction (E/e′ > 15). Those patients who had severe systolic dysfunction had significantly lower attention scores (Digit Span Test [DST] backward, t = 2.62, p = 0.011), while those with concomitant severe diastolic dysfunction had significantly lower verbal fluency (t = 2.84, p = 0.006) and executive function (Korean-Trail Making Test Part B) (t = -2.14, p = 0.036) scores than those without severe diastolic dysfunction. After controlling for age and education, systolic patients with HF with concomitant severe diastolic dysfunction had worse cognitive performance in verbal fluency than those without severe diastolic dysfunction (F = 4.33, p = 0.041, partial eta = 0.057). Concomitant moderate to severe systolic and severe diastolic dysfunction further reduced verbal fluency (F = 8.42, p = 0.005, partial eta = 0.106).ConclusionsCognitive performance, particularly executive function, was worse in patients with HF with systolic dysfunction when diastolic dysfunction was concomitantly present. Routine monitoring of and surveillance for diastolic dysfunction and cognitive screening are warranted in the management of patients with HF.

A new scoring system for evaluating coronary artery disease by using blood pressure variability.

The aim of this study was to develop a new scoring system using ambulatory blood pressure monitoring (ABPM) to assist in the evaluation of coronary artery disease (CAD). One hundred twenty-five subjects (53.1 ± 9.6 years of age) were included. Pearson's tests were first performed to identify the parameters that correlated with Duke Treadmill Score (DTS). Blood test parameters and blood pressure variability (BPV) measures that were extracted from the ABPM were included. Next, a multiple linear regression analysis was performed to train a new scoring system in the 84 patients from the 125 patients. Then, a correlation analysis was conducted to validate the correlation between the new scoring system and DTS in the remaining 41 subjects. A further correlation analysis was used to verify the clinical value of the new scoring system using ultrasonic cardiogram (UCG) and brachial-ankle pulse wave velocity (baPWV). Our new scoring system, which had a 24.096 - 0.083 × residual standard deviation of night systolic blood pressure (SBP) - 0.130 × age - 0.206 × average real variability of night SBP, was correlated with DTS (r = 0.312, P = 0.047). Moreover, our new scoring system was also correlated with various markers of cardiac function (r = -0.290, P = 0.001; r = -0.262, P = 0.004; r = -0.303, P = 0.001; r = -0.306, P = 0.001, respectively) measured by UCG and with baPWV (r = 0.529, P = 0.001). Furthermore, the r-values for the BPV Score versus the markers were closer to -1 than the corresponding r-values for the Duke Score vs the same parameters. And the differences in r-values between Duke Score and BPV Score were statistically significant (P = 0.022). In conclusion, the new scoring system based on ABPM has potential as a non-invasive tool for evaluating CAD.

Abstract 1826: Bioavailability, pharmacodynamics and safety profile of a novel anti-angiogenic compound JFD in pre-clinical models

Abstract JFD, isoindole (1, 3-dioxo-2, 3-dihydro-1H-isoindol-4-yl)-amide, is a small molecule that was developed using molecular modeling to specifically antagonize Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) and associated kinase activity, thereby producing anti-angiogenic and anti-cancer effects. Since the original form of JFD is hydrophobic, it was recently modified into a water soluble form (JFD-WS) to increase its water solubility and bioavailability. Initially, we investigated the in vitro pharmacodynamics effect of both JFD and JFD-WS by utilizing Matrigel® tube formation assays, scratch and cell migration assays followed by inhibition of VEGFR2 phosphorylation in human umbilical vein endothelial cells (HUVECs). In vivo tumor growth inhibition of JFD and JFD-WS was tested using GI-101A breast adenocarcinoma cells implanted xenograft animals. Subsequently, the blood samples and the tumor proteins were extracted from the control and experimental animals to measure the pro-apoptotic signals and the levels of plasma biomarker such as MUC1 (mucin 1). The safety profile was established using Balb-c mice that were injected intraperitoneally (i.p) with JFD (6 mg/Kg body weight) and JFD-WS (100 mg/Kg body weight) for 30 days. The pharmacokinetics (PK) of JFD including the plasma concentration, excretion, elimination and distribution in the experimental animals were analyzed using a simple HPLC method. As expected, the JFD effectively inhibited HUVECs migration, tube formation, and VEGFR2 phosphorylation. Moreover, both JFD and JFD-WS exhibited strong anti-tumorigenic effects in xenograft implanted experimental animals that were evidenced by the decreasing plasma levels of MUC1. The western blot analysis of apoptotic markers and DNA fragmentation analysis further confirmed the pro-apoptotic effects of JFD as well as JFD-WS in our experimental system. Following i.p. injection, there was a significant distribution of JFD original into the liver, kidney, and brain, which contained the highest concentration compared to other two organs. When hematological, hepatic, renal and cardiac function markers were analyzed in the experimental animals, that were treated with JFD-WS for four weeks, no significant alterations were found in the test group compared to the control animals. Thus, whether used as a single agent or in combination with the other anti-cancer drugs, JFD shows strong antitumor effects without producing severe toxicities. The efficient delivery of JFD original to the brain suggests that this drug would be useful in treating solid tumors of the brain with pro-angiogenic abilities. (This project was supported by the Community Foundation of Broward, Ft. Lauderdale, FL and The Royal Dames of Cancer Research Inc., Ft. Lauderdale, FL). Note: This abstract was not presented at the meeting. Citation Format: Sivanesan Dhandayuthapani, Thanigaivelan Kanagasabai, Khadija Cheema, Appu Rathinavelu. Bioavailability, pharmacodynamics and safety profile of a novel anti-angiogenic compound JFD in pre-clinical models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1826. doi:10.1158/1538-7445.AM2017-1826

LVOT-VTI is a Useful Indicator of Low Ventricular Function in Young Patients.

Left ventricular outflow tract velocity time integral (LVOT-VTI), a Doppler-derived measure of stroke distance, is used as a surrogate marker of cardiac function in adults. LVOT-VTI is easily obtained, independent of ventricular geometry and wall motion abnormalities. We investigated the relationship between LVOT-VTI and conventional measures of function in young patients by comparing controls to children with dilated cardiomyopathy (DCM). Sixty-two healthy and 52 DCM patients over 1year were studied retrospectively. The average pulsed (PW) and continuous wave (CW) LVOT-VTIs from apical views were measured from three cycles. Body surface area (BSA) and Ejection fraction (EF) were obtained. We compared LVOT-VTIs between study and control groups and assessed BSA's impact on LVOT-VTI. The entire cohort was classified into three levels of LV function which were compared. We determined LVOT-VTI cutoff values that indicated an EF<50%. The mean PW-LVOT-VTI in the DCM group was significantly lower than that of the normal group (0.15 vs. 0.18m; p<0.0012). The mean CW-LVOT-VTI was significantly lower in DCM (0.20 vs. 0.24m; p<0.0001). There was no impact of BSA on LVOT-VTI except when comparing BSA and CW-LVOT-VTI in the normal group. There was a positive relationship between LVOT-VTI and EF for PW (Rs=0.29, p=0.0022) and CW (Rs=0.22, p=0.0364) and a difference in mean LVOT-VTI between EF groups (p<0.0001). ROC analysis demonstrated that PW-LVOT-VTI<0.17m (AUC=0.73; p<0.0001) and CW-LVOT-VTI<0.22m (AUC=0.76; p<0.0001) was associated with EF<50%. This study indicates that LVOT-VTI can be a useful alternative measure of LV performance in children over 1year.

Associations between Left Ventricular Cavity Size and Cardiac Function and Overload Determined by Natriuretic Peptide Levels and a Covariance Structure Analysis

The effects of left ventricular (LV) cavity size on cardiac function and overload have not yet been fully elucidated. We performed a covariance structure analysis and drew theoretical path models to clarify the effects of hemodynamic parameters on the stroke volume index (SVI) as a marker of cardiac function and on the plasma B-type natriuretic peptide (BNP) level as a marker of cardiac overload. We simultaneously measured various hemodynamic parameters and the BNP levels during cardiac catheterization in 1,715 inpatients of our institution. The current path models tested the validity of the Frank-Starling law in patients with heart failure using the SVI, the LV end-systolic volume index (LVESVI) and the LV end-diastolic volume index (LVEDVI). Using the BNP levels, the path models clearly demonstrated that LVESVI substantially augmented cardiac overload, whereas LVEDVI palliated this parameter. These volume indices exerted opposite effects on cardiac function and overload. These results advance the understanding of the relationships between LV cavity size and both cardiac function and overload and indicate the increasing importance of LV diastolic volume in heart failure and the utility of LVESVI as an important marker of cardiac remodeling for further relevant studies.