Marker Of Cardiac Dysfunction Research Articles

Correlation of global longitudinal strain with disease severity in liver cirrhosis

Abstract Funding Acknowledgements Type of funding sources: None. Introduction/purpose Cirrhotic cardiomyopathy is characterized by high cardiac output, reduced peripheral resistance and diastolic dysfunction and has been correlated with cirrhosis severity and prognosis. Global longitudinal strain (GLS) is a sensitive marker of cardiac dysfunction which is considered relatively independent of preload and afterload conditions and thus may be of high diagnostic significance in this special population. We sought to investigate alterations of GLS relating to disease severity in cirrhotic patients. Methods Echocardiographic analysis of 51 consecutive cirrhotic patients was performed. Images were acquired and analyzed off-line. GLS was calculated with a semi-automatic way using dedicated software. Clinical and biochemical examination were used to assess severity of liver disease by calculating Child-Pugh class (class C patients have more severe disease than class B and A patients) and MELD-Na score (increased score as the disease progresses). Results Mean age was 58.4 ± 8.7 years, 38 (74.5%) were males. Among patients, 22 (43.1%) were Child-Pugh class A, 17 (33.3%) Child-Pugh B and 12 (23.5%) Child-Pugh C and mean MELD-Na score was 15.3 ± 7.5. Mean left ventricular end-systolic volume (LVEDV) was 117 ± 29ml, mean stroke volume (SV) 72.5 ± 19.9ml , mean left ventricular ejection fraction (LVEF) 61.0 ± 5.0%, mean systolic blood pressure (SBP) 128 ± 13mmHg, mean ratio of peak transmitral to peak annular (septal) velocity during early diastole (E/e’ ratio) 10.4 ± 4.5, mean left atrial volume index (LAVI) 37.4 ± 11.8 ml/cm2 and mean GLS -21.6 ± 2.6%. GLS of Child-Pugh class A patients (-20.3 ± 2.4) was higher (less negative) than GLS of Child-Pugh class B (-22.2 ± 2.2) and class C (-23.0 ± 2.8) patients. Difference between groups B and C was non-significant (figure). Severity of cirrhosis as determined by higher MELD-Na score correlated with LAVI (r = 0.592, p < 0.001), SV (r = 0.554, p < 0.001), GLS (r=-0.441, p = 0.001) and LVEDV (r = 0.428, p = 0.002). GLS correlated with SV (r=-0.369, p = 0.008) but not with preload (LVEDV), or afterload (SBP). In a linear regression model, GLS was independently associated with Meld-Na score when adjusting for age, SBP, LVEDV and NASH etiology [B=-0.139 (-0.252; -0.025), p = 0.018]. Conclusions GLS is lower (more negative) in patients with liver cirrhosis as disease progresses a relation not affected by preload and afterload conditions. Further research works are required to explain the underlying pathophysiology and to assess prognostic significance of reduced GLS values in patients with advanced cirrhosis. Abstract Figure. GLS stratified by Child-Pugh score

Biomarkers and Their Relation to Cardiac Function Late After Peripartum Cardiomyopathy

BackgroundAngiogenic imbalance involving the placental protein soluble Fms-like tyrosine kinase-1 (sFlt-1) and cleavage of the nursing-hormone prolactin by the enzyme cathepsin D (CD) both play a role in the pathogenesis of peripartum cardiomyopathy (PPCM). We hypothesized that angiogenic imbalance and increased activity of CD have a long-lasting impact in women with PPCM. Methods and ResultsA nationwide Danish cohort of women with PPCM (PPCM group, n = 28), age matched women with previous preeclampsia (n = 28) and uncomplicated pregnancies (n = 28) participated in a follow-up study including biomarker analysis, exercise testing and cardiac magnetic resonance imaging. The median time to follow-up was 91 months (range 27–137 months) for the PPCM group. Levels of sFlt-1, placental growth factor, N-terminal pro-natriuretic brain peptide, and copeptin were all significantly higher in the PPCM group. More women in the PPCM group had detectable CD activity (68%) compared with the preeclampsia group (29%) and uncomplicated pregnancies group (36%) (P = .0002). Levels of angiogenic factors and biomarkers correlated inversely with maximal exercise capacity and cardiac functional parameters assessed with cardiac magnetic resonance imaging. ConclusionsWomen with PPCM had higher biomarker levels and CD activity up to 7 years after diagnosis. Higher biomarker levels correlated inversely with maximal exercise capacity and markers of cardiac dysfunction suggesting that persistent angiogenic imbalance and increased CD activity is associated with residual cardiac dysfunction.

NT-Pro-BNP levels during spontaneous breathing test and its association with successful weaning in patients undergoing mechanical ventilation in the Intensive Care Unit: Original Article

Introduction: Weaning of the patient is one of the important medical challenges. One of the most important causes of failure in weaning is cardiovascular disorders. NT-Pro-BNP is a serum marker for cardiac dysfunction. This study conducted to evaluate the level of NT-Pro-BNP during the spontaneous breathing test (SBT) in patients undergoing mechanical ventilation in ICU and its association with successful weaning. Methods: In this cross-sectional study, we enrolled 42 intubated patients who were admitted to the ICU ward of Imam Reza Hospital and were clinically weaned. After obtaining informed consent, SBT was started for the patient. One and a half hours after SBT onset, a venous blood sample was obtained and the patients were followed for SBT test success and the results were recorded. Patients were extubated in stabilized condition or continued mechanical ventilation if needed. Then Data were analyzed. Results: SBT was successful in 45.2% of patients. 54.8% of patients were male. The most common cause of hospitalization was COPD (35.7%). The mean age of patients with successful SBT was 67.53±6.14 years and in patients with unsuccessful SBT was 68.70±5.44 years. There was a significant difference between NT-Pro-BNP levels half an hour after SBT between two groups of patients with successful (7.15±31.18) and unsuccessful (59.61±196.51) SBT. NT-ProBNP changes before and half an hour after SBT in both groups were statistically significant. Conclusion: NT-Pro-BNP is a predictor criteria of success in weaning in patients and as the level of NT-Pro-BNP increases, the rate of failure in weaning increases.

Multisystem inflammatory syndrome in children (MIS-C) during SARS-CoV-2 pandemic in Brazil: a multicenter, prospective cohort study

ObjectiveTo describe the clinical, laboratory, and radiological characteristics, as well as the outcomes of children with MIS-C. MethodMulticenter, prospective cohort study, conducted in 17 pediatric intensive care units in five states in Brazil, from March to July 2020. Patients from 1 month to 19 years who met the MIS-C diagnostic criteria were included consecutively. ResultsFifty-six patients were included, with the following conditions: Kawasaki-like disease (n = 26), incomplete Kawasaki disease (n = 16), acute cardiac dysfunction (n = 10), toxic shock syndrome (n = 3), and macrophage activation syndrome (n = 1). Median age was 6.2 years (IQR 2.4−10.3), 70% were boys, 59% were non-whites, 20% had comorbidities, 48% reported a contact with COVID-19 cases, and 55% had a recent SARS-CoV-2 infection confirmed by RT-PCR and/or serology. Gastrointestinal symptoms were present in 71%, shock symptoms in 59%, and severe respiratory symptoms in less than 20%. d-Dimer was increased in 80% and cardiac dysfunction markers in more than 75%. Treatment included immunoglobulin (89%); corticosteroids, antibiotics, and enoxaparin in about 50%; and oseltamivir and antifungal therapy in less than 10%. Only 11% needed invasive mechanical ventilation, with a median duration of five days (IQR 5–6.5). The median length of PICU stay was six days (IQR 5–11), and one death occurred (1.8%). ConclusionsMost characteristics of the present MIS-C patients were similar to that of other cohorts. The present results may contribute to a broader understanding of SARS-CoV-2 infection in children and its short-term consequences. Long-term multidisciplinary follow-up is needed, since it is not known whether these patients will have chronic cardiac impairment or other sequelae.

Ethanolic and Aqueous Extracts of Avocado (Persea americana) Seeds Attenuates Doxorubicin-Induced Cardiotoxicity in Male Albino Rats

Cardiotoxicity from long-term use of the anticancer drug, doxorubicin (DOX), imposes a strict limitation its administration. The health benefits of avocado seeds (AS) stem from essential nutrients and phytochemicals. This study aimed to compare effects of ethanol (EAS), and water (WAS) extracts from AS on DOX-induced cardiotoxicity. Forty adult male albino rats were divided into four groups: GI were control rats. GII rats received DOX alone over a 2 week period. GIII animals received the DOX treatment plus AS. GIV rats received the DOX treatment plus EAS. AS extract treatments were administered after initiation of cardiotoxicity. Total flavonoids, polyphenols, and antioxidant capacity of both AS extracts were measured. Serum markers of cardiac dysfunction were evaluated, oxidative stress and inflammatory biomarkers were measured in cardiac tissue homogenates and histopathology of heart tissues was evaluated. The AS ethanolic extract had a higher content of active compounds. DOX treatment increased markers of cardiac dysfunction Matrix Metalloproteinase-1 (MMP-1), Serum Cardiac Troponin I (cTnI), Lactate Dehydrogenase (LDH), Serum Creatine Kinase Isoenzyme-MB (CK-MB), and Heart-Type Fatty Acid-Binding Protein (FABP3) and produced increases in levels of Advanced Oxidation Protein Products (AOPP) and Malondialdehyde (MDA) in cardiac tissue homogenates with a significant reduction in Catalase (CAT), Total Antioxidant Capacity (TAC). It also increased levels of Tumor Necrosis Factor (TNF-a), Interleukin-6 (IL-6), Interleukin-1 beta (IL-1s) and Caspase-3, in the cardiac tissue homogenates. EAS was more effective than WAS, but both acted as cardioprotective agents following DOX treatment as evidenced by mitigation of impacts on biochemical markers.

COVID-19: a retrospective cohort study with focus on the over-80s and hospital-onset disease

BackgroundData from the UK COVID-19 outbreak are emerging, and there are ongoing concerns about a disproportionate effect on ethnic minorities. There is very limited information on COVID-19 in the over-80s, and the rates of hospital-onset infections are unknown.MethodsThis was a retrospective cohort study from electronic case records of the first 450 patients admitted to our hospital with PCR-confirmed COVID-19, 77% of the total inpatient caseload to date. Demographic, clinical and biochemical data were extracted. The primary endpoint was death during the index hospital admission. The characteristics of all patients, those over 80 years of age and those with hospital-onset COVID-19 were examined.ResultsThe median (IQR) age was 72 (56, 83), with 150 (33%) over 80 years old and 60% male. Presenting clinical and biochemical features were consistent with those reported elsewhere. The ethnic breakdown of patients admitted was similar to that of our underlying local population. Inpatient mortality was high at 38%.Patients over 80 presented earlier in their disease course and were significantly less likely to present with the typical features of cough, breathlessness and fever. Cardiac co-morbidity and markers of cardiac dysfunction were more common, but not those of bacterial infection. Mortality was significantly higher in this group (60% vs 28%, p < 0.001). Thirty-one (7%) patients acquired COVID-19 having continuously been in hospital for a median of 20 (14, 36) days. The peak of hospital-onset infections occurred at the same time as the overall peak of admitted infections. Despite being older and more frail than those with community-onset infection, their outcomes were no worse.ConclusionsInpatient mortality was high, especially among the over-80s, who are more likely to present atypically. The ethnic composition of our caseload was similar to the underlying population. While a significant number of patients acquired COVID-19 while already in hospital, their outcomes were no worse.

Cardio-Diagnostic Assisting Computer System.

The mathematical analysis and the assessment of heart rate variability (HRV) based on computer systems can assist the diagnostic process with determining the cardiac status of patients. The new cardio-diagnostic assisting computer system created uses the classic Time-Domain, Frequency-Domain, and Time-Frequency analysis indices, as well as the nonlinear methods (Poincaré plot, Recurrence plot, Hurst R/S method, Detrended Fluctuation Analysis (DFA), Multi-Fractal DFA, Approximate Entropy and Sample Entropy). To test the feasibility of the software developed, 24-hour Holter recordings of four groups of people were analysed: healthy subjects and patients with arrhythmia, heart failure and syncope. Time-Domain (SDNN < 50 ms, SDANN < 100 ms, RMSSD < 17 ms) and Frequency-Domain (the spectrum of HRV in the LF < 550 ms2, and HF < 540 ms2) parameter values decreased in the cardiovascular disease groups compared to the control group as a result of lower HRV due to decreased parasympathetic and increased sympathetic activity. The results of the nonlinear analysis showed low values of (SD1 < 56 ms, SD2 < 110 ms) at Poincaré plot (Alpha < 90 ms) at DFA in patients with diseases. Significantly reducing these parameters are markers of cardiac dysfunction. The examined groups of patients showed an increase in the parameters (DET% > 95, REC% > 38, ENTR > 3.2) at the Recurrence plot. This is evidence of a pathological change in the regulation of heart rhythm. The system created can be useful in making the diagnosis by the cardiologist and in bringing greater accuracy and objectivity to the treatment.

(E)-N’-(1-(3-oxo-3H-benzo[f]chromen-2-yl)ethylidene)benzohydrazide protecting rat heart tissues from isoproterenol toxicity: Evidence from in vitro and in vivo tests

The current study was aimed to assess the protective effect of a new molecule (E)-N’-(1-(3-oxo-3H-benzo[f]chromen-2-yl)ethylidene)benzohydrazide, denoted 1c, against cardiac remodeling process in isoproterenol (Isop) induced myocardial infarction (MI) in rats. Male Wistar rats were randomly divided into four groups, control, Isop (85 mg/kg body weight was injected subcutaneously into rats at an interval of 24 h for 2 days (6th and 7th day) to induce MI and pretreated animals with acenocoumarol (Ace) (150 μg/kg bw) and 1c (150 μg/kg bw) by oral administration during 7 days and injected with isoproterenol (Isop + Ace) and (Isop + 1c) groups. Results in vitro showed that 1c is endowed with potent inhibition of angiotensin-converting enzyme (ACE) with an IC50 39.12 μg/ml. The in vivo exploration evidenced alteration in the ECG pattern, notable cardiac hypertrophy and increase in plasma level of fibrinogen, troponin-T, CK-MB and LDH, AST and ALT by 171%, 300%, 50%, 64% and 75% respectively with histological myocardium necrosis and cells inflammatory infiltration. However, pre-treatment with 1c improved the ECG pattern reduced significantly the cardiac dysfunction markers and ameliorated the thrombolytic process by decreasing fibrinogen level as compared to untreated infracted rats. Overall, (E)-N’-(1-(3-oxo-3H-benzo[f]chromen-2-yl)ethylidene)benzohydrazide 1c could be used as anticoagulant agent to prevent thrombosis in acute myocardial infarction.

Cardiac Doppler in poorly controlled gestational diabetics and its link to markers of intra-uterine hypoxia and adverse outcome

The aim of the study was to investigate foetal cardiac function using the modified myocardial performance index (Mod-MPI) in poorly controlled gestational diabetics and its link with intrauterine markers for hypoxia and to an adverse outcome. In a prospective, cross sectional study, 44 consecutive women with severe or poorly controlled gestational diabetic pregnancies in their third trimester on insulin therapy were recruited and matched with 44 women with normal pregnancies which served as the control group. Using Doppler echocardiography the foetal Mod-MPI was calculated. The foetal Mod-MPI was significantly higher in the diabetic group compared to the controls indicating significant myocardial dysfunction. The Mod-MPI served as an excellent marker of adverse outcomes. Foetal myocardial function was significantly impaired in poorly controlled gestational diabetics and there was a significant link of Mod-MPI to intrauterine markers of hypoxia, as well as to an adverse outcome. Mod-MPI has the potential to improve foetal surveillance in gestational diabetes. IMPACT STATEMENT What is already known on this subject? Abnormal foetal cardiac function, as reflected in the modified myocardial performance index, has been reported to be significantly increased in foetuses of poorly controlled diabetics managed on insulin. What do the results of this study add? There is a significant link between abnormal foetal cardiac function to intrauterine markers of hypoxia, as well as to an adverse outcome; and that development of myocardial dysfunction could be one of the main mechanisms, inducing foetal compromise in poorly controlled gestational diabetes. What are the implications of these findings for clinical practice and/or further research? This study explores an interesting concept of foetal pathophysiology in gestational diabetes, namely the concept of “pseudo-hypoxia” in a foetus of a gestational diabetic mother, and this intrauterine “hypoxic stress” in turn leading to myocardial dysfunction. The Mod-MPI, a clinical marker for cardiac dysfunction, can therefore be used in the clinical setting to track a deteriorating metabolic state.

LPS-Induced Hypotension in Pregnancy: The Effect of Progesterone Supplementation.

Our previous work has shown that pregnancy exacerbates the hypotensive response to both infection and lipopolysaccharide (LPS). The high levels of progesterone (P4) associated with pregnancy have been suggested to be responsible for the pregnancy-induced changes in the cardiovascular response to infection. Here, we test the hypothesis that P4 supplementation exacerbates the hypotensive response of the maternal cardiovascular to LPS.Female CD1 mice had radiotelemetry probes implanted to measure hemodynamic function noninvasively and were time-mated. From day 14 of pregnancy, mice received either 10 mg of P4 or vehicle alone per day and on day 16, intraperitoneal LPS (10 μg of serotype 0111:B4) was injected. In two identically treated cohorts of mice, tissue and serum (for RNA, protein studies) were collected at 6 and 12 h.Administration of LPS resulted in a fall in blood pressure in vehicle treated, but not P4 supplemented mice. This occurred with similar changes in the circulating levels of cytokines, vasoactive factors and in both circulating and tissue inflammatory cell numbers, but with reduced left ventricular expression of cytokines in P4-supplemented mice. However, left ventricular expression of markers of cardiac dysfunction and apoptosis were similar.This study demonstrates that P4 supplementation prevented LPS-induced hypotension in pregnant mice in association with reduced myocardial inflammatory cytokine gene expression. These observations suggest that rather than being detrimental, P4 supplementation has a protective effect on the maternal cardiovascular response to sepsis.

Prognostic role of B-type natriuretic peptide in adults with acute dyspnea requiring emergency admission

Objective:The aim of the study was to evaluate the role of B-type natriuretic peptide (BNP) in patients presenting with acute dyspnea admitted in emergency services.Materials and Methods:A prospective observational study was conducted on 100 patients presenting to the emergency of Dayanand Medical College and Hospital and Hero DMC Heart Institute with acute dyspnea of <48 h duration, in which BNP levels were done on arrival to emergency.Results:BNP levels were significantly higher in patients having left ventricular dysfunction, both systolic and diastolic. Patients with systolic dysfunction had slightly higher BNP (1251.50 ±950.14 pg/mL) compared to patients with diastolic dysfunction (905.62±618.10 pg/mL) though statistically insignificant (P = 0.055). BNP levels were also inversely related to ejection fraction. Mean BNP levels in patients with EF <31%, 31%–45%, 46%–59%, and ≥60% were 1464.63 ± 1058.29, 968.24 ± 751.59, 841.64 ± 503.41 and 781.67 ± 504.21 (P = 0.009), respectively. Patients having higher BNP levels had significantly prolonged duration of stay compared to patients with lower BNP. Patients who expired had slightly higher levels of BNP though statistically nonsignificant. BNP had no significant statistical relation with age, heart rate, creatine phosphokinase-MB, Trop-T levels, systolic blood pressure.Conclusion:We conclude that high BNP levels are a marker of cardiac dysfunction and increased duration of hospital stay in patients presenting to the emergency with acute dyspnea. Hence, BNP can be used as a screening test for the evaluation and management of dyspnea.

Peripheral Microangiopathy in Patients with Precapillary Pulmonary Hypertension: Correlation with Cardiac Function and Patients' Functional Capacity. Study Design and Rationale.

Pulmonary hypertension (PH) is a rare, heterogenous clinical entity characterised by a progressive remodelling of pulmonary arterioles, which leads to obstructive pulmonary arteriopathy, increased pulmonary vascular resistance, and eventually, right heart failure. Inflammation, endothelial dysfunction, and microvascular changes of the pulmonary vasculature constitute the hallmarks of pulmonary arterial hypertension (PAH), explaining much of the pathophysiology and clinical manifestations of the disease. Besides pulmonary vasculature, a systemic component of endothelial dysfunction and microcirculation may be involved in PAH, affecting different vascular beds. Nailfold videocapillaroscopy (NVC) is an established method for the assessment of the microvasculature with clinical implications in the diagnostic assessment of individuals with Raynaud syndrome and systemic sclerosis (SSc). Nowadays, growing amounts of evidence suggest that NVC changes in SSc are correlated with other vascular complications such as PAH, supporting a potential link between peripheral and internal organ vasculopathy. The purpose of the current prospective observational study is to explore: 1. the presence of peripheral microangiopathy in precapillary PH using NVC, 2. possible NVC differences among PH subgroups, 3. a potential relationship between NVC morphological abnormalities and clinical, functional, biochemical, echocardiographic and hemodynamic markers of cardiac dysfunction in precapillary PH.

P890 Heart transplantation and antibody-mediated rejection: role of the strain as an early marker of cardiac dysfunction in patients with anti-HLA antibody

Abstract Background Antibody-mediated rejection of the transplated heart is essentially diagnosed through endomyocardial biopsy whereas clinical elements, anti- Human Leukocite Antigens (HLA) antibody and graft dysfunction are supplementary components. Over the years, several studies have tried to define early diagnostic markers, but to date a univocal consensus has not been achieved. Purpose The aim of the study was to identify though a non-invasive technique, such as transthoracic echocardiography, early signs of impaired cardiac function in heart transplanted patients, in presence of anti-HLA antibodies but without any histological sign of antibody-mediated rejection, assessed through endomyocardial biopsy. Methods In the study 29 heart transplanted patients were enrolled, and they were divided into two groups ‘HLA+’ (15 patients) and ‘HLA-’ (14 patients), based on the presence and the absence of circulating anti-HLA antibodies, respectively. None of the patients had evidence of either coronary allograft vasculopathy or antibody-mediated rejection, attested by endomyocardial biopsy. Each patient underwent through echocardiographic exam, within one month from the biopsy, analysing standard parameters of both systolic and diastolic function, together with strain analysis of right and left ventricle (RV and LV) and left atrium (LA). Results Clinical and demographic characteristics did not different significantly between the two groups, and neither did standard echocardiographic parameters. The only significant parameter that show a statistically significant different was Deceleration Time of E wave (DecT E), which resulted to be lower in the ‘HLA+’ group. Regarding strain analysis, peak atrial longitudinal strain was significantly different between HLA+ and HLA- patients (10,9 ± 5,6 vs 14,9 ± 4,5; p &amp;lt; 0.005), whereas peak atrial contraction strain did not. The study attested a strong difference of both LV global longitudinal strain (- 20,2 ± 5,9 vs - 23,2 ± 3,3; p &amp;lt; 0.005) and RV strain between the two analysed subsets (-16,9 ± 3,4 vs -19,3 ± 3,1 p &amp;lt; 0.005). The figure shows the most significant correlations found in the study, respectively RV strain (on the left), LV strain (in the middle) and DecT E (on the right), the figures on top are representative of HLA- patients, whereas the ones at the bottom are representative of HLA+ patients. Conclusion The presence of circulating anti-HLA antibodies seems to be correlated with a mild cardiac dysfunction, even in the absence of antibody-mediated rejection. This subtle dysfunction is not completely detectable by standard echocardiographic parameters, whereas strain analysis has showed promising results since it revealed more clearly an impaired function of both ventricles in heart transplanted HLA+ patients, with potentially important clinical repercussion. Abstract P890 Figure.

P1358 New insights into cardiac dysfunction assessed by left atrial function in patients with type 1 diabetes mellitus

Abstract BACKGROUND There have been many reports of heart failure due to diabetic cardiomyopathy and decreased left ventricular (LV) function with increasing age in patients with type 1 diabetes mellitus (T1DM). Recently, although left atrial (LA) function has been occasionally reported to be a more useful prognostic indicator than LV function in acquired heart diseases, LA function in patients with T1DM has not yet been studied. PURPOSE To investigate LA dysfunction in patients with T1DM. METHODS Fifty patients with T1DM were recruited (age, 5–41 years). We excluded patients who had a history of heart disease, hypertension, and those taking cardioprotective agents. The patients and 50 age-matched controls were classified into 3 age groups (D1, C1, 5–14 years; D2, C2, 15–29 years; D3, C3, 30–41 years). The LA phasic function serving as the reservoir, conduit, and pump strains; the LA strain rate (SR) in the systole, early diastole, and late diastole; and the LV global longitudinal strain (LV-LS) as determined via 2-dimensional speckle tracking imaging were measured from the apical four- and two-chamber views. We also calculated the LA stiffness index as the ratio of E/e’ to the LA reservoir strain. RESULTS There was no significant difference in left ventricular ejection fraction in each age group. The LA reservoir strains in D2 and D3 were significantly lower than those in C2 (40.8 ± 5.7% vs. 47.2 ± 5.5%, p = 0.005) and C3 (39.2 ± 5.5% vs. 47.3 ± 5.7%, p = 0.004), respectively. The LA conduit strain in D2 was significantly lower than that in C2 (28.9 ± 5.8% vs. 35.0 ± 5.0%, p = 0.006). The LA pump strain and the three phases of LA SR were not significantly different among the age groups. The LA stiffness index in D3 increased significantly compared to that in N3 (0.18 ± 0.05 vs. 0.13 ± 0.01, p &amp;lt;0.001). The LV-LS in D2 and D3 was significantly lower than that in C2 (-15.7 ± 1.7% vs. -18.7 ± 2.1%, p &amp;lt;0.001) and C3 (-15.3 ± 1.8% vs. -19.3 ± 2.0%, p &amp;lt;0.001), respectively. The LA reservoir strain significantly correlated with LV-LS (r = -0.468, p &amp;lt; 0.001). Both the LA reservoir strain and LV-LS in patients with T1DM decreased significantly (p = 0.028, p &amp;lt; 0.042, respectively) and correlated with increasing age (r = -0.323, r = 0.286, respectively). The LV stiffness index did not correlate with age or LV-LS. CONCLUSIONS The LA reservoir strain might be as useful as LV-LS as an early marker of cardiac dysfunction in patients with T1DM. The correlation coefficient between the LA reservoir strain and LV-LS was not strong. Therefore, although LV-LS might affect the LA reservoir strain, it might represent other aspects of cardiac dysfunction. The increase of LA stiffness might represent the changes in LA wall properties and could be another useful indicator of cardiac dysfunction during long-term follow-ups, which is independent of LV-LS. Overall, these findings provide new insights into cardiac dysfunction in patients with T1DM.

152: The DECIDE study: Correlating adverse neonatal outcome and biochemical markers of cardiac dysfunction

152: The DECIDE study: Correlating adverse neonatal outcome and biochemical markers of cardiac dysfunction

Quantitative [18F]florbetapir PET/CT may identify lung involvement in patients with systemic AL amyloidosis.

The clinical diagnosis of pulmonary involvement in individuals with systemic AL amyloidosis remains challenging. [18F]florbetapir imaging has previously identified AL amyloid deposits in the heart and extra-cardiac organs. The aim of this study is to determine quantitative [18F]florbetapir pulmonary kinetics to identify pulmonary involvement in individuals with systemic AL amyloidosis. We prospectively enrolled 58 subjects with biopsy-proven AL amyloidosis and 9 control subjects (5 without amyloidosis and 4 with ATTR cardiac amyloidosis). Pulmonary [18F]florbetapir uptake was evaluated visually and quantified as distribution volume of specific binding (Vs) derived from compartmental analysis and simpler semiquantitative metrics of maximum standardized uptake values (SUVmax), retention index (RI), and target-to-blood ratio (TBR). On visual analysis, pulmonary tracer uptake was absent in most AL subjects (40/58, 69%); 12% (7/58) of AL subjects demonstrated intense bilateral homogeneous tracer uptake. In this group, compared to the control group, Vs (median Vs 30-fold higher, 9.79 vs. 0.26, p < 0.001), TBR (median TBR 12.0 vs. 1.71, p < 0.001), and RI (median RI 0.310 vs. 0.033, p < 0.001) were substantially higher. Notably, the AL group without visually apparent pulmonary [18F]florbetapir uptake also demonstrated a > 3-fold higher Vs compared to the control group (median 0.99 vs. 0.26, p < 0.001). Vs was independently related to left ventricular SUVmax, a marker of cardiac AL deposition, but not to ejection fraction, a marker of cardiac dysfunction. Also, intense [18F]florbetapir lung uptake was not related to [11C]acetate lung uptake, suggesting that intense [18F]florbetapir lung uptake represents AL amyloidosis rather than heart failure. [18F]florbetapir PET/CT offers the potential to noninvasively identify pulmonary AL amyloidosis, and its clinical relevance warrants further study.

Ameliorative effect of rosiglitazone, a peroxisome proliferator gamma agonist on adriamycin-induced cardio toxicity via suppressing oxidative stress and apoptosis.

We investigated the rosiglitazone (RSG) effect on adriamycin (ADM)-induced cardio toxicity in experimental animals. Forty adult Wistar male rats were separated into four groups as follows: normal control; RSG (10 mg/kg)-treated; ADM (10 mg/kg)-administered; and ADM (10 mg/kg) + RSG (10 mg/kg)-treated. Serum lipid level, different biochemical biomarkers, histological analysis, and nuclear factor erythroid 2-related factor/heme oxygenase-1 (Nrf2/HO-1), Caspase 3, B-cell lymphoma 2 (Bcl-2), and Bax gene expression were assessed in serum and cardiac tissue samples. Our results show that RSG treatment in ADM-administered animals significantly diminished low-density lipoprotein cholesterol, triglyceride, and total cholesterol, and increases high-density lipoprotein cholesterol (HDL-c) in comparison with the ADM group. RSG treatment reduced the effect of ADM administration on cardiac dysfunction markers such as cardiac troponin T Creatine Kinase-MB, aspartate aminotransferase, and lactate dehydrogenase, showing the amelioration of cardio toxicity in ADM-administered rats. Additionally, RSG treatment significantly decreased the level of malondialdehyde and nitric oxide in cardiovascular tissue. RSG-treated rats in combination with ADM likewise showed a significant increase in reduced glutathione, superoxide dismutase, catalase content, and the activity of glutathione peroxidase (GPx) as compared with ADM group. Moreover, RSG treatment in ADM rats significantly increased an Nrf2 and HO-1 expression in comparison with ADM group. While in apoptosis parameters, RSG treatment in ADM rats significantly diminished a cleaved caspase-3 and Bax expression as well as expanded Bcl-2 expression when contrasted with ADM group of rats. In conclusion, RSG is capable of protecting heart toxicity in ADM-treated animals through defensive effects on oxidative stress and biochemical markers.

Torsional motion of the left ventricle does not affect ventricular fluid dynamics of both foetal and adult hearts

Left ventricular torsion is caused by shortening and relaxation of the helical fibres in the myocardium, and is thought to be an optimal configuration for minimizing myocardial tissue strains. Characteristics of torsional motion has also been proposed to be markers for cardiac dysfunction. However, its effects on fluid and energy dynamics in the left ventricle have not been comprehensively investigated. To investigate this, we performed image-based flow simulations on five healthy adult porcine and two healthy human foetal left ventricles (representing two different length scales) at different degrees of torsional motions. In the adult porcine ventricles, cardiac features such as papillary muscles and mitral valves, and cardiac conditions such as myocardial infarctions, were also included to investigate the effect of twist. The results showed that, for all conditions investigated, ventricular torsional motion caused minimal changes to flow patterns, and consistently accounted for less than 2% of the energy losses, wall shear stresses, and ejection momentum energy. In contrast, physiological characteristics such as chamber size, stroke volume and heart rate had a much greater influence on flow patterns and energy dynamics. The results thus suggested that it might not be necessary to model the torsional motion to study the flow and energy dynamics in left ventricles.

P3640Association of ceramide and phospholipid levels and cardiovascular events in stable coronary heart disease: findings from the STABILITY Biomarkers substudy

Abstract Background Both levels of protein and lipid biomarkers have been found associated with cardiovascular outcomes in patients with stable coronary heart disease (CHD). There are few large-scale studies comparing the prognostic value of and interactions between these two groups of biomarkers in CHD. Methods In the 15,828 CHD patients included in the STABILITY trial 10,205 provided plasma samples at baseline allowing measurements of distinct ceramide and phospholipid species by mass spectrometry and markers of cardiac dysfunction (N-terminal pro-B-type natriuretic peptide [NT-proBNP]), high sensitivity cardiac troponin-T [cTnT-hs]), renal dysfunction (cystatin-C), oxidative stress (growth differentiation factor 15 [GDF-15]) by electro-immunoassays. During 3.7 years median follow-up, 1291 CVD, MI, and stroke events occurred. A previously developed ceramide and phospholipid species based risk score (CERT) and its associations to outcomes before and after adjustment were evaluated by Cox-regression models. Results The CERT model was significantly associated to all cardiovascular outcomes before and after adjustment for clinical characteristics and routine laboratory tests. However, the associations were attenuated after adjustment for other prognostic biomarkers. The data are summarized in Table 1 below. Table 1. HR per 1 SD increase in CERT HR (95% CI) p-value MACE Model 1 1.30 (1.24–1.37) &lt;0.0001 Model 2 1.23 (1.16–1.31) &lt;0.0001 Model 3 1.08 (1.02–1.15) 0.0120 CVD Death Model 1 1.57 (1.45–1.69) &lt;0.0001 Model 2 1.38 (1.26–1.50) &lt;0.0001 Model 3 1.14 (1.04–1.26) 0.0052 MACE = CVD death, stroke and MI. Model 1 includes score and randomized treatment. Model 2 includes score, randomized treatment, age, gender, and prior (MI, coronary revas., multivessel CHD), B/L diabetes, hypertension, history of smoking, PVD, region, B/L systolic BP, B/L BMI, HB, WBC, CKD-EPI, LDL-C, HDL-C and TG. Model 3 includes the following covariates in addition to Model 2: TnT-hs, proBNP, Cystatin-C, CRP-hs and IL-6. Conclusion A ceramide/phospholipids based risk score is associated with the risk of fatal and non-fatal cardiovascular events in patients with stable CHD. The score is attenuated by adjustment for biomarkers indicating cardiorenal dysfunction and inflammatory activity and may be related to underlying mechanisms for adverse outcomes in stable CHD. Acknowledgement/Funding The original STABILITY study was funded by GlaxoSmithKline

Cardiac function assessed by myocardial deformation in adult polycystic kidney disease patients

BackgroundPatients with autosomal dominant polycystic kidney disease (ADPKD) have an increased risk of cardiovascular morbidity and mortality. Impaired left ventricular (LV) global longitudinal strain (GLS) can be a sign of subclinical cardiac dysfunction even in patients with otherwise preserved ejection fraction (EF). Transmitral early filling velocity to early diastolic strain rate (E/SRe) is a novel measure of LV filling pressure, which is often affected early in cardiac disease.MethodsA total of 110 ADPKD patients not on dialysis were included in this prospective study. All patients underwent an extensive echocardiographic examination including two-dimensional speckle tracking. GLS and strain rates were measured. The distribution of GLS and E/SRe was determined and patient characteristics were compared by median levels of GLS (− 17.8%) and E/SRe (91.4 cm). Twenty healthy participants were included as control group.ResultsThere was a significantly worse GLS in the ADPKD patients (mean: − 17.8 ± 2.5%) compared to the healthy controls (mean: − 21.9 ± 1.9%), p < 0.001. The same was true for E/SRe (mean: 10.0 ± 0.3 cm) compared to the control group (mean: 6.5 ± 0.3 cm), p < 0.001. In simple logistic regression, male gender (OR: 4.74 [2.10–10.71], p < 0.001), fasting glucose (odds ratio (OR) 1.05 [1.01–1.10], p = 0.024), htTKV (OR: 1.07 [1.01–1.13], p = 0.013), HDL cholesterol (OR: 0.97 [0.94, 0.996], p = 0.025), triglycerides (OR: 1.01 [1.00–1.02], p = 0.039), hemoglobin (OR: 1.50 [1.11–2.04], p = 0.009), and β-blocker use (OR: 1.07 [1.01, 1.13], p = 0.013) were all associated with higher GLS. After multivariate logistic regression with backward model selection, only male gender (OR: 5.78 [2.27–14.71], p < 0.001) and β-blocker use (OR: 14.00 [1.60, 122.51], p = 0.017) remained significant. In simple logistic regression models, BMI (OR: 1.11 [1.02–1.20], p = 0.015), systolic blood pressure (OR: 1.03 [1.00–1.06], p = 0.027) and β-blocker use (OR: 17.12 [2.15–136.20], p = 0.007) were associated with higher E/SRe - a novel measure of left ventricular filling pressure. After backward elimination, only β-blocker use (OR: 17.22 [2.16, 137.14], p = 0.007) remained significant.ConclusionHigher GLS and E/SRe are common in ADPKD patients, even in patients with preserved eGFR and normal left ventricular EF. GLS and E/SRe may aid in cardiovascular risk stratification in patients with ADPKD as they represent early markers of cardiac dysfunction.