Defining the metabolomic profile associated with early cardiotoxicity in patients with breast cancer treated with anthracyclines

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D Cocco ◽  
E.G Ferro ◽  
S Ricci ◽  
M Deidda ◽  
A Noto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Heart Failure ◽  
Global Longitudinal Strain ◽  
Partial Least Square ◽  
Least Square ◽  
Public Institution ◽  
Funding Source ◽  
Dependent Manner ◽  
Metabolomic Profile ◽  
Clinical Heart Failure

Abstract Background Anthracycline (ANT) therapy has dramatically improved clinical outcomes for patients with breast cancer, but it causes cardiotoxicity (CTX) in a dose-dependent manner. Current cardiac biomarkers (troponin, brain natriuretic peptide) and 2D echocardiography only detect CTX in advanced and often irreversible stages. Metabolomic analysis may allow early diagnosis of CTX, and prompt initiation of cardio protective therapies. Purpose To diagnose early CTX via speckle tracking echocardiography (STE), and to characterize the metabolomic fingerprint of patients affected by ANT-mediated CTX. Methods In 2019, patients with breast cancer and normal baseline ejection fraction (EF) were enrolled and longitudinally monitored through clinical assessment, blood sample collection and echocardiography, before initiation of ANT therapy and at 180, 270 and 360 mg/m2 of ANT. CTX, defined as >15% reduction in Global Longitudinal Strain (GLS), was monitored at each ANT dose increment. Unsupervised Principal Component Analysis, supervised Partial Least Square and Partial Least-Square Discriminant Analyses were used to compare the metabolomic profiles of patients who did and did not develop CTX during the study period. Results In the study sample (n=33), no patient developed clinical heart failure, but 8 patients (25%) developed CTX by GLS criteria. Patients with CTX had a significant decrease in GLS compared to patients without CTX at 270 mg/m2 (GLS 20.5 vs 17.9, p=0.01) and 360 mg/m2 ANT (GLS 21.6 vs 17.7, p<0.001), but no significant differences in EF or other 2D echocardiographic parameters. The PLS-DA model at 360 mg/m2 ANT (R2=0.92, Q2=0.53, p=0.03) identified a significantly higher prevalence of Krebs cycle intermediates (like fumarate and succinate), and fatty acids (like linoleic acid) in patients with CTX. On the contrary, patients without CTX at 360 mg/m2 ANT had significantly higher levels of cardioprotective metabolites, like tryptophan. Conclusions For the first time in a human population of breast cancer patients, we show that early ANT-induced CTX (diagnosed via asymptomatic GLS reduction) is associated with a unique metabolomic profile, which affects molecular pathways of energy production. Notably, CTX damage upregulates similar metabolites to those previously identified in clinical heart failure and in mouse CTX models. Our results suggest that a metabolomic fingerprint can be leveraged to create prediction models to identify patients at higher risk of developing cardiovascular complications from ANT therapy. This, in turn, will allow to personalize both chemotherapy and cardioprotective treatments. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): University of Cagliari

scholarly journals Reduced NT-proBNP threshold for risk prediction in high-risk elderly with subclinical heart failure: support from cardiopulmonary exercise testing

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Potter ◽  
M Woessner ◽  
T.H Marwick
Keyword(s):  
Heart Failure ◽  
High Risk ◽  
Risk Prediction ◽  
Global Longitudinal Strain ◽  
Cardiopulmonary Exercise Testing ◽  
Left Ventricular ◽  
Public Institution ◽  
Funding Source ◽  
Cardiopulmonary Exercise ◽  
Cardiac Phenotype

Abstract Background Subclinical heart failure (HF) is divided into Stage A and B (SAHF and SBHF) depending on structural or functional cardiac abnormalities. However, risk of HF progression is not solely dependent on echocardiographic abnormalities. Data on oxygen consumption (VO2) and other prognostic cardiopulmonary exercise test (CPET) markers in subclinical HF, particularly in the elderly, is lacking. VO2 may refine risk prediction and provide pathological insight in subclinical HF. Methods Asymptomatic individuals were recruited through primary care if they were ≥65 years with ≥1 non-ischaemic risk factor for HF. Clinical evaluation determined risk profile, biometrics and NT-proBNP. Treadmill CPET was undertaken with a modified Bruce protocol. Low V02 was defined as ≤20th percentile of age and gender specific VO2 in healthy individuals. SBHF defined as systolic (global longitudinal strain, GLS ≤16%), diastolic (E/e' ≥15, E/e' >10 with left atrial enlargement or impaired relaxation with other changes or left ventricular (LV) hypertrophy (LV mass index >95 g/m2 in women or >115 g/m2 in men). Results Of the 91 included individuals (age 71±4 years, 53% female), 46 (51%) had SBHF, average NT-proBNP was 60pg/ml (26–99mg/ml) and did not differ by HF stage (59 [26–85] pg/ml vs. 60 [30–99] pg/ml for Stage A vs. B respectively, p=0.94). Average peak VO2 was 19.8 (16–22.6) ml/kg/min and was low in 71 (78%). VO2 did not differ by HF stage (19.9 [17.7–22.4] ml/kg/min vs. 19.7 [16–22.8] ml/kg/min for SAHF vs. SBHF respectively, p=0.62). NT-proBNP was significantly higher in those with abnormal VO2 (66 [34–110] pg/ml vs 31 [20–70] pg/ml, p=0.016). Within each HF stage, low VO2 was associated with higher NT-proBNP (Figure). Of those with NT-proBNP >100pg/ml, 95% (22/23) had low VO2 compared with 72% of those ≤100pg/ml, p=0.02 (non-signifcant for 125pg/ml cut-off). No associations were found between SBHF or individual echo abnormalities and VO2. In logistic regression analysis NT-proBNP was a significant univariable predictor of low VO2 and remained significant after adjustment for other significant univariables (BMI) (OR 1.02 [95% CI 1.0001–1.03], p=0.048). Conclusion Low VO2 identifies a high-risk cardiac phenotype within subclinical HF stages, but is not necessarily associated with LV dysfunction. Levels of NT-proBNP beneath the cut-off used for HF exclusion may assist risk stratification in this population. NT-proBNP by VO2 in subclinical HF Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Dr E Potter is supported by a PhD Scholarship from Monash University, Melbourne, Australia

Coronary sinus catalase and ceruloplasmin levels predict all-cause mortality in patients with end-stage heart failure awaiting heart transplantation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
W Szczurek ◽  
M Gasior ◽  
M Skrzypek ◽  
G Kubiak ◽  
A Kuczaj ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Transplantation ◽  
Coronary Sinus ◽  
Public Institution ◽  
Funding Source ◽  
Organ Shortage ◽  
Number Of Patients ◽  
End Stage ◽  
Medical University

Abstract   Background, As a consequence of the worldwide increase in life expectancy and due to significant progress in the pharmacological and interventional treatment of heart failure (HF), the proportion of patients that reach an advanced phase of disease is steadily growing. Hence, more and more numerous group of patients is qualified to the heart transplantation (HT), whereas the number of potential heart donors has remained invariable since years. It contributes to deepening in disproportion between the demand for organs which can possibly be transplanted and number of patients awaiting on the HT list. Therefore, accurate identification of patients who are most likely to benefit from HT is imperative due to an organ shortage and perioperative complications. Purpose The aim of this study was to identify the factors associated with reduced survival during a 1.5-year follow-up in patients with end-stage HF awating HT. Method We propectively analysed 85 adult patients with end-stage HF, who were accepted for HT at our institution between 2015 and 2016. During right heart catheterization, 10 ml of coronary sinus blood was additionally collected to determine the panel of oxidative stress markers. Oxidative-antioxidant balance markers included glutathione reductase (GR), glutathione peroxidase (GPx), glutathione transferase (GST), superoxide dismutase (SOD) and its mitochondrial isoenzyme (MnSOD) and cytoplasmic (Cu/ZnSOD), catalase (CAT), malondialdehyde (MDA), hydroperoxides lipid (LPH), lipofuscin (LPS), sulfhydryl groups (SH-), ceruloplasmin (CR). The study protocol was approved by the ethics committee of the Medical University of Silesia in Katowice. The endpoint of the study was mortality from any cause during a 1.5 years follow-up. Results The median age of the patients was 53.0 (43.0–56.0) years and 90.6% of them were male. All included patients were treated optimally in accordance with the guidelines of the European Society of Cardiology. Mortality rate during the follow-up period was 40%. Multivariate logistic regression analysis showed that ceruloplasmin (odds ratio [OR] = 0.745 [0.565–0.981], p=0.0363), catalase (OR = 0.950 [0.915–0.98], p=0.0076), as well as high creatinine levels (OR = 1.071 [1.002–1.144], p=0.0422) were risk factors for death during 1.5 year follow-up. Conclusions Coronary sinus lower ceruloplasmin and catalase levels, as well as higher creatinine level are independently associated with death during 1.5 year follow-up. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Medical University of SIlesia, Katowice, POland

Echocardiographic assessment of CRT candidates. Does it work equally well in intermediate QRS duration?

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Duchenne ◽  
M Cvijic ◽  
J.M Aalen ◽  
C.K Larsen ◽  
E Galli ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mechanical Dyssynchrony ◽  
Public Institution ◽  
Cardiac Resynchronization ◽  
Funding Source ◽  
Entire Study ◽  
Qrs Duration ◽  
Echocardiographic Assessment ◽  
Echocardiographic Images ◽  
Crt Response

Abstract Background The presence of mechanical dyssynchrony – such as apical rocking (ApRock) and septal flash (SF) – on echocardiography is associated with favourable outcome after cardiac resynchronization therapy (CRT). Myocardial scar on the other hand, has a considerable negative impact on CRT response. There is growing evidence that a visual echocardiographic assessment of mechanical dyssynchrony by ApRock, SF and scar predicts CRT response. Little is known however if this works equally well in patients with intermediate QRS duration (120–150ms), where guideline recommendation for CRT is weaker. Methods A total of 400 unselected patients referred for CRT, who fulfil the contemporary guidelines, were enrolled in this multicentre study. Echocardiographic images were visually assessed before CRT implantation, focussing on the presence of ApRock, SF and location and extent of scar segments in the left ventricle (LV), resulting in a CRT response prediction (i.e. Reader Interpretation). Readers were blinded to all patient information other than ischaemic aetiology of heart failure. CRT response was defined as ≥15% reduction in LV end-systolic volume on echocardiography, on average 15 months after device implantation. Results Overall, 321 (80%) patients had a left bundle branch block (LBBB), with an average QRS duration of 166±25ms. Ischemic aetiology of heart failure was found in 131 (33%) patients. Before CRT, ApRock and SF were present in 254 (64%) and 244 (61%) patients, respectively. ApRock and SF alone predicted CRT response with an area under the curve (AUC) of 0.79 (95% CI: 0.74–0.84) and 0.78 (95% CI: 0.73–0.83) (Figure A), while the echocardiographic Reader Interpretation had an AUC of 0.85 (95% CI: 0.81–0.89), with a sensitivity of 89% and a specificity of 82% for the prediction of CRT response (Figure B) (p<0.0001 vs. ApRock and SF alone). A total of 92 patients had a QRS duration of 120–150ms, and 48 of them responded to CRT. In these patients, the AUC of Reader Interpretation was comparable to that of the entire study cohort [0.83 (95% CI: 0.75–0.92)], as was sensitivity and specificity (90% and 79%, respectively, p=0.717 vs. the AUC of the entire cohort) (Figure C). Conclusions A visual assessment of LV function, by means of mechanical dyssynchrony and scar, has an excellent predictive value for CRT response, and requires only apical echocardiographic images. Responders were identified equally well in the challenging subgroup of patients with a QRS duration of 120–150 ms. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): KU Leuven

scholarly journals Prognostic value and reversibility of liver stiffness in patients undergoing tricuspid annuloplasty

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Chen ◽  
Y.H Chan ◽  
M.Z Wu ◽  
Y.J Yu ◽  
Q.W Ren ◽  
...  
Keyword(s):  
Heart Failure ◽  
Adverse Events ◽  
Prognostic Value ◽  
Adverse Outcome ◽  
Liver Stiffness ◽  
Vena Cava ◽  
Public Institution ◽  
Funding Source ◽  
Cox Regression Analysis ◽  
Tricuspid Annuloplasty

Abstract Background Hepatic dysfunction was previously suggested to be related to poor outcome in patients undergoing tricuspid annuloplasty (TA), the predictive value of liver stiffness (LS) for adverse events is nonetheless uncertain. Purpose The aim of this study was to evaluate the prognostic value and reversibility of LS in patients undergoing TA. Methods A total of 158 patients (age 63, male 35%) who underwent TA during left-sided valve surgery were prospectively evaluated. Transient elastography was used to assess LS. Patients were divided into three groups according to tertiles of LS. Adverse outcome was defined as heart failure requiring hospital admission or mortality. Results The median LS was 13.9 (8.1–22.3) kPa which independently correlates with tricuspid regurgitation severity (assessed by effective regurgitant orifice area), inferior vena cava diameter and tricuspid annular plane systolic excursion. During a median follow-up of 31 months, 49 adverse events occurred. Multivariable Cox regression analysis demonstrated that LS was an independent predictor of adverse events. Furthermore, a higher LS tertile was predictive for adverse events (Hazard Ratio 4.19, P<0.01) even after adjusting for the other prognosticators. Kaplan-Meier curve showed that patients in the third tertile LS group had the highest percentage of adverse events followed by patients in the second tertile. Significant improvement of LS at 1-year post-TA was noted only in patients who had no adverse events but not in those who experienced heart failure. Conclusions The present study demonstrates that LS is predictive of adverse outcome in patients undergoing TA. These findings suggested that assessing LS, an integrative assessment of right heart condition, may aid the management of patients undergoing TA. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The Health and Medical Research Fund from the Food and Health Bureau, the Government of Hong Kong Special Administrative Region.

scholarly journals Moderating Role of Demographic Characteristics in Breast Cancer Awareness and the Behavioural Disposition of Women in Ogun State, Nigeria

2018 ◽  
Author(s):  
Tolulope Allo ◽  
Patrick Edewor ◽  
Imhonopi, David O.
Keyword(s):  
Breast Cancer ◽  
Demographic Characteristics ◽  
Partial Least Square ◽  
Least Square ◽  
Cancer Awareness ◽  
Cross Sectional ◽  
Ogun State ◽  
Breast Cancer Awareness ◽  
Moderating Role

<p>This study is aimed at examining the moderating role of demographic characteristics in facilitating breast cancer awareness among women in relation to their behavioural disposition to the disease. The study adopted the descriptive (survey) and cross-sectional research designs to elicit information from women of adult age selected across five Local Government Areas in Ogun state. The data, collected through questionnaire were analysed through the use of a variance-based SEM Partial Least Square (PLS). The result shows that demographic characteristics (age and education) had a positive significant effect and jointly explain 74.9% of the variance in the breast cancer awareness and behavioural disposition among women in the study area. The findings revealed that a significant number of women with breast cancer have not acquired useful knowledge that could potentially be used to diagnose, prevent, and manage the disease. Unfortunately, the practice of Breast Self-Examination is grossly low among Nigerian women, as a consequence, only 20-30% of the women in study areas, including professionals know of the benefits of BSE and only a smaller percentage practice BSE. There is therefore a need to educate women on the benefits of this simple life saving procedure through the consistent use of media platforms.</p>

Optimal doses of heart failure medication in women and men: perspective from daily clinical care

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Bots ◽  
N.C Onland-Moret ◽  
I.I Tulevski ◽  
G.A Somsen ◽  
H.M Den Ruijter
Keyword(s):  
Heart Failure ◽  
Clinical Care ◽  
Daily Practice ◽  
Left Ventricular ◽  
Cubic Splines ◽  
Public Institution ◽  
Angiotensin Ii Receptor Blocker ◽  
Funding Source ◽  
Target Dose ◽  
Natural Cubic Splines

Abstract Background Heart failure (HF) guidelines recommend equal target doses for women and men. Recently, these recommendations have been challenged as research suggested that women with HF with reduced Ejection Fraction (HFrEF) may reach optimal treatment effect at half of the guideline-recommended dose while men may require the full dose. However, it is unclear how often women and men reach guideline-recommended target doses in daily practice. Purpose To evaluate whether women and men with HF reach guideline-recommended target doses for Angiotensin-converting enzyme inhibitors (ACEI)/angiotensin II receptor blocker (ARB), β-blockers (BB) and mineralocorticoid receptor antagonists (MRA) in daily practice. Methods We extracted data from 13 outpatient cardiology clinics for all individuals diagnosed with HF within 14 days leading up to their visit who were prescribed at least one guideline-recommended HF medication. HF was defined based on a combination of the cardiologist's diagnosis and left ventricular systolic or diastolic dysfunction determined during echocardiography. Guideline-recommended medication groups and target doses were taken from the 2016 ESC HF guidelines or from literature for medications not mentioned in the guidelines. To enable comparison between medications and medication groups, daily dose was converted to percentage of target dose. Mean change in percentage of target dose over consecutive medication prescriptions was modelled for men and women using natural cubic splines. Results We included 1254 patients with HF (48% women). Women were on average older at diagnosis (71 vs 67 years) and more often had hypertension (54.9 vs 44.3%), but less often had diabetes mellitus (13.5 vs 19.4%), a history of coronary heart disease (7.8 vs 19.6%,) or past cardiovascular interventions (8.7 vs 23.0%) than men. In total, 1069 patients were prescribed an ACEI/ARB (46% women), 920 a BB (48% women) and 243 an MRA (43% women). Women were more often prescribed only one medication than men (39.6 vs 33.2%, p=0.014). Approximately 14% of first prescriptions for all medications were at 100% of target dose or higher for both women and men, with the majority of prescriptions being either at 1–49% of target dose (47.2 vs 45.5%, respectively) or 50–99% of target dose (39.1 vs 40.8%, respectively). The natural cubic splines showed that this distribution did not change over consecutive drug prescriptions in either women or men. Only MRA prescriptions for men showed an upward trend and reached 100% of target dose. Conclusion In daily practice, both women and men were unlikely to reach guideline-recommended target doses for both ACEI/ARBs and BBs. For MRAs, women were less likely to reach target dose than men. Optimal dosing in HF is difficult for both sexes, but in light of recent evidence, the challenge in daily practice seems to lie more in undertreatment of men than overtreatment of women. Figure 1 (women in red, men in blue) Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): ZonMw

scholarly journals Validation of the HFA-PEFF- and H2FPEF score in Japanese patients with heart failure with preserved ejection fraction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Iwakura ◽  
T Onishi ◽  
M Okada ◽  
K Inoue ◽  
Y Koyama ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Global Longitudinal Strain ◽  
Japanese Patients ◽  
Mean Value ◽  
Diagnostic Tools ◽  
Funding Source ◽  
Preserved Ejection Fraction ◽  
Private Company ◽  
Patients With Heart Failure

Abstract Background Diagnosing heart failure with preserved ejection fraction (HFpEF) still remains challenging, and simple and reliable diagnostic tools have been required. Recently, novel and evidence-based diagnostic algorithms for HFpEF were proposed, such as H2FPEF score (Circulation. 2018) and HFA-PEFF score (Eur Heart J 2019), and their accuracy was validated in the outside patient group. However, there are regional and ethnic variations in patient characteristics of HFpEF, particularly between Western and Asian countries, and it is not elucidated whether these diagnostic scores are useful in Asian population. Purpose To investigate the validity of the HFA-PEFF- and H2FPEF score in Japanese patients with HFpEF. Methods We calculated H2FPEF score and the second step of HFA-PEFF score among the registered patients in the PURSUIT-HFpEF (Prospective, Multicenter, Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) study, which is a multicenter registration of patients hospitalized for HFpEF. The obtained scores were compared with the scores of the HFpEF cohort in the previous validation studies. We followed the study patients for median of 360 days (IQR 237–630 days) to observe the major adverse cardiovascular events (MACE; composite of death, heart failure hospitalization and stroke). Results We enrolled 757 patients hospitalized for HFpEF between June 2016 and August 2019 for the present study. H2FPEF score was obtained in 588 (77.7%) patients among them. Compared with the HFpEF cohorts in the previously reported sub-analysis of TOPCAT trial, the PURSUIT-HFpEF cohort had lower mean value of HFpEF score (4.0±1.8 points vs. 6.0±2.0 points in Americans or 5.3±1.9 points in Russians). It had significantly higher proportion (40.3%, p&lt;0.001) of patients in the low likelihood of HFpEF category (0–3 points) than the TOPCAT cohorts (8.0% in Americans and 19.6% in Russians). HFA-PEFF score was obtained in 615 (81.2%) patients, though global longitudinal strain was not available. The mean value of HFA-PEFF score was 5.0±0.8, and all patients had ≥2 points. The proportion of patients in the high likelihood of HFpEF category (5–6 points) was 88.3%, which was significantly higher (p&lt;0.001) than those of the HFpEF cohort from Europe and USA in the previous validation study (Eur J Heart Fail 2019). There was no correlation between H2FPEF score and HFA-PEFF score (R=0.06, p=0.14). Cox proportional hazard model selected HFA-PEFF score as a significant predictor for MACE during follow-up period, whereas H2PEF score was not selected. Kaplan-Meier survival analysis demonstrated that patients with 6 points of HFA-PEFF score had higher incidence rate of MACE than those with ≤5 points (p=0.002). Conclusion The HFA-PEFF score could be more useful for the diagnosis and risk stratification for HFpEF than the H2PEF score in the Japanese cohort. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Roche Diagnostics K.K.; Fuji Film Toyama Chemical Co. Ltd.

scholarly journals Heat stress modifies the lactational performances and the urinary metabolomic profile related to gastrointestinal microbiota of dairy goats

2018 ◽  
Author(s):  
Alexandra Contreras-Jodar ◽  
Nazri Nayan ◽  
Soufiane Hamzaoui ◽  
Gerardo Caja ◽  
Ahmed A.K. Salama
Keyword(s):  
Heat Stress ◽  
Milk Yield ◽  
Partial Least Square ◽  
Least Square ◽  
Proton Nuclear Magnetic Resonance ◽  
Metabolomic Profile ◽  
Dairy Goats ◽  
Gastrointestinal Microbiota ◽  
Toxic Compounds ◽  
H Nmr

AbstractThe aim of the study was to identify the candidate biomarkers of heat stress (HS) in the urine of lactating dairy goats through the application of proton Nuclear Magnetic Resonance (1H NMR)-based metabolomic analysis. Dairy does (n = 16) in mid-lactation were submitted to thermal neutral (TN; indoors; 15 to 20°C; 40 to 45% humidity) or HS (climatic chamber; 37°C day, 30°C night; 40% humidity) conditions according to a crossover design (2 periods of 21 days). Thermophysiological traits and lactational performances were recorded and milk composition analyzed during each period. Urine samples were collected at day 15 of each period for 1H NMR spectroscopy analysis. Principal component analysis (PCA) and partial least square–discriminant analysis (PLS-DA) assessment with cross validation were used to identify the goat urinary metabolome from Human Metabolome Data Base. HS increased rectal temperature (1.2°C), respiratory rate (3.5-fold) and water intake (74%), but decreased feed intake (35%) and body weight (5%) of the lactating does. No differences were detected in milk yield, but HS decreased the milk contents of fat (9%), protein (16%) and lactose (5%). Metabolomics allowed separating TN and HS urinary clusters by PLS-DA. Most discriminating metabolites were hippurate and other phenylalanine (Phe) derivative compounds, which increased in HS vs. TN does. The greater excretion of these gut-derived toxic compounds indicated that HS induced a harmful gastrointestinal microbiota overgrowth, which should have sequestrated aromatic amino acids for their metabolism and decreased the synthesis of neurotransmitters and thyroid hormones, with negative impact on milk yield and composition. In conclusion, HS markedly changed the thermophysiological traits and lactational performances of dairy goats, which were translated into their urinary metabolomic profile through the presence of gut-derived toxic compounds. Hippurate and other Phe-derivative compounds are suggested as urinary biomarkers to detect heat stressed dairy animals in practice.

scholarly journals Significance of left ventricular global longitudinal strain assessment in patients with preserved ejection fraction after acute myocardial infarction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Luvsansuren ◽  
S Chimed
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Ejection Fraction ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Longitudinal Strain ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Clinical Heart Failure

Abstract Background Depression of left ventricular function is common phenomenon after acute myocardial infarction and it's often associated with poor prognosis. However, substantial portion of patients with acute myocardial infarction had normal left ventricular function by assessment of left ventricular ejection fraction. Purpose In this study, we examined role of left ventricular global longitudinal strain assessment in patients who had normal ejection fraction after acute myocardial infarction. Methods We choose patients with acute myocardial infarction who were successfully treated with primary percutaneous coronary intervention (PCI). All of those patients had normal ejection fraction (EF≥55%) in routine echocardiographic examination within 3 days after acute myocardial infarction. Two dimensional speckle tracking echocardiography was used to assess left ventricular global longitudinal strain. Based on existence of newly onset clinical signs (pulmonary edema, lung crackles, peripherial edema etc.) of heart failure patients divided into case and control group. Patients who had other etiology or previous heart failure were excluded. Results A total of 153 patients with AMI were selected and newly onset heart failure is occurred in 20 patients. Left ventricular global strain was significantly different between patients with clinical heart failure and patients without clinical heart failure (−11.1±1.85% vs. −16.6±3.38%, p&lt;0.001). After adjustment of possible predictors of impaired left ventricular function such as, age, gender, hypertension, diabetes, previous coronary artery disease, cardiac troponin, mitral inflow EA ratio, deceleration time, left ventricular end diastolic volume, ejection fraction, mitral annulus EE' ratio and wall motion score index, global longitudinal strain was independent predictor of clinical heart failure (odds ratio 1.79, 95% CI 1.22–2.65, p=0.003). Adding global longitudinal strain into above mentioned predictors of clinical heart failure after acute myocardial infarction is associated with significantly increased c-statistic (0.93, 95% CI 0.87–0.99 vs. 0.97, 95% CI 0.94–0.99, p&lt;0.001). Conclusion Left ventricular global longitudinal strain is independently associated with clinical heart failure in patients with preserved ejection fraction after acute myocardial infarction. Adding global longitudinal strain parameter into screening model may increase rate of precise determination of clinical heart failure after acute myocardial infarction. Funding Acknowledgement Type of funding source: None

scholarly journals Multiclass Prediction with Partial Least Square Regression for Gene Expression Data: Applications in Breast Cancer Intrinsic Taxonomy

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Chi-Cheng Huang ◽  
Shih-Hsin Tu ◽  
Ching-Shui Huang ◽  
Heng-Hui Lien ◽  
Liang-Chuan Lai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Molecular Subtypes ◽  
Expression Profiles ◽  
Weighted Kappa ◽  
Partial Least Square ◽  
Least Square ◽  
Partial Least Square Regression ◽  
Training Dataset ◽  
Pls Regression

Multiclass prediction remains an obstacle for high-throughput data analysis such as microarray gene expression profiles. Despite recent advancements in machine learning and bioinformatics, most classification tools were limited to the applications of binary responses. Our aim was to apply partial least square (PLS) regression for breast cancer intrinsic taxonomy, of which five distinct molecular subtypes were identified. The PAM50 signature genes were used as predictive variables in PLS analysis, and the latent gene component scores were used in binary logistic regression for each molecular subtype. The 139 prototypical arrays for PAM50 development were used as training dataset, and three independent microarray studies with Han Chinese origin were used for independent validation (n=535). The agreement between PAM50 centroid-based single sample prediction (SSP) and PLS-regression was excellent (weighted Kappa: 0.988) within the training samples, but deteriorated substantially in independent samples, which could attribute to much more unclassified samples by PLS-regression. If these unclassified samples were removed, the agreement between PAM50 SSP and PLS-regression improved enormously (weighted Kappa: 0.829 as opposed to 0.541 when unclassified samples were analyzed). Our study ascertained the feasibility of PLS-regression in multi-class prediction, and distinct clinical presentations and prognostic discrepancies were observed across breast cancer molecular subtypes.

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