bluuebunny/crossref_metadata_2025_split huggingface dataset:
P5423Exercise oscillatory ventilation improves the performance of prognosis scores currently used for heart failure
Authors: Gama F , Freitas P , Aguiar C , Ferreira A , Strong C , Ventosa A , Ferreira F , Mendes M 
Published: October 2019

Abstract

Background and aim
Several prognostic risk scores are available for heart failure with reduced ejection fraction (HFrEF), and are used, together with other criteria, to help decide the ideal timing for listing candidates for a heart transplant. The detection of an oscillatory ventilatory pattern (OVP) during cardiopulmonary exercise testing (CPET) has been associated with more advanced HF and a worse prognosis, but was not considered in the development of all the current risk scores. We evaluated whether OVP adds significant prognostic information to four contemporary HF scores.

Methods
Single-centre retrospective cohort study of consecutive HFrEF patients undergoing CPET for functional and prognostic assessment from October 1996 till May 2018. The Heart Failure Survival Score (HFSS), Seattle Heart Failure Model (SHFM), Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) and Metabolic Exercise Cardiac Kidney Index (MECKI) were obtained in each patient. Cox model was fit with time to death or urgent transplant (whichever came first within 2 years) as the dependent variable and OVP and respective HF score as the independent variables. We further assessed the added discriminative power by performing ROC curve comparisons.

Results
We studied 387 patients, median age 58 (IQR 49; 65) years, and 77% were male. The most common HFrEF aetiology was ischemic heart disease (54%). Median peak oxygen consumption was 15,7 mL/kg/min (IQR 12,8; 20,0). OVP was present in 150 (39%) patients. Over the 2-year follow-up period, 48 patients died, and 52 underwent heart transplantation (of which 25 were urgent). HFSS showed the weakest (c-statistic 0,625; 95% [CI] 0,54–0,71) and MECKI score the strongest (c-statistic 0,819; 95% [CI] 0,76–0,88) discriminatory ability. Contrasting with NTproBNP value, the presence of OVP predicted the study endpoint independently of the HF prognosis score used (see table). Adding the occurrence of OVP to the HFSS and the MAGGIC scores significantly improved their prognostic performance (see Table).

Conclusion
An OVP is a common finding in HFrEF patients undergoing CPET, and adds prognostic information to contemporary HF prognosis scores. Systematic evaluation of this easily available criterion may assist the decision on the appropriate timing for heart transplantation listing.
P5434P300-mediated inactivation of p53 protects against doxorubicin-induced cardiotoxicity
Authors: Adam M , Singh K K , Connelly K A 
Published: October 2019

Abstract

Introduction
Doxorubicin is amongst the most widely prescribed chemotherapy drugs due to its effectiveness in cancer treatment. However, progressive treatment using doxorubicin severely increases the risk of congestive heart failure. Mechanistically, researchers have shown that doxorubicin (i) intercalates into DNA and disrupts topoisomerase-II-mediated DNA repair and (ii) generates free radicals which then causes damage to cellular membranes, DNA, and proteins. Ultimately these cellular insults induce cardiomyocyte (CM) death mediated by the tumour suppressor, p53. Currently, there are no clinically applicable preventative treatments for doxorubicin-induced cardiotoxicity and so, extensive research is being done in discovering a potential therapy. One such candidate is curcumin – a natural polyphenol compound non-toxic to humans. We have previously demonstrated that curcumin inhibits lysine acetyltransferase activity of p300, therefore reducing both histone and non-histone protein acetylation. To induce CM death, p53 requires acetylation by p300. Therefore, we hypothesize that curcumin protects against doxorubicin-induced CM death and cardiotoxicity via p300-mediated inactivation of p53.

Methods
Rat H9c2 cardiomyoblast cells were cultured and treated with a 2.5 μM dose of doxorubicin for 16 hours. One group of cells were pre-treated with curcumin (15μM) 4 hours prior to doxorubicin treatment, and controls were cultured with only diluent added. Following treatment, the cells were harvested for total protein. At end point, we performed immunoblotting to measure protein expression of key proteins involved in DNA damage (y-H2A.X, p53), and apoptosis (cleaved-Caspase 3).

Results
Our findings show that following doxorubicin treatment, p53 expression was significantly increased (p<0.001), confirming its role in doxorubicin-associated cardiotoxicity. Furthermore, doxorubicin was associated with increased DNA-damage as evidenced by increased expression and activation of DNA double-stranded breaks (DSBs) marker, y-H2A.X (p<0.001). Elevated levels of DNA-damage were further associated with significantly increased doxorubicin-induced apoptosis as measured by immunoblotting for cleaved-Caspase 3 (p<0.001). However, DNA-damage and apoptosis were attenuated by pre-treatment of cells with curcumin. Curcumin treatment led to a significant decrease in both y-H2A.X (p<0.01) and cleaved-Caspase 3 (p<0.01) expression compared to cells treated with only doxorubicin.

Conclusions
Our data provides the first evidence that curcumin protects against doxorubicin-induced apoptosis in rat cardiomyoblast cells in vitro. Further studies are warranted in vivo to confirm the potential of curcumin as a cardio-protective drug. Curcumin is a natural compound with little to no side-effects in humans, therefore our finding may provide a novel therapeutic target and treatment approach for doxorubicin-associated cardiotoxicity.

Acknowledgement/Funding
Heart & Stroke Foundation of Canada
P5435Epigenetic modifications and gene expressions in Mybpc3 knockout mice
Authors: Hossain M , Elbeck Z , Li X , Siga H , Esfahani P , Knoell R 
Published: October 2019

Abstract

Background
DNA methylation and hydroxymethylation plays critical role in important biological processes, including differentiation of tissues in the embryo and cellular response to different diseases and diverse environmental factors. The epigenetic landscape in heart failure might be altered.

Purpose
Our objective was to determine how Mybpc3 deficiency, which produces hypertrophic cardiomyopathy, affects epigenetic landscape, gene expression, and regulation.

Methods
We generated and analysed genome-wide DNA methylomes and hydroxymethylomes from cardiac tissues of 12-week old Mybpc3−/− mice and littermate controls, and performed whole genome RNA sequencing (RNA-seq) for gene expression and validated the findings using qPCR.

Results
Single base resolution revealed overall lower 5-mC level in Mybpc3 deficient mice. In deficient mice, different genic regions including transcription start site, exons, and introns, had low levels of 5-mC. Although there was no overall difference in 5-hmC content, knockout mice had lower levels of 5-hmC in the distal part of the genes (last exon, transcription termination site, and 3'-flanking regions). The 5-hmC enrichment in the intronic regions was associated with higher gene expression, whereas, the presence of 5-mC in the 5'-flanking regions was associated with lower gene expression in both knockout and wildtype mice. Ingenuity pathway analysis (IPA) of differentially expressed genes revealed overrepresentation of genes involved in axonal-guidance pathway. Tet activity was downregulated in Mybpc3−/− mice, and it may explain the overall difference of 5-mC in deficient mice. We also observed that Mybpc3 ablation affected alternative splicing of Myh6 and Myh7.

Conclusion
This study establishes that knocking out of Mybpc3 changes epigenetic landscape in cardiac tissue, which is tightly linked to gene expression and regulation.

Acknowledgement/Funding
LeDucq 13CVD04, Hjärt och Lungfonden (Sweden)
P5447Prognostic significance of carboxy-terminal telopeptide (ICTP) and Caspase-3 in patients with non-ischemic dilated cardiomyopathy
Authors: Kazukauskiene I , Baltruniene V , Bironaite D , Cibiras S , Rucinskas K , Grabauskiene V 
Published: October 2019

Abstract

Background
Non-ischemic dilated cardiomyopathy (niDCM) is a common debilitating disease leading to heart failure and poor prognosis. Therefore, a reliable diagnosis of niDCM and search of prognostic biomarkers is a task of paramount importance preventing final destruction of myocardium and improving the outcomes of the disease.
The aim of the study was to evaluate the prognostic value of carboxy-terminal telopeptide (ICTP), a marker of myocardial collagen I degradation, and Caspase-3, a marker of apoptosis, in serum and endomyocardium biopsies (EMBs) of patients with niDCM.

Methods
34 consecutive patients (male 25 (78%); 43.83±12.17 years) with niDCM (average of left ventricle (LV) end-diastolic diameter 6.94±0.78 cm, LV ejection fraction 24.97±6.93%, mean pulmonary capillary wedge pressure 32.9±8.7 mmHg) were enrolled in the study. The levels of ICTP and Caspase-3 in patients' serum and EMBs were measured by ELISA. After a follow-up period of 5 years, 18 patients (53%) have reached the primary composite end-point of heart failure: 6 patients (17.6%) died, 6 patients (17.6%) had heart transplantation and 6 patients (17.6%) underwent left ventricle assist device implantation.

Results
Univariate Cox proportional hazard model and ROC curve analysis identified levels of ICTP and Caspase-3 in serum as predictors of composite end-point (Table 1). However, the levels of ICTP and Caspase-3 in EMBs had no prognostic value.
The cut-off values of serum biomarkers for prediction of the outcome were 13.43 pg/mg protein (sensitivity 67%; specificity 81%) for ICTP and 10.21 pg/mg protein (sensitivity 53%; specificity 87%) for Caspase-3. Univariate Cox regression analysis revealed that patients with higher levels of ICTP and Caspase-3 than cut-off values in serum had higher risk of reaching the composite end-point compared to the patients with lower cut-off values (HR 4.4 (95% CI: 1.6–12.1) and 3.15 (95% CI: 1.2–8.29), respectively). Kaplan-Meier survival analysis demonstrated that patients with serum Caspase-3 and ICTP levels above cut-off values had significantly worse outcome (p=0.01 and p=0.002, respectively).
Table 1 Biomarkers (pg/mg protein) Mean ± SD HR (95% CI) p-value AUC (95% CI) ICTP in serum 15.26±10.59 1.052 (1.013–1.093) 0.009 0.71 (0.53–0.89) ICTP in EMB 132±295 0.999 (0.998–1.001) 0.56 0.45 (0.28–0.61) Caspase-3 in serum 7.78±9.86 1.047 (1.002–1.093) 0.04 0.69 (0.51–0.87) Caspase-3 in EMB 283±282 1 (0.998–1.002) 0.92 0.50 (0.28–0.72)

Conclusion
The findings show that increased serum levels of Caspase-3 and ICTP are significantly associated with poor outcome in patients with niDCM.

Acknowledgement/Funding
the Research Council of Lithuania (Grants nos. MIP-086/2012 and MIP-011/2014), the European Union, EU-FP7, SARCOSI Project (no. 291834)
P5464Visit-to-visit glomerular filtration rate variability as a predictor for cardiovascular and renal outcomes in essential hypertension: Data from a Greek 8-year-follow-up study
Authors: Laina A , Tsioufis C , Dimitriadis K , Kasiakogias A , Liatakis I , Koutra E , Leontsinis I , Konstantinidis D , Kouremeti M , Dri E , Iliakis P , Vogiatzakis N , Thomopoulos K , Tousoulis D 
Published: October 2019

Abstract

Background/Introduction
Renal dysfunction is related with adverse prognosis in hypertension, however there are scarce data on the predictive cardiovascular and renal impact of kidney function variability in this setting.

Purpose
The aim of the present study was to assess the predictive role of visit-to-visit renal function changes on the incidence of coronary artery disease (CAD), stroke and end-stage renal disease in a cohort of essential hypertensive patients.

Methods
We followed up 2380 essential hypertensives (mean age 58.9 years, 1240 males, office blood pressure (BP)=144/91 mmHg) free of cardiovascular disease for a mean period of 8 years. All subjects had at least one annual visit and blood sampling was performed in all visits for estimation of glomerular filtration rate (GFR). We calculated standard deviation (SD) of mean GFR from visits from 6 months onward in patients with ≥5 visits during follow-up. CAD was defined as the history of myocardial infarction or significant coronary artery stenosis revealed by angiography or coronary revascularization procedure, while stroke was defined as rapid onset of a new neurological deficit persisting at least 24 hours unless death supervened confirmed by imaging findings. End-stage renal disease was defined as GFR<15 mL/min/1.73 m2 or the need for long-term dialysis or transplantation.

Results
The incidence of CAD, stroke and end-stage renal disease over the follow-up period were 2.8% (n=68), 1.09% (n=26) and 0.6% (n=14). Hypertensives who developed CAD compared to those without CAD at follow-up (n=2312) had at baseline higher left ventricular mass index (115.7±24.6 vs 103.7±27.3 g/m2, p<0.0001), whereas there was no difference with respect to baseline GFR (78±19.6 vs 79.3±18.6 mL/min/1.73 m2 (p=0.573). In multivariate Cox regression models visit-to-visit glomerular filtration rate predicted end-stage renal disease (hazard ratio=1.758, p=0.01) but not CAD and stroke (p=NS for both). Baseline left ventricular mass index independently predicted CAD (hazard ratio=1.042, p=0.015) and stroke (hazard ratio=1.035, p=0.002).

Conclusions
In essential hypertensive patients GFR variability predicts future development of end-stage renal disease but exhibits no independent prognostic value for CAD and stroke. These results suggest that fluctuations of renal function are related with damage at the kidneys and not at the cardiac and cerebrovascular level.
P5470Studying target organ damage indices in newly diagnosed and never treated extreme dipper patients with essential hypertension
Authors: Triantafyllidi H , Schoinas A , Benas D , Varoudi M , Birba D , Voutsinos D , Ikonomidis I 
Published: October 2019

Abstract

Background
Cardiovascular risk estimation in arterial hypertension includes the investigation for target organ damage indices (TOD). 24h ambulatory blood pressure monitoring (ABPM) represents the gold standard method for the confirmation of the arterial hypertension disease. Dipping phenomenon, defined as blood pressure decrease >10% during night-time measurements, leads to hypertension burden reduce during night and carries a positive prognostic significance. However, there are doubts regarding its prognosis when it becomes augmented (extreme dipping defined as blood pressure decrease >20% during night-time measurements). Aim of our study is to explore TOD existence between extreme dipper and dipper hypertensive patients with newly diagnosed and never treated arterial hypertension.

Methods
From the 480 total patients with newly diagnosed and never treated arterial hypertension who subjected to ABPM, we excluded 190 non-dipper patients and we divided the rest 290 hypertensives (mean age 49±11 years, 193 males) in normal dippers (n=245, mean age 49±11 years, 160 males) and extreme dippers (n=45, mean age 49±10 years, 33 males). Both groups were subjected to the following measurements: arterial stiffness (PWV), 24h microalbumin levels (MAU), carotid intima-media thickness (IMT), diastolic dysfunction (E/Ea), left ventricular mass index (LVMI) and coronary flow reserve (CFR).

Results
We did not find any differences within groups regarding age, sex distribution, BMI, office SBP/DBP, cenrtal SBP/DBP and daytime average SBP/DBP as well as PWV, MAU, IMT, E/Ea and CFR. We noticed that extreme dippers had reduced 24h average SBP/DBP (p=0.001 and p=0.02, respectively) and increased LVMI (86±18 vs. 79±20 gr/m2, p=0.04) compared to normal dippers.
Differences in LVMI

Conclusions
Extreme dipper hypertensive patients have an increased LVMI, probably as a result of myocardial hypoxia due to severe blood pressure reduction over night. Our results point to the possible increased cardiovascular risk in this group of hypertensive patients.
P5471Baseline characteristics, healthcare resource use and clinical outcomes of stable post-myocardial infarction patients with diabetes: insights from the global prospective TIGRIS study
Authors: Nicolau J C , Brieger D , Goodman S , Cohen M G , Simon T , Westermann D , Granger C B , Grieve R , Chen J Y , Hedman K , Mellstrom C , Brandrup-Wognsen G , Owen R , Pocock S 
Published: October 2019

Abstract

Background
There is a growing prevalence of diabetes worldwide in patients in the general population, including those with prior myocardial infarction (MI).

Purpose
To describe the characteristics, health status, resource utilization and clinical adverse events of stable post-MI patients with diabetes.

Methods
The long-Term rIsk, clinical manaGement and healthcare Resource utilization of stable coronary artery dISease (TIGRIS) prospective observational study (NCT01866904) obtained data from 8985 stable patients 1–3 years post-MI from 369 centres in 25 countries, who provided diabetes status (no, yes, insulin-treated) and follow-up. Diabetes status, other patient characteristics, medications, medical history and healthcare resource utilization were recorded at enrolment. Health status was assessed at enrolment, 1 and 2 years by EQ-5D-3L and converted to an EQ-5D score. Deaths, cardiovascular (CV) events, bleeding events and related hospitalizations were recorded during 2 years of follow-up.

Results
Diabetes mellitus (DM) was prevalent at enrolment in 2966 (33%) patients of whom 872 (29%) were insulin-treated. Compared to patients without DM, those with DM had a higher mean body mass index (28.2 vs 26.6kg/m2) and heart rate (71 vs 67bpm), were more likely to have had ≥2 prior MIs (12% vs 10%), chronic kidney disease (10% vs 6%), peripheral artery disease (10% vs 5%), heart failure (15% vs 10%), anaemia (4% vs 2%), angina (12% vs 9%), stroke (6% vs 4%) and chronic obstructive pulmonary disease (9% vs 7%). Patients with DM reported more problems for each domain of the EQ-5D (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), which resulted in a lower mean EQ-5D utility score at enrolment (0.83±0.22 for no-diabetes vs 0.86±0.19 for diabetes). Moreover, they also had higher CV hospitalization rates in the 6 months prior to enrolment (6.4% vs 5%). All these measures were more marked in insulin-dependent diabetics. The incidences of all-cause death, CV death and the composite of CV death, MI and stroke were all significantly higher in patients with DM, especially those on insulin (see Figure). For CV death, MI and stroke the 2-year risk ratios, compared to patients without DM, were 2.64 (P<0.001) and 1.48 (P<0.001) respectively for those with insulin-treated DM and non-insulin treated.
Figure 1

Conclusions
Within a global population of stable post-MI patients, those with DM (especially those on insulin) have poorer health status and EQ-5D utility score, higher hospitalization rates and worse clinical outcomes compared with those without DM. Thus, in cardiac clinics worldwide, patients with DM require particularly close attention.

Acknowledgement/Funding
The study was funded by AstraZeneca
P5476Usefulness of haemoglobin level combined with CAMI-STEMI score for predicting MACCE in patients with acute ST-elevation myocardial infarction after PCI
Authors: Luo E , Wang D , Tang C , Yan G , Hou J , Liu B 
Published: October 2019

Abstract

Background
Early risk stratification was strongly recommended to guide therapeutic management and to improve outcome for ST elevation myocardial infarction (STEMI) patients. Anaemia and high haemoglobin levels are common in STEMI patients, but the effect of the haemoglobin level on the prognosis of STEMI patients remains in dispute. The China Acute Myocardial Infarction registry-ST Elevation Myocardial Infarction (CAMI-STEMI) score can predict in-hospital mortality among Chinese STEMI patients, with similar performance to the well-established Thrombolysis in Myocardial Infarction (TIMI) score, while relying solely on simple and practical variables. This study aimed to evaluate the prognostic value of the haemoglobin level combined with the CAMI-STEMI score in STEMI patients after percutaneous coronary intervention (PCI).

Methods
We included 360 STEMI patients who underwent PCI. The patients were divided into 3 groups according to the first haemoglobin value after PCI, group 1 (male: Hb<120 g/L, female: Hb<110 g/L; 42 cases), group 2 (male: 120 g/L ≤ Hb<160 g/L, female: 110 g/L≤Hb<150 g/L; 278 cases), and group 3 (male: Hb ≥160 g/L, female: Hb ≥150 g/L; 40 cases). Clinical characteristics, and the incidence of major adverse cardiovascular and cerebral events (MACCE) during the follow-up period were recorded.

Results
The incidence of MACCE in the 3 groups increased with a decrease in the haemoglobin level. Multivariate regression analysis showed that the CAMI-STEMI score was an independent predictor of MACCE incidence at 30 days after PCI and that anaemia was an independent predictor of MACCE incidence at 6 months and 1 year after PCI. A high haemoglobin level was an independent predictor of MACCE incidence at 1 year after PCI. The area under receiver operating characteristic curves (AUCs) of the haemoglobin level, CAMI-STEMI score and haemoglobin level combined with CAMI-STEMI score predicting the occurrence of MACCE in STEMI patients within 30 days after PCI were 0.604, 0.614, and 0.639, respectively.
Figure 1. MACCE-free survival curve

Conclusion
The CAMI-STEMI score was an independent predictor of MACCE incidence at 30 days after PCI. The haemoglobin level combined with the CAMI-STEMI score improved the predictive value of MACCE in STEMI patients within 30 days after PCI.

Acknowledgement/Funding
This study was supported by grants to Chengchun Tang from the National Natural Science Foundation of China (Research Grant #81670237)
P5477Usefulness of hypocalcemia at admission as a prognostic marker in patients with acute coronary syndromes
Authors: Gomez Polo J C , Ferrera C F , Ruiz-Pizarro V , Gomez-Alvarez Z , Romero-Delgado T , Rico C , Noriega F J , Macaya C , Fernandez-Ortiz A , Viana-Tejedor A 
Published: October 2019

Abstract

Background
Few studies have focused on the role of serum calcium levels (SCa) in patients with acute myocardial infarction (AMI).

Purpose
This study aimed to analyze the value of SCa as a prognostic marker in patients with AMI, including both with or without ST elevation.

Methods
From January-2015 to December-2017, all consecutive patients with AMI admitted to a tertiary care hospital were included. For the purpose of this study, total SCa levels were recorded at admission in each patient. Blood samples were obtained at the first medical contact when the patient arrived to the hospital. Patients were classified according to quartiles depending on their SCa at admission: Q1, under 8.3 mg/dl (N=300); Q2, between 8.4–8.7 mg/dl (N=264); Q3, between 8.8–9.1 mg/dl (N=279) and Q4, over 9.1 mg/dl (N=283).

Results
A total cohort of 1126 patients was included, 679 (60.3%) had STEMI and 447 (39.7%) were NSTEMI patients. Patients in the Q1 had more in-hospital complications, such as heart failure, bleeding events, new onset AMI, atrioventricular block and contrast induced nephropathy. Patients in the Q1 had higher in-hospital and one-year mortality as compared to that of patients in the Q2-Q4. After multivariate adjustment (Table), low SCa (<8.3mg/dl) remained as an independent predictor of in-hospital mortality (OR 2.91, 95% CI (1.15–7.41), p=0.025). These results were consistent in STEMI and NSTEMI patients.
Multivariable analysis Variable OR (95% CI) p GRACE score 1.00 (0.99–1.02) 0.727 CRUSADE score 1.03 (1.01–1.06) 0.011 Age (per year) 1.05 (1.00–1.09) 0.034 STEMI 1.35 (0.41–4.46) 0.617 Diabetes 2.57 (0.97–6.79) 0.056 Low SCa (<8.3) 2.91 (1.15–7.41) 0.025 Killip class at admission   1 Reference   2 4.73 (1.31–17.1) 0.018   3 6.83 (1.70–27.5) 0.007   4 9.83 (1.44–67.1) 0.020 STEMI: ST segment elevation myocardial infarction; SCa: Serum calcium levels; OR: Odds ratio; CI: Confidence interval.

Conclusion
In patients with AMI, low SCa levels at admission (<8.3mg/dl) are independently associated with higher mortality.