bluuebunny/crossref_metadata_2025_split huggingface dataset:
P1578Outcomes in patients with renal impairment and myocardial injury or infarction identified by high-sensitivity cardiac troponin testing: a secondary analysis of the High-STEACS trial
Authors: Gallacher P J , Miller-Hodges E , Shah A , Anand A , Lee K K , Chapman A R , Farrah T , Halbesma N , Blackmur J , Newby D E , Mills N L , Dhaun N 
Published: October 2019

Abstract

Background
Patients with renal impairment are at increased risk of myocardial infarction (MI), but the interpretation of cardiac troponin is challenging in this setting. The use of high-sensitivity cardiac troponin (hs-cTn) assays increases the detection of myocardial injury, yet may contribute to uncertainty in the diagnosis of MI in those with renal impairment.

Purpose
To describe the diagnosis and outcomes of patients with myocardial injury or infarction identified using a hs-cTnI assay, stratified by renal function.

Methods
In a pre-specified secondary analysis of a stepped-wedge cluster-randomised controlled trial, we identified consecutive patients with a hs-cTnI concentration greater than the sex-specific 99th centile between June 2013 and March 2016. The diagnoses of type 1 or type 2 MI were adjudicated and classified according to the 4th Universal Definition of Myocardial Infarction. Renal impairment was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73m2.The primary outcome of type 1 or type 4b MI or cardiovascular death was compared in patients with and without renal impairment at 1 year.

Results
A measure of renal function was available in 47,334 (98.0%) patients, of whom 7,933 (16.8%) had renal impairment (mean age 76±12 years; 54% female). Plasma hs-cTnI concentrations were >99th centile in 47.9% (3,800/7,933) of patients with renal impairment and 16.3% (6,439/39,401) of patients with normal renal function. In those with and without renal impairment, the adjudicated diagnosis was type 1 MI in 35.2% (1,336/3,800) and 55.8% (3,596/6,439) of patients, and type 2 MI in 12.6% (480/3,800) and 9.7% (626/6,439) of patients, respectively (P<0.001 for both). In patients with hs-cTnI concentrations >99th centile, the primary outcome occurred in 24.9% (945/3,800) of patients with renal impairment, compared to 12.1% (779/6,439) of patients with normal renal function (P<0.001). In patients with type 1 MI, the primary outcome occurred in 32.6% (436/1,336) of those with renal impairment and 11.7% (419/3,596) of those without (P<0.001). In patients with type 2 MI, the primary outcome occurred in 20.4% (98/480) and 9.9% (62/626) of patients with and without renal impairment, respectively (P<0.001).

Conclusion
Almost half of all patients with suspected acute coronary syndrome and renal impairment have hs-cTnI concentrations greater than the sex-specific 99th centile. Whilst only one in three had a diagnosis of type 1 MI, an elevated troponin concentration was associated with a poorer prognosis in those with concomitant renal impairment compared to those without, irrespective of the index diagnosis.

Acknowledgement/Funding
British Heart Foundation
P1589Thiazides and skin cancer risk: should we be worried?
Authors: Sousa J P , Puga L , Lopes J , Saleiro C , Lourenco C , Goncalves L 
Published: October 2019

Abstract

Introduction
Diuretic thiazides represent a first-line therapeutic option for arterial hypertension. However, this drug class is regarded as having photosensitizing properties, and, as such, may act as a carcinogen, by triggering phototoxic reactions. Whether or not its long-term use increases skin malignancy risk remains unclear.

Purpose
To examine a possible association between thiazide usage and the risk of skin cancer, namely basal cell carcinoma, squamous cell carcinoma and malignant melanoma.

Methods
MEDLINE, EMBASE, Cochrane Library and Google Scholar databases were comprehensively searched, from inception to the first of February of 2019, for observational studies mentioning thiazide diuretic usage and incidence or prevalence of cutaneous basal cell carcinoma, squamous cell carcinoma and malignant melanoma. Literature review, study selection and appraisal, including methodological quality assessment, and data extraction were independently led by two investigators. Meta-analysis was conducted using generic inverse variance outcome and, due to heterogeneity of the original studies, a random effects model. Confounder-adjusted summary relative risk (RR), with 95% confidence interval (CI), was pooled.

Results
Ten studies met eligibility criteria. Of these, six had a case-control design and the remaining were cohort studies. Overall, 7,079,530 patients were included; 125,946 were diagnosed with basal cell carcinoma, 21,775 with squamous cell carcinoma and 31,191 with malignant melanoma. One study encompassed only squamous cell carcinoma of the lip. In five articles, individual thiazides employed were not addressed, whereas three embraced solely hydrochlorothiazide and other two exclusively bendroflumethiazide. Thiazides were found to be associated with increased risk of basal cell carcinoma (six studies, RR=1.05, 95% CI=1.01–1.10, p=0.02, i2=62%), squamous cell carcinoma (seven studies, RR=1.35, 95% CI=1.05–1.74, p=0.02, i2=92%) and malignant melanoma (six studies, RR=1.17, 95% CI 1.11–1.23, p<0.ehz748.03491, i2=0%).

Conclusion
Risk of all three major forms of skin malignancy is heightened in thiazide diuretic users. Increased awareness and education, especially for those who are at high risk and under the form of intense solar irradiation avoidance, are warranted for both patients and healthcare providers.
P1600Querecetin prevents electrophysiolgical remodeling and reperfusion arrhythmias in dysmetabolic rats
Authors: Diez E R , Prado N J , Vazquez Prieto M A , Miatello R M , Ponce Zumino A Z 
Published: October 2019

Abstract

Background
Severe arrhythmias during reperfusion of myocardial infarctions are associated with increased mortality. High fat and fructose diet (HFFD) increases arrhythmic risk and predispose to diseases such as diabetes, hypertension, and dyslipidemia. Quercetin is a bioactive flavonol found in grapes and grapes derived products. This flavonoid has been proposed to prevent cardiovascular disease, but little is known about its electrophysiological properties.

Objective
To evaluate the electrophysiological effects of chronic quercetin administration in rats with increased arrhythmogenesis during the reperfusion due to a HFFD.

Methods
Male Wistar rats were fed for six weeks with control diet (C), HFFD (20% fat and 20% fructose w/w), HFFD supplemented with quercetin in a dose of 20 mg/kg/day (HFFDQ) or quercetin alone (Q). Isolated hearts were perfused with a Krebs-Henseleit solution and after 15 min stabilization, submitted to 10 min of regional ischemia followed by10 min of reperfusion. Epicardial action potential and arrhythmic events were analyzed.

Results
HFFD and HFFDQ developed metabolic syndrome, but action potential at 90% of repolarization lengthening only increased in HFFD (78±4 vs 55±3 ms, P<0.01 by ANOVAII). HFFD increased ventricular fibrillation incidence (HFFD 8 of 9; C 2 of 9 P=0.0152 by Fisher Exact test). Both groups treated with quercetin had low arrhythmic incidence (HFFDQ 2 of 10 and Q 1 of 9; P<0.0055 and P<0.0034, respectively when compared with HFFD). The severity of arrhythmias persisted high during reperfusion only in HFFD. Other less severe arrhythmias like salvos and extra beats occurred in similar proportion in the three other groups.

Conclusion
The above results confirm that a HFFD facilitates the occurrence of severe arrhythmias during reperfusion. Quercetin reduces arrhythmias and electrophysiological remodeling despite metabolic syndrome. Since quercetin is one of the most abundant dietary flavonoids, our results reinforce its nutraceutical potential.

Acknowledgement/Funding
I+D+i UNCuyo 2015
P1618A polymethoxy flavonoid, Nobiletin, Has a therapeutic potency against the development of heart failure through NBP1 activation
Authors: Sunagawa Y , Funamoto M , Shimizu K , Shimizu S , Katanasaka Y , Miyazaki Y , Wada H , Kan T , Hasegawa K , Morimoto T 
Published: October 2019

Abstract

Introduction
Maladaptive hypertrophy is being recognized as a critical event during the development of heart failure. The control of cardiac hypertrophy may be one of the therapeutic strategy for heart failure therapy. In our previous study, we screened natural compound library and found that a natural compound, Nobiletin, could inhibit cardiomyocyte hypertrophy in culture. Nobiletin has various useful effects such as anti-cancer, anti-inflammation, and anti-oxidant and may be applicable to pharmacological therapy for heart failure.

Hypothesis
We thought that nobiletin might prevent the development of heart failure in vivo and investigated the target molecule of Nobiletin in the heart.

Methods and results
In primary cardiomyocytes, Nobiletin significantly inhibited phenylephrine (PE)-induced hypertrophic responses such as increases in cell size and hypertrophic gene transcription, such as ANF and BNP. C57BL6 mice were subjected to sham or transarotic constriction (TAC). Oral administrations of Nobiletin (20 mg/kg/day) or vehicle were repeated for 8 weeks. Nobiletin treatment significantly prevented TAC-induced increases in PWT and systolic dysfunction. Nobiletin also suppressed TAC-induced myocardial cell hypertrophy, perivascular fibrosis, and hypertrophic gene transcriptions. To investigate the target molecule of Nobiletin, Nobiletin-binding proteins were purified from rat heart using biotin-conjugated Nobiletin. We identified 162 novel binding protein of Nobiletin by LC/MS-MS. One of them, Nobiletin-binding protein 1 (NBP1) related to cellular metabolic pathway. Pulldown assay demonstrated that biotin-conjugated Nobiletin, but not biotin, directly interacted with recombinant NBP1. In vitro enzyme assay showed that Nobiletin enhanced NBP1 activity. Although NBP1 knockdown could not affect PE-induced hypertrophic response gene transcriptions and cardiomyocyte hypertrophy, NBP1 knockdown failed to exhibit Nobiletin-mediated anti-hypertrophic effects. NBP1-KO mice and WT mice were subjected to sham or TAC and randomly divided into two groups: Nobiletin (20 mg/kg/day) and vehicle. After 8 weeks, Nobiletin significantly improved TAC-induced cardiac hypertrophy and systolic dysfunction in WT mice but not in NBP1-KO mice. Nobiletin also prevented TAC-induced increases in HW/BW rate, myocardial cell hypertrophy, and mRNA levels of ANF and β-MHC in WT mice but not in NBP1-KO mice.

Conclusions
In this study, we demonstrate that Nobiletin inhibits cardiomyocyte hypertrophy and the development of heart failure in vivo. NBP1 activity is required to exhibit therapeutic potency of Nobiletin for heart failure. These finding suggest that a natural compound, nobiletin, might be a candidate for heart failure agent in human.

Acknowledgement/Funding
This work was supported by JSPS KAKENHI Grant.
P1635A risk score for prediction of TIA/ischemic stroke in patients with heart failure and sinus rhythm
Authors: Hjalmarsson C , Fu M , Zverkova-Sandstrom T , Schaufelberger M , Ljungman C , Andersson B , Bollano E , Dahlstrom U , Rosengren A 
Published: October 2019

Abstract

Background
Prediction of ischemic cerebral events in patients with heart failure (HF) in the absence of atrial fibrillation (AF) is challenging.

Purpose
To prospectively test a staged approach to identify patients with HF and sinus rhythm who are at high risk of developing TIA/ischemic stroke (TIA/IS) during the first two years after diagnosis.

Methods
The analysis is based on patient data reported in the Swedish Heart Failure Register from January 2003 until December 2013. Patients with AF and those treated with anticoagulants were excluded. The study population was categorized in two groups according to left ventricular ejection fraction: LVEF ≤40% and LVEF >40%. Factors associated with TIA/IS were determined by univariate proportional hazard regression. The risk score included: age (1p for 65–74y; 2p for 75–84y; 3p for ≥85y), previous ischemic heart disease (1p), hypertension (1p), diabetes mellitus (1p), TIA/IS (2p), and kidney dysfunction (1p). Two-year hazard ratios with death as competing risk were computed. The probability of observing the outcome was calculated using the cumulative incidence function.

Results
A total of 16,865 patients (mean age 72.1±13.2y) were included in the study, 39.9% women; 59.7% had LVEF ≤40%. The two-year crude rate of TIA/IS, hemorrhagic stroke, and all-cause mortality were 3.3%, 0.3%, and 26%, respectively.
An incremental absolute risk for TIA/IS was observed for patients with LVEF ≤40% and score 1- ≥6: 1.6, 2.3, 3.6, 2.9, 6.3, and 7.1%, respectively. The corresponding HRs with 95% confidence interval (CI) and the patients with 0 points as reference group were: 2.8 (1.1–7.3), 4.0 (1.6–10.1), 6.6 (2.7–16.2), 5.5 (2.2–13.8), 14.4 (5.8–35.9) for score 1- ≥6, where all p-values were less than 0.05 and Wald χ2 for overall model fit <0.0001. The cumulative incidence per 1000 person-years was: 8.2 (5.4–12.5), 11.8 (8.3–16.7), 19.4 (15.1–24.8), 16.3 (12.6–21.1), 36.6 (29.4–45.4), and 42.1 (33.0–53.8), respectively.
In patients with LVEF >40% and score 1–≥6, the absolute TIA/IS risk was: 1.3, 3.1, 3.1, 3.3, 4.6, and 5.3%, respectively. The corresponding HRs with 95% CI and patients with 1 point as reference group was: 2.4 (1.1–5.2), 2.5 (1.2–5.3), 2.7 (1.3–5.7), 3.9 (1.8–8.2); and 4.6 (2.2–9.8), for score 1- ≥6 (all p<0.05 and Wald χ2 for overall model fit p=0.0002). The cumulative incidence per 1000 person-year was: 6.7 (3.4–13.2), 16.0 (10.8–23.8), 16.7 (12.5–22.2), 18.0 (13.9–23.4), 25.8 (19.4–34.3), and 30.6 (21.7–43.0), for score 1- ≥6, respectively.

Conclusion
In the current study, a risk score compiling age and specific comorbidity was shown to predict increased risk of TIA/IS, regardless of LVEF, during the first two years after diagnosis in patients with incident HF in sinus rhythm.
P1636Causes and risk factors for non-cardiovascular hospital readmissions among heart failure patients
Authors: Keidan T , Olmer L , Ziv A , Benderly M , Kalter-Leibovici O 
Published: October 2019

Abstract

Background/Introduction
Despite better patient-management and technological improvements, patients with heart failure (HF) have poor prognosis and impaired health-related quality of life (HRQoL). HF patients also experience significant non-cardiovascular morbidity leading to higher disease burden and recurrent hospitalizations, which also put a heavy burden on healthcare systems.

Purpose
To describe causes and risk factors for non-cardiovascular hospital readmissions among HF patients.

Methods
We analyzed 3,172 hospital discharge summaries for 927 patients enrolled in a clinical trial testing the efficacy of a disease management program compared to usual care between August 2007 and June 2011. The study intervention had no effect on hospital admission and mortality rates. Baseline information on patient characteristics included age, gender, LVEF, NYHA classification, 6-minute walk test, BNP level, BMI, chronic comorbidity and HRQoL score. Analysis of hospital discharge summaries included identification and coding of the primary hospital admission cause. These causes were further grouped to HF-related, other cardiovascular disease-related and non-cardiovascular causes. Information on follow-up prescription purchases of HF drugs was also collected. Factors associated with non-cardiovascular hospital admission rate were tested in multivariable models, adjusted for study group, study period and year of recruitment.

Results
Non-cardiovascular hospital admissions (of which 77% were non-elective) accounted for 45% of all hospital readmissions. Of these hospitalizations, 23% were due to infectious diseases, 13% due to gastrointestinal causes, 12% due to respiratory causes and 8% due to falls and associated trauma. Patients with two or more non-cardiovascular hospital admissions during follow-up were significantly older, more commonly female, had higher proportion of preserved LVEF (≥50%), worse baseline functional capacity and HRQoL score, and higher co-morbidity score, BNP level and mortality rates compared to other patients. Factors significantly and independently associated with higher acute non-cardiovascular hospitalization rate included [rate ratios (RRs), 95% confidence intervals (CIs)]: non-preserved vs. reduced LVEF [1.48 (1.14, 1.92)]; higher baseline comorbidity score [1.14 (1.08, 1.21) per 1-point increment]; and higher loop diuretics, beta-adrenergic receptor blockers and ACE-I/ARBs treatment level during follow-up; 4th vs. 1st quartiles: 4.13 (2.93, 6.32), 1.51 (1.07, 2.13) and 1.32 (0.96, 1.82), respectively. Baseline overweight/obesity and greater 6-min. walking distance [0.93 (0.89, 0.93) per 50m increment] were found protective.

Conclusion
This study indicates a higher disease burden and mortality rate among HF patients with recurrent non-cardiovascular hospital admissions. It provides pertinent information needed for the design and implementation of effective interventions to reduce disease burden in HF patients.
P1645Vascular endothelial growth factor-D and mortality in suspected or known coronary heart disease patients with a history of heart failure: a subanalysis of the ANOX study
Authors: Iguchi M , Suzuki M , Matsuda M , Ajiro Y , Shinozaki T , Sakagami S , Yonazawa K , Shimizu M , Funada J , Takenaka T , Wada M , Abe M , Akao M , Hasegawa K , Wada H 
Published: October 2019

Abstract

Background
Vascular endothelial growth factor-D (VEGF-D) is a secreted glycoprotein that can act as lymphangiogenic and angiogenic growth factors through binding to its specific receptors, VEGFR-3 (Flt-4) and VEGFR-2 (KDR/Flk-1). VEGF-D signaling via VEGFR-3 plays an important role in lipoprotein metabolisms which may contribute to coronary heart disease (CHD). Recent studies suggest that VEGF-D appears to be a biomarker of pulmonary congestion and heart failure in both dyspnea patients and the general population. However, the prognostic value of VEGF-D in suspected or known CHD patients with a history of heart failure is unknown.

Methods
Serum VEGF-D levels were measured in 253 suspected or known CHD patients with a history of heart failure undergoing elective coronary angiography, enrolled in the development of novel biomarkers related to angiogenesis or oxidative stress to predict cardiovascular events (ANOX) study, and followed up for 3 years. The primary outcome was all-cause death. The secondary outcomes were cardiovascular death, and major adverse cardiovascular events (MACE) defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.

Results
During the follow-up, 54 patients died from any cause, 24 died from cardiovascular disease, and 35 developed MACE. After adjustment for established risk factors, VEGF-D levels were significantly associated with all-cause death (hazard ratio [HR] for 1-SD increase, 1.44; 95% confidence interval [CI], 1.18–1.75), cardiovascular death (HR, 1.73; 95% CI, 1.32–2.25), and MACE (HR, 1.49; 95% CI, 1.14–1.89). Even after incorporation of N-terminal pro-brain natriuretic peptide, contemporary sensitive cardiac troponin-I, and high-sensitivity C-reactive protein into a model with established risk factors, the addition of VEGF-D levels further improved the prediction of all-cause death (continuous net reclassification improvement [NRI], 0.471; 95% CI, 0.176–0.766; P=0.002; integrated discrimination improvement [IDI], 0.036; 95% CI, 0.008–0.064; P=0.011) and cardiovascular death (NRI, 0.722; 95% CI, 0.326–1.118; P<0.001; IDI, 0.063; 95% CI, 0.005–0.122; P=0.033), but not that of MACE (NRI, 0.453; 95% CI, 0.100–0.805; P=0.012; IDI, 0.028; 95% CI, −0.007–0.063; P=0.116).

Conclusions
In suspected or known CHD patients with a history of heart failure undergoing elective coronary angiography, elevated VEGF-D levels may predict all-cause and cardiovascular mortality independent of established risk factors and cardiovascular biomarkers.

Acknowledgement/Funding
The ANOX study is supported by a Grant-in-Aid for Clinical Research from the National Hospital Organization.
P1720Survival analysis in a population of patients with cardiogenic shock after acute myocardial infarction: characterization of the population and identification of mortality predictors
Authors: Da Conceicao Pedro Pais J A , Picarra B , Carrington M , Santos A R , Guerreiro R A , Bras D , Congo K I S A , Carvalho J , Neves D , Aguiar J 
Published: October 2019

Abstract

Introduction
The presence of cardiogenic shock (CC) after acute myocardial infarction (AMI) is associated with high mortality.

Purpose
To compare the clinical characteristics, cardiac and non-cardiac complications among survivors and non-survivors of CC after AMI in order to identify predictors of in-hospital mortality.

Population and methods
An observational study involving 467 patients (P) with CC after AMI included in a national multicenter registry. Considered 2 groups: Group 1 - P with CC who died (n=190) and Group 2 - P with CC who survived (n=277). We recorded age, gender, personal history, coronary angiography and angioplasty performed, in-hospital therapy and ejection fraction, cardiac complications (Re-infarction, mechanical complications, high-grade atrial ventricular block, sustained ventricular tachycardia) and non-cardiac complications [acute renal injury (ARI), major bleeding and stroke]. Multivariate analysis was performed to identify predictors of in-hospital mortality.

Results
Mortality in patients with CC after AMI was 40.6%. Group 1 P were older (77±10 vs 68±13 years, p<0.001), presented higher prevalence of diabetes mellitus (41.8% vs 28.2%, p=0.003), previous AMI (23.8% vs. 12%, p<0.001) 7%, p=0.002), previous angor (31.9% vs 14.1%, p=0.001), heart failure (18.6% vs 8.7%, p=0.002) and peripheral arterial disease (11.8% vs 6.2%, p=0.03). There were fewer coronary angiographies (64.2% vs 87.7%, p<0.001), with no difference in the number or type of vessels with lesions in both groups, as well as inotropic therapy. With the exception of mechanical complications, more prevalent in group 1 (12.6% vs 5.4%, p=0.006), there were no differences in the prevalence of the remaining cardiac complications. Among the non-cardiac complications considered, only the presence of ARI was more prevalent in Group 1 (72.1% vs 37.5%, p<0.001). After multivariate analysis the presence of age>75 years [OR: 2.21 (CI: 1.39–3.51)], previous angor [OR: 1.91 (CI: 1.09–2.92)], LRA [OR: 3.14 (CI: 4.0–7.04)] and mechanical complications [OR: 3.82 (CI: 2.39–6.10] were independent predictors of in-hospital mortality of P with CC post-AMI.

Conclusions
Mortality in patients with CC after AMI remains high. Age>75 years, prior angor, ARI and mechanical complications are independent predictors of in-hospital mortality in P with CC post-AMI.