bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of polyvascular disease and renal dysfunction on cardiovascular outcomes in diabetes: post hoc analyses from EMPA-REG OUTCOME
Authors: Verma S , Mazer C.D , Inzucchi S.E , Wanner C , Ofstad A.P , Johansen O.E , Zwiener I , George J.T , Butler J , Zinman B 
Published: November 2020

Abstract

Background
Individuals with polyvascular disease and impaired renal function are at high risk of cardiovascular (CV) events, but this relationship is not well investigated in people with type 2 diabetes (T2D). Furthermore, the impact of polyvascular disease plus renal dysfunction on the risk for hospitalisation for heart failure (HHF) remains unclear.

Purpose
We investigated this in a post hoc analysis of the EMPA-REG OUTCOME trial in which empagliflozin reduced risk of CV death and HHF versus placebo in people with T2D and vascular disease. In addition, we explored the treatment effect of empagliflozin on CV, HF and mortality outcomes across the spectrum of baseline polyvascular disease and impaired renal function.

Methods
Patients with T2D, CV disease and estimated glomerular filtration rate (eGFR) of ≥30 ml/min/1.73 m2 received empagliflozin 10 mg, 25 mg, or placebo. Vascular beds (VBs) were defined as coronary artery disease, peripheral artery disease, and cerebrovascular disease (Fig). By use of Cox regression, we explored the association between baseline eGFR &lt; or ≥60 ml/min/1.73 m2, with or without polyvascular disease (1 vs ≥2 VBs involved), and CV death, HHF, CV death (excl. fatal stroke)/HHF, and all-cause mortality (ACM), as well as the treatment effect of empagliflozin versus placebo on these outcomes.

Results
Patients with ≥2 VBs involved and eGFR &lt;60 ml/min/1.73 m2 [n=463], were slightly older (mean age 68.2 vs. 64.3 or 62.6 years), had T2D duration &gt;10 years more often (73.4% vs. 63.2% or 54.9%), and a higher HF prevalence at baseline (19.4% vs. 11.1% or 9.2%) versus those with ≥2 VBs involved and eGFR ≥60 ml/min/1.73 m2 [n=866], or those with only 1 VB involved regardless of eGFR [n=5630], respectively. However, characteristics were generally balanced between treatment groups. Notably, co-existing polyvascular disease and eGFR &lt;60 ml/min/1.73 m2 was strongly associated with increased risk of all outcomes. The placebo incidence rates per 1000 patient-years for CV death were 14.4 (95% CI 10.9, 18.3) and 19.6 (12.8, 27.8) in those with 1 VB involved and eGFR ≥60 or eGFR &lt;60, respectively, and 32.7 (21.7, 45.8), and 52.4 (32.9, 76.5) in those with 2 VBs and eGFR ≥60 or eGFR &lt;60 ml/min/1.73 m2, respectively. Importantly, empagliflozin reduced the risk for all outcomes regardless of number of VBs affected and kidney function (Fig).

Conclusions
Co-existing polyvascular disease and eGFR &lt;60 ml/min/1.73 m2 confer an extremely high risk of CV and all-cause mortality, and HHF. Empagliflozin lowered this risk consistently compared with placebo, regardless of polyvascular disease and impaired kidney function.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance
Effects of linagliptin vs glimepiride stratified by prior insulin secretagogue use in the cardiovascular outcome study of linagliptin versus glimepiride in type 2 diabetes (CAROLINA) trial
Authors: McGuire D.K , Rosenstock J , Johansen O.E , Zinman B.J , Khunti K , Mattheus M , Lund S.S , Espeland M.A , Marx N 
Published: November 2020

Abstract

Background/Introduction
The cardiovascular outcome study of linagliptin versus glimepiride in type 2 diabetes (CAROLINA) was designed to compare the effects on cardiovascular (CV) events, and other outcomes, of linagliptin with glimepiride in patients with relatively early type 2 diabetes with elevated CV risk

Purpose
These post hoc analyses of the CAROLINA randomized controlled trial explore outcomes in subgroups stratified by prior sulfonylurea (SU) or glinide use.

Methods
Participants with relatively early type 2 diabetes, high CV risk and HbA1c 6.5–8.5% were randomized to linagliptin 5 mg or glimepiride 1–4 mg once daily with standard of care. 29.5% of patients had prior SU/glinide use. SU/glinides were discontinued at trial entry. Outcomes included time to first CV death/MI/stroke (3P-MACE), time to all-cause mortality, HbA1c change from baseline and time to first hypoglycaemia event.

Results
6033 participants received ≥1 study drug dose (mean [SD] age 64.0 [9.5] yrs, HbA1c 7.2 [0.6] %, median diabetes duration 6.3 yrs, 42% with CV disease); 897 linagliptin and 884 glimepiride participants had prior SU/glinide use. Results for 3P-MACE and all-cause mortality were consistent across subgroups with/without prior SU/glinide use (interaction p&gt;0.05; Fig). After some initial differences, there was no meaningful difference in HbA1c between linagliptin vs glimepiride across SU/glinide subgroups and overall. Hypoglycaemia rates were lower with linagliptin vs glimepiride overall and across SU/glinide subgroups, with some heterogeneity for prior SU/glinide use (interaction p&lt;0.01; Fig).

Conclusion
There was no difference in linagliptin versus glimepiride on 3P-MACE and all-cause mortality, with consistent results across subgroups irrespective of prior SU/glinide use. Hypoglycaemia rates were consistently lower with linagliptin vs glimepiride, regardless of prior SU/glinide use.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Boehringer Ingelheim and Eli Lilly and Company
Reduced gastric injury with a novel, liquid lipid-aspirin formulation: results from a pooled, patient level analysis of two randomized endoscopy studies In healthy volunteers
Authors: Bhatt D.L , Scheiman J , Angiolillo D.J , Steg P.G , Dangas G.D , Fan W , Prats J , Deliargyris E.N 
Published: November 2020

Abstract

Background
Gastrointestinal (GI) toxicity from aspirin is high at the time of initiation of therapy.

Objective
The current analysis aimed to determine rates of endoscopically detected gastroduodenal erosions and ulcers after 7 days of either immediate release aspirin (IR-ASA) or a novel, pharmaceutical lipid-aspirin complex (PL-ASA) liquid formulation that has an antiplatelet effect similar to IR-ASA.

Methods
Two randomized, single blind, multicenter active control studies comparing upper GI damage after 7 days of 325 mg PL-ASA or IR-ASA in healthy volunteers not taking a gastroprotectant and who had a negative baseline endoscopy were pooled at the patient level. The primary outcome was the composite of &gt;5 erosions and/or ≥1 ulcer (≥3 mm deep) assessed by a treatment-blinded reviewer at repeat endoscopy on day 7.

Results
Out of 451 randomized subjects (mean age 57 years, 47% males), 441 completed the 7-day endoscopy and represent the full analysis set. PL-ASA significantly reduced the primary outcome by 34% compared with IR-ASA (25.7% vs. 39%, p=0.0032) (figure). Notably, for ulcers there was a 61% reduction with PL-ASA (6.0% vs. 14.8%, p=0.0018) (Figure 1). The mean number of gastric erosions per patient was also reduced with PL-ASA (2.8±7.3 vs. 4.2±7.5, p&lt;0.0001), while erosions in the duodenum were not different (1.4±7.1 vs. 0.9±2.3, p=0.45).

Conclusion
The novel PL-ASA liquid capsules reduced rates of GI injury compared with IR-ASA tablets. The combination of reliable platelet inhibition with less GI injury makes PL-ASA an attractive new aspirin therapy option.
Figure 1

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): PLx Pharma
Premorbid, cardioselective beta-blocker exposure decreases ICU mortality in septic patients defined by sepsis-3
Authors: Kuo M , Chou R.H , Wu C.H , Huang P.H , Lin S.J 
Published: November 2020

Abstract

Introduction
Beta-blockers may exert a protective effect against the catecholaminergic myocardial injury in septic patients. The difference between cardioselective and non-selective beta blockers was not fully elaborated. The aim of this study was to investigate the association between premorbid prescriptions of different class of beta-blockers and mortality rate in septic patients.

Methods
We retrospectively screened 2678 patients admitted to the ICU during December 2015 to July 2017. Premorbid beta-blocker exposure was defined as prescription of any beta blocker for at least 1 month. Bisoprolol, esmolol, and atenolol were classified as cardioselective beta-blockers, and others were classified as non-selective beta-blockers.

Results
Among 1262 septic patients, 209 (16.6%) cases were long-term beta-blockers users. Patients with premorbid beta-blocker exposure were associated with higher BP, lower HR, lactate concentration, and improved ICU mortality. However, only premorbid cardioselective beta-blocker users (adjusted HR 0.26; 95% CI 0.11–0.64; p=0.003), but not non-selective beta-blocker users (adjusted HR 0.66; 95% CI 0.29–1.51; p=0.326), were associated with reduced ICU mortality.

Conclusion
Only premorbid cardioselective beta-blockers, but not non-selective beta-blockers, were associated with improved mortality in septic patients. These findings supported the cardioprotective effect and clinical benefits of beta-blocker in septic patients.
Kaplan-Meier Curve of ICU Mortality

Funding Acknowledgement
Type of funding source: None
Medically induced bradycardia in the elderly and senile patients
Authors: Nikulina N.N , Iakushin S.S , Chernysheva M.B , Seleznev S.V 
Published: November 2020

Abstract

Background
Elderly and senile people are most likely to develop cardiovascular diseases, while they have a higher risk of adverse drug reactions. Systemic analysis of medically induced bradycardia (MIB) has not been performed.

Aim
To analyze the clinical features of MIB in patients ≥65 and ≥75 years according to the Hospital Register of Cardiac Drug Overdoses (storm) data.

Materials and methods
Analyzed 17,826 cases of hospitalization in the Regional Vascular Center from 01 Jan 2017 to 31 Dec 2019, of them with all types of cardiac drug overdoses – 363, of them with MIB – 52.6% (n=191).

Results
Average age of those hospitalized with MIB – 74.0 [65.0; 80.0] years: 76.0% were ≥65 years, 49.4% – ≥75 years. Among the cohort ≥65 years, there were more women – 74.3% (vs 52.3%, p=0.003), ≥75 years – 74.4% vs 65.5% (p=0.107). The ratio of absolute and relative overdoses did not depend on age and was 1:9. The frequency of pulse-reducing drug admission before hospitalization did not differ in age groups. In General, in the cohort with MIB: 68.4% – beta-blockers, 25.8% – digoxin, 38.9% – antiarrhythmic drugs with pulse-reducing action (PRA), 9.5% – imidazoline receptor agonists, 10.5% – calcium channel blockers with PRA, 7.4% – other drugs with PRA, while 54.5% of patients received a combination of ≥2 drugs with PRA, 15.7% – ≥3, and even 3.1% – ≥4. In older age groups, a Glomerular Filtration Rate (GFR) decrease in was more often: among ≥65 years GFR &lt;60 ml/min × 1.73 m2 – 83.2% (vs 40.0% in younger patients, p&lt;0.001), &lt;45 ml/min × 1.73 m2 – 61.5% (vs 22.5%, p&lt;0.001), &lt;30 ml/min × 1.73 m2 – 34.5% (vs 15.0%, p&lt;0.001), &lt;15 ml/min × 1.73 m2 – 11.1% (vs 7.5%, p&lt;0.264); among patients ≥75 years: GFR &lt;60 ml/min × 1.73 m2 – 87.4% (vs 60.8%, p&lt;0.001), &lt;45 ml/min × 1.73 m2 – 66.0% (vs 40.2%, p&lt;0.001), &lt;30 ml/min × 1.73 m2 – 37.1% (vs 23.4%, p&lt;0.018), &lt;15 ml/min × 1.73 m2 – 12.0% (vs 8.4%, p&lt;0.357). Patients ≥65 and ≥75 years were more likely to require: emergency hospitalization (97.0% vs 84.1% in younger patients, p&lt;0.001 and 97.0% vs 91.1%, p=0.033), treatment in the intensive care unit (44.7% vs 20.5%, p=0.003 and 48.8% vs 29.2%, p=0.001), temporary pacemaker (58.3% vs 20.0%, p=0.107 and 57.1% vs 40.0%, p=0.284). Hospital mortality in persons ≥75 was 7.7% (vs 1.8% in younger patients, p=0.047), ≥65 – 3.8% (vs 4.6%, p=0.814).

Conclusions
Older age groups predominate among those hospitalized for MIB. They are characterized by a more pronounced lesion of glomerular filtration, a more severe condition, and a higher risk of death. Practical physicians underestimate the danger of prescribing drugs with PRA, especially in the form of combined therapy, in patients of older age groups, with impaired glomerular filtration, which requires drawing attention to this problem.

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): Ryazan State Medical University
Impact of ventricular assistance devices on patients submitted to heart transplantation
Authors: Perez-Ortega S , Prats J , Querol E 
Published: November 2020

Abstract

Background
The introduction of veno-arterial extracorporeal life support (v-a ECLS) widens the spectrum of patients that can be included in the heart transplant program, some examples are extended myocardial infarction, fulminant myocarditis or advanced cardiac insufficiency. In addition to this, the implementation of extracorporeal cardiopulmonary resuscitation (ECPR) extends even more the range of patients that can be benefitted of this therapy as a bridge to transplant.

Purpose
Our objective is to describe the incidence of v-a ECLS in those patients submitted to a heart transplant and to establish whether or not this technique increases the risk of mortality in this population.

Methods
Retrospective and descriptive statistical analysis of 82 consecutive patients submitted to heart transplant between 2015 and 2019 in a High Technology University Hospital.
Demographic and clinical data, extracorporeal life support, extracorporeal cardiopulmonary resuscitation and assistance device type, together with survival at 30 days and one year were collected.

Results
82 patients were transplanted during the study period distributed as follows:
47 (51.69%) were elective and 35 (48.1%) emergent being 25 (30.12%) of grade 1A and 10 (12.19%) of grade 1B. 52% had prior intra-aortic balloon contrapulsation.
Patients transplanted under ECLS were 80% men and average age of 53 (SD 15) years old. The most prevalent diagnosis was acute myocardial infarction Killip IV (32%), followed by terminal heart failure (28%).
32% of the patients were under peripheral ECMO, 36% under left ventricular assistance, 20% under biventricular assist device, and 12% required ECPR. 72% of devices were implanted in the operating room and 16% in the ICU.
The one-year survival of the sample was 88%. 2 patients died after transplantation (8%) during the first month, and 1 patient died within the first year. All three patients had terminal heart failure and the VAD implant was inserted electively

Conclusions
ECLS prior to cardiac transplantation allow selected patients to arrive alive to the transplant. The choice among devices is related to the diagnosis and expected duration of the therapy but we have not found in our series effects on subsequent mortality. Survival at one year in the subjects analysed is greater than the national registry of the last 10 years, although the tendency is to improve every year.
This new scenario implies an increment of the complexity in the management of these patients and requires an special effort in terms of staff ratio and training. In our centre, the implementation of ECLS resulted in an increment of our staff and formative sessions.

Funding Acknowledgement
Type of funding source: None
Elderly patients with chronic heart failure have higher risk of geriatric syndromes: results of the nursing study
Authors: Tsareva I , Vorobyeva N , Semochkina G , Kotovskaya Y , Tkacheva O 
Published: November 2020

Abstract

Background
The prevalence of chronic heart failure (CHF) and geriatric syndromes increases with age, however the associations between these conditions have not yet been studied.

Purpose
To evaluate the associations between CHF and geriatric syndromes in elderly patients.

Methods
Four hundred and seventy-two in-patients (18% male) aged 75–100 (mean 81±4) years were included in the nursing study. Patients were examined by nurses with a specially designed nursing assessment algorithm that included Mini-Cog test, Morse Fall scale, Norton scale, Barthel Activities of daily living Index, Short Physical Performance Battery (SPPB) tests, Mini Nutritional Assessment (MNA) scale, Geriatric Depression Scale (GDS-15), and a number of other questionnaires.

Results
CHF was observed in 180 patients (38%). Functional class (FC) of II (NYHA) was diagnosed in 133 (74%) of them, FC of III – in 47 (26%). Patients with and without CHF did not differ by age and gender. CHF patients had lower points on Norton scale (17,6±2,0 vs 18,2±1,8; p&lt;0,001), Barthel Index (92,0±13,9 vs 95,0±9,1; p=0,009), SPPB (5,3±3,2 vs 6,0±3,3; p=0,018), and higher points on Morse Fall scale (44,3±19,9 vs 39,3±21,1; p=0,007) and GDS-15 (4,7±3,2 vs 4,2±3,3; p=0,041) compared to non-CHF patients. CHF patients had higher frequency of frailty (75% vs 65%; p=0,029), depression (47% vs 38%; p=0,041), and cognitive impairment (54% vs 41%; p=0,008). Univariate regression analysis showed that CHF presence increased the frailty risk by 1,6 times (OR 1,59; 95% CI 1,05–2,40; p=0,029), the depression risk – by 1,5 times (OR 1,48; 95% CI 1,02–2,16; p=0,041), and the cognitive impairment risk – by 1,7 times (OR 1,65; 95% CI 1,14–2,40; p=0,009). Among CHF patients, severity of CHF clinical manifestations correlated with severity of geriatric syndromes. CHF patients with FC of II had higher points of Norton scale (17,8±1,9 vs 16,9±2,1; p=0,005), Barthel Index (93,4±12,9 vs 88,3±15,8; p=0,005), SPPB (4,4±3,3 vs 3,9±3,0; p=0,001), walk speed (0,58±0,26 vs 0,45±0,22 m/s; p=0,002), and lower points of GDS-15 (4,4±3,3 vs 5,5±2,9; p=0,008) compared to CHF patients with FC of III. The frequency of depression was higher in CHF patients with FC of III (64% vs 41%; p=0,008). Univariate regression analysis showed that in CHF patients with FC of III the depression risk was higher by 2,5 times (OR 2,50; 95% CI 1,26–4,98; p=0,009) compared to CHF patients with FC of II.

Conclusion
Elderly CHF patients had higher risk of geriatric syndromes such as frailty, depression, and cognitive impairment. Among CHF patients, severity of CHF clinical manifestations correlated with severity of geriatric syndromes.

Funding Acknowledgement
Type of funding source: None
Deep neural network trained on surface ECG improves diagnostic accuracy of prior myocardial infarction over Q wave analysis
Authors: Rogers A , Tung J.S , Tooley J , Bhatia N.K , Kang G , Alhusseini M.I , Baykaner T , Wang P.J , Perez M , Clifford G , Tereshchenko L , Narayan S.M 
Published: November 2020

Abstract

Background
Detection of prior myocardial infarction (MI) may inform arrhythmia treatment and prognosis, yet cardiac imaging is resource intensive. ECG Q-wave analysis is quick and inexpensive but has poor accuracy for assessing prior MI.

Purpose
To evaluate the ability of a deep neural network (DNN) trained on the surface ECG to identify patients with prior MI.

Methods
We assessed 608 well-characterized patients (61.4±14.5 years, 31.2% female) at 2 academic centers. From one 12-lead ECG, median beats were calculated in 3 orthogonal planes (X, Y, Z; Fig. 1A) and used to train a DNN to identify a history of prior MI. Accuracy was compared to manual assessment of pathologic Q waves, defined as a deflection &gt;25% of the subsequent R wave, &gt;40ms in width, and &gt;0.2mV amplitude in 1 of 3 ECG planes.

Results
Of 608 patients, 175 had history of MI (28.7%). The DNN outperformed the accuracy of pathologic Q waves. In training, DNN converged to &gt;98% accuracy and in testing, its accuracy was 71±5% (Fig. 1B) (k=5-fold cross validation). This outperformed the 62% accuracy of pathologic Q waves in this study (red dotted line, Fig. 1B). In the validation cohort, DNN provided an area under the receiver operating characteristics curve of 0.730 (Fig. 1C).

Conclusion
Deep learning of a 12-lead ECG can identify features of prior myocardial injury more accurately than Q-wave analysis. In attempting to improve these results further, studies should explain what inputs weighted DNN decisions, and identify those that reflect abnormalities detectable clinically or on imaging.
Figure 1

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): NIH NRSA F32
The impact of digital flashcards on cardiovascular physiology academic performance in a medical course – a dose-dependent effect between the amount of training and academic success
Authors: Santos-Ferreira D , Guimaraes B , Tsisar S , Goncalves-Teixeira P , Ladeiras-Lopes R , Fontes-Carvalho R , Leite-Moreira A 
Published: November 2020

Abstract

Background
Digital flashcards are used to review factual knowledge through active-recall and spaced-repetition, while allowing subsequent self-assessment.

Purpose
To assess if using digital flashcards is associated with cardiovascular physiology academic success and better knowledge retention in short- and medium-terms, through a dose-dependent effect.

Methods
We conducted a single-faculty cohort study of 2nd-year medical students enrolling in cardiovascular physiology course, using a platform comprising 676 original flashcards. The grades from 0–20 scale of three exams were analyzed, being the latest optional and performed 1 month after the end of the course. One-sample t-test was used to compare the grades between flashcard users versus non-users, and the amount of training was correlated with the exams results using Pearson's correlation. Also, multiple linear regression models were created, using the respective grades as the dependent variable. A p value of &lt;0.05 was considered statistically significant.

Results
From 312 students enrolled, 279 agreed to participate in this study, and 87% used the platform. Flashcard-users exhibited higher grades versus non-users (11.83±3.57 vs. 9.50±3.55, p&lt;0.001; 12.47±3.03 vs. 11.45±3.24, p=0.225; 10.24±4.66 vs. 7.51±4.46, p=0.041; 1st, 2nd and 3rd exams, respectively). Among flashcard-users, the amount of training was positively correlated with the academic success (r=0.366, r=0.350, r=0.286; 1st, 2nd and 3rd exams, respectively, p≤0.001 for all). Multiple linear regression models showed a statistically significant association between the theoretical exam results and the number of flashcards studied – for every 1000, there was an increase in 0.98 (p=0.001), 1.22 (p=0.017) and 1.00 (p=0.022) in the grades of the 1st, 2nd and 3rd exams, respectively.

Conclusion
Studying cardiovascular physiology through digital flashcards has a moderate correlation with the exams results, exhibiting a positive and consistent dose-dependent effect, both in short- and medium-terms. Therefore, this strategy seems to improve academic success by increasing knowledge retention.
Study algorithm

Funding Acknowledgement
Type of funding source: None