bluuebunny/crossref_metadata_2025_split huggingface dataset:
1406Inhaled iloprost, exercise hemodynamics, and ventricular performance in heart failure with preserved ejection fraction
Authors: Cheng J.-F , Wu C.-K , Huang C.-Y , Chen Z.-W , Chen S.-Y , Lin L.-Y 
Published: October 2019

Abstract

Background
A dramatic increase in pulmonary capillary wedge pressure (PCWP) during exercise is observed in patients with heart failure with preserved ejection fraction (HFpEF). The prostacyclin pathway is involved in pulmonary hypertension and iloprost is a prostacyclin analogue. The acute onset vasodilator effect of inhaled iloprost makes it a good candidate to decrease exercise-induced PCWP. This study determined whether iloprost inhalation could improve exercise hemodynamics and cardiac reserve in HFpEF.

Methods
Thirty-four HFpEF subjects were enrolled in this double-blind, randomized, placebo-controlled, parallel-group trial. Subjects received invasive cardiac catheterization and underwent expired gas analysis at rest and during exercise, before and 15 minutes after treatment with either inhaled iloprost or placebo.

Results
At baseline, enrolled subjects showed an increase in PCWP during exercise (PCWP = 16 (14–23) mmHg to 27 (21–36) mmHg; p<0.0001). After drug inhalation treatment, the primary endpoint was achieved whereby exercise PCWP was significantly reduced by iloprost compared to placebo (adjusted mean: 20 (16–29) mmHg vs. 23 (17–32) mmHg; p=0.002). Iloprost showed a trend for better cardiac output reserve with exercise (0.2 (−1.3 to 1.2) L/min vs. −0.7 (−1.9 to 0.1) L/min; p=0.099) and normalized the increase in cardiac output relative to oxygen consumption. Iloprost improved the pulmonary artery pressure flow relationships in HFpEF and showed a trend for increased left ventricular stroke work with exercise compared to placebo, indicating an improvement in ventricular performance with stress.
Table shows exercise baseline-corrected values (exercise values after receiving study drug minus exercise values prior to study drug) Placebo (n=17) Iloprost (n=17) p Value PA systolic, mmHg 0 (−4 to 6) −11 (−23 to −5) <0.0001 PCWP, mmHg −2 (−3 to 2) −7 (−12 to −5) <0.0001 PVR, mmHg/l/min 0 (−0.5 to 0.3) −0.1 (−0.5 to 0.4) 0.9 SVR, DSC 102 (16 to 188) 5 (−162 to 108) 0.057 LVSW, g/beat −3 (−30 to 6) 7 (−13 to 20) 0.079 CO, l/min −0.7 (−1.9 to 0.1) 0.2 (−1.3 to 1.2) 0.099 Stroke volume, ml −8 (−24 to 1) 0 (−19 to 10) 0.3 Values are median (interquartile range).

Conclusions
Iloprost inhalation improved hemodynamic deficit during exercise in patients with HFpEF. Prospective trials testing long-term iloprost therapy in this population are warranted.
1415Dose antihypertensive medication improve accelerated age-dependent decline of GFR in hypertension?
Authors: Ohno K , Takase H , Machii M , Nonaka D , Sugiura T , Ohte N , Dohi Y 
Published: October 2019

Abstract

Background/Introduction
An impairment of kidney function is a risk not only for end stage renal disease but also for cardiovascular events. Hypertension is known to accelerate an age-dependent decline in glomerular filtration rate (GFR).

Purpose
Effects of antihypertensive medications on yearly changes of estimate GFR (eGFR) in hypertensive patients were investigated.

Methods
Consecutive 5110 subjects (male=3196, 52.3±11.3 year-old) who participated in our physical check-up program during 2010 and 2012 were enrolled and followed up for 5 years. The average and the yearly change of eGFR during the 5 years were calculated in each individual and the both values were compared in hypertensive and normotensive subjects. Effect of antihypertensive medication on eGFR was also investigated. The modified Modification of Diet in Renal Disease study formula for the Japanese population was used for calculating eGFR.

Results
In hypertensive subjects (n=1408), the baseline and the average of eGFR were smaller (74.8±14.6 vs. 80.4±13.6, p<0.001 and 72.1±13.2 vs. 77.9±11.9 mL/min per 1.73 m2, p<0.001, respectively) and the yearly decline of eGFR was greater (0.96±1.41 vs. 0.84±1.19 mL/min per 1.73 m2 per year, p<0.01) than in normotensive subjects (n=3702). The baseline and the average of eGFR were smaller in hypertensive patients with (n=1234) than without (n=174) antihypertensive medication (74.3±14.6 vs. 78.3±13.8, p<0.001 and 71.7±13.2 vs. 74.9±12.7 mL/min per 1.73 m2, p<0.01, respectively). Although the yearly decline of eGFR in hypertensive patients with medication tended to be smaller than the decline in those without medication (0.94±1.41 vs. 1.09±1.42 mL/min per 1.73 m2 per year), this did not reach a statistical significance (p=0.213). Neither the number, classes of antihypertensive medications nor systolic blood pressure during the follow-up period did affect the average or yearly decline of eGFR in hypertensive patients.

Conclusions
As compared to normotensive subjects, eGFR was reduced and a yearly decrease in eGFR during the 5 years was accelerated in hypertensive patients. Although antihypertensive medication may reduce an accelerated age-dependent decline of kidney function in hypertension, observational period in this study was too short to clarify such beneficial effects of antihypertensive medications.
1436Overexpression of Cytotoxic T-Lymphocyte Associated Antigen-4 suppresses aortic immunoinflammatory responses and prevents angiotensin II-induced abdominal aortic aneurysm formation in mice
Authors: Amin H , Sasaki N , Yamashita T , Mizoguchi T , Hayashi T , Emoto T , Matsumoto T , Yoshida N , Tabata T , Horibe S , Kawauchi S , Rikitake Y , Hirata K 
Published: October 2019

Abstract

Aims
Vascular inflammation via T-cell-mediated immune responses has been shown to be critically involved in the pathogenesis of abdominal aortic aneurysm (AAA). T-cell coinhibitory molecule cytotoxic T-lymphocyte–associated antigen-4 (CTLA-4) is known to act as a potent negative regulator of immune responses. However, the role of this molecule in the development of AAA remains completely unknown. In the present study, we determined the effects of CTLA-4 overexpression on experimental AAA.

Methods and results
We continuously infused 12-week-old CTLA-4 transgenic (CTLA-4-Tg)/apolipoprotein E–deficient (Apoe−/−) mice (n=35) or control Apoe−/− mice (n=40) fed a high-cholesterol diet with angiotensin II by implanting osmotic mini-pumps and evaluated the development of AAA. Ninety percent of angiotensin II-infused mice developed AAA, with 50% mortality because of aneurysm rupture. Overexpression of CTLA-4 significantly reduced the incidence (66%), mortality (26%), and diameter (18%) of AAA (incidence: P=0.0104; mortality: P=0.031; diameter: P=0.011). These protective effects were associated with a decreased number of effector CD4+ T cells and the downregulated expression of costimulatory molecules CD80 and CD86, ligands for CTLA-4, on CD11c+ dendritic cells in lymphoid tissues. In addition, by performing in situ zymography of the abdominal aortic aneurysm lesions, we observed a trend toward a decrease in MMP activity in the aneurysmal lesion following overexpression of CTLA-4. Finally, CTLA-4-Tg/Apoe−/− mice had reduced macrophage and CD4+ T cell accumulation and MMP activity in the aneurysmal lesion, leading to attenuated aortic inflammation, preserved vessel integrity, and decreased susceptibility to AAA and aortic rupture.

Conclusion
Our findings suggest that CTLA-4 protects against AAA by suppressing immunoinflammatory responses and could be an attractive therapeutic target for AAA.
1446A greater healthy behaviors score is associated with a lower risk of all-cause and cause specific mortality: insight from two prospective multi-ethnic surveys
Authors: Mazidi M , Katsiki N , Mikhailidis D P , Rysz J , Banach M 
Published: October 2019

Abstract

Background
Mortality from non-communicable diseases (NCDs) is influenced bymodifiable risk factors. Simple tools which do not require laboratory tests, (blood pressure (BP) [B], exercise [E], weight [W], alimentation [A] (fruit and vegetable consumption), and tobacco [T] (BEWAT) may estimate the risk of all-cause and cause specific mortality.

Purpose
Therefore, we evaluated the link between BEWAT and mortality in a randomly selected sample of the US population.

Method
Adults aged ≥20 years, enrolled in the Third National Health and Nutrition Examination Survey (NHANES-III, 1988–1994) and continuous NHANES (2005–2010), and followed up to December 31st 2011, were included in the present analysis. Multiple Cox regressionswere applied to evaluate the associations between the total BEWAT score and each of its components with all-cause and cause specific mortality.

Results
Overall, 22,968 participants (47.1% men) were included in the present analysis (mean age: 47.4 years). Individuals in the highest BEWAT tertile (T3) had a 25% lower risk of mortality compared with T1 [hazard ratio (HR): 0.75, 95% confidence interval (CI): 0.71–0.79], further corrections slightly diluted the magnitude of link to 22% (HR: 0.78, 95% CI: 0.75–0.81) (Figure). In a fully adjusted model, individuals in T3 also had a 26% lower risk of cardiovascular disease (CVD) mortality compared with those in T1 (HR: 0.74, 95% CI: 0.64–0.83), similar trends were observed across the BEWAT tertiles for cancer mortality risk (participants in T3 had a 31 and 26% lower risk for cancer death in Models 1 and 2, respectively). For sensitivity analyses after excluding smoking from the total BEWAT score, in the fully adjusted model the association between the BEWAT score and cancer death was attenuated but remained significant (HR: 0.80, 95% CI: 0.72–0.89 for T3 vs T1). Furthermore, total BEWAT score (without the BP component) could still predict CVD mortality (T3= HR: 0.71, 95% CI: 0.61–0.82).
All-cause death and BEWAT tertiles.

Conclusion
A higher BEWAT status is beneficial regarding all-cause and cause specific mortality. Our results highlight the value of modifiable risk factors as a simple and affordable variable for evaluating the risk of mortality.
2166A multicenter echocardiographic comparison on pacemaker-induced tricuspid valve regurgitation: leadless versus transvenous single-chamber and dual-chamber pacing therapy
Authors: Beurskens N E G , Van Drooge J , Tjong F , Bon R , Dasselaar K , Gorter T , Maass A , Knops R 
Published: October 2019

Abstract

Background
Pacemaker (PM) lead interference with tricuspid valve (TV) function is an important determinant of hemodynamic compromise and is associated with substantial morbidity and mortality. Lead-related TV regurgitation (TR) can potentially be mitigated by leadless pacemaker (LP) therapy by eliminating the presence of a transvalvular lead.

Purpose
This large multicenter study aimed to evaluate the impact of LP therapy on TV function in comparison with an age –, sex, and follow-up duration -matched cohort of transvenous single-chamber (VVI) and dual-chamber (DDD) PM recipients.

Methods
Leadless, and transvenous VVI and DDD-PM recipients who underwent an echocardiographic study prior to the procedure and 15±6 months thereafter between January 2013 and September 2018 at two tertiary centers in the Netherlands were included. We used the data of a prospectively acquired population that comprised consecutive patients who underwent LP implantation who were 1:1 matched to transvenous VVI-PM and DDD-PM patients.

Results
A total of 198 patients (129 males, age 79±8.2 years) were included, of whom 66 were implanted with a LP (two models: Nanostim, Micra LP), and 66 with a transvenous VVI and 66 with DDD-PM. In the total cohort, the Wilcoxon signed-rank test revealed that TR severity was graded more severe in 87 (44%), equally in 104 (53%), and less severe in 7 (4%) patients (p<0.001) compared with baseline echocardiographic findings. Worsening TR was observed in 28 (42%) of the LP (p<0.001) and 34 (52%) of transvenous VVI-PM (p<0.001), and 25 (38%) of the DDD-PM recipients (p<0.01). Binary logistic regression analysis showed that LP recipients were equally prone to increasing TV dysfunction compared with transvenous PMs (p=0.42). Septal position of the leadless intracardiac device (odds ratio 3.6, p=0.03) was associated with worsening TR. In the total cohort, 30 (15%) patients had heart failure hospitalization during the follow-up period.

Conclusions
TR is a malignant disease which can result in high rates of heart failure hospitalization. This study revealed an unexpected high proportion of patients with worsening TR following LP therapy, yet it was comparable to conventional PM systems. The mechanical impact of the LP near the TV apparatus is the most likely cause of this phenomenon since the septal positioning of the device was associated with increasing TV incompetence. The general consensus was that LP therapy mitigates the risk for TV dyfunction due to the circumvention of transvalvular leads. Therefore, the current results are highly clinically relevant as the contradict expected performance of the LP approach.
2201Coronary angioplasty patients' preferences for information about treatment risks: a survey study
Authors: Astin F , Stephenson J , Probyn J , Holt J , Marshall K , Conway D 
Published: October 2019

Abstract

Background
Percutaneous Coronary Intervention (PCI) is the commonest invasive procedure in cardiology. Before treatment consent must be given. As part of this communication process patients receive information about the risks and benefits of PCI and alternative treatments. Published studies tell us that the amount and quality of the information received by patients undergoing PCI is variable; benefits are often overestimated, risks forgotten and alternative treatments not always considered. Very little is known about patients' preferences for PCI risk information. Aim: To describe patients' preferences for formation about PCI treatment risk as part of the informed consent process Methods: A cross-sectional survey was distributed to 350 participants treated with PCI across 10 PCI centres in England.

Results
Three hundred and twenty six participants completed the survey. Thirty percent of the sample reported needing help to understand written medical information. Fifty-one percent were treated with elective PCI, 75% were male, average age of 66.5 years. Recall and comprehension of PCI information given during the consent process was generally limited; 47% and 61% agreed that patients do not usually understand, or remember, the information given to them respectively. Eighty-eight percent of urgent PCI patients wanted to know about all possible risks compared to 90% of elective cases. Most participants (88% urgent and 94% elective) believed that PCI would reduce their risk of a future heart attack.

Conclusion
A significant proportion of PCI patients find it difficult to recall or understand information about treatment risks. It is recommended that patients are given health-related information designed to accommodate different health literacy levels in advance of their treatment.

Acknowledgement/Funding
National Institute for Health Research Research for Patient Benefit Programme Grant Reference Number PB-PG-0712-28089
2202Instant analysis of the ECG with a new digital technique during palpitations reduce symptoms, anxiety, depression, and increase HRQOL in women
Authors: Carnlof C , Insulander P , Jensen-Urstad M , Schenck-Gustafsson K 
Published: October 2019

Abstract

Background
Palpitation is common, particularly in women, and usually benign caused by premature atrial/ventricular beats or stress-induced sinus tachycardia. Palpitations may cause disturbing symptoms, anxiety, depression, and decreased health related quality of life (HRQOL). Uncommonly, arrhythmias of clinical importance such as atrial fibrillation or paroxysmal supraventricular or ventricular tachycardia may be the cause.

Purposes
To evaluate if instant analysis of underlying heart rhythm during palpitations reduce symptoms, anxiety, depression, and increase HRQOL.

Methods
In all, 913 women (age 56±11 years) with palpitations causing anxiety were recruited from social web sites. Coala Heart Monitor® was used by participants and ECG recorded twice a day and at symptoms for 60 days. The system uses a well-validated algorithm to analyze heart rhythm, is connected to the user's smartphone and provides immediate response to the user. In cases of non-benign arrhythmias, the result was also analyzed manually. Questionnaires addressing symptom (Symptom severity and frequency checklist (SCL), anxiety, depression Hospital anxiety and depression scale (HADS), Generalized Anxiety Disorder (GAD-7) and HRQOL (RAND-36)) were analyzed before and after two months. Exclusion criterium was known atrial fibrillation.

Results
Between June 2018 and November 2018, 280 474 recordings (both chest and thumbs) ECG recordings were automatically analyzed. Frequency and severity of symptoms decreased (frequency from 23.7±8.4 to 19.7±8.5 (p<0.001), severity from 22.7±4.9 to 21±4.4 (p<0.001)). Total anxiety measured by HADS decreased from 6.4±4.2 to 5.7±4.2 (p<0.001) and depression from 5.1±3.9 to 4.6±4.1 (p<0.001). Generalized anxiety disorder decreased from 5.6±4.8 to 4.7±4.6 (p<0.001) and HRQOL increased in all domains (p<0.001). In 83% of recordings during symptomatic palpitation, benign premature atrial or ventricular beats, sinus tachycardia, or normal sinus rhythm were found.

Conclusions
Instant analysis of the ECG with direct response to the user during palpitations reduce symptoms, anxiety, depression, and increase HRQOL in women.
2207Cardiovascular outcome in THEMIS -like type 2 diabetes patients in Sweden: a nationwide observational study
Authors: Hasvold L P , Erlinge D , Svennblad B , Janzon M , Lindholm D , Sundell K A , Jernberg T , James S 
Published: October 2019

Abstract

Background
The THEMIS study (NCT01991795; in analysis phase; n=19,349) compares the effect of dual antiplatelet therapy (DAPT) vs ASA alone for the prevention of major cardiovascular (CV) events in type 2 diabetes (T2D) patients with coronary artery disease (CAD) at high CV risk, but without prior myocardial infarction (MI) or stroke. However, there is a lack of real-life data on CV risk in a THEMIS-like population compared to MI patients, where treatment with DAPT is guideline standard. The aim of this study was to investigate the CV risk in a THEMIS-like population vs an MI population

Methods
Patients invasively managed in Sweden (2006–2014) were identified using the SWEDEHEART registry and the National Patient Registry. Two populations were studied: a THEMIS-like population including patients with CAD and T2D, ≥1 vessel disease or elective percutaneous coronary intervention [PCI], and no prior stroke or MI), and a MI patient population alive at discharge. The cumulative incidence of the primary composite outcome (CV death (CVD)/MI/stroke) was estimated 3 years after index using the Kaplan-Meier method, and with probability plots adjusted for age, sex, atrial fibrillation, and heart failure. A 30 days blanking period for outcome was added to ensure capture of new events (index THEMIS-pop.: after angiography; index MI-pop.: after discharge).

Results
Overall, 6,534 THEMIS-like patients and 96,638 MI patients were included. At index, the THEMIS-like patients (CAD and T2D without previous MI/stroke) were aged 67.1 years (mean), 26.6% women, 9.2% AF, and 4.7% HF, while the MI patients were aged 67.3 years (mean), 30.7% women, 15.5% T2D, 17.9% previous MI, 5.2% stroke, 6.4% AF, and 4.8% HF. Three-year cumulative incidence for the composite outcome CVD/MI/stroke was 0.149 (95% CI 0.140, 0.158) for THEMIS-like patients, and 0.148 (95% CI 0.145, 0,15) for MI patients (p=0.88 log rank test) (Figure). Corresponding adjusted probably plots: 0.135 (95% CI 0.127, 0.143) and 0.131 (95% CI 0.128, 0.133). MI was the main risk driver with greatest cumulative incidence in both populations (0.091 vs 0.087) (Figure).
Figure 1

Conclusions
In this Swedish real-life setting, THEMIS-like patients, followed from 30 days after invasive intervention, had a similar long-term risk for CV events compared with MI patients surviving 30 days after discharge, with MI as the main risk driver, despite having no previous ischemic events. The present data indicate that long-term ischemic risk prevention should be a key strategy in coronary artery disease patients with diabetes requiring elective invasive intervention.

Acknowledgement/Funding
AstraZeneca
2208The interaction effect between myocardial infarction and comorbidity: nationwide cohort study
Authors: Schmidt M , Horvath-Puho E , Ording A G , Lash T L , Botker H E , Sorensen H T 
Published: October 2019

Abstract

Background
Comorbid diseases may influence the prognosis of acute myocardial infarction (MI) directly by increasing the mortality hazard and indirectly by modifying treatment intensity.

Purpose
To examine whether comorbid diseases and MI interact to increase mortality beyond the sum of their independent effects.

Methods
Using Danish medical databases, we conducted a nationwide cohort study of patients diagnosed with MI between 1995 and 2016 (n=179,515) and a comparison cohort of persons without MI (n=880,347)matched on age, sex, and comorbidities in the Charlson Comorbidity Index. The study outcome was time-to-death and the cohorts were followed from the MI/index date until death, emigration, five years of follow-up, or 31 December 2016, whichever came first. Standardized mortality rates with 95% confidence intervals (CIs) were computed using age and sex weights based on the inception MI cohort. The interaction was examined on the additive scale by calculating the interaction contrasts (the difference in rate differences), which measure the combined mortality effect of MI and comorbidity that cannot be explained by summing their individual effects. The follow-up period was stratified by the first 30 days, 31-days to one year, and >1–5 year after the index date. Analyses were repeated within strata of comorbidity levels (1, 2–3, 4+).

Results
62% of patients were male. The median age was 70 (interquartile range: 60, 80) years. Among individuals without comorbidity, the mortality rate per 1000 person-years during 30-day follow-up was 1,851 (95% confidence interval: 1,818 to 1,884) for myocardial infarction patients and 22 (21 to 24) for comparison cohort members, yielding a rate difference of 1,829. For individuals with low comorbidity, corresponding baseline mortality rates per 1,000 person-years were 2,498 (2,436 to 2,560) in the myocardial infarction and 54 (50 to 57) in the comparison cohort (rate difference=2,444). The interaction contrast was 616, indicating that the interaction accounted for 25% (616/2,498) of the total mortality rate in MI patients with low comorbidity. The percentage of the 30-day mortality rate explained by interaction increased further for moderate (35%) and severe (45%) comorbidity levels. Absolute and relative interaction effects were largest within the first 30 days, but similar dose-response patterns were observed during 31–365 days and 1–5 years of follow-up (all p-values for trends<0.002).

Conclusions
Comorbidities interact with myocardial infarction to increase short- and long-term mortality beyond that explained by the additive effect of myocardial infarction and comorbid diseases acting alone

Acknowledgement/Funding
Department of Clinical Epidemiology's Research Foundation; Program for Clinical Research Infrastructure (PROCRIN)