bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progression of Electrocardiographic Abnormalities in Type 1 Diabetes During 16 Years of Follow‐up: The Epidemiology of Diabetes Interventions and Complications (EDIC) Study
Authors: Soliman Elsayed Z. , Backlund Jye‐Yu C. , Bebu Ionut , Li Yabing , Zhang Zhu‐Ming , Cleary Patricia A. , Lachin John M. ,   for the DCCT/EDIC Research Group
Published: September 2018

Background

The electrocardiogram (
ECG
) is an objective tool for cardiovascular disease (
CVD
) risk assessment.

Methods and Results

We evaluated distribution of
ECG
abnormalities and risk factors for developing new abnormalities in 1314 patients with type 1 diabetes (T1D) from the Epidemiology of Diabetes Interventions and Complications (
EDIC
) study. Annual
ECG
s were centrally read.
ECG
abnormalities were classified as major and minor according to the Minnesota
ECG
Classification. At
EDIC
year 1 (baseline), 356 (27.1%) of the participants had at least 1
ECG
abnormality (major or minor) whereas 26 (2%) had at least one major abnormality. During 16 years of follow‐up, 1016 (77.3%) participants developed at least 1 new
ECG
abnormality (major or minor), whereas 172 (13.1%) developed at least 1 new major abnormality. Independent risk factors for developing new major
ECG
abnormalities were: age, current smoking, increased systolic blood pressure, and higher glycosylated hemoglobin (hazard ratio [
HR
] [95%
CI
]: 1.04 [1.02–1.06] per 1‐year increase, 1.75 [1.22–2.53], 1.03 [1.01–1.05] per 1 mm Hg increase, and 1.16 [1.04–1.29] per 10% increase, respectively). Independent risk factors for developing any new
ECG
abnormalities (major or minor) were age and systolic blood pressure (
HR
[95%
CI
]: 1.02 [1.01–1.03] per 1‐year increase and 1.01 [1.00–1.02] per 1 mm Hg increase, respectively).

Conclusions

New
ECG
abnormalities commonly occur in the course of T1D, consistent with the recognized increasing risk for
CVD
as patients age. Advanced age, increased systolic blood pressure, smoking, and higher HbA1c are independent risk factor for developing major
ECG
abnormalities, which underscores the importance of tight glucose control in T1D in addition to management of common
CVD
risk factors.
Percutaneous Patent Ductus Arteriosus (PDA) Closure in Very Preterm Infants: Feasibility and Complications
Authors: Backes Carl H. , Cheatham Sharon L. , Deyo Grace M. , Leopold Scott , Ball Molly K. , Smith Charles V. , Garg Vidu , Holzer Ralf J. , Cheatham John P. , Berman Darren P. 
Published: September 2018

Background

Percutaneous closure of patent ductus arteriosus (
PDA
) in term neonates is established, but data regarding outcomes in infants born very preterm (<32 weeks of gestation) are minimal, and no published criteria exist establishing a minimal weight of 4 kg as a suitable cutoff. We sought to analyze outcomes of percutaneous
PDA
occlusion in infants born very preterm and referred for
PDA
closure at weights <4 kg.

Methods and Results

Retrospective analysis (January 2005–January 2014) was done at a single pediatric center. Procedural successes and adverse events were recorded. Markers of respiratory status (need for mechanical ventilation) were determined, with comparisons made before and after catheterization. A total of 52 very preterm infants with a median procedural weight of 2.9 kg (range 1.2–3.9 kg) underwent attempted
PDA
closure. Twenty‐five percent (13/52) of infants were <2.5 kg. Successful device placement was achieved in 46/52 (88%) of infants. An adverse event occurred in 33% of cases, with an acute arterial injury the most common complication. We observed no association between weight at time of procedure and the risk of an adverse event. No deaths were attributable to the
PDA
closure. Compared to precatheterization trends, percutaneous
PDA
closure resulted in improved respiratory status, including less exposure to mechanical ventilation (mixed effects logistic model,
P
<0.01).

Conclusions

Among infants born very preterm, percutaneous
PDA
closure at weights <4 kg is generally safe and may improve respiratory health, but risk of arterial injury is noteworthy. Randomized clinical trials are needed to assess clinically relevant differences in outcomes following percutaneous
PDA
closure versus alternative (surgical ligation) management strategies.
Prognostic Value of Aortic Valve Area by Doppler Echocardiography in Patients With Severe Asymptomatic Aortic Stenosis
Authors: Maréchaux Sylvestre , Ringle Anne , Rusinaru Dan , Debry Nicolas , Bohbot Yoan , Tribouilloy Christophe 
Published: September 2018

Background

The aim of this study was to evaluate the relationship between aortic valve area (
AVA
) obtained by Doppler echocardiography and outcome in patients with severe asymptomatic aortic stenosis and to define a specific threshold of
AVA
for identifying asymptomatic patients at very high risk based on their clinical outcome.

Methods and Results

We included 199 patients with asymptomatic severe aortic stenosis (
AVA
≤1.0 cm
2
). The risk of events (death or need for aortic valve replacement) increased linearly on the scale of log hazard with decreased
AVA
(adjusted hazard ratio 1.17; 95%
CI
1.06–1.29 per 0.1 cm
2
AVA
decrement;
P
=0.002). Event‐free survival at 12, 24, and 48 months was 63±6%, 51±6%, and 34±6%, respectively, for
AVA
0.8 to 1 cm
2
; 49±6%, 36±6%, and 26±6%, respectively, for
AVA
0.6 to 0.8 cm
2
; and 33±8%, 20±7%, and 11±5%, respectively, for
AVA
≤0.6 cm
2
(
P
trend
=0.002). Patients with
AVA
≤0.6 cm
2
had a significantly increased risk of events compared with patients with
AVA
0.8 to 1 cm
2
(adjusted hazard ratio 2.22; 95%
CI
1.41–3.52;
P
=0.001), whereas patients with
AVA
0.6 to 0.8 cm
2
had an increased risk of events compared with those with
AVA
0.8 to 1 cm
2
, but the difference was not statistically significant (adjusted hazard ratio 1.38; 95%
CI
0.93–2.05;
P
=0.11). After adjustment for covariates and aortic valve replacement as a time‐dependent variable, patients with
AVA
≤0.6 cm
2
had a significantly greater risk of all‐cause mortality than patients with
AVA
>0.6 cm
2
(hazard ratio 3.39; 95%
CI
1.80–6.40;
P
<0.0001).

Conclusions

Patients with severe asymptomatic aortic stenosis and
AVA
≤0.6 cm
2
displayed an important increase in the risk of adverse events during short‐term follow‐up. Further studies are needed to determine whether elective aortic valve replacement improves outcome in this high‐risk subgroup of patients.
Relationship of the American Heart Association's Impact Goals (Life's Simple 7) With Risk of Chronic Kidney Disease: Results From the Atherosclerosis Risk in Communities (ARIC) Cohort Study
Authors: Rebholz Casey M. , Anderson Cheryl A. M. , Grams Morgan E. , Bazzano Lydia A. , Crews Deidra C. , Chang Alex R. , Coresh Josef , Appel Lawrence J. 
Published: September 2018

Background

As part of its 2020 Impact Goals, the American Heart Association developed the Life's Simple 7 metric for cardiovascular health promotion. The relationship between the Life's Simple 7 metric and incident chronic kidney disease (
CKD
) is unknown.

Methods and Results

We estimated the association between Life's Simple 7 and incident
CKD
in 14 832 Atherosclerosis Risk in Communities study participants. Ideal levels of Life's Simple 7 health factors were the following: nonsmoker or quit >1 year ago; body mass index <25 kg/m
2
; ≥150 minutes/week of physical activity; healthy dietary pattern (high in fruits and vegetables, fish, and fiber‐rich whole grains; low in sodium and sugar‐sweetened beverages); total cholesterol <200 mg/dL; blood pressure <120/80 mm Hg; and fasting blood glucose <100 mg/dL. At baseline, mean age was 54 years, 55% were women, and 26% were African American. There were 2743 incident
CKD
cases over a median follow‐up of 22 years. Smoking, body mass index, physical activity, blood pressure, and blood glucose were associated with
CKD
risk (all
P
<0.01), but diet and blood cholesterol were not.
CKD
risk was inversely related to the number of ideal health factors (
P
‐trend<0.001). A model containing the Life's Simple 7 health factors was more predictive of
CKD
risk than the base model including only age, sex, race, and estimated glomerular filtration rate (Life's Simple 7 health factors area under the
ROC
curve: 0.73, 95%
CI
: 0.72, 0.74 versus base model area under the
ROC
curve: 0.68, 95%
CI
: 0.67, 0.69;
P
<0.001).

Conclusions

The
AHA
's Life's Simple 7 metric, developed to measure and promote cardiovascular health, predicts a lower risk of
CKD
.
Ribonuclease (RNase) Prolongs Survival of Grafts in Experimental Heart Transplantation
Authors: Kleinert Eike , Langenmayer Martin C. , Reichart Bruno , Kindermann Jana , Griemert Barbara , Blutke Andreas , Troidl Kerstin , Mayr Tanja , Grantzow Tobias , Noyan Fatih , Abicht Jan‐Michael , Fischer Silvia , Preissner Klaus T. , Wanke Ruediger , Deindl Elisabeth , Guethoff Sonja 
Published: September 2018

Background

Cell damage, tissue and vascular injury are associated with the exposure and release of intracellular components such as
RNA
, which promote inflammatory reactions and thrombosis. Based on the counteracting anti‐inflammatory and cardioprotective functions of ribonuclease A (
RN
ase A) in this context, its role in an experimental model of heart transplantation in rats was studied.

Methods and Results

Inbred
BN
/OrlRj rat cardiac allografts were heterotopically transplanted into inbred
LEW
/OrlRj rats. Recipients were intravenously treated every other day with saline or bovine pancreatic
RN
ase A (50 μg/kg). Toxic side effects were not found (macroscopically and histologically). Heart tissue flow cytometry and quantitative morphological analyses of explanted hearts at postoperative day 1 or postoperative day 4 showed reduced leukocyte infiltration, edema, and thrombus formation in
RN
ase A‐treated rats. In allogeneic mixed lymphocyte reactions,
RN
ase A decreased the proliferation of effector T cells.
RN
ase A treatment of rats resulted in prolonged median graft survival up to 10.5 days (interquartile range 1.8) compared to 6.5 days (interquartile range 1.0) in saline treatment (
P
=0.001). Treatment of rats with a new generated (recombinant) human pancreatic
RN
ase 1 prolonged median graft survival similarly, unlike treatment with (recombinant) inactive human
RN
ase 1 (each 50 μg/kg
IV
every other day, 11.0 days, interquartile range 0.3, versus 8.0 days, interquartile range 0.5,
P
=0.007).

Conclusions

Upon heart transplantation,
RN
ase administration appears to present a promising and safe drug to counteract ischemia/reperfusion injury and graft rejection. Furthermore,
RN
ase treatment may be considered in situations of critical reperfusion after percutaneous coronary interventions or in cardiac surgery using the heart–lung machine.
Long‐Term Outcomes of Cardiac Resynchronization Therapy Using Apical Versus Nonapical Left Ventricular Pacing
Authors: Leyva Francisco , Zegard Abbasin , Taylor Robin J. , Foley Paul W. X. , Umar Fraz , Patel Kiran , Panting Jonathan , van Dam Peter , Prinzen Frits W. , Marshall Howard , Qiu Tian 
Published: September 2018

Background

Experimental evidence indicates that left ventricular (
LV
) apical pacing is hemodynamically superior to nonapical
LV
pacing. Some studies have shown that an LV apical lead position is unfavorable in cardiac resynchronization therapy. We sought to determine whether an apical
LV
lead position influences cardiac mortality after cardiac resynchronization therapy.

Methods and Results

In this retrospective observational study, the primary end point of cardiac mortality was assessed in relation to longitudinal (basal, midventricular, or apical) and circumferential (anterior, lateral, or posterior)
LV
lead positions, as well as right ventricular (apical or septal), assigned using fluoroscopy. Lead positions were assessed in 1189 patients undergoing cardiac resynchronization therapy implantation over 15 years. After a median follow‐up of 6.0 years (interquartile range: 4.4–7.7 years), an apical
LV
lead position was associated with lower cardiac mortality than a nonapical position (adjusted hazard ratio: 0.74; 95% confidence interval, 0.56–0.99) after covariate adjustment. There were no differences in total mortality or heart failure hospitalization. Death from pump failure was lower with apical than nonapical positions (adjusted hazard ratio: 0.69; 95% confidence interval, 0.51–0.94). Compared with a basal position, an apical
LV
position was also associated with lower risk of sudden cardiac death (adjusted hazard ratio: 0.34; 95% confidence interval, 0.13–0.93). No differences emerged between circumferential
LV
lead positions or right ventricular positions with respect to any end point.

Conclusions

In recipients of cardiac resynchronization therapy, an apical
LV
lead position was associated with better long‐term cardiac survival than a nonapical position. This effect was due to a lower risk of pump failure and sudden cardiac death.
Activin Receptor‐Like Kinase 4 Haplodeficiency Mitigates Arrhythmogenic Atrial Remodeling and Vulnerability to Atrial Fibrillation in Cardiac Pathological Hypertrophy
Authors: Wang Qian , Chen Yihe , Zhang Daoliang , Li Changyi , Chen Xiaoqing , Hou Jianwen , Fei Yudong , Wang Yuepeng , Li Yigang 
Published: September 2018

Background

Activin receptor‐like kinase 4 (
ALK
4) is highly expressed in mammal heart. Atrial fibrillation (
AF
) is closely related to ventricular pressure overload. Because pressure overload increases atrial pressure and leads to atrial remodeling, it would be informative to know whether
ALK
4 exerts potential effects on atrial remodeling and
AF
vulnerability in a pressure‐overload model.

Methods and Results

Wild‐type littermates and
ALK
4
+/−
mice were subjected to abdominal aortic constriction or a sham operation. After 4 or 8 weeks, echocardiographic and hemodynamic measurements were performed, and inducibility of
AF
was tested. The hearts were divided into atria and ventricles and then were fixed in formalin for staining, or they were weighted and snap‐frozen for quantitative real‐time polymerase chain reaction and Western blot analysis. Compared with wild‐type littermates,
ALK
4
+/−
mice demonstrated a similar extent of atrial hypertrophy but significantly suppressed atrial fibrosis at 8 weeks post–abdominal aortic constriction.
ALK
4 haplodeficiency partially blocked abdominal aortic constriction–induced upregulation of monocyte chemotactic protein 1 and interleukin‐6, and the increased chemotaxin of macrophages.
ALK
4 haplodeficiency also blunted a reduction of connexin 40 and redistribution of connexin 43 from the intercalated disk to the lateral membranes, thereby improving localized conduction abnormalities. Meanwhile,
ALK
4 haplodeficiency inhibited abdominal aortic constriction–induced decreased

I
N

a
,

I
C

a‐L
and

I
K

1
densities as well as the accompanying action potential duration shortening. Mechanistically,
ALK
4 haploinsufficiency resulted in the suppression of Smad2/3 activity in this model.

Conclusions

Our results demonstrate that
ALK
4 haplodeficiency ameliorates atrial remodeling and vulnerability to
AF
in a pressure‐overload model through inactivation of the Smad2/3 pathway, suggesting that
ALK
4 might be a potential therapeutic target in combating pressure overload–induced
AF
.
Efficacy and Safety of Edoxaban in Patients With Active Malignancy and Atrial Fibrillation: Analysis of the ENGAGE AF‐TIMI 48 Trial
Authors: Fanola Christina L. , Ruff Christian T. , Murphy Sabina A. , Jin James , Duggal Anil , Babilonia Noe A. , Sritara Piyamitr , Mercuri Michele F. , Kamphuisen Pieter W. , Antman Elliott M. , Braunwald Eugene , Giugliano Robert P. 
Published: September 2018

Background
Anticoagulation in patients with malignancy and atrial fibrillation is challenging because of enhanced risks for thrombosis and bleeding and the frequent need for invasive procedures. Data on direct oral antagonists in such patients are sparse.

Methods and Results

The
ENGAGE AF
‐
TIMI
48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction Study 48) trial randomized 21 105 patients with atrial fibrillation to edoxaban or warfarin. Patients with malignancy, defined as a postrandomization new diagnosis or recurrence of remote cancer, were followed up over a median of 2.8 years. Adjusted Cox proportional hazard models were used to evaluate the safety and efficacy of edoxaban versus warfarin. Over a median of 495 days (interquartile range, 230–771 days), 1153 patients (5.5%) were diagnosed with new or recurrent malignancy, most commonly involving the gastrointestinal tract (20.6%), prostate (13.6%), and lung (11.1%). Malignancy was associated with increased risk of death (adjusted hazard ratio [HR], 3.12; 95% confidence interval [CI], 2.78–3.50) and major bleeding (adjusted HR, 2.45; 95% CI, 2.07–2.89), but not stroke/systemic embolism (adjusted HR, 1.08; 95% CI, 0.83–1.42). Relative outcomes with higher‐dose edoxaban versus warfarin were consistent regardless of malignancy status for stroke/systemic embolism (
HR
, 0.60 [95% CI, 0.31–1.15] for malignancy versus
HR
, 0.89 [95% CI, 0.76–1.05] for no malignancy; interaction
P
=0.25) and major bleeding (
HR
, 0.98 [95% CI, 0.69–1.40] for malignancy versus
HR
, 0.79 [95% CI, 0.69–1.05] for no malignancy; interaction
P
=0.31). There was, however, a significant treatment interaction for the composite ischemic end point (ischemic stroke/systemic embolism/myocardial infarction), with greater efficacy of higher‐dose edoxaban versus warfarin in patients with malignancy (
HR
, 0.54; 95% CI, 0.31–0.93) compared with no malignancy (
HR
, 1.02; 95% CI, 0.88–1.18; interaction
P
=0.026).

Conclusions
In patients with atrial fibrillation who develop malignancy, the efficacy and safety profile of edoxaban relative to warfarin is preserved, and it may represent a more practical alternative.
Osteoprotegerin and Cardiovascular Events in High‐Risk Populations: Meta‐Analysis of 19 Prospective Studies Involving 27 450 Participants
Authors: Tschiderer Lena , Klingenschmid Gerhard , Nagrani Rajini , Willeit Johann , Laukkanen Jari A. , Schett Georg , Kiechl Stefan , Willeit Peter 
Published: September 2018

Background

Osteoprotegerin is a cytokine involved in bone metabolism as well as vascular calcification and atherogenesis. Although circulating osteoprotegerin levels are robustly associated with incident cardiovascular disease (
CVD
) in the general population, its relevance as a biomarker among populations at high
CVD
risk is less clear.

Methods and Results

Three independent reviewers systematically searched PubMed,
EMBASE
, and Web of Science to identify prospective studies that had recruited participants on the basis of having conditions related to high
CVD
risk. A total of 19 studies were eligible for inclusion, reporting on 27 450 patients with diabetes mellitus (2 studies), kidney disease (7 studies), preexisting heart disease (5 studies), or recent acute coronary syndromes (5 studies) at baseline. Over a mean follow‐up of 4.2 years, 4066
CVD
events were recorded. In a random‐effects meta‐analysis, the pooled risk ratio for
CVD
events comparing people in the top versus the bottom tertile of osteoprotegerin concentration was 1.30 (95% confidence interval, 1.12–1.50;
P
<0.001; I
2
=68.3%). There was evidence for presence of publication bias (
P
value from Egger's test=0.013). Correction for publication bias using the trim‐and‐fill method reduced the risk ratio to 1.21 (95% confidence interval, 1.03–1.42;
P
<0.001). The risk ratios did not vary significantly by population type, geographical region, statistical adjustment, sample or assay type, age, sex, or length of follow‐up.

Conclusions

In populations at high
CVD
risk, elevated circulating osteoprotegerin levels are associated with a higher risk for future
CVD
events. The magnitude of association appears weaker than in the general population.
Estimated Life Expectancy Without Recurrent Cardiovascular Events in Patients With Vascular Disease: The SMART‐REACH Model
Authors: Kaasenbrood Lotte , Bhatt Deepak L. , Dorresteijn Jannick A.N. , Wilson Peter W.F. , D'Agostino Ralph B. , Massaro Joseph M. , van der Graaf Yolanda , Cramer Maarten J.M. , Kappelle L. Jaap , de Borst Gert J. , Steg Ph. Gabriel , Visseren Frank L. J. 
Published: September 2018

Background
In patients with vascular disease, risk models may support decision making on novel risk reducing interventions, such as proprotein convertase subtilisin/kexin type 9 inhibitors or anti‐inflammatory agents. We developed and validated an innovative model to estimate life expectancy without recurrent cardiovascular events for individuals with coronary, cerebrovascular, and/or peripheral artery disease that enables estimation of preventive treatment effect in lifetime gained.

Methods and Results

Study participants originated from prospective cohort studies: the
SMART (Secondary Manifestations of Arterial Disease)
cohort and
REACH (Reduction of Atherothrombosis for Continued Health)
cohorts of 14 259 (
REACH
Western Europe), 19 170 (
REACH
North America) and 6959 (
SMART
, The Netherlands) patients with cardiovascular disease. The SMART‐REACH model to estimate life expectancy without recurrent events was developed in
REACH
Western Europe as a Fine and Gray competing risk model incorporating cardiovascular risk factors. Validation was performed in
REACH
North America and
SMART
. Outcomes were (1) cardiovascular events (myocardial infarction, stroke, cardiovascular death) and (2) noncardiovascular death. Predictors were sex, smoking, diabetes mellitus, systolic blood pressure, total cholesterol, creatinine, number of cardiovascular disease locations, atrial fibrillation, and heart failure. Calibration plots showed high agreement between estimated and observed prognosis in
SMART
and
REACH
North America. C‐statistics were 0.68 (95%
confidence interval,
0.67–0.70) in
SMART
and 0.67 (95%
confidence interval,
0.66–0.68) in
REACH
North America. Performance of the SMART‐REACH model was better compared with existing risk scores and adds the possibility of estimating lifetime gained by novel therapies.

Conclusions
The externally validated SMART‐REACH model could be used for estimation of anticipated improvements in life expectancy without recurrent cardiovascular events in individual patients with cardiovascular disease in Western Europe and North America.