bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic Risk Stratification Predicts All-Cause Mortality After Cardiac Catheterization
Authors: Levin Michael G. , Kember Rachel L. , Judy Renae , Birtwell David , Williams Heather , Arany Zolt , Giri Jay , Guerraty Marie , Cappola Tom ,   Regeneron Genetics Center, Chen Jinbo , Rader Daniel J. , Damrauer Scott M. 
Published: January 2019

Background:
Coronary artery disease (CAD) is influenced by genetic variation and traditional risk factors. Polygenic risk scores (PRS), which can be ascertained before the development of traditional risk factors, have been shown to identify individuals at elevated risk of CAD. Here, we demonstrate that a genome-wide PRS for CAD predicts all-cause mortality after accounting for not only traditional cardiovascular risk factors but also angiographic CAD itself.

Methods:
Individuals who underwent coronary angiography and were enrolled in an institutional biobank were included; those with prior myocardial infarction or heart transplant were excluded. Using a pruning-and-thresholding approach, a genome-wide PRS comprised of 139 239 variants was calculated for 1503 participants who underwent coronary angiography and genotyping. Individuals were categorized into high PRS (hiPRS) and low-PRS control groups using the maximally selected rank statistic. Stratified analysis based on angiographic findings was also performed. The primary outcome was all-cause mortality following the index coronary angiogram.

Results:

Individuals with hiPRS were younger than controls (66 years versus 69 years;
P
=2.1×10
-5
) but did not differ by sex, body mass index, or traditional risk-factor profiles. Individuals with hiPRS were at significantly increased risk of all-cause mortality after cardiac catheterization, adjusting for traditional risk factors and angiographic extent of CAD (hazard ratio, 1.6; 95% CI, 1.2–2.2;
P
=0.004). The strongest increase in risk of all-cause mortality conferred by hiPRS was seen among individuals without angiographic CAD (hazard ratio, 2.4; 95% CI, 1.1–5.5;
P
=0.04). In the overall cohort, adding hiPRS to traditional risk assessment improved prediction of 5-year all-cause mortality (area under the receiver-operating curve 0.70; 95% CI, 0.66–0.75 versus 0.66; 95% CI, 0.61–0.70;
P
=0.001).

Conclusions:
A genome-wide PRS improves risk stratification when added to traditional risk factors and coronary angiography. Individuals without angiographic CAD but with hiPRS remain at significantly elevated risk of mortality.
Simultaneous Assessment of Cardiac Inflammation and Extracellular Matrix Remodeling After Myocardial Infarction
Authors: Ramos Isabel T. , Henningsson Markus , Nezafat Maryam , Lavin Begonña , Lorrio Silvia , Gebhardt Pierre , Protti Andrea , Eykyn Thomas R. , Andia Marcelo E. , Floögel Ulrich , Phinikaridou Alkystis , Shah Ajay M. , Botnar Reneé M. 
Published: January 2019

Background:
Optimal healing of the myocardium after myocardial infarction (MI) requires a suitable degree of inflammation and its timely resolution, together with a well-orchestrated deposition and degradation of ECM (extracellular matrix) proteins.

Methods and Results:

MI and SHAM-operated animals were imaged at 3, 7, 14, and 21 days with 3T magnetic resonance imaging using a
19
F/
1
H surface coil. Mice were injected with
19
F-perfluorocarbon nanoparticles to study inflammatory cell recruitment, and with a gadolinium-based elastin-binding contrast agent to evaluate elastin content.
19
F magnetic resonance imaging signal colocalized with infarction areas, as confirmed by late gadolinium enhancement, and was highest 7 days post-MI, correlating with macrophage content (MAC-3 immunohistochemistry; ρ=0.89,
P
<0.0001).
19
F quantification with in vivo (magnetic resonance imaging) and ex vivo nuclear magnetic resonance spectroscopy correlated linearly (ρ=0.58,
P
=0.020). T
1
mapping after gadolinium-based elastin-binding contrast agent injection showed increased relaxation rate (R
1
) in the infarcted regions and was significantly higher at 21 days compared with 7 days post-MI (R
1
[s
−1
]: 21 days=2.8 [interquartile range, 2.69–3.30] versus 7 days=2.3 [interquartile range, 2.12–2.5],
P
<0.05), which agreed with an increased tropoelastin content (ρ=0.89,
P
<0.0001). The predictive value of each contrast agent for beneficial remodeling was evaluated in a longitudinal proof-of-principle study. Neither R
1
nor
19
F at day 7 were significant predictors for beneficial remodeling (
P
=0.68;
P
=0.062). However, the combination of both measurements (R
1
<2.34 Hz and 0.55≤
19
F≤1.85) resulted in an odds ratio of 30.0 (CI 95%, 1.41–638.15;
P
=0.029) for favorable post-MI remodeling.

Conclusions:

Multinuclear
1
H/
19
F magnetic resonance imaging allows the simultaneous assessment of inflammation and elastin remodeling in a murine MI model. The interplay of these biological processes affects cardiac outcome and may have potential for improved diagnosis and personalized treatment.
Molecular Imaging of VWF (von Willebrand Factor) and Platelet Adhesion in Postischemic Impaired Microvascular Reflow
Authors: Ozawa Koya , Packwood William , Varlamov Oleg , Qi Yue , Xie Aris , Wu Melinda D. , Ruggeri Zaverio , López Jose A. , Lindner Jonathan R. 
Published: January 2019

Background:
Complete mechanistic understanding of impaired microvascular reflow after myocardial infarction will likely lead to new therapies for reducing infarct size. Myocardial contrast echocardiography perfusion imaging and molecular imaging were used to evaluate the contribution of microvascular endothelial-associated VWF (von Willebrand factor) and platelet adhesion to microvascular no-reflow.

Methods and Results:

Myocardial infarction was produced by transient LAD ligation in WT (wild type) mice, WT mice treated with the VWF proteolytic enzyme ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13), and ADAMTS13-deficient (ADAMTS13−/−) mice. Myocardial contrast echocardiography perfusion imaging and molecular imaging of VWF and platelet GP (glycoprotein) Ibα were performed 30 minutes after ischemia-reperfusion. Infarct size was measured at 3 days. Mortality during ischemia-reperfusion incrementally increased in WT+ADAMTS13, WT, and ADAMTS13−/− mice (14%, 43%, and 63%, respectively;
P
<0.05). For WT mice, molecular imaging signal for platelets and VWF in the postischemic risk area was 4- to 5-fold higher (
P
<0.05) compared with both the remote nonischemic regions or to sham-treated mice. Signal enhancement in the risk area was completely abolished by ADAMTS13 treatment for both platelets (12.8±3.3 versus −1.0±4.4 IU;
P
<0.05) and VWF (13.9±4.0 versus −1.0±3.0 IU;
P
<0.05). ADAMTS13−/− compared with WT mice had 2- to 3-fold higher risk area signal for platelets (33.1±8.5 IU) and VWF (30.9±1.9 IU). Microvascular reflow in the risk area incrementally decreased for WT+ADAMTS13, WT, and ADAMTS13−/− mice (
P
<0.05), whereas infarct size incrementally increased (
P
<0.05).

Conclusions:
Mechanistic information on microvascular no-reflow is possible by combining perfusion and molecular imaging. In reperfused myocardial infarction, excess endothelial-associated VWF and secondary platelet adhesion in the risk area microcirculation contribute to impaired reflow and are modifiable.
Echocardiographic Predictors of Mortality in Women With Heart Failure With Reduced Ejection Fraction
Authors: Lundorff Ingrid Josefine , Sengeløv Morten , Jørgensen Peter Godsk , Pedersen Sune , Modin Daniel , Eske Bruun Niels , Fritz-Hansen Thomas , Skov Jensen Jan , Biering-Sørensen Tor 
Published: January 2019

Background:
Previous studies found that global longitudinal strain is a superior predictor of mortality in male patients with heart failure with reduced ejection fraction (EF). This does not apply to women. Our aim was to investigate sex-specific differences in cardiac function and identify echocardiographic predictors of mortality in women with heart failure with reduced EF.

Methods and Results:

Echocardiographic examinations were retrieved from 968 patients with heart failure with reduced EF (26.7% women). Images were analyzed offline, and the end point was all-cause mortality. During follow-up (median: 41 months) 163 patients (16.8 %) died. Women had significantly higher left ventricular (LV) EF (27.1% versus 25.4%,
P
=0.004), global longitudinal strain (−9.9% versus −8.9%,
P
<0.001), and global circumferential strain (−10.9% versus −9.7%,
P
<0.001). Moreover, women displayed higher E/e′ (14.4 versus 13.0,
P
=0.004), LV diastolic elastance (1.16 versus 0.75,
P
<0.001), and lower e′ (6.2 cm/s versus 6.9 cm/s,
P
<0.001). In women, tricuspid annular plane systolic excursion and LV isovolumetric relaxation time were significant predictors of outcome after multivariable adjustment (tricuspid annular plane systolic excursion: hazard ratio, 1.11; 95% CI, 1.04–1.18;
P
=0.003 per 1 mm decrease; isovolumetric relaxation time: hazard ratio, 1.07; 95% CI, 1.03–1.10;
P
=0.001 per 5 ms decrease). LVEF and global longitudinal strain were significant predictors in men (LVEF: hazard ratio, 0.94; 95% CI, 0.90–0.99;
P
=0.014 per 1% increase; global longitudinal strain: hazard ratio, 1.20; 95% CI, 1.04–1.38;
P
=0.013 per 1% decrease).

Conclusions:
Tricuspid annular plane systolic excursion and LV isovolumetric relaxation time provide prognostic information in women but not in men. Hence, in women with heart failure with reduced EF, right ventricular function, and LV diastolic function seem paramount in predicting mortality, whereas LV systolic function is more important in men.
Relationship Between Intravascular Ultrasound Guidance and Clinical Outcomes After Drug-Eluting Stents
Authors: Maehara Akiko , Mintz Gary S. , Witzenbichler Bernhard , Weisz Giora , Neumann Franz-Josef , Rinaldi Michael J. , Metzger D. Christopher , Henry Timothy D. , Cox David A. , Duffy Peter L. , Brodie Bruce R. , Stuckey Thomas D. , Mazzaferri Ernest L. , McAndrew Thomas , Généreux Philippe , Mehran Roxana , Kirtane Ajay J. , Stone Gregg W. 
Published: January 2019

Background
In the large-scale ADAPT-DES study (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents), drug-eluting stent implantation with intravascular ultrasound (IVUS) guidance was associated with a reduction in 1-year rates of stent thrombosis, myocardial infarction (MI), and major adverse cardiac events (cardiac death, MI, or stent thrombosis) compared with angiography guidance alone. We assessed whether the benefits of IVUS guidance were maintained, reduced, or increased at 2 years.

Methods and Results

ADAPT-DES was a prospective, multicenter, nonrandomized all-comers study of 8582 consecutive patients at 11 US and German sites designed to determine the frequency, timing, and correlates of adverse events after drug-eluting stents. Propensity-adjusted multivariable analysis was performed to examine the impact of IVUS guidance on 2-year outcomes. IVUS guidance (n=3361; 39%) compared with angiography guidance (n=5221; 61%) was associated with reduced 2-year adjudicated rates of (1) major adverse cardiac events (cardiac death, MI, or stent thrombosis; 4.9% versus 7.5%; adjusted hazard ratio, 0.72; 95% CI, 0.59–0.89;
P
=0.003), (2) definite/probable stent thrombosis (0.55% versus 1.16%; adjusted hazard ratio, 0.40; 95% CI, 0.22–0.73;
P
=0.003), and (3) MI (3.5% versus 5.6%; adjusted hazard ratio, 0.65; 95% CI, 0.51–0.83;
P
=0.0006). By landmark analysis, IVUS guidance compared with angiography guidance was also associated with significantly reduced rates of major adverse cardiac events, MI, stent thrombosis, and clinically driven target lesion revascularization between 1 and 2 years after drug-eluting stent implantation. The number needed to treat with IVUS guidance to prevent 1 major adverse cardiac event was reduced from 64 (42–137) at 1 year to 41 (29–69) at 2 years.

Conclusions
In ADAPT-DES, the early improvement in event-free survival after drug-eluting stent implantation with IVUS guidance compared with angiography guidance was further increased with longer term follow-up to 2 years.

Clinical Trial Registration

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT00638794.
Clinical Valve Thrombosis After Transcatheter Aortic Valve-in-Valve Implantation
Authors: Abdel-Wahab Mohamed , Simonato Matheus , Latib Azeem , Goleski Patrick J. , Allali Abdelhakim , Kaur Jatinderjit , Azadani Ali N. , Horlick Eric , Testa Luca , Orvin Katia , Kornowski Ran , Kass Malek , Don Creighton W. , Richardt Gert , Webb John G. , Dvir Danny 
Published: January 2019

Background
Limited data exist on clinical valve thrombosis after transcatheter aortic valve-in-valve (ViV) implantation. Our objective was to determine the incidence, timing, clinical characteristics, and treatment outcomes of patients diagnosed with clinical ViV thrombosis.

Methods and Results

Centers participating in the Valve-in-Valve International Data Registry were surveyed for thrombosis cases, and clinical valve thrombosis was defined based on a combination of the presence of new valve dysfunction and an imaging evidence of leaflet thrombosis. Three hundred ViV implantations were included. The surgical valve was stented in 86.3% and stentless in 13.7% of cases; and the transcatheter heart valve was self-expanding in 50%, balloon-expandable in 49%, and mechanically expanding in 1.0%. The incidence of clinical valve thrombosis was 7.6% (n=23), diagnosed at a median time of 101 days (interquartile range, 21–226) after the procedure. Fifteen patients (65%) presented with worsening symptoms and 21 (91%) with transvalvular mean gradient elevation. The mean gradient at the time of diagnosis (median 39 mm Hg; interquartile range, 30–44) was significantly higher than immediately post-ViV (13 mm Hg; interquartile range, 8–20.5;
P
<0.001) and was significantly reduced after oral anticoagulation therapy (17.5 mm Hg; interquartile range, 11–20.5;
P
<0.001). There were no deaths or strokes related to valve thrombosis. Factors associated with valve thrombosis were oral anticoagulation (odds ratio [95% confidence limits]: 0.067 [0.008–0.543],
P
=0.011), surgical valve true internal diameter indexed to body surface area (0.537 [0.331–0.873],
P
=0.012), and Mosaic or Hancock II stented porcine bioprostheses (4.01 [1.287–12.485],
P
=0.017).

Conclusions
Clinical valve thrombosis after transcatheter aortic ViV implantation is common, especially in patients not on oral anticoagulation. Although aortic ViV is commonly associated with elevated gradients, valve thrombosis should be ruled out if gradients increase compared with early postprocedural values. A higher incidence was observed after treatment of certain stented porcine surgical valve types, suggesting a specific adjustment of the adjunctive antithrombotic therapy in this subset of ViV patients.
Projected Future Cancer Risks in Children Treated With Fluoroscopy-Guided Cardiac Catheterization Procedures
Authors: Journy Neige , Dreuil Serge , Rage Estelle , De Zordo-Banliat François , Bonnet Damien , Hascoët Sebastien , Malekzadeh-Milani Sophie , Petit Jérôme , Laurier Dominique , Bernier Marie-Odile , Baysson Hélène 
Published: January 2019

Background
Children treated with cardiac catheterization procedures have now a long life expectancy and consequently potential long-term radiation-induced risks. We projected lifetime attributable risks (LARs) of cancer incidence from the most frequent procedures in pediatrics: atrial septal defect closure, patent ductus arteriosus occlusion, or pulmonary valvuloplasty.

Methods and Results
Organ equivalent doses were estimated for 1251 procedures performed in children aged ≤15 years at 2 reference catheterization centers in France from 2009 to 2013. Sex-specific LARs were projected in lifelong nonsmokers using extended Committee on Biological Effects of Ionizing Radiation VII risk models and considering various sources of risk projection uncertainties and dose variability (Radiation Risk Assessment Tool software). Median LARs ranged between 0.3 and 1.4 (atrial septal defect closure), 0.6 and 5.0 (patent ductus arteriosus occlusion), and 1.0 and 12.0 (pulmonary valvuloplasty) per 1000 procedures, depending on patient sex and age at treatment. These radiation-related risks would represent 0.4% to 6.0% of children’s total lifetime cancer risk. For the 10% of procedures (all types combined) with highest exposures, LARs reached 4.2 per 1000 (95% uncertainty interval, 0.8–13.1) in boys and 22.2 per 1000 (95% uncertainty interval, 7.4–45.6) in girls. In boys, lung cancer accounted for 70% to 80% of the projected LARs, whereas in girls it accounted for 20% to 60% and breast cancer for 30% to 80% of the excess risks, depending on the type of procedure and patient age.

Conclusions
Radiation exposure may lead to substantial radiation doses and increased cancer risks in some cases. This suggests the need for dose reporting to support recommendations for long-term surveillance and prevention strategies when it is necessary.
Periprocedural Myocardial Injury Predicts Short- and Long-Term Mortality in Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Michail Michael , Cameron James N. , Nerlekar Nitesh , Ihdayhid Abdul Rahman , McCormick Liam M. , Gooley Robert , Niccoli Giampaolo , Crea Filippo , Montone Rocco A. , Brown Adam J. 
Published: January 2019

Background:
The aim was to assess whether periprocedural myocardial injury (PPMI) predicts outcomes in patients undergoing transcatheter aortic valve replacement (TAVR). PPMI is a strong predictor of outcomes following coronary intervention, but its impact in the context of TAVR remains unclear. We performed a systematic review and meta-analysis to ascertain the association between PPMI and short- or long-term outcomes.

Methods and Results:

Electronic searches identified studies reporting PPMI following TAVR. Primary end point was 30-day all-cause mortality, with secondary end points, including 1-year all-cause mortality, neurological events, post-TAVR pacemaker implantation, and aortic regurgitation. Analyses were performed using random effects modeling and reported as summary odds ratio (OR) with 95% CI. Nine studies comprising 3442 patients (mean age 81.0±6.6 years, 51.2% female) were included. PPMI occurred in 25.5% of patients following TAVR. The pooled all-cause mortality at 30-days and 1-year was 5.2% and 18.6%, respectively. The occurrence of PPMI following TAVR was associated with significantly increased risk of both 30-day (OR, 4.23; CI, 1.95–9.19;
P
<0.001) and 1-year all-cause mortality (OR, 1.77; CI, 1.05–2.99;
P
<0.001). Similarly, PPMI was associated with post-TAVR neurological events (OR, 2.72; CI, 1.69–4.37;
P
<0.001) and post-TAVR permanent pacing (OR, 1.43; CI, 1.02–2.00;
P
=0.04) but not with a statistically significant increase in aortic regurgitation post-TAVR (OR, 1.39; CI, 0.93–2.08;
P
=0.11).

Conclusions:
PPMI is common following TAVR and is strongly associated with 30-day and 1-year mortality. Detection of PPMI has potential to identify TAVR patients at highest risk of subsequent adverse events.
Physician-Specific Practice Patterns About Discharge Readiness and Heart Failure Utilization Outcomes
Authors: Bhatt Anish B. , Cheeran Daniel D. , Shemisa Kamal , Roy Lonnie , Manz Boryana N. , Vigen Rebecca , de Lemos James A. , Das Sandeep R. 
Published: January 2019

Background:
Although hospitalization for acute decompensated heart failure (HF) is common and associated with poor outcomes and high costs, few evidence-based recommendations are available to guide patient management. Thus, management of inpatient HF remains heterogeneous. We evaluated if physician-specific self-reported HF practice patterns were associated with 2 important contributors to resource utilization: length of stay (LOS) and 30-day readmission.

Methods and Results:

A 5-point Likert scale survey was created to assess physician-specific HF discharge strategies and administered to all cardiologists and hospitalists at a single large academic teaching hospital. Practice patterns potentially impacting LOS and discharge decisions were queried, including use of physical examination findings, approaches to diuretic use and influence of kidney function. Likert scale responses are reported as means with any value above 3.00 considered more influential and any value below 3.00 considered less influential. Physician-specific LOS and 30-day readmission rates from July 1, 2015, to June 30, 2016, were extracted from the electronic record. We received survey responses and HF utilization metrics from 58 of 69 surveyed physicians (32 hospitalists and 26 cardiologists), encompassing 753 HF discharges over a 1-year period. Median LOS was 4.5 days (interquartile range, 4.0–5.8) and total 30-day readmission rate was 17.0% (128 unique readmissions). Physicians with below-median LOS placed less importance on observing a patient on oral diuretics for 24 hours before discharge (Likert 2.54 versus 3.30,
P
=0.01), reaching documented dry weight (Likert 2.93 versus 3.60,
P
=0.02), and complete resolution of dyspnea on exertion (Likert 3.64 versus 4.10,
P
=0.03) when compared with those above-median LOS. In contrast, no surveyed discharge practices were associated with physician-specific 30-day readmission.

Conclusions:
We identified specific inpatient HF discharge practice patterns that associated with shorter LOS but not with readmission rates. These may be targets for future interventions aimed at cost reduction; additional larger studies are needed for further exploration.
Body Weight Variability and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus
Authors: Bangalore Sripal , Fayyad Rana , DeMicco David A. , Colhoun Helen M. , Waters David D. 
Published: January 2019

Background:
Some studies have shown that body weight variability is a risk factor for cardiovascular events, but this has not been studied in subjects with diabetes mellitus.

Methods and Results:

We measured intraindividual variations in body weight from baseline and follow-up visits in 6408 subjects with type 2 diabetes mellitus from 3 clinical trials. The primary end point, any coronary event, was a composite of coronary heart disease death, myocardial infarction, resuscitated cardiac arrest, coronary revascularization, and unstable or new-onset angina. After adjustment for risk factors, baseline lipid levels, mean body weight, and weight change, each increase of 1 SD in body weight variability, measured as average successive variability and used as a time-dependent covariate, was associated with an increase in the risk of any coronary event (hazard ratio, 1.08; 95% CI, 1.01–1.14;
P
=0.017), major coronary event (hazard ratio, 1.12; 95% CI, 1.04–1.20;
P
=0.002), any cardiovascular event (hazard ratio, 1.08; 95% CI, 1.03–1.14;
P
=0.0015), and death (hazard ratio, 1.16; 95% CI, 1.10–1.22;
P
<0.0001). Among patients in the quintile with the highest variation in body weight compared with the lowest, the risk of any coronary event was 59% higher; the risk of a major coronary event, 82% higher; any cardiovascular event, 75% higher; death, 82% higher; myocardial infarction, 99% higher; and stroke, 92% higher in adjusted models. The results were consistent in a number of sensitivity analyses.

Conclusions:
Among subjects with type 2 diabetes mellitus, fluctuation in body weight was associated with higher mortality and a higher rate of cardiovascular events, independent of traditional cardiovascular risk factors.

Clinical Trial Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00327691 and NCT00327418.