bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of Spontaneous Reporting Systems to Detect Host‐Medication Interactions: Sex Differences in Oral Anti‐Diabetic Drug‐Associated Myocardial Infarction
Authors: Wang Shi‐Heng , Chen Wei J. , Hsu Le‐Yin , Chien Kuo‐Liong , Wu Chi‐Shin 
Published: December 2018

Background
Medical treatment should be tailored to an individual's characteristics to optimize treatment benefits. We examined whether case‐only analyses from spontaneous reporting systems can detect host‐medication interactions in oral antidiabetic drug‐associated myocardial infarction.

Methods and Results

Interaction between sex and use of oral antidiabetic drugs was mined among patients with myocardial infarction in the US Food and Drug Administration Adverse Event Reporting System from 2004 to 2014, including 55 718 males and 42 428 females. The odds ratio (
OR
) of multiplicative interactions was used to estimate sex‐drug interaction. Detected signs of these interactions were then validated by a nested case‐control study utilizing a healthcare record database, Taiwan's National Health Insurance Research Database, from 2001 to 2014, including 31 585 cases and 126 340 controls. In the US Food and Drug Administration Adverse Event Reporting System, a higher proportion of male than female patients used metformin (10.32% in males versus 7.82% in females) and sulfonylureas (4.75% in males versus 3.43% in females); after adjusting for patients’ pharmacy‐based chronic disease score, males had a higher risk of metformin‐associated (
OR
=1.07; 99% confidence interval, 1.00–1.14) and sulfonylureas‐associated (
OR
=1.21; 99% confidence interval, 1.10–1.33) myocardial infarction than females. Detected signs of sex‐drug interactions were validated in the National Health Insurance Research Database (
OR
for metformin=1.14; 99% confidence interval, 1.03–1.26; OR for sulfonylureas=1.13; 99% confidence interval, 1.02–1.25).

Conclusions
Males have a higher risk of metformin‐ and sulfonylureas‐associated myocardial infarction than females, which suggests that sex‐drug interactions are a key issue in diabetes mellitus treatment plan development. This case‐only approach using information from spontaneous reporting systems may be a potential tool for screening host‐medication interactions that cause adverse events.
Relationship Between Noninvasive Assessment of Lung Fluid Volume and Invasively Measured Cardiac Hemodynamics
Authors: Uriel Nir , Sayer Gabriel , Imamura Teruhiko , Rodgers Daniel , Kim Gene , Raikhelkar Jayant , Sarswat Nitasha , Kalantari Sara , Chung Ben , Nguyen Ann , Burkhoff Daniel , Abbo Aharon 
Published: December 2018

Background

Right heart catheterization is the gold standard in clinical practice for the assessment of cardiovascular hemodynamics, but it is an invasive procedure requiring expertise in both insertion and reading. Remote dielectric sensing (Re
DS
) is a noninvasive electromagnetic‐based technology intended to quantify lung fluid content.

Methods and Results

In this prospective single‐center study, Re
DS
readings were obtained in supine position just before right heart catheterization procedure in patients with heart failure. Agreement between Re
DS
and pulmonary artery wedge pressure (
PAWP
) was analyzed. Of all, 139 patients with heart failure received hemodynamic assessment and Re
DS
measurement. A good correlation was found between Re
DS
and
PAWP
measurement (
r
=0.492,
P
<0.001). Receiver operating characteristic analysis of the ability to identify a
PAWP
≥18 mm Hg resulted in a Re
DS
cutoff value of 34%, with an area under the curve of 0.848, a sensitivity of 90.7%, and a specificity of 77.1%. Overall, Re
DS
<34% carries a high negative predictive value of 94.9%.

Conclusions

Lung fluid content, as measured by Re
DS
, correlates well with
PAWP
. The high sensitivity and specificity and especially the high negative predictive value make Re
DS
a reliable noninvasive tool at the point of care, to rule out elevated
PAWP
in patients with heart failure and to help with medical management of patients with heart failure. Further studies are warranted to compare this tool with existing tests and to relate the findings to the clinical outcomes.
Reduction in Subtypes and Sizes of Myocardial Infarction With Ticagrelor in PEGASUS–TIMI 54
Authors: Bonaca Marc P. , Wiviott Stephen D. , Morrow David A. , Steg P. Gabriel , Hamm Christian , Bhatt Deepak L. , Storey Robert F. , Cohen Marc , Kuder Julia , Im KyungAh , Magnani Giulia , Budaj Andrzej , Nicolau José C. , Parkhomenko Alexander , López‐Sendón José , Dellborg Mikael , Diaz Rafael , Van de Werf Frans , Corbalán Ramón , Goudev Assen , Jensen Eva C. , Johanson Per , Braunwald Eugene , Sabatine Marc S. 
Published: December 2018

Background
Ticagrelor reduced cardiovascular death, myocardial infarction (MI), or stroke in patients with prior MI in PEGASUS‐TIMI 54 (Prevention of Cardiovascular Events [eg, Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin). MI can occur in diverse settings and with varying severity; therefore, understanding the types and sizes of MI events prevented is of clinical importance.

Methods and Results

MIs were adjudicated by a blinded clinical events committee and categorized by subtype and fold elevation of peak cardiac troponin over the upper limit of normal. A total of 1042 MIs occurred in 898 of the 21 162 randomized patients over a median follow‐up of 33 months. The majority of the MIs (76%) were spontaneous (Type 1), with demand MI (Type 2) and stent thrombosis (Type 4b) accounting for 13% and 9%, respectively; sudden death (Type 3), percutaneous coronary intervention–related (Type 4a) and coronary artery bypass graft–related (Type 5) each accounted for <1%. Half of MIs (520, 50%) had a peak troponin ≥10x upper limit of normal and 21% of MIs (220) had a peak troponin ≥100× upper limit of normal. A total of 21% (224) were ST‐segment–elevation MI STEMI. Overall ticagrelor reduced MI (4.47% versus 5.25%, hazard ratio 0.83, 95% confidence interval 0.72–0.95,
P
=0.0055). The benefit was consistent among the subtypes, including a 31% reduction in MIs with a peak troponin ≥100× upper limit of normal (hazard ratio 0.69, 95% confidence interval 0.53–0.92,
P
=0.0096) and a 40% reduction in ST‐segment elevation MI (hazard ratio 0.60, 95% confidence interval 0.46–0.78,
P
=0.0002).

Conclusions
In stable outpatients with prior MI, the majority of recurrent MIs are spontaneous and associated with a high biomarker elevation. Ticagrelor reduces the MI consistently among subtypes and sizes including large MIs and ST‐segment elevation MI.

Clinical Trial Registration

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01225562.
Jeopardized Myocardium Defined by Late Gadolinium Enhancement Magnetic Resonance Imaging Predicts Survival in Patients With Ischemic Cardiomyopathy: Impact of Revascularization
Authors: Kwon Deborah H. , Obuchowski Nancy A. , Marwick Thomas H. , Menon Venu , Griffin Brian , Flamm Scott D. , Hachamovitch Rory 
Published: December 2018

Background

The prognostic impact of jeopardized myocardium (
JM
) in patients with advanced ischemic cardiomyopathy (
ICM
) is unclear. We hypothesized that
JM
is an independent predictor of mortality in patients with advanced
ICM
.

Methods and Results

Patients with ICM who underwent cardiac magnetic resonance imaging between January 2002 and January 2013 were included in our study.
JM
was identified as a vascular territory with <50% myocardial scarring on cardiac magnetic resonance imaging and with >70% stenosis in a major coronary vessel that was not subsequently revascularized. A propensity score was developed for revascularization. A multivariable Cox proportional hazards model was used to evaluate the association of
JM
with all‐cause mortality. We evaluated 631 patients over a mean follow‐up of 5.1 years. Overall, 336 patients underwent subsequent revascularization during the follow‐up period, among whom 23% had remaining
JM
, while 295 patients were medically treated (57% with
JM
). There were 204 deaths (32%). On multivariable analysis,
JM
(hazard ratio, 1.88; 95% confidence interval, 1.38–2.55 [
P
<0.001]) was independently associated with all‐cause mortality after adjusting for multiple other factors. The risk associated with the presence of
JM
increased by 5% for every 10‐unit increase in left ventricular end‐systolic volume index.

Conclusions

JM
is an independent and incremental predictor of mortality in patients with advanced
ICM
. Patients undergoing revascularization with residual
JM
had similar risk of mortality compared with medically treated patients with
JM
. The risk associated with
JM
significantly increased in the presence of worsening adverse left ventricular remodeling. Cardiac magnetic resonance viability assessment may provide important risk stratification in patients with
ICM
.
Neonatal and Maternal Outcomes in Pregnant Women With Cardiac Disease
Authors: Owens Amanda , Yang Jie , Nie Lizhou , Lima Fabio , Avila Cecilia , Stergiopoulos Kathleen 
Published: December 2018

Background

Pregnant women with underlying heart disease (
HD
) are at increased risk for adverse maternal, obstetric, and neonatal outcomes.

Methods and Results

Inpatient maternal delivery admissions and linked neonatal stays for women with cardiomyopathy, adult congenital HD, pulmonary hypertension (
PH
), and valvular HD were explored utilizing the Statewide Planning and Research Cooperative System (New York), January 1, 2000, through December 31, 2014, with the
International Classification of Diseases, Ninth Revision
,
Clinical Modification (ICD‐9‐CM)
. Maternal major adverse cardiac events, neonatal adverse clinical events (
NACE
), and obstetric complications were recorded. Outcomes were compared using multiple logistic regression modeling. Among 2 284 044 delivery admissions, 3871 women had
HD
; 676 (17%) had cardiomyopathy, 1528 (40%) had valvular HD, 1367 (35%) had adult congenital HD, and 300 (8%) had
PH
. Major adverse cardiac events occurred in 16.1% of women with
HD
, with most in the cardiomyopathy (45.9%) and
PH
(25%) groups.
NACE
was more common in offspring of women with
HD
(18.4% versus 7.1%), with most in the cardiomyopathy (30.0%) and
PH
(25.0%) groups. Increased risk of
NACE
was noted for women with
HD
(odds ratio [
OR
]: 2.8; 95% confidence interval [
CI
], 2.5–3.0), with the highest risk for those with cardiomyopathy (
OR
: 5.9; 95%
CI
, 5.0–7.0) and
PH
(
OR
: 4.5; 95%
CI
, 3.4–5.9). Preeclampsia (
OR
: 5.1; 95%
CI
, 3.0–8.6), major adverse cardiac events (
OR
: 2.3; 95%
CI
, 1.8–2.9), preexisting diabetes mellitus (
OR
: 4.3; 95%
CI
, 1.5–12.3), and obstetric complications (
OR
: 2.9; 95%
CI
, 1.7–5.2) were independently associated with higher
NACE
risk.

Conclusions

Neonatal complications were higher in offspring of pregnant women with
HD
, particularly cardiomyopathy and
PH
. Preeclampsia, major adverse cardiac events, obstetric complications, and preexisting diabetes mellitus were independently associated with a higher risk of
NACE
.
Digoxin and Platelet Activation in Patients With Atrial Fibrillation: In Vivo and In Vitro Study
Authors: Pastori Daniele , Carnevale Roberto , Nocella Cristina , Bartimoccia Simona , Novo Marta , Cammisotto Vittoria , Piconese Silvia , Santulli Maria , Vasaturo Fortunata , Violi Francesco , Pignatelli Pasquale ,   Atherosclerosis in Atrial Fibrillation (ATHERO‐AF) Study Group
Published: December 2018

Background

Digoxin use was shown to be associated with an increased risk of cardiovascular events in atrial fibrillation (
AF
). We hypothesized that digoxin may affect cardiovascular risk by increasing platelet activation.

Methods and Results

Post hoc analysis of a prospective study of anticoagulated
patients with AF
. Patients were divided into 2 groups balanced for age, sex, and cardiovascular risk factors: digoxin users (n=132) and nonusers (n=388). Urinary excretion of 11‐dehydro‐thromboxane B
2
(TxB
2
), a marker of platelet activation, and serum digoxin concentration (
SDC
) were measured. In vitro experiments were performed on platelets from healthy subjects and AF patients, which were incubated with scalar doses of digoxin (0.6–2.4 ng/mL) with or without prestimulation with a sub‐threshold of collagen. Median 11‐dehydro‐TxB
2
was 105.0 (
interquartile range,
60.0–190.0) ng/mg creatinine, and median
SDC
was 0.65 (
interquartile range,
0.40–1.00) ng/mL. Urinary 11‐dehydro‐TxB
2
and
SDC
were correlated (
r
s
=0.350,
P
<0.001). Patients in the upper tertile of
SDC
showed higher 11‐dehydro‐TxB
2
compared with non–digoxin users (
P
=0.019). In vitro study showed an increased basal platelet activation in
patients with AF
compared with
healthy subjects
. Digoxin (2.4 ng/mL) induced calcium mobilization,
PAC
‐1 (procaspase‐activating compound 1) and platelet aggregation in
AF
patients but not in
healthy subjects
. After pretreatment with a sub‐threshold of collagen, digoxin dose‐dependent induced calcium mobilization, arachidonic acid release, TxB
2
biosynthesis,
PAC
‐1 and soluble platelet selectin expression, and platelet aggregation, which were inhibited by antibody against digoxin.

Conclusions

We found a significant in vivo correlation between
SDC
and platelet activation. Supratherapeutic
SDC
increased in vitro platelet aggregation via calcium‐related phospholipase A
2
phosphorylation. Our findings may have clinical implications for AF patients treated with digoxin.
Association of Oral Anticoagulant Type With Risk of Dementia Among Patients With Nonvalvular Atrial Fibrillation
Authors: Chen Nemin , Lutsey Pamela L. , MacLehose Richard F. , Claxton J'Neka S. , Norby Faye L. , Chamberlain Alanna M. , Bengtson Lindsay G. S. , O'Neal Wesley T. , Chen Lin Y. , Alonso Alvaro 
Published: December 2018

Background

Oral anticoagulants (
OACs
) in patients with atrial fibrillation (
AF
), in addition to reducing stroke risk, could also prevent adverse cognitive outcomes. The purpose of this study was to compare the risk of dementia incidence across patients with AF initiating different
OAC
s.

Methods and Results

We identified patients with nonvalvular
AF
initiating
OAC
s in 2
US
healthcare claim databases, MarketScan (2007–2015) and Optum Clinformatics (2009–2015). Dementia, comorbidities, and use of medications were defined on the basis of inpatient and outpatient claims. We performed head‐to‐head comparisons of warfarin, dabigatran, rivaroxaban, and apixaban in propensity score–matched cohorts. We calculated hazard ratios (
HR
s) and 95% confidence intervals (
CI
s) of incident dementia for each propensity score–matched cohort and meta‐analyzed database‐specific results. We analyzed 307 099 patients with AF from the MarketScan database and 161 346 from the Optum database, of which 6572 and 4391, respectively, had a diagnosis of incident dementia. The mean follow‐up of each cohort ranged between 0.7 and 2.2 years. Patients initiating direct OACs experienced lower rates of dementia than those initiating warfarin (dabigatran:
HR
, 0.85; 95%
CI
, 0.71–1.01; rivaroxaban:
HR
, 0.85; 95%
CI
, 0.76–0.94; apixaban:
HR
, 0.80; 95%
CI
, 0.65–0.97). There were no differences in rates of dementia comparing direct OAC user groups (dabigatran versus rivaroxaban:
HR
, 1.02; 95%
CI
, 0.79–1.32; dabigatran versus apixaban:
HR
, 0.92; 95%
CI
, 0.63–1.36; apixaban versus rivaroxaban:
HR
, 1.01; 95%
CI
, 0.86–1.19).

Conclusions

Patients with
AF
initiating direct OACs experienced lower rates of incident dementia than warfarin users. No obvious benefit was observed for any particular direct OAC in relation to dementia rates.
Inpatient and Outpatient Infection as a Trigger of Cardiovascular Disease: The ARIC Study
Authors: Cowan Logan T. , Lutsey Pamela L. , Pankow James S. , Matsushita Kunihiro , Ishigami Junichi , Lakshminarayan Kamakshi 
Published: December 2018

Background

Acute infections are known cardiovascular disease (
CVD
) triggers, but little is known regarding how
CVD
risk varies following inpatient versus outpatient infections. We hypothesized that in‐ and outpatient infections are associated with
CVD
risk and that the association is stronger for inpatient infections.

Methods and Results

Coronary heart disease (CHD) and ischemic stroke cases were identified and adjudicated in the ARIC (Atherosclerosis Risk in Communities Study). Hospital discharge diagnosis codes and Medicare claims data were used to identify infections diagnosed in in‐ and outpatient settings. A case‐crossover design and conditional logistic regression were used to compare in‐ and outpatient infections among
CHD
and ischemic stroke cases (14, 30, 42, and 90 days before the event) with corresponding control periods 1 and 2 years previously. A total of 1312 incident
CHD
cases and 727 incident stroke cases were analyzed. Inpatient infections (14‐day odds ratio [
OR
]=12.83 [5.74, 28.68], 30‐day
OR
=8.39 [4.92, 14.31], 42‐day
OR
=6.24 [4.02, 9.67], and 90‐day
OR
=4.48 [3.18, 6.33]) and outpatient infections (14‐day
OR
=3.29 [2.50, 4.32], 30‐day
OR
=2.69 [2.14, 3.37], 42‐day
OR
=2.45 [1.97, 3.05], and 90‐day
OR
=1.99 [1.64, 2.42]) were more common in all
CHD
case periods compared with control periods and inpatient infection was a stronger
CHD
trigger for all time periods (
P
<0.05). Inpatient infection was also a stronger stroke trigger with the difference borderline statistically significant (
P
<0.10) for the 42‐ and 90‐day time periods.

Conclusions

In‐ and outpatient infections are associated with
CVD
risk. Patients with an inpatient infection may be at particularly elevated
CVD
risk and should be considered potential candidates for
CVD
prophylaxis.
Low‐Voltage Type 1 ECG Is Associated With Fatal Ventricular Tachyarrhythmia in Brugada Syndrome
Authors: Nagase Satoshi , Kamakura Tsukasa , Kataoka Naoya , Wada Mitsuru , Yamagata Kenichiro , Ishibashi Kohei , Inoue Yuko Y. , Miyamoto Koji , Noda Takashi , Aiba Takeshi , Izumi Chisato , Noguchi Teruo , Yasuda Satoshi , Shimizu Wataru , Kamakura Shiro , Kusano Kengo 
Published: December 2018

Background

Epicardial mapping can reveal low‐voltage areas on the right ventricular outflow tract in patients with Brugada syndrome with several ventricular fibrillation (
VF
) episodes. A type 1
ECG
is associated with an abnormal electrogram on right ventricular outflow tract epicardium. This study investigated the clinical significance of the amplitude of type 1
ECGs
in patients with Brugada syndrome.

Methods and Results

In 209 patients with Brugada syndrome with a spontaneous type 1
ECG
(26 resuscitated from
VF
, 54 with syncope, and 129 asymptomatic), the amplitude of the
ECG
in leads exhibiting type 1 was measured among V1 to V3 leads positioned in the standard and upper 1 and 2 intercostal spaces. The number of ECG leads exhibiting type 1 did not differ among groups. The averaged amplitude of type 1
ECG
was, however, significantly smaller in the group resuscitated from
VF
than in the asymptomatic group (
P
<0.05). Moreover, the minimum amplitude of type 1
ECG
was significantly smaller in the group resuscitated from
VF
than in the group with syncope and the asymptomatic group (
P
<0.05 and
P
<0.01, respectively). During follow‐up (56±48 months),
VF
occurred in 29 patients. Kaplan‐Meier analysis revealed that patients with the minimum amplitude of type 1
ECG
lower than or at the median value had a higher incidence of
VF
(log‐rank test,
P
<0.01). In multivariate analysis, syncope, past
VF
episode, and minimum amplitude of type 1
ECG
≤0.8
mV
were independent predictors of
VF
events during follow‐up.

Conclusions

Low‐voltage type 1
ECG
is highly and independently related to fatal ventricular tachyarrhythmia in patients with Brugada syndrome.
Estradiol Treatment Initiated Early After Ovariectomy Regulates Myocardial Gene Expression and Inhibits Diastolic Dysfunction in Female Cynomolgus Monkeys: Potential Roles for Calcium Homeostasis and Extracellular Matrix Remodeling
Authors: Michalson Kristofer T. , Groban Leanne , Howard Timothy D. , Shively Carol A. , Sophonsritsuk Areepan , Appt Susan E. , Cline J. Mark , Clarkson Thomas B. , Carr J. Jeffrey , Kitzman Dalane W. , Register Thomas C. 
Published: December 2018

Background

Left ventricular (
LV
) diastolic dysfunction often precedes heart failure with preserved ejection fraction, the dominant form of heart failure in postmenopausal women. The objective of this study was to determine the effect of oral estradiol treatment initiated early after ovariectomy on
LV
function and myocardial gene expression in female cynomolgus macaques.

Methods and Results

Monkeys were ovariectomized and randomized to receive placebo (control) or oral estradiol at a human‐equivalent dose of 1 mg/day for 8 months. Monkeys then underwent conventional and tissue Doppler imaging to assess cardiac function, followed by transcriptomic and histomorphometric analyses of
LV
myocardium. Age, body weight, blood pressure, and heart rate were similar between groups. Echocardiographic mitral early and late inflow velocities, mitral annular velocities, and mitral E deceleration slope were higher in estradiol monkeys (all
P
<0.05), despite similar estimated
LV
filling pressure. MCP1 (monocyte chemoattractant protein 1) and
LV
collagen staining were lower in estradiol animals (
P
<0.05). Microarray analysis revealed differential myocardial expression of 40 genes (>1.2‐fold change; false discovery rate,
P
<0.05) in estradiol animals relative to controls, which implicated pathways associated with better calcium ion homeostasis and muscle contraction and lower extracellular matrix deposition (
P
<0.05).

Conclusions

Estradiol treatment initiated soon after ovariectomy resulted in enhanced
LV
diastolic function, and altered myocardial gene expression towards decreased extracellular matrix deposition, improved myocardial contraction, and calcium homeostasis, suggesting that estradiol directly or indirectly modulates the myocardial transcriptome to preserve cardiovascular function.