bluuebunny/crossref_metadata_2025 huggingface dataset:
Parametric Level Set-Based Multimaterial Topology Optimization of Heat Conduction Structures
Authors: Shen Yadong , Feng Jianhu
Published: September 2018

This paper presents a parametric level set-based method (PLSM) for multimaterial topology optimization of heat conduction structures with volume constraints. A parametric level set-based optimization model of heat conduction structures is built with multimaterial level set (MM-LS) model, which describes the boundaries of different materials by the combination of all level set functions. The heat dissipation efficiency which means the quadratic temperature gradient is conducted as the objective function. The adjoint method is utilized to calculate the sensitivities of the objective function with respect to expansion coefficients of the compactly supported radial basis functions (CSRBFs). The optimal configuration is achieved by updating the expansion coefficients gradually with the method of moving asymptotes (MMA). Several numerical examples are discussed to demonstrate effectiveness of the proposed method for multimaterial topology optimization of heat conduction structures.
Translating Evidence of HDL and Plaque Regression
Authors: Di Bartolo Belinda A. , Psaltis Peter J. , Bursill Christina A. , Nicholls Stephen J.
Published: September 2018

Considerable evidence from preclinical and population studies suggests that HDLs (high-density lipoproteins) possess atheroprotective properties. Reports from HDL infusion studies in animals and early clinical imaging trials reported evidence of plaque regression. These findings have stimulated further interest in developing new agents targeting HDL. However, the results of more recent imaging studies in the setting of high-intensity statin use have been disappointing. As the concept of plaque changes with HDL therapeutics evolves and imaging technology to evaluate these effects advances, there will become increasing opportunity to determine the effects of HDL agents on atherosclerotic plaque (Graphic Abstract).
Impact of PI3Kα (Phosphoinositide 3-Kinase Alpha) Inhibition on Hemostasis and Thrombosis
Authors: Laurent Pierre-Alexandre , Hechler Béatrice , Solinhac Romain , Ragab Ashraf , Cabou Cendrine , Anquetil Typhaine , Severin Sonia , Denis Cécile V. , Mangin Pierre H. , Vanhaesebroeck Bart , Payrastre Bernard , Gratacap Marie-Pierre
Published: September 2018

Objective—

PI3Kα (phosphoinositide 3-kinase alpha) is a therapeutic target in oncology, but its role in platelets and thrombosis remains ill characterized. In this study, we have analyzed the role of PI3Kα in vitro, ex vivo, and in vivo in 2 models of arterial thrombosis.

Approach and Results—

Using mice selectively deficient in p110α in the megakaryocyte lineage and isoform-selective inhibitors, we confirm that PI3Kα is not mandatory but participates to thrombus growth over a collagen matrix at arterial shear rate. Our data uncover a role for PI3Kα in low-level activation of the GP (glycoprotein) VI-collagen receptor by contributing to ADP secretion and in turn full activation of PI3Kβ and Akt/PKB (protein kinase B). This effect was no longer observed at high level of GP VI agonist concentration. Our study also reveals that over a vWF (von Willebrand factor) matrix, PI3Kα regulates platelet stationary adhesion contacts under arterial flow through its involvement in the outside-in signaling of vWF-engaged α
IIb
β
3
integrin. In vivo, absence or inhibition of PI3Kα resulted in a modest but significant decrease in thrombus size after superficial injuries of mouse mesenteric arteries and an increased time to arterial occlusion after carotid lesion, without modification in the tail bleeding time. Considering the more discrete and nonredundant role of PI3Kα compared with PI3Kβ, selective PI3Kα inhibitors are unlikely to increase the bleeding risk at least in the absence of combination with antiplatelet drugs or thrombopenia.

Conclusions—

This study provides mechanistic insight into the role of PI3Kα in platelet activation and arterial thrombosis.
Epicardial Substrate as a Target for Radiofrequency Ablation in an Experimental Model of Early Repolarization Syndrome
Authors: Yoon Namsik , Patocskai Bence , Antzelevitch Charles
Published: September 2018

Background:

Early repolarization syndrome (ERS) is an inherited cardiac arrhythmia syndrome associated with sudden cardiac death. Approaches to therapy are currently very limited. This study probes the mechanisms underlying the electrocardiographic and arrhythmic manifestation of experimental models of ERS and of the ameliorative effect of radiofrequency ablation.

Methods:

Action potentials, bipolar electrograms, and transmural pseudo-ECGs were simultaneously recorded from coronary-perfused canine left ventricular wedge preparations (n=11). The
I
to
agonist NS5806 (7–10 μmol/L), calcium channel blocker verapamil (3 μmol/L), and acetylcholine (1–3 μmol/L) were used to pharmacologically mimic the effects of genetic defects associated with ERS.

Results:

The provocative agents induced prominent J waves in the ECG secondary to accentuation of the action potential notch in epicardium but not endocardium. Bipolar recordings displayed low-voltage fractionated potentials in epicardium because of temporal and spatial variability in appearance of the action potential dome. Concealed phase 2 reentry developed when action potential dome was lost at some epicardial sites but not others, appearing in the bipolar electrogram as discrete high-frequency spikes. Successful propagation of the phase 2 reentrant beat precipitated ventricular tachycardia/ventricular fibrillation. Radiofrequency ablation of the epicardium destroyed the cells displaying abnormal repolarization and thus suppressed the J waves and the development of ventricular tachycardia/ventricular fibrillation in 6/6 preparations.

Conclusions:

Our findings suggest that low-voltage fractionated electrical activity and high-frequency late potentials recorded from the epicardial surface of the left ventricle can identify regions of abnormal repolarization responsible for ventricular tachycardia/ventricular fibrillation in ERS and that radiofrequency ablation of these regions in left ventricular epicardium can suppress ventricular tachycardia/ventricular fibrillation by destroying regions of ER.
Length of Stay and Discharge Disposition After Transcatheter Versus Surgical Aortic Valve Replacement in the United States
Authors: Arora Sameer , Strassle Paula D. , Kolte Dhaval , Ramm Cassandra J. , Falk Kristine , Jack Godly , Caranasos Thomas G. , Cavender Matthew A. , Rossi Joseph S. , Vavalle John P.
Published: September 2018

Background:

As transcatheter aortic valve replacement (TAVR) extends its reach to lower surgical risk patients, the differences between resource utilization for TAVR and surgical AVR (SAVR) will become increasingly important.

Methods and Results:

AVR procedures between January 2012 and September 2015 at hospitals performing TAVR were identified using the National Inpatient Sample databases. Adults aged ≥50 years with aortic stenosis who underwent isolated TAVR or SAVR were eligible for inclusion. Standardized morbidity ratio weights were calculated using patient demographics, comorbidities, and hospital characteristics. Weighted linear and generalized logistic regression models were used to estimate the effect of undergoing TAVR, compared with undergoing SAVR, on length of stay (LOS) and discharge disposition. In TAVR-performing hospitals, 7266 (40%) patients underwent TAVR (6107 endovascular approach and 1159 transapical approach), while 10 833 (60%) underwent isolated SAVR. Patients undergoing TAVR were older, more likely to be female, and had more comorbidities. From 2012 to 2015, average LOS declined for both TAVR (6.3 days to 4.6 days;
P
<0.0001) and SAVR (7.5 days to 6.8 days;
P
<0.0001), with greater reduction in the TAVR group (
P
<0.0001). An increase in home/home health discharge was noted with TAVR (67.7%–77.4%;
P
<0.0001) but not with SAVR (76.8%–79.5%;
P
=0.25). After standardizing, patients undergoing TAVR had significantly shorter LOS (change in estimate, −2.93, 95% CI, −3.26 to −2.60) and lower incidence of transfer to skilled nursing facility (odds ratio, 0.45; 95% CI, 0.40–0.51) but no difference in in-hospital mortality (odds ratio, 0.85; 95% CI, 0.61–1.20) compared with if they had undergone SAVR. As compared with SAVR, patients who had TAVR performed via an endovascular approach had shorter LOS and lower rates of skilled nursing facility transfer, whereas in the transapical cohort, LOS, and skilled nursing facility transfer were similar to SAVR.

Conclusions:

As compared with if they undergo SAVR, patients undergoing TAVR (by a nontransapical approach) had a shorter LOS and higher likelihood of home discharge, as opposed to skilled nursing facility. From 2012 to 2015, there was a greater trend towards a reduction of LOS and more home discharges among TAVR, as opposed to SAVR. These data have important implications in the era of constrained resources with a growing emphasis on reducing health care costs.
The Effect of Medicare Accountable Care Organizations on Early and Late Payments for Cardiovascular Disease Episodes
Authors: Sinha Shashank S. , Moloci Nicholas M. , Ryan Andrew M. , Markovitz Adam A. , Colla Carrie H. , Lewis Valerie A. , Hollenbeck Brent K. , Nallamothu Brahmajee K. , Hollingsworth John M.
Published: September 2018

Background:

Initial evaluations of the Pioneer and Shared Savings Programs have shown modest savings associated with care receipt in a Medicare accountable care organization (ACO). Whether these savings are affected by disease chronicity and the mechanisms through which they occur are unclear. In this context, we examined the association between Medicare ACO implementation and episode spending for 2 different cardiovascular conditions.

Methods and Results:

We analyzed a 20% sample of national Medicare data, identifying fee-for-service beneficiaries aged ≥65 years admitted for acute myocardial infarction (AMI) or congestive heart failure (CHF) between January 2010 and October 2014. We distinguished admissions to hospitals participating in a Medicare ACO from those to hospitals that were not. We calculated 365-day, price-standardized episode spending made on behalf of these beneficiaries, differentiating between early (index admission to 90 days postdischarge) and late payments (91-365 days postdischarge). Using an interrupted time series design, we fit longitudinal multivariable models to estimate the association between hospital ACO participation and episode spending. Our study included 153 476 beneficiaries admitted for AMI to 401 ACO participating hospitals and 2597 nonparticipating hospitals and 260 420 beneficiaries admitted for CHF to 412 ACO participating hospitals and 2796 nonparticipating hospitals. On multivariable analysis, admission to an ACO participating hospital was not associated with changes in early episode spending (AMI, $95 per beneficiary; 95% CI, −$481 to $671; CHF, $158; 95% CI, −$290 to $605). However, it was associated with significant reductions in late episode spending for both cohorts (AMI, −$680; 95% CI, −$1348 to −$11; CHF, −$889; 95% CI, −$1465 to −$313).

Conclusions:

For beneficiaries with AMI or CHF, admission to ACO participating hospitals was not associated with changes in early episode spending, but it was associated with significant savings during the late episode. ACO effects on late episode spending may complement other value-based payment reforms that target the early episode.
Population-Based Assessment of the Incidence of Aortic Dissection, Intramural Hematoma, and Penetrating Ulcer, and Its Associated Mortality From 1995 to 2015
Authors: DeMartino Randall R. , Sen Indrani , Huang Ying , Bower Thomas C. , Oderich Gustavo S. , Pochettino Alberto , Greason Kevin , Kalra Manju , Johnstone Jill , Shuja Fahad , Harmsen W. Scott , Macedo Thanila , Mandrekar Jay , Chamberlain Alanna M. , Weiss Salome , Goodney Philip P. , Roger Veronique
Published: September 2018

Background

Aortic syndromes (ASs), including aortic dissection, intramural hematoma, and penetrating aortic ulcer, carry significant acute and long-term morbidity and mortality. However, the contemporary incidence and outcomes of AS are unknown.

Methods and Results

We used the Rochester Epidemiology Project record linkage system to identify all Olmsted County, MN, residents with AS (1995–2015). Diagnostic imaging, medical records, and death certificates were reviewed to confirm the diagnosis and AS subtype. Age- and sex-adjusted incidence rates were estimated using annual county-level census data. Survival for patients with AS was compared with age- and sex-matched controls using Cox regression to adjust for comorbid conditions. We identified 133 patients with AS (77, aortic dissection; 21, intramural hematoma; and 35, penetrating aortic ulcer). Average age was 71.8 years (SD=14.1), and 57% were men. The age- and sex-adjusted incidence was 7.7 per 100 000 person-years, was higher for men than women (10.2 versus 5.7 per 100 000 person-years), and increased with age. Among subtypes, the incidence of aortic dissection was highest (4.4 per 100 000 person-years), whereas the incidence of penetrating aortic ulcer and intramural hematoma was lower (2.1 and 1.2 per 100 000 person-years). Overall, the incidence of AS was stable over time (
P
trend=0.33), although the incidence of penetrating aortic ulcer seemed to increase from 0.6 to 2.6 per 100 000 person-years (
P
=0.008) with variability over the study interval. Patients with AS had more than twice the mortality rate at 5, 10, and 20 years when compared with population-based controls (5-, 10-, and 20-year mortality 39%, 57%, and 91% versus 18%, 41%, and 66%; overall adjusted mortality hazards ratio=2.1;
P
<0.001). Survival was lower than expected up to 90 days after AS diagnosis and did not differ significantly by subtype or by 5-year strata of diagnosis.

Conclusions

Overall, the incidence of aortic dissection and intramural hematoma has remained stable since 1995, despite the decline noted for other cardiovascular disease. AS confers increased early and long-term mortality that has not changed. These data highlight the need to improve long-term care to impact the prognosis of this patient group.
Prevalence of Hypertension and Cardiovascular Risk According to Blood Pressure Thresholds Used for Diagnosis
Authors: Lamprea-Montealegre Julio A. , Zelnick Leila R. , Hall Yoshio N. , Bansal Nisha , de Boer Ian H.
Published: September 2018

We sought to estimate the prevalence of hypertension and characteristics of hypertensive adults in the United States according to blood pressure (BP) thresholds used for diagnosis and estimate their associated cardiovascular disease risk. Analyses included adults 20 years of age or older in the 2013 to 2014 National Health and Nutrition Examination Survey (N=5389) and enrolled participants in SPRINT (Systolic Blood Pressure Intervention Trial; N=9361) and the ACCORD-BP trial (Action to Control Cardiovascular Risk in Diabetes-Blood Pressure; N=4733). In the National Health and Nutrition Examination Survey, prevalence estimates incorporated the probability of observing elevated BP on 2 separate occasions. Using the new BP thresholds of ≥130/80 mm Hg, ≈24 million new American adults would be diagnosed as having hypertension and 4.3 million would be recommended to start antihypertensive medications. These individuals would have a lower mean atherosclerotic cardiovascular disease risk (17%) than participants in SPRINT and ACCORD-BP (22% and 27%) and would be less likely to have prevalent cardiovascular disease (9% versus 17% and 34%). In SPRINT and ACCORD-BP, only a minority (9% and 13%) of participants were not on antihypertensive medications at baseline, and rates of incident cardiovascular disease in these participants were substantially lower compared with those on baseline BP medications. We conclude that adopting the American College of Cardiology/American Heart Association guidelines would lead to a substantial increase in the prevalence of hypertension and in the number of American adults recommended to start antihypertensive medications. These individuals would have a substantially lower cardiovascular risk than most participants previously studied in 2 large BP trials.
Cardiovascular and Mortality Outcomes in the Elderly With Impaired Cardiac and Pulmonary Function: The Cardiovascular Health Study (CHS)
Authors: Waheed Salman , Chaves Paulo H. M. , Gardin Julius M. , Cao Jie Jane
Published: September 2018

Background

Impaired pulmonary function (
IPF
) and left ventricular systolic dysfunction (
LVSD
) are prevalent in the elderly and are associated with significant morbidity and mortality. The main objectives of this study were to examine the relative impact and joint association of
IPF
and
LVSD
with heart failure, cardiovascular mortality and all‐cause mortality, and their impact on risk classification using a continuous net reclassification index.

Methods and Results

We followed 2342 adults without prevalent cardiovascular disease (mean age, 76 years) from the Cardiovascular Health Study for a median of 12.6 years.
LVSD
was defined as
LV
ejection fraction <55%.
IPF
was defined as: forced expiratory volume in 1 second:forced vital capacity <70%, and predicted forced expiratory volume in 1 second <80%. Outcomes included heart failure hospitalization, cardiovascular mortality, all‐cause mortality, and composite outcome.
LVSD
was detected in 128 subjects (6%),
IPF
in 441 (19%) and both in 38 (2%). Compared to those without
LVSD
or
IPF
, there was a significantly increased cardiovascular risk for groups of
LVSD
only,
IPF
only, and
LVSD
plus
IPF
, adjusted hazard ratio (95%
CI
) 2.1 (1.5–3.0), 1.7 (1.4–2.1), and 3.2 (2.0–5.1) for
HF
; 1.8 (1.2–2.6), 1.4 (1.1–1.8), and 2.8 (1.7–4.7) for cardiovascular mortality; 1.3 (1.0–1.8), 1.7 (1.4–1.9), and 2.1 (1.5–3.0) for all‐cause mortality, and 1.6 (1.3–2.1), 1.7 (1.5–1.9), and 2.4 (1.7–3.3) for composite outcome, respectively. Risk classification improved significantly for all outcomes when
IPF
was added to the adjusted model with
LVSD
or
LVSD
to
IPF
.

Conclusions

While risk of cardiovascular outcomes was the highest among elderly with both
LVSD
and
IPF
, risk was comparable between subjects with
IPF
alone and those with
LVSD
alone. This observation, combined with improved risk classification by adding
IPF
to
LVSD
or
LVSD
to
IPF
, underscore the importance of comprehensive heart and lung evaluation in cardiovascular outcome assessment.
Disruption of VEGF Mediated Flk‐1 Signaling Leads to a Gradual Loss of Vessel Health and Cardiac Function During Myocardial Infarction: Potential Therapy With Pellino‐1
Authors: Thirunavukkarasu Mahesh , Selvaraju Vaithinathan , Joshi Mandip , Coca‐Soliz Vladimir , Tapias Leonidas , Saad IbnalWalid , Fournier Craig , Husain Aaftab , Campbell Jacob , Yee Siu‐Pok , Sanchez Juan A. , Palesty J. Alexander , McFadden David W. , Maulik Nilanjana
Published: September 2018

Background

The present study demonstrates that the ubiquitin E3 ligase, Pellino‐1 (Peli1), is an important angiogenic molecule under the control of vascular endothelial growth factor (VEGF) receptor 2/Flk‐1. We have previously reported increased survivability of ischemic skin flap tissue by adenovirus carrying Peli1 (Ad‐Peli1) gene therapy in Flk‐1
+/−
mice.

Methods and Results

Two separate experimental groups of mice were subjected to myocardial infarction (
MI
) followed by the immediate intramyocardial injection of adenovirus carrying LacZ (Ad‐LacZ) (1×10
9
 pfu) or Ad‐Peli1 (1×10
9
 pfu). Heart tissues were collected for analyses. Compared with wild‐type (
WTMI
) mice, analysis revealed decreased expressions of Peli1, phosphorylated (p‐)Flk‐1, p‐Akt, p‐
eNOS
, p‐
MK
2, p‐IκBα, and
NF
‐κB and decreased vessel densities in Flk‐1
+/−
mice subjected to
MI
(Flk‐1
+/−
MI
). Mice (
CD
1) treated with Ad‐Peli1 after the induction of
MI
showed increased β‐catenin translocation to the nucleus, connexin 43 expression, and phosphorylation of Akt,
eNOS
,
MK
2, and IκBα, that was followed by increased vessel densities compared with the Ad‐LacZ–treated group. Echocardiography conducted 30 days after surgery showed decreased function in the Flk1
+/−
MI
group compared with
WTMI
, which was restored by Ad‐Peli1 gene therapy. In addition, therapy with Ad‐Peli1 stimulated angiogenic and arteriogenic responses in both
CD
1 and Flk‐1
+/−
mice following
MI
. Ad‐Peli1 treatment attenuated cardiac fibrosis in Flk‐1
+/−
MI
mice. Similar positive results were observed in
CD
1 mice subjected to
MI
after Ad‐Peli1 therapy.

Conclusion

Our results show for the first time that Peli1 plays a unique role in salvaging impaired collateral blood vessel formation, diminishes fibrosis, and improves myocardial function, thereby offering clinical potential for therapies in humans to mend a damaged heart following
MI
.
Incidence of Long‐Term Structural Valve Dysfunction and Bioprosthetic Valve Failure After Transcatheter Aortic Valve Replacement
Authors: Barbanti Marco , Costa Giuliano , Zappulla Paolo , Todaro Denise , Picci Andrea , Rapisarda Giulia , Di Simone Emanuela , Sicuso Rita , Buccheri Sergio , Gulino Simona , Pilato Gerlando , La Spina Ketty , D'Arrigo Paolo , Valvo Roberto , Indelicato Antonino , Giannazzo Daniela , Immè Sebastiano , Tamburino Claudia , Patanè Martina , Sgroi Carmelo , Giuffrida Angelo , Trovato Danilo , Monte Ines Paola , Deste Wanda , Capranzano Piera , Capodanno Davide , Tamburino Corrado
Published: September 2018

Background

Long‐term data on durability of currently available transcatheter heart valves are sparse. We sought to assess the incidence of long‐term (8‐year) structural valve dysfunction and bioprosthetic valve failure in a cohort of patients with transcatheter aortic valve replacement (
TAVR
) who reached at least 5‐year follow‐up.

Methods and Results

Consecutive patients with at least 5‐year follow‐up available undergoing
TAVR
from June 4, 2007 to March 30, 2012 were included.
Structural valve dysfunction
and bioprosthetic valve failure were defined according to newly standardized European Association of Percutaneous Cardiovascular Interventions/
European Society of Cardiology/European Association for Cardio‐Thoracic Surgery
criteria and reported as cumulative incidence function to account for the competing risk of death. A total of 288 consecutive patients with a mean age of 80.7±5.3 years and with a mean
Society of Thoracic Surgery
mortality score of 8.1±5.1% were analyzed. Survival rate at 8 years was 29.8%. Mean pressure gradients decreased from 53.3±15.9 mm Hg (pre‐
TAVR
) to 10.5±4.5 mm Hg (in‐hospital post‐
TAVR
) (
P
<0.001). There was a small, not significant, increase in the transaortic gradient throughout follow‐up.
Bioprosthetic valve failure
was observed in a total of 11 patients (8‐year cumulative incidence function: 4.51%; 95% confidence interval
,
1.95%–8.76%). Severe and moderate
structural valve dysfunctions
were reported in 7 patients (8‐year
cumulative incidence function:
2.39%; 95%
confidence interval,
0.77%–5.71%) and 13 patients (8‐year
cumulative incidence function:
5.87%; 95%
confidence interval
, 3.06%–9.96%), respectively. Aortic valve reintervention (redo
TAVR
) was successfully performed in 2 patients (0.7%) presenting with symptomatic severe restenosis and intraprosthetic regurgitation subsequent to endocarditis.

Conclusions

In an aged population of patients with symptomatic severe
aortic stenosis
treated with first‐generation bioprostheses,
TAVR
was associated with a survival rate of 30% but low rates of bioprosthetic valve failure and structural valve dysfunction at 8 years.
Mitochondrial‐Mediated Oxidative Ca
2+
/Calmodulin‐Dependent Kinase II Activation Induces Early Afterdepolarizations in Guinea Pig Cardiomyocytes: An In Silico Study
Authors: Yang Ruilin , Ernst Patrick , Song Jiajia , Liu Xiaoguang M. , Huke Sabine , Wang Shuxin , Zhang Jianyi Jay , Zhou Lufang
Published: September 2018

Background

Oxidative stress–mediated Ca
2+
/calmodulin‐dependent protein kinase
II
(Ca
MKII)
phosphorylation of cardiac ion channels has emerged as a critical contributor to arrhythmogenesis in cardiac pathology. However, the link between mitochondrial‐derived reactive oxygen species (md
ROS
) and increased Ca
MKII
activity in the context of cardiac arrhythmias has not been fully elucidated and is difficult to establish experimentally.

Methods and Results

We hypothesize that pathological md
ROS
can cause erratic action potentials through the oxidation‐dependent Ca
MKII
activation pathway. We further propose that Ca
MKII
‐dependent phosphorylation of sarcolemmal slow Na
+
channels alone is sufficient to elicit early afterdepolarizations. To test the hypotheses, we expanded our well‐established guinea pig cardiomyocyte
e
xcitation‐
c
ontraction coupling,
m
itochondrial
e
nergetics, and

R
OS

‐
i
nduced‐

R
OS

‐
r
elease model by incorporating oxidative Ca
MKII
activation and Ca
MKII
‐dependent Na
+
channel phosphorylation in silico. Simulations show that md
ROS
mediated‐Ca
MKII
activation elicits early afterdepolarizations by augmenting the late Na
+
currents, which can be suppressed by blocking L‐type Ca
2+
channels or Na
+
/Ca
2+
exchangers. Interestingly, we found that oxidative Ca
MKII
activation–induced early afterdepolarizations are sustained even after md
ROS
has returned to its physiological levels. Moreover, mitochondrial‐targeting antioxidant treatment can suppress the early afterdepolarizations, but only if given in an appropriate time window. Incorporating concurrent md
ROS
‐induced ryanodine receptors activation further exacerbates the proarrhythmogenic effect of oxidative Ca
MKII
activation.

Conclusions

We conclude that oxidative Ca
MKII
activation–dependent Na channel phosphorylation is a critical pathway in mitochondria‐mediated cardiac arrhythmogenesis.
Coronary Thermodilution Waveforms After Acute Reperfused ST‐Segment–Elevation Myocardial Infarction: Relation to Microvascular Obstruction and Prognosis
Authors: Yew Shu Ning , Carrick David , Corcoran David , Ahmed Nadeem , Carberry Jaclyn , Teng Yue May Vannesa , McEntegart Margaret , Petrie Mark C. , Eteiba Hany , Lindsay Mitchell , Hood Stuart , Watkins Stuart , Davie Andrew , Mahrous Ahmed , Mordi Ify , Ford Ian , Oldroyd Keith G. , Berry Colin
Published: September 2018

Background

Invasive measures of microvascular resistance in the culprit coronary artery have potential for risk stratification in acute ST‐segment–elevation myocardial infarction. We aimed to investigate the pathological and prognostic significance of coronary thermodilution waveforms using a diagnostic guidewire.

Methods and Results

Coronary thermodilution was measured at the end of percutaneous coronary intervention, (PCI) and contrast‐enhanced cardiac magnetic resonance imaging (MRI) was intended on day 2 and 6 months later to assess left ventricular (LV) function and pathology. All‐cause death or first heart failure hospitalization was a pre‐specified outcome (median follow‐up duration 1469 days). Thermodilution recordings underwent core laboratory assessment. A total of 278 patients with acute ST‐segment elevation myocardial infarction EMI (72% male, 59±11 years) had coronary thermodilution measurements classified as narrow unimodal (n=143 [51%]), wide unimodal (n=100 [36%]), or bimodal (n=35 [13%]). Microvascular obstruction and myocardial hemorrhage were associated with the thermodilution waveform pattern (
P
=0.007 and 0.011, respectively), and both pathologies were more prevalent in patients with a bimodal morphology. On multivariate analysis with baseline characteristics, thermodilution waveform status was a multivariable associate of microvascular obstruction (odds ratio [95% confidence interval]=5.29 [1.73, 16.22];,
P
=0.004) and myocardial hemorrhage (3.45 [1.16, 10.26];
P
=0.026), but the relationship was not significant when index of microvascular resistance (IMR) >40 or change in index of microvascular resistance (5 per unit) was included. However, a bimodal thermodilution waveform was independently associated with all‐cause death and hospitalization for heart failure (odds ratio [95% confidence interval]=2.70 [1.10, 6.63];
P
=0.031), independent of index of microvascular resistance>40, ST‐segment resolution, and TIMI (Thrombolysis in Myocardial Infarction) Myocardial Perfusion Grade.

Conclusions

The thermodilution waveform in the culprit coronary artery is a biomarker of prognosis and may be useful for risk stratification immediately after reperfusion therapy.
Dual Healthcare System Use During Episodes of Acute Care Heart Failure Associated With Higher Healthcare Utilization and Mortality Risk
Authors: Axon R. Neal , Gebregziabher Mulugeta , Everett Charles J. , Heidenreich Paul , Hunt Kelly J.
Published: September 2018

Background

Individuals receiving cross‐system care (dual users) have higher rates of healthcare utilization and worse outcomes for heart failure (
HF
) and other conditions. Individuals can be dual users or single‐system users at different times, though, and little is known about utilization and mortality within discrete episodes of care.

Methods and Results

A retrospective cohort of 3439 patients with 5231 discrete episodes of
HF
exacerbation were identified between 2007 and 2011. Episodes encompassed the period from 2 weeks before an initial
HF
emergency department (
ED
) visit or hospitalization, included any acute care visits within 30 days after initial visit, and ended 30 days after the last acute care visit in the episode chain. All‐cause and
HF
‐specific
ED
visits and hospitalization within 30 days of index visit were analyzed using generalized estimating equations with robust variance. Hazard for death within episodes of acute illness was analyzed using Cox proportional hazards models. In adjusted analyses, dual use acute
HF
episodes were associated with higher odds of all‐cause
ED
visits (odds ratio 1.61, 95% confidence interval [
CI
], 1.33, 1.95),
HF
‐specific
ED
visits, (odds ratio 1.54, 95%
CI
, 1.12, 2.13), all‐cause hospitalization (odds ratio 1.89, 95%
CI
, 1.50, 2.38), and
HF
‐specific hospitalization (odds ratio 1.62, 95%
CI
, 1.15–2.30) as compared with Veterans Health Administration–only episodes of acute
HF
care. Dual use episodes of care were associated with higher hazard for mortality (hazard ratio=1.52, 95%
CI
1.07, 2.16) as compared with all–Veterans Health Administration episodes of care.

Conclusions

Episodes of acute
HF
care spanning across healthcare systems appear to be associated with higher risk of subsequent
ED
visits, hospitalization, and mortality.
Postinfarction Hearts Are Protected by Premature Senescent Cardiomyocytes Via GATA4‐Dependent CCN1 Secretion
Authors: Cui Sumei , Xue Li , Yang Feihong , Dai Shuai , Han Ziqi , Liu Kai , Liu Baoshan , Yuan Qiuhuan , Cui Zhaoqiang , Zhang Yun , Xu Feng , Chen Yuguo
Published: September 2018

Background

Stress‐induced cell premature senescence participates in a variety of tissue and organ remodeling by secreting such proteins as proinflammatory cytokines, chemokines, and growth factors. However, the role of cardiomyocyte senescence in heart remodeling after acute myocardial infarction has not been thoroughly elucidated to date. Therefore, we sought to clarify the impact of premature myocardial senescence on postinfarction heart function.

Methods and Results

Senescence markers, including p16

INK

4a
, p21

CIP

1/

WAF

1
, and
SA
‐β‐gal staining, were analyzed in several heart disease models by immunostaining. Both postinfarction mouse hearts and ischemic human myocardium demonstrated increased senescence markers. Additionally, senescence‐related secretory phenotype was activated after acute myocardial infarction, which upregulated senescence‐related secretory phenotype factors, including
CCN
family member 1 (
CCN
1), interleukin‐1α, tumor necrosis factor α, and monocyte chemoattractant protein‐1. In vivo, a tail vein injection of
AAV
9‐
Gata4
‐sh
RNA
significantly attenuated senescence‐related secretory phenotype secretion and aggravated postinfarction heart dysfunction. Furthermore, among activated senescence‐related secretory phenotype factors,
CCN
1 administration reduced myofibroblast viability in vitro and rescued the deleterious effect of
AAV
9‐
Gata4
‐sh
RNA
in vivo.

Conclusions

Myocardial premature senescence was observed in the ischemic hearts and improved postinfarction heart function, partly through the GATA‐binding factor 4‐
CCN
1 pathway.
Systematic Review of Studies That Have Evaluated Screening Tests in Relatives of Patients Affected by Nonsyndromic Thoracic Aortic Disease
Authors: Mariscalco Giovanni , Debiec Radoslaw , Elefteriades John A. , Samani Nilesh J. , Murphy Gavin J.
Published: September 2018

Background

Nonsyndromic thoracic aortic diseases (
NS
‐
TADs
) are often silent entities until they present as life‐threatening emergencies. Despite familial inheritance being common, screening is not the current standard of care in
NS
‐
TAD
s. We sought to determine the incidence of aortic diseases, the predictive accuracy of available screening tests, and the effectiveness of screening programs in relatives of patients affected by
NS
‐
TADs
.

Methods and Results

A systematic literature search on PubMed/
MEDLINE
, Embase, and the Cochrane Library was conducted from inception to the end of December 2017. The search was supplemented with the Online Mendelian Inheritance in Man database. A total of 53 studies were included, and a total of 2696
NS
‐
TAD
relatives were screened. Screening was genetic in 49% of studies, followed by imaging techniques in 11% and a combination of the 2 in 40%. Newly affected individuals were identified in 33%, 24%, and 15% of first‐, second‐, and third‐degree relatives, respectively. Familial
NS
‐
TAD
s were primarily attributed to single‐gene mutations, expressed in an autosomal dominant pattern with incomplete penetrance. Specific gene mutations were observed in 25% of the screened families. Disease subtype and genetic mutations stratified patients with respect to age of presentation, aneurysmal location, and aortic diameter before dissection. Relatives of patients with sporadic
NS
‐
TAD
s were also found to be affected. No studies evaluated the predictive accuracy of imaging or genetic screening tests, or the clinical or cost‐effectiveness of an
NS
‐
TAD
screening program.

Conclusions

First‐ and second‐degree relatives of patients affected by both familial and sporadic
NS
‐
TAD
s may benefit from personalized screening programs.
Sex‐Dependent Phenotypic Variability of an
SCN5A
Mutation: Brugada Syndrome and Sick Sinus Syndrome
Authors: Aizawa Yoshiyasu , Fujisawa Taishi , Katsumata Yoshinori , Kohsaka Shun , Kunitomi Akira , Ohno Seiko , Sonoda Keiko , Hayashi Hidemori , Hojo Rintaro , Fukamizu Seiji , Nagase Satoshi , Ito Shogo , Nakajima Kazuaki , Nishiyama Takahiko , Kimura Takehiro , Kurita Yasuo , Furukawa Yoshiko , Takatsuki Seiji , Ogawa Satoshi , Nakazato Yuji , Sumiyoshi Masataka , Kosaki Kenjiro , Horie Minoru , Fukuda Keiichi
Published: September 2018

Background

Brugada syndrome (
BS
) is known to be 9 times more prevalent in males than females. However, little is known about the development of sick sinus syndrome in female members with familial
BS
.

Methods and Results

Familial
BS
patients and family members, both from our institutions and collaborating sites that specialize in clinical care of
BS
, participated in this study. We collected information on their clinical and genetic background, along with the inheritance patterns of
BS
. Detailed information on each case with familial
BS
is described. A total of 7 families, including 25
BS
patients (12 females and 13 males), were included. Seven were probands and 18 were family members. Ten out of the 12 female patients and none of the 13 male patients developed sick sinus syndrome. Sudden death or spontaneous ventricular fibrillation occurred in 7 out of 13 male patients and 2 out of 12 female patients.

Conclusions

Familial
BS
existed in which female patients developed sick sinus syndrome but male patients did not. Some of those female patients with sick sinus syndrome had unrecognized
BS
. Information should be collected not only regarding a family history of sudden death or
BS
, but also whether a pacemaker was implanted in female members.
Epidermal Growth Factor Receptor–Targeted Cytotoxin Inhibits Neointimal Hyperplasia In Vivo
Authors: Pastore Christopher J. , Isner Jeffrey M. , Bacha Patricia A. , Kearney Marianne , Pickering J. Geoffrey
Published: September 2018

Abstract
Smooth muscle cell accumulation is a key feature of restenosis that may be inhibited by the delivery of receptor-targeted cytotoxins. DAB
389
EGF is a recombinant fusion protein in which the receptor-binding domain of diphtheria toxin has been replaced by human epidermal growth factor (EGF). We investigated the effectiveness of DAB
389
EGF to inhibit neointimal hyperplasia in the balloon-injured rat carotid artery. Incubation of rat carotid arteries with
125
I-labeled EGF revealed extensive EGF binding sites in the neointima of balloon-injured arteries. Sixty rats subsequently received either saline or DAB
389
EGF (total dose, 0.15 mg) delivered immediately following balloon injury either systemically, via 14-day continuous osmotic pump infusion, or locally, via 30-minute intraluminal incubation. The effect of both treatment strategies was measured 2 weeks after injury by cross-sectional morphometric analysis of intimal area, the ratio of intimal/medial area (I/M), and the percent luminal narrowing (%LN). In addition, proliferative activity was assessed by immunostaining for the presence of the proliferating cell nuclear antigen (PCNA). Compared with controls, systemic delivery of fusion toxin significantly reduced intimal area, I/M, and %LN by 40%, 40%, and 29%, respectively. However, these rats exhibited 2% weight loss, indicating mild systemic toxicity. Local, intraluminal administration of DAB
389
EGF yielded a more pronounced reduction in intimal area, I/M, and %LN by 74%, 79%, and 72%, respectively. This inhibitory effect was preserved at 3 weeks postinjury, and PCNA immunostaining of locally treated arteries revealed a virtual absence of proliferative activity in the neointima and media at this timepoint. In contrast to systemically treated rats, rats receiving fusion toxin locally gained weight at a rate similar to controls, indicating avoidance of systemic toxicity. We conclude that DAB
389
EGF is a potent inhibitor of neointimal hyperplasia in vivo and that whereas an inhibitory effect may be achieved by systemic delivery, local delivery appears to be more potent, avoids systemic toxicity, and thus represents a feasible strategy to preempt restenosis.
Reconceptualizing Aesthetic Cosmopolitanism: Evidence From the Early Consecration of Anglo-American Pop-Rock in Italy
Authors: Varriale Simone
Published: September 2018

This article explores how foreign, recently imported cultural forms can redefine the dynamics of legitimation in national cultural fields. Drawing on archival research, the article discusses the early consecration of Anglo-American pop-rock in 1970s Italy and analyzes the articles published by three specialist music magazines. Findings reveal the emergence of a shared pop-rock canon among Italian critics, but also that this “cosmopolitan capital” was mobilized to implement competing editorial projects. Italian critics promoted both different strategies of legitimation vis-à-vis contemporary popular music and opposite views of cultural globalization as a social process. Theoretically, the article conceptualizes “aesthetic cosmopolitanism” as a symbolic resource that can be realized through competing institutional projects, rather than as a homogeneous cultural disposition.
Polyurethane nanocomposite coating with silanized graphene and hexagonal boron nitride as nanoadditives for improved resistance against ultraviolet degradation
Authors: Tran Thu Van , Abedin Farhana , Usta Aybala , Asmatulu Ramazan
Published: September 2018

Polyurethane coatings modified with silanized graphene and/or hexagonal boron nitride as nanoadditives were synthesized, characterized, and tested for ultraviolet degradation and hydrophobicity. These coatings containing various weight percentages (wt%) of nanoadditives were prepared and investigated. The coating composition was characterized using Fourier transform infrared spectroscopy. The silanization of nanoadditives was characterized using scanning electron microscopy. The glass transition temperatures (Tg) of the nanocomposite coatings were determined using differential scanning calorimeter; it was observed that the presence of nanoadditives in the coatings impacted the Tg indicating their interference with the polyurethane chains and structures. The change in the coating thickness and water contact angle after ultraviolet light exposure was also studied. Exposure of the coatings to ultraviolet light led to a decrease in the coating thickness and hydrophobicity. With the increasing content of nanoadditives, the decrease in the coating thickness was lower and the rate of decrease of water contact angle was slow. Polyurethane coatings with 0.8 wt% silanized hexagonal boron nitride nanoparticles exhibited minimum reduction in coating thickness and the slowest rate of decrease in the water contact angle.
Adults’ Markers of Face Processing Are Present at Age 6 and Are Interconnected Along Development
Authors: Mardo Elite , Avidan Galia , Hadad Bat-Sheva
Published: September 2018

Recent studies on the development of face processing argue for a late, quantitative, domain-specific development of face processing, and face memory in particular. Most previous findings were based on separately tracking the developmental course of face perception skills, comparing performance across different age groups. Here, we adopted a different approach studying the mechanisms underlying the development of face processing by focusing on how different face skills are interrelated over the years (age 6 to adulthood). Specifically, we examined correlations within and between different categories of tasks: face domain-specific skills involving face recognition based on long-term representations (famous face), and short-term memory retention (Cambridge Face Memory Test), perceptual face-specific marker (inversion effect), global effects in scene perception (global–local task), and the perception of facial expressions. Factor analysis revealed that face identity skills have a similar pattern of interrelations throughout development, identifying two factors: a face domain-specific factor comprising adultlike markers of face processing and a general factor incorporating related, but nonspecific perceptual skills. Domain-specific age-related changes in face recognition entailing short- and long-term retention of face representations were observed, along with mature perceptual face-specific markers and more general perceptual effects predicting face perception skills already at age 6. The results suggest that the domain-specific changes in face processing are unlikely to result from developmental changes in perceptual skills driving face recognition. Instead, development may either involve improvement in the ability to retain face representations in memory or changes in the interactions between the perceptual representations of faces and their representations in long-term memory.
Visibilities and Visual Discourses: Rethinking the Social With the Image
Authors: Traue Boris , Blanc Mathias , Cambre Carolina
Published: September 2018

With this special issue, we aim to address visibility not just as a representation of the social, but as an aspect and element of social and cultural orders and actions sui generis. The texts in this volume are dedicated to understanding the practices, power relations and the technological infrastructures in which (audio)-visual practices unfold. To make our proposition clear, we lay out a methodological strategy that we—drawing from French, German and Anglo-Saxon debate—call sociology with the image. Then we provide an overview of the articles in this special issue and point to some ongoing tensions within qualitative inquiry more broadly.
Prescribing Home Narrowband UVB Phototherapy: A Review of Current Approaches
Authors: Hum Matthew , Kalia Sunil , Gniadecki Robert
Published: September 2018

Conventional, full-body phototherapy equipment is costly and therefore patients are usually treated in dermatology centres. Such office-based therapy is often not feasible for those patients who live far away from a phototherapy centre due to lost time and wages, inability to travel because of extensive skin disease, or prohibitive travel costs. Home phototherapy has emerged as a modality that meets the needs of those patients. Our aim was to review available studies on UV sources, treatment protocols, efficacy, and safety of home phototherapy. A literature review was conducted on PubMed using the terms “home” AND “phototherapy” AND (“guide” OR “approach” OR “review” OR “protocol”). From the data extracted, narrowband UVB (311 nm) offers the best balance between safety and efficacy and is recommended for home phototherapy by most authors. Treatment is safe and possible adverse effects are related to overexposure (erythema, blistering). The usual treatment protocol was administering treatments on alternating days, including weekends, with dosing based on the patient’s Fitzpatrick skin type. We also provide information on the available home phototherapy systems in Canada and their reimbursement. Home phototherapy is underused in Canada. Narrowband UVB phototherapy sources equipped with a 3-dimensional panel provides a practical and safe option.
Minimal important change and patient acceptable symptom state for patients after proximal interphalangeal joint arthroplasty
Authors: Marks Miriam , Hensler Stefanie , Wehrli Martina , Schindele Stephan , Herren Daniel B.
Published: September 2018

Our aim was to determine the minimal important change and patient acceptable symptom state for pain and the brief Michigan Hand Outcomes Questionnaire in patients 1 year after proximal interphalangeaI joint arthroplasty. We analysed data of 100 patients from our prospective registry. The minimal important change and patient acceptable symptom state were determined with anchor-based methods, and patients with better or worse baseline status were examined. The minimal important change for pain at rest and during activities, and the brief Michigan Hand Outcomes Questionnaire was −1.2, −2.8 and 18, respectively, with corresponding patient acceptable symptom state values of 1.5, 2.5 and 64. Patients with higher baseline symptoms rated more severe postoperative symptoms as acceptable, whereas patients with lower baseline symptoms were only satisfied with a low level of pain and high level of hand function. The minimal important change and patient acceptable symptom state are useful estimates for patient outcomes and study results.

Level of evidence: IV
Noninvasive Monitoring of Blood Glucose Using Color-Coded Photoplethysmographic Images of the Illuminated Fingertip Within the Visible and Near-Infrared Range: Opportunities and Questions
Authors: Vahlsing Thorsten , Delbeck Sven , Leonhardt Steffen , Heise H. Michael
Published: September 2018

Noninvasive blood glucose assays have been promised for many years and various molecular spectroscopy-based methods of skin are candidates for achieving this goal. Due to the small spectral signatures of the glucose used for direct physical detection, moreover hidden among a largely variable background, broad spectral intervals are usually required to provide the mandatory analytical selectivity, but no such device has so far reached the accuracy that is required for self-monitoring of blood glucose (SMBG). A recently presented device as described in this journal, based on photoplethysmographic fingertip images for measuring glucose in a nonspecific indirect manner, is especially evaluated for providing reliable blood glucose concentration predictions.