bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
Microglial Cells Impact Gut Microbiota and Gut Pathology in Angiotensin II-Induced Hypertension
Authors: Sharma Ravindra K. , Yang Tao , Oliveira Aline C. , Lobaton Gilberto O. , Aquino Victor , Kim Seungbum , Richards Elaine M. , Pepine Carl J. , Sumners Colin , Raizada Mohan K.
Published: January 2019

Rationale:

Increased microglial activation and neuroinflammation within autonomic brain regions have been implicated in sustained hypertension, and their inhibition by minocycline—an anti-inflammatory antibiotic—produces beneficial effects. These observations led us to propose a dysfunctional brain-gut communication hypothesis for hypertension. However, it has been difficult to reconcile whether an anti-inflammatory or antimicrobial action is the primary beneficial effect of minocycline in hypertension. Accordingly, we utilized chemically modified tetracycline-3 (CMT-3)—a derivative of tetracycline that has potent anti-inflammatory activity—to address this question.

Objective:

Test the hypothesis that central administration of CMT-3 would inhibit microglial activation, attenuate neuroinflammation, alter selective gut microbial communities, protect the gut wall from developing hypertension-associated pathology, and attenuate hypertension.

Methods and Results:

Rats were implanted with radiotelemetry devices for recording mean arterial pressure. Ang II (angiotensin II) was infused subcutaneously using osmotic mini-pumps to induce hypertension. Another osmotic mini-pump was surgically implanted to infuse CMT-3 intracerebroventricularly. Intracerebroventricular CMT- 3 infusion was also investigated in SHR (spontaneously hypertensive rats). Physiological, pathological, immunohistological parameters, and fecal microbiota were analyzed. Intracerebroventricular CMT-3 significantly inhibited Ang II-induced increases in number of microglia, their activation, and proinflammatory cytokines in the paraventricular nucleus of hypothalamus. Further, intracerebroventricular CMT-3 attenuated increased mean arterial pressure, normalized sympathetic activity, and left ventricular hypertrophy in Ang II rats, as well as in the SHR. Finally, CMT-3 beneficially restored certain gut microbial communities altered by Ang II and attenuated pathological alterations in gut wall.

Conclusions:

These observations demonstrate that inhibition of microglial activation alone was sufficient to induce significant antihypertensive effects. This was associated with unique changes in gut microbial communities and profound attenuation of gut pathology. They suggest, for the first time, a link between microglia and certain microbial communities that may have implications for treatment of hypertension.
From Machine Learning to Artificial Intelligence Applications in Cardiac Care
Authors: Tsay David , Patterson Cam
Published: January 2019

Artificial intelligence offers the potential for transformational advancement in cardiovascular care delivery, yet practical applications of this technology have yet to be embedded in clinical workflows and systems. Recent advances in machine learning algorithms and accessibility to big data sources have created the ability for software to solve highly specialized problems outside of health care, such as autonomous driving, speech recognition, and game playing (chess and Go), at superhuman efficiency previously not thought possible. To date, high-order cognitive problems in cardiovascular research such as differential diagnosis, treatment options, and clinical risk stratification have been difficult to address at scale with artificial intelligence. The practical application of artificial intelligence in the underlying operational processes in the delivery of cardiac care may be more amenable where adoption has great potential to fundamentally transform care delivery while maintaining the core quality and service that our patients demand. In this article, we provide an overview on how these artificial intelligence platforms can be implemented to improve the operational delivery of care for patients with cardiovascular disease.
Antiangiogenic VEGF
165
b Regulates Macrophage Polarization via S100A8/S100A9 in Peripheral Artery Disease
Authors: Ganta Vijay Chaitanya , Choi Min , Farber Charles R. , Annex Brian H.
Published: January 2019

Background:

Atherosclerotic occlusions decrease blood flow to the lower limbs, causing ischemia and tissue loss in patients with peripheral artery disease (PAD). No effective medical therapies are currently available to induce angiogenesis and promote perfusion recovery in patients with severe PAD. Clinical trials aimed at inducing vascular endothelial growth factor (VEGF)–A levels, a potent proangiogenic growth factor to induce angiogenesis, and perfusion recovery were not successful. Alternate splicing in the exon-8 of VEGF-A results in the formation of VEGFxxxa (VEGF
165
a) and VEGFxxxb (VEGF
165
b) isoforms with existing literature focusing on VEGF
165
b’s role in inhibiting vascular endothelial growth factor receptor 2–dependent angiogenesis. However, we have recently shown that VEGF
165
b blocks VEGF-A–induced endothelial vascular endothelial growth factor receptor 1 (VEGFR1) activation in ischemic muscle to impair perfusion recovery. Because macrophage-secreted VEGF
165
b has been shown to decrease angiogenesis in peripheral artery disease, and macrophages were well known to play important roles in regulating ischemic muscle vascular remodeling, we examined the role of VEGF
165
b in regulating macrophage function in PAD.

Methods:

Femoral artery ligation and resection were used as an in vivo preclinical PAD model, and hypoxia serum starvation was used as an in vitro model for PAD. Experiments including laser-Doppler perfusion imaging, adoptive cell transfer to ischemic muscle, immunoblot analysis, ELISAs, immunostainings, flow cytometry, quantitative polymerase chain reaction analysis, and RNA sequencing were performed to determine a role of VEGF
165
b in regulating macrophage phenotype and function in PAD.

Results:

First, we found increased VEGF
165
b expression with increased M1-like macrophages in PAD versus non-PAD (controls) muscle biopsies. Next, using in vitro hypoxia serum starvation, in vivo pre
c
linical PAD models, and adoptive transfer of VEGF
165
b-expressing bone marrow–derived macrophages or VEGFR1
+/–
bone marrow–derived macrophages (M1-like phenotype), we demonstrate that VEGF
165
b inhibits VEGFR1 activation to induce an M1-like phenotype that impairs ischemic muscle neovascularization. Subsequently, we found S100A8/S100A9 as VEGFR1 downstream regulators of macrophage polarization by RNA-Seq analysis of hypoxia serum starvation-VEGFR1
+/+
versus hypoxia serum starvation-VEGFR1
+/–
bone marrow–derived macrophages.

Conclusions:

In our current study, we demonstrate that increased VEGF
165
b expression in macrophages induces an antiangiogenic M1-like phenotype that directly impairs angiogenesis. VEGFR1 inhibition by VEGF
165
b results in S100A8/S100A9-mediated calcium influx to induce an M1-like phenotype that impairs ischemic muscle revascularization and perfusion recovery.
Multiple Arterial Grafting Is Associated With Better Outcomes for Coronary Artery Bypass Grafting Patients
Authors: Rocha Rodolfo V. , Tam Derrick Y. , Karkhanis Reena , Nedadur Rashmi , Fang Jiming , Tu Jack V. , Gaudino Mario , Royse Alistair , Fremes Stephen E.
Published: January 2019

Background:

Observational studies have shown better survival in patients undergoing coronary artery bypass grafting (CABG) with 2 arterial grafts compared with 1. However, whether a third arterial graft is associated with incremental benefit remains uncertain. We sought to analyze the outcomes of 3 versus 2 arterial grafts during CABG. As a secondary objective, we compared CABG with 2 or 3 arterial grafts (multiple arterial grafts [MAG]) with CABG using a single arterial graft (SAG).

Methods:

Retrospective cohort analyses of all patients undergoing primary isolated CABG in Ontario, Canada, from October 2008 to March 2016. Propensity score matching was performed between patients with 3 arterial grafts (3Art group) versus 2 (2Art group). The primary outcome was time to first event of a composite of death, myocardial infarction, stroke, and repeat revascularization (major adverse cardiac and cerebrovascular events). Additional analyses were performed to evaluate the association between MAG versus SAG and long-term outcomes using propensity score matching.

Results:

Fifty thousand, two hundred thirty patients underwent isolated CABG during our study period; 3044 (6.1%) and 8253 (16.4%) patients had 3 and 2 arterial grafts, respectively, resulting in 2789 propensity score matching pairs for the primary analyses. Mean and maximum follow-up was 4.2 and 8.5 years, respectively. Radial artery grafting was more common in the 3Art versus 2Art group (79.3% versus 65.6%,
P
<0.01). In-hospital outcomes were not significantly different, including death (3Art 0.8% versus 2Art 0.5%,
P
=0.26). Up to 8 years, there were no differences in major adverse cardiac and cerebrovascular events (3Art 27%, 95% confidence interval [CI], 24% to 30% versus 2Art 25%, 95% CI, 22% to 28%; hazard ratio [HR], 1.08, 95% CI, 0.94–1.25), death (HR, 1.08; 95% CI, 0.90–1.29), myocardial infarction (HR, 1.15; 95% CI, 0.87–1.51), stroke (HR, 1.39; 95% CI, 0.95–2.06), or repeat revascularization (HR, 1.04; 95% CI, 0.82–1.32). When evaluating MAG versus SAG, 8629 patient pairs were formed using propensity score matching. At 8 years, cumulative incidences of major adverse cardiac and cerebrovascular events (HR, 0.82, 95% CI, 0.77–0.88), survival (HR, 0.80; 95% CI, 0.73–0.88), repeat revascularization (HR, 0.79; 95% CI, 0.69–0.90), and myocardial infarction (HR, 0.83; 95% CI, 0.72–0.97) were superior in the MAG group.

Conclusions:

CABG with 3 arterial grafts was not associated with increased in-hospital death nor with better clinical outcomes at 8-year follow-up, compared with CABG with 2 arterial grafts. MAG was associated with superior outcomes compared with SAG.
Association Between Ambient Air Pollution and Cardiac Morpho-Functional Phenotypes
Authors: Aung Nay , Sanghvi Mihir M. , Zemrak Filip , Lee Aaron M. , Cooper Jackie A. , Paiva Jose M. , Thomson Ross J. , Fung Kenneth , Khanji Mohammed Y. , Lukaschuk Elena , Carapella Valentina , Kim Young Jin , Munroe Patricia B. , Piechnik Stefan K. , Neubauer Stefan , Petersen Steffen E.
Published: January 2019

Background:

Exposure to ambient air pollution is strongly associated with increased cardiovascular morbidity and mortality. Little is known about the influence of air pollutants on cardiac structure and function. We aim to investigate the relationship between chronic past exposure to traffic-related pollutants and the cardiac chamber volume, ejection fraction, and left ventricular remodeling patterns after accounting for potential confounders.

Methods:

Exposure to ambient air pollutants including particulate matter and nitrogen dioxide was estimated from the Land Use Regression models for the years between 2005 and 2010. Cardiac parameters were measured from cardiovascular magnetic resonance imaging studies of 3920 individuals free from pre-existing cardiovascular disease in the UK Biobank population study. The median (interquartile range) duration between the year of exposure estimate and the imaging visit was 5.2 (0.6) years. We fitted multivariable linear regression models to investigate the relationship between cardiac parameters and traffic-related pollutants after adjusting for various confounders.

Results:

The studied cohort was 62±7 years old, and 46% were men. In fully adjusted models, particulate matter with an aerodynamic diameter <2.5 µm concentration was significantly associated with larger left ventricular end-diastolic volume and end-systolic volume (effect size = 0.82%, 95% CI, 0.09–1.55%,
P
=0.027; and effect size = 1.28%, 95% CI, 0.15–2.43%,
P
=0.027, respectively, per interquartile range increment in particulate matter with an aerodynamic diameter <2.5 µm) and right ventricular end-diastolic volume (effect size = 0.85%, 95% CI, 0.12–1.58%,
P
=0.023, per interquartile range increment in particulate matter with an aerodynamic diameter <2.5 µm). Likewise, higher nitrogen dioxide concentration was associated with larger biventricular volume. Distance from the major roads was the only metric associated with lower left ventricular mass (effect size = −0.74%, 95% CI, −1.3% to −0.18%,
P
=0.01, per interquartile range increment). Neither left and right atrial phenotypes nor left ventricular geometric remodeling patterns were influenced by the ambient pollutants.

Conclusions:

In a large asymptomatic population with no prevalent cardiovascular disease, higher past exposure to particulate matter with an aerodynamic diameter <2.5 µm and nitrogen dioxide was associated with cardiac ventricular dilatation, a marker of adverse remodeling that often precedes heart failure development.
Is There a Role for Preoperative Platelet Function Testing in Patients Undergoing Cardiac Surgery During Antiplatelet Therapy?
Authors: Mahla Elisabeth , Tantry Udaya S. , Prüller Florian , Gurbel Paul A.
Published: January 2019

Up to 11% of patients presenting with acute coronary syndromes undergo coronary artery bypass grafting. Guidelines largely recommend a one-size-fits-all preoperative discontinuation period for P2Y
12
receptor blockers to avoid bleeding. These recommendations do not account for highly variable pharmacodynamic responsiveness and for variable recovery of platelet reactivity following discontinuation of P2Y
12
receptor blockers. Several observational studies have demonstrated that an objective measurement of platelet function among these patients may reduce the waiting period while mitigating the risk of bleeding. Based on these findings, 2 recent guidelines included a Class IIa and IIb recommendation for platelet function testing in patients undergoing cardiac surgery. The following review article describes the rationale for discontinuation of dual antiplatelet therapy before cardiac surgery and the limitations with this approach, available platelet function assays to assess pharmacodynamic effects, and the association between platelet inhibition and other clinical factors with surgery-related bleeding. The information will assist the reader in determining which patients undergoing cardiac surgery might benefit from preoperative platelet function monitoring.
Rapid Self-Assembly of Bioengineered Cardiovascular Bypass Grafts From Scaffold-Stabilized, Tubular Bilevel Cell Sheets
Authors: von Bornstädt Daniel , Wang Hanjay , Paulsen Michael J. , Goldstone Andrew B. , Eskandari Anahita , Thakore Akshara , Stapleton Lyndsay , Steele Amanda N. , Truong Vi N. , Jaatinen Kevin , Hironaka Camille , Woo Y. Joseph
Published: January 2019

Background:

Cardiovascular bypass grafting is an essential treatment for complex cases of atherosclerotic disease. Because the availability of autologous arterial and venous conduits is patient-limited, self-assembled cell-only grafts have been developed to serve as functional conduits with off-the-shelf availability. The unacceptably long production time required to generate these conduits, however, currently limits their clinical utility. Here, we introduce a novel technique to significantly accelerate the production process of self-assembled engineered vascular conduits.

Methods:

Human aortic smooth muscle cells and skin fibroblasts were used to construct bilevel cell sheets. Cell sheets were wrapped around a 22.5-gauge Angiocath needle to form tubular vessel constructs. A thin, flexible membrane of clinically approved biodegradable tissue glue (Dermabond Advanced) served as a temporary, external scaffold, allowing immediate perfusion and endothelialization of the vessel construct in a bioreactor. Subsequently, the matured vascular conduits were used as femoral artery interposition grafts in rats (n=20). Burst pressure, vasoreactivity, flow dynamics, perfusion, graft patency, and histological structure were assessed.

Results:

Compared with engineered vascular conduits formed without external stabilization, glue membrane–stabilized conduits reached maturity in the bioreactor in one-fifth the time. After only 2 weeks of perfusion, the matured conduits exhibited flow dynamics similar to that of control arteries, as well as physiological responses to vasoconstricting and vasodilating drugs. The matured conduits had burst pressures exceeding 500 mm Hg and had sufficient mechanical stability for surgical anastomoses. The patency rate of implanted conduits at 8 weeks was 100%, with flow rate and hind-limb perfusion similar to those of sham controls. Grafts explanted after 8 weeks showed a histological structure resembling that of typical arteries, including intima, media, adventitia, and internal and external elastic membrane layers.

Conclusions:

Our technique reduces the production time of self-assembled, cell sheet–derived engineered vascular conduits to 2 weeks, thereby permitting their use as bypass grafts within the clinical time window for elective cardiovascular surgery. Furthermore, our method uses only clinically approved materials and can be adapted to various cell sources, simplifying the path toward future clinical translation.
Dysfunctional and Proinflammatory Regulatory T-Lymphocytes Are Essential for Adverse Cardiac Remodeling in Ischemic Cardiomyopathy
Authors: Bansal Shyam S. , Ismahil Mohamed Ameen , Goel Mehak , Zhou Guihua , Rokosh Gregg , Hamid Tariq , Prabhu Sumanth D.
Published: January 2019

Background:

Heart failure (HF) is a state of inappropriately sustained inflammation, suggesting the loss of normal immunosuppressive mechanisms. Regulatory T-lymphocytes (Tregs) are considered key suppressors of immune responses; however, their role in HF is unknown. We hypothesized that Tregs are dysfunctional in ischemic cardiomyopathy and HF, and they promote immune activation and left ventricular (LV) remodeling.

Methods:

Adult male wild-type C57BL/6 mice, Foxp3-diphtheria toxin receptor transgenic mice, and tumor necrosis factor (TNF) α receptor-1 (TNFR1)
−
/−
mice underwent nonreperfused myocardial infarction to induce HF or sham operation. LV remodeling was assessed by echocardiography as well as histological and molecular phenotyping. Alterations in Treg profile and function were examined by flow cytometry, immunostaining, and in vitro cell assays.

Results:

Compared with wild-type sham mice, CD4
+
Foxp3
+
Tregs in wild-type HF mice robustly expanded in the heart, circulation, spleen, and lymph nodes in a phasic manner after myocardial infarction, beyond the early phase of wound healing, and exhibited proinflammatory T helper 1-type features with interferon-γ, TNFα, and TNFR1 expression, loss of immunomodulatory capacity, heightened proliferation, and potentiated antiangiogenic and profibrotic properties. Selective Treg ablation in Foxp3-diphtheria toxin receptor mice with ischemic cardiomyopathy reversed LV remodeling and dysfunction, alleviating hypertrophy and fibrosis, while suppressing circulating CD4
+
T cells and systemic inflammation and enhancing tissue neovascularization. Tregs reconstituted after ablation exhibited restoration of immunosuppressive capacity and normalized TNFR1 expression. Treg dysfunction was also tightly coupled to Treg-endothelial cell contact- and TNFR1-dependent inhibition of angiogenesis and the mobilization and tissue infiltration of CD34
+
Flk1
+
circulating angiogenic cells in a C-C chemokine ligand 5/C-C chemokine receptor 5-dependent manner. Anti-CD25-mediated Treg depletion in wild-type mice imparted similar benefits on LV remodeling, circulating angiogenic cells, and tissue neovascularization.

Conclusions:

Proinflammatory and antiangiogenic Tregs play an essential pathogenetic role in chronic ischemic HF to promote immune activation and pathological LV remodeling. The restoration of normal Treg function may be a viable approach to therapeutic immunomodulation in this disease.
Association Between Variation in Preoperative Care Before Arterial Switch Operation and Outcomes in Patients With Transposition of the Great Arteries
Authors: O’Byrne Michael L. , Glatz Andrew C. , Song Lihai , Griffis Heather M. , Millenson Marisa E. , Gillespie Matthew J. , Dori Yoav , DeWitt Aaron G. , Mascio Christopher E. , Rome Jonathan J.
Published: January 2019

Background:

The arterial switch operation (ASO) is the gold standard operative correction of neonates with transposition of the great arteries and intact ventricular septum, with excellent operative survival. The associations between patient and surgeon characteristics and outcomes are well understood, but the associations between variation in preoperative care and outcomes are less well studied.

Methods:

A multicenter retrospective cohort study of infants undergoing neonatal ASO between January 2010 and September 2015 at hospitals contributing data to the Pediatric Health Information Systems database was performed. The association between preoperative care (timing of ASO, preoperative use of balloon atrial septostomy, prostaglandin infusion, mechanical ventilation, and vasoactive agents) and operative outcomes (mortality, length of stay, and cost) was studied with multivariable mixed-effects models.

Results:

Over the study period, 2159 neonates at 40 hospitals were evaluated. Perioperative mortality was 2.8%. Between hospitals, the use of adjuvant therapies and timing of ASO varied broadly. At the subject level, older age at ASO was associated with higher mortality risk (age >6 days: odds ratio, 1.90; 95% CI, 1.11–3.26;
P
=0.02), cost, and length of stay. Receipt of a balloon atrial septostomy was associated with lower mortality risk (odds ratio, 0.32; 95% CI, 0.17–0.59;
P
<0.001), cost, and length of stay. Later hospital median age at ASO was associated with higher odds of mortality (odds ratio, 1.15 per day; 95% CI, 1.02–1.29;
P
=0.03), longer length of stay (
P
<0.004), and higher cost (
P
<0.001). Other hospital factors were not independently associated with the outcomes of interest.

Conclusions:

There was significant variation in preoperative care between hospitals. Some potentially modifiable aspects of perioperative care (timing of ASO and septostomy) were significantly associated with mortality, length of stay, and cost. Further research on the perioperative care of neonates is necessary to determine whether modifying practice on the basis of the observed associations translates into improved outcomes.
Comprehensive Analysis of Stroke in the Long-Term Cohort of the MOMENTUM 3 Study
Authors: Colombo Paolo C. , Mehra Mandeep R. , Goldstein Daniel J. , Estep Jerry D. , Salerno Christopher , Jorde Ulrich P. , Cowger Jennifer A. , Cleveland Joseph C. , Uriel Nir , Sayer Gabriel , Skipper Eric R. , Downey Francis X. , Ono Masahiro , Hooker Robert , Anyanwu Anelechi C. , Givertz Michael M. , Mahr Claudius , Topuria Ia , Somo Sami I. , Crandall Daniel L. , Horstmanshof Douglas A.
Published: January 2019

Background:

The MOMENTUM 3 study (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3) has demonstrated that the HeartMate 3 (HM3) pump is associated with reduced strokes compared with the HeartMate II (HMII) device. We now perform a comprehensive analysis of stroke events to evaluate their longitudinal occurrence, clinical correlates, patterns, and impact on outcome across the 2-year duration of support.

Methods:

MOMENTUM 3 is a randomized controlled trial of the HM3 centrifugal-flow pump versus the HMII axial-flow pump in patients with advanced heart failure, regardless of the intended goal of support (bridge to transplantation or destination therapy). Baseline and postimplantation clinical correlates of stroke events were assessed with multivariable analyses. Longitudinal patterns, including device association, type of stroke (hemorrhagic versus ischemic), changing severity of impairment assessed with the modified Rankin Scale (disabling [modified Rankin Scale score >3] versus nondisabling [modified Rankin Scale score ≤3]) over time, and association with outcome, were determined.

Results:

In 361 patients with the intended implant (189 HM3 and 172 HMII), 65 strokes (40 ischemic strokes and 25 hemorrhagic strokes) occurred in 52 patients at a median of 131 (range, 1–733) days. No difference in stroke rate was noted between 0 and 180 days of follow-up between devices. However, stroke incidence in the long-term period (181–730 days after left ventricular assist device) was 3.3 times lower for the HM3 group (HM3: 0.04 versus HMII: 0.13 events per patient-year; odds ratio, 0.23; 95% CI, 0.08–0.63;
P
=0.01). Treatment with the HM3 pump was the only independent predictor of lower stroke events. We found no direct association of blood pressure or antithrombotic regimens with observed stroke rates. A stroke event significantly lowered 2-year postimplantation survival regardless of subtype or initial severity of neurological impairment compared with patients without a stroke (43±12% for hemorrhagic stroke, 57±9% for ischemic stroke, 51±11% for disabling, and 51±11% for nondisabling compared with 85±2% 2-year survival for patients without stroke).

Conclusions:

The HM3 pump is associated with a marked reduction in stroke rates compared with the HMII device, with benefits observed in the long-term period (>6 months). The occurrence of stroke of any type (hemorrhagic and ischemic) or of any functional severity (disabling and nondisabling) is predictive of a poor 2-year clinical outcome.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov/
. Unique identifier: NCT02224755.
Diagnostic Thresholds for Blood Pressure Measured at Home in the Context of the 2017 Hypertension Guideline
Authors: Vongpatanasin Wanpen , Ayers Colby , Lodhi Hamza , Das Sandeep R. , Berry Jarett D. , Khera Amit , Victor Ronald G. , Lin Feng-Chang , Viera Anthony J. , Yano Yuichiro , de Lemos James A.
Published: January 2019

Most guidelines have recommended lower home blood pressure (BP) threshold when clinic BP threshold of 140/90 mm Hg is used for diagnosis of hypertension. However, home BP thresholds to define hypertension have never been determined in the general population in the United States. We identified home BP thresholds for stage 1 (BP ≥130/80 mm Hg) hypertension using a regression-based approach in the DHS (Dallas Heart Study; n=5768) and the NCMH study (North Carolina Masked Hypertension; n=420). Home BP thresholds were also assessed using outcome-derived approach based on the composite of all-cause mortality or cardiovascular events in the DHS cohort. For this approach, BP thresholds were identified only for systolic BP because diastolic BP was not associated with the outcome. Among untreated participants, the regression-derived thresholds for home BP corresponding to clinic BP for stage 1 hypertension were 129/80 mm Hg in blacks, 130/80 mm Hg in whites, and 126/78 mm Hg in Hispanics, respectively. The results are similar in the North Carolina cohort. The 11-year composite cardiovascular and mortality events corresponding to clinic systolic BP >130 mm Hg were higher in blacks than in whites and Hispanics (13.3% versus 5.98% versus 5.52%, respectively). Using a race/ethnicity-specific composite outcome in the untreated DHS participants, the outcome-derived home systolic BP thresholds corresponding to stage 1 hypertension were 130 mm Hg in blacks, 129 mm Hg in whites, and 131 mm Hg in Hispanics, respectively. Our data based on both regression-derived and outcome approach support home BP threshold of 130/80 mm Hg for diagnosis of hypertension in blacks, whites, and Hispanics.
Creatinine Rise During Blood Pressure Therapy and the Risk of Adverse Clinical Outcomes in Patients With Type 2 Diabetes Mellitus
Authors: Collard Didier , Brouwer Tom F. , Peters Ron J.G. , Vogt Liffert , van den Born Bert-Jan H.
Published: January 2019

Lowering blood pressure may affect renal function. Current guidelines state that reducing antihypertensive therapy should be considered in patients with a >30% serum creatinine increase after initiation of antihypertensive therapy. We examined the association between a serum creatinine increase and adverse clinical outcomes in the ACCORD-BP trial (Action to Control Cardiovascular Risk in Diabetes Blood Pressure), were patients with type 2 diabetes mellitus were randomized to intensive (target systolic blood pressure <120 mm Hg) and standard antihypertensive (<140 mm Hg) treatment. The primary outcome was a combined end point consisting of all-cause mortality, major cardiovascular events, and renal failure. Patients were stratified into 3 groups according to serum creatinine increase between baseline and 4 months (<10%, 10%–30%, >30%). A total of 4733 patients, aged 62.2 years, 52% men with a mean estimated glomerular filtration rate 81.5 mL/min per 1.73 m
2
were included. Follow-up was available for 4446 patients, 2231 were randomized to intensive and 2215 to standard therapy. Kaplan-Meier analysis showed no association between a serum creatinine increase and the composite end point in the intensive (
P
=0.20) and the standard treatment group (
P
=0.17). After adjusting for possible confounders, a >30% serum creatinine increase was associated with a higher risk of clinical adverse outcomes in both treatment groups, but to a similar extent. These data suggest that a >30% serum creatinine increase that coincides with lower blood pressure values should not directly lead to a reduction in antihypertensive medication in patients with type 2 diabetes mellitus.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00000620.