bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathogenic Variants Associated With Dilated Cardiomyopathy Predict Outcome in Pediatric Myocarditis
Authors: Seidel Franziska , Holtgrewe Manuel , Al-Wakeel-Marquard Nadya , Opgen-Rhein Bernd , Dartsch Josephine , Herbst Christopher , Beule Dieter , Pickardt Thomas , Klingel Karin , Messroghli Daniel , Berger Felix , Schubert Stephan , Kühnisch Jirko , Klaassen Sabine 
Published: July 2021

Background:
Myocarditis is one of the most common causes leading to heart failure in children and a possible genetic background has been postulated. We sought to characterize the clinical and genetic characteristics in patients with myocarditis ≤18 years of age to predict outcome.

Methods:
A cohort of 42 patients (Genetics in Pediatric Myocarditis) with biopsy-proven myocarditis underwent genetic testing with targeted panel sequencing of cardiomyopathy-associated genes. Genetics in Pediatric Myocarditis patients were divided into subgroups according to the phenotype of dilated cardiomyopathy (DCM) at presentation, resulting in 22 patients without DCM (myocarditis without phenotype of DCM) and 20 patients with DCM (myocarditis with phenotype of DCM).

Results:

Myocarditis with phenotype of DCM patients (median age 1.4 years) were younger than myocarditis without phenotype of DCM patients (median age 16.1 years;
P
<0.001) and were corresponding to heart failure–like and coronary syndrome–like phenotypes, respectively. At least one likely pathogenic/pathogenic variant was identified in 9 out of 42 patients (22%), 8 of them were heterozygous, and 7 out of 9 were in myocarditis with phenotype of DCM. Likely pathogenic/pathogenic variants were found in genes validated for primary DCM (
BAG3, DSP, LMNA, MYH7, TNNI3, TNNT2
, and
TTN
). Rare variant enrichment analysis revealed significant accumulation of high-impact disease variants in myocarditis with phenotype of DCM versus healthy individuals (
P
=0.0003). Event-free survival was lower (
P
=0.008) in myocarditis with phenotype of DCM patients compared with myocarditis without phenotype of DCM and primary DCM.

Conclusions:
We report heterozygous likely pathogenic/pathogenic variants in biopsy-proven pediatric myocarditis. Myocarditis patients with DCM phenotype were characterized by early-onset heart failure, significant enrichment of likely pathogenic/pathogenic variants, and poor outcome. These phenotype-specific and age group–specific findings will be useful for personalized management of these patients. Genetic evaluation in children newly diagnosed with myocarditis and DCM phenotype is warranted.
Ex Vivo Assessment of Different Oral Anticoagulant Regimens on Pump Thrombosis in a HeartWare Ventricular Assist Device
Authors: Rao Sriram D. , Connor David E. , Shehab Sajad , Kerr Nicholas P. , Joseph Joanne , Muthiah Kavitha , Jain Pankaj , Robson Desiree , Jansz Paul , Hayward Christopher S. 
Published: July 2021

Background:
In light of decreased intracranial hemorrhage with direct oral anticoagulants and concerns about their safety in continuous flow left ventricular assist devices, we conducted an ex vivo study of thrombus formation using multiple anticoagulation agents.

Methods:
A continuous flow left ventricular assist device (HeartWare ventricular assist device) hemocompatibility loop was run using human blood under 7 conditions: control (no anticoagulation or antiplatelet); in vitro addition of aspirin; in vitro addition of apixaban at low dose (equivalent 2.5 mg twice daily); addition of apixaban at high dose (equivalent 5 mg twice daily); patients on warfarin; patients on apixaban (5 mg twice daily); and patients on dabigatran (150 mg twice daily). The primary outcome was time to formation of intrapump thrombosis. Secondary outcomes were reduction in clotting times over 1 hour, hemolysis, reduced platelet aggregation, and von Willebrand activity.

Results:

Twenty-one runs were completed. Times to thrombosis in median (interquartile range) were control, 131 (127–134.5); in vitro aspirin, 124 (114.5–137); and patients on dabigatran, 131 (130.5–135.5) minutes, respectively. Times in patients on warfarin were, 137 (136.5–143.5); in vitro low-dose apixaban, 141 (138.5–142); and patients on apixaban, 140 (138–142.5) minutes, respectively. No thrombus formed in the in vitro high-dose apixaban group. There were no significant differences between the individual groups. When all apixaban groups were compared with nonapixaban groups, the time to thrombosis formation was significantly longer, 143 (137–150) versus 133.5 (128.5–140) minutes,
P
=0.02. There were similar changes in lactate dehydrogenase levels and other secondary end points.

Conclusions:
In an in vitro study of anticoagulation using human blood in a mock loop with a HeartWare HVAD, we demonstrated similar thrombosis times for apixaban and warfarin. Time to clotting was longer in the combined apixaban groups compared with combined other groups, but thrombosis times between individual groups were not significantly different.
Abstract 343: Cardiovascular Device Recalls in 2012
Authors: Buckles Roberta A 
Published: July 2021

Background:
For the fiscal year 2012, the Food and Drug Administration (FDA) classified 1,190 medical device recalls. Of these, 132 (11%) were for cardiovascular (CV) devices. Class I recalls, representing the greatest health risk, result from finding a reasonable probability that device use will cause serious adverse health consequences or death. FDA approves or clears devices for the US market through either the Pre-Market Approval (PMA) pathway or, more commonly, through a substantial equivalence determination known as 510(k) clearance.

Methods:
Recalled devices were categorized into nine broad CV device groups. Recall data was included on class, marketing path, and the number of distributed devices.

Results:
PMA devices represented 14% of the CV device recalls and 510(k) devices represented 82%. There were four Class I recalls -- two PMA and two 510(k). Circulatory support and surgical (CS) was the device group with highest number of recalls (43, 33%). Physiologic monitors (PM) had the second highest (28, 21%) and Vascular catheters (VC) the third highest (17, 13%). The remaining recalls (44, 33%) were included in these device groups: Implanted pacemakers, defibrillators and leads (ID), Non-implantable EP devices (EP), External defibrillators (ED), Vascular access (VA), Stents/grafts/valves (SG), and Others (OT).

Over 16 million distributed devices were recalled in the year, with the highest average number per recall seen in the CS group and the lowest in the EP group. Class I recalls varied based both on market pathway and the number of distributed devices.
Thoratec’s Heartmate II - PMA - 3,852
St Jude Medical’s Riata - PMA -128,000
Draeger’s Infinity System - 510(k) -1
Cardiac Science Powerheart - 510(k) -12,782

Conclusion:
Most of the CV recalls in 2012 were 510(k) devices that were in the CS, PM, or VC device group. Failures in medical devices pose risk to the public and FDA strives to mitigate risk to the public health through the promotion of safe and effective devices, and the removal from the US market of those determined to be unsafe or ineffective.
Abstract 302: Echocardiographic Parameters in Perioperative Atrial Fibrillation in Cardiac and Non-Cardiac Surgery Patients
Authors: Arora Jaspreet , Nair Arjun , Cagino Leigh , Du Le , Torosoff Mikhail 
Published: July 2021

Background:
We hypothesized that patients with new onset atrial fibrillation (AFib) following cardiac or non-cardiac surgery have similar echocardiographic features, regardless of the type of surgery.

Methods:
Study cohort included 4562 consecutive patients without history of atrial fibrillation undergoing general, thoracic or cardiovascular surgeries at a single tertiary academic medical center. Retrospective chart and echocardiogram review was performed. Chi-square, logistic regression, and analysis of variance were performed. Long-term all cause mortality was determined through Social Security Death Index. The study was approved by the institutional IRB.

Results:
Post-operative AFib was noted in 24% (275/1141) after cardiac surgery, 1.2 % (10/804) after thoracic non-cardiac surgery, and 0.7% (18/2617) after general non-cardiac non-thoracic surgery (p<0.0001).

On available echocardiograms, 18% (48/264) had LV dilatation and 38% (98/261) had moderate or severe LV dysfunction. The left atrium was dilated in 53% (139/260). Moderate or severe tricuspid regurgitation was noted in 11% (15/128), mitral regurgitation in 28% (45/16), mitral stenosis in 13% (11/82), aortic insufficiency in 27% (37/135), and aortic stenosis in 63% (19/135).
When adjusted for the presence of coronary artery disease, valvular disease, age, and gender, only aortic valve stenosis remained an important independent predictor of post-operative atrial fibrillation in non-cardiac surgery patients, HR=13.9 (95%CI 1.5-132.3, p<0.022).

Conclusion:
Despite significantly increased prevalence of new onset AFib after cardiac surgery, pre-existing cardiovascular conditions, specifically aortic valve stenosis, confer an increased risk of post-operative atrial fibrillation rather than the procedure itself. Improved resource utilization can be expected if post-operative ECG monitoring is limited to the high risk patients, identifiable during peri-operative screening. Prospective studies of this important subject are needed.
Abstract 266: Heparin Documentation Improvement to Safely Manage Heparin Infusions
Authors: Manuel Venus , Morrison Jay 
Published: July 2021

Background:
Documentation of intravenous (IV) heparin infusion dose/hold by nurses is a vital component in heparin infusion management. The barcode electronic medication administration system is used when administering and documenting medications but precludes the documentation of continuous IV infusion doses such as heparin.

Aim:
To increase documentation of IV Heparin Administration Documentation in the electronic nursing documentation system.

Methods:
We reviewed multiple adverse patient events that involved heparin infusions. When discussing these events, we identified a common trend regarding the inability for nurses to document heparin IV doses/holds in the nursing electronic documentation. Although heparin volume infusion is charted every 4 hours, this does not reflect the exact heparin dose that the patient received when factoring heparin hold orders and boluses. With the involvement of clinical informatics, physicians, nurses, and a quality consultant (QC), we developed a method for nurses to document heparin IV doses and holds via the electronic documentation (Figure 1). On October 30
th
2012, two Cardiovascular Step-Down (CVSD) units championed the heparin process improvement documentation. The nurses on these units receive targeted education about the process improvement change. Audits were performed daily during the first month of implementation and periodically by the QC. Electronic communication was also sent out throughout VUH regarding the changes in heparin documentation.

Results:
Documentation of administered dose increased from 46% to 71% across VUH regardless of the type or level of education to the change.

CVSD: Pre / Post n = 16/21
DOSE: 37.5% / 81%
Both DOSE & VOLUME: 31.3% / 71.4%
HOLD: 75% / 81%
Drop Down: 43% use (68.8% annotation)
Non ICU Control: Pre / Post n = 12 / 17
DOSE: 16.7% / 41.2%
BOTH DOSE & VOLUME: 8.3% / 11.8%
HOLD: 50% / 41.2%
Drop Down: 11.1% use (88.9% annotation)
ICU units were 100% in dose documentation post changes

Conclusion:
The heparin documentation change has increased the accuracy of the documentation of heparin dose, volume, and hold across VUH. Targeted education has the potential to increase compliance and adoption. The heparin dose documentation is now exported to an electronic heparin dashboard that physicians/providers can easily access.
Abstract 251: The Association Between Receipt of Healthcare Services and Post-stroke Hypertension Control
Authors: Kohok Dhanashri , Sico Jason J , Baye Fitsum , Myers Laura , Masoor Kamalesh , Bravata Dawn M 
Published: July 2021

Hypertension is a known risk factor for primary as well as recurrent stroke. Improving blood pressure (BP) control has been associated with decreased risk of recurrent stroke. Several factors have been associated with poor BP control among stroke patients such as non-compliance and clinical inertia. We examined the receipt of health care services by patients in the one-year period following discharge for ischemic stroke.
This was a retrospective cohort study of patients who were admitted for acute ischemic stroke at a Veterans Affairs hospital during year 2011 and who were discharged with a BP >140/90 mmHg. The following were reviewed: primary care visits; sub-specialty clinic visits; emergency department (ED) visits; hospitalizations; utilization of ancillary care (i.e., telehealth, pharmacy, nutrition services); medications upon discharge; adherence to medications and occurrence of recurrent stroke during the one-year post-discharge period.
The cohort included 124 patients with an average age of 66.4 years (± standard deviation of10.3); 123 were male; 62.9% were white; diabetes mellitus was present in 32.5%; and 13.0% had history of coronary artery disease. The average BP at the time of discharge from the index stroke hospitalization was 149.5/82.6 (±11.3/9.8) mmHg. Only 38.7% of patients had an average BP over the one year period of <140/90 mmHg. The average number of primary care visits during this period was 2.8 (±1.6). The overwhelming majority of patients had at least one primary care visit (N=119, 95.9%) however the median time from discharge to the first primary clinic visit was 32 days (IQR 59). Forty four percent of patients were seen as outpatient by neurology, 19.4% by cardiology, 9.7% by nephrology, 5.7% by nutrition, 23.4% by clinical pharmacy, and 9.7% by the telehealth service. BP monitors were issued to or being used by 39.5% patients. Non-adherence was documented in the medical record as an interfering issue in 25.8% of patients. More than two antihypertensive agents were prescribed at discharge in 50.8% patients. During the one-year post-discharge period 29.0% of patients were hospitalized at least once and 24.2% had at least one ED visit. Recurrent stroke occurred in 3.2% of patients. The stroke rate was 4.23% among patients with uncontrolled BP compared with 2.08% among patients with well-controlled BP (p=0.40).
This indicates that patients with elevated BP at the time of discharge from an ischemic stroke hospitalization remain with poorly controlled BP in the year post-discharge. Although patients appear to be receiving primary care services, these visits are not successfully achieving BP control. Relative underuse of certain resources for hypertension management such as ancillary services and home BP monitoring is observed.Future intervention studies seeking to improve the hypertension management of post-stroke patients should address these observed gaps in care.
Abstract 320: Urinary Albumin Excretion at Follow Up Predicts Cardiovascular Outcomes in Subjects With Resistant Hypertension
Authors: Oliveras Anna , Armario Pedro , Sierra Cristina , Arroyo José , Hernández del Rey Raquel , Vázquez Susana , Larrousse María , Sans Atxer Laia , Roca-Cusachs Alexandre , de la Sierra Alejandro 
Published: July 2021

Renal function and albuminuria predict CV disease in general population, but their predictive value in resistant hypertension (RH) is rather unknown.

Aim:
to determine the ability of renal parameters to predict adverse CV outcomes in RH patients.

Methods:
One hundred thirty-three (59% males, aged 61yr) RH pts. (BP ≥140/90 mmHg despite treated with ≥3 antihypertensive drugs) were evaluated. Mean follow-up: 88±5 months. Primary composite end-point: first occurrence of a CV event (nonfatal myocardial infarction, nonfatal stroke, new-onset heart failure, coronary or peripheral by-pass) or CV death. Renal function was assessed by serum creatinine, creatinine clearance (CrCL) and urine albumin/creatinine ratio (UACR). Microalbuminuria (MAB) was defined as UACR >30mg/g.

Results:
Twenty-two subjects (16.5%) reached the primary end-point. After adjustments for previous CV disease, systolic BP both at baseline and during follow-up and CrCl, high UACR during follow-up was significantly associated with a worse CV outcome (Table). More patients who had a CV event developed MAB at follow-up (28% vs. 6%), whereas the proportion with MAB regression in this group was lower (11% vs. 19%); p=0.005. Although renal function was also associated with outcome in unadjusted analyses, the significance was lost after baseline risk and BP adjustment.

Conclusion:
in patients with resistant hypertension, microalbuminuria at follow-up but not at baseline independently predicts CV outcomes.

* adjusted for SBP both at baseline and during follow-up and previous CV disease
** adjusted for the aforementioned confounders plus CrCl both at baseline and at follow-up; UACR tested after log transformation.
Abstract 11: Improved Prediction of Adverse Pregnancy Outcome With the sFlt-1/PlGF Ratio in Patients Suspected of Preeclampsia?
Authors: Verdonk Koen , van Ingen Manon , Smilde Johanna E , Steegers Eric A , Danser A. H. Jan , van den Meiracker Anton H , Visser Willy 
Published: July 2021

The sFlt-1/PlGF ratio has high sensitivity and specificity to diagnose preeclampsia (PE) and to predict pregnancy outcome. Especially in patients with preexisting hypertension and/or proteinuria, diagnosis and management of PE is challenging. We studied the predictive value of the sFlt-1/PlGF ratio for the occurrence of adverse outcome in patients with a high prevalence of preexisting hypertension or proteinuria, clinically suspected of having PE.
A sFlt-1/PlGF ratio >= 85 was considered to be a positive test. Adverse pregnancy outcome was defined as HELPP syndrome, intra-uterine growth restriction, or perinatal death. The predictive value of adverse pregnancy outcome of preeclampsia based on clinical grounds (clinical PE) or of a positive ratio was compared using a logistic regression model corrected for gestational age at testing.

Results:
So far 64 patients with a gestational age (GA) of 29.3 wks (range 20-37 wks) were included. 19 had preexisting hypertension, 5 had preexisting proteinuria and 6 had both conditions. At time of measurement 23 patients had clinical PE (4 with a negative ratio) and 30 patients had a positive sFlt-1/PlGF test (11 without clinical PE at testing of whom 7 developed clinical PE within 2 wks).

27% of patients had an adverse outcome of pregnancy. GA between patients with clinical PE or a positive test did not differ. Patients with clinical PE at the time of testing had an odds ratio of 2.5 (95% CI: 0.75 - 7.8) and patients with a positive test had an odds ratio of 6.8 (95% CI;2.1 - 33.9) for an adverse outcome. Patients with clinical PE had an absolute risk for an adverse outcome of 39% (9/23) compared to 46%(14/30) for patients with a positive sFlt-1/PlGF test (p=.075)
In patients where the diagnosis of PE is challenging because of preexisting hypertension and/or proteinuria a positive sFlt-1/PlGF is a stronger determinant for poor pregnancy outcome than the clinical diagnosis of PE. An explanation could be that a positive ratio can select patients that will develop PE in the near future and because of misclassification of patients with preexisting hypertension and/or proteinuria.
Abstract 153: Angiotensin II-induced Hypertension Alters Endothelial CaMKII
Authors: Charbel Chimene , Toussaint Fanny , Béziau Delphine , Blanchette Alexandre , Comtois Philippe , Ledoux Jonathan 
Published: July 2021

The endothelial dysfunction associated with arterial hypertension is characterized by a Ca2+ dyshomeostasis resulting in an alteration of the delicate balance between reactive oxygen species (ROS) and nitric oxide (NO). However, the underlying mechanisms remain controversial.
It has been recently suggested that CaMKII, a Ca2+-calmodulin dependent kinase plays an important role in cardiovascular diseases such as diabetes-associated hypertension. Paradoxically, CaMKII also modulates eNOS expression and activity, and is thereby involved in the regulation of endothelial function. Indeed, acting as a Ca2+ sensor, CaMKII has the unique ability to integrate oscillatory Ca2+ signals into specific outcomes. We recently provided the first evidence that endothelial CaMKII is activated by a local Ca2+ signal, the Ca2+ pulsars, localized within myoendothelial projections (MEP), and results in an increased NO production. The characterization of this novel endothelial CaMKII signalling pathway in pathophysiological conditions will strengthen our understanding of endothelial dysfunction associated with hypertension.
This study aimed at the characterization of the impact of AngII-induced hypertension on the correlation between endothelial Ca2+pulsars and CaMKII in microvasculature.
Real-time confocal imaging showed that acute exposure to AngII (10 μM) increases both ROS intracellular levels (52%) and Ca2+ pulsars frequency (35%). Exposure to lower AngII levels (100 nM) only increased Ca2+ pulsars frequency (49%). However, CaMKIIα and β clustering (and activation) within MEP was observed at both AngII levels. Acute AngII also stimulated NO production (42%), an increase blunted by CaMKII inhibition with KN-93 (17%). Although a significant increase in Ca2+ pulsars frequency was observed (147%) in AngII-hypertensive mice, an AngII-induce increased in endothelial ROS levels was recorded independently of blood pressure levels. Recruitment of CaMKIIα and β at the MEP by chronic AngII was also increased regardless of blood pressure (60% and 43%). Our finding strongly suggests that AngII stimulates CaMKII through both ROS and Ca2+ pulsars . This study consolidates our understanding of CaMKII as a key regulatory component of endothelial function.
Abstract 380: Short-term Treatment with Lercanidipine May Modulate Insuling Signalling and Oxidative Stress in Hypertensive Patients
Authors: Rossini Claudia , De Ciuceis Carolina , Flati Vincenzo , Rufo Anna , Porteri Enzo , Di Gregorio Jacopo , Petroboni Beatrice , La Boria Elisa , Sarkar Annamaria , Agabiti Rosei Claudia , Rizzoni Damiano , Agabiti Rosei Enrico 
Published: July 2021

We investigated the effects of antihypertensive treatment with two drug combinations on insulin signalling and oxidative stress.
Twenty essential hypertensive patients were included in the study and treated for 4 weeks with lercanidipine orally. Then they were treated for 6 months with lercanidipine+enalapril (n=10) or lercanidipine+hydrochlorothiazide (n=10). Investigations were performed in basal condition, after 4 weeks of monotherapy with lercanidipine, and at the end of the combination treatment. Insulin signalling was evaluated in mononuclear cells by Wester-Blot. Circulating levels of C-reactive protein (CRP), proinflammatory cytokines interleukin-6 and interleukin-18 (IL-18), macrophage chemotactic factor-1 (MCP-1), soluble vascular cell adhesion molecule 1 and soluble inter-cellular adhesion molecule 1, malonyldialdehyde and lipid peroxidation were measured in plasma.
Results are summarized in the Table (*P<0.05, **p<0.01 vs. Basal; #p<0.05 vs. lercanipine alone). An increased expression of insulin receptor, GLUT-4 and an increased activation of p70S6K1 were observed during treatment with lercanidipine+enalapril but not with lercanidipine+hydrochlorothiazide. A reduction in circulating levels of IL 18, CRP and MCP-1 was observed after treatment with lercanidipine alone, which persisted or further improved after treatment with lercanidipine+enalapril but not with lercanidipine+hydrochlorothiazide.
Therefore the combination treatment lercanidipine+enalapril seems more effective than lercanidipine+hydrochlorothiazide in activating insulin signalling, possibly due to a more marked antioxidant/antiinflammatory effect.