bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17016: Cardiovascular Safety Profile of Gonadotropin Releasing Hormone (GnRH) Antagonist Compared to GnRH Agonist Among Patients With Prostate Cancer: A Meta-Analysis
Authors: Campbell Courtney , Addison Daniel , Baliga Ragavendra , Vallakati Ajay
Published: May 2021

Introduction:
Androgen deprivation therapy (ADT) is the cornerstone of advanced prostate cancer therapy. The degree that ADT contributes to cardiovascular disease remains uncertain with conflicting studies. ADT can be achieved through the use of gonadotrophin releasing (GnRH) hormone agonist or, more recently, GnRH antagonists. The objective of this study was to determine whether cardiovascular events differ after the initiation of GnRH agonist compared with GnRH antagonist in randomized control trials.

Methods:
From PubMed, Cochrane Central, and Embase we identified all randomized studies comparing GnRH antagonists with GnRH agonists in patients with prostate cancer from 2000-2020. Outcomes studied included major adverse cardiovascular events (MACE), coronary artery disease (CAD), cerebrovascular accidents (CVA), atrial fibrillation (AF), and heart failure (HF). A random effects model using the Mantel-Haenszel method was used to assess outcomes.

Results:
Overall, we identified 7 studies (n = 3298) which reported outcomes in prostate cancer patients receiving GnRH antagonists (n = 2127) compared with those receiving GnRH agonists (n = 1171). When compared to men receiving GnRH agonists, the incidence of MACE (RR 0.52, 95% CI 0.35-0.76, p<0.001) and CAD (RR 0.46, 95% CI 0.27 - 0.77, p=0.004) was lower in men receiving GnRH antagonists. There was no difference in the rates of CVA (RR 0.93, 95% CI 0.31-2.77, p=0.89), AF (RR 0.49, 95% CI 0.09-2.72, p=0.41), or HF (RR 0.55, 95% CI 0.19-1.59, p=0.52) between the two groups.

Conclusion:
For men with prostate cancer receiving ADT, GnRH antagonists decreased the incidence of MACE and coronary artery disease by half compared to men treated with GnRH agonists. GnRH antagonists have a more favorable cardiovascular safety profile than GnRH agonists.
Abstract 17025: Myeloid Rage Protects From Insulin Resistance in Mice Fed High Fat Diet
Authors: Arivazhagan Lakshmi , Ruiz Henry , Wilson Robin , Frye Laura , Ramasamy Ravichandran , SCHMIDT Ann Marie
Published: May 2021

Introduction:
Obesity is a major global health problem, with over one third of adults in the US classified as obese. Obesity often leads to a state of insulin resistance (IR), type 2 diabetes (T2D) and its complications. We previously showed that the receptor for advanced glycation end products (RAGE) and its ligands contribute to the pathogenesis of obesity and IR, as whole body and adipocyte-specific
Ager
(gene encoding RAGE) deleted mice fed a high fat diet (HFD) were significantly protected from weight gain and IR. Here, we hypothesize that myeloid RAGE contributed to IR upon HFD feeding.

Methods:
We generated mice with myeloid-specific (MDR) LyzMCre(+/+).Ager

flox/flox

and adipocyte and myeloid-specific (Double Knockouts) AdipoQCre(-/+)LyzMCre(+/+).Ager

flox/flox

deletion of
Ager
and LysMCre mice were used as control. Mice were fed either standard chow (LFD) or HFD (60% kcal/fat) for 3 months starting at age 6 weeks. Mice were assessed for body mass and composition, glucose and insulin sensitivity and whole body glucose metabolism by hyperinsulinemic-euglycemic clamp studies.

Results:
After 3 months HFD, there were no significant differences in body mass, body composition, food intake, energy expenditure and physical activity of the MDR mice vs. controls. Similar findings were observed in mice fed LFD. However, surprisingly, in HFD-fed mice, insulin tolerance tests and hyperinsulinemic-euglycemic clamp studies showed decreased insulin sensitivity and insulin action in the MDR vs. control mice, indicating that the MDR mice were more insulin resistant. The Double Knockout (myeloid/adipocyte) Cre (+) mice were more glucose tolerant and insulin sensitive compared to MDR mice, showing that deletion of
Ager
in the adipocytes rescued the adverse effects of
Ager
deletion in myeloid cells.

Conclusions:
Myeloid
Ager
protects from IR in mice fed HFD. Furthermore, in MDR mice, concomitant adipocyte-specific deletion of
Ager
rescues these mice from IR and, at the same time, reduces HFD-induced adiposity. The mechanisms underlying these findings are under active investigation.
Abstract 17050: Pulmonary Vein Isolation Leads to Decreased Stability of Rotational Activities in Atrial Regions Remote From the Site of Ablation - A New Mechanism by Which Pulmonary Vein Isolation Leads to Beneficial Remodeling in the Atria
Authors: Rottmann Markus , Yoo Shin , Pfenniger Anna , Johnson David , Geist Gail Elizabeth , Mandava Suman , Burrell Amy , Wasserstrom Andrew , Knight Bradley P , Passman Rod S , Arora Rishi
Published: May 2021

Introduction:
Pulmonary vein isolation (PVI) is thought to be efficacious in patients with paroxysmal and persistent atrial fibrillation (AF). However, the underlying mechanisms by which PVI leads to beneficial atrial remodeling are not clear.

Hypothesis:
We hypothesized that PVI leads to beneficial atrial remodeling by affecting electrophysiological characteristics at sites ‘remote’ from the site of ablation. We examined the effect of PVI on stability of rotational activity throughout both atria.

Methods:
AF was induced in 12 dogs by rapid atrial pacing for 3-6 weeks. PVI was performed in 3 dogs, 9 dogs were used as controls. Epicardial high-density mapping was performed (117 electrodes, inter-elec. distance 2.5mm) before and after PVI. The AF characteristics were analyzed in 6 regions in the left (LA) and right atrium (RA): Cycle length (CL), stability, number of observed rotational activities based on local activation time (LAT) maps.

Results:
Multiple interacting rotational activities were detected in all regions with highest stability in the appendages (Figure A). PVI led to a significant increase in CL (range: 2.26 %-14.1%) in all regions (Figure B). Stability of rotational activity decreased (baseline vs after PVI) in all atrial regions: LAA (594±344ms, median 525ms vs 354±126ms, median 300ms), PLA (564±491ms, median 360ms vs 180±25ms, median 180ms), LAFW (323±248ms, median 240ms vs 240±70ms, median 240ms), in PRA (260±1167ms, median 210ms vs 239±75ms, median 240ms), RAA (1521±1301ms, median 975ms vs 457±251ms, median 450ms), P<=0.05 for all comparisons, RAFW (1521±1301ms, median 975ms vs 457±251ms, median 450ms, P=0.46) (Figure C). PVI reduced number of observed rotational activities by 25.76% in all regions (P>0.5).

Conclusions:
PVI significantly reduces the stability of rotational drivers in atrial regions remote from the site of ablation. We believe we have discovered a new mechanism by which PVI leads to beneficial remodeling in both the LA and RA.
Abstract 17051: Bromocriptine Improves Central Aortic Stiffness in Adolescents With Type 1 Diabetes Mellitus: Arterial Health Results From the BCQR-T1D Study
Authors: Schafer Michal , Browne Lorna , Truong Uyen , Bjornstad Petter M , Baumgartner Amy , Barker Alexander J , Hunter Kendall , Tell Shoshana , Snell-bergeon Janet , Reusch Jane E , Shauer Irene , Nadeau Kristen
Published: May 2021

Introduction:
The presence of global vascular dysfunction is a well-recognized feature in youth with type 1 diabetes (T1D). This predisposes young patients to the life-long exposure and increased incidence of cardiovascular events. Therapeutic strategies to mitigate vascular dysfunction are urgently needed.

Hypothesis:
We hypothesized that bromocriptine quick release (BCQR) therapy would improve vascular health in youth with T1D.

Methods:
This was a placebo-controlled, random-order, double-blinded, cross-over study investigating BCQR as adjunct therapy on central aortic stiffness as measured by phase-contrast MRI. Participants also underwent flow mediated dilation test and brachial distensibility evaluation using tonometry. Adolescents with T1DM were randomized 1:1 to phase-1 of 4-week BCQR (minimum dose 1.6 mg daily) or placebo therapy after which all vascular measurements were performed. Following a 4-week washout period, phase 2 was performed in identical fashion with the alternate treatment.

Results:
Forty-two adolescents (mean age 15.9 yrs, HbA1c 8.6%, BMI %ile 71.4, TD duration 5.8 yrs) with T1D were enrolled. BCQR therapy decreased systolic (Δ = -5 mmHg,
p
< 0.001) and diastolic blood pressure (Δ = -2 mmHg,
p
= 0.039). BCQR therapy reduced ascending aortic PWV (Δ = -0.4 m/s,
p
= 0.005), and increased RAC (Δ = -2.6%,
p
= 0.022), and distensibility (Δ = 0.08 %/mmHg,
p
= 0.010). In the thoraco-abdominal aorta, BCQR decreased PWV (Δ = -0.2 m/s,
p
= 0.013) and increased distensibility (Δ = 0.05 %/mmHg, P = 0.032) (FIGURE). In contrast, BCQR decreased RHI (Δ = -0.34,
p
= 0.006).

Conclusions:
BCQR therapy improved central aortic stiffness and pressure hemodynamics in adolescents with T1D over 4 weeks. However, BCQR decreased peripheral RHI. BCQR therapy might serve as a potential clinical intervention to attenuate accelerated aortic stiffness in youth with T1D supporting future longer-term studies.
Abstract 17063: Angiotensin-Neprilysin Inhibition and Renal Outcomes in Heart Failure
Authors: Mc Causland Finnian R , Lefkowitz Marty , Claggett Brian , Anavekar Nagesh , SENNI MICHELE , Gori Mauro , Jhund Pardeep S , McGrath Martina , Packer Milton , SHI Victor , van Veldhuisen Dirk , ZANNAD Faiez , Comin-Colet Josep , Pfeffer Marc A , McMurray John J , Solomon Scott
Published: May 2021

Background:
In patients with heart failure, chronic kidney disease (CKD) is associated with a higher risk of renal events than in patients without CKD, irrespective of the ejection fraction. We assessed the renal effects of angiotensin/neprilysin inhibition in patients with heart failure in a pooled analysis of 13,195 patients with reduced and preserved ejection fraction.

Methods:
We combined data from PARADIGM-HF (LVEF eligibility≤40%; n=8,399) and PARAGON-HF (LVEF eligibility≥45%; n=4,796) in a prespecified pooled analysis. We assessed the effect of treatment (sacubitril/valsartan compared with enalapril or valsartan) on the renal composite outcome, defined as the time to first occurrence of either: ≥50% reduction in eGFR, end-stage renal disease, or death from renal causes. We also assessed the influence of therapy on eGFR slope.

Results:
At randomization, eGFR was 68±20 ml/min/1.73m
2
in PARADIGM-HF and 63±19 ml/min/1.73m
2
in PARAGON-HF. The composite renal outcome occurred in 70 of the 6594 patients (1.1%) in the sacubitril/valsartan group and 123 of the 6601 patients (1.9%) in the valsartan or enalapril group, with a risk reduction of 44% (HR 0.56, 95%CI 0.42-0.75; P<0.001). The treatment effect on the composite renal endpoint did not differ according to the baseline eGFR (<60 vs ≥ 60 ml/min/1.73 m
2
; P-interaction=0.46) or baseline ejection fraction (P-interaction=0.35). From randomization, the mean decline in eGFR was -1.8 (95%CI -1.9 to -1.7) ml/min/1.73 m
2
per year for the sacubitril/valsartan group, compared with -2.4 (95%CI -2.5 to -2.2) ml/min/1.73 m
2
per year for the valsartan or enalapril group, with an adjusted mean difference of 0.6 (95%CI 0.4 to 0.7; P<0.001) ml/min/1.73 m
2
per year.

Conclusions:
In patients with heart failure, sacubitril/valsartan reduced the risk of renal events, and slowed decline in eGFR, compared with valsartan or enalapril, across the spectrum of ejection fraction.
Abstract 17097: Non-Synonymous Mitochondrial DNA Variants Are Common in Myocardial Tissue of Heart Failure Patients
Authors: Ananya Pappu , Binder Michael , Wanjun Yang , McClellan Rebecca , Murray Brittney , James Cynthia , Barth Andreas S
Published: May 2021

Introduction:
Mitochondrial heart disease due to pathogenic mitochondrial DNA (mtDNA) mutations can present as hypertrophic or dilated cardiomyopathy, ventricular arrhythmias and conduction disease. It is estimated that the mutation rate of mtDNA is 10 to 20-fold higher than that of nuclear DNA genes due to damage from reactive oxygen species released as byproducts during oxidative phosphorylation. When a new mtDNA mutation arises, it creates an intracellular heteroplasmic mixture of mutant and normal mtDNAs, called heteroplasmy. Heteroplasmy levels can vary in various tissues and examining mtDNA variants in blood may not be representative for the heart. The frequency of pathogenic mtDNA variants in myocardial tissues in unknown.

Hypothesis:
Human ventricular tissue may contain mtDNA mutations which can lead to alterations in mitochondrial function and increase individual risk for heart failure.

Methods:
Mitochondrial DNA was isolated from 61 left ventricular myocardial samples obtained from failing human hearts at the time of transplantation. mtDNA was sequenced with 23 primer pairs. In silico prediction of non-conservative missense variants was performed via PolyPhen-2. Heteroplasmy levels of variants predicted to be pathogenic were quantified using allele-specific ARMS-PCR.

Results:
We identified 21 mtDNA non-synonymous variants predicted to be pathogenic in 17 hearts. Notably, one heart contained four pathogenic mtDNA variants (ATP6: p.M104; ND5: p.P265S; ND4: p.N390S and p.L445F). Heteroplasmy levels exceeded 90% for all four variants in myocardial tissue and were significantly lower in blood. No pathogenic mtDNA variants were identified in 44 hearts. Hearts with mtDNA mutations had higher levels of myocardial GDF-15 (growth differentiation factor-15; 6.2±2.3 vs. 1.3±0.18, p=0.045), an established serum biomarker in various mitochondrial diseases.

Conclusions:
Non-synonymous mtDNA variants predicted to be pathogenic are common in human left ventricular tissue and may be an important modifier of the heart failure phenotype. Future studies are necessary to correlate myocardial mtDNA mutations with cardiovascular outcomes and to assess whether serum GDF-15 allows identifying patients with myocardial mtDNA mutations.
Abstract 17257: Stroke Volume Reserve Index in HFrEF: A Non-Invasive Predictor of Early Clinical Outcomes and Marker of Inotropic Reserve
Authors: Selevany Ibrahim , Vaida Florin , Adler Eric D , Morris Timothy , Kim Paul
Published: May 2021

Introduction:
We investigated whether stroke volume reserve index (SVRI), a novel non-invasive measure of inotropic reserve at submaximal exercise, would predict 1-year mortality and need for advanced therapies in heart-failure with reduced ejection fraction (HFrEF) patients.

Methods:
We retrospectively studied a consecutive series of 245 ambulatory patients (57±11 years, 84% men) with HFrEF at a single center who underwent cardiopulmonary exercise testing (CPET) from January 2013 to December 2018. The primary outcome was defined as heart-transplantation, urgent left ventricular assist device (LVAD) implantation or death within 1 year of evaluation. SVRI was estimated at rest and at anaerobic threshold by VO
2
(oxygen consumption)/pulse and previously validated estimates of C[a-v]O
2
(arteriovenous difference in oxygen content). Multivariate regression selected the optimal predictors.

Results:
Among HFrEF patients studied, 82 (33.5%) deteriorated: 34 required heart-transplantation, 20 required LVADs and 28 died. SVRI of less than 130% was the best predictor of clinical deterioration (OR 3.98, p<0.005), followed by cardiac index of less than 2 L/min/m
2
(OR 3.74, p<0.005), and peak VO
2
below the International Society for Heart and Lung Transplantation (ISHLT) cut-off (OR 3.01, p=0.008). Kaplan-Meier curves showed that 1-year event-free survival was significantly better amongst patients with normal SVRI, compared to patients with impaired inotropic reserve. Notably, HFrEF patients with an abnormal SVRI had a poor 1-year prognosis regardless of their peak VO
2
.

Conclusions:
SVRI is a non-invasive measurement that provides a measure of inotropic reserve at submaximal exercise, provides valuable prognostic information independent of other known and validated CPET parameters, and may predict deterioration in HFrEF patients more accurately than currently recommended CPET predictors. SVRI and peak VO
2
provide complementary prognostic information.
Abstract 17354: Clinical Outcomes for Children With Paediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2 (PIMS-TS)
Authors: Kang Heechan , Whittaker Elizabeth , Piccinelli Enrico , Altamar Ivan , Krupickova Sylvia , Singh Yogen , fraisse alain , Bautista-Rodriguez Carles
Published: May 2021

Background:
PIMS-TS is heterogeneous in presentation, with significant proportion showing cardiac involvement. Data on cardiac outcomes is sparse and no consensus yet exists on follow-up management.

Aim:
To describe clinical and cardiac features during and soon after the acute phase of PIMS-TS patients.

Methods:
Prospective analysis and comparison of biochemical, electrocardiographic (ECG) and echocardiographic (TTE) data obtained during admission and on follow-up within 2 weeks of discharge. Cardiac MRI (CMR) was done mainly in those with myocardial hit (high Troponin, ECG changes or left ventricular dysfunction on TTE if available) during admission.

Results:
35 patients met criteria for PIMS-TS, (23 males, 66%) with a mean age 5 years. 49% were of Black, Asian or Minority Ethnicity (BAME). 75% of tested were IgG positive. Mean interval from symptom onset to admission was 5 days (range 1-12 days). Features included fever (100%), conjuctivitis (66%) oral mucositis/pharyngitis (60%), gastrointestinal symptoms (54%), rash (51%), erythema/oedema of extremities (31%) and cervical lymphadenopathy (31%). Presentation grouped into 3 types - 7/35 (20%) met AHA criteria for Kawasaki Disease (KD), 5 (14%) presented with shock and 23 (66%) had atypical presentations. 1 patient was treated for KD 6 years ago, no other co-morbidities noted in the cohort. Six (17%) needed PICU support (mean 1.8 days, range 1-4). 80% had normal ECGs during admission but abnormal repolarisation (11%), ischaemic changes (3%), arrhythmia (9%) were seen. 26% (9/35) had left ventricular (LV) dysfunction, of whom 7 had high serum Troponin (mean 183ng/mL SD 250) and Brain Natriuretic Peptide (BNP, mean 627ng/L SD 287). Coronary abnormalities were noted in 12 (34%). All blood markers (Troponin, BNP, Platelet count, C-reactive protein, D-dimer, Ferritin) returned to normal levels by discharge/follow-up. Follow-up global longitudinal strain (GLS) was normal in 94% (33/35). 5 (14%) had mild coronary ectasia. Of 16 CMR’s done <4 weeks of illness onset, 1 had subtle myocarditis, 1 late Gadolinum enhancement, 3 central vein ectasia, 1 pericardial effusion.

Conclusions:
Most biochemical and cardiac derangement during the acute phase normalised within weeks. Further study is on-going.
Abstract 17356: Cardiovascular Findings on Chest Computed Tomography Predict Clinical Outcomes in COVID-19
Authors: Camara Planek Maria Isabel , Kyung Stella , Ruge Max A , du Fay de Lavallaz Jeanne , Volgman Annabelle S , Williams Kim A , Suboc Tisha B , Simmons J. Alan , Rao Anupama
Published: May 2021

Background:
Computed tomography (CT) chest is routinely used for the diagnosis and management of COVID-19 patients. Though COVID-19 disease-specific pulmonary findings have been well described, the significance of concomitant cardiovascular findings on chest CT are less studied. We examined the presence of various cardiovascular findings as markers for predicting significant outcomes in COVID-19.

Methods:
A retrospective cohort study was conducted on 163 patients with confirmed COVID-19 who underwent chest CT. In addition to the reported pulmonary findings, specific cardiovascular CT variables were collected, including right and left ventricular dimensions, pulmonary artery and aortic size, reflux of contrast into the IVC, septal position, coronary artery and aortic calcifications. Multivariable analysis was used to determine whether cardiovascular findings predict a composite outcome consisting of in-hospital and 30-day mortality, Intensive Care Unit admission, intubation, extracorporeal membrane oxygenation, proning, and renal replacement therapy.

Results:
Among our cohort, aortic calcification significantly predicted an increased risk of the composite outcome (odds ratio (OR) 4.73, p < 0.0001). Larger RV diameter predicted composite outcome (OR 1.08, p < 0.01). RV/LV ratio > 0.9 (normal ratio < 0.9) showed borderline significant trend towards 30-day mortality (OR 1.12, p < 0.05). A combination of cardiac findings to discriminate between patients at higher or lower risk of a negative outcome (AUC 0.67, 95% CI 0.57 - 0.76) was non-inferior to a combination of pulmonary CT findings (AUC 0.68, 95% CI 0.6 - 0.76, p = 0.81).

Discussion:
Our data suggest that cardiovascular findings such as a dilated right ventricle and aortic calcification are important imaging markers in symptomatic patients with COVID-19. These findings highlight the importance of right ventricular parameters and vascular disease in predicting adverse clinical outcomes in these patients.

Conclusions:
Cardiovascular findings should be recognized and reported when imaging patients with COVID-19. Future, higher-power analyses of long-term outcomes in our cohort are anticipated to yield further results.
Abstract 17378: “If My Doctors Had Recommended a Mobile App to Me Back Then, I Wouldn't Have Been in This Situation Today”: Identifying the Barriers and Facilitators to the Utilization of mHealth Apps to Improve Self-Care in Patients With Heart Failure
Authors: Madujibeya Ifeanyi , Alreshidi Salman , Aroh Adaze
Published: May 2021

Background:
Mobile Health applications (mHealth apps) have been demonstrated as an effective strategy for improving self-care abilities in patients with heart failure (HF). However, the uptake of the apps by patients remains low. Little is known about the patient’s perspectives on the factors that influence their uptake of the apps. This study explored HF patients’ perspectives on the barriers and motivators to the uptake and utilization of mHealth apps.

Method:
Semi-structure interviews and demographic questionnaires were used to gather data from patients with HF (N= 43) recruited from an academic medical center. An in-depth analysis of the interviews was conducted using a deductive thematic approach with the help of qualitative software, Atias.ti version 8.

Results:
Among the participants ( median age = 62 [35-92] years, mean±SD ejection fraction = 37.3±17, 41.9% female, 70% smartphone owners), 90.7% (n =39) had no prior use of mHealth apps for self-care. The majority of the participants with no prior use of mhealth (79.5%, n = 31), including 64.7% (n= 17) of participants aged 65yrs and above, expressed an intention to use the apps for self-care. All the participants (100%) stated that their healthcare providers (HCP) had never recommended the use of mHealth apps for self-care. Other barriers included lack of knowledge of the apps, the perceived financial cost of mHealth apps or smartphones, concern for privacy, and security of personal information, resistance to the change of previous self-care strategies, and perceived technology incompetence. Motivators to the uptake of mHealth included perceived usefulness of mHealth apps, mHealth apps’ ease of use, and the belief that the use of mHealth apps may alleviate perceived threat to health, and availability of technical support.

Conclusion:
This study suggests that patients with HF are willing to use mHealth apps to improve their self-care abilities. Thus, the effort to improve patients’ perceptions of mHealth apps’

usefulness and HCP recommendation of the apps are warranted to turn patients' “intention to use” to actual apps usage.
Abstract 17380: Can Understanding of National Search Engine Queries Inform Heart Failure Prevention? National Internet Search Engine Queries Correlates With CHF Prevalence but Not Outcomes
Authors: atanda adebayo , Buhari Olajide , Alarfaj Mohammed , Khalil Hassan , Batresh Alberto , Weerakoon Shaneke , Nwagbara Kenechukwu , Atanda Oluwafunmilayo , Choi Andrew
Published: May 2021

Introduction:
Congestive heart failure (CHF) remains an epidemic with rising prevalence and a contributing cause of 1 in 9 deaths in the United States. An understanding of internet search engines for congestive heart failure as informational and initial diagnostic tools may enable targeted education strategies.

Hypothesis:
There is a correlation between CHF google search and outcomes.

Methods:
We used google trends, a publicly available google tool, to identify search frequency for CHF and related terms like early signs of heart failure, congestive heart failure facts over a 2 year period from 2014-2016 across regions of the United States. We then evaluated the prevalence of hospitalization and mortality rates among Medicare beneficiaries based on Center for Disease Control (CDC) data. Utilizing Pearson correlation (R) test, we determined the association between relative search frequency (RSF) in various states versus CHF hospitalization and mortality rates.

Results:
Across the 50 states in United States, there were 25 searches related to the search terms. There was a moderate positive correlation (R 0.4-0.7) between CHF hospitalization (R= 0.43) and mortality (R=0.51) with relative search frequency in google trends.

Conclusions:
We demonstrated a correlation between internet search and CHF prevalence and hospitalization. The emergence of data analytics in CHF care may enable greater understanding of patient questions in CHF to better target education and prevention.
Abstract 17413: Determination of Etiology of Left Ventricular Ejection Fracture Decline in Chemotherapy Related Cardiac Dysfunction
Authors: Patel Jay B , Hussain Muzna , Moudgil Rohit , Cheng Feixiong , Collier Patrick
Published: May 2021

Introduction:
Chemotherapy related cardiac dysfunction (CTRCD) is an undesired complication of anticancer treatment, roughly affecting 10% of patients undergoing therapy. The American Society of Echocardiography (ASE) and the European Association of Cardiovascular imaging (EACVI) defines CTRCD as a decrease in left ventricular ejection fraction (LVEF) greater than 10% from the lower limit of normal. Using this definition, several patients are diagnosed with CTRCD. Our study aims to understand the context of LVEF decline to help delineate the etiology of LVEF dysfunction in these patients.

Methods:
A retrospective descriptive study was conducted on registry of adult cancer patients (N=6754) referred to cardio-oncology clinic at the Cleveland Clinic between January 2011 and June 2018. The context of each LVEF decline event was independently adjudicated into one of nine categories: Chemotherapy induced, Valvular Heart Disease, Arrhythmia, Ischemia, Acute Hospitalization, Infiltrative disease, Misdiagnosed, Undifferentiated, or Other.

Results:
A cohort of patients (N=616) were identified to have CTRCD based on the ASE/EACVI definition. This cohort was 54% female and 80% Caucasian, with a median age of 58 years. In terms of therapy, 50% were exposed to anthracyclines, 15% exposed to HER2 neu inhibitors, 24% exposed to VEGF inhibitors. Upon adjudication of LVEF decline events, 31% of patients had isolated chemotherapy related decline, 24% caused by acute hospitalizations. 13% of events were multifactorial/undifferentiated and 11% of reported events were misdiagnosed.

Conclusion:
Our findings suggest left ventricular dysfunction in patients undergoing anticancer therapies can be multifaceted. Moreover, only a small proportion of reported CTRCD events were solely due to chemotherapy.
Abstract 17414: Combination Therapy of Sildenafil and Rapamycin Alleviates Doxorubicin Induced Cardiotoxicity With Improvement of Skeletal Muscle Function
Authors: Samidurai Arun , Kraskauskas Donatas , XI Lei , Kukreja Rakesh C , Das Anindita
Published: May 2021

Background:
Doxorubicin (DOX) is a chemotherapeutic agent for multiple cancers, however, it causes systemic inflammation with multi-organ injury, including irreversible skeletal muscle (SM) dysfunction and cardiotoxicity. Treatment either with phosphodiesterase 5 inhibitor, sildenafil (SILD) or mammalian target of rapamycin (mTOR) inhibitor, Rapamycin (RAPA) protects against myocardial infarction (MI), heart failure and also has anti-tumor effects. We contemplated that unique combination of SILD and RAPA may enhance protective effect against DOX-induced SM dysfunction and cardiotoxicity with attenuation of inflammation.

Methods and Results:
Adult female C57 mice were treated with DOX (5 mg/kg/week; i.p.) with/without RAPA (0.25 mg/kg/d, i.p.) and/or SILD (1.4 mg/kg/day; in drinking water) for 4 weeks. Cardiac function (ejection fraction) and SM grip strength were significantly decreased in DOX-treated mice (
Fig. A, B
), which were improved by co-treatment with SILD+RAPA. Myostatin which inhibits myogenesis, was significantly upregulated upon DOX treatment, but was reduced by SILD+RAPA in SM (
Fig. C)
. Adult mouse cardiomyocytes were treated with 1 μM DOX with/without 100 nM RAPA and/or 10 μM SILD for 24 hours. SILD+RAPA reduced DOX-induced apoptosis (assessed by TUNEL assay,
Fig. D
) and ROS-generation (assessed by H2DCFDA,
Fig. E
) while maintaining mitochondrial membrane potential (Δψ
m
; measured by JC-1 staining,
Fig. F
). Immunofluorescence staining revealed enhanced aggregation of ASC (adaptor molecule of inflammasome) following DOX treatment, which was inhibited by SILD+RAPA in cardiomyoblast (H9C2;
Fig. G)
and SM sol 8 cells (
Fig. H).

Conclusion:
Combination therapy with SILD+RAPA protects against DOX-induced cardiac and SM injury. Dual strategy of mTOR-PDE5 inhibition may be a novel approach to alleviate DOX toxicity during cancer treatment.
Abstract 17415: Mitochondrial Ca2+/Calmodulin-Dependent Kinase II Inhibition Changes the Calcium Homeostasis in the Endothelium and Decreases the Vascular Relaxation in Mesenteric Arteries
Authors: Damacena De Angelis Celio , Nuno Daniel W , Koval Olha , Lamping Kathryn G , Grumbach Isabella M
Published: May 2021

Introduction:
The Ca2+/Calmodulin-dependent Kinase II (CaMKII) is present in mitochondria and cytosol. In mitochondria, it regulates the mitochondrial Ca
2+
uptake via the mitochondrial Ca2+ uniporter. Since endothelial nitric oxide synthase activity is regulated by intracellular [Ca2+], we hypothesized that it affects cytosolic Ca2+, NO production and ACh-dependent vasodilation.

Hypothesis:
Inhibition of mitochondrial CaMKII in endothelium increases the cytosolic [Ca2+], and decreases vasorelaxation by Acetylcholine.

Methods:
CaMKII in mitochondria was inhibited through expression of the mitochondria-targeted CaMKII inhibitor peptide (mito-CaMKIIN) in a novel transgenic mouse model (endo-mtCaMKIIN) in endothelial cells only or delivered by adenoviral transduction (Ad-mtCaMKIIN) in human Aortic Endothelium cells (HAEC). In HAEC, cytosolic Ca2+ levels (by FURA-2 AM), eNOS activation and NOx levels were measured.

Results:
The basal Ca2+ levels were higher in the cytosol of mitoCaMKIIN cells (1.08 ± 0.02 Fura-2 ratio normalized by control, p<0.05). Thapsigargin-induced ER Ca
2+
release was significantly higher with mitoCaMKIIN (AUC 0.252 ± 0.027 versus 0.112 ± 0.01275, p<0.05), whereas cytosolic Ca
2+
levels after ACh were reduced (AUC 0.191 ± 0.025 versus 0.435 ± 0.054). Higher levels of phosphorylation of eNOS at Ser1177 and Thr495 sites were seen at baseline. The concentration-response curve of vascular relaxation to acetylcholine and SNP shifted to the right (p<0.05) in mesenteric resistance artery of mitoCaMKIIN mice.

Conclusions:
The inhibition of mitochondrial CaMKII in the endothelium increases the cytosolic levels, endoplasmic reticulum storage of calcium and eNOS phosphorylation. However, there are lower calcium release and lower sensitivity to acetylcholine and SNP.
Abstract 17425: Prevalence of Heart Failure in Polyarteritis Nodosa. A Descriptive Analysis From the National Inpatient Sample
Authors: Gopalakrishnan Akshaya , Amanullah Aman M , Rangaswami Janani , Reddy Sarath , Vasudevan Viswanath
Published: May 2021

Introduction:
Polyarteritis Nodosa (PAN) is a systemic necrotizing vasculitis of medium sized arteries. Congestive heart failure (CHF) in PAN could be due to coronary artery disease, coronary artery aneurysm or renal artery vasculitis. We utilized a national database to study the prevalence of CHF in patients with PAN.

Hypothesis:
We hypothesized that patients with PAN might have increased prevalence of CHF.

Methods:
All inpatients more than 18 years of age from the National Inpatient Sample (NIS) between 2009-10 with a diagnosis of PAN were extracted using 9th revision of International Classification of Diseases (ICD-9) code 446.0. Prevalence of CHF and other cardiac risk factors were identified using ICD-9 codes. Logistic regression analysis was performed to examine the association between PAN and CHF.

Results:
PAN was prevalent in 0.01% (n=3,944) of all inpatient hospitalizations. Patients with PAN were slightly older, more commonly females and had higher rates of CHF (11.3% vs 6.4%; p<0.0001) when compared to the general population. Diabetes mellitus, hypertension, atrial fibrillation, chronic renal insufficiency and chronic lung disease were more prevalent in patients with PAN (p<0.0001 for all). PAN independently predicted CHF both in unadjusted [OR 1.88 (1.49-2.38); p<0.001] and multivariable model adjusted for demographics and other risk factors for CHF [OR 1.36 (1.05-1.78); p=0.02.

Conclusions:
PAN was associated with increased prevalence and independent predictor of CHF. Further studies are recommended to validate this finding and consider it as a part of routine work up.
Abstract 17484: Prevalence, Prognosis and Predictors of Neurological Complications After Heart Transplantation
Authors: Caraviello Camila , Harsanyi Daniela , Mangini Sandrigo , Trevizan Ligia , Bacal Fernando
Published: May 2021

Introduction:
Heart transplantation (HT) is the gold-standard treatment for end-stage heart failure. In spite of its benefits, this therapy still involves complications. Among them, neurological complications may impact significantly patient’s morbidity and mortality. The aim of this study is to identify the prevalence, prognosis and predictors of neurological complications after HT.

Methods:
Data from all patients who underwent orthotopic HT between 2007 and 2017 in a single center were collected and analyzed. Neurological complications were defined as seizures, ischemic and hemorrhagic stroke. Univariate and multivariate analysis were performed to identify significant predictors and ROC curves were generated to determine cutoff values that could influence the presence of neurological complications.

Results:
We assessed 132 patients from 15-76 years of age, mean age of 51.8 (73.5% men), who were mainly in INTERMACS profile 3 (78.8%). Cardiomyopathy etiologies included Chagas disease (26.7%), ischemic cardiomyopathy (26.7%), idiopathic dilated (24.4%) and other etiologies (22.2%). Neurological events before transplant were present in 16.7%. Neurological complications after HT occurred in 17.4% of patients (8.7% ischemic stroke, 60.9% hemorrhagic stroke and 30.4% seizures), mainly in the first 10 postoperative days (71.4%) and were not related to a higher mortality risk (p=0.159). In the multivariate analysis, pre-transplant adrenaline use (p-value=0.044; 95% CI of 1.07-179.25, OR 13.84) and the difference between mean systolic blood pressure before HT and on the 3rd postoperative day (p-value=0.011; 95% CI of 1.38-11.56, OR 3.99) were independent predictors of neurological complications. A cutoff value higher than 32 mmHg (between mean systolic blood pressure before HT and on the 3rd postoperative day) increased the risk of neurological complications (64.3% sensitivity, 63% specificity; AUROC 0.652).

Conclusion:
In this single center study, prevalence of neurological complications was high, however had no impact on prognosis. Pre-transplant adrenaline use and systolic blood pressure elevation in the 3rd postoperative day in comparison to the pre-transplant period were predictors of neurological complications.
Abstract 17491: Abstract
Authors: Azam Tariq , Berlin Hanna , Shadid Husam , Pan Michael , Anderson Elizabeth , Meloche Chelsea , Feroze Rafey , Leya Jeff , O'Hayer Patrick , Kaakati Rayan , bitar abbas , Padalia Kishan , Perry Daniel , Blakely Pennelope , Zhao Peiyao , Zhao Lili , Hayek Salim
Published: May 2021

Introduction:
Mortality and demographic data during the COVID-19 pandemic demonstrate a disproportionate prevalence and mortality among patients identifying as Black and Native American.

Hypothesis:
We hypothesized minority patients would have worse COVID-19 outcomes and be less likely to receive COVID-19 specific therapies compared to Caucasian patients.

Methods:
We used the Michigan Medicine COVID-19 Cohort to extract treatment and outcome data on adult patients with COVID-19 who had been discharged or died by June 17
th
, 2020. We calculated crude rates of COVID-19 specific treatments and outcomes between patients identifying in different racial groups using Caucasian patients as a baseline.

Results:
Of 553 patients analyzed, 486 patients were included, 213 (43.8%) identified as Caucasian, 232 (47.7%) identified as Black, 33 (6.8%) identified as Asian, 6 (1.2%) had an unknown racial group, and 1 identified as more than one race and 1 identified as Native American. Given this distribution, analysis was focused on Black and Caucasian patients. Black patients were less likely to receive remdesivir (3.9% vs 12.2%, P-value = 0.001) or be enrolled in COVID-19 clinical trials (10.3% vs 19.7%, P-value = 0.005). Black patients were more likely than Caucasian patients to have acute kidney injury (63.8% vs 45.5%, P-value = <0.001) and need renal replacement therapy (20.3% vs 9.9%, P-value = 0.002). No significant differences were noted in mortality, ARDS, need for renal replacement therapy at discharge, or length of stay.

Conclusions:
Racial disparities exist in both treatment and outcomes in COVID-19. We report a stark difference in the rate of receipt of remdesivir between Black and Caucasian patients and lower Black patient enrollment in clinical trials, matching trends in other areas of medicine. Further study is needed to determine if these differences in treatment are associated with the differential renal outcomes seen, and how comorbidities impact outcomes.
Preterm Delivery and Long-Term Risk of Stroke in Women: A National Cohort and Cosibling Study
Authors: Crump Casey , Sundquist Jan , Sundquist Kristina
Published: May 2021

Background:

Stroke has a high burden of disease in women, and adverse pregnancy outcomes have been identified as important risk factors for stroke later in life. However, long-term risks of stroke associated with preterm delivery and whether such risks are attributable to familial confounding are unclear. Such knowledge is needed to improve long-term risk assessment and stroke prevention in women.

Methods:

A national cohort study was conducted of all 2 188 043 women with a singleton delivery in Sweden in 1973 through 2015 who were followed up for stroke identified from nationwide diagnoses through 2015. Cox regression was used to compute adjusted hazard ratios (aHRs) for stroke associated with pregnancy duration, and cosibling analyses assessed for confounding by shared familial (genetic or environmental) factors.

Results:

In 48.0 million person-years of follow-up, 36 372 (1.7%) women were diagnosed with stroke. In the 10 years after delivery, the aHR for stroke associated with preterm delivery (gestational age <37 weeks) was 1.61 (95% CI, 1.45–1.79) and further stratified was 2.81 (95% CI, 2.02–3.91) for extremely preterm (22–27 weeks), 2.07 (95% CI, 1.74–2.46) for very preterm (28–33 weeks), 1.38 (95% CI, 1.21–1.57) for late preterm (34–36 weeks), and 1.15 (95% CI, 1.06–1.24) for early term (37–38 weeks), compared with full-term (39–41 weeks) delivery. These risks remained similarly elevated at 10 to 19 years after delivery (preterm versus full-term: aHR, 1.61 [95% CI, 1.50–1.74]) and then declined but remained significantly elevated at 20 to 29 years (aHR, 1.35 [95% CI, 1.28–1.44]) and 30 to 43 years (aHR, 1.35 [95% CI, 1.27–1.42]). Preterm delivery was associated with both hemorrhagic (aHR, 1.31 [95% CI, 1.25–1.38]) and ischemic (aHR, 1.54 [95% CI, 1.47–1.61]) stroke across the entire follow-up period (up to 43 years). These findings were not explained by shared determinants of preterm delivery and stroke within families. Stroke risks were higher after either spontaneous or medically indicated preterm delivery, and recurrent preterm delivery was associated with further increases in risk.

Conclusions:

In this large national cohort, preterm delivery was associated with higher future risks of both hemorrhagic and ischemic stroke. These associations remained substantially elevated at least 40 years later, and were largely independent of covariates and shared familial factors. Preterm delivery should be recognized as a risk factor for stroke in women across the life course.
Hemostatic Efficacy and Anti-FXa (Factor Xa) Reversal With Andexanet Alfa in Intracranial Hemorrhage: ANNEXA-4 Substudy
Authors: Demchuk Andrew M. , Yue Patrick , Zotova Elena , Nakamya Juliet , Xu Lizhen , Milling Truman J. , Ohara Tomoyuki , Goldstein Joshua N. , Middeldorp Saskia , Verhamme Peter , Lopez-Sendon Jose Luis , Conley Pamela B. , Curnutte John T. , Eikelboom John W. , Crowther Mark , Connolly Stuart J. ,   on behalf of the ANNEXA-4 Investigators
Published: May 2021

Background and Purpose:

Andexanet alfa is a recombinant modified human FXa (factor Xa) developed to reverse FXa inhibition from anticoagulants. Hemostatic efficacy and reversal of anti-FXa activity with andexanet were assessed in patients from the ANNEXA-4 study (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXa Inhibitors) with intracranial hemorrhage (ICrH).

Methods:

ANNEXA-4 was a single-arm study evaluating andexanet in patients presenting with major bleeding ≤18 hours after taking an FXa inhibitor. Patients received a bolus plus 2-hour infusion of andexanet. Brain imaging in patients with ICrH was performed at baseline and at 1 and 12 hours postandexanet infusion. Coprimary efficacy outcomes were change in anti-FXa activity and hemostatic efficacy at 12 hours (excellent/good efficacy defined as ≤35% increase in hemorrhage volume/thickness). Safety outcomes included occurrence of thrombotic events and death at 30 days.

Results:

A total of 227 patients with ICrH were included in the safety population (51.5% male; mean age 79.3 years) and 171 in the efficacy population (99 spontaneous and 72 traumatic bleeds). In efficacy evaluable patients, excellent/good hemostasis 12 hours postandexanet occurred in 77 out of 98 (78.6%) and in 58 out of 70 (82.9%) patients with spontaneous and traumatic bleeding, respectively. In the subanalysis by FXa inhibitor treatment group in the efficacy population, median of percent change in anti-FXa from baseline to nadir showed a decrease of 93.8% for apixaban-treated patients (n=99) and by 92.6% for rivaroxaban-treated patients (n=59). Within 30 days, death occurred in 34 out of 227 (15.0%) patients and thrombotic events occurred in 21 out of 227 (9.3%) patients (safety population).

Conclusions:

Andexanet reduced anti-FXa activity in FXa inhibitor-treated patients with ICrH, with a high rate of hemostatic efficacy. Andexanet may substantially benefit patients with ICrH, the most serious complication of anticoagulation.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02329327.
Patient-Reported Experience Measures in Stroke Care
Authors: Cornelis Cosette , den Hartog Sanne J. , Bastemeijer Carla M. , Roozenbeek Bob , Nederkoorn Paul J. , Van den Berg-Vos Renske M.
Published: May 2021

Background and Purpose:

Patient-reported experience measures (PREMs) assess patients’ perception of health care. We aimed to identify all reported PREMs for stroke care and critically appraise psychometric properties of PREMs validated for patients with stroke.

Methods:

Studies on the development, validation, or utilization of PREMs for adult patients with stroke were systematically identified. The Consensus-Based Standards for the Selection of Health Measurement Instruments criteria were used to appraise psychometric performance.

Results:

We included 18 studies, examining 13 PREMs. Two PREMs had been developed for stroke care: Consumer Quality Index: Cerebrovascular Accident and Riksstroke. Consumer Quality Index: Cerebrovascular Accident was given a positive psychometric assessment, but its length and limited language applicability impede clinical implementation. Riksstroke was appraised as doubtful. Eleven PREMs were generic. The psychometric performance of 5 generic PREMS, validated for patients with stroke, received conflicting assessments. Six generic PREMs had not been validated in patients with stroke and were therefore not assessed for instrument performance.

Conclusions:

Thirteen PREMs have been published for use in stroke care. The stroke-specific Consumer Quality Index: Cerebrovascular Accident has favorable psychometric performance but lacks practical feasibility. Other PREMs have inadequate or unknown psychometric properties. This indicates the need for developing stroke-specific PREMs to support quality improvement and enhance patient-centered care.
A Maqāma on Same-Sex Marriage in the Thirteenth Century
Authors: Pomerantz Maurice
Published: May 2021

This article provides an editio princeps and English translation of al-Maqāma al-Hītiyya al-Šīrāziyya by al-Šābb al-Ẓarīf al-Tilimsānī (d. 688/1289) preserved in Berlin MS Wetzstein 1847. The maqāma describes a romantic liaison conducted between an older Mamluk and a younger boy. The analysis considers the various literary forms deployed by the author in the course of the maqāma, such as: an erotic epigram, a love letter, mujūn verse, and a marriage ḫuṭba. The conclusion of the article explores what this work reveals about the history of the maqāma form, language, and truth.
Kapgateophyllum gen. nov. (Acanthaceae)

Authors: DESHMUKH UMAKANT  BHOOPATI
Published: May 2021

Acanthophyllum C.A.Meyer (1831: 210) (Caryophyllaceae Juss.), a genus comprising 80–90 perennial sub-shrubby species with Irano-Turanian distribution pattern extending from Syria to Western China (Bittrich 1993, Ghaffari 2004, Pirani et al. 2014), was first established by Meyer (1831: 210) [type species: Acanthophyllum mucronatum C.A.Meyer (1831: 210)].
Morphology of pupae of Synanthedon codeti (Oberthür, 1881) and Synanthedon theryi Le Cerf, 1916 (Lepidoptera: Sesiidae)
Authors: BĄKOWSKI MAREK
Published: May 2021

This work presents the first description of the pupal morphology of the clearwing moth species Synanthedon codeti (Oberthür, 1881) and S. theryi Le Cerf, 1916.                All diagnostic morphological features are described in detail, compared with the closely related species S. vespiformis (Linnaeus, 1761), and the features are illustrated with photographs and line drawings.