bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13781: Recurrence of Papillary Fibroelastoma
Authors: Sorour Ahmed , Kurmann Reto , El-Am Edward , Bois Melanie , Scott Christopher , Lee Alexander , Dearani Joseph A , Maleszewski Joseph J , Klarich Kyle W
Published: May 2021

Background:
Papillary fibroelastoma (PFE) is the most common benign cardiac tumor. Because PFEs have the potential to embolize, they typically are surgically excised. Prior studies have suggested that postoperative recurrence of PFE is rare or does not occur.

Objectives:
To determine the rate at which PFEs recurred after surgical removal and to identify any risk factors associated with recurrence.

Methods:
Patients with pathologically proven PFE were retrospectively identified from a single center. Patients were included in the study if they had an echocardiographic examination at least 1 year after surgery. Echocardiographic images obtained intraoperatively (after excision) and at dismissal were compared with those of the most recent examination to assess the possibility of PFE recurrence.

Results:
Ninety eight patients were identified. The mean (SD) duration of follow-up was 5.4 (3.7) years (range, 1-17 years). Twelve patients (12.2%) had echocardiographically proven PFE recurrence. Three patients had the recurrent lesion surgically re-excised, and pathologic analysis showed that 2 were recurrent PFEs and 1 was a Lambl excrescence. Clinical presentation of stroke or TIA was more common for the recurrence patients (for the first PFE) than for the nonrecurrence patients (83% vs 26%;
P
<.001).

Conclusions:
Contrary to published data, PFEs do recur after surgical excision. This emphasizes the importance of postoperative follow-up with transesophageal echocardiography for identifying recurrent masses.

Table. Characteristics of Patients With Recurrent PFE

Abbreviations: AV, aortic valve; LA, left atrium; LE, Lambl excrescence; LVOT, left ventricular outflow tract; MV, mitral valve; PV, pulmonary valve; RA, right atrium; RC, right cusp; TV, tricuspid valve.
a
Corresponds to the same location.
b
Corresponds to a different location

.
Abstract 13787: Efficacy of Lowering Low-density Lipoprotein Cholesterol in Elderly Subjects: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Gencer Baris , Marston Nicholas A , Im KyungAh , Sever Peter S , Keech Anthony C , Giugliano Robert , Sabatine Marc S
Published: May 2021

Introduction:
The clinical benefit from LDL-C lowering therapy in the elderly remains debated.

Aim:
To synthesize the efficacy of lowering LDL-C in patients aged ≥75 years in the light of most recently published data.

Methods:
Medline database was searched for the most recent evidence (2015-2020). The key inclusion criterion was a randomized controlled cardiovascular outcome trial testing an LDL-C lowering therapy with data available in patients aged ≥75 years at randomization. For efficacy, we meta-analyzed the risk ratio (RR) of major vascular events (a composite of cardiovascular (CV) death, myocardial infarction, stroke or coronary revascularization) per 1-mmol/L reduction in LDL-C.

Results:
Among 244,090 patients from 29 trials, 21,492 (8.8%) were elderly; 11,750 from statin trials, 6209 from ezetimibe trials, and 3533 from PCSK9 inhibitor trials. Median follow-up ranged from 2.2-6.0 years. LDL-C lowering therapy significantly reduced major vascular events (n=3519) in the elderly by 26% per 1-mmol/L LDL-C reduction (RR 0.74 [0.61-0.89], P=0.002), which was at least as good as the magnitude of effect seen in the non-elderly patients (RR 0.85 [0.78-0.92]; P
interaction
=0.24). Amongst the elderly, the RR was similar for statin (0.81 [0.70-0.94]) and non-statin therapy (0.67 [0.47-0.95]; P
interaction
=0.60). The benefit of LDL-C lowering in the elderly was observed for each component of the composite, including CV death (RR 0.85 [0.73-0.996], P=0.045), myocardial infraction (RR 0.80 [0.70-0.92], P=0.001), stroke (RR 0.71 [0.58-0.87], P=0.001) and coronary revascularization (RR 0.78 [0.63-0.96], P=0.017).

Conclusion:
In patients 75 years and older, lipid-lowering therapy is as effective in reducing CV events as it is in younger adults. These results should strengthen guideline recommendations for the use of lipid-lowering therapies, including non-statin therapy, in the elderly.
Abstract 13830: Soluble Klotho Suppresses Human Aortic Valve Interstitial Cell Fibrocalcification Induced by Fibroblast Growth Factor 23
Authors: The Erlinda , Ao Lihua , Zhai Yufeng , Fullerton David A , Meng Xianzhong
Published: May 2021

Aortic valve interstitial cells (AVIC) play a major role in the pathogenesis of calcific aortic valve disease (CAVD). Higher fibroblast growth factor 23 (FGF23) levels are associated with chronic kidney disease (CKD), an important risk factor of CAVD. The role of FGF23 in AVIC pathobiology associated with CAVD remains unclear. Klotho (KL) is an anti-aging protein present in membrane (mKL) and soluble (sKL) forms. While mKL is a coreceptor for FGF23, sKL may function as a FGF23 antagonist. We have found that KL inhibits osteogenic activity in AVIC exposed to CKD-associated high phosphate condition. We
hypothesized
that FGF23 mediates AVIC fibrocalcification, and sKL inhibits the effect of FGF23.

Methods and Results:
Protein levels of FGF23 and KL were analyzed in AVIC and aortic valves from CAVD patients. Diseased aortic valves and AVIC had higher FGF23 and lower KL levels than normal valves and AVIC, and diseased AVIC secreted greater amount of FGF23. Knockdown or neutralization of FGF23 in diseased AVIC suppressed their spontaneous fibrocalcification. Treatment of normal AVIC with recombinant FGF23 (40 ng/ml) for 72h enhanced the expression of collagens I and IV, Runx2, and alkaline phosphatase. Prolonged treatment of normal AVIC with FGF23 resulted in collagen and calcium deposition. Elevated levels of FGF receptor (FGFR) 1 and 4 were detected in normal AVIC after FGF23 stimulation. Inhibition of FGFR1 attenuated FGF23-induced fibrogenic response, while inhibition of FGFR4 abrogated FGF23-induced osteogenic response. Recombinant KL (0.5 μg/ml) reduced FGFR expression and fibrocalcification induced by FGF23. Further, KL attenuated FGF23-induced collagen and calcium deposition in normal AVIC. In vitro incubation of KL and FGF23 led to the formation of a complex.

Conclusion:
Diseased aortic valves and AVIC have higher levels of FGF23 and lower levels of KL. FGF23 is capable of inducing fibrocalcification in normal AVIC via FGFR1 and FGFR4. sKL suppresses FGF23 activities by inhibiting FGFR upregulation and direct interaction with FGF23. Our novel findings suggest that FGF23 may accelerate CAVD progression. sKL suppresses the pro-fibrocalcific effect of FGF23 and may offer therapeutic potential for slowing CAVD progression, especially in CKD patients.
Abstract 13834: Low Coronary Microvascular Vasodilator Capacity Relative to Myocardial Mass Predicts Cardiovascular Risk in Hypertensive Heart Disease
Authors: Brown Jenifer , Zhou Wunan , Weber Brittany , Divakaran Sanjay , Hainer Jon , Bibbo Courtney , Taqueti Viviany R , Dorbala Sharmila , Blankstein Ron , DI CARLI MARCELO
Published: May 2021

Introduction:
Increased left ventricular (LV) mass and coronary microvascular disease (CMD) have been independently associated with risk of heart failure (HF) and mortality in hypertensive heart disease. Inability to match increased LV mass and corresponding metabolic demand with adequate perfusion may be important in the development of HF.

Hypothesis:
PET-derived coronary microvascular vasodilator capacity indexed to LV mass (stress P/M) is associated with LV structure (end-diastolic volume index, EDVi, and end-systolic volume index, ESVi), LV function (LVEF) and identifies patients at elevated risk for HF hospitalization and death.

Methods:
We studied a retrospective cohort of consecutive symptomatic patients with hypertension presenting for rest/stress myocardial perfusion PET with LVEF ≥ 40%, normal perfusion (summed stress score < 3), and no prior CAD, cardiomyopathy, or HF. Stress P/M was defined as stress myocardial blood flow (MBF) divided by LV mass. CMD was defined by myocardial flow reserve (MFR = stress/rest MBF) ≤ 1.8. Associations between stress P/M and LV structure and function were assessed, and prognostic value for HF hospitalization and all-cause mortality was evaluated.

Results:
We studied 358 patients: mean age 62.7±12.3y, 72.4% female. Global stress MBF was negatively associated with LV mass (β=-0.023, P<0.001). Lower stress P/M was independently associated with greater EDVi (β=-0.557, p<0.001), greater ESVi (β=-0.943, p<0.001), and lower LVEF (β=0.819, p<0.001). A below-median stress P/M conferred increased risk of mortality or incident HF hospitalization (adjusted HR=1.73 [95% CI: 1.10-2.73], p=0.02) (Figure 1A) and conferred comparable risk to CMD in those with preserved MFR (Figure 1B).

Conclusions:
Coronary microvascular vasodilator capacity relative to myocardial mass integrates microvascular physiology with LV structure and function and refines risk of HF and all-cause death in hypertensive heart disease.
Abstract 13883: The Presence of Coronary Calcifications on the Chest CT Scan Performed to Diagnose Covid-19 is Associated With a Worse Prognosis
Authors: DILLINGER Jean Guillaume , Benmessaoud Fatima Azzahra , Pezel Theo , Voicu Sebastian , Sideris Georgios , Hamzi Lounis , Chauvin Anthony , Gautier Jean François , Sène Damien , Henry Patrick
Published: May 2021

Introduction:
With the coronavirus disease (COVID-19) outbreak, early identification of the most severely impacted patients is essential. Previous cardiovascular (CV) and metabolic diseases affect the COVID-19 prognosis. In high CV risk patients, coronary artery calcification (CAC) is associated with a higher incidence of CV outcomes.

Hypothesis:
To assess the association between the presence of CAC on the chest CT performed to diagnose COVID-19 and the occurrence of severe COVID-19 outcomes.

Methods:
Cross-sectional study on consecutive patients from 40 to 80 years of age, hospitalized for COVID-19 infection, with a chest CT without contrast injection performed on the day of admission. Patients with CV disease history were excluded. CAC was defined as any area ≥1mm2 with a density >130 Hounsfield units on the known coronary track. The primary outcome was the rate of patients with severe progression, defined as a score of 5 to 7 on the WHO Blueprint expert group scale (noninvasive or invasive mechanical ventilation, extracorporeal membrane oxygenation, death) within 8 days following hospital admission.

Results:
134 consecutive patients (60±8 years) were included. CAC was detected in 61 patients (46%). The primary outcome occurred in 29 (48%) of those 61 patients with CAC compared to 15 (21%) without CAC (HR 2.9; 95% CI [1.6 - 5.3]; p=0.0008). In patients ≤60 years (n=69), CAC was detected in 28% and the primary outcome occurred in 58% of patients with CAC compared to 16% without CAC (p=0.0006). In patients >60 years (n=65), CAC was detected in 63% of patients. In this population, the primary outcome occurred in 43% of patients with CAC compared to 30% without CAC without significant interaction. Multivariate analysis showed that CAC was independently associated with poor prognosis (HR 3.4; 95% CI [1.5 - 7.8]; p= 0.004).

Conclusions:
The evidence of CAC on initial chest CT performed in patients with COVID-19 is associated with a worse prognosis.
Abstract 13887: Cardiac Troponin I and Bnp for Predicting Zero Agatston Score in Patients With Diabetes Mellitus
Authors: Pezel Theo , DILLINGER Jean Guillaume , Bonnet Guillaume , Vidal Trecan Tiphaine , Asselin Anouk , Sideris Georgios , Logeart Damien , Manzo-Silberman Stéphane , Gautier Jean François , Riveline Jean Pierre , Henry Patrick
Published: May 2021

Introduction:
Coronary artery calcifications (CAC) Agatston score has shown an excellent prognostic value and particularly in diabetic patients, with a very low rate of cardiovascular (CV) events in patients with zero CAC score. Recent studies have suggested that high-sensitive cardiac troponin I (hs-cTnI) and brain natriuretic peptide (BNP) may be useful to detect subclinical atherosclerosis.

Hypothesis:
To assess the predictive value of hs-cTnI and BNP to predict zero CAC score in diabetic patients.

Methods:
Between 2015 and 2019, CAC score was performed in consecutive patients with diabetes mellitus. Patients with symptoms, coronary artery disease or atrial fibrillation were excluded. Within 24h from CT examination, blood samples were taken to measure hs-cTnI and BNP. The relationship between hs-cTnI/BNP concentrations and zero CAC score was evaluated using univariate and multivariate binomial models, and nested models associated with Chi-squared test of independence.

Results:
Among 844 diabetic patients (61±7 years, 57% men, duration of diabetes 18 years), 35% had zero CAC score, 30% a score from 1-100, 19% from 101-400, and 16% >400. Hs-cTnI/BNP were associated with zero CAC score (OR 2.63, 95%CI[1.51-5.01]; p<0.001; OR 1.09, 95%CI[1.01-1.22]; p=0.03 respectively). In multivariate analysis, hs-cTnI/BNP were associated with zero CAC score (OR 2.38, 95%CI[1.51-4.76]; p=0.009; OR 1.18, 95%CI[1.07-1.32]; p=0.001 respectively). Among 77 variables, the multivariate model including age, gender, smoking, dyslipidaemia, duration of the diabetes, hypertension, diabetic neuropathy, hs-cTnI and BNP significantly discriminated the zero CAC score (AUC=0.81; p<0.001). In nested models, both hs-cTnI and BNP brought information to this multivariate model to predict zero CAC score (p<0.001).

Conclusions:
Biomarkers hs-cTnI and BNP are associated with zero CAC score in diabetic patients.
Abstract 13918: Prognostic Value of Plasma Ngal in the 12-month All-cause Mortality of Acute Heart Failure or Acute Decompensated Heart Failure
Authors: Phan Hao T
Published: May 2021

Introduction:
The presence of acute kidney injury in the setting of acute heart failure (AHF) or acute decompensated heart failure (ADHF) is very common occurrence and was termed cardiorenal syndrome 1 (CRS1). Renal dysfunction is common in patients with AHF or ADHF and is associated with significant early and late morbidity and mortality. Neutrophil gelatinase-associated lipocalin (NGAL) is an early predictor of acute kidney injury and adverse events in various diseases; however, in AHF or ADHF patients, its significance remains poorly understood. This study was aimed to evaluate the 12 month prognostic value of plasma NGAL in AHF or ADHF patients

Hypothesis:
plasma NGAL has value in prognosis of 12-month all-cause mortality of Acute Heart Failure or Acute Decompensated Heart Failure

Methods:
This was a prospective cohort study

Results:
there were 46 all-cause mortality cases (rate 33.1%) 12 months follow up after discharge. There were 11 cases (rate 7.9%) lost to follow-up; mean age 66.12 ± 15.77, men accounted for 50.4%. The optimal cut-off of NGAL for 12-month all-cause mortality prognosis was > 383.74 ng/ml, AUC 0.632 (95% CI 0.53-0.74, p = 0.011), sensitivity 58.7 %, specificity 68.29 %, positive predictive value 50.9%, negative predictive value 74.7%. Kaplan-Meier analysis revealed that the high plasma NGAL (≥ 400 ng/ml) group exhibited a worse prognosis than the low plasma NGAL (< 400 ng/ml) group in 12-month all-cause death (Hazard Ratio 2.56; 95%CI 1.35-4.84, P=0.0039. Independent predictors of 12-month all-cause-mortality were identified using multivarable Cox proportional-hazards regression models with backward-stepwise selection method consisted of two variables: level of NGAL, mechanical ventialtion at admission.

Conclusions:
Plasma NGAL and mechanical ventilation at admission were independent predictors of 12-month all-cause mortality in patients with AHF or ADHF. The survival probability 12-month follow-up of high level NGAL (≥ 400 ng/ml) groups were lower than that of low level NGAL (<400 ng/ml,), difference was statistically significant χ2 = 8.31; p = 0.0047 by Kaplan-Meier curves.
Abstract 13933: High Urgency Candidates for Heart Transplantation Does Not Correlate to the Development of Primary Graft Dysfunction
Authors: Skorka Rafael , Nishihara Keith , Shen Adriana , Kransdorf Evan P , Benck Lillian , Patel Jignesh K , Kobashigawa Jon A
Published: May 2021

Introduction:
Primary Graft Dysfunction (PGD) after Heart Transplantation (HTx) is seen in approximately 7-30% of heart transplant patients as described by the literature. Many of these patients have severe PGD which requires support with ECMO. It has been reported that patients who are severely ill on high dose inotropes or on assists devices have greater propensity to develop severe PGD. Many of these patients have borderline blood pressure due to poor cardiac function which may contribute to PGD with its associated vasoplegia. In order to asses risk for the development of PGD we evaluated our patients in terms of their status at the time of transplant to assess risk.

Methods:
Between 2010 and 2019 we assessed 44 Heart Transplant patients who developed severe PGD immediately after HTx. The UNOS Status at the time of Transplant was recorded along with the presence of a durable assist device, temporary assist device, or no Inotropes or assist device. 30 Day and 1 Year survival were assessed for all status groups including a control group (no PGD, n=799).

Results:
High urgency status at the time of transplant was not the overwhelming majority of patients that developed severe PGD. Approximately 32% of these patients were patients who were waiting for transplant at home, who were not on Intravenous Inotropes and not on assist devices. 1 Year survival was compromised in all patients who developed severe PGD with survival rates that were significantly lower than patients without PGD in our program (47.7% vs 93.6%, p<0.001) (see Table).

Conclusions:
High urgency status is not solely associated with the development of severe PGD. Further assessment into these non-urgent patients who develop severe PGD is warranted and is under investigation. Inflammatory markers should be assessed in all patients who develop severe PGD.
Abstract 13936: Practitioners’ Inaccuracy in Decision-making With Assessing NYHA Functional Class of Patients With Heart Failure
Authors: Prasun Marilyn A , Stamp Kelly D , McCoy Thomas P , Rathman Lisa
Published: May 2021

Introduction:
Heart failure (HF) is a major public health problem and timely evidence-based guideline directed treatment is essential to ensure optimal patient outcomes. New York Heart Association (NYHA) functional class of HF patients is a clinically important assessment as it relates to treatment recommendations.

Purpose:
The purpose of this study was to examine HF providers’ decision making and ability to correctly assign NYHA functional class.

Methods:
A cross-sectional, correlational study using survey methods with 244 physicians, advanced practice nurses and physician assistants practicing in the United States in acute and ambulatory care settings that treat adult patients with HF was conducted. Providers completed 8 validated clinical vignettes focused on decision making that related to the four NYHA functional classes. Descriptive statistics and multivariable regression were used to analyze the data.

Results:
Participants were predominately female (83%), Caucasian (87%) and were on average 51 years of age (SD=11). Sixty-five percent were nurse practitioners and 18% physicians, most were certified in HF (59%) and on average worked with HF patients for 15.1 years (SD=9.6). Providers reported assigning NYHA class to 83% of their patients, with 39% reporting it was useful. Accurate identification of NYHA Class I was 78.7%, for Class II 57.4%, for Class III 59.8% and for Class IV 36.9%. Correct NYHA class scores were associated with providers who typically reported assigning HF stage (p<0.001), increased number of HF patients seen per week (p=0.024) and MD/DO providers relative to other advanced practice providers (p=0.021). Correct NYHA class scores were not associated with years working in a healthcare role, years working in HF, or years of certification adjusting for other provider and practice characteristics.

Conclusions:
Advanced practice providers who saw fewer HF patients had greater difficulty with accurately assigning NYHA Functional Class. When patients are incorrectly classed, they may not be recommended for evidence-based therapies at the optimal time, thus decreasing patient outcomes. Future research should focus on ways to improve accuracy in assigning NYHA Functional Class to improve patient outcomes.
Abstract 13940: Using an Angiotensin Converting Enzyme Inhibitor to Treat Cardiovascular and Cognitive Decline in a Rat Model of Vascular Dementia
Authors: SHEARON JENNIFER , Fenner Rachel , Grigorova Yulia , McDevitt Ross , Ajamu Samuel , Zernetkina Valentina , Wei Wen , Long Jeffrey , Rapp Peter R , LAKATTA Edward G , Fedorova Olga V
Published: May 2021

Background:
Aged Dahl salt sensitive rats (DSS) rats represent a model of vascular dementia, i.e., they develop central arterial stiffness (CAS), hypertension, and cognitive decline. DSS rats have compromised renin-angiotensin system (RAS) which is activated with age and contributes to hypertension. This study examined whether angiotensin converting enzyme (ACE) inhibitor, lisinopril, affects CAS and cognitive functions in aged male DSS (n=26).

Methods & Results:
Following initial measurements at 16-mo of age (baseline; BL), DSS were administered lisinopril through their water (LISI; 15mg/kg/day, n=11) or control treatment (n=15) for 2-mo. Pulse wave velocity (PWV), a marker of CAS, and systolic blood pressure (SBP) were measured at BL and at 18-mo of age. Open field test (OFT) to assess anxiety-like behavior and Morris water maze (MWM) to assess spatial memory were performed at 18-mo, then aortae and hearts were collected and weighed. Aortic wall collagen abundance was estimated by histochemistry. Statistical analyses were performed by 2-way ANOVA mixed effects model and t-test. The data are presented as mean ± SEM. At 18-mo of age, control animals had high SBP similar to BL (187±4 vs. 184±7 mmHg), while LISI-treated DSS had lower SBP by 39±4 mmHg vs. BL (p<0.01). PWV in control rats increased from 16 to 18-mo (7.0±0.6 vs. 10.8±1.0 m/s; p<0.05), while PWV in LISI-treated DSS decreased after 2-mo of treatment (7.1±0.3 vs. 5.4±0.3 m/s; p<0.01). Lower heart weights (2.9±0.1 vs. 3.7±0.3 g/kg BW; p<0.01), aortic weights (4.4±0.1 vs. 5.0±0.2 mg/mm/kg BW; p<0.01), and aortic medial collagen abundance (14.0±0.3 vs. 19.6±1.0 % of total; p<0.01) were observed in the LISI-treated rats vs. control rats. No differences between LISI-treated and control groups at 18-mo (38±10 vs. 25±6 cm traveled in center) were found in OFT. MWM results indicated that neither group at 18-mo of age was able to learn the task and therefore could not be accurately assessed for differences in spatial memory.

Conclusion:
Initiation of anti-hypertensive treatment in old age was effective in reducing aortic fibrosis and lowering SBP and PWV in DSS rats. Longer treatment may be needed to improve cognitive function in this model of vascular dementia. Supported by the NIH/NIA Intramural Research Program
Abstract 13945: Omega-3 Fatty Acids, Triglyceride Concentrations, and Cardiovascular Outcomes: The Systolic Blood Pressure Intervention Trial (SPRINT)
Authors: Kreft Lisa , Byrne Christina , Vaduganathan Muthiah , Biering-srensen Tor , Olsen Michael H , Bhatt Deepak L , Pareek Manan
Published: May 2021

Background:
Mixed omega-3 fatty acid preparations have shown inconsistent effects on triglyceride concentrations and cardiovascular (CV) events. Nevertheless, several formulations are widely available as prescription medications.

Purpose:
To assess the frequency of omega-3 fatty acid use and its association with triglyceride concentrations and CV outcomes in high-risk subjects from the Systolic Blood Pressure Intervention Trial (SPRINT).

Methods:
SPRINT was a randomized, controlled trial in which non-diabetic individuals aged ≥50 years, at high CV risk, and with a systolic blood pressure (BP) 130-180 mmHg were randomized to intensive (systolic BP target <120mmHg) or standard BP control (systolic BP target 135-139 mmHg). The primary outcome was the composite of acute coronary syndromes, stroke, heart failure, or CV death. Omega-3 fatty acid use was extracted via review of medication records of study participants. We first assessed the association between use of omega-3 fatty acids and triglyceride levels at baseline. We then examined associations between omega-3 fatty acid use and CV events. Finally, we tested whether use of omega-3 fatty acids affected the efficacy of other lipid-lowering agents and of intensive BP control.

Results:
Of 9361 participants, 680 (7.3%) used omega-3 fatty acids at baseline (632 marine-based, 27 plant-based, and 21 both). Median triglyceride concentrations did not differ between patients on omega-3 fatty acids versus those without (110 (range 25-1701) mg/dl versus 106 (range 23-3340) mg/dl; P=0.08). Median follow-up duration was 3.3 (range 0-4.6) years. Omega-3 fatty acid use was not associated with a reduction in the primary endpoint (adjusted hazard ratio 0.90, 95% confidence interval: 0.65-1.25; P=0.54), any of its individual components, or death from any cause (P≥0.05 for all). Moreover, omega-3 fatty acid use did not modify the effect of any other lipid-lowering agent or of intensive versus standard BP control (P≥0.05 for all).

Conclusions:
More than 7% of high-risk individuals in SPRINT used omega-3 fatty acid preparations. These agents did not affect CV outcomes. Indiscriminate prescription of omega-3 fatty acids should be discouraged, and only preparations with documented efficacy and safety should be used.
Abstract 13950: Predicted Heart Mass and BMI: Evaluating Undersized Heart Transplantation in Obese vs. Non-Obese Patients
Authors: Kim Samuel T , Helmers Mark R , Altshuler Peter , Iyengar Amit , Han Jason , Smood Benjamin , Birati Edo , Atluri Pavan
Published: May 2021

Introduction:
Although guidelines for heart transplant currently recommend against donors weighing ≥ 30% less than the recipient, recent studies have shown that the detriment of under-sizing may not be as severe in obese recipients. Furthermore, predicted heart mass (PHM) has been shown to be more reliable for size matching compared to metrics such as weight and body surface area. In this study, we use PHM to characterize the effects of undersized heart transplantation (UHT) in obese vs. non-obese recipients.

Methods:
Retrospective analysis of the UNOS database was performed for heart transplants from Jan. 1995 to Sep. 2020. Recipients were stratified by obese (BMI ≥ 30) and non-obese (30 > BMI ≥ 18.5). Undersized donors were defined as PHM ≥ 20% less than recipient PHM. Obese and non-obese populations separately underwent propensity score matching, and Kaplan-Meier estimates were used to graph survival. Multivariable Cox proportional-hazards analyses were used to adjust for confounders and estimate the hazard ratio for death attributable to under-sizing.

Results:
Overall, 50,722 heart transplants were included in the analysis. Propensity-score matching resulted in 2,214, and 1,011 well-matched pairs, respectively, for non-obese and obese populations. UHT in non-obese recipients resulted in similar 30-day mortality (5.7% vs. 6.3%, p = 0.38), but worse 15-year survival (38% vs. 35%, P = 0.04). In contrast, obese recipients with UHT saw similar 30-day mortality (6.4% vs. 5.5%, p = 0.45) and slightly increased 15-year survival (31% vs. 35%, P = 0.04). Multivariate Cox analysis showed that UHT resulted in an adjusted hazard ratio of 1.08 (95% CI 1.01 - 1.16) in non-obese recipients, and 0.87 (95% CI 0.78 - 0.98) in obese recipients.

Conclusions:
Non-obese patients with UHT saw worse long-term survival, while obese patients with UHT saw slightly increased survival. These findings may warrant reevaluation of the current size criteria for obese patients awaiting a heart.
Abstract 14040: Hospitalizations for Respiratory Syncytial Virus and Vaccine Preventable Infections Following Pediatric Heart Transplantation: A PHIS Database Analysis
Authors: Hayes Emily A , Hart Stephen , Gowda Charitha , Nandi Deipanjan
Published: May 2021

Introduction:
Despite improvements in pediatric heart transplant outcomes, respiratory syncytial virus (RSV) and vaccine preventable infections (R/VPI) are a major cause of morbidity and hospital resource use. The frequency and risk factors for hospitalizations due to R/VPI in heart transplant recipients are unknown.

Methods:
Patients ≤18 years who underwent heart transplantation at hospitals contributing to the Pediatric Health Information System database from 9/2003 to 12/2018 were identified. The transplant hospitalization and subsequent hospitalizations for R/VPI through 12/2018 were analyzed. Risk factors for R/VPI hospitalizations were evaluated using negative regression binomial models adjusted for potential demographic and clinical confounders. Total hospital costs were determined adjusted for 2018 US $.

Results:
Of 3,815 transplant recipients, 681 (17.9%) had a R/VPI hospitalization during 23,746 available person-years of follow-up after transplant. There were 984 R/VPIs diagnosed during 951 hospitalizations, and 440 (44.7%) occurred in the first year after transplant (Figure). The most common causes were RSV (n=380; 38.6%), influenza (n=265; 26.9%), and pneumococcus (n=105; 10.7%). In adjusted analyses, there was an increased risk of R/VPI hospitalization in patients requiring mechanical circulatory support prior to transplant, those who received induction with ≥ 2 immunosuppressive agents, and patients <2 years old. The median length of stay for a R/VPI hospitalization was 4 days (interquartile range [IQR]: 2-8 days) with a median total cost of $11,081 (IQR: $6,215 - $24,322).

Conclusions:
Hospitalization for R/VPIs occurred frequently following pediatric heart transplantation and were associated with significant cost. Potential strategies to minimize R/VPI could include expanding vaccine use through accelerated immunization schedules in younger patients and routine monitoring of immunogenicity after vaccination.
Abstract 14044: Engineering Bioactive Nanoparticles to Rejuvenate Vascular Progenitor Cells
Authors: Bui Loan T , Edwards Shanique , Alderfer Laura , Haneline Laura , Hanjaya-putra Donny
Published: May 2021

Introduction:
Fetal exposure to gestational diabetes mellitus (GDM) predisposes children to future health complications including hypertension and cardiovascular disease. A key mechanism by which these complications occur is through stress-induced dysfunction of vascular progenitor cells, including endothelial colony-forming cells (ECFCs). In particular, overexpression of transgelin (TAGLN), also known as SM22α, in GDM-ECFCs is associated with actin cytoskeletal rearrangement, which results in reduced cell migration and impaired vasculogenesis. We hypothesized that bioactive nanoparticles (NPs) conjugated on the surface of GDM-ECFCs can provide a sustained pseudo-autocrine stimulation to improve
in vitro
and
in vivo
vasculogenesis.

Methods & Results:
We designed multilamellar lipid NPs with an average size of 147±63 nm in diameter to deliver small molecules SB-431542 (TGF-β inhibitor) directly to the surface of GDM-ECFCs. Bioactive NPs can be robustly conjugated to the surface of ECFCs using thiol-maleimide coupling without altering cell viability and key progenitor phenotypes. By controlling the release kinetic of TGF-β inhibitor from the NPs, we can normalize TAGLN expression and improve cell migration, a critical key step in establishing functional vascular networks. Moreover, bioactive NPs can restore the vasculogenic potential of GDM-ECFCs in both 2D Matrigel and 3D collagen assays. Finally, when transplanted into immunodeficient mice, GDM-ECFCs conjugated with bioactive NPs exhibit robust
de novo
blood vessel formation with high engraftment rate, comparable to normal ECFCs.

Conclusions:
Collectively, these findings highlight a simple, yet promising strategy to rejuvenate GDM-ECFCs and improve their therapeutic potentials, which can be clinically-translated to address various cardiovascular complications, as well as toward a range of approaches in tissue repair and regenerative medicine.
Abstract 14055: Impact of a Boxed Meal Facilitated Plant-based Diet on Cardiometabolic Endpoints: A Clinical Trial
Authors: Keller Amanda L , Ziad Sanaz , Stephens Allison M , Tesch Elizabeth A , Sky Joseph , Shih Eric , Brooks Kirbee A , Howarth Vina E , Shah Sachin A
Published: May 2021

Background:
Plant-based diets (PBD) are increasingly recommended to reduce the risk of cardiovascular disease. Boxed meal-delivery services are a growing market facilitating consumer convenience; however, their effects on health require further study. We compared cardiometabolic changes between a boxed meal facilitated PBD (f-PBD) and Standard Omnivorous Diet (f-SOD).

Methods:
A prospective, controlled, parallel-designed trial assessing the impact of a f-PBD (n=16) to a f-SOD (n=16) on cardiometabolic endpoints was conducted in military beneficiaries. Participants with a BMI >25 kg/m
2
consuming a standard omnivorous diet volunteered to adopt a f-PBD or f-SOD for a 4-week period. Participants had the option to consume breakfast and lunch according to their adopted diet at the military dining facility. Dinner was facilitated by shipping a commercially available plant-based or standard omnivorous boxed meal kit to participants as appropriate. Lipid parameters were monitored at baseline and at 4 weeks. Weight, blood pressure (BP) and other clinical endpoints were assessed weekly. The primary endpoints were change from baseline at 4 weeks in calculated low-density lipoproteins (LDL-c) and weight. A student’s t-test was performed to assess differences between groups using the intention-to-treat methodology.

Results:
A total of 32 participants were enrolled in the f-PBD and f-SOD groups. Average age of participants was 33.3±7.8 years, BMI was 29.6±3.5 kg/m
2
and 50% were male. Change in LDL-c from baseline in the f-PBD and f-SOD groups were -9.41±21.7 mg/dl and +5.63±15.9 mg/dl, respectively (p=0.033). The change in weight from baseline in the f-PBD and f-SOD groups were -3.82±4.4 pounds and +0.87±2.7 pounds, respectively (p=0.001). Systolic BP decreased non-significantly in the f-PBD group (-4.88±5.4 mmHg vs -0.38±9.2 mmHg for f-PBD and f-SOD, respectively, p=0.103).

Conclusion:
Incorporating a meal-delivery f-PBD significantly reduced LDL-c and weight over a 4-week period. Plant-based meal kits could serve as a novel dietary intervention in the optimization of cardiovascular disease burden.
Abstract 14205: Aortic Vorticity, Helicity and Aortopathy in Adult Patients With Tetralogy of Fallot: Preliminary Study Using Four-dimensional Flow Magnetic Resonance Images
Authors: Shiina Yumi , Inai Kei , Nagao Michinobu
Published: May 2021

Introduction and hypothesis:
Flow hemodynamic parameters may relate to aortopathy in adults with tetralogy of Fallot. We aimed to employ quantitative analysis in the vorticity and helicity of the aortic root and the ascending aorta (AAo) in adults with tetralogy of Fallot (TOF), and to evaluate aortopathy and the relevant factors.

Methods:
Prospectively, 51 consecutive adults with TOF underwent 4 dimensional flow magnetic resonance imaging study for the assessment of vorticity and helicity of in the aortic root and AAo, wall shear stress (WSS), viscous energy loss (EL), and the left ventricular outflow tract - aortic root (LVOT-Ao) angle. Patients were divided into the two groups: dilated aortic root and/or AAo (indexed dimeter>25mm/cm2), Group A (15 patients); non-dilated aortic patients, Group B (36 patients). Ten age matched controls were also enrolled.

Results:
Group A showed acute LVOT-Ao angle, higher incidence of aortic regurgitation, and initial anatomy of pulmonary atresia, compared to Group B (P<0.0001, 0.02, 0.043). Group A showed greater vorticity at the level of Valsalva, AAo, and proximal arch, helicity, WSS, and EL than in Group B (P<0.001, <0.001, 0.049, 0.02, 0.026). Acute LVOT-Ao angle correlated with the diameter of the aortic root and AAo, vorticity, helicity, WSS, and EL (P=0.004, 0.023, 0.045, 0.004, 0.0004, 0.017). On a univariate logistic analysis, age, acute LVOT-Ao angle, AAo vorticity, AAo helicity, and maximum WSS were relevant factors of AAo dilatation (P=0.03, 0.02, 0.004, 0.03, 0.046). On a multivariate analysis, LVOT-Ao angle was the most important factor of AAo dilatation (odds ratio 0.66, 95%CI 0.46-0.95, P<0.024).

Conclusions:
TOF Adults with TOF presenting dilated AAo have greater vorticity, helicity, and acute LVOT-Ao angle. Flow eccentricity correlates with vorticity and helicity, which may affect the aortopathy in adults with TOF. AAo vorticity and helicity are also relevant factors of aortic dilatation, and these flow hemodynamic parameters may be adjunctive predictions of aortopathy in this population.
Abstract 14206: Assessing a Clinical Risk Score and the Impact of Race in Breast Cancer Patients at Risk of Cardiotoxicity
Authors: Brumberger Zachary , Branch Mary , Rigdon Joseph , Vasu Suji
Published: May 2021

Introduction:
Cardiotoxicity is a well-known risk in breast cancer patients treated with anthracyclines and trastuzumab. Ezaz et al. developed a clinical risk score (CRS) to risk stratify these patients. Despite evidence that African American (AA) race is a significant risk factor for cardiotoxicity, no study has assessed the impact of AA race on this CRS. Here we assess the discrimination ability of the Ezaz et al. CRS with the addition of AA race.

Methods:
This is a retrospective cohort utilizing a registry of 118 patients with stage I-IV breast cancer treated with anthracyclines and/or trastuzumab. Patients without baseline echocardiography data or with baseline LVEF < 50% were excluded. The CRS from Ezaz et al. consisting of age, adjuvant chemotherapy, coronary artery disease, atrial fibrillation or flutter, diabetes mellitus, hypertension, and renal failure was calculated with the addition of AA race. Cardiotoxicity was defined by an LVEF decline of ≥ 10% to LVEF < 53% from baseline.

Results:
In our 118 patient cohort, the mean age was 59 years, 23 (20%) AA patients, 65 (55%) patients considered low risk (scores of 0-3) and 53 (45%) considered moderate to high risk (scores ≥4). After a follow up of 3 months to 5 years, 14 (12%) patients developed cardiotoxicity.
Table 1
lists the CRS changes in statistical characteristics and predictability with the addition of AA race. In comparing the models, the AUC c-statistic increased from 0.609 to 0.642 (95% CI 0.47-0.75, 95% CI 0.49-0.79 respectively; P value = 0.56) with the addition of AA race (
Figure 1
).

Conclusions:
In this study, the Ezaz et al. CRS demonstrated improved discrimination and sensitivity with the addition of AA race. This study suggests AA race improves the predictive ability of the Ezaz et al. CRS. Given the limited size of our study, we promote that this should be hypothesis-driving and encourage further investigation on the path to develop an important risk stratification tool.
Abstract 14212: Sex Differences in the Age of Diagnosis for Cardiovascular Disease and Its Risk Factors Among Us Adults; Trends From 2008-2017, the Medical Expenditure Panel Survey
Authors: Okunrintemi Victor , Tibuakuu Martin , Virani Salim S , Sperling Laurence , Volgman Annabelle S , Gulati Martha , Cho Leslie , Leucker Thorsten M , Blumenthal Roger S , Michos Erin D
Published: May 2021

Introduction:
Although data up to 2016 suggests that mortality from cardiovascular disease (CVD) in the US appears to be on a decreasing trend, there is evidence of stagnation in progress among young adults, especially women. Sex differences in the trends for control of CVD risk factors have been described, but the temporal trends in the age at which CVD and its risk factors are diagnosed in the US, and whether there are sex-specific differences in these trends is unknown.

Methods:
We used the Medical Expenditure Panel Survey (MEPS) 2008-2017, a nationally representative sample of the US population. Individuals ≥18 years, with a diagnosis of hypercholesterolemia, hypertension, coronary heart disease (CHD) or stroke and reported the age at which these conditions were diagnosed were included. The trend in the age at diagnosis was calculated from the annual change overall and by sex, using a linear regression model.

Results:
There were 100,709 participants (50.2% women), representing 91.9 million US adults with the above disease conditions. The mean age at diagnosis of CVD risk factors has decreased over time, with steeper declines among women [(Hypercholesterolemia: women - annual decrease of 0.31 years, men-annual decrease of 0.24 years, all Ps<0.001); (Hypertension: women - annual decrease of 0.23 years, men - annual decrease of 0.20 years, all Ps<0.001); the annual decrease in the age at diagnosis for CHD was not statistically significant. For stroke, while the age at diagnosis decreased by 0.19 years annually for women (p=0.03), it increased by 0.22 years annually for men (p=0.02)

Conclusion:
The decreasing trend in the age at diagnosis for CVD and its risk factors in the US appears to be more pronounced among women. While earlier identification of CVD risk factors may provide an opportunity to initiate preventive treatment, younger age at diagnosis of CVD highlights the need for the prevention of CVD at the earliest opportunity and sex-specific interventions may be needed.
Abstract 14219: Oxidation of PKA-RIα Protects Against Ischemia-reperfusion Injury by Inhibiting Lysosomal-triggered Calcium Release
Authors: Simon Jillian N , VRELLAKU BESARTE , Monterisi Stefania , Chu Sandy , Rawlings Nadiia , Lomas Oliver , Marchal Gerard A , Waithe Dominic , Gajendragadkar Parag R , Jayaram Raja , Sayeed Rana , Channon Keith M , Swietach Pawel , Zaccolo Manuela , Eaton Phil , Casadei Barbara
Published: May 2021

Introduction:
Kinase oxidation is a critical signaling mechanism through which changes in the intracellular redox state alter cardiac function. In the myocardium, the regulatory Iα subunit of Protein Kinase A (PKARIα) can be reversibly oxidised, forming interprotein disulfide bonds within the holoenzyme complex. However, the impact of disulfide formation on kinase function, and its influence on PKA signaling in the context of heart disease remains unknown.

Methods & Results:
Myocardial ischemia-reperfusion (I/R) was found to be a potent inducer of PKARIα disulfide formation
in vivo
, both in mice and in humans. Using imaging modalities with high spatial and temporal resolution, we found that this conformation did not increase intrinsic PKA catalytic activity, but rather facilitated enhanced AKAP-dependent compartmentation of PKARIα in the adult mouse left ventricular (LV) myocyte, with preferential localization to the lysosome under oxidized conditions (n=38-41 myocytes, N=3 animals, p<0.01). Investigations in isolated LV myocytes revealed disulfide-modified PKARIα to be a significant regulator of lysosomal two pore channel (TPC)-dependent calcium-induced calcium release, with myocytes from ‘redox dead’ PKARIα mice (Cys17Ser) displaying spontaneous sarcoplasmic reticulum calcium release events and pronounced intracellular calcium oscillations. These events were prevented by ryanodine receptor blockade (1 mM tetracaine; n=14, p<0.01), acute depletion of lysosomal calcium stores (100 nM bafilomycin; n=7; p<0.01), or TPC inhibition (5 μM Ned-19; n=9; p<0.05). Absence of I/R-induced disulfide formation in “redox dead” PKARIα mouse hearts resulted in larger infarcts (2-fold increase, p<0.001) and a concomitant reduction in LV contractile recovery (1.6-fold, p<0.001), which could be fully prevented by administering the TPC inhibitor, Ned-19, at the time of reperfusion.

Conclusions:
Oxidised PKARIα acts as a potent inhibitor of intracellular calcium release in the heart through its redox-dependent interaction with the lysosome. In the setting of I/R, where PKA oxidation is induced, this regulatory mechanism is critical for protecting the heart from injury and offers a novel target for the design of cardioprotective therapeutics.
Abstract 14231: Balancing Exercise Risk With Cardiovascular Health in Pediatric Hypertrophic Cardiomyopathy
Authors: Sobierajski Frances , Bird Melissa , Anthony Samantha , Pol Sarah , Storey Kate , Pidborochynski Tara , Balmer-Minnes Diana , Power Alyssa , Jeewa Aamir , Conway Jennifer
Published: May 2021

Introduction:
Physical activity is vital to long-term cardiovascular health. However, patients with hypertrophic cardiomyopathy (HCM) are often advised to avoid strenuous physical activity due to the risk of sudden cardiac death.

Objective:
Given activity restrictions and recommendations for patients with HCM, our objective was to explore children and parents’ perceptions of a heart healthy lifestyle.

Methods:
Children with HCM and their parents were purposefully recruited at two Canadian sites for participation in a photovoice project. Participants (children and parents) were given a camera and asked to take pictures of everyday heart healthy or unhealthy choices. Photos were discussed during one-on-one qualitative interviews with children and parents separately to understand the photos meaning and significance. Inductive descriptive thematic analysis was used.

Results:
Thirteen child/parent pairs participated. Children (median 15.9 yrs old (range: 13.6-17.7), median BMI 28.5kg/m
2
(range: 17.8-36.7)) were mostly male (62%). Parents were all female. Most children were activity restricted (n=12). Participants took photos to represent being physically active, the majority being non-competitive activities. Specifically, they emphasized the importance of regular activity to support physical, emotional and heart health. While physical activity was identified as a healthy choice, participants learned from the cardiologist that certain activities were too risky to participate in. Despite these restrictions, children engaged in other types of activity and were supported by their parents and cardiologist. Two categories (self-limiting and finding the right sport) explained strategies children used to engage in physical activity in heart healthy ways. One child stated, “I think it got easier [over the years] because now I know my limits, and I know what I can and can’t do”.

Conclusions:
Children with HCM and their parents want to be physically active and sought guidance from the cardiologist. These data demonstrated how children with HCM used self-awareness to make heart healthy decisions about physical activity. This study supports the need for patient-centered, individualized physical activity counselling for patients with HCM.