bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18038: Gender Differences in Anticoagulation and Stroke Outcomes in Atrial Fibrillation
Authors: Kassim Natasha A , Qin Dingxin , Richards Thomas , Leef George , Saba Samir
Published: March 2022

Introduction:
Women with atrial fibrillation (AF) have a higher risk of ischemic stroke than men.

Hypothesis:
The primary hypothesis is that rates of anticoagulation differ between men and women with AF. The secondary hypothesis is that a difference in rate of anticoagulation results in difference in ischemic stroke-free survival in men and women with AF.

Methods:
We analyzed the records of 5,976 consecutive AF patients who were prescribed at least one antiarrhythmic drug between 2006 and 2013. Time to clinical outcome events was assessed using the survival analysis method and adjusted for covariates using Cox regression.

Results:
Compared to men, women (N=2,448, 41%) were older (73 vs. 67 years, p<0.001) , had higher CHADS2 scores (3.4 vs. 2.3, p<0.001), and less comorbidities including CHF, coronary artery disease, prior cardiac arrest, depression, and alcohol/tobacco use. Overall, women were less likely to be anticoagulated than men (77% vs. 83%, p<0.001). The cohort was divided into low, intermediate, or high risk of stroke by CHADS2 score, and difference in rates of anticoagulation by gender was seen in each subgroup (77% vs. 81% low, 75% vs. 83% intermediate, and 80% vs. 87% high, p<0.05). Stroke-free survival was worse in women compared to men (unadjusted p=0.05, HR 0.77), though this difference lost statistical significance when adjusted for multiple covariates (adjusted p=0.5, HR 0.93). The difference in stroke outcome between men and women was most prominent in the low risk group (Figure).

Conclusions:
In our cohort, women with AF were less likely than men to be anticoagulated. In the subgroup with lowest risk of stroke, women had worse stroke-free survival.
Abstract 18044: Predictors of Bicuspid Aortic Valve Associated Aortopathy in Pediatric Patients
Authors: Grattan Michael , Prince Andrea , Franco-Cereceda Anders , Petrovic Michele , Mohamed Salah A , Loeys Bart , Dietz Harry , Mital Seema , Manlhiot Cedric , Andelfinger Gregor , Mertens Luc
Published: March 2022

Bicuspid aortic valve (BAV) is the most common congenital heart disease and is commonly associated with significant ascending aorta dilation. Valve morphology and function have been proposed as potential risk factors; however evaluating their role is difficult, as BAV morphology and valve function are inherently related. Our objective was to determine whether BAV morphology and function are independently associated with ascending aorta dilation in pediatric patients.

We performed a multicenter, retrospective, cross-sectional study of pediatric patients with BAV that were followed after 2003. The last patient echocardiogram prior to valve intervention was analyzed for BAV morphology, presence and severity of aortic stenosis (AS) and insufficiency (AI), and aortic root and ascending aorta dimensions. The relationship of potential risk factors to ascending aorta dimensions at different ages was determined using linear regression.

Data was obtained from 1725 patients (68% male). The most common BAV morphology was right-left (R-L) coronary cusp fusion (65%) followed by right-non (R-N) fusion (34%) and left-non fusion (1%). Fourteen percent of patients had at least moderate AS and 7% had at least moderate AI. R-L fusion was associated with coarctation (55%), while R-N fusion was less associated with coarctation (19%) and more associated with valve dysfunction (24% and 12% with at least moderate AS and AI). Twenty-seven percent of patients had significant ascending aorta dilation (Z score >3). AS and AI were associated with more significant ascending aorta dilation and a faster Z-score progression over time. R-N fusion was associated with ascending aorta dilation; however, when valves with AS and AI were excluded, there were no differences related to morphology. In patients with no AS or AI, 15% had significant ascending aorta dilation.

In this large pediatric cohort of patients with BAV, we show that valve morphology is not independently associated with ascending aorta dilation. Valve dysfunction (both AS and AI) is associated with more significant dilation; however, even in valves with normal function, there is significant ascending aorta dilation. We suggest that there is an inherent arterial abnormality, possibly modified by aortic flow patterns.
Abstract 18046: Emergency Coronary Artery Bypass Grafting for Cardiogenic Shock Complicating Acute Myocardial Infarction is Associated With Satisfactory Long-term Outcomes in Hospital Survivors
Authors: Davierwala Piroze M , Verevkin Alexander , Leontyev Sergey , Rastan Ardawan J , Mohr Matthias , Bakhtiary Farhad , Misfeld Martin , Mohr Friedrich W
Published: March 2022

Introduction:
Cardiogenic shock (CS), which is one of the most dreadful complications following acute myocardial infarction (AMI), is an indication for emergent coronary artery bypass graft surgery (CABG) in patients not amenable for percutaneous coronary intervention. Our study aimed to identify risk factors for 30-day and long-term mortality in patients presenting with AMI complicated by CS requiring emergency CABG.

Methods:
Preoperative characteristics, operative parameters, and postoperative outcomes were prospectively collected for 508 patients undergoing CABG for CS complicating AMI (ST-elevation MI [STEMI]:42.9%;non-STEMI:57.1%) in our database between January 2000 and June 2014. Predictors of 30-day and long-term mortality were identified by logistic and Cox regression analyses, respectively.

Results:
Mean age was 69±10 years. 78.3% of patients had 3-vessel and 47% left main disease. Almost 50% of patients had left ventricular function <30% with 29.6%, 37.9%, 46.7% and 9.8% requiring preoperative resuscitation, ventilator, intra-aortic balloon pump and extracorporeal membrane oxygenation support (ECMO), respectively. 30-day mortality was 31.9% and was independently predicted by peripheral vascular disease [PVD] (odds ratio [OR]:1.8; 95% confidence interval [CI]:1.1-2.9;p=0.02), STEMI (OR:1.9;95%CI:1.2-2.8;p=0.004), lactate levels >4mmol/l (OR:3.3;95%CI:1.7-6.5;p<0.0001) and ECMO support (OR:5.0;95%CI:2.6-9.9;p<0.0001). Cumulative survival was 51% at 1 year, 44% at 3 years and 33% at 5 years and correspondingly improved to 74%, 64% and 48%, when 30-day mortality was excluded from the analysis. Incremental age (OR:1.04,p<0.0001), STEMI (OR:1.3,p=0.02), PVD (OR:1.4,p=0.03), diabetes (OR:1.5,p=0.001), lactate levels >4mmol/l (OR:2.3,p<0.0001) and high preoperative inotropic (OR:1.3,p=0.02), and ECMO support (OR:3.3,p<0.0001) predicted late mortality.

Conclusion:
Emergency CABG in patients with AMI complicated by CS was associated with high 30-day mortality, which was independently predicted by severe preoperative hemodynamic instability and presence of STEMI. Satisfactory long-term survival is observed in patients who survived the operation, demonstrating the benefit of emergency CABG.
Abstract 18066: What Empowers Trained Bystanders to Initiate and Perform Cardiopulmonary Resuscitation?
Authors: Malta Hansen Carolina , Rosenkranz Simone M , Folke Fredrik , Zinckernagel Line , Tjørnhøj-Thomsen Tine , Torp-Pedersen Christian , Søndergaard Kathrine B , Nichol Graham , Rod Morten H
Published: March 2022

Introduction:
Cardiopulmonary resuscitation (CPR) training has been implemented widely across communities but little is known about what empowers trained bystanders to initiate and perform CPR. We sought to identify which factors that empower bystanders to initiate and perform CPR.

Methods:
From January 2012-April 2015, we conducted 128 semi-structured qualitative telephone interviews with bystanders to consecutive out-of-hospital cardiac arrests (OHCA) in Denmark. Purposive maximum variation sampling was used to select interviews and capture a wide range of perspectives using the following characteristics: (1) diverse demographics, (2) location of OHCA, (3) type of initial contact with OHCA, (4) resuscitation attempt alone or with others. Interviews were included until data saturation was reached. We used NVIVO software (QSR International Pty Ltd, Doncaster, VIC) to conduct in-depth qualitative thematic analysis. According to these methods, a small size is common because study validity is based upon the information richness of the selected participants rather than reaching a representative sample.

Results:
Bystander characteristics are shown in Table 1. Among bystanders previously trained in CPR, the following were described as empowering to initiate and perform CPR: (1) knowledge that intervention cannot cause harm and is decisive to improve survival, (2) the ability to work with other bystanders, (3) bystander leadership skills, (5) use of a ventilation mask and (6) use of an AED.

Conclusions:
Trained bystanders were empowered by: knowing the intervention could not cause harm and was decisive to improve survival; their leadership skills and ability to work with others; using a ventilation mask and an AED. Promoting these conditions through CPR courses, emergency dispatcher instructions as well as access to ventilation masks and AEDs is likely to increase bystander CPR rates. Implementing compression-only CPR may increase bystander CPR rates.
Abstract 18163: A Prospective Study of Fatty Liver Index and Incident Hypertension
Authors: Kim Jangyoung , Lee Junwon , Youn Young Jin , Ahn Min Su , Yoo Byung Su , Lee Seung Hwan , Yoon Junghan
Published: March 2022

Background:
Although non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome, its influence on hypertension development is poorly understood. Hypothesis: We investigated whether fatty liver disease, as assessed by the fatty liver index (FLI), could predict the development of hypertension independently of systemic insulin resistance and inflammatory status.

Methods:
Prospective cohort study of 1,521 adults (484 men and 1037 women) aged 40 to 70 years without baseline hypertension examined in 2005 to 2008 as a baseline and 2008 to 2011 for follow-up. An equation was used to calculate FLI and classify patients as follows: FLI<30, no NAFLD; FLI ≥60, NAFLD; and 31<FLI<59, intermediate FLI.

Results:
During an average of 2.6 years of follow-up, 153 subjects (10.06 %) developed hypertension. FLI was positively associated with baseline blood pressure, homeostasis model assessment of insulin resistance (HOMA-IR), leptin, urinary albumin/creatinine excretion, and high sensitivity C-reactive protein (hsCRP). After adjustment for confounding factors, including markers of insulin resistance and systemic inflammation, the odds ratio (95% confidence interval) for the incident hypertension increased in a graded manner with FLI (<30 vs. 30-59 vs. ≥60= 1 vs. 1.77 [1.16-2.71] vs. 2.06 [1.09-3.89], respectively). Conclusions: NAFLD assessed by FLI was an independent risk factor for hypertension. Our findings suggest that FLI, a simple surrogate indicator of fatty liver disease, might be useful for identifying subjects at high risk for incident hypertension in clinical practice.
Abstract 18255: Gastric Mucosal Devitalization Reduces Blood Pressure, Cardiac Lipotoxicity and Endothelial Function in Diet Induced Obese Rats
Authors: Oberbach Andreas , Schlichting Nadine , Lehmann Stefanie , Kullnick Yvonne , Heinrich Marco , Retschlag Ulf , Feder Stefan , Khashab Mouen A , Kalloo Anthony Nicholas , Kumbhari Vivek
Published: March 2022

Background:
Metabolic surgery induces a substantial reduction in cardiovascular mortality and comorbidities such as blood pressure (BP), cardiac lipotoxicity and endothelial function. Metabolic surgery, such as vertical sleeve gastrectomy (VSG), reduces gastric volume and excludes the gastric mucosa. The gastric mucosa is recognized as an endocrine organ and is involved in the regulation of neurohormonal pathways effecting cardiovascular status. Our study aims to investigate the independent effects of altering gastric mucosa on blood pressure, cardiac lipotoxicity and vascular function in a diet induced obese rat model.

Methods:
Four-week old male Sprague-Dawley rats were fed a high fat diet for 11 weeks. At week 15, HFD rats (n=64) were randomized to undergo either gastric mucosal devitalization GMD, VSG or Sham (SH) surgery with HFD being continued in all cohorts. GMD of 80% of the stomach was achieved by argon plasma coagulation and compared to VSG and SH. At 8 weeks follow-up (week 23), we quantified blood pressure, cardiac lipid content (ELISA) and related metabolic active proteins adipophilin and periphilin (western blott analysis). Additionally we measured acetylcholine-induced relaxation response of aortic rings.

Results:
GMD and VSG resulted in a significant reduction of arterial blood pressure (MABP) compared to sham. Cardiac lipid content was significantly reduced in GMD (41%) and VSG (53) compared with SH. Adipophilin was significantly increased in GMD and VSG compared to SH, whereas periphilin was significantly opposite regulated in both intervention groups compared to SH. Area under the curve (AUC) for aortic ring relaxation was statistically relevant lower both in GMD and VSG compared to SH.

Conclusions:
Devitalization of the gastric mucosa (independent of altering gastric volume) reduces blood pressure, cardiac lipid content and regulate metabolic active proteins involved in cardiac muscle lipid storage as well as vascular function. Therefore, GMD deserves further attention as a promising method to treat obesity related cardiovascular comorbidities.
Abstract 18359: Long Term Follow-up of Aortic Coarctation Repair Using Leg-arm Blood Pressure Difference to Assess Hemodynamic Profiles
Authors: Labuz Daniel F , Berry James A , Pyles Lee A
Published: March 2022

Introduction:
Patients with successfully repaired coarctation (CoA) need long term follow up due to the risk of abnormal arterial elasticity and complications of hypertension. We hypothesize that even subtle hemodynamic abnormalities are marked by lack of a blood pressure standing wave effect to the lower extremities (arm ≥ leg systolic BP: ARM Group) and is associated with elevated aortic flow velocities, increased left ventricular posterior wall thickness (LVPWd), higher arm BP and a greater requirement for interventions compared to subjects with the normal standing wave effect (leg > arm SBP: LEG Group).

Methods:
CoAs repaired between 1990 and 2008 with at least two documented right arm and leg SBPs at clinic visits along with M-mode, 2D and Doppler echocardiography were selected. The largest recorded peak instantaneous (PeakV) and mean velocities (MeanV) in the descending aorta were reviewed, as were measures of the proximal transverse arch (TA) and LVPWd. Measurements were indexed by Z-score. Patient records were also reviewed for reintervention and antihypertensive medical therapy.

Results:
Eighty patients met our criteria with 29 ARM (median age 12 years) and 51 LEG (median 13 years) Group members. Compared to LEG, ARM had significantly increased arm SBP Z-score (p <0.001), PeakV (p <10
-4
), MeanV (p <10
-6
), and LVPWd (p <0.01) (Figure). There was no difference in arm diastolic BP (p =0.7) or TA diameter (p =0.3). Even without overt markers such as hypertension or medication, otherwise healthy ARM subjects were still found to have the same relationships. Furthermore, 11/29 (38%) ARM compared to 39/51 (76%) LEG were normotensive with no previous intervention and no BP medicine (Fisher’s p <0.001).

Conclusions:
Higher leg SBP after CoA repair is a marker for salutary hemodynamic and echo parameters as well as freedom from interventions post repair. Follow-up tailored by recognizing good outcome in LEG Group could be accomplished with less expense and obtrusive testing.
Abstract 18366: Clinical Modifiers of Renal Disease Progression in APOL1 Carriers in a Large Cardiovascular Cohort
Authors: Wang Hanghang , Pun Patrick , Kwee Lydia , Craig Damian , Haynes Carol , Chryst-Ladd Megan , Hauser Elizabeth , Gregory Simon , Pollak Martin , Svetkey Laura , Patel Uptal , Kraus William , Shah Svati
Published: March 2022

Objective:
Two alleles in the apoliprotein L1 (
APOL1
) gene confer increased risk of chronic kidney disease (CKD) in African Americans. However, harboring these alleles is not sufficient to cause CKD. This study sought to examine clinical modifiers of kidney disease progression in
APOL1
homozygote African Americans in a large cardiovascular cohort.

Methods:
We sequenced
APOL1
in 1733 African Americans (by self-report) enrolled in the CATHGEN biorepository, which consists of sequential individuals referred for cardiac catheterization at Duke University Hospital from 2001-2010. The genotype distribution was: n = 1493 non-carriers and heterozygotes, and n = 240 homozygotes. Analysis, with a multivariable logistic regression model, was restricted to homozygotes with an eGFR ≥60 mL/min at baseline (64.6%, n = 155). The main outcome measure was development of incident CKD, defined as at least two subsequent eGFR < 60 separated by at least 3 months. Potential clinical modifiers examined included age, sex, hypertension, type 2 diabetes status, smoking, HDL-C, LDL-C, ejection fraction and number of diseased coronary arteries.

Results:
The median age for homozygotes was 55.6 years (25th/75th: 47, 64) and 56% (n = 135) were male. During follow-up, 45.3% of homozygotes with an eGFR ≥60 at baseline developed incident CKD. For individuals without type 2 diabetes on baseline, 38.8% (n = 26) developed incident CKD; 56.1% (n = 23) individuals with baseline type 2 diabetes developed incident CKD (p = 0.08). Of clinical variables examined, only presence of type 2 diabetes at baseline was a significant predictor of developing CKD (univariate odds ratio 1.7, 95% CI 1.3-2.3, p = 0.0002), and remained significant after adjusting for the other covariables (OR 2.2, 95% CI 1.4 - 3.7, p=0.001).

Conclusions:
A large proportion of
APOL1
homozygote African Americans with preserved kidney function at baseline enrollment in a large cardiovascular study developed incident CKD. Type 2 diabetes status was the only significant independent predictor for incident CKD in these individuals. These results highlight the potential need for greater diabetes-related efforts to prevent CKD progression in African Americans already at high-risk for adverse cardiovascular outcomes.
Abstract 18406: Ulk1 Induces Mitochondrial Autophagy Through Rab9-dependent Phagophore Formation in Cardiomyocytes
(Best of Basic Science Abstract)
Authors: Saito Toshiro , Sadoshima Junichi
Published: March 2022

Rationale:
Mitochondrial quality control mediated by mitochondrial autophagy (MA) is essential for cardiac homeostasis. Although the role of the Parkin-Pink1 pathway in MA is well established, recent reports have uncovered the existence of unconventional autophagy in mediating MA in embryonic reticulocytes and fibroblasts.

Objective:
To investigate the molecular mechanism of MA in cardiomyocytes (CMs) during energy stress.

Methods and Results:
MA in CMs was evaluated with mitochondria-targeted (Mito)-Keima, which fluoresces with a high 560nm/440nm ratio after lysosomal translocation. In control CMs, high ratio dots represented 1.1±0.3 % of the area in cells at baseline, and glucose deprivation (GD) upregulated this area to 6.7±0.6 % (p<0.01), indicating stimulation of MA. Although knockdown of Ulk1 reduced the area to 1.3±0.1 % (p<0.01) during GD, that of Atg7 did not (6.6±0.8 %), suggesting that MA takes place during GD in Ulk1-dependent but Atg7-independent fashion. Since Ulk1-dependent alternative autophagy utilizes membrane trafficking from the trans-Golgi to form autophagosomes, we examined the effect of Brefeldin A (BFA), an inhibitor of the membrane trafficking, on MA. Treatment with BFA reduced the high-ratio dot area to 0.4±0.1 % (p<0.01) during GD without affecting the protein level of LC3-II, suggesting that MA induced by GD is mainly mediated by alternative autophagy. BFA did not suppress the Parkin-induced area of high-ratio dots, suggesting that GD-induced MA is distinct from Parkin-dependent MA. GFP-Rab9 formed puncta during GD. These puncta were upregulated in the presence of Bafilomycin, whereas they were downregulated by the knockdown of Ulk1 or Beclin1. The puncta merged with the acidic dots of Mito-Keima during GD. Treatment with Bafilomycin, which inhibits the fusion of autophagosomes with lysosomes, increased the puncta merged with neutral Mito-Keima during GD. RFP-Rab9 did not co-localize with GFP-LC3. These results indicate that Rab9 induces formation of autolysosomes or autophagosomes in MA independently of LC3. Knockdown of Rab9 reduced the area of Mito-Keima high-ratio dots to 3.3±0.4% during GD (p<0.01).

Conclusions:
Ulk1 regulates Rab9-dependent phagophore formation and induces MA during energy stress in CMs.
Abstract 18407: Identifying Patients With Acute Heart Failure who Require a Critical Care Admission: ASCEND-HF Insights
Authors: Raslan Ismail R , Westerhout Cynthia M , Ezekowitz Justin A , Hernandez Adrian F , Starling Randall C , O’Connor Christopher M , Armstrong Paul W , Diepen Sean v
Published: March 2022

Background:
The benefit of critical care unit (CCU) admission in acute heart failure (AHF) remains unclear. The risk factors for in-hospital events best managed in a CCU including the need for CCU restricted therapies (including invasive and non-invasive mechanical ventilation, mechanical circulatory support devices, and intravenous vasopressors or vasodilators) have not yet been formulated. The purpose of this study was to develop a clinical prediction model for adverse outcomes or CCU restricted therapies in patients with AHF.

Methods:
Using data from the ASCEND-HF trial, patients with AHF who did not require critical care related therapies within the preceding 12 hours of randomization were selected. The primary outcome was an in-hospital composite of the requirement of CCU specific therapies, death, myocardial infarction, cardiogenic shock, resuscitated sudden cardiac death, or ventricular arrhythmias requiring intervention. Model discrimination and calibration were evaluated using the c-index and the Hosmer-Lemeshow test, respectively.

Results:
The study cohort included 4772 patients and the primary composite outcome occurred in 547 (11.5%) patients. A total of 11 variables were independent predictors of the primary composite outcome as follows (Figure): chronic respiratory disease, prior ACE inhibitor, angiotensin receptor blocker or aldosterone antagonist use, Asian race, body mass index, diastolic blood pressure, respiratory rate, resting dyspnea, hemoglobin, sodium, and blood urea nitrogen. The simplified clinical prediction model demonstrated modest discrimination (c-index= 0.66) and good calibration (Hosmer-Lemeshow Goodness of Fit=7.017, p=0.535).

Conclusions:
In an international dataset of patients with AHF, we derived a clinical prediction describing patients who are likely to need a CCU. This model may be useful as a triage tool to identify patients with AHF who may benefit from admission to a higher acuity CCU.
Abstract 18426: Impact of Body Mass Index on Heart Failure With Preserved or Reduced Ejection Fraction: Outcomes According to Race and Ethnicity From Get With The Guidelines-Heart Failure (GWTG-HF) Registry
Authors: Kebede Selomie , Powell-Wiley Tiffany , Ngwa Julius , Lu Di , Schulte Phillip J , Bhatt Deepak L , Yancy Clyde , Fonarow Gregg C , Albert Michelle A
Published: March 2022

Introduction:
Research supports a J-shaped association between body mass index (BMI) and mortality in patients with coronary artery disease (CAD) regardless of race/ethnicity. However, whether a similar pattern is noted among heart failure (HF) patients is unclear, particularly since black patients are at highest risk for both obesity and heart failure.

Methods:
Patients ≥65 years old from the GWTG-HF registry linked to Medicare claims data from 2005-2011, were stratified by preserved (HFpEF) and reduced (HFrEF) ejection fraction HF and categorized by 5 racial/ethnic populations (white, black, Hispanic, Asian, and other). Adjusted-Cox regression assessed the association between BMI and 30-day mortality from live discharge. Restricted cubic splines illustrate the relationship. We used interaction terms to test whether the relationship between BMI and outcomes differed by race/ethnicity.

Results:
A total 39647 HF patients were included [white=32434 (81.8%); black=3809 (9.6%); Hispanic=1928 (4.9%); Asian=544 (1.4%);other=932 (2.3%)]. Blacks and Hispanics with HF were more likely class I obese or higher (BMI≥30) than whites or Asians (P
<
0.0001). Among HFpEF, higher BMI was associated with lower 30 day mortality, up to 30 kg/m
2
with little change in risk above 30 (Figure; BMI=30 vs BMI=15 hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.38 - 0.61). A smaller relationship was observed in HFrEF (BMI=30 vs BMI=15 HR 0.64, 95%CI 0.47 - 0.87). There were no significant BMI by race interactions related to mortality (P
all
>0.05).

Conclusions:
Although black and Hispanic HF patients were more likely to be obese than whites or Asians, higher BMI was associated with lower 30 day mortality in each racial/ethnic group in a manner not consistent with a J-shaped relationship as noted for CAD. Additionally, the differential slope of the association of obesity and mortality among HFpEF and HFrEF patients suggests differing mechanistic factors requiring further exploration.
Abstract 18444: Low and Exacerbated Levels Of 1,5-anhydroglucitol are Associated With Cardiovascular Events in Patients After First-time Elective Percutaneous Coronary Intervention
Authors: Takahashi Shuhei , Shimada Kazunori , Miyauchi Katsumi , Sai Eiryu , Miyazaki Tetsuro , Shiozawa Tomoyuki , Tamura Hiroshi , Okazaki Shinya , Isoda Kikuo , Daida Hiroyuki
Published: March 2022

Background:
There has recently been great interest in the association between postprandial hyperglycemia and coronary artery disease. Serum 1,5-anhydroglucitol (1,5-AG) is reported to be a clinical marker of postprandial hyperglycemia. However, the impact of 1,5-AG on cardiovascular events has not been fully investigated.

Methods:
We enrolled 270 consecutive patients who had undergone first-time elective percutaneous coronary intervention (PCI) with follow-up angiography within 1 year. Fasting blood glucose (FBS) levels, HbA1c, and 1,5-AG were measured prior to PCI and at the time of follow-up angiography. Clinical events, including ACS and coronary revascularization, were also evaluated. Subjects were divided into two groups according to clinical outcomes: event group (EV, n=48) and non-event group (NEV, n=222). Patients were also divided into four groups according to 1,5-AG levels prior to PCI and at follow-up: increased 1,5-AG group (Group A), persistently low 1,5-AG group (Group B), persistently high 1,5-AG group (Group C) and decreased 1,5-AG group (Group D).

Results:
No significant differences in baseline clinical characteristics were observed between the two or the four 1,5-AG groups. Serum levels of 1,5-AG at follow-up were significantly lower in the EV group than in the NEV group (P=0.04). Significant reduction in 1,5-AG level was observed in the EV group than in the NEV group (P = 0.03). The association between 1,5-AG levels and clinical events remained significant after adjustment for independent variables, including FBS and HbA1c levels (P=0.04). The incidence of cardiovascular events was significantly higher in Group D than the other 1,5-AG groups. (Figure)

Conclusion:
Low and exacerbated levels of 1,5-AG were associated with cardiovascular events, suggesting that postprandial hyperglycemia and low 1,5-AG are important risk factors for adverse clinical events in patients after first-time elective PCI.
Abstract 18488: Metabolic Modulation of the Diseased Human Lung; A Translational, Novel ex vivo Lung Perfusion Model
Authors: Gurtu Vikram , Kinnaird Adam , White Christopher , Paulin Roxane , Freed Darren , Nagendran Jayan , Michelakis Evangelos
Published: March 2022

Introduction:
Pulmonary arterial hypertension (PAH) and idiopathic pulmonary fibrosis (IPF) are deadly diseases that often require lung transplantation. Preclinical evidence suggests that mitochondrial suppression underlies the pro-proliferative and anti-apoptotic phenotype of pulmonary artery smooth muscle cells and pulmonary fibroblasts, respectively. Two therapies to improve mitochondrial function are a) dichloroacetate (DCA), an activator of pyruvate dehydrogenase (PDH), the gate-keeping enzyme for glucose oxidation, and b) 4-phenylbutyrate (4-PBA), an inhibitor of endoplasmic reticulum stress, a response that suppresses mitochondrial function during cellular stress. Although these drugs can be studied in vitro or in animals, their metabolic effects on the whole human lung may only by studied through ex vivo lung perfusion (EVLP).

Methods:
We used a custom-made EVLP system to study explanted, diseased human lungs of patients undergoing lung transplant for PAH (n=2), or IPF (n=4). The bronchi were connected to a ventilator, while a pump-driven system perfused the pulmonary artery (PA) with modified Krebs-Henseleit buffer or STEEN solution™ in recirculation. Lung biopsies were collected to measure mitochondrial respiration (using a Seahorse analyzer) and PDH activity at baseline, and after drug intervention with DCA or 4-PBA for 1 hour.

Results:
In the PAH lungs, hypoxic pulmonary vasoconstriction, a validated marker of lung health, was absent. However administrating the prostacyclin analogue treprostinil reduced PA pressure by 31.6% (at a level of flow corresponding to the patient’s cardiac output), confirming abnormal but present vasoreactivity in the model. DCA caused a 61.1% increase in oxygen consumption, and a 34-fold increase in PDH activity. In IPF lungs, PBA increased oxygen consumption by 62.0%.

Conclusions:
EVLP is a feasible model to study the direct effects of drugs on diseased human lungs. Since before-after biopsies are not possible in clinical trials, this is a valuable model to facilitate translation of preclinical therapies to clinical trials. Our results show, for the first time in human lungs, that the metabolic remodeling of the PAH and IPF can be reversed by clinically available small molecules like DCA and 4-PBA.
Abstract 18509: Defining Renal Uptake of Circulating Lipids
Authors: Scerbo Diego , Huiping-Son Ni , Susztak Katalin , Goldberg Ira
Published: March 2022

A prominent histological feature of chronic kidney disease, including that due to diabetes, is the accumulation of neutral lipids in the nephron. However, existing research on kidney lipid metabolism is limited. Therefore we characterized lipid accumulation in mouse models. We hypothesized that the major source of lipids in the kidney is circulating triglyceride (TG)-rich lipoproteins brought into the cells of the kidney via the coordinated action of lipoprotein lipase (LPL) and cluster of differentiation 36 (CD36). To test this hypothesis, we fasted mice overnight and inhibited LPL and CD36. We did not observe a change in TG accumulation in the kidney when LPL action was blocked using with poloxmer 407. We then used a microsomal TG transfer protein inhibitor, which inhibits TG-rich lipoprotein assembly, to lower circulating TG-rich lipoproteins. Intracellular kidney TG did not decrease but in fact increased up to 40% in the fasted state after the inhibitor was given, mirroring what was seen in the liver. There was no difference in TG accumulation in the kidneys of fasted Cd36
-/-
mice. Furthermore, we did not observe a change in uptake of radiolabeled oleic acid in the kidneys of these mice. Genes which regulate fatty acid oxidation or de novo lipogenesis were also unchanged in Cd36
-/-
compared to Cd36
+/+
. Surprisingly, apoC-III deficiency increased renal uptake of a TG-emulsion, as had been found in the liver. Finally, we measured TG in kidneys from streptozotocin-treated and Akita diabetic mice without renal failure. Neither of these models accumulated higher amounts of TG compared to non-diabetic controls; however, Akita mice down regulated fatty acid oxidation genes and had twice the intracellular free fatty acids. These findings provide novel insight into the lipid biochemistry of the kidney, showing it differs from other high energy requiring peripheral organs such as heart.
Abstract 18520: Endogenous Cardiotonic Steroids in Salt- sensitive Hypertension
Authors: Estape Estela S , Torres-Negron Ivette , Fedorova Olga V , Gonzalez-Rodriguez Claribel , Gonzalez-Sepulveda Lorena , Bagrov Alexei Y , Wei Wen , Franqui Sandra , Rodriguez-Rivera Ingrid , Garcia-Rivera Enid , Santiago Fernando , Lopez-Candales Angel , Martinez-Maldonado Manuel
Published: March 2022

Introduction:
An endogenous inhibitor of Na,K-ATPase (CTS) is increased in Dahl salt-sensitive (DS) rats and in human cardiovascular pathologies.

Hypothesis:
Chronic hypertension is a major cause of CTS release which will not be corrected by treatment, and that effectively treated hypertensive patients (HT) will have increased plasma CTS, compared to ischemic stroke patients (STR) after thrombolytic treatment and controls ( CTL).

Methods:
Forty (40) subjects (age and sex matched) were recruited and grouped into three groups: STR (n = 13), HT (n = 13), and CTL (n = 14). Plasma was collected 1-2 days after diagnosis of ischemic stroke and thrombolytic treatment. CTS levels was determined in all groups by measuring the bufadienolide CTS marinobufagenin (MBG) using a fluoroimmunoassay. Fisher Exact test, Kruskal-Wallis test, and Mann-Whitney test with Bonferroni correction were used, when appropriate, to analyze all data.

Results:
Participants mean age was 61 ± 12 years; 56% were male. CTS levels within the normal range (200-400 pmoles/L) were found in 62% of the whole cohort. Median plasma CTS was significantly higher in HT as compared to CTL (437.6 vs. 326.8 pmoles/L, p= 0.018) and STR (437.6 vs. 286.9 pmoles/L, p=0.005). Blood pressure did not differ between HT and CTL groups (p>0.05). Extreme CTS values (> 1,000 pmoles/L) were observed in four HT and one CTL, despite normal BP.

Conclusion:
As predicted, HT patients had high CTS levels compared to CTL suggesting a strong relationship between hypertension and CTS. Plasma CTS may be lowered by thrombolytic but not anti-hypertension therapy. Further studies are required to define the role of CTS in human pathological states.
Abstract 18526: Electrogram Amplitude is Reduced at Rotor Sites Critical to Maintenance of Human Persistent Atrial Fibrillation
Authors: Zaman Junaid A , Lalani Gautam G , Baykaner Tina , Park Shirley , Krummen David E , Wang Paul J , Narayan Sanjiv M
Published: March 2022

Introduction:
Increasing studies find human AF is driven by rotors, but their detection remains challenging. Theoretically, rotor cores display low amplitude and multiphasic signals, but human AF rotors fail to display such signatures. This may reflect rotor precession (obscuring analysis site chosen), poor basket contact or bipoles (that do not register orthogonal wavefronts). We hypothesized that studying unipolar signals at rotor precession areas may reveal hitherto hidden electrogram signatures.

Methods:
We studied 22 persistent AF patients (60±11 years, CHADS2=1.9), in whom phase mapping of 64 pole basket signals revealed rotors/sources where ablation terminated AF (fig A). Unipolar electrograms over the rotor precession area were measured by 3 blinded observers for spectral dominant frequency (DF), peak-to-peak amplitude and duration. This was compared to a paired source in each patient where ablation did not terminate AF (‘controls’) (fig B).

Results:
Patients had 3.3±1.7 AF rotor/focal sources. At the index source, AF terminated to sinus rhythm (n=14) or atrial tachycardia by targeted ablation (mean 4.0 mins). Compared to control areas, AF sustaining rotors/sources had lower amplitude (fig C) (0.60±0.30mV vs. 0.87±0.70mV, p=0.02). Conversely, electrogram spectra (90±45Hz vs. 80±46Hz, p=ns), duration (125±45ms vs. 116±47ms, p=ns) and AF cycle length (174±8ms vs. 174±6ms, p=ns) did not differ.

Conclusions:
Rotors/sources that maintain human persistent AF have lower unipolar amplitude than non-termination sites. This is the first identified electrogram signature for functionally critical human AF rotors, and motivates definition of structure/function correlations at these sites.
Abstract 18536: Nanoparticle-mediated Simultaneous Targeting to Mitochondria and Inflammatory Monocytes Confers Additive Cardioprotection Against Myocardial Ischemia-reperfusion Injury
Authors: Ikeda Gentaro , Matoba Tetsuya , Egashira Kensuke
Published: March 2022

Introduction:
Mitochondrial injury and inflammation play temporally and spatially different roles in myocardial ischemia-reperfusion (IR) injury, which demand novel strategy to target these 2 mediators specifically. Previously, we have engineered poly (lactic-co-glycolic acid) nanoparticle containing cyclosporine A (CsA-NP) or pitavastatin (Pit-NP), and reported that the former inhibits the opening of mitochondrial permeability transition pore (mPTP) and the latter reduces monocyte-mediated inflammation in IR hearts.

Hypothesis:
Nanoparticle-mediated simultaneous targeting to mPTP and monocytes confer additive cardioprotection against IR injury.

Methods and Results:
We produced mice lacking both cyclophilin D (CypD, a key molecule for mPTP opening) and CCR2 (a receptor for monocyte chemoattractant protein-1), and found that the double KO mice displayed dramatic reduction in myocardial IR injury model (Fig. A). Fluorescence reflectance image (FRI) revealed that CypD deficiency reduced Annexin-positive infarct area in the center of ischemic area, compared with WT mice at 10 min after reperfusion (Fig. B). Although infarct areas were equivalent between WT and CCR2 KO mice at 10 min after reperfusion, CCR2 deficiency inhibited the expansion of the infarct area during 24 hours. Flow cytometric analysis and fluorescence molecular tomography showed that inflammation was markedly inhibited in CCR2 KO and double KO mice, but not in CypD KO mice at 24 hours after reperfusion (Fig. C). In CypD KO mice, Pit-NP reduced recruitment of Ly6Chigh inflammatory monocytes and infarct size, whereas CsA-NP reduced infarct size in CCR2 KO mice. Simultaneous treatment with CsA-NP and Pit-NP at the time of reperfusion reduced infarct size by an additive manner (Fig. D).

Conclusions:
Nanoparticle-mediated simultaneous targeting to mitochondria and inflammatory monocytes can be developed as a novel therapeutic strategy for myocardial IR injury.
Abstract 18559: Double or Compound Sarcomere Mutations in Hypertrophic Cardiomyopathy is Not Associated With Worsened Outcomes: A Single Center Cohort Study
Authors: Fourey Dana , Almansoori Ghadeera , Care Melanie , Rakowski Harry , Chan Raymond H.
Published: March 2022

Background:
The presence of two or more pathogenic sarcomere mutations in patients with hypertrophic cardiomyopathy (HCM) has been reported to be associated with early disease onset, particularly marked left ventricular (LV) hypertrophy, and advanced heart failure.

Objective:
The aim of the study was to clarify the relationship between multiple disease-causing sarcomere mutations and major cardiovascular outcomes in a large HCM cohort.

Methods and Results:
Between June 1, 1995, and January 2015, 1104 probands with a diagnosis of HCM were routinely referred for systematic sarcomeric mutational screening at a single HCM center. Pathogenic mutations were identified in 273 (25%). Of these patients, 10 (3.6%) were identified with double/compound sarcomere mutations. They were mostly male (70%), presented at an average age of 33±13 years (range, 21-58), with an average maximal wall thickness of 17 mm (range, 13-26). Of the 9 patients who had a cardiac MRI, 8 (88%) had late gadolinium enhancement (LGE), none of which were considered to be extensive (>20% of LV myocardium).

Over a mean follow up of 17.4 ±14 years (range, 3-48 years) there were no sudden cardiac death events. Adverse cardiovascular events or severe disease progression occurred in 4 (40%) patients, with an event rate of 3.4 per 100 patient-years follow up including: 2 (20%) with stroke, 3 (30%) with progression to end-stage HCM (EF<50%), and 1 (10%) with progression to New York Heart Association III/IV symptoms. One patient had myectomy for obstructive symptoms, while none required cardiac transplantation. Three (30%) patients had implantable cardioverter-defibrillator (ICD) for primary prevention. However, over a mean follow-up of 6 years (range 1-14 years), no ICD discharges were documented.

Conclusion:
These observations do not support the hypothesis that double (or compound) mutations confer a gene dosage effect in HCM, nor is it associated with an adverse prognosis. Mutation analysis has proven imprecise in predicting the phenotype or prognosis for patients with HCM, suggesting that genome-wide association studies and gene expression profiling may be needed for better understanding of its utility in the management of HCM patients.
Abstract 18647: Functional Evaluation of a Patient-specific 3D Printed Model of Aortic Regurgitation
Authors: Vukicevic Marija , Maragiannis Dimitrios , Jackson Matthew , Little Stephen H
Published: March 2022

Introduction:
Quantification of aortic regurgitation (AR) can be challenging using non-invasive imaging methods. In vitro simulation of patient-specific AR would allow reference standard measurement of the regurgitant flow volume and a comparison against Doppler methods of AR quantification.

Hypothesis:
We sought to build a functional patient-specific 3D printed model of the aortic valve (AV) and to replicate AR Doppler parameters recorded during a clinical echocardiogram.

Methods:
We identified a clinical multi-detector CT dataset (mid-diastolic phase) of a selected patient with generative AV disease and mild AR. Segmentation software was used to segment the calcified and non-calcified components of the aortic root. Fused-material 3D printed was used to create a patient-specific physical model of the aortic root, AV cusps, regional calcification and left ventricle. The 3D model was coupled to a flow loop to replicate the trans-valvular hemodynamic conditions recorded during a clinical echocardiogram. The accuracy of hemodynamic replication was evaluated using Doppler imaging and compared to the clinical study.

Results:
Functional Doppler imaging of the 3D printed model demonstrated similar quantitative parameters to the clinical Doppler findings, respectively; peak velocity 4.6 vs 4.7 m/s; regurgitant time 460 vs 458 ms; pressure half time 312 vs 331 ms; time-velocity index 167vs 162 cm. Regurgitant jets were qualitatively similar. Doppler velocity profiles for the patient and the 3D model, shown in Figure 1. We demonstrate an in vitro method to mimic and quantify AR using patient-specific anatomic and functional 3D modeling.

Conclusion:
We describe the development of a functional patient-specific 3D printed model of the AV replicating both the geometry and function of AV regurgitation. This initial functional modeling may extend to studies of AR severity using novel imaging modalities (e.g. 3D color Doppler) or structural heart interventions.
Abstract 18703: Impact of Implantable Cardioverter-defibrillators on Outcome of Patients With Left Ventricular Assist Devices
Authors: Agrawal Sahil , Nanda Sudip , Allen David , Vefali Huseng , Shirani Jamshid
Published: March 2022

Background:
Ventricular arrhythmias are common in patients supported by left ventricular assist devices (LVAD). However, the benefit of de-novo implantable cardiac defibrillators (ICD) in patients with LVAD is not well established.

Methods/Results:
The Nationwide Inpatient Sample database identified 12010 LVAD implantations from 2008 to 2012. Among these, 24.8% (n=2975) had a prior ICD while 6.8% (n=614) received an ICD at the time of LVAD implantation. An increase in the rate of ICD implantation during the study period was noted [4.1% in 2008 vs. 6.6% in 2012, p
trend
= 0.019; adjusted odds ratio (OR) per year= 0.839; 95% confidence interval (CI)= 0.724-0.972]. De-novo ICD implantation was independently associated with reduction in in-hospital mortality in new LVAD recipients [OR=0.141 (95% CI=0.080-0.248); p<0.001]. Patients receiving ICD implants were younger (50.1 vs. 55.8 years, p<0.001). Female sex was an independent negative predictor of ICD implantation [0.601 (0.429- 0.843); p=0.003] and ICD recipients were more likely to be white. Acute myocardial infarction, ventricular tachycardia, ventricular fibrillation (VF), cardiac arrest and atrial fibrillation were independent predictors (p=0.001 for VF; P<0.001 for remainder) of de novo ICD implantation while the etiology of left ventricular dysfunction (ischemic vs. non-ischemic cardiomyopathy) did not predict ICD implantation [OR=0.824 (95% CI=0.593 -1.146); p=0.25].

Conclusion:
De novo ICDs were implanted in a small proportion of LVAD recipients. However, it was associated with a significant reduction in in-hospital mortality.
Abstract 18725: Predictors of Adverse Outcomes in Peripartum Cardiomyopathy
Authors: Peters Andrew , Caroline Malka , Zhao Huaqing , Tsai Emily
Published: March 2022

Introduction:
Peripartum cardiomyopathy (PPCM) is a devastating condition leading to heart failure (HF) in the final trimester of pregnancy or within five months postpartum. Nearly half of women with PPCM suffer chronic HF, and some progress towards advanced HF requiring cardiac transplantation. While risk factors for developing PPCM have been identified, predictors of poor long-term outcome are not well defined.

Hypothesis:
We believe that right heart failure may predict adverse outcomes in PPCM.

Methods:
We performed a single-center retrospective cohort study of patients with at least one pregnancy and live birth and diagnosis of PPCM between 1994 and 2014. The primary outcome was a lack of improvement in LVEF and NYHA, and the secondary outcome was cardiac transplantation within 5 years. We used univariate logistic regression to assess associations between these outcomes and various clinical and echocardiographic characteristics at the time of PPCM diagnosis.

Results:
Of the 57 subjects who met inclusion criteria, 19 (33%) showed no improvement in NYHA class and LVEF and 10 (18%) underwent cardiac transplantation. Median (IQR) follow-up period was 4.9 (2.9-5.8) years; 2-year mortality was 4%. Diabetes was associated with no improvement in LVEF and NYHA (OR 5.0 [95% CI 1.3 to 19.7]). LVEF <30% at diagnosis was associated with no improvement in LVEF and NYHA class (OR 22.5 [95% CI 2.6 to 194]). LV internal diameter at end-diastole (LVIDd) ≥56mm was associated with no improvement in LVEF and NYHA class (OR 11.1 [95% CI 1.2 to 99]). Every 1 mm increase in LVIDd above 50 mm was associated with 22% greater odds of no improvement in LVEF and NYHA class (OR 1.22 [95% CI 1.07 to 1.38]). RV dysfunction was associated with lack of improvement in LVEF and NYHA class (OR 10.5 [95% CI 2.0 to 54]). Moderate to severe RV dysfunction was associated with cardiac transplantation (OR 4.38 [95% CI 1.0 to 19.3]).

Conclusions:
Diabetes is associated with chronic heart failure in PPCM. PPCM patients at risk for adverse long-term outcomes, including cardiac transplantation, may be identified by LVEF <30%, LVIDd≥56mm, and RV dysfunction at time of diagnosis. Such high-risk PPCM patients could benefit from early referral to advanced heart failure specialty programs.