bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9592: Acute Kidney Injury Subphenotypes in Critically Ill Patients with Cardiovascular Diseases by Latent Class Analysis: A Retrospective Cohort Study
Authors: Guo Qi , Xie Yong , Huang Yongqing , Zhou Shuxian , Chen Yangxin , Wang Jingfeng
Published: April 2022

Introduction:
According to the potential heterogeneity of acute kidney injury (AKI) in critically ill patients with cardiovascular diseases, we explored the subphenotypes of AKI and evaluated the prognostic differences among AKI subphenotypes.

Hypothesis:
We hypothesized that patients with different AKI subphenotypes would suffer different prognosis.

Methods:
Clinical information from the Medical Information Mart for Intensive Care (MIMIC)-III database was enrolled. Latent class analysis (LCA) was used to explore the potential subphenotypes of AKI in critically ill patients with cardiovascular diseases. The number of classes was identified using the Bayesian information criterion and entropy. The differences in prognostic ability among the AKI subphenotypes were evaluated by logistic regression analysis.

Results:
In this study, a total of 7738 AKI patients were enrolled and divided into 4 heterogeneous subphenotypes by using LCA. The subphenotypes showed remarkable dofference from kidney disease classified by improving Global Outcomes (KDIGO) stages. Notedly, though both dominated by stage 2, the mortality between class 4 and class 1 classified by LCA were significantly different (15.2% vs. 1.6%,
p
<0.05). The trend remained the same after further adjustment, with an odds ratio of 12.31 (95% confidence interval, 8.96-16.89).

Conclusions:
LCA was feasible for AKI classification and different subphenotypes prognosis prediction in critically ill patients with cardiovascular disease. Our study revealed the potential heterogeneity of AKI patients, which is worthy of further investigation.
Abstract 9601: Sarcolipin Reduction Prevents Mitochondrial Dysfunction in Dystrophic Myocardium
Authors: Mareedu Satvik , Fefelova Nadezhda , Xie Lai-hua , Babu Gopal J
Published: April 2022

Rationale & Hypothesis:
Sarcolipin (SLN), an inhibitor of sarco/endoplasmic reticulum Ca
2+
ATPase (SERCA) is abnormally high and enriched in the mitochondrial associated membrane (MAM) fractions of dystrophic hearts. We, therefore, hypothesized that in the dystrophic cardiomyocytes, SLN upregulation causes abnormal elevation of intracellular Ca
2+
(Ca
2+
i
) including Ca
2+
mishandling in the MAM region, resulting in sustained elevation of mitochondrial Ca
2+
(Ca
2+
m
), which in turn affects mitochondrial structure and function.

Approach:
We chose dystrophin mutant and utrophin deficient,
mdx:utr
-/-
mice for our studies and generated SLN haploinsufficient

mdx:utr
-/-
(mdx:utr
-/-
:sln
+/-
)

mice. Single-cell Ca
2+
transients and Ca
2+
m
efflux were measured in isolated cardiomyocytes (CM's) to determine

Ca
2+
i

handling and Ca
2+
m
content,
respectively.
Mitochondrial membrane potential was assessed with membrane-permeant dyes in isolated CM's followed by confocal imaging. Mitochondrial respiration was measured using Complex activity assays and Seahorse metabolic profiling in ventricular tissue lysates and isolated mitochondria respectively. Mitochondrial structure, number, and area were evaluated using electron micrographs (EM).

Results:
Heterozygous deletion of the SLN gene normalized SLN expression and improved Ca
2+
i
cycling and prevented Ca
2+
m
overload in dystrophic CM's. Furthermore, reducing SLN expression prevents loss of membrane potential and improves mitochondrial respiration in the dystrophic cardiac myocytes. TEM analyses of the dystrophic heart revealed significant cristae loss in the mitochondria globally as well as in the MAM-associated mitochondria. On the other hand, the reduction in SLN expression prevents these changes.

Conclusions:
In conclusion, reduction in SLN expression preserves the SR-mitochondrial interface and restores the mitochondrial function by mitigating the Ca
2+
overload, membrane potential loss, and structural damage. These changes improve cardiac function and prevent the development of cardiomyopathy in
mdx:utr
-/-
mice. Our findings suggest that SLN reduction could be a potential therapeutic strategy for the treatment of Duchenne muscular dystrophy and associated cardiomyopathy.
Abstract 9606: Prognostic Significance of Interventricular and Mitral Calcification on Permanent Pacemaker Implantation Post Tavr. Is All That Glitters Gold?
Authors: Vashistha Kirtivardhan , Tobaa Amel , Doyle Mark , Bartley Susan , Bailey Stephen , Biederman Robert W
Published: April 2022

Background:
Despite growing demand, TAVR implantation is not free of complications, conduction defects being one of the major barriers to its widespread usage. We sought to evaluate the prognostic implications of interventricular (IVS) and mitral annular calcification (MAC) on post-TAVR conduction abnormalities.

Methods:
We performed a retospective chart review on patients who underwent TAVR at our center (Pittsburgh, PA) during the year 2016-2020 and identified two groups ranked via presence or absence of permanent pacemaker (PPM) implantation post-TAVR. These groups were compared based on baseline demographics, comorbidities, transthoracic echocardiogram (TTE) parameters, and evidence of IVS/MAC calcification via TTE.

Results:
Extracted from a database of >2500 pts, an aged-matched cohort of 75 pts requiring a post-TAVR PPM were identified along with 53 patients undergoing TAVR with no post-procedure conduction defects that were utilized as the control group. In the former group, 66 patients had on-site echocardiographic imaging of which 36 had evidence of IVS calcification (54%). The latter group had 51 patients with imaging of which 22 had evidence of IVS calcification (43%); p=NS; Table 1). Although via a binary logistic model, association of post-TAVR PPM with IVS confirmed no relation with PPM, MAC was strongly associated with PPM with a sensitivity of 82% and specificity of 81%; area under the ROC curve of 0.91. The coefficients in the model are <0.1 level; p<0.001 (Fig 1). PPM placement was directly related to MAC presence and inversely related to LVEF.

Conclusion:
Inherently, IVS calcification should predict post-TAVR PPM given its' proximity to the conduction system. Unexpectedly, however, MAC was a very strong predictor of post-TAVR 30d PPM placement. Moreover, once MAC is present there is ~3-fold increase in PPM while for every 1%
increase
in LVEF, there is a 1.2% increase in PPM. This simple predictor may have relevance in prognostication even more than EKG.
Abstract 9607: CIED and Non-CIED MRI Imaging; Should Capped or Uncapped Abandoned Leads Remain a Contraindication?
Authors: Gevenosky Loretta , Biederman Robert W
Published: April 2022

Introduction:
Infrequently, MRI is performed on patients with conventional pacemakers or ICDs. While multiple studies have documented the safety of MRI scans when performed with an approved protocol, retained leads (capped or uncapped) remain a significant concern.

Hypothesis:
We hypothesize that non-CIED and CIED devices in the presence of capped and uncapped leads, while inherently having no ability to for interrogation, can be performed under a similar MRI-device protocol in a safe and reliable fashion.

Methods:
Adapting the same MRI-device protocol as for either CIED or non-CIEDs as appropriate, tracking of patient safety to include chest pain, sustained arrhythmias or change in any device setting was performed.

Results:
A total of 311 pts with CIED (81%) and non-CIED (19%) from 2019-2021 at Allegheny General Hospital incorporating a total of 16 (5%) pts with retained/abandoned/fragmented leads (56% capped and 44% uncapped; p=NS) as well as 3 epicardial leads underwent MRI (GE; EXCITE, 1.5T; WI) of several regions (Brain; 72%, Ortho; 17% and CV; 11%). Repeat imaging was common (12%). Utilizing an established device protocol according to CIED or non-CIED, pts were programmed based on pt-specific pacing requirements. There were no episodes of abnormal vital signs, chest pain, sustained arrhythmias or any clinically significant device setting changes. No significant changes to impedance, amplitude, voltage or sensitivity to RA or RV/LV parameters occurred. There were no differences, naturally, between capped, uncapped or epicardial lead metrics. Likewise, no power-on resets or pacing changes were noted in the primary device system. Altogether, this supports the absence of myocardial or extra-cardiac thermal-induced injury. Infrequent, clinically insignificantly decreased RA sensing, a common natural observation in contemporary interrogation, was infrequently and transiently noted.

Conclusions:
Following a standard MRI protocol, according to CIED and non-CIED in pts with either capped or uncapped abandoned leads, pts suffered no ill consequences when tracked for CP, arrhythmias or device setting changes supporting a
proof-of-concept
notion for removing yet another obstacle for often life-changing MRI in patients with PM/ICDs.
Abstract 9608: Overuse of Cardiac Evaluation and Testing in Patients at Low Cardiac Risk Prior to Laparoscopic Bariatric Surgery
Authors: Peterson Brandon R , Calisi Olivia , Caldwell Catherine , King Steven , Berger Daniel , Rich Alyson , Dan Yongwook , Qureshi Umer , Ramedani Shayann
Published: April 2022

Introduction:
Preoperative cardiac testing is common prior to bariatric surgery despite the low incidence of postoperative cardiac events. We sought to determine what proportion of patients who underwent preoperative cardiac testing and evaluation prior to laparoscopic bariatric surgery were at low cardiac risk.

Methods:
We reviewed preoperative cardiac testing and evaluations performed for patients undergoing laparoscopic bariatric surgery at Hershey Medical Center from January 1
st
2015 through December 31
st
2019. Cardiac risk was evaluated using the Revised Cardiac Risk Index (RCRI) and the National Surgical Quality Improvement Program Myocardial Infarction and Cardiac Arrest risk calculator (NSQIP MICA). Patients with a RCRI score ≤1, or a NSQIP MICA cardiac risk estimate less than 1%, were considered to be at low cardiac risk.

Results:
1,134 patients underwent laparoscopic bariatric surgery during the study time period, of which 1,093 (96.4%) were low cardiac risk by RCRI and 1,133 (99.9%) were low cardiac risk by NSQIP MICA. 587 patients (51.8%) were referred to cardiology for preoperative evaluation. 643 patients (56.7%) underwent one or more preoperative cardiac tests (see figure for breakdown of cardiac risk for each cardiac evaluation). Out of 1,134 patients, 1 (0.1%) had myocardial infarction within 30 days of surgery. There were 0 patients with either cardiac arrest or death within 30 days of surgery.

Conclusions:
A large majority of patients undergoing cardiac evaluation and testing prior to laparoscopic bariatric surgery were at low cardiac risk, regardless of whether cardiac risk was assessed by the RCRI or by the NSQIP MICA. Preoperative cardiac testing and evaluation were common despite excellent cardiac outcomes. Use of tools such as the RCRI or NSQIP MICA to identify patients at low cardiac risk at the time of bariatric enrollment may help to reduce the overuse of preoperative cardiac evaluation and testing in low risk patients.
Abstract 9649: Challenging The Dogma: Increasing Cardiac Fatty Acid Rather Than Glucose Utilisation Improves Cardiac Function in Severe Non-Ischaemic Heart Failure With Reduced Ejection Fraction (HFrEF)
Authors: Watson William , Green Peregrine , Lewis Andrew J , Neubauer Stefan , De Maria Giovanni Luigi , Herring Neil , Rider Oliver J
Published: April 2022

Introduction:
Based on the premise that in HFrEF the heart is metabolically inflexible and oxygen limited, current metabolic therapies aim to increase glucose oxidation. However, if the human failing heart is neither inflexible nor oxygen limited, this approach is called into question.

Methods:
During either insulin-glucose (GI) or Intralipid infusion (IL) (random order), 20 non-ischaemic HFrEF patients underwent cardiac magnetic resonance imaging and
31
P-spectroscopy at rest and during dobutamine infusion (mean 100 bpm). 10 patients underwent invasive arteriovenous blood sampling (left main–coronary sinus), coronary flow and left ventricular (LV) pressure-volume loop measurements, during GI and IL infusion, at rest and during rapid atrial pacing (100 bpm).

Results:
At rest, during IL fatty acid (FA) uptake was higher (61±53 vs 5±13 μmol/min, p=0.03) and during GI, glucose uptake was higher (97±53 vs 45±36 μmol/min, p=0.04). Compared to fasting conditions, LV ejection fraction was higher during IL (40±9 vs 35±9%, p<0.001), but unchanged during GI (34±8%). Cardiac work was higher during IL (466±148 vs 549±163 mmHg.L/min, p=0.02), as was LV developed pressure (by 6mmHg, p=0.049). At rest, during IL, myocardial oxygen uptake (MVO
2
20±9 vs 15±9 ml/min, p=0.05) and phosphocreatine/ATP ratio (PCr/ATP 2.01±0.33 vs 1.86±0.25, p=0.02) were higher and lactate was consumed. Stress cardiac work was again higher during IL (by 62mmHg.L/min, p=0.009). Despite higher cardiac work and MVO
2
during IL at stress, PCr/ATP was again unchanged and lactate consumed. During GI, with atrial pacing (100 bpm) FA uptake was increased >4 fold (5±14 vs 24±32 μmol/min, p=0.04), suggesting selective FA preference.

Conclusions:
In severe HFrEF cardiac metabolic flexibility is retained changing substrate use to match arterial supply and workload. At rest and stress, increased FA uptake, but not glucose is associated with increased contractility. Cardiac preference to FA was observed during stress. Despite increased MVO
2
, the phosphocreatine pool remains stable and lactate is consumed, showing that mitochondrial oxygen supply was not fixed or limited. This challenges existing dogma, suggesting increasing FA oxidation and not glucose should be the therapeutic target in HFrEF.
Abstract 9676: Inflammation Mediated Vitamin K Protective Effect Against Vascular Calcifications in Antiretroviral Treated People Living with HIV
Authors: Janus Scott E , Durieux Jared , Hajjari Jamal , Labbato Danielle , McComsey Grace
Published: April 2022

Background:
People living with HIV (PLWH) experience increased inflammation, risk of cardiovascular (CV) events, and coronary artery calcium scores (CACs). In cross-sectional analyses, vitamins D and K have been associated with CACs and may have an anti-inflammatory effect. The anti-inflammatory effects of Vitamins D and K in successfully treated PLWH is less understood.

Methods:
We prospectively recruited 237 PLWH on antiretroviral treatment and 67 HIV- healthy controls. CACs were derived from non-contrast CT and levels of 25-hydroxyvitamin D (vitamin D) and inactive vitamin K dependent dephosphorylated-uncarboxylated matrix G1a protein (MGP, marker of vitamin K deficiency) were measured in plasma. The relationship between inflammation markers, MGP, and vitamin D on CACs were estimated using zero-inflated negative binomial regression. Adjusted models included 25(OH)D, MGP, gender, race, age, and markers of inflammation.

Results:
Controls had lower median age (45.8 vs. 48.8; p=0.03) and a larger proportion of females (55.2% vs. 23.6%; p<.0001). Among PLWH, <1% had detectable viral load and the median CD4 was 682.0(IQR: 473.0, 899.0). 62.17% of the sample had zero CACs and 51.32% were vitamin D deficient (<20 ng/mL). There was no difference in detectable CACs (p=0.19) or MGP (p=0.42) between PLWH and controls. In adjusted models, every one-unit increase in (
log2
)25(OH)D is associated with >200% increase in the expected CACs among PLWH. Every one-unit increase in MGP (worse K status) decreases the probability of having CACs equal to zero 21.3% (p=0.01). Evidence suggests that the effects of 25(OH)D and MGP are inflammation mediated, specifically through VCAM and TNF-α pathways.

Conclusion:
Vitamins K deficiency is a modifiable preventive factor against coronary calcification in PLWH. Further research should determine whether vitamin K supplementation would reduce vascular calcification and risk of CV events in PLWH and increased inflammation
Abstract 9677: Therapeutic Improvements in Pulmonary Arterial Hypertension Are Related to Cardiopulmonary Function but Not Skeletal Muscle Oxygen Extraction
Authors: Stroud Steven , Insel Michael , Acharya Tushar , Rischard Franz
Published: April 2022

Introduction:
World Symposium Group 1 pulmonary arterial hypertension (PAH) patients have impaired function from both central oxygen delivery and skeletal muscle oxygen extraction. The effect of PH-directed therapy on skeletal muscle oxygen extraction is unknown. The aim of this study is to determine if therapy associated changes in muscle extraction parallel changes in cardiopulmonary function.

Methods:
Retrospective analysis was performed on twenty-nine PAH patients (24 female, mean age 54±11.4 years) receiving prostacyclin therapy (18 on monotherapy). Subjects underwent invasive cardiopulmonary exercise testing (iCPET) for treatment response evaluation followed by repeat surveillance iCPET with mean follow-up of 10.4±5.2 months. Skeletal muscle oxygen extraction was quantified by arterio-venous difference indexed to hemoglobin (Ca-vO
2
/Hgb) and systemic oxygen extraction ratio (SER) (Ca-vO
2
/CaO
2
). Central oxygen delivery (DO
2
) was calculated as peak cardiac output X CaO2 at peak exercise. Functional capacity was semi-quantified by six-minute walk test (6MWT) distances between assessments (n=20). Subjects were stratified into two groups: those with improvement (n=10) vs unimproved (n=19) in currently accepted ERS/COMPERA score (
Figure
).

Results:
Improvements in ERS/COMPERA score were related to DO
2
(318.3±273.1 vs -38.3±684.9 mL/min,
P=.016
) and PVR (-4.8±3.0 vs -0.6±3.2 WU,
P=.002
)
(Figure A & B).
However, there was not a detectible difference between assessments in Ca-vO
2
/hgb (-0.01±0.14 vs 0.00±0.27 mL/g,
P=.573
), SER (-0.01±0.10 vs 0.00±0.20,
P=.573
), or 6MWT (7 improved, 13 unimproved) (77±115 vs 25±104 meters,
P=.877
) (
Figure C & D
).

Conclusions:
Although PH-directed therapy improves both PVR and oxygen delivery, its effects on skeletal muscle extraction are questionable. Clinicians should consider that oxygen extraction may influence functional capacity when evaluating therapeutic improvement.
Abstract 9684: Admission Ecg May Predict Short-Term Mortality Among Adults Hospitalized With Covid-19 Infection
Authors: O'Day Kevin , Ferreira Sarah , Asaker Jean-Claude , Hamad Hannah , Mahagaokar Kedar , O'Connor Laurel , Phelan Christopher , Tighe Dennis , McManus David , Soni Apurv , Kovell Lara
Published: April 2022

Introduction:
Cardiovascular complications of novel SARS-CoV-2 infection remain poorly understood with outcomes limited to index hospitalizations.

Methods:
This retrospective cohort study included patients with proven COVID-19 who received care at a single hospital network in Massachusetts from March 11, 2020 to May 23, 2020 and received an electrocardiogram (ECG) within 24 hours of hospital presentation. We investigated mortality and cardiovascular complications within 90 days from initial COVID-19 diagnosis. Data were electronically abstracted and confirmed by manual chart review.

Results:
A total of 1,744 patients tested positive within the hospital network during the study period. Nearly half of them (49.3%) were hospitalized and 15.5% died within 90 days. A total of 278 patients received an ECG within 24 hours, representing 23.6% of all hospitalized patients. These patients were disproportionately older (38.5 vs 58.1% over the age of 60, p < 0.01), male (49.6 vs 56.2%, p = 0.05), and white (48.1 vs 56.2, p < 0.01). Admission ECGs demonstrating ischemic changes (ST-elevations, ST-depressions, and T-wave inversions) or new arrhythmias (atrial fibrillation/flutter, bradyarrhythmia, supraventricular tachycardia) were identified among 10.1% and 9.0% of the patients, respectively. Heart failure and cardiomyopathy were rare findings (<1%). After adjusting for age, sex, and past medical history, ischemic changes or new-onset arrhythmias were associated with nearly five-times greater risk of death (OR: 4.9; 95% CI 1.7 - 14.4).

Conclusions:
In this retrospective study among hospitalized adults with a proven COVID-19 infection, admission ECGs demonstrating ischemic changes or new-onset dysrhythmia predict a higher risk of death in the short-term.
Abstract 9691: Lipoprotein Subclasses Are Associated With Hepatic Steatosis: Insights from the Prospective Multicenter Imaging Study for the Evaluation of Chest Pain (PROMISE) Clinical Trial
Authors: Ferencik Maros , McGarrah Robert W , Nguyen Maggie , Navar Ann M , Meyersohn Nandini , Giamberardino Stephanie , Lu Michael , Staziaki Pedro , Puchner Stefan B , Bittner Daniel , Foldyna Borek , Pagidipati Neha J , Kraus William E , Ginsburg Geoffrey S , Douglas Pamela S , Hoffmann Udo
Published: April 2022

Introduction:
Hepatic steatosis (HS) is associated with coronary artery disease (CAD) and cardiovascular (CV) events. Previously, we have demonstrated that granular measures of lipids (lipoprotein particle number/size) are associated with CAD and CV events and incremental to traditional lipid measures.

Hypothesis:
Granular measures of lipids are associated with HS detected by cardiac computed tomography (CT) and with HS detected by histopathology.

Methods:
We included 1524 subjects from the PROMISE trial. HS was defined as CT attenuation of the liver <40HU or liver<spleen HU on CT. Plasma lipoprotein particle parameters were measured by NMR. Principal components analysis was used for dimensionality reduction and logistic regression was used to test the association of lipoprotein factors and individual lipoproteins with HS cases and controls in uni/multivariable models. The association of lipoproteins with HS was validated in an independent cohort of 58 subjects (Laval U) with and without HS defined by histopathology on liver biopsy.

Results:
Subjects with HS (n=413) were slightly younger (59±8 vs 61±8 yrs) and more likely men (53 vs 44%) as compared to controls (n=1111). Three lipoprotein factors were associated with HS: LDL/LDL particle size (OR 1.36, 95%CI 1.21-1.53, p<0.001); HDL/HDL size (OR 1.75, 95%CI, 1.53-2.02, p<0.001), and TG-rich-lipoprotein particles (OR 0.74, 95% CI 0.65-0.84, p<0.002). Individual lipoproteins heavily loaded in these factors were also significant in multivariable analysis (Figure). These lipoproteins were also associated with HS in the validation cohort: small LDL (OR 6.36, p<0.05), large HDL (OR 0.29, p<0.05), and large TG particles (OR 13.83, p<0.05).

Conclusions:
We found association of small LDL, large HDL and large TG particles, previously associated with CV event risk, with HS phenotyped by CT and histopathology. These results suggest that use of lipoprotein subclasses may improve CV risk assessment in patients with HS.
Abstract 9693: Predicting Biventricular Repair in Common Atrioventricular Canal by Cardiac Magnetic Resonance Imaging: The New Normal?
Authors: Jones Andrea L , White Brian R , Ghosh Reena M , Mondal Antara , Ampah Steve B , Ho Deborah Y , Biko David M , Harris Matthew A , Partington Sara , Whitehead Kevin K , Cohen Meryl S , Fogel Mark A
Published: April 2022

Introduction:
Patients with malaligned common atrioventricular (AV) canal (CAVC) are difficult to manage when one ventricle is borderline hypoplastic. The decision between the single ventricle pathway or attempting a biventricular repair depends upon pre-operative parameters which have previously been studied only by echocardiography. The purpose of this study was to determine the utility of cardiac magnetic resonance (CMR) in predicting success of a biventricular repair in CAVC.

Methods:
We performed a single center, retrospective cohort study of children with varying degrees of CAVC malalignment who underwent CMR prior to definitive repair (7/1/10 to 2/28/21). The primary outcome was successful biventricular repair. CMR measurements were performed by the investigators. To account for both dominant right ventricles (RV) and left ventricles (LV), ratios of ventricular and AV valve size were normalized as differences from their expected values. Associations were tested using univariable logistic regression. Multivariable regression models using combinations of two variables with p-values less than 0.2 were tested.

Results:
We included 28 patients (median age at CMR: 5.2 months, 43% male). Clinical and CMR variables are shown in Table 1. The optimal multivariable predictive model included the normalized LV end diastolic volume (EDV) to total ventricular EDV ratio and the LV-RV angle in diastole. Area under the receiver operator characteristic curve was 0.83 (p = 0.041). An LV EDV to total EDV ratio between 0.30 and 0.66 had a sensitivity of 92% and specificity of 63% for predicting successful biventricular repair. Including an LV-RV angle in diastole of less than 72 degrees resulted in a sensitivity of 83% and specificity of 81%.

Conclusions:
Multiple CMR measures were associated with surgical outcomes. CMR measures such as LV EDV to total ventricular EDV ratio and LV-RV angle in diastole can accurately predict successful biventricular canal repair.
Abstract 9703: Prevalence and Outcomes of Low Ankle Brachial Index in ASCVD Risk Categories- from the National Health and Nutrition Examination Survey
Authors: Chobufo Muchi Ditah , Amir Meesum , Munir Muhammad , SINGLA ATUL , Ali Abbas , Aronow Wilbert S , balla Sudarshan
Published: April 2022

Introduction:
The utility of Ankle Brachial Index(ABI) as a risk-enhancer to the pooled cohort equations(PCE) in assessing cardiovascular risk for primary prevention of atherosclerotic cardiovascular disease(ASCVD) is uncertain. We aim to assess the prevalence and all-cause mortality of people with low ABI across ASCVD risk categories.

Hypothesis:
Would the addition of ABI to standard ASCVD risk assessment improve all cause mortality risk stratification?

Methods:
Participants were recruited as part of the National Health and Nutrition Examination Survey from 1999-2004 and mortality assessed on 12/31/2015. We included participants aged 40-75years with ABI values≤1.3 and data for ASCVD computation using the PCE. Persons with ABI<0.9 and ABI 0.9-1.3 were classified as having low ABI and normal ABI, respectively.

Results:
The mean follow-up time was 156months(95%CI 154-158). Persons with low ABI were older(61 Vs 53years) and had higher mean systolic blood pressure(135 Vs 126mmHg). There was no difference in mean total cholesterol(mg/dl)[212(95%CI 210-214) vs. 208( 202-215)], LDL(mg/dl) [128 (95%CI 125-130) vs. 121(112-129)] and HDL(mg/dl) [54 (95%CI 53-54) vs. 52(50-55)] between the two ABI categories. The all-cause mortality was higher among persons with low ABI(43.1%) compared to those with normal ABI(12.2%), p<0.001. The all-cause mortality in the normal ABI and low ABI categories was 4.8% and 8.8% in the low risk ASCVD group and 7.8% and 41.6% in the borderline/intermediate ASCVD risk group, respectively.

Conclusions:
Approximately 67% of participants with low ABI were classified as low, borderline or intermediate risk by PCE. Low ABI was associated with increased all-cause mortality in the intermediate/borderline and high ASCVD risk categories but not in the low ASCVD risk category. Our study supports the use of ABI in risk stratification for primary prevention of ASCVD in individuals with borderline or intermediate risk.
Abstract 9704: Mortality and Readmissions in Patients With Heart Failure With Preserved Ejection Fraction versus Heart Failure With Reduced Ejection Fraction
Authors: Carcora Yaser , Gravely Amy , Tholakanahalli Venkatakrishna N , Adabag Selcuk
Published: April 2022

Introduction:
Heart failure (HF) is a large public health problem with a 12 month mortality rate of 22% and a 30 day standardized readmission rate of 23%. We aimed to determine the differences in readmissions and long-term survival in patients with Heart Failure with Preserved Ejection Fraction (HFpEF) compared to Heart Failure with Reduced Ejection Fraction (HFrEF).

Hypothesis:
Heart Failure patients will have high mortality regardless of ejection fraction, with similar readmission rates across groups.

Methods:
We studied 3200 consecutive patients discharged from the hospital with a primary diagnosis of HF from October 2015 to March 2019. Patients were classified as HFpEF (EF >50%) or HFrEF (EF<50%).

Results:
At baseline, patients had a mean age of 75.0±10.3 and 97.9% were male. Patients with HFrEF were more likely to have coronary artery disease, myocardial infraction, diabetes, and more likely to be on beta blockers and ACE inhibitors (all p<0.0001)(Table 1). Over 11.2±11.3 months of follow-up, patients with HFrEF were more likely to be readmitted (49.2 vs 37.5%, p<0.0001)(Table 2). However, 3-year cumulative all cause death was no different between groups (34.6% vs. 34%; p=0.512) (Figure).

Conclusions:
Patients with HFrEF were more likely to have readmissions than those with HFpEF. But the long-term mortality was unacceptably high in both groups.
Abstract 9706: Sex Differences in Symptoms During Arrhythmias
Authors: Russo Andrea M , Dziubinski Marek J , Napiorkowski Natan , Witkowska Olga , Grotek Agnieszka , Slusarczyk Magdalena E , Johnson Linda
Published: April 2022

Introduction:
Prior studies have reported sex differences in symptoms and quality of life in patients (pts) with atrial fibrillation (AF). It is currently unclear if this is also true for other arrhythmias or if symptoms occurring at the time of arrhythmia recordings differ by sex.

Hypothesis:
We hypothesized that women may be more symptomatic than men during atrial and ventricular arrhythmias and that differences may be associated with differences in heart rate (HR).

Methods:
We examined 27,203 pts (58% women) with up to 30-day ECGs recorded using the PocketECG (MediLynx), which transmits a 3-lead ambulatory ECG and uses an algorithm based on rhythm and morphology. VT and SVT were defined as 3 or more beats, and AV block included 2nd- or 3rd-degree block. A sustained arrhythmia was ≥30s. The rhythm occurring 30 s prior to symptoms was analyzed. Chi2 tests were used to compare women to men.

Results:
Men were older than women (68.9 ± 13.9 vs 67.7 ±15.6, 95% CI of the difference: [-1.55; -0.84]). Mean HR in SR was faster in women than in men (73.1 ± 10.3 vs. 70.2 ± 10.3 bpm, [2.64; 3.16]). Women were more likely to have SVT (76 vs. 74%) and less likely to have AF (15% vs. 21%), VT (23% vs. 41%), PVCs (45% vs. 61%), PACs (55% vs. 57%) or AV block (21% vs. 28%). Women were more likely than men to report symptoms (66.4% vs. 55.6%, p<0.001), including greater frequency of palpitations, chest discomfort, and shortness of breath (p<0.001 for all). (Figure 1) Women were more likely to report symptoms during PACs and SVT while men were more likely to report symptoms during AF (p <0.001 for all). Mean HR in AF is faster in women (106.5 ± 26.6 vs. 98.7 ± 27.4, 95% CI: [6.29 ; 9.36]). (Figure 2)

Conclusions:
Symptoms experienced during arrhythmias differ by sex. Reasons for these differences are currently unclear but could be related to ventricular function, underlying heart disease or medications, and are not clearly related to HR. Further study is needed to help identify reasons for differences in symptoms.
Abstract 9708: Direct Normal Irradiance from Solar Radiation Negatively Correlates With Af Hospitalization in the United States
Authors: Modi Malak , Mohammad Zoya , Bhandari Ruchi , Boerma Marjan , Gopinathannair Rakesh , Olshansky Brian , Dominic Paari
Published: April 2022

Introduction:
Medical radiation has been linked to increased risk of AF but any association between solar irradiation and AF remains unexplored.

Aim:
To study the role of solar radiation on AF.

Methods:
State-wise and county-wise CDC data with AF hospitalization rates in Medicare beneficiaries from 2015 to 2017 was used. Data regarding solar irradiation and other meteorological parameters, specifically, the midpoints of direct normal irradiation (DNI), direct horizontal irradiation (DHI), global horizontal irradiation (GHI), global tilted irradiation (GTI), terrain elevation, sunny hours, clear day and air temperature were collected from publicly available sources for 49 states. Bivariate and multivariable regression were carried out with environmental factors as the independent and AF as the dependent variables.

Results:
AF hospitalization correlated negatively with DNI [Standardized Beta Coefficient (β) = -0.352, p = 0.013], GHI (β = -0.146, p = 0.316), GTI (β = -0.264, p = 0.067) and terrain elevation (β = -0.590, p = 0.000), whereas DHI correlated positively with AF hospitalization rate (β = 0.480, p = 0.000). Other environmental factors such as sunny hours (β = -0.296, p = 0.046) and clear days (β = -0.198, p = 0.172) negatively correlated with AF hospitalization rates, but air temperature positively correlated with AF hospitalization rates (β = 0.374, p = 0.008). Multivariable regression analysis showed that DHI and DNI independently had a positive and negative correlation, respectively, to AF hospitalization rates after adjusting for potential confounders including age, COPD, hypertension, diabetes and air quality index. A sensitivity analysis with multivariate regression, adjusting for air temperature showed that DNI had a significant negative correlation (β = -0.277, p = 0.000) and DHI had a significant positive correlation (β = 0.370, p = 0.000) with AF hospitalization rates for the counties with five largest cities of each state.

Conclusions:
DNI (direct radiation without diffusion) negatively correlates with AF hospitalization rate, whereas DHI (rays scattering due to clouds, particulate matter and ozone) has a positive correlation. Further research may shed light on the mechanisms behind solar radiation-induced protection from AF.
Abstract 9710: Prevention of Doxorubicin-Induced Cardiotoxicity Through Targeted Degradation of Topoisomerase 2b
Authors: Chang Hui-Ming , Yeh Edward T
Published: April 2022

Introduction:
Doxorubicin-induced cardiotoxicity is a serious complication of cancer therapy recognized 40 years ago and remains to be a major clinical challenge today. Doxorubicin poisons topoisomerase 2a to kill cancer cells, whereas doxorubicin induces cardiotoxicity through topoisomerase 2b. When topoisomerase 2b was genetically deleted in the cardiomyocytes of adult mice, doxorubicin-induced cardiomyopathy can be prevented.

Hypothesis:
Pharmacological depletion of topoisomerase 2b in cardiac tissue could prevent doxorubicin-induced cardiomyopathy.

Methods:
Cell lines were treated with dexrazoxane (100 μM) for different time intervals with or without the proteasome inhibitor MG132 (10 μM). Cell lysates were immunoblotted with anti-topoisomerase 2a or 2b antibodies or anti-actin. Mice were injected with dexrazoxane (100 mg/kg IP) and cardiac tissues were analyzed for expression of topoisomerase 2b over time using western blot analysis. To study the effect of dexrazoxane pre-treatment on doxorubicin-induced chronic heart failure, C57BL/6 mice (n=7) were pre-treated with dexrazoxane (100 mg/kg IP) 8 hours before doxorubicin (5 mg/kg IP). Single injection of dexrazoxane (n=6), doxorubicin (n=8), or saline control (n=6) were also administered to three different cohorts of mice. This protocol was repeated weekly for 5 weeks. Pre-treatment and post-treatment cardiac MRI were obtained to evaluate the change in left ventricular ejection fraction.

Results:
Dexrazoxane induced a ubiquitin-dependent degradation of topoisomerase 2b, but not 2a in cell lines. In dexrazoxane-treated mice, topoisomerase 2b was not detectable 8 hours after dexrazoxane administration, but gradually returned to normal levels by 48 hours. Dexrazoxane pre-treatment 8 hours before doxorubicin prevented doxorubicin-induced reduction in ejection fraction as determined by cardiac MRI in a chronic heart failure model.

Conclusions:
Targeted degradation of topoisomerase 2b by dexrazoxane prevented doxorubicin-induced cardiotoxicity. Through selective degradation of topoisomerase 2b, but not 2a, doxorubicin's tumoricidal activity is preserved. This preventive strategy will be tested in a prospective clinical trial in breast cancer patients.
Abstract 9711: Unexplained Dyspnea on Exertion: The Difference the Right Test Can Make
Authors: Rao Vishal N , BLAZING Michael A , Pagidipati Neha J , Fudim Marat
Published: April 2022

A 66-year-old male with past history of coronary atherosclerosis by angiography was referred for chronic dyspnea. He is a pastor and had noted dyspnea with prolonged standing or walking that resolved with sitting. Serial orthostatic vitals and natriuretic peptides were normal. Subsequent diagnostics included normal pulmonary function and ventilation-perfusion tests, and echocardiography with normal biventricular function, sizes, and estimated pressures. Given ongoing dyspnea, he underwent supine invasive cardiopulmonary exercise testing (iCPET). Resting invasive pressures and cardiac output were normal. At peak exercise, exertional dyspnea was absent but pressures increased to mean PAP 40 and PCWP 28 with preserved cardiac output and 77% predicted maximal aerobic capacity (pVO2). He was diagnosed with exercise induced heart failure with preserved ejection fraction and started on furosemide and spironolactone. On follow-up, he reported worsened dyspnea on therapy, most notably when upright. Stress cardiac MRI showed no scar. Given the positional nature of his symptoms, an iCPET was repeated in the upright position. His diuretics were stopped. Resting supine measurements were similar to the prior iCPET. Upright resting to peak exercise pressures changed minimally (
Figure
). His profound dyspnea recurred at peak exertion as MAP dropped unexpectedly with paradoxical bradycardia (Bezold-Jarisch reflex) and 62% pVO2. His diagnosis was reclassified as cardiac preload failure. He was advised to increase fluid and salt intake alongside use of leg stockings which remarkably improved his upright and exercise dyspnea symptoms at follow-up. This case highlights an advantage of upright iCPET over supine diagnostics in the comprehensive evaluation of unexplained dyspnea. Cardiac preload failure is the failure to augment preload with exercise and is a common but under-recognized cause of dyspnea often undiagnosed during supine resting and exercise testing.
Abstract 9712: Impact of Heart Failure on Prognosis in Cancer Patients (Kurume-CREO Study)
Authors: Morikawa Nagisa , Shibata Tatsuhiro , Nohara Shoichiro , Fukumoto Yoshihiro
Published: April 2022

Introduction:
With recent progress in treatment of cancers, cancer survivors have an increased risk of cardiovascular diseases (CVDs) due to aging or toxicities of anti-cancer drugs. However, more evidence regarding CVD risk in cancer survivors is required.

Hypothesis:
CVD as comorbidity has a big impact on prognosis in cancer patients.

Methods:
We enrolled 400 patients with hematological malignancy and breast cancer visiting Kurume University Hospital between October in 2016 and December in 2019 in Kurume-CREO study, a prospective observational study. We evaluated blood test and chest X-ray, electrocardiogram and echocardiography at baseline and follow up every 6 months after baseline. Outcomes were defined as all-cause deaths and CVD mortality due to myocardial infarction, heart failure (HF) and pulmonary thromboembolism. HF was defined as either N-terminal prohormone of brain natriuretic peptide elevation or findings in chest X-ray or diagnosed HF by cardiologists. We followed up until September 23th in 2019.

Results:
Mean age (± standard deviation) of participants was 64.1 (± 12.9) years old, and 280 of 400 patients (70%) were enrolled before chemotherapy. Among hematological malignancies, non-Hodgkin’s lymphoma (n=223, 68.2%) and multiple myeloma (n=55, 16.8%) were most frequently observed. During the follow-up period, 85 patients (21.3%) died, 2 patients (0.5%) died from CVD and 50 patients (12.5%) had HF. Survival curves showed a significantly worse survival rate in patients with hematological malignancy compared to those with breast cancer (Log-rank p = 0.002)(Fig 1). All cancer patients with HF during the period had significantly worse prognosis than those without HF (Log-rank p = 0.003)(Fig 2).

Conclusions:
Mortality in cancer patients with HF comorbidities was significantly higher than in those without HF. CVD death was very rare in the present study, but HF comorbidity was a significant prognostic factor in cancer.
Abstract 9714: Deep Learning on 12-Leads Electrocardiography Can Predict Recurrence After Pulmonary Vein Isolation in Patients with Persistent Atrial Fibrillation
Authors: Shimizu Masato , Miyazaki Hiroko , cho shummo , Misu Yoshiki , Takeishi Ryo , Yamaguchi Masao , Yamakami Yosuke , Shimada Hiroshi , Manno Tomoko , Isshiki Ami , Kimura Shigeki , Fujii Hiroyuki , Suzuki Makoto , Nishizaki Mitsuhiro , Sasano Tetsuo
Published: April 2022

Introduction:
In patients with persistent atrial fibrillation (per-AF) who were treated by pulmonary vein isolation (PVI), several patients suffer from recurrence. Various methods to predict the recurrence were tried, but prognostic value of deep learning on 12-leads electrocardiography (ECG) just after PVI was not studied.

Hypothesis:
Deep learning on 12-leads ECG after PVI has high diagnostic performance in patients with per-AF.

Methods:
We enrolled consecutive 109 patients with per-AF who underwent PVI (68.8±10.0 years, 83 males) excluding failure cases. We defined recurrence in 3-12 months after PVI. From the ECG just after PVI, five beats of each lead were sampled separately. Deep learning (convolutional neural network on bitmap ECG image) was performed by transfer learning of Inception-Resnet-V2 model. Gradient weighted class activation color mapping (GradCam) was performed to detect convolutional importance in the lead.

Results:
Thirty-six patients showed recurrence in the period. Lead II (accuracy 0.701), aVR (0.690) were the top 2 leads of prediction, which showed larger accuracy than statistical accuracies of Non PV foci = SVC (accuracy = 0.541) and left atrial diameter > 50mm (0.596). In lead II, GradCam spotlighted strong convolution of latter half of P wave in recurrent case, and former half of P wave and T wave in no-recurrent case.

Conclusions:
Deep learning on ECG was a powerful tool to predict recurrence of per-AF after PVI.
Abstract 9715: Feasibility of Using Machine Learning to Establish a Risk Prediction Model for Sudden Cardiac Death in Patients with Hypertrophic Cardiomyopathy
Authors: Liu Jie , Wu Guixin , Feng Xinxing , Zhang Shuai , Wang Dong , Xu Lianjun , Jiang Wen , sun xiaolu , Kang Lianming , Huang Xin , Wang Jizheng , song lei
Published: April 2022

Introduction:
Risk stratification for sudden cardiac death (SCD) is a great challenge in managing hypertrophic cardiomyopathy (HCM).

Hypothesis:
This study attempted for the first time to build a machine learning (ML) model for SCD risk prediction.

Methods:
The present study consisted of 1631 consecutive adult HCM patients without a history of SCD events. Extreme gradient boosting (XGBoost) was applied for ML model construction. We compared the predictive performance of the ML model with that of conventional models by calculating C-statistics and interpreted the ML model output using the SHapley Additive exPlanation (SHAP) value.

Results:
Fifty patients reached SCD endpoints during a median follow-up of 4.6 years. The C-statistic of the ML model was 0.745 [95% confidence interval (CI), 0.723-0.766], which was significantly higher than that of the model recommended in the 2014 European Society of Cardiology guidelines (C-statistics =0.609; 95% CI 0.585-0.623) and the model recommended in the 2020 American College of Cardiology/American Heart Association guidelines (C-statistics =0.628; 95% CI 0.604-0.652). The ML model incorporated 12 features as predictors, including 5 conventional SCD risk markers (NSVT, quantification of LGE, family history of SCD, LVEF 50%, unexplained syncope), WBC, creatine, uric acid, TBIL and cholesterol, NT-proBNP and family history of HCM. Using SHAP values, we quantified the contribution of each feature within the ML model to the final prediction and visualized the relationship between features and SCD risk.

Conclusion:
Our study constructed an ML model for the prediction of SCD risk in

patients with HCM and provided a clinically intuitive interpretation. The ML model showed better discrimination performance than conventional models, demonstrating the feasibility of ML in SCD risk prediction for patients with HCM.
Abstract 9725: Autonomic Modulation Mitigates Perivascular and Perirenal Adipose Inflammation and Consequent Cardiorenal Involvement in Prediabetes
Authors: Hammoud Safaa , AlZaim Ibrahim , Bekdash Amira , Mougharbil Nahed , Itani Hana A , El-Yazbi Ahmed F
Published: April 2022

Background:
Early metabolic impairment is associated with significant cardiorenal risk. Specifically, subtle serum insulin and lipids changes in prediabetes trigger cardioautonomic and renovascular deterioration. Interestingly, data from our laboratory suggest that these insidious alterations are triggered by perirenal and perivascular adipose inflammation in response to hypoxia evoked by a localized increase in uncoupling protein1 (UCP1) expression and activity. This affects the adjacent organs in a paracrine manner.

Hypothesis:
Increased UCP1 expression is triggered by sympathetic stimulation. The sympathovagal imbalance in early metabolic dysfunction underlies the observed localized adipose pool involvement. Pharmacological interventions to offset the sympathetic predominance should prevent increased UCP1 expression and inflammation, and reverse cardiorenal manifestations.

Methods:
A non-obese prediabetic rat model was induced by twelve weeks of hypercaloric feeding. Moxonidine and galantamine were administered orally at daily doses of 2.4 mg/Kg and 4 mg/Kg for the last two weeks of feeding to reduce and facilitate sympathetic and parasympathetic discharge, respectively. Baroreflex sensitivity and renovascular reactivity were assessed by invasive hemodynamics and in isolated perfused kidneys, respectively. Adipose tissue T Cell distribution and macrophage polarization were examined by flow cytometry.

Results:
Correcting the autonomic imbalance in prediabetic rats with either moxonidine or galantamine restored cardioautonomic and renovascular activity to those observed in control rats. Although prediabetic rats showed an increased oxidative stress and proinflammatory cytokine production in both adipose pools, no change in T Cell population distribution was observed. However, the increased M
1
/M
2
macrophage polarization profile observed in prediabetic rats was reversed by either drug treatment. This was associated with a normalization of UCP1 expression and hypoxic status.

Conclusions:
Pharmacological interventions to reverse sympathetic predominance could be of therapeutic value treating perivascular and perirenal adipose inflammation that cause early cardiorenal manifestations of prediabetes.