bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12026: Correlates of Sleep Disordered Breathing and Cheyne-Stokes Respiration in Patients With Atrial Fibrillation Undergoing Pulmonary Vein Isolation
Authors: Sato Akihiro , Kasai Takatoshi , Matsumoto Hiroki , Suda Shoko , Ishiwata Sayaki , Kato Takao , Kurita Azusa , Naito Ryo , Hayashi Hidemori , Minamino Tohru
Published: April 2022

Background:
Sleep disordered breathing (SDB) is known as a common comorbidity in patients with atrial fibrillation (AF). Indeed, patients undergoing pulmonary vein isolation (PVI) for AF had a high prevalence of SDB in particular, Cheyne-Stokes respiration (CSR). The aim of the present study is to assess the correlates of SDB severity and CSR in AF patients undergoing PVI.

Methods and Results:
The study was conducted under a single-center, observational design. We enrolled 140 consecutive patients undergoing PVI. All participants underwent home sleep apnea test (ApneaLink Air, ResMed, Australia) which could determine the severity of SDB as assessed by apnea-hypopnea index (AHI) and the percent of CSR (%CSR) pattern. Overall, 33 (27.9%) patients was no SDB (AHI<5), 53 (37.9%) patients was mild SDB (5≦AHI<15), 33 (23.6%) patients was moderate SDB (15≦AHI<30), and 15 (10.7%) patients was severe SDB(30≦AHI). Correlates of the increased AHI includes male sex (β=0.27, p=0.001), high age (β=0.19, p=0.0028), high body mass index (BMI) (β=0.29, p=0.0013), hypertension (β=0.18, p=0.038), and non-paroxysmal AF (β=0.17, p=0.047). On the other hand, correlates to %CSR rate includes male sex (β=0.17, p=0.026), high age (β=0.22, p=0.0054), non-paroxysmal AF (β=0.27, p=0.0005), high value of HbA1c (β=0.3, p<0.0001), and greater N-terminal fragment of the Brain natriuretic peptide (NT-proBNP) (β=0.26, p=0.0007).

Conclusion:
Increased SDB severity correlated with male sex, high age, obesity, hypertension and chronicity of AF in patients with PVI. Correlates the percent of %CSR were male sex, high age, the chronicity of AF, high value of HbA1c, and greater NT-proBNP. Treatment for SDB should be consider for these AF patients, because SDB increases the recurrence ratio of AF after PVI.
Abstract 12030: Impact of High-Resolution Epiaortic Ultrasonographic Imaging on Evaluating Aortic Wall Pathology
Authors: Henmi Soichiro , Izumi So , Kanno Reiko , Hoshino Masato , NAKAGAWA Kazunori , Nakashima Yutaka , Okada Kenji , Tsukube Takuro
Published: April 2022

Introduction:
Innovative imaging modality for preclinical diagnosis of aortic dissection (AD) has been awaited.

Hypothesis:
We previously reported that synchrotron radiation-based X-ray phase-contrast tomography (XPCT) imaging revealed densitometrical changes in the tunica media in the aortic wall (TM) of AD. To replicate XPCT findings in clinical practice, we investigated the application of high-resolution ultrasound in intraoperative epi-aortic scan (EAS) imaging.

Methods:
Twelve patients (normal aorta (5), chronic AD (3), acute type-A AD(4)) were selected. Before beginning cardiopulmonary bypass, the mid-ascending aorta was exposed and an EAS was conducted using EPIQ CVx and an eL18-4 transducer. After aortic repairs, the aortic samples of AD were fixed and applied XPCT, to compare ultrasonographic intensity (UI) of EAS and densitometric changes in XPCT in the same samples.

Results:
In normal aorta, UI remained unchanged throughout the TM (Figure-1A). In chronic AD, high linear changes in the UI in the middle of the TM was observed in the aorta that had not been dissected (yellow arrow in Figure-1B). In acute AD, high linear changes in the UI were clearly observed in the middle of TM, and aortic dissection was observed as an extension of those liner changes (Figure-1C). A line profile of the UI between the intima and the adventitia showed that the UI remained unchanged in normal aorta, and exhibited a high peak in the middle of the TM in chronic and acute AD (Figure-1A,B,C). These results indicated differences in the UI throughout the TM between normal and pathological aortas. These findings were well consistent with changes in the TM of patients with AD, which were obtained using XPCT (Figure-1D,E).

Conclusions:
High-resolution ultrasonographic imaging could replace XPCT findings in clinical settings and lead to significant improvements in the presymptomatic diagnosis of various aortic wall pathologies, including aortic dissection.
Abstract 12043: Computed Tomography Angiography Assessment of Left Atrial Appendage Post Occluder Device
Authors: Miller Tyler , Hana David , Patibandla Saikrishna , Brito Guzman Daniel , Avalon Juan Carlo C , Zeb Irfan , Kadiyala Madhavi , Mills Jim , Balla Sudarshan , Kawsara Mohammad , Raybuck Bryan , Daggubati Ramesh , Sengupta Partho P , Hamirani Yasmin S
Published: April 2022

Introduction:
Device related thrombosis (DRT) is an indication for continuation of anticoagulation for patients undergoing left atrial appendage (LAA) occlusion. There is a paucity of data in regards to the definition of DRT on coronary CT angiography (CTA) in patients with WATCHMAN FLX
TM
(Boston scientific) device implantation.

Methods:
This is a single center experience of using CTA for follow up in patients post WATCHMAN FLX
TM
implantation. 37 consecutive patients who underwent WATCHMAN FLX
TM
implantation at our center and had CTA performed at first follow up were included. CTA images were analyzed for the presence of hypo-attenuated thickening (HAT) on the device, device positioning, peridevice gap, angulation, compression percentage, depth of implant from coumadin ridge and enhancement in the LAA compared to left atrium (LA).

Results:
Among 37 patients with CTA follow up, HAT was noted in 28 patients (75%). 38% of these patients had HAT >3 mm. LAA patency (LAA/LA ratio of >25%) was seen in 7 patients (10%), 4 with gaps around the device and the rest secondary to trans-fabric leak. Gap around the device was noted in 13 patients (35%). 6 of these 13 patients had >4 mm gap; 5/6 patients had HAT and 3/6 patients had >25% enhancement in the LAA compared to LA. Increased compression % on both CTA and intraprocedural TEE was associated with absence of HAT (p=0.0003) as well as better sealing on CTA (LAA/LA ratio of >25%) (p=0.04). 6 months follow up is available on only 18 patients; only one of these patients had stoke and that patient did not have HAT on the CT scan.

Conclusions:
Definition of thrombus on WATCHMAN FLX
TM
device is not clearly defined on CTA. HAT on CTA could be artifact from the device knob and gutter or visible endothelialization around the device. Further studies with multimodality imaging and clinical correlation are needed to help determine normal cut offs for HAT on these CTAs.
Abstract 12054: Evinacumab Reduces Atherogenic Lipids and Apolipoprotein B in Patients With Severe Hypertriglyceridemia
Authors: Rosenson Robert S , Banerjee Poulabi , Gonzaga-Jauregui Claudia , McGinniss Jennifer , Vitali Cecilia , Pordy Robert , Zhao Jian , Ponda Manish P , Rader Daniel J
Published: April 2022

Background:
Hypertriglyceridemia (HTG) is the consequence of elevated triglyceride-rich lipoproteins (TGRLs) containing apolipoprotein B (apoB), such as VLDL and chylomicrons. Epidemiological and genetic studies indicate that triglycerides (TGs) and the cholesterol within TGRLs causally contribute to coronary heart disease risk (CHD). Evinacumab (EVIN), an angiopoietin-like 3 inhibitor, lowers TGs by derepressing lipoprotein lipase (LPL) and endothelial lipase activity. In a Phase 2 trial in patients (pts) with severe HTG (sHTG, fasting TGs ≥500 mg/dL), EVIN was previously shown to reduce TGs in patients (pts) without familial chylomicronemia syndrome (FCS) and to be generally well tolerated (NCT03452228). This post-hoc analysis reports further details on the efficacy of EVIN in reducing atherogenic lipids/lipoproteins.

Methods:
Pts (N=51) were treated and assigned to cohorts based on genotype: Cohort 1 (n=17), FCS pts with bi-allelic loss-of-function (LOF) LPL pathway mutations; Cohort 2 (n=15), multifactorial chylomicronemia syndrome (MCS) pts with heterozygous LOF LPL pathway mutations; Cohort 3 (n=19), MCS pts without LPL pathway mutations. Pts were randomized (2:1) to IV EVIN 15 mg/kg or placebo every 4 weeks over a 12-week double-blind treatment (tx) period (DBTP), followed by a 12-week single-blind tx period where all pts received EVIN.

Results:
Of 51 pts with sHTG treated in the DBTP, 70.6% were categorized as high cardiovascular risk, and 21.6% had a history of CHD. In non-FCS pts (Cohorts 2 and 3), in addition to reducing TGs, EVIN reduced atherogenic lipids and apolipoproteins at Week (W) 12 compared with baseline (Table), including non-HDL-C, remnant cholesterol, and apoB (including apoB100 and apoB48). Overall, reductions observed at W12 were maintained through W24.

Conclusions:
In this post-hoc analysis, EVIN reduced atherogenic lipids and apoB, indicating it may have the potential to reduce CHD risk in pts with sHTG without genetic FCS.
Abstract 12064: Accurate Detection of Severe Aortic Stenosis Using Wavelet Analysis and Machine Learning for Heart Murmur
Authors: Masuda Hirotada , Miyagawa Shigeru , Sakashita Yuji , Shimamura Kazuo , Kuratani Toru , Sawa Yoshiki
Published: April 2022

Introduction:
Auscultation is a well-accepted screening method for valvular disease. However, it is not adequate for the screening because the detecting rate of valvular disease by non-cardiologist is about 43% only.

Hypothesis:
Artificial intelligence (AI)-assisted heart murmur analysis could detect valvular disease following a heart murmur record using a digital stethoscope.

Methods:
The current study included 71 patients admitted to our hospital to undergo transcatheter aortic valve replacement due to aortic stenosis (AS). We recorded preoperative and postoperative heart murmur using digital stethoscope Eko. Three of 71 cases were diagnosed with severe AS due to prosthetic valve dysfunction. After denoise processing, an acoustic analysis was done to set objective parameters of the murmur. Machine learning was performed to detect severe AS by utilizing the characteristic parameters of severe AS as essential features. A total of 142 sound sources were acquired, 100 cases were used as training data, and the remaining were used as test data to verify the detection accuracy of severe AS.

Results:
The prolonged duration of the first sound and the peak frequency of systolic murmur with 300 Hz or higher were important for detecting severe AS. The detection accuracy of severe AS was 98% in the support vector machine model. All were detected in PVD cases, but not in the low flow & low gradient cases.

Conclusions:
It was suggested that severe AS could be detected by AI-assisted heart murmur analysis. We are developing the auscultation device, which is designed to be easy for elderly outpatients, to detect severe AS and to classify the severity of AS with differences in the peak frequency of the murmur.
Abstract 12066: The Long-Term Safety and Efficacy of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia
Authors: Raal Frederick J , Rosenson Robert S , Reeskamp Rens , Kastelein John J , Rubba Paolo , Duell Bart , Koseki Masahiro , Stroes Erik S , Ali Shazia , Banerjee Poulabi , Chan KuoChen , Khilla Nagwa , McGinniss Jennifer , Pordy Robert , Zhang Yi , Gaudet Daniel
Published: April 2022

Background:
Homozygous familial hypercholesterolemia (HoFH) is a rare genetic lipid disorder characterized by marked elevations in LDL-C and premature atherosclerotic cardiovascular disease (ASCVD). EU guidelines recommend LDL-C treatment goals of <55 mg/dL and <70 mg/dL for pts with HoFH with and without ASCVD, respectively. Evinacumab (EVIN; an angiopoietin-like 3 inhibitor) significantly reduced LDL-C and was generally well tolerated in pts with HoFH during the 24-week double-blind treatment period (DBTP) of a pivotal Phase 3 study (NCT03399786).

Methods:
This post-hoc analysis assessed the long-term effect of EVIN on LDL-C goal attainment in pts with HoFH who participated in the subsequent 24-week open-label treatment period (OLTP) of the pivotal Phase 3 study. All pts received intravenous EVIN 15 mg/kg every 4 weeks. Efficacy by background lipid lowering medication (LLM) subgroups and the effect of EVIN on eligibility for apheresis were also assessed.

Results:
In total, 65 pts entered the OLTP and 64 pts (98.5%) received OL EVIN. Overall, 50.0% achieved LDL-C <100mg/dL, 31.7% achieved LDL-C <70 mg/dL and 23.3% achieved LDL-C <55 mg/dL at Week 48 (end of OLTP) (Figure 1). For the subgroup with ASCVD (n=36), 50.0%, 37.5% and 31.3% achieved LDL-C <100 mg/dL, <70 mg/dL and <55 mg/dL, respectively. Overall, 43.1%, 24.6% and 38.5% of pts qualified for apheresis at baseline and did not qualify for apheresis at Week 48 (using new US, US and EU criteria); no patient discontinued apheresis. EVIN markedly reduced LDL-C, irrespective of background LLM. Overall, treatment-emergent adverse events (TEAEs) occurred in 47 pts (73.4%) during the OLTP. Serious AEs (all unrelated to EVIN) were reported by 7 pts (10.9%), none led to death or EVIN discontinuation.

Conclusions:
EVIN enabled 31.7% of all pts to achieve LDL-C <70 mg/dL and 31.3% of those with ASCVD to achieve LDL-C <55 mg/dL. EVIN markedly reduced the proportion of pts qualifying for apheresis.
Abstract 12076: Whole Genome Sequencing Association Study for Coronary Heart Disease in a Middle Eastern Cohort Validates Polygenic Risk Scores and Replicates Known Loci
Authors: Saad Mohamad , Kunji Khalid , Ullah Ehsan , El-Menyar Ayman , Kullo Iftikhar J , Al Suwaidi Jassim
Published: April 2022

Introduction:
The potential use of polygenic risk scores (PRSs) in clinical practice is tempered by concern about their portability among diverse populations. To prevent disparities in genomic medicine, there is an urgent need to conduct genome-wide association studies in non-European ancestry cohorts.

Methods:
We conducted whole genome sequencing (WGS) with 30x coverage on coronary heart disease patients (n=1,067, mean age ± SD = 59.96 years ± 10.99; 70.32% males) and controls (n=6,170, mean age ± SD = 40.02 years ± 12.56; 43.45% males) in a Middle Eastern cohort to compare the performance of available PRSs for CHD (LDpred, metaGRS, lassosum, and P+T) and identify common variants associated with CHD (via generalized linear mixed models).

Results:
Excepting lassosum, all PRSs performed well. LDpred and metaGRS performed similarly (AUC= ~0.685) and outperformed P+T (AUC=0.667). Based on the OR per 1 SD increase (OR
1sd
), P+T (OR
1sd
=1.85 [1.69-2.02],
P
=3.69x10
-41
) outperformed other PRSs (OR
1sd
=1.61 [1.48-1.74],
P
=3.02x10
-31
for LDpred and OR
1sd
=1.61 [1.49-1.75],
P
=9.47x10
-31
for metaGRS). After binning PRSs into 10 deciles, the odds of CHD in the top decile compared to all others was highest for metaGRS (3.87 [3.07-4.88]) and LDpred (3.45 [2.74-4.341]). Thirty-two known GWAS loci (e.g.,
ABCG8
,
CELSR2
, and
SLC22A4
) were replicated in our analysis with
P
<0.05. Seven suggestive new loci/genes (
P
<10
-6
) with relevant biological function were identified (e.g.,
CORO7
,
RBM47
, and
PDE4D
). The well-established 9p21 locus was not replicated.

Conclusions:
Genome-wide PRSs derived from European ancestry cohorts performed well in a Middle Eastern cohort. Further studies are needed to develop and validate an ancestry specific PRS and to confirm the suggestive loci/genes.
Abstract 12078: Pre-Glenn Aorto-Pulmonary Collaterals and Its Impact on Outcomes in Single Ventricle Patients
Authors: Sharma Varun , Carlson Laura , Esch Jesse , Gopal Mallika , Gauvreau Kim , Wamala Isaac , Muter Angelika , Porras Diego , Nathan Meena
Published: April 2022

Introduction:
In single-ventricle patients undergoing bi-directional Glenn (BDG), 36-59% have angiographically detectable aorto-pulmonary collateral (APC) flow. However, predictors, hemodynamic and clinical outcomes are unknown.

Hypothesis:
We hypothesize that (a) shunt type, hemodynamic findings at the pre-Glenn catheterization predict pre-BDG APC burden and (b) APC burden at BDG catheterization may predict post BDG death/transplantation, pulmonary artery (PA) or APC intervention.

Methods:
Retrospective cohort study of patients following Norwood Procedure for single ventricle anatomy. Covariates included demographics; clinical and hemodynamic at Pre-BDG catheterization. APC burden at pre-BDG catheterization was assessed dichotomously by a single reader (moderate/severe vs. none/mild). Logistic regression was used to identify predictors of APC burden and Cox regression for time to clinical outcomes.

Results:
Among 104 patients, 89.4% (n=93/104) underwent pre-BDG catherization, of which 55% (n=51/93) had APC intervention and 91% (n=85/93) progressed to BDG. Post-BDG, 60% (n=51/85) had no/mild and 40% (n=34/85) had moderate/severe APC burden. Within 36 months, APC intervention occurred in 74% (n=69/63) with no difference between groups (84% vs. 79%, Logrank 0.75). Predictors of APC burden were male sex (OR 3.59; 95% CI 1.18-10.98), older age at BDG (1.02 per year; 1.01-1.04), PA saturations (1.80;1.18-2.75), and Qp:Qs ratio (OR 1.23 per 0.10 unit increase;1.08-1.41). APC burden is not predictive of death/transplantation or future APC intervention but may show a trend towards future PA intervention (HR 2.11, 95% CI 0.98-4.52, p=0.056)(Figure 1). Sano shunt is a predictor of APC intervention following BDG (HR 2.07, 95%CI 1.09-3.90, p=0.03).

Conclusions:
Moderate or severe APC burden was present in 40% after stage I Norwood and QP:QS is a strong predictor for APC burden; patients with moderate/severe APC’s may be at higher risk of PA interventions.
Abstract 12085: Impact of Pre-Fontan Hemodynamics on Long-Term Outcomes of Patients With Fontan Palliation
Authors: Suthar Divya , Beshish Asaad , Thomas Amanda S , Claxton J'Neka , Knight Jessica , Shaw Fawwaz , Mahle William T , Oster Matthew , Kochilas Lazaros
Published: April 2022

Introduction:
Fontan procedure for single ventricle (SV) is frequently preceded by cardiac catheterization. The impact of pre-Fontan hemodynamics on long-term outcomes is not completely understood.

Methods:
This is a cohort study of patients undergoing Fontan in the Pediatric Cardiac Care Consortium (PCCC), a US-based registry of congenital heart surgeries. Deaths and transplants were captured through 2019 in the PCCC and by linkage with the National Death Index and the Organ Procurement Transplant Network. The relationship between pre-Fontan hemodynamics and post-Fontan transplant-free survival were evaluated with Kaplan Meier (KM) and Cox regression with adjustment for age at Fontan, sex, era of surgery, Fontan type, and type of systemic ventricle.

Results:
Between 1986 and 2003, 1498 patients were enrolled in the PCCC and underwent pre-Fontan cardiac catheterization. Table 1 demonstrates the relationship of patient characteristics on the risk of death or transplant after Fontan discharge. After adjustment for other risk factors PVRi (aHR 1.28; 95% CI 1.09 - 1.49) and mPAP (aHR 1.07; 95% CI 1.02- 1.12) were the main factors associated with risk of death or transplant. KM survival curves stratified by PVRi and mPAP tertile depict the loss of transplant-free survival years for the top tertile of mean PAP (>13 mmHg) or PVRi (>2.3 WU m
2
) (Figures A and B).

Conclusions:
This study of a large cohort of single ventricle patients demonstrates that abnormal pre-Fontan hemodynamics are associated with increased risk of death or transplant even many years after Fontan procedure. Such data may help to guide therapeutic considerations and monitoring intensity after Fontan completion.
Abstract 12088: Coronary Angiography and Revascularization After Out-of-Hospital Cardiac Arrest in Coronary Artery Disease Patients Without ST-segment Elevation
Authors: Nitta Giichi
Published: April 2022

Introduction:
The emergent coronary angiography and revascularization after out-of-hospital cardiac arrest (OHCA) in coronary artery disease (CAD) patients without ST-segment elevation remains controversial.

Methods:
There were 2391OHCA patients transferred to 2 hospitals. We included 405 cardiovascular arrest patients, who got return of spontaneous circulation (ROSC) from January 2015 to December 2018. Among them, 110 patients were diagnosed CAD with no ST-segment elevation in electro-cardiogram (51%: multi-vessel disease, 33%: chronic total occlusion). To predict mortality in hospital and neurological outcome at 1-year, we investigated basic patients’ characteristics, pre-hospital information, post-hospital care including coronary angiography (CAG) and revascularization.

Results:
In the Cox proportional hazards model, emergent coronary angiography (hazards ratio; HR: 0.90, 95%confidence interval (CI) 0.45-1.79, P=0.758) and emergent coronary revascularization (HR: 1.51, 95%CI 0.87-2.61, P=0.142) were not associated to predict the mortality. At 1-year, VF survivor (P=0.004), younger age (P=0.010), without ECMO support (P<0.001), pre-hospital ROSC (P<0.001), and low lactate level on admission (P<0.001) were associated with low mortality. The higher number of coronary vessel disease (P=0.020) such as multi-vessel disease (P=0.019), the coronary lesion of LAD (P=0.043), and larger infarct size (max CK level; P=0.014, max CK-MB level; P<0.001) were associated with high 1-year mortality. Zero-vessel disease (VSA, P=0.007) had lower mortality.

Conclusions:
Emergent coronary assessment and revascularization were not associated with the prognosis.
Abstract 12092: IMB-1018792, an Investigational Agent Designed to Augment Cardiac Glucose Utlization and Energetics Reduces Cardiac Remodelling and Preserves Cardiac Function in a Model of Pressure Overload-Induced Heart Failure
Authors: Harding Matthew , Patel Jaikrishna , Chamberlin Paul , Calcagno Claudia , Levin Andrew
Published: April 2022

Introduction:
Energetic impairments play a key role in heart failure (HF). Contributors include reduced pyruvate dehydrogenase activity partially uncoupling glycolysis from glucose oxidation, increased dependence on fatty acid (FA) metabolism yielding less ATP than glucose per O
2
molecule consumed, a lower phosphate-to-O
2
ratio, mitochondrial uncoupling and futile cycling of FA intermediates. IMB-1018972 (IMB-101) is a novel investigational agent designed to increase cardiac glucose uptake to promote glucose oxidation (Randle effect) through partial inhibition of FA oxidation enhancing cardiac energetics and mechanical efficiency.

Hypotheses:
Administration of IMB-101 will: 1) increase cardiac glucose uptake and 2) attenuate LV hypertrophic remodelling and progression of HF resulting from chronic pressure overload.

Methods:
1) Cardiac glucose metabolism was evaluated using dynamic
18
F-FDG PET/CT imaging in vivo in fasted normal rats following a subcutaneous dose of IMB-101 or saline. Each animal had 2 randomized sequenced scan sessions (n=16). 2) Male C57BL/6 mice aged 12 weeks underwent transverse aortic constriction (TAC) or sham surgery (n=15) and were treated with IMB-101 (10 mg/kg/day, n=15) or saline (n=15) from day 1 (D1) for 6 weeks by osmotic minipump. Cardiac function was assessed by conscious echocardiography (D1, week 3 and 6). Cardiac fibrosis was measured by Masson’s Trichrome staining.

Results:
IMB-101 robustly increased in vivo cardiac
18
F-FDG uptake vs saline in rats. In mice subjected to TAC, compared to saline controls, IMB-101 treatment: preserved LV systolic function (fractional shortening 46%±3% vs 34%±3%, at week 6, p<0.05); improved LV relaxation with less prolonged isovolumic relaxation time (32±1 ms vs 36±1 ms, p<0.05); reduced cardiac hypertrophy (LV mass 156±10 mg vs 195±12 mg, p<0.05; and heart:body weight ratio 7.4±0.3 mg/g vs. 9.1±0.5 mg/g, p<0.05); and attenuated cardiac fibrosis (6.6±0.6% vs 10.7±1%, p<0.01).

Conclusions:
IMB-101 increases cardiac glucose uptake and protects against LV dysfunction, hypertrophic remodelling and interstitial fibrosis after chronic pressure overload.
Abstract 12104: Treatment With Exogenous Atrial Natriuretic Peptide Ameliorates Myocardial Insulin Resistance and Protects Against Ischemia-Reperfusion Injury in Diet-Induced Obesity
Authors: Oi Yuhei , Nagoshi Tomohisa , Kimura Haruka , Tanaka Yoshiro , Takahashi Hirotake , Yasutake Rei , Kashiwagi Yusuke , Tanaka Toshikazu D , Yoshii Akira , Yoshimura Michihiro
Published: April 2022

Increasing evidence suggests natriuretic peptide (NP) coordinate inter-organ metabolic crosstalk in addition to its classical actions on hemodynamic regulation. We recently reported exogenous atrial NP (ANP) treatment ameliorated systemic insulin resistance by inducing adipose tissue browning and by attenuating hepatic steatosis in diet-induced obesity. We herein hypothesized that exogenous ANP treatment also ameliorates insulin resistance of the myocardium in which endogenous NP is produced, leading to the cardioprotection during ischemia-reperfusion injury (IRI) in diet-induced obesity. The mice fed a high fat diet (HFD) or normal fat diet (NFD) for 13 weeks were treated with or without ANP infusion subcutaneously via osmotic pump for another 3 weeks (0.5 μg/kg/min). Intraperitoneal administration of insulin induced Akt phosphorylation in NFD hearts, which was reduced in HFD. ANP treatment restored the impaired insulin-induced Akt phosphorylation in HFD hearts, suggesting that exogenous ANP ameliorated myocardial insulin resistance. To test the functional significance of this, hearts were exposed to IRI using Langendorff model. After IRI, HFD resulted in an impaired left ventricular developed pressure (LVDP) recovery with corresponding increase in infarct size. However, ANP treatment improved functional recovery and reduced injury along with restoration of the impaired IRI-induced Akt phosphorylation in HFD hearts. (% LVDP recovery of baseline: NFD 62.9%±3.6 , NFD+ANP 64.5%±4.2% , HFD 20.8%±3.3 , HFD+ANP 31.4%±2.8% , p<0.05) Myocardial ultrastructural analyses by electron microscopy showed number of peri-mitochondrial lipid droplets was increased in HFD treated with ANP, suggesting that ANP protects mitochondria from lipid overload. Of note, ANP treatment substantially attenuated mitochondria cristae disruption after IRI in HFD hearts. In conclusion, exogenous ANP treatment ameliorates myocardial insulin resistance and protects against IRI associated with restoration of disrupted mitochondrial structure in diet-induced obesity. The findings that exogenous NP has significant impact on the NP-rich failing myocardium provide new insight into the biological properties and dynamics of NP.
Abstract 12112: Near Infrared Spectroscopic Characterization of Cardiac and Renal Fibrosis
Authors: Adegoke John Adeola , Gassner Callum , Afara Isaac O , Sharma Varun , Patel Sheila K , Kochan Kamila , Burrell Louise M , RAMAN Jaishankar , Wood Bayden R
Published: April 2022

Introduction:
Fibrosis is significantly associated with nearly all forms of heart and kidney disease. Clinical diagnosis of fibrosis is currently reliant on conventional methods that do not have the sensitivity and specificity required for effective diagnosis.

Hypothesis:
An handheld portable near-infrared (NIR) spectrometer, usable intraoperatively coupled to machine learning algorithms can discriminate between fibrotic and healthy cardiac and renal tissue. We sought to validate this in an animal model.

Methods:
10 Male Sprague Dawley rats (SDR) with either induced cardiac (SDR-H) and renal (SDR-K) fibrosis (n=5) compare to normal controls (n=5). Hearts from all rats were used as tissue screening in model validation as they contain a high amount of collagen. Multiple tissue samples were harvested from SDR-K (
n
fibrosis
= 12,
n
control
= 4) and SDR-H (
n
fibrosis
= 12,
n
control
= 4) groups. NIR spectra (1350 - 2500 nm) were acquired from all tissue sections.

Results:
Stained sections showed insignificant differences between the fibrotic SDR-H and their corresponding controls as collagen fibrils dominated both groups. SDR-K showed distinguishable features between examined groups. NIR absorption at 1509, 1725, 2055, and 2306 nm were found to be highly indicative of fibrosis (Figure1). PCA (57% explained variance) and PLS-DA (sensitivity: 96%) showed excellent discrimination for SDR-K groups while the heart shows no meaningful discrimination for SDR-H groups. SVM and LR analysis corroborated these results by achieving a 98% classification accuracy for SDR-K and no discrimination for SDR-H. All machine learning models were cross-validated with outcomes of histological staining to establish a robust interpretation and underpin their pathological meanings.

Conclusions:
NIR accurately diagnoses cardiac and renal fibrosis in rats model. There is potential for this technology to be translated into an intraoperative instrument for tissue diagnosis
Abstract 12122: Impact of Periodontal Bacteria Detected in Periodontal Pockets in Patients with Congestive Heart Failure on Long-Term Clinical Outcomes
Authors: Matsuda Yuji , Yonetsu Taishi , Aoyama Norio , Maejima Yasuhiro , Isobe Mitsuaki , Iwata Takanori , Sasano Tetsuo
Published: April 2022

Backgrounds:
Periodontal disease is known as a risk of cardiovascular events, but the impact of periodontal bacteria on the clinical outcomes has not been elucidated in patients with congestive heart failure (CHF).

Aim:
We sought to investigate the association between the presence of periodontal bacteria in periodontal pockets.

Methods:
Between May 2012 and August 2015, consecutive 149 patients who admitted in our department due to non-ischemic CHF were retrospectively included. Periodontal examinations including the presence of major periodontal bacteria (MPB) were performed by the independent trained periodontists. MPB consisted of
Porphyromonas gingivalis
,
Aggregatibacter actinomycetemcomitans
and
Prevotella intermedia
, known as inflammatory bacteria of severe periodontitis. The clinical events of these patients were assessed, and major adverse cardiovascular cerebrovascular event (MACCE) was defined as the composite of cardiovascular death, non-fetal myocardial infarction, non-fetal stroke.

Results:
A total of 135 patients composed of 98 patients with MPB in the periodontal pocket and 37 patients without that were identified. Median follow up duration was 4.6 years (interquartile: 1.8 - 6.6 years). The Kaplan-Meier curve analysis about MACCE suggested that the free survival rate in MPB group was significantly worse than non-MPB group (p for log-rank test = 0.01). Regarding Kaplan-Meier curve analysis of each MACCE component, only that of cardiovascular death showed MPB group had significantly worse free survival rate (p = 0.02). Multivariate Cox hazard regression model analysis revealed that MPB group was an independent risk of MACCE (HR 9.70; 95% CI 1.27 - 74.39, p = 0.03), and this finding appeared to be obtained from mainly cardiovascular death (HR 8.74; 95% CI 1.13 - 67.71, p = 0.04).

Conclusions:
In non-ischemic CHF patients with MPB in periodontal pocket were associated with an increased risk of long-term cardiovascular events.
Abstract 12130: Statin Use is Associated With Lower Risk of New Onset Dementia in Patients With Heart Failure: A Population-Based Study
Authors: Ren Qingwen , Yi Kei Stephanie Tse , Yu Si-Yeung , Li Hang Long , Pui Fai Wong , mei zhen Wu , Yiu Kai Hang
Published: April 2022

Introduction:
Increasing number of heart failure (HF) patients diagnosed with dementia due to improved treatment and aging population. Data relating to the association of statin use on the risk of dementia incidence among patients with HF are sparse.

Hypothesis:
The use of statin is associated with lower risk of new-

onset dementia in HF population.

Methods:
Using a previously validated territory-wide clinical information registry, statin use was ascertained among all eligible patients with HF (N=241,995) from 1996 to 2019. Propensity score matching was used to balance baseline covariates between statin nonusers (167,738 patients) with statin users (74,257 patients). Competing risk regression with Cox proportional-hazard models was performed to estimate the risk of incident dementia associated with statin use.

Results:
Of all eligible subjects, the mean age was 76.5±13.0 years, 115,371(47.7%) was male. Over a median follow-up of 2.7 years (interquartile range [IQR]: 0.6 to 6.7), 13,482 (5.6%) patients were diagnosed with dementia including Alzheimer's disease (N=5,253), senile dementia uncomplicated (N=4,273), arteriosclerotic dementia (N=3,262), and others (N=694). Statin use (vs. none) was associated with a 58% lower risk of dementia incidence (multivariable-adjusted sub-distribution hazard ratio [SHR]=0.42; 95% Confidence Interval [CI], 0.38 to 0.46) after accounting for death as a competing risk. Moreover, the male gender was associated with a 51% lower risk of dementia incidence (multivariable-adjusted SHR=0.59; 95%CI (0.54-0.65) compared with females.

Conclusions:
Our study suggests that there is substantial sex difference in the incidence of dementia among HF patients. Moreover, statin use is associated with a significantly lower risk of incident dementia in HF.
Abstract 12140:
SCN1B
Expression Modulates Sodium Influx in Cardiomyocytes and Diastolic Function in the Adult Heart
Authors: Cervantes Daniel O , Pizzo Emanuele , Tang Samantha , Cianflone Eleonora , Vinukonda Govindaiah , Jacobson Jason , Jain Sudhir , Rota Marcello
Published: April 2022

Voltage-gated sodium channels (VGSCs) are macromolecular complexes composed of a number of proteins regulating channel biophysical properties. VGSCs generate Na
+
current (I
Na
) in myocytes and play fundamental roles in excitability and impulse conduction in the heart. Moreover, VGSCs condition mechanical properties of the myocardium, a process that appears to involve the late component of I
Na
. Variants in the gene
SCN1B
, encoding the VGSC β1 and β1B subunits, result in inherited neurological disorders and cardiac arrhythmias. But the precise contributions of β1/β1B subunits and VGSC integrity to the overall function of the adult heart remain to be clarified. For this purpose, adult mice with cardiac-restricted, inducible deletion of
Scn1b
(conditional knock-out, cKO) were studied. Myocytes from cKO mice had decreased levels of
Scn1b
transcripts (-85%) and increased densities of fast- (+20%) and slow-inactivating (+140%) components of I
Na
, with respect to cells from corresponding control (Ctrl) animals. By echocardiography, left ventricular (LV) mass, chamber volume, and systolic function were preserved in both male and female cKO mice, with respect to sex- and age-matched Ctrl animals. However, by transmitral flow Doppler echocardiography, cKO mice presented reduced velocity of the passive filling wave (-~20%), attenuated ratio of the passive-to-active filling velocity waves (-~20%), and prolonged isovolumic relaxation time (+~16%). Moreover, by pressure-volume (PV) loop assessment, cKO mice had steeper slope of the LV end diastolic PV relation and prolonged LV relaxation tau, suggesting impairment of diastolic function. Importantly, inhibition of late I
Na
with GS967 (0.5 mg/kg body weight) normalized left ventricular filling pattern and isovolumic relaxation time in cKO mice, but had no consequences in Ctrl animals. At the cellular level, cKO myocytes presented delayed kinetics of Ca
2+
transients decay and cell shortening with respect to Ctrl myocytes. These defects were partly corrected by inhibition of the late I
Na
. Collectively, these results document that VGSC β1/β1B subunits modulate electrical and mechanical function of the heart by regulating, at least in part, Na
+
influx in cardiomyocytes.
Abstract 12141: Echocardiographic Characteristics and Outcomes Between African American and Caucasians in Acute Pulmonary Embolism
Authors: Cires-drouet Rafael S , Sama Jacob , Han Paul , Miller Taylor , Alston Lateaqua , Cires-Drouet Rafael , Mayorga-Carlin Minerva , Sorkin John , Hong Susie , Ramani Gautam , Haase Daniel , Lal Brajesh , Taylor Bradley
Published: April 2022

Introduction:
Socio-economical differences and delayed medical care have been associated to a higher mortality in African American (AA) PE patients.

Hypothesis:
Peri-PE mortality is higher in AA than Caucasian (CC) patients in a single medical center.

Methods:
A 26 months retrospective review of AA and CC patients admitted with an acute PE.

Results:
A total of 303 AA and 343 CC were identified. African Americans were younger, had more females, diabetes, chronic kidney disease and smokers than CC. A history of recent surgery and trauma were more common in CC. (Table I) Both groups had similar clinical presentations, biomarkers, and radiologic characteristics (CTA); except for RV strain that was more common among AA. In the initial echocardiogram, LV function was similar in both groups, although, AA had more often an underfilled LV and an abnormal RV. (Table II) There was no difference in hospital mortality between AA (n=21[6.9%]) and CC (n=21[6.1%]), p=0.67. Among 107 (AA=54, CC=53) patients who received advanced therapies, the mortality was higher in AA (18.5% vs.3.8% p=0.01). In a logistic regression analysis, the risk of death was increased by age (OR 1.04; 95%CI 1.020-1.073) and the need of advanced therapies (OR 2.43; 95%CI 1.029-5.769). Although AA race (OR 1.77; 95%CI 0.862-3.647), BMI (OR 0.99; 95%CI 0.950-1.038), abnormal RV (OR 0.71; 95%CI 0.321-1.601) and abnormal LV function (OR 1.737; 95%CI 0.754-4.005) did not increase significantly the risk of death.

Conclusion:
Despite hemodynamic changes of the LV and RV appreciated in AA, there was no difference in overall mortality. The risk of death was increased by age and need for advanced therapies.
Abstract 12145: N
6
-methyladenosine and Adenosine-to-Inosine Modifications as Biomarkers for Ischemic Heart Disease
Authors: Sikorski Vilbert T , Vento Antti E , Kankuri Esko M , Consortium IHD-EPITRAN
Published: April 2022

Introduction:
Chemical modifications in RNA have unveiled as a layer of molecular regulation with notable effects to the flow of genetic information from DNA through RNA to proteins. These epitranscriptomic modifications guide and contribute to normal and pathological cellular responses. To date, more than 170 epitranscriptomic modifications have been identified. Most interest has been attracted by RNA adenosines, which are also the ones most often modified. Especially N-6-methylation or deamination resulting in N
6
-methyladenosine (m
6
A) and inosine (A-to-I), respectively, have been associated with cardiovascular diseases, including atherosclerosis and myocardial ischemia, the lead causes of mortality. Remarkably, m
6
A and A-to-I modifications have emerged as early drivers of atherosclerosis and promising druggable targets.

Hypothesis:
The
I
schemic
H
eart
D
isease
Epitran
scriptomics and Biomarkers (IHD-EPITRAN) study aims to determine those features of IHD that are mirrored in the circulating blood epitranscriptome. In particular, the study focuses on changes in m
6
A and A-to-I in blood RNA.

Methods:
Patients (initial subgoal n=200) are recruited from four cohorts: (1) patients with myocardial infarction undergoing angioplasty and revascularization; (2) patients with stable IHD undergoing coronary artery bypass surgery; (3) controls without coronary obstructions undergoing valve replacement surgery due to aortic stenosis and (4) controls with healthy coronaries verified by computed tomography. The profiles of m
6
A and A-to-I in blood RNA will be charted using a combinatory approach including mass spectrometry and DNA/RNA sequencing and referenced to other modified nucleosides and candidate biomarkers for IHD and heart failure. The study is registered (ClinicalTrials.gov NCT04533282), is seeking collaborators (www.ihd-epitran.com), and has recruited 40 patients at the time of abstract submission.

Conclusion:
Comparison of blood m
6
A and A-to-I profiles combined with meticulous clinical evaluations can be expected to unveil epitranscriptomic biomarker candidates and drug targets for IHD.
Abstract 12146: Acute Nitroglycerin Treatment Improves Exercise Hemodynamics, but Not Ventilation-Perfusion Matching in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Balmain Bryce N , Tomlinson Andrew R , Macnamara James P , Sarma Satyam , Hearon Christopher M , Livingston Sheryl A , Morris Margot , Moran Raksa B , Alcala Jessica N , Payne Marcus , Samels Mitchel , Boyd Teverick , Lee David , Baird Stephanie , Levine Benjamin D , Babb Tony G
Published: April 2022

Introduction:
Heart failure with preserved ejection fraction (HFpEF) patients exhibit a marked rise in PCWP during exercise, which may contribute to ventilation-perfusion (V/Q) mismatch and manifest as an increase in alveolar dead space (alveolar V
D
) and alveolar-arterial PO
2
difference (AaPO
2
). Nitrates reduce PCWP during exercise in HFpEF, but whether nitrates also reduce V/Q mismatch during exercise is unknown.

Hypothesis:
The increase in PCWP and V/Q mismatch during exercise would be attenuated with acute nitroglycerin (NTG) treatment compared with placebo in HFpEF patients.

Methods:
13 patients performed a 6min cycling test at 20W and an incremental cycling test (with right-heart and arterial catheterization) with placebo and NTG treatment. The physiologic dead space to tidal volume (V
D
/V
T
) was calculated using the Enghoff modification of the Bohr equation. Alveolar V
D
was calculated as: V
D
/V
T
x V
T
- anatomic dead space (anatomic V
D
, estimated as 2mL/kg lean body mass). AaPO
2
was calculated using the alveolar gas equation. Data were analyzed using a 2-way ANOVA.

Results:
PCWP decreased with NTG at 20W (placebo: 21.1±6.2 vs. NTG: 16.5±6.1mmHg, p=0.02) and peak exercise (placebo: 33.7±7.1 vs. NTG: 26.2±5.6mmHg, p<0.01). However, alveolar V
D
did not differ between treatments at rest (placebo: 0.11±0.07 vs. NTG:0.12±0.06L/breath, p=0.91), 20W (placebo: 0.22±0.09 vs. NTG: 0.24±0.10L/breath, p=0.62), or peak exercise (placebo: 0.34±0.14 vs. NTG:0.36±0.16L/breath, p=0.83). Nor did AaPO
2
differ between treatments at rest (placebo: 17.6±4.3 vs. NTG: 18.3±5.7mmHg, p=0.76), 20W (placebo: 22.0±6.9 vs. NTG: 22.1±8.1mmHg, p=0.99), or peak exercise (placebo: 25.1±9.1 vs. NTG: 27.8±9.9mmHg, p=0.41). No significant exercise-by-treatment interaction was detected for V
D
/V
T
(p=0.80).

Conclusions:
This study showed that NTG attenuated the increase in PCWP, but had no effect on the increase in alveolar V
D
or AaPO
2
during exercise. These findings suggest that the exercise-induced increase in V/Q mismatch may not be exclusively related to abnormal exercise hemodynamics. Further study is required to determine the clinical consequences and the mechanism(s) responsible for the progressive increase in V/Q mismatch during exercise in HFpEF patients.
Abstract 12154: Exploring Differences in Race and Ethnicity in Sudden Death in the Young, 2015-2019
Authors: Whitted Austin , MacLeod Heather , Yashar Beverly , Shaw Esther , Erck Lambert Alexa
Published: April 2022

Background:
In 2015, the National Institutes of Health and Centers for Disease Control and Prevention collaborated to create the Sudden Death in the Young (SDY) Case Registry, a population-based surveillance and research initiative. The Registry monitors SDY incidence and identifies characteristics to inform data-driven prevention efforts. Previous analyses using 2015-2017 data identified differences in SDY by race/ethnicity. Further investigation into SDY demographics and the circumstances at death by race/ethnicity may help identify reasons for disparities and priority areas for future research.

Objective:
To explore racial/ethnic differences in SDY by demographic and circumstantial characteristics.

Methods:
We analyzed sudden and unexpected deaths that occurred during 2015-2019 among infants (<1 year old) and children (1-18 years old) in the 13 states/jurisdictions participating in the Registry. We excluded cases with explained causes including explained suffocation, motor

vehicle accidents and drownings, and those missing race/ethnicity (n=15). We reported percentages and performed χ
2
tests to assess differences in demographic and circumstantial characteristics by race/ethnicity.

Results:
Among 1,370 SDY cases included, 46% were non-Hispanic White (NHW), 35% non-Hispanic Black (NHB), 10% Hispanic, and 9% non-Hispanic other (NHO). Most occurred among infants (68%), and most infants (92%) were sleeping at the time of the incident. Among children, sleeping at the time of the incident ranged from 45% for NHW to 29% for Hispanic (P<0.0073). More NHW infants/children had metabolic and genetic testing than infants/children of other race/ethnicities. Metabolic testing ranged from 52% for NHW to 36% for NHB (p<0.0001). Genetic testing ranged from 11% for NHW to 5% for NHB (p<0.0056).

Conclusion:
Our findings show that among SDY, there are key demographic and circumstantial differences by race/ethnicity: NHW children were more likely to be sleeping at the time of the incident, and NHW infants/children more commonly had metabolic and genetic testing. This analysis contextualizes the racial/ethnic differences in SDY, offering focus for further research and prevention efforts.
Abstract 12165: The Ratio of Right Ventricular Global Longitudinal Strain and Pulmonary Artery Systolic Pressure Determines Persistent Tricuspid Regurgitation After Closure of Atrial Septal Defect
Authors: lee seonhwa , Kim Dae-Young , Seo Jiwon , Cho Iksung , Hong Geu-Ru , Ha Jong-Won , Shim Chi Y
Published: April 2022

Introduction:
Functional tricuspid regurgitation (TR) will decrease after atrial septal defect (ASD) closure, but it may persist and require additional tricuspid valve (TV) surgery or intervention.

Hypothesis:
We aimed to find echocardiographic predictors for persistent TR after successful ASD closure.

Methods:
Among 348 adults who underwent isolated ASD closure between January 2010 and September 2020, 91 (26.1%) patients with significant TR (at least moderate degree) before ASD closure were included. Persistent TR was defined as a significant TR even after ASD correction on echocardiogram after 6 months to 1 year. To find echocardiographic predictors for persistent TR, conventional and speckle tracking echocardiography performed before ASD closure were analyzed. The right ventricular (RV)-pulmonary arterial coupling was assessed by the ratio of RV global longitudinal strain (RV GLS) and pulmonary arterial systolic pressure (PASP) (RV GLS/PASP).

Results:
Persistent TR was observed in 22 (24.2%) patients. Patients with persistent TR were significantly older, with larger TR jet area and lower RV GLS/PASP (0.46
±
0.14 vs. 0.37
±
0.13, p = 0.013) than those without persistent TR. However, there were no significant differences in RV volumes, RV systolic function, and TV annular diameter between the two groups. On multivariable logistic regression, persistent TR was independently associated with age (HR:2.031, 95% CI, 1.113-2.046; p=0.003) and RV GLS/PASP (HR:0.009, 95% CI, 0.000-0.790; p=0.039). RV GLS/PASP showed a good predictive value for persistent TR after ASD closure (cut off 0.39, the area under the curve 0.702, p=0.003).

Conclusions:
Persistent TR after successful ASD closure is not uncommon in patients with ASD and significant TR. RV GLS/PASP can predict persistent TR after ASD closure. It can be suggested that concomitant or subsequent TR intervention should be considered in elderly patients and patients with abnormal RV-pulmonary arterial coupling.