bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12035: Higher Numbers of Circulating CD34+ Cells Are Associated With More Pronounced Effects of Neprilysin Inhibitors in Patients With Chronic Heart Failure
Authors: Poglajen Gregor , orž Neža , Gomezelj Ema Ajda , Milovanovic Ana , Frljak Sabina , Vrtovec Bojan
Published: April 2022

Introduction:
Preliminary evidence suggests that neprilysin inhibitors (ARNI) may affect angiogenesis in heart failure with reduced ejection fraction (HFrEF).

Hypothesis:
Since CD34+ cells represent one of the key determinants of vasculogenesis and angiogenesis, we investigated a potential association between clinical effects of ARNI and circulating CD34+ cell count in HFrEF.

Methods:
We performed a prospective single center pilot cohort study in 27 HFrEF patients. After enrollment, all patients received standard heart failure therapy including ACE inhibitors (ACE-I) or angiotensin receptor blockers (ARB) for 3 months. At this point, ACE-I/ARB were switched to ARNI. At the time of switch, we measured circulating CD34+ cell count using Beckman-Coulter Navios EX flow cytometry with standard antibodies according to ISAGE protocol. All patients were followed for 6 months after the switch. Favorable response to ARNI therapy was defined as an increase in left ventricular ejection fraction (LVEF) ≥5% at 6-month follow-up.

Results:
At 6 months we found a favorable response to ARNI in 18 patients (64%, Group A), and 10 had less favorable response (36%, Group B). Before ARNI introduction the groups did not differ in gender (male: 94% in Group A vs. 78% in Group B, P=0.21), heart failure etiology (ischemic: 35% vs. 23%, P=0.49), diabetes (11% vs. 22%, P=0.46), renal dysfunction (22% vs. 43%, P=0.25), hypertension (28% vs. 55%, P=0.17), LVEF (36±5% vs. 34±7%, P=0.41), LVEDV (181±57 mL vs. 185±36 mL, P=0.83), TAPSE (1.8±0.8 vs. 1.9±0.4, P=0.91) or NT-proBNP (980±1438 pg/mL vs. 780±603 pg/mL, P=0.70). Compared to Group B, patients in Group A were younger (52±13 years vs. 64±9 years, P=0.03) and had a higher CD34+ cell count (2.9±2.0x106/L vs. 1.2±0.5x106/L, P=0.02). When compared to the remainig cohort, patients with CD34+ cell count above the median displayed a significantly higher increase in LVEF (+8.1±3.2% vs. +4.7±3.7%, P=0.03), and a trend of increase in TAPSE (+0.4±0.4 cm vs. -0.1±0.7 cm, P=0.06).

Conclusion:
Higher numbers of circulating CD34+ cells appear to be associated with more pronounced beneficial effects of ARNI therapy in HFrEF patients. Thus, the effects or ARNI in heart failure may be partly mediated through modulation of vascular homeostasis.
Abstract 12049: Orthostatic Hypertension is Associated With Lower Plasma aβ
42
/aβ
40
Ratio: The Multidomain Alzheimer Preventive Trial (MAPT)
Authors: Rouch Laure , Rolland Yves , Hanon Olivier , Vidal Jean-Sébastien , Andrieu Sandrine , de Souto Barreto Philipe , Vellas Bruno
Published: April 2022

Introduction:
Orthostatic hypertension (OHYPER), an emerging hemodynamic cardiovascular risk factor, is associated with cardiovascular events and mortality. Recent findings indicated that it could be an important risk factor for cognitive decline and dementia, including Alzheimer’s disease (AD).

Hypothesis:
We aimed to assess the association between OHYPER and low plasma Aβ
42
/Aβ
40
ratio, a surrogate biomarker for brain amyloidosis.

Methods:
We included 483 non-demented community-dwelling participants aged ≥ 70 years from the Multidomain Alzheimer Preventive Trial (MAPT). OHYPER was assessed at baseline and defined as an increase of at least 20 mmHg in systolic blood pressure (BP) and/or 10 mmHg in diastolic BP after standing. Plasma Aβ
42
and Aβ
40
were measured at 12 months, using an immunoprecipitation and liquid chromatography-mass spectrometry assay. Low plasma Aβ
42
/Aβ
40
ratio was defined as ≤ 0.107. Logistic regression models were used to assess the association between OHYPER and low plasma Aβ
42
/Aβ
40
ratio.

Results:
Of 483 participants (mean age 76 years, 59% female), 113 (23.6%) had OHYPER and 161 (33.3%) low plasma Aβ
42
/Aβ
40
ratio. OHYPER was associated with low plasma Aβ
42
/Aβ
40
ratio (OR = 1.58, 95% CI [1.02-2.44]) in unadjusted models. Adjustment for age, sex, education, MAPT randomization group, lying BP, antihypertensive drug use, MCI, and presence of 1 or 2 ApoE ε4 alleles did not change the results (OR = 1.67, 95% CI [1.02-2.72]). Sensitivity analyses using the 25
th
percentile of plasma Aβ
42
/Aβ
40
ratio (≤ 0.103) as an alternative cutoff and long-term OHYPER (at least two-thirds of visits over 12 months) reported consistent findings.

Conclusions:
OHYPER was associated with lower plasma Aβ
42
/Aβ
40
ratio in community-dwelling older adults, even after accounting for potential confounders. Monitoring OHYPER may have clinical utility for identifying patients who are at risk for cognitive decline, AD or in the preclinical stages of the disease.
Abstract 12060: Comparison of Sites of Wall Thickening and Abnormal Late Enhancement on Cardiac CT and Magnetic Resonance Imaging with Electrocardiography Findings in Patients with Confirmed Cardiac Amyloidosis
Authors: Funabashi Nobusada , Nakamura Kohki , sasaki takehio , Naito Shigeto , Kobayashi Yoshio
Published: April 2022

Introduction:
Left ventricular (LV) wall thickening and diastolic dysfunction on a TTE without a high voltage R wave on V5 leads on an ECG to a diagnosis of cardiac amyloidosis (CA). However, amyloid sometimes invades right ventricle (RV), and left (LA) and right (RA) atria, causing ECG changes such as sick sinus syndrome (SSS), arrhythmia, and QRS wave axis deviation.

Hypothesis:
We hypothesize that there is the relationship between sites of wall thickening and abnormal late enhancement (LE) on cardiac CT and MRI, suggesting amyloid invasion, with ECG findings in patients with CA confirmed by biopsy.

Methods:
A total of 26 patients (11 females) with suspected CA, who had LV wall thickening by TTE without a high voltage R wave in V5 leads, underwent cardiac CT. 5 patients (3 females, mean age 73 years) were diagnosed with CA. 4 patients underwent MRI.

Results:
Case 1 had wall thickening in the basal interventricular septum (IVS), LV inferior-posterior wall, LA on CT, LE in endocardium in whole LV, RV, and RA on CT, and LE in endocardium in whole LV, RV, LA, and IVS on MRI. ECG showed SSS (junctional rhythm), left QRS axis deviation, no low voltage R wave in limb leads, and a mild LA load. Case 2 had wall thickening in whole LV, RV, LA, and IVS on CT, and unclear (CT) or no (MRI) LE. ECG revealed SSS (junctional rhythm), a normal QRS axis, no low voltage R wave in limb leads, and no LA load. Case 3 had wall thickening in LA and basal IVS on CT, abnormal LE in the LA and basal IVS on CT, and LE in the LA only on MRI. ECG revealed atrial tachycardia, a normal QRS axis with low voltage R wave in limb leads, and no LA load. Case 4 had wall thickening in the LA, an RV moderator band on CT, an unclear LE on CT, and LE in whole LV, endocardium in the RV, and whole IVS on MRI. ECG showed a normal sinus rhythm, left QRS axis deviation, with low voltage R wave in limb leads, and no LA load. Case 5 had wall thickening in the IVS, LV lateral wall, LV anterior wall, RA, RV outflow tract, and RA appendage, and no abnormal LE on CT (MRI not performed). ECG revealed a normal sinus rhythm, right QRS axis deviation, with low voltage R wave in limb leads, and a mild LA load.

Conclusions:
This pilot study revealed the presence of wall thickening and abnormal LE in RV, LA, and RA in addition to LV would be important which may influence ECG changes in patients with CA.
Abstract 12087: Device-Related Infection Associated With Increased Mortality Risk in
de novo
Transvenous Implantable Cardioverter-Defibrillator Medicare Patients
Authors: El-Chami Mikhael F , Liu Yiyan , Griffiths Robert , Knight Bradley P , Weiss Raul , Mark George , Biffi Mauro , probst vincent , Lambiase Pier , Miller Marc , Jacobsen Caroline , Baddour Larry M
Published: April 2022

Introduction:
Device-related infection is estimated to occur in 1.9% of the Medicare patients with
de novo
transvenous (TV) implantable cardioverter-defibrillators (ICD) within 2 years post-implant. TV-ICD infection is a serious complication that frequently requires complete device removal for attempted cure, which can be associated with patient morbidity and mortality. The objective of this study is to expand on limited published data and assess mortality risk associated with TV-ICD infection in a large Medicare population with
de novo
TV-ICD implants.

Methods:
A survival analysis was conducted using 100% fee-for-service Medicare facility-level claims data to identify patients who underwent
de novo
TV-ICD implantation between 7/2016 and 1/2018. TV-ICD infection within 2 years of implantation was identified using ICD-10 and CPT codes. Baseline patient risk factors associated with mortality were identified using the Charlson Comorbidity Index categories. Infection was treated as a time-dependent variable in a multivariate Cox proportional hazards model to account for immortal time bias.

Results:
Among 26,742 Medicare patients with
de novo
TV-ICD, 518 (1.9%) had a device-related infection. The overall number of decedents was 4,721 (17.7%) over 2 years, with 4,555 (17%) in the non-infection group and 166 (32%) in the infection group. After adjusting for baseline patient demographic characteristics and various comorbidities, the presence of TV-ICD infection was associated with an increase of 2.4 [95% CI: 2.08-2.85] times in the mortality hazard ratio (see attached Figure). Most of the baseline patient risk factors were also associated with higher risk of mortality in the Cox model.

Conclusion:
The rate of
de novo
TV-ICD infection and associated mortality in a large, real-world Medicare population is noteworthy. The positive association between device-related infection and risk of mortality further highlights the need to reduce infections.
Abstract 12091: Incidence and Predictors of Progression to Chagas Cardiomyopathy: Long-Term Follow-Up of a Large Cohort of
Trypanosoma cruzi-
Infected Individuals
Authors: Nunes Maria P , Buss Lewis , da Silva JosÃ© Luiz Padilha , Oliveira Claudia , Cardoso Clareci , Brito Bruno , Ferreira Ariela , Oliveira Lea , Bierrenbach Ana , Fernandes Fabio , Hotta Viviane , Martinelli Luiz Mario , Soeiro Maria Carolina , Brentegani Adriana , Salemi Vera , Menezes Marcia , Ribeiro Antonio , Sabino Ester
Published: April 2022

Introduction:
There are few contemporary prospective cohorts of
Trypanosoma cruzi
(
T.cruzi
)-infected individuals. This study aimed to determine the incidence of new-onset cardiomyopathy and death attributable to
T. cruzi
infection.

Methods:
We enrolled 1088 individuals: 499
T. cruzi
-seropositive blood donors identified in routine donor screening, 488 age- and sex-matched
T. cruzi
- seronegative blood donors, and 101 patients with established Chagas cardiomyopathy recruited from a tertiary center. Subjects underwent cardiovascular evaluation with ECG and echocardiogram at the baseline (2008-2010) and follow-up (2018-2019) visits. Cardiomyopathy was diagnosed based on ECG and echocardiographic findings at baseline and follow-up. Vital status was determined by linkage with the national Brazilian mortality system.

Results:
Mortality was 80.9 deaths/1000 person-years (py) in established cardiomyopathy and 15.1 deaths/1000py in
T. cruzi
-seropositive donors with cardiomyopathy at baseline. The mortality rate among
T. cruzi
-seropositive blood donors without cardiomyopathy at baseline and
T. cruzi
-seronegative controls was similar, with mortality rates of 3.67 and 3.62 events/1000 py, respectively. In
T. cruzi
-seropositive donors, age (hazard ratio [HR] = 1.05 per year), anti-T.cruzi antibody level (HR = 1.40 per unit increase in serology assay signal/cut off) and the presence of cardiomyopathy at baseline (HR = 3.01) were independent predictors of mortality. The incidence of new-onset cardiomyopathy in
T. cruzi
-seropositive donors was 13.8 events/1000 py (95% CI 9.5-19.6) compared with 4.6 events/1000 py (95% CI 2.3-8.3) in controls, with an absolute incidence difference attributable to
T. cruzi
infection of 9.2 (95% CI 3.6 - 15.0) events/1000py.
T. cruzi
antibody level at baseline was the main independent predictor of subsequent new-onset cardiomyopathy with an adjusted odds ratio of 1.37 (95% CI 1.07-1.76) per unit increase in antibody level.

Conclusions:
We present a comprehensive description of the natural history of
T. cruzi
infection in a contemporary patient population. The results highlight the central importance of total anti-
T. cruzi
antibody titer as a marker of Chagas disease activity and risk of progression.
Abstract 12096: Satellite-Based Urbanization Measures Are Independent Predictors of Metabolic Syndrome
Authors: Thanikachalam Mohan , Lane Kevin , thanikachalam sadagopan
Published: April 2022

Introduction:
In India, with rapid urbanization, there is a significant increase in the prevalence of cardiovascular diseases at younger ages despite lower rates of obesity. While urbanization has led to nutrition transition, psychosocial stress and behavioral changes, these conventional risk factors do not fully explain the rapid increase in the prevalence.

Hypothesis:
Urbanization has had a profound impact on the physical environment leading to air pollution, urban heat islands and other effects, which are known to have an impact on metabolic health. Here we assess the impact of built environmental changes on the prevalence of metabolic syndrome (MS) in a rapidly urbanizing population in South India.

Methods:
Based on census data, a random sample included 8080 participants (20 to 76 years of age; 56% female) from urban, semi-urban, or rural areas spread over 80 x 80 kms. The MODIS satellite land cover data (urban, crops, trees, shrubs and grass land cover) at a 1 km x 1 km resolution was joined to participant's geolocated residential position in ArcGIS. Plus, the distance of the residential location to the urban center was mapped. MS was defined according to the AHA criteria. Multivariable regression models tested the independent association between MS and urban/built environment measures after adjusting for age, sex, physical activity, smoking, alcohol intake, socioeconomic, stress, anxiety, depression, family history of diabetes and hypertension, and energy intake levels.

Results:
The prevalence was higher in urban (44.6%) and semi-urban communities (35.2%) compared to rural (31.8%). In fully adjusted models, urban participants [OR: 2.11 (1.89, 2.36)], participants in urban land cover [OR: 1.57 (1.38, 1.78)) and those residing within 0 to 20 kms to the urban center [OR: 1.99 (1.7, 2.33)], had significantly higher odds for MS, when compared to rural, participants in crops land cover and those residing 60 to 80 kms from urban center, respectively.

Conclusions:
There is a significantly higher prevalence of MS in urban regions. After adjusting for traditional risk factors, there is an independent association between urbanization measures and MS suggesting unaccounted factors in the physical or built environment driving the prevalence MS in urban India.
Abstract 12098: A Physics-Based Machine Learning Approach for Instantaneous Classification of Myocardial Infarct Size
Authors: Alavi Rashid , Dai Wangde , Kloner Robert A , Pahlevan Niema M
Published: April 2022

Introduction:
Intrinsic frequency (IF) method is a novel systems-based approach that uses a single uncalibrated arterial waveform for the analysis of the left ventricle (LV) and arterial function. In a recent Framingham Heart Study, it was shown that IFs derived from carotid waveforms predict incident of heart failure and composite cardiovascular disease events (Hypertension. 2021, 77(2):338-346). The predictive and diagnostic values of IF for acute events such as myocardial infarction (MI) is not fully known. Here, we propose a hybrid IF-machine learning (ML) method to classify the MI size (mass percentage of necrosis over total LV).

Methods:
We used standard MI rat models (Sprague Dawley;
n
=27). Necrosis was ensured by occluding proximal left coronary artery for 30 minutes, followed by 3 hours of reperfusion. IFs were computed from carotid waveforms 2 hours after the reperfusion. MI sizes were obtained via histopathology (white areas of LV slices are the necrotic areas in Fig.1). The range of rats’ MI size was from 10.9% to 59.9%. MI sizes of 18% and 36% were considered as the cut-offs for ML classification. A 8-split decision tree was trained as the classifier model using the IFs as predictors. The
k
-fold cross-validation (
k
=3) was used to avoid overfitting. Gini’s diversity index was considered as the split criterion.

Results:
Our ML model showed accuracies of 86.7%, 85.7%, and 60% for predicting the true class of MI sizes (i.e., large, mid-sized, and small, respectively) (Fig.1). The accuracy was particularly strong (86.7%) for detecting large MI sizes.

Conclusions:
The results suggest that an IF-based ML model (a physics-based approach) can instantaneously classify the severity of the anatomic infarct size using a single arterial waveform without advanced imaging. Since IFs can be measured noninvasively and remotely (i.e., using a smartphone or wearable devices), our proposed method can have potential clinical impact in management and treatment of patients post MI.
Abstract 12102: TNNI3-K183del Mutation in Dilated Cardiomyopathy Patient-Specific iPSC-Derived Cardiomyocytes Affects Structural Proteins and Ion Channels, Leading to Impair the Function of Cardiomyocytes
Authors: Sougawa Nagako , Kawamura Takuji , Matsuura Ryohei , Li Junjun , LIU Li , Harada Akima , Takeda Maki , Oda-Mochizuki Noriko , Sawa Yoshiki , Miyagawa Shigeru
Published: April 2022

Background:
One of the causes for Dilated cardiomyopathy (DCM) are thought to be genetic defect. One mutation, Lys183 del mutation of the TNNI3, is suggested to be associated with left ventricular systolic dysfunction and transition from hypertrophic cardiomyopathy to DCM. However, the precise disease mechanism is not fully understood. Because cardiomyocytes derived from induced pluripotent stem cells (hiPSC-CMs) possess many of the same characteristics as primary human CMs and can be generated in unlimited quantities from pluripotent cell sources, they are thought to be a promising research tools to model genetic cardiomyopathies. Therefore, we hypothesized that iPS-CMs with mutations in TNNI3 is useful for elucidating the pathological mechanism of DCM and examined the phenotype of iPS-CMs with mutations in TNNI3.

Methods and Results:
We generated iPSCs from the patient with Lys183 del mutation of the TNNI3, and simultaneously induced iPS-CMs. By immunofluorescence stain analysis, we identified well-formed parallel arrays of repeating sarcomeres in myofibrils from WT iPS-CMs. On the other hand, iPS-CMs with Lys183 del mutation of the TNNI3 had fewer myofibrils and abnormal, irregular sarcomeres. In addition, sarcomere length was shorter in iPS-CMs with mutation in TNNI3 than in WT iPS-CMs. By gene expression analysis, we identified that iPS-CMs with mutation in TNNI3 had lower expression of some molecules including structural proteins or ion channels than WT iPS-CM. Cell motion analysis revealed that WT iPS-CMs were synchronously beating in multi wells, whereas iPS-CMs with mutation in TNNI3 were not. In addition, contraction velocity (CV) and relaxation velocity (RV) were significantly lower in iPS-CMs with mutation in TNNI3 (CV; 4.98±0.05 μm/sec, RV; 4.01±0.01 μm/sec) compared with WT iPS-CM (CV; 14.25±0.03 μm/sec, RV; 7.04±0.03 μm/sec). Moreover, significant decrease in contraction deformation distance and relaxation deformation distance were observed in iPS-CMs with mutation in TNNI3 (0.96±0.004 μm, 0.91±0.01 μm, respectively), compared to WT iPS-CMs (2.56±0.004 μm, 2.18±0.008 μm, respectively).

Conclusion:
iPS-CMs with Lys183 del mutation of the TNNI3 showed the morphological and functional phenotypes of DCM at a cellular level.
Abstract 12114: Endothelial Extracellular Signal-Regulated Kinase 2 Contributed to the Development of Pulmonary Arterial Hypertension in Mice Through the Impairment of Endothelial Nitric Oxide Synthase Function
Authors: Yumita Yusuke , Kagami Kazuki , Ishinoda Yuki , Iwashita Midori , Yasuda Risako , Toya Takumi , Ikegami Yukinori , Namba Takayuki , Masaki Nobuyuki , Ido Yasuo , Nagatomo Yuji , Adachi Takeshi
Published: April 2022

Introduction:
Pulmonary arterial hypertension (PAH) is a progressive disease, characterized by abnormal muscularization and endothelial dysfunction in pulmonary artery (PA). Previous study showed that endothelial extracellular signal-regulated kinase 2 (eERK2) released vasoconstrictive factors and decreased NO bioactivity resulting in obese-induced hypertension and endothelial dysfunction. However, the role of eERK2 in the pathogenesis of PAH remains to be elucidated.

Hypothesis:
We hypothesized eERK2 impaired eNOS function and progressed the pathogenesis of PAH.

Methods and Results:
We generated eERK2 knock out mice (EE2KO) crossing Tie2-Cre mice and ERK2 flox mice and induced PAH by exposing mice to chronic hypoxia (10%) for 4 weeks. The littermate ERK2 flox mice without Cre expression were used as Control (Ctr). Immuno-histochemical staining showed the deficiency of eERK2 expression in the PA of EE2KO. We assessed the medial thickness of pulmonary arteries (MTPA) and measured right ventricular systolic pressure (RVSP). Although Ctr exhibited the progression of PA muscularization with an increase in MTPA, EE2KO revealed the significantly attenuated MTPA under hypoxic condition. Moreover, we found the lower RVSPs in EE2KO than those in Ctr under hypoxia in spite of similar RVSPs in normoxia. In RT-PCR, lung endothelin1 (ET1) gene expression was significantly lower in EE2KO than Ctr under hypoxia. Interestingly, hypoxia increased eNOS protein expression both in Ctr and EE2KO with Western blot analysis. The phosphorylation of AMPKα and eNOS were up-regulated in the lungs of EE2KO relative to Ctr under hypoxia. In addition, eNOS dimer/monomer ratios with non redusing SDS-PAGE was significantly increased in EE2KO compared to the Ctr under hypoxia (1.29±0.10 vs. 0.87±0.02, P=0.02, dimer / monomer ratios), suggesting improved eNOS uncoupling.

Conclusions:
These findings suggest that hypoxia increased eNOS expression and function, and that eERK2 impaired eNOS function by decreasing the phosphorylation of AMPKα and eNOS, and inducing eNOS uncoupling. In addition, ET1 synthesis through eERK2 might contribute to these pathogenesis of PAH with hypoxia.
Abstract 12119: Silencing of Notch Signaling Tempers the Occurrence of Arrhythmic Events in the Post-Infarcted Heart
Authors: Pizzo Emanuele , Cervantes Daniel O , Jain Sudhir , Jacobson Jason , Rota Marcello
Published: April 2022

Notch1 receptor signaling is active during cardiac development and is upregulated in the adult myocardium following ischemic damage. We previously documented that Notch1 signaling modulates the electrical activity of myocytes, but whether activation of the Notch receptor system contributes to the functional properties of the injured heart remains to be clarified. In the current study, we assessed the consequences of silencing of Notch1 signaling on electrical activity and arrhythmogenic behavior of the mouse heart, in physiological condition and following myocardial infarction (MI). For this purpose, mice with cardiac-restricted, inducible deletion of
Notch1
gene (conditional knock-out, cKO) and corresponding control (Ctrl) mice were studied at baseline and up to one month after permanent coronary artery ligation. By echocardiography, left ventricular (LV) mass, chamber volume, and systolic function were comparable in both male and female naïve cKO and Ctrl mice. At ~2 and ~4 weeks after MI, chamber dilation occurred and ejection fraction was equally reduced in cKO and Ctrl animals. By electrocardiographic recordings in the conscious state over a period of 10 minutes, no arrhythmic events were observed in naïve Ctrl and cKO mice. In contrast, at one day after MI, a large fraction of Ctrl mice developed premature ventricular complexes (PVCs, 72%, n=18) and ventricular tachycardia (VT, 28%), but the fraction of cKO mice with PVCs was substantially reduced (31%, n=32) and VT was not observed. From 3-~30 days after MI, arrhythmic events occurred sporadically and no major differences were detected between the two groups of mice. Following euthanasia at 30 days after MI, infarcted hearts were perfused in a Langendorff system and monophasic action potential and pseudo-ECGs collected. Spontaneous VT were found in both Ctrl (18%, n=11) and cKO (7% n=14) hearts in sinus rhythm. Importantly, programmed electrical stimulation (S1-S2 protocol) induced PVCs and/or VT in 55% of Ctrl infarcted hearts (n=11), but only in 23% of cKO organs (n=13). Collectively, these findings support the possibility that Notch1 signaling modulates the electrical activity of the injured heart and its propensity to develop arrhythmias.
Abstract 12128: The Inflammatory Response to Percutaneous Coronary Intervention is Related to Myocardial Injury in Patients with Chronic Ischemic Heart Disease
Authors: Frisso Priscilla T , Mattos Fernando R , Trombini Pinesi Henrique , De Lemos James A , Pesaro Antonio E , Rached Fabiana H , Franken Marcelo , Caixeta Adriano M , Lemos Neto Pedro A , Chagas Antonio C , Serrano Jr Carlos V
Published: April 2022

Introduction:
In the setting of acute coronary syndromes, the association between a major release of both multiple inflammatory and myocardial injury markers after PCI is linked with a subsequent poor prognosis. However, little is known concerning the association between these markers in stable patients.

Objective:
We aimed to describe the association between systemic inflammatory response and myocardial injury after percutaneous coronary intervention (PCI) in patients with chronic ischemic heart disease (CIHD). C-reactive protein (CRP) and hematological indices were assessed to depict inflammation.

Methods:
In this retrospective, observational study, blood samples were taken before and 48 hours after successful PCI in 329 patients (65.3±11.7 y, 67% men) with CIHD. Inflammatory markers (IM) were determined: CRP, white blood cells (WBC) and subtypes, platelets, mean platelet volume (MPV), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR). High-sensitivity cardiac troponin I (hs-cTnI) was measured post-PCI. Procedural myocardial injury was arbitrarily defined by increases of hs-cTnI values and no new electrocardiographic changes nor flow-limiting complications.

Results:
PCI produced a systemic inflammatory response with a rise in IM levels. 66.7% of the patients presented myocardial injury. To determine the strength and direction of the association between increased IM and hs-cTnI, Spearman's rank-order correlation was determined: CRP 0.570 (p<0.001), NLR 0.190 (p<0.001), MPV 0.182 (p<0.001), PLR 0.180 (p<0.001), WBC 0.166 (p<0.001), neutrophils 0.145 (p<0.001), eosinophils 0.142 (p<0.001), lymphocytes -0.130 (p<0.001), monocytes 0.031 (p=0.344), and platelets -0.009 (p=0.778).

Conclusion:
Thus, PCI in patients with CIHD induces a systemic inflammatory reaction, which is associated with burden of procedural myocardial injury.
Abstract 12143: Differences in Outcomes Among Adults Hospitalized for Infective Endocarditis in the United States: The Impact of Congenital Heart Disease
Authors: Byrne Ryan D , Broda Christopher R , Dolgner Stephen J
Published: April 2022

Introduction:
Increased life expectancy for patients with adult congenital heart disease (ACHD) has created new and unique challenges, including management of complications such as infective endocarditis (IE).

Hypothesis:
Significant IE outcome differences exist between ACHD and non-ACHD patients.

Methods:
Hospital discharges with IE in patients >=18 years from the National Inpatient Sample were identified between 2001 and 2016. Weighting was used to create national annual estimates indexed to the United States (U.S.) population. Patients were categorized into age groups: 18-44 years, 45-64 years, and 65+ years. Demographic, clinical, microbiologic, and outcome data were compared stratifying by ACHD status.

Results:
ACHD-related IE hospitalizations increased over time, from 1.6% in 2001 to 3.5% in 2016 (p<0.001 for trend) with a 315% increase in annualized number of ACHD IE hospitalizations from 0.41/100,000 adults to 1.29/100,000 adults. ACHD patients were younger (mean age 49 vs. 65 years, p<0.001). In-hospital mortality was lower in ACHD patients than non-ACHD patients (5.9% vs. 9.5%, respectively, p<0.001); mortality did not change significantly over time among ACHD patients, while mortality decreased in non-ACHD patients (p<0.001). Mortality was lower in ACHD patients across all age groups (all p<0.01). ACHD patients were more likely to undergo valve surgery during their IE hospitalization (29.8% vs. 6.4%, p<0.001). The etiology of IE varied between groups (p<0.001), with increased streptococcal disease in ACHD patients (29.4% vs. 14.4%).

Conclusions:
A significant increase in the overall proportion of ACHD IE hospitalizations in the U.S. was identified between 2001 and 2016. ACHD patients had lower in-hospital mortality than non-ACHD patients and were more likely to undergo valve surgery. Further research is needed to better understand factors underlying the increase in ACHD IE cases as well as why ACHD patients have decreased mortality.
Abstract 12149: Prognostic Benefit of Heart Rate Reduction of Hospitalized Heart Failure Patients is Different Between Atrial Fibrillation and Sinus Rhythm
Authors: Kishihara Makoto , Jujo Kentaro , Takada Takuma , Abe Takuro , Shirotani Shota , Yoshida Ayano , Watanabe Shonosuke , Hata Takehiro , Minami Yuichiro , Terajima Yutaka , Hagiwara Nobuhisa
Published: April 2022

Introduction:
Heart rate (HR) reduction is a key strategy for improving clinical prognosis of patients with heart failure (HF) regardless of presenting atrial fibrillation (AF) or sinus rhythm (SR). However, the prognostic impact of HR reduction during hospitalization is still unclear.

Hypothesis:
The degree of HR reduction during hospitalization between HF patients with AF and SR differently contributes to the prognosis after discharge.

Methods:
This observational study included 1,930 hospitalized HF patients who were discharged alive. After excluding patients who were implanted pacing devices, those presenting paroxysmal AF, and those with missing data of HR, 1,137 patients were ultimately analyzed. Of them, 456 patients presented AF and 681 presented SR at admission. Change of HR was defined as the difference between HR at admission and discharge. We evaluated the association between in-hospital HR change and the incidence of a composite of cardiovascular death after discharge and HF re-hospitalization in patients with AF and SR, respectively.

Results:
During the observation period (median 528 (IQR: 135-736) days), the composite endpoint developed in 169 (37%) and 187 (27%) patients with AF and SR, respectively. The ROC curves for the composite endpoint showed the cut-off values of HR reduction were 0 bpm and 28 bpm in patients with AF and SR, respectively. Kaplan-Meier analysis showed a significantly lower incidence of a composite endpoint in patients who achieved HR reduction greater than the cut-off value in both groups (log-rank test: p<0.05). HR reduction greater than the cut-off value was still an independent predictor for a composite endpoint in patients with AF after adjusting age, sex, HR at admission and LVEF (hazard ratio: 0.65, 95% confidence interval: 0.45-0.96). However, this finding was not observed in patients with SR (hazard ratio: 0.81, 95% confidence interval: 0.50-1.33).

Conclusions:
The ideal HR reduction level during hospitalization was different between AF and SR. Target HR reduction in HF patients with AF could lead to better clinical outcomes, but the benefit is limited in patients with SR.
Abstract 12150: Incorporation of Natriuretic Peptides With Clinical Risk-Scores to Predict Heart Failure Among Individuals With Dysglycemia
Authors: Segar Matthew W , Khan Mohammad S , Patel Kershaw , Vaduganathan Muthiah , Kannan Vaishnavi , Willett Duwayne , Peterson Eric D , Tang Wai Hong W , Butler Javed , Everett Brendan M , Fonarow Gregg C , Wang Thomas J , McGuire Darren K , Pandey Ambarish
Published: April 2022

Introduction:
The WATCH-DM score can predict risk of heart failure (HF) in patients with diabetes.

Hypothesis:
Addition of natriuretic peptide (NP) levels will improve WATCH-DM performance in individuals with dysglycemia.

Methods:
Adults with diabetes/pre-diabetes free of HF at baseline from 4 cohort studies (ARIC, CHS, FHS, and MESA) were included. The integer- [WATCH-DM(i)] and machine learning-based [WATCH-DM(ml)] scores were used to estimate the 5-year risk of incident HF. Discrimination was assessed by Harrell's concordance index (C-index) and calibration by the Greenwood-Nam-D'Agostino (GND) statistic. Improvement in model performance with the addition of NP-levels was assessed by C-index, Brier score, and continuous net reclassification improvement (NRI).

Results:
Of the 8,938 participants included, 3,554 (39.8%) had diabetes and 432 (4.8%) developed HF within 5-years. Among 5,384 (60.2%) participants with pre-diabetes, 647 (12.0%) developed incident HF. The WATCH-DM(ml) and (i) scores demonstrated high discrimination for predicting HF risk in diabetes (C-indices=0.76 and 0.69), pre-diabetes (0.83 and 0.72), and overall cohort (0.80 and 0.71), respectively, with no evidence of miscalibration (GND=P >0.10). A greater improvement in C-index was observed with the addition of NP-levels at lower WATCH-DM(i) scores with degradation of risk discrimination at higher scores (Fig. A). Calibration was also improved with addition of NP-levels at lower compared to higher WATCH-DM(i) scores (Fig. B). A greater improvement in reclassification was observed by combing WATCH-DM(i) score with selected NP-levels assessment in low (score<13) vs. high-risk (≥13) participants (NRI=0.45 vs. 0.17; p-value<0.001).

Conclusions:
The WATCH-DM risk score can accurately predict incident HF risk in community-based individuals with dysglycemia. The addition of NP-levels improves risk prediction among adults with low/intermediate but not high HF risk.
Abstract 12153: Gender Differences in Patients with Val122ile Hereditary Transthyretin Cardiac Amyloidosis
Authors: Yalamanchili Sreeram , Rim Austin , Bigham Thomas , Brown Matthew T , Bhatt Kunal
Published: April 2022

Introduction:
Hereditary Transthyretin Cardiac Amyloidosis (hATTR-CA) of the Valine 122 Isoleucine (Val122Ile) variant is prevalent among 3.4% African Americans. More commonly diagnosed in men, there is limited data on sex differences in clinical characteristics and outcomes in patients with Val122Ile hATTR-CA.

Methods:
Retrospective chart review identified a total of 90 patients with a genetic confirmation of Val122Ile hATTR-CA and either positive technetium pyrophosphate (PYP) scanning or endomyocardial biopsy. Cohorts were divided based on sex and clinical and demographic data was collected from time of diagnosis.

Results:
Among our cohort, 64 (71%) were males and 26 (28%) were females. All were African Americans. Women were significantly older at the time of diagnosis compared to men, 76 ± 6 vs 71 ± 7, p=0.001. New York Heart Association (NYHA) Functional Classification scores were similar between sexes with the majority presenting with NYHA class II and III symptoms. Men had significantly higher rates of coronary artery disease compared to women, 17 (26.6%) vs 2 (7.7%), p=0.047, but all other comorbidities and extra-cardiac manifestations were similar. Troponin I, BNP, eGFR, and prealbumin did not differ significantly between sexes. Electrocardiographic variables, arrhythmia rates, and cardiac implantable electronic distribution were also similar between gender. However, several echocardiographic variables at diagnosis significantly differed: left ventricular ejection fraction (LVEF, %) was lower in men compared to women (41 ±17 vs 33 ± 15, p=0.024) whereas left ventricular end-diastolic diameter (LVeDd, mm) and mass index (LVMI, g/m2) were both higher in men (44.3 ± 6.7 vs 38.4 7.6, p = 0.001 and 168 ± 63 vs 131 ± 38, p = 0.009 respectively). There was no difference in time to diagnosis or survival between men and women in our cohort.

Conclusions:
Consistent with prior data, women with Va1122Ile hATTR-CA were significantly older with higher LVEF at diagnosis when compared to men. Despite this, women were found to have similar NYHA classification, extra-cardiac manifestation rates, biomarkers, and survival. These findings support a delayed, but equally infiltrative phenotype that should be considered in women with preserved heart failure.
Abstract 12158: Higher Body Mass Index is Associated With More Heart Failure-Related Hospitalizations in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Schmidt Morgen Camilla , Haase Christiane L , Kalayci Oral Tugce , Schnecke Volker , Varbo Anette , Borlaug Barry A
Published: April 2022

Introduction:
In people with heart failure (HF) with preserved ejection fraction (HFpEF), the associations between BMI, comorbidities and outcomes are not well-defined. This retrospective cohort study examined the association between BMI and hospitalizations in patients with HFpEF.

Hypothesis:
Higher BMI is associated with more HF-related hospitalizations and shorter time to HF-related hospitalization.

Methods:
Data for patients with BMI ≥25 kg/m
2
at the time of HFpEF diagnosis were extracted from LCED, a US claims-electronic medical record data set. Patients were categorized into 5 BMI groups: overweight and obesity classes I-IV (Figure A). Negative binomial and Cox proportional hazard models were used to estimate associations between BMI and number of HF-related hospitalizations and risk of HF-related hospitalization during follow-up. Analyses were adjusted for relevant baseline comorbidities, with age, sex and diabetes status as effect modifiers.

Results:
Among 4,975 patients, median age was 74 years and 57.5% were female. Compared with the overweight group, higher BMI groups had a lower median age (years: overweight 80; obesity III 68; obesity IV 64), fewer patients with cardiovascular (CV) history (overweight 81.0%; obesity III 77.0%; obesity IV 66.0%) and a greater proportion of female patients (overweight 56.4%; obesity III 57.9%; obesity IV 69.0%) (Figure A). Mean HF-related hospitalizations/100 patient-years was higher for obesity III (12) and IV (16) vs overweight (10) (effect of BMI: p=0.002; Figure B). The hazard ratio [95% CI] for HF-related hospitalization was 1.36 [0.97; 1.91] and 1.86 [1.32; 2.64] for obesity III and IV, relative to overweight (effect of BMI: p=0.010).

Conclusions:
Results suggest even though patients with HFpEF in higher BMI groups are younger and have less CV history at baseline, higher BMI is associated with greater burden of HF-related hospitalizations during follow-up, irrespective of age, sex and diabetes status.
Abstract 12166: Biomechanical Impact of Valve Sparing Procedure Onto the Native Aorta, a Multi-Patient in silico Study
Authors: Scarponi Valentina , Caimi Alessandro , Saitta Simone , palumbo maria chiara , Girardi Leonard N , Gaudino Mario F , Roman Mary J , Kim Jiwon , Weinsaft Jonathan W , redaelli alberto
Published: April 2022

Introduction:
Ascending thoracic aortic aneurysms (TAA) provide a nidus for dissection, which can be prevented by surgical prosthetic graft replacement. Grafts eliminate risk in resected regions, but are stiffer than native aortic tissue and can thus alter downstream hemodynamics. This study used computational modeling of fluid structure interaction (FSI) to study biomechanical impact of proximal aortic graft replacement on the descending aorta.

Methods:
TAA pts undergoing cardiac MRI (CMR) prior to and after valve sparing proximal aortic graft replacement (VSR) surgery were studied via FSI. Patient-specific anatomy was reconstructed by segmentation of 3D MR angiography. 4D flow was used to prescribe velocity at the inlet of the model and to define three-elements Windkessel parameters used to impose outlet boundary conditions.

Results:
FSI models were constructed in 5 male patients (61±10.6 years old) who underwent CMR pre (1.7±1.5 weeks) and post (28.5±2.3 weeks) proximal aortic graft replacement. Qualitative and quantitative comparison of numerical results with 4D-flow data confirmed FSI model’s ability to reproduce patients’ fluid-dynamics (mean RRMSE 0.244±0.059). Regarding post-operative hemodynamics, a post-operative oscillatory shear index (OSI) increment (Pt1:
p-value
< 0.05) and systolic peak wall shear stress (WSS) variation (Pt1:
p-value
<0.001, Pt3: <0.01, Pt5: <0.0001) were observed, particularly in proximal descending aorta (
Fig 1
). Furthermore, from 9 to 63% post-operative distensibility increment was detected. Finally, a mean 4% principal strain intensification was noticed at graft’s suture site if compared to the native portion of the ascending aorta (
Fig 1
).

Conclusion:
Computational FSI modeling analysis demonstrates VSR technique to alter downstream biomechanics, including wall shear stress variation and increased strain immediately distal to grafted territories.
Abstract 12168: Long-Term Effects of Pulmonary Endarterectomy on Pulmonary Hemodynamics and RV Function in Chronic Thromboembolic Pulmonary Hypertension
Authors: Kianzad Azar , Braams Natalia J , Van Wezenbeek Jessie , Oosterveer Frank P , Symersky Petr , Nossent Esther J , Boonstra Anco , Vonk Noordegraaf Anton , De Man Frances S , Meijboom Lilian J , Bogaard Harm
Published: April 2022

Background:
Surgical removal of thromboembolic material by pulmonary endarterectomy (PEA) leads within months to improvement in right ventricular (RV) function in the majority of chronic thromboembolic pulmonary hypertension (CTEPH) patients. However, little is known about the long-term effects of PEA on RV function. We aimed to describe long-term changes in RV function in PEA treated CTEPH-patients.

Methods:
In this prospective study we included patients diagnosed with CTEPH who underwent PEA. Structured follow-up measurements were performed using right heart catheterization (RHC) and cardiac magnetic resonance (CMR) imaging before PEA and 6 and 18 months after treatment. Single beat pressure-volume loop analysis was used to determine load-independent RV contractility (Ees) and RV afterload (Ea). RV volume, mass and function were derived from CMR.

Results:
The study protocol was completed in 25 CTEPH-patients. PEA led to a significant decline in mean pulmonary arterial pressure (mPAP 45±11 to 24±9 mmHg; p<0.0001), pulmonary vascular resistance (PVR 561 [427-711] to 132 [112-194] dynes/s/cm
5
; p<0.0001) and RV afterload (Ea 0.6 [0.49-0.81] to 0.2 [0.2-0.3] mmHg/ml; p<0.0001) 6 months after treatment. In addition, RV dimensions improved 6 months after PEA as demonstrated by a decrease in indexed RV end-diastolic volume (RVEDVi 91±28 to 71±13 ml/m
2
; p=0.0009), indexed RV mass (43±15 to 27±11 g/m
2
; p <0.0001) and increase in RV ejection fraction (RVEF 41±14 to 52±9%; p=0.0003) and Ees (0.7 [0.5-1.1] to 0.3 [0.2-0.4] mmHg/ml; p<0.0001). No further changes were seen in pulmonary hemodynamics and RV dimensions between 6 and 18 months after PEA.

Conclusion:
Restoration in pulmonary hemodynamics and RV dimensions occurs within 6 months after PEA. No further improvements are observed between 6 and 18 months after PEA.
Abstract 12171: Recruitment and Enrollment of Midlife Latinas in a Multi-Component Intervention to Reduce Cardiovascular Disease Risk: Challenges and Innovations During COVID-19
Authors: Cortes Yamnia I , Duran Mayra , Marginean Valentina , Harris Latesha K , Cazales Andrea , Santiago Lymari , Diaz Mislan Margarita , Perreira Krista
Published: April 2022

Introduction:
Latinos continue to be underrepresented in clinical research. The novel coronavirus (COVID-19) pandemic has presented additional challenges to conducting clinical research among Latino communities.
Menopausia, Salud y Corazón
is a two-group pilot intervention designed to reduce cardiovascular disease (CVD) risk in Latinas during the menopause transition. The purpose of this report is to summarize the innovative recruitment methods developed in response to COVID-19, which may enhance future clinical research with Latinas.

Methods:
This is a two-group, repeated measures experimental study. Eligible participants are Latinas age 40-60 years, who are perimenopausal or early postmenopausal, and free of CVD. In response to COVID-19, the recruitment and enrollment protocol was adjusted to include: remote modalities of recruitment, limited in-person visits, and adhering to COVID-19 safety guidelines (i.e., social distancing, personal protective equipment, sanitizing, temperature and symptom checklists). We recruited at drive-thru health fairs, churches, social media, and word of mouth. A bilingual research team was able to establish rapport and build relations. We developed communication strategies via mailings, infographics, phone calls, video conferencing and text messages that addressed Latino cultural values such as
respeto
(respect),
familismo
(loyalty to family), and
confianza
(trust).

Results:
After 8 months of recruitment, 79 women were screened for eligibility, with mean age 47.9 ± 5.2 years. All participants completed screening in Spanish and 16.4% (n=13) rated their overall health as “very good/excellent.” Twenty-eight (35.4%) participants screened were recruited through word of mouth and 29.1% were recruited through their parish. Of the individuals screened, 38 (48.1%) were eligible. The most common reason for ineligibility was menopause status (n=21, 26.5%)

Conclusions:
Despite the challenges presented by COVID-19, we found that midlife Latinas are receptive to research engagement. Researcher flexibility, multiple modalities of recruitment, a bilingual research team, and communication strategies that address cultural values are important elements for the representation of Latinas in research.
Abstract 12180: Comparison of Hemodynamically Measured Systemic Arterial Pulsatility Index With Measured Aortic Pulsatility on Gated Computed Tomography in Pre-TAVR Patients
Authors: Strickling Jarred , Selinksi Christian , Shah Kajal , Makepeace Joshua , Jalenak Jay , Ondigi Olivia , Harrison Kara , Lim Scott , Sodhi Nishtha , Salerno Michael , Bilchick Kenneth , Mazimba Sula
Published: April 2022

Introduction:
Systemic Arterial Pulsatility Index, (SAPi), [systemic pulse pressure/left ventricular end diastolic pressure (LVEDP)] has emerged as a useful prognostic tool in many cardiac diseases. We aimed to compare this hemodynamically derived index of pulsatility with directly measured pulsatility on gated CT imaging (SAPi-CT) in pre-TAVR patients, as well as with SAPi calculated from pre-TAVR transthoracic echocardiography (SAPi-TTE). We also evaluated the correlation of each of these measurements with the patients’ pre-TAVR 5-meter walk times (5MWT).

Methods:
The three SAPi were calculated as; SAPi-Cath using invasive hemodynamics, SAPi-TTE using the Nagueh formula (PCWP = 1.24 X (E/e’) +1.9) as surrogate for LVEDP, and SAPi-CT by calculating the difference in aortic cross-sectional area during systole and diastole on gated CT imaging at the level of the ascending aorta (the level of right pulmonary artery). Correlational comparisons of these methods with each other and with pre-TAVR 5MWT were made using R software.

Results:
Among 110 patients studied (mean age 77.3, 56% female), the mean SAPi-Cath, SAPi-TTE, and cross-sectional area on CT were 3.15, 3.03, and 53.83mm
2
respectively. There was a significant positive correlation between SAPi-Cath and SAPi-CT [(r=0.275, p=0.0073); shown in Figure 1a], but not between SAPi-Cath and SAPi-TTE (r=0.163, p=0.1852). SAPI-Cath was significantly associated 5MWT (r=0.287, p=0.0064); shown in Figure 1b. Using a linear regression, the relationship between SAPi-Cath and the 5MWT is estimated to be: 5MWT=4+SAPI. SAPi-CT did not correlate with 5MWT (r=0.021, p=0.8478).

Conclusions:
SAPi-Cath and SAPi-CT showed a significant positive correlation. Only SAPi-Cath showed a significant correlation with 5MWT. Given the known prognostic value of SAPi-Cath, future studies utilizing imaging variables should be performed to enhance prognostication with multi-modal data.