bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12010: Penalizing Hospitals for Excess Heart Failure Readmissions: Probability of Hospital Misclassification Error
Authors: Sosunov Eugene A , Egorova Natalia N , McCardle Ken , Gelijns Annetine C , Moskowitz Alan J , Lin Hung-Mo
Published: April 2024

Introduction:
The Centers for Medicare & Medicaid Services (CMS) adjust hospital payments for heart failure (HF) admissions if the estimate of risk-standardized excess readmission ratio (ERR) is above 1. The 2012 Inpatient Prospective Payment Systems Final Rule does not take into account the uncertainty of ERR measurement raising concerns about possible consequences.

Hypothesis:
Ignoring the uncertainty of ERR measurement results in significant probability of hospital misclassification error (HME) in HF, the most costly of applicable conditions.

Methods:
For a cohort of 1,085,568 Medicare fee-for-service patients undergoing 1,494,993 HF admissions in 4,930 U. S. hospitals between July 1, 2005 and June 30, 2008, we reproduced ERR distributions for individual hospitals using hierarchical logistic regression model and bootstrap method employed by CMS to obtain confidence intervals of ERR. Based on ERR distributions, we calculated probability of HME for each hospital and stratified results by hospital volume.

Results:
Mean probability of HME due to ignoring the uncertainty of ERR measurement is 28.2% (95% CI: 27.7%, 28.6%). Probability of HME varies with hospital volume: 41.5, 33.9, 26.9, 21.5, 16.7% in the 1st-5th volume quintiles (p<.001). In the subset of 2,381 hospitals with ERR above 1 (subject to payment adjustment per existing regulations), the falsely penalized rate was 27.5% (95% CI: 26.7%, 28.3%). In the subset of 2,549 hospitals with point estimate ≤ 1 (not subject to payment adjustment), the probability of not penalizing a poorly performing hospital was 28.8% (95% CI: 28.2%, 29.4%). (Possible maximum of probability of HME is 50% equivalent to no discrimination).

Conclusions:
Ignoring uncertainty of ERR measurement leads to errors in imposing financial penalties on hospitals associated with heart failure readmissions: good performers are penalized and poor performers escape penalties with estimated probability ~30%. Furthermore, disparity exists among hospitals with different volume: probability of erroneous adjustment of payment is inversely related to hospital volume.
Abstract 12036: Title: Improving RBC K-O2 Binding by Amiloride HCl Dihydrate in CHD: A Novel Treatment for Reversion of Angina and ST-T Alterations
Authors: Delgado Carlos Luis , Delgado-Leon Antonio Javier , Delgado-Almeida Antonio
Published: April 2024

Introduction:
Following our discovery of K-O2 binding by oxyhemoglobin we tested the hypothesis that increasing erythrocyte K (K
i
) by Amiloride HCl Dihydrate (AHD) improves K-O2 binding in CHD.

Aim:
to evaluate the novel AHD in patients with angina and ST-T alterations.

Methods:
195 patients (63% males, 59±7 years, central aortic BP 166 ±12/95±9 mmHg) with CHD (angina 73%, MI 49%, 3-vessel disease 66% and HF 48%) were randomized to double-blind trial of AHD (5 mg)+Optimal Medical Therapy (n=104 vs 91 OMT, 1
st
year), followed by open-label trial of AHD+OMT vs OMT (2
nd
year). Both phases were intention-to-treat.

Methods:
All cases had serial ECG, Ion Transport Laboratory (RBC, plasma and 12-hours overnight urinary electrolytes) and noninvasive central aortic BP and hemodynamic (DynaPulse 200M). SAS statistic analysis,
p
<0.05 was significant.

Results:
1
st
Month, compared to OMT, 87% of subjects on AHD had increased K
i
(92.1±6 vs 85±5 mmol/lc, p<0.001), reduction in angina class (1.6±0.7 vs 3.1±0.8,
p
<0.0001), improved ST-T alterations (54%) and HF symptoms (35%) vs less angina (21%), and unchanged ST-T and HF in placebo.
At 2-M,
in severe HT (n=35) AHD+OMT decreases central aortic BP in 20 patients (158 ± 12/97 ±11 vs 190±14/112±9 mmHg,
p
<0.0001), but was unchanged in 15 patients on OMT (179 ±11/107 ±9 mmHg,
p
NS).
At 6-M
, subjects on AHD had low recurrence of angina (17 vs 46% OMT), while the ST-T was normal in 34%, improved in 43%, and unchanged in 14%, but not improved ST-T was recorded in patients receiving OMT.

At 1
st

year, no cardiovascular events were reported during treatment with AHD and 25 cases (24%) showed R-voltages in areas of previous infarcts, suggesting improved LV function or electrical regeneration of LV. In OMT group significant recurrence of angina (28%) and CV events (12%) were reported.

At 2
nd

year, the trial was halted (Declaration of Helsinki, WMA 2000, Part C) and all subjects received AHD+OMT: Angina was reversed in 87% of 195 subjects, ST-T alteration improved (54%), reversed (31%) or were unchanged (15%). No CV event was reported in the 195 patients enrolled.

Conclusions:
This study confirms that AHD improves RBC K-O2 binding by oxyhemoglobin, and rapidly reverses angina, ST-T alterations and induces electrical regeneration of the LV in older infarcts.
Abstract 12125: The CHARGE-AF Risk Score Performs Better at Predicting Risk of Atrial Fibrillation than the CHA2DS2-VASc Risk Score in the Framingham Heart Study
Authors: Christophersen Ingrid E , Yin Xiaoyan , Larson Martin G , Lubitz Steven A , Magnani Jared W , McManus David D , Ellinor Patrick T , Benjamin Emelia J
Published: April 2024

Introduction:
Atrial fibrillation (AF) is a common arrhythmia that affects more than 30 million individuals worldwide and confers serious complications, such as stroke, heart failure, dementia and death. The CHARGE-AF risk score was developed in 2013 to predict risk of AF in the general population. It was derived from the Framingham Heart Study, the Cardiovascular Health Study and the Atherosclerosis Risk In Communities study and validated in the Age, Gene/Environment Susceptibility Study and the Rotterdam Study, with more than 26,000 individuals of European, European-American, and African-American ancestry in total. The CHA2DS2-VASc risk score was derived in 2010 to predict risk of stroke in individuals already diagnosed with AF. CHA2DS2-VASc has not been validated for prediction of AF, but it has been used for this purpose in recent studies.

Hypothesis:
We hypothesized that the CHARGE-AF risk score would perform better than the CHA2DS2-VASc risk score for predicting risk of AF in a community-based cohort.

Methods:
Individuals from the Framingham Heart Study aged 45-94 years, without missing covariates or prevalent AF were included. For both risk scores, we performed Cox proportional hazards regression to assess the predicted risk of AF. Model fit was assessed using the likelihood ratio X2 statistic. We evaluated discrimination and calibration of each model using the C-statistic and Hosmer-Lemeshow X2 statistic.

Results:
We included 9722 observations (mean age 63.9±10.6 years, 56% women) from 4548 unique individuals: 752 (16.5%) developed incident AF and 793 (17.4%) died. The mean CHARGE-AF score was 12±1.2 and mean CHA2DS2-VASc score 2.0±1.5. The CHARGE-AF risk score was associated with a 115% increased risk of AF (95% CI, 99-131%; p<0.0001) per unit increase, corresponding numbers for CHA2DS2-VASc were 43% (95% CI, 37-51%; p<0.0001). CHARGE-AF had better model fit than CHA2DS2-VASc (Wald X2 = 403 vs. 209, both with 1 df), improved discrimination (C-statistic=0.75, 95% CI, 0.73-0.76 vs. C-statistic=0.71, 95% CI, 0.69-0.73) and better calibration (X2=5.6, p=0.69 vs. X2=28.5, p<0.0001).

Conclusions:
The CHARGE-AF risk score performed better than the CHA2DS2-VASc risk score at predicting AF in a European-American ancestry cohort.
Abstract 12131: Mechanism of Hypokalemia-dependent Arrhythmias in a New Porcine Model of Advanced Heart Failure: Insights Into the Pathophysiology of Increased Afterload in Chronic Myocardial Infarction
Authors: Ishikawa Kiyotake , Xie Chaoqin , Motloch Lukas J , Aguero Jaume , Hu Jun , Leonardson Lauren , Fish Kenneth M , Hajjar Roger J , Akar Fadi G
Published: April 2024

Introduction:
Hypertension worsens the prognosis of post-myocardial infarction (MI) patients. To examine the underlying mechanisms, we developed a new porcine model of post-MI heart failure with chronically increased afterload (HF/iAL). We identified the mode-of-initiation and mechanism-of-arrhythmias in this model, which accounts for arterial hypertension observed in a significant proportion of post-MI patients.

Methods and Results:
Yorkshire pigs underwent aortic banding 1-month following large anterior MI, and were allowed to survive for another 2-months. Aortic banding resulted in 1.3-fold increase in systemic vascular resistance index. HF/iAL pigs presented with mildly decreased left ventricular ejection fraction without significant changes in the end-diastolic and end-systolic volume indexes. Pressure-volume relationship during the preload reduction study revealed stiffer left ventricle in the HF/iAL pigs consistent with remote non-ischemic myocardial hypertrophy found in macroscopic and histological assessment. Increased afterload in HF/iAL pigs also led to a major increase in interstitial fibrosis in non-ischemic remote areas. HF/iAL pigs were highly prone to pacing-induced VT/VF, specifically under conditions of hypokalemia. Investigation of the electrophysiological substrate revealed the dependence of hypokalemia-mediated arrhythmias on conduction rather than repolarization abnormalities. HF/iAL pigs exhibited conduction slowing down to critical levels that were not achieved in normal preparations. Altered rate-dependent kinetics of conduction slowing in HF/iAL were consistent with a higher safety margin for successful propagation of abnormally slow wavefronts that gave rise to reentrant activity.

Conclusions:
Increased afterload in the post-MI heart is associated with cellular hypertrophy, widespread interstitial fibrosis, and increased ventricular stiffness. These changes predispose patients to congestive HF and promote reentrant arrhythmias during hypokalemia by facilitating the successful propagation of critically-slow wavefronts. Our findings reveal a novel mechanism by which non-K sparing diuretics promote lethal arrhythmias in hypertensive post-MI patients.
Abstract 12176: Outcomes and Genetic Characteristics of Hypertrophic Cardiomyopathy With Severe Right Ventricular Hypertrophy
Authors: Guo Xiying , Tian Lei , Liu Yanling , Zhao Shihua , Duan Fujian , Li Yishi , Fan Chaomei
Published: April 2024

Introduction:
Severe right ventricular hypertrophy (SRVH) is extremely rare in hypertrophic cardiomyopathy (HCM).

Hypothesis:
We assessed the hypothesis that patients with HCM with SRVH may have multiple mutations and poor prognosis.

Methods:
We performed a retrospective cohort study involving 2415 HCM patients. Patients with HCM with a maximum right ventricular wall thickness ≥10 mm, either with or without a pressure gradient at the RV outflow tract (RVOT) exceeding 25 mmHg, were enrolled. Deep (30X) whole-genome sequencing was performed in 11 patients using the Illumina HiSeq X platform. The patients'clinical features, cardiovascular mortality and morbidity were analyzed. The survival estimates were calculated using the Kaplan-Meier method, and risk of either cardiovascular death or event was determined using a multivariate Cox hazards regression model.

Results:
Of the 2415 HCM patients, 43 patients (1.6%) with SRVH were identified and 12 of them demonstrated isolated RVOT obstruction. The mean age at diagnosis was 31.1 ± 16.3 years, and 24 (55.8%) of them were women. The maximum average RV wall thickness was 13.3 ± 2.4 mm. The multivariate Cox regression analysis identified 2 independent predictors of cardiovascular death, including NYHA class ≥III, with a hazard ratio of 8.6 (95% CI: 1.70-43.38, p = 0.009), and a left ventricular end-diastolic diameter ≥50 mm, with a hazard ratio of 6.0 (95% CI: 1.67-21.92, p = 0.006). Age ≤18 years was with a 3-fold increased risk cardiovascular events (95% CI: 1.14-7.16, p = 0.002). At least one variant in a specific sarcomere gene was identified in 10 patients (90.9%), of which the MYH7 mutation was the most common (n = 6, 54.5%), and 10 novel locations were detected. Double mutations involving HCM-related genes were observed in 8 (73%) patients. All patients exhibited either double or multiple mutations, either in arrhythmogenic right ventricular, dilated cardiomyopathy or ion-channel disease genes.

Conclusions:
HCM with SRVH was characterized by an early onset of disease and increased cardiovascular mortality and morbidity. Double or multiple sarcomere gene mutations might be responsible for this phenotype with multiple mutations in other forms of cardiomyopathy and ion-channel disease associated genes.
Abstract 12188: Combined Effect of BMI and Renal Function on Long-term Clinical Outcomes in the Elderly Following Percutaneous Coronary Intervention
Authors: Naito Ryo , Miyauchi Katsumi , Shitara Jun , Endo Hirohisa , Wada Hideki , Doi Shinichiro , Konishi Hirokazu , Tsuboi Shuta , Ogita Manabu , Dohi Tomotaka , Kasai Takatoshi , Tamura Hiroshi , Okazaki Shinya , Isoda Kikuo , Daida Hiroyuki
Published: April 2024

Introduction:
Accompanied by aging society, percutaneous coronary intervention (PCI) has been widely performed in the elderly for the past few decades. However, a paucity of data examining clinical features and outcomes is available. Previously, low body mass index (BMI) and renal insufficiency were demonstrated to be negative predictors in patients with coronary artery disease. However, the effect of BMI and renal insufficiency on clinical outcome in elderly following PCI was not fully examined.

Methods:
We analyzed data of patients with the age of 70 to 85 following PCI in Juntendo University (Tokyo, Japan) from 1985 to 2010. Cox regression analysis was performed to assess an effect of combination with BMI less than 22 and eGFR less than 60 on all-cause mortality that was evaluated at 3-year after the index PCI.

Results:
Of 3824 patients, 1019 patients with the age of between 70 and 85 were examined. Mean age, BMI and eGFR were 75.2, 23.3 and 59.6, respectively. The population was divided into 3 groups according to the value of BMI and eGFR (BMI < 22 and eGFR < 60; high risk, BMI < 22 or eGFR < 60; intermediate risk, BMI ≥ 22 and eGFR ≥ 60; low risk). The higher incidence of all-cause mortality was observed in accordance with the greater risk determined by BMI and eGFR (P for trend < 0.0001) (Figure 1). Kaplan-Meier estimation for all-cause mortality was significantly different between the three groups (Figure 2). In multivariable Cox regression analysis including traditional coronary risk factors, combined effect of BMI and eGFR was associated with all-cause mortality.

Conclusions:
Combination of BMI and eGFR was independently associated with all-cause mortality in the elderly following PCI.
Abstract 12216: Age-Related Macular Degeneration as a Predictor of Incidence and Progression of Subclinical Cardiovascular Disease and Cardiovascular Outcomes: The Multi-Ethnic Study of Atherosclerosis
Authors: Fernandez Antonio B , Ballard Kevin D , Guo Mengye , Wong Tien Y , Klein Ronald , Thompson Paul D , Cotch Mary Frances , McClelland Robyn L , Klein Barbara , Allison Matthew A , Burke Gregory L
Published: April 2024

Introduction:
Age-related macular degeneration (AMD) is a leading cause of vision loss in US adults and shares many similarities with CVD pathophysiology.

Hypothesis:
We assessed the hypothesis that the presence of AMD would independently predict the incidence and progression of subclinical CVD and CVD events in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods:
Our cohort consisted of 5,803 adults free of known CVD who had retinal photographs taken during the first follow-up examination of the MESA (Exam 2; Aug 2002-Jan 2004). Photographs were evaluated for AMD using the Wisconsin age-related maculopathy grading system. Coronary artery calcium (CAC), carotid intima-media thickness (cIMT), ankle brachial index (ABI), and brachial artery flow-mediated dilation (FMD) were assessed at baseline (Exam 1; July 2000-Aug 2002). Changes in CAC and cIMT from Exam 1 were determined at follow-up Exam 5 (April 2010-Dec 2011). Incident CVD events were ascertained from 2002 through 2012.

Results:
Participants were categorized as AMD+ (n = 244) or AMD- (n = 5,559). Groups did not differ at baseline for cIMT, ABI, or FMD (P>0.19). At Exam 5, 92 AMD+ and 2684 AMD- participants had CAC scores. In those with CAC = 0 at baseline, CAC incidence did not differ between AMD+ (n = 21) and AMD- groups (n = 761). In those with CAC>0, CAC progression was greater in the 46 AMD+ vs. the 1170 AMD- participants after a mean follow-up of 10.4 ± 2.4 years using multivariable-adjusted models (530 ± 537 vs. 339 ± 426 Agatston units, P = 0.004). Ten year cIMT progression (P = 0.85) and incident CVD events (multivariable-adjusted HR (95% CI) = 1.3 (0.9, 1.8); P = 0.20) did not differ between groups.

Conclusions:
In conclusion, the presence of AMD in a diverse population without known CVD was independently associated with higher 10-year CAC progression in participants with baseline CAC>0. AMD was not associated with CAC incidence, other subclinical CVD markers or CVD events. The association between AMD and CAC progression suggests that AMD is associated with a greater degree of atherosclerosis. Longer follow up of individuals with AMD is warranted to clarify whether greater CAC progression increases risk of CVD events.
Abstract 12226: Combined Impact of Acute Kidney Injury and Chronic Kidney Disease on In-hospital Mortality in Patients With Acute Myocardial Infarction
Authors: Kuji Shotaro , Ishihara Masaharu , Fujino Masashi , Ogawa Hisao , Nakao Koichi , Yasuda Satoshi , Noguchi Teruo , Ozaki Yukio , Suwa Satoru , Fujimoto Kazuteru , Nakama Yasuharu , Morita Takashi , Shimizu Wataru , Saito Yoshihiko , Hirohata Atsushi , Morita Yasuhiro , Inoue Teruo , Okamura Atsunori , Uematsu Masaaki , Hirata Kazuhito , Tanabe Kengo , Shibata Yoshisato , Owa Mafumi , Hokimoto Seiji , Nishimura Kunihiro , Miyamoto Yoshihiro , Kosuge Masami , Kimura Kazuo ,   on behalf of J-MINUET investigators
Published: April 2024

Introduction:
Renal dysfunction such as acute kidney injury (AKI) as well as chronic kidney disease (CKD) is associated with poor outcomes after acute myocardial infarction (AMI). We examined the combined impact of AKI and CKD on in-hospital clinical outcomes in patients with AMI.

Hypothesis:
Both CKD and AKI, i.e., acute-on-chronic kidney injury, might amplify the increased risk of mortality and morbidity after AMI.

Methods:
J-MINUET is a prospective, multicenter registry that enrolled consecutive AMI patients who were admitted within 48 h after symptom onset between July 2012 and March 2014 at 28 hospitals in Japan. We studied serum creatinine (Cr) on admission and for the following 48 h in 2987 patients of this registry. CKD was defined as estimated glomerular filtration rate on admission <60 ml/min/1.73m2, and AKI was defined as Cr increase ≥0.3 mg/dl or ≥50% within 48 h.

Results:
The incidences of CKD and AKI were 41.0% and 10.5%, respectively. AKI developed more frequently in CKD patients than non-CKD patients (21.0% vs 3.1%, p<0.001). Both CKD and AKI were associated with in-hospital mortality (1.9% and 11.7% for non-CKD and CKD patients, p<0.001; 3.8% and 24.3% for non-AKI and AKI patients, p<0.001) and major adverse cardiac events (MACE) (9.3% vs 30.5% for non-CKD and CKD patients, p<0.001; 14.4% vs 49.2% for non-AKI and AKI patients, p<0.001). Multivariate analysis showed that both CKD and AKI were independent predictors of in-hospital death (CKD, odds ratio [OR] 2.02, 95%CI 1.18-3.45, p=0.010; AKI, OR 3.72, 95%CI 2.29-6.02, p<0.001) and MACE (CKD, OR 2.19, 95%CI 1.66-2.87, p<0.001; AKI, OR 2.30, 95%CI 1.62-3.25, p<0.001). When a combination of these 2 variables was analyzed, a stepwise increase in in-hospital death and MACE was observed (Figure).

Conclusions:
Both CKD and AKI were independent predictors of in-hospital mortality and MACE, and combined evaluation of these 2 variables enhanced the ability to predict in-hospital clinical outcomes in patients with AMI.
Abstract 12388: Left Ventricular Layer Torsion in Hypertensive Patients using One-beat Real-time Three-dimensional Speckle Tracking Echocardiography With High Volume Rates
Authors: Miwa Hirotaka , Kawasaki Masanori , Tanaka Ryuhei , Nagaya Maki , Minatoguchi Shingo , Ueno Takahiro , Sato Hidemaro , Sawada Shigeki , Watanabe Ryota , Kato Takashi , Hirose Takeshi , Iwama Makoto , Kaneda Mayumi , Ono Koji , Noda Toshiyuki , Watanabe Sachiro , Minatoguchi Shinya
Published: April 2024

Background:
Left ventricle (LV) is composed of three myocardial layers and LV torsion caused by inner and outer oblique muscle contraction plays an important role in squeezing blood out of the heart. However, LV layer torsion has not been examined using echocardiography. We sought to examine LV layer torsion and the relation between layer torsion and systolic function in hypertension (HTN) by one-beat 3-dimensional speckle tracking echocardiography (3D-STE).

Methods:
We enrolled 31 controls (age 65±12), 47 HTN without hypertrophy (LVH) (age 67±12), 47 HTN with LVH (age 70±11) and 37 patients with hypertensive heart failure (HHF) (age 74±15) to characterize LV layer torsion {endocardium (end), midwall (mid) and epicardium (epi)} using 3D-STE with volume rate of 70-80vps. LV twist was defined as maximum difference in rotation angle between base and apex (°). LV torsion was defined as twist / long axis length (°/cm). Time to peak torsion was expressed as % systole by dividing the time by total systolic time.

Results:
LV ejection fraction (EF) by STE in HHF decreased (control; 58±6, HTN without LVH; 56±9, HTN with LVH; 55±11, HHF; 39±11* %, *p<0.05 vs control). The amplitudes of peak torsion at 3 layers were correlated with LVEF (end: r=0.30, mid: r=0.26, epi: r=0.27, p<0.001). End peak torsion was significantly greater than the corresponding mid and epi torsion by 50 % and 78 %. LV torsion in HHF was the lowest in all 3 layers among 4 groups. The decreasing LV layer torsion from end to epi was observed in 4 groups (Control: end; 2.5±0.4, mid; 1.2±0.2, epi; 0.5±0.2 °/cm. HTN without LVH: end; 2.5±0.5, mid; 1.3±0.3, epi; 0.6±0.3 °/cm. HTN with LVH: end; 2.6±0.5, mid; 1.3±0.3, epi; 0.6±0.3 °/cm. HHF: end; 2.2±0.3*, mid; 1.1±0.2*, epi; 0.4±0.2* °/cm, *p<0.05 vs control). Time to peak torsion is earliest at end layer in HHF and latest at epi layer in HTN with LVH (85±13 % systole and 97±5 % systole, p<0.05).

Conclusion:
The amplitude of LV torsion assessed by 3D-STE was greater in endocardium and followed by midwall and epicardium and the smallest in all 3 layers of HHF. The difference in LV torsion among 3 layers seemed to diminish in association with LV systolic dysfunction. Assessment of layer torsion may be useful to understand mechanism of LV systolic function and to detect LV layer damage in HTN.
Abstract 12405: Left Ventricular Phasic Strain Rate and Slice Rotation by Novel One-beat Real-time Three-dimensional Speckle Tracking Echocardiography With High Volume Rates
Authors: Minatoguchi Shingo , Kawasaki Masanori , Tanaka Ryuhei , Houle Helen , Ueno Takahiro , Miwa Hirotaka , Watanabe Takatomo , Nagaya Maki , Sato Noriaki , Kaneda Mayumi , Fujii Tomoko , Kojima Tai , Warita Shunichiro , Abe Shintaro , Ono Koji , Goto Yoshiaki , Amano Kazuo , Noda Toshiyuki , Watanabe Sachiro , Minatoguchi Shinya
Published: April 2024

Background:
Left ventricular (LV) strain rate (SR) at systole (S) and isovolumic relaxation (IVR) by speckle tracking echocardiography (STE) are reported as an index of LV contractility and relaxation. LV rotation contributes a part of LV ejection fraction. However, heart is a complex organ that undergoes cyclic changes in multiple directions, thus mechanics seem to be best represented by 3D-STE. We developed a novel software and 3D-STE with high volume rates to measure LV phasic and global SR and rotation.

Methods:
We examined the reproducibility of the novel 3D-STE in 20 subjects. We measured 5 phasic SRs {SR at isovolumic contraction (IC), S, IVR, early diastole (ED) and atrial contraction (AC)} in longitudinal, circumferential and radial direction and slice rotation in 60 controls (age 69±10), 90 hypertensive patients (HTN) and 17 hypertensive heart failure (HHF) (age 70±12). HTN was divided into 2 groups; A: HTN without hypertrophy (LVH) (n=45, age 70±8) and B: HTN with LVH (n=45, age 70±5). LV slice rotation was measured dividing LV into 9 slices from base to apex according to long axis.

Results:
The interobserver correlation coefficient and variability in radial SR-S from data format by 2 operators were 0.92 and 6.7±22.4%. LV radial SR-IC and SR-S in HTN reduced compared to control and those in HHF further reduced (SR-IC; control: 1.16±0.57, A: 1.05±0.44*, B: 0.82±0.32*. HHF: 0.75±0.39*. SR-S; 2.59±0.61, 2.27±0.55*, 1.88±0.34*, 1.72±0.34*, *p<0.05 vs control). LV radial SR-IVR and SR-ED in HTN reduced and those in HHF further reduced (SR-IVR; -0.94±0.58, -0.66±0.39*, -0.50±0.34*, -0.34±0.23*. SR-ED; -1.28±0.51, -1.05±0.42*, -0.82±0.25, -0.68±0.23*). LV circumferential SR-AC reduced in HHF. LV slice rotation angle decreased from apex to base (Figure).

Conclusion:
The phasic and global SR and slice rotation of LV myocardium could be assessed by 3D-STE with high volume rates. This method may be useful to evaluate LV properties including contractility and relaxation.
Abstract 12584: Combined Treatment With Irbesartan and Amlodipine Potently Prevents Acute Myocardial Infarction in Subtotally Nephrectomized Triple Nitric Oxide Synthases-Deficient Mice
Authors: Tsutsui Masato , Uchida Taro , Furuno Yumi , Tanimoto Akihide , Kina-Tanada Mika , Kubota Haruaki , Sakanashi Mayuko , Matsuzaki Toshihiro , Noguchi Katsuhiko , Noguchi Katsuhiko , Nakasone Junko , Ohya Yusuke , Yanagihara Nobuyuki , Shimokawa Hiroaki , Tamura Masahito , Otsuji Yutaka
Published: April 2024

Background:
Since there are few experimentally useful models that develop acute myocardial infarction (AMI), research and development of therapeutic strategies for preventing AMI have made little progress. We have recently demonstrated that 2/3 nephrectomized (NX) triple nitric oxide synthases (NOSs)-deficient mice cause sudden death due to AMI as early as 4 months after the surgery, succeeding in the establishment of an experimentally useful AMI model (
JMCC
2014). In this study, we examined the effects of an angiotensin II type 1 receptor blocker, irbesartan (irbe), and a calcium channel antagonist, amlodipine (amlo), in this model.

Method and Results:
The 2/3NX triple NOSs
-/-
mice were treated with irbe (50 mg/ml/day in chow); amlo (250 mg/ml in drinking water); a combination of both; or an anti-hypertensive agent, hydralazine (0.25 mg/ml in drinking water) for 6 months (n=20-49). We used the clinical therapeutic dosage. In this model, the mono-treatment with irbe or amlo significantly reduced the incidence of AMI and mortality, while the co-treatment with irbe and amlo more potently suppressed them. The 2/3NX triple NOSs
-/-
mice exhibited cardiovascular risk factors (hypertension, hypercholesterolemia, and hyperglycemia), higher urinary 8-isoprostane levels (a marker of oxidative stress), and increased circulating bone marrow (BM)-derived vascular smooth muscle cell (VSMC) progenitor cells (a pro-arteriosclerotic factor). The sole treatment with irbe or amlo significantly improved these pro-arteriosclerotic parameters, while the simultaneous treatment with irbe and amlo more powerfully ameliorated them. Although the hydralazine treatment significantly lowered blood pressure to the same extent as the irbe/amlo treatment, it did not significantly affect any other pro-arteriosclerotic parameters, suggesting a minor role of an anti-hypertensive effect.

Conclusions:
Combined treatment with the clinical dosage of irbesartan and amlodipine potently prevented AMI and improved prognosis in the 2/3NX triple NOSs
-/-
mice via ameliorating cardiovascular risk factors, oxidative stress, and increased BM-derived VSMC progenitor cells. These results suggest the therapeutic importance of those agents to prevent AMI in humans.
Abstract 12715: Aortic Arch Width Adds to Coronary Artery Calcium for Prediction of Incident Adverse Cardiovascular Disease Events: The Framingham Heart Study
Authors: Chuang Michael L , Gona Philimon , Qazi Saadia , Musgrave Rebecca M , Fox Caroline S , Massaro Joseph M , Hoffmann Udo , O'Donnell Christopher J
Published: April 2024

Introduction:
Aortic arch width (AAW) is cross-sectionally associated with multiple cardiovascular disease (CVD) risk factors. We sought to determine whether AAW would add to standard Framingham risk factors (FRF) and coronary artery calcium (CAC) as a predictor of incident adverse CVD events.

Methods:
AAW, the distance between the centroids of the ascending and descending aorta at the level of main pulmonary artery bifurcation, was measured in 3026 Framingham Offspring and Third Generation cohort members who underwent computed tomography (CT) for CAC assessment over 2002-2005. Upper 90th percentile (P90) limits, based on sex, age and body surface area, were determined from a healthy referent group (no hypertension, diabetes, dyslipidemia, smoking; N=1471). Participants with prevalent CVD (N=119) or missing covariates (N=27) were excluded from further analysis, leaving 2880 who were dichotomized by AAW ≥P90 (high AAW) or <P90. Cox proportional hazards models were used to estimate hazard ratio (HR) of high AAW on time-to-CVD (composite of: CVD death; myocardial infarction, MI; unstable angina, USA; stroke; first admission for heart failure, HF) after adjustment for FRF (listed in Table) and log(CAC+1). The category-free net reclassification improvement (NRI) metric was used to assess the effect of adding AAW to the baseline FRF+CAC model.

Results:
Overall prevalence of high AAW was 19.2%. There were 135 incident CVD events (6 CVD death, 49 MI, 4 USA, 42 stroke, 34 HF) over median 8.9-y follow up. High AAW was independently predictive of CVD, HR=1.55, p=0.032, and improved prediction over FRF+CAC (Table) with NRI=0.31; 95%CI=0.15-0.48.

Conclusions:
AAW is commonly visualized on MRI or CT of the chest and is simple to measure. High AAW adds to traditional CVD risk factors and CAC for prediction of incident CVD events among community dwelling adults. These data suggest AAW has utility for CVD risk stratification; findings remain to be replicated in other cohorts.
Abstract 12716: Ruptured Biceps Tendon: A Novel Non-Cardiac Clue to TTR Cardiac Amyloidosis
Authors: Geller Hallie I , Trota Danielle , Falk Rodney H
Published: April 2024

Introduction:
Senile cardiac amyloidosis (SCA) is caused by deposition in the heart of protein derived from transthyretin (TTR), resulting in a restrictive cardiomyopathy, usually in elderly men. TTR deposition may also cause carpal tunnel syndrome which can precede the cardiomyopathy by 5-10 years.TTR deposits in other organs including tendons and ligaments has been described, but no clinical sequelae are recognized. Ruptured biceps tendon (RBT) has an annual incidence of < 2/100,000 in the general population. After seeing this condition in several patients with SCA we sought to determine the prevalence of RBT in a series of patients with SCA.

Methods:
All patients with documented SCA seen at a specialized cardiac amyloidosis center were questioned about carpal tunnel syndrome and examined for RBT, characterized by a “popeye” muscle on arm flexion (figure).

Results:
99 patients with SCA (97 men) were seen over an 18 month period. 20 had RBT which had been unrecognized by the patient in four. 5/16 were unaware of the time of rupture. In the remainder, RBT occurred an average of 5.5 years prior to diagnosis of SCA. 13 (64%) patients with RBT also had carpal tunnel syndrome compared to 17/79 without RBT (p< 0.0001). RBT was not associated with more severe cardiac disease.

Conclusions:
Ruptured biceps tendon, a rare disease in the general population is seen in 1/5 patients with SCA and, like carpal tunnel syndrome, precedes the cardiomyopathy by several years. The strong association with carpal tunnel syndrome in SCA suggests that the mechanism is due to TTR tendon deposition, and the rarity of ruptured biceps tendon in the general population indicates that its presence in an elderly male with heart failure should prompt consideration of a diagnosis of senile cardiac amyloidosis.
Abstract 12756: Peripheral Organ nd Systemic Metabolism Respond Early to Cardiac Overload in the Absence of Underlying Metabolic Syndrome and Present in Multiaphasic Fashion During the Transition Toward Cardiac Decompensation
Authors: Liew Chong Wee , Xu Shanshan , Wang Xuerong , Kong Hyerim Whang , Hughes Amy , Fischer Susan K , Fantuzzi Giamila , O'Donnell J. Michael , Lewandowski E. Douglas
Published: April 2024

Reduced long chain fatty acid (LCFA) oxidation in pressure overloaded, hypertrophied hearts coincides with an isoform shift of carnitine palmitoyl transferase I from muscle (mCPT1) to liver (LCPT1). Normal rodent hearts expressing exogenous gene for LCPT1 were recently found to recapitulate the reduced LCFA oxidation of hypertrophied hearts, with surprising elevations of atrial natriuretic peptide (ANP) message consistent with hypertrophic signaling and potentially, peripheral fat mobilization. We therefore studied peripheral and systemic metabolism in male C57BL/6 mice subjected to transverse aortic constriction (TAC). At 2 wks, echocardiography showed LV hypertrophy in TAC and increased heart mass to tibia length (52%) at 6 wks compared to hearts of sham-operated mice (SHAM). Functional decline occurred by 16 wks TAC, with reduced ejection fraction (45.6%) and fractional shortening (22.6%) vs SHAM, weeks after changes in peripheral and systemic metabolism. Surprisingly, glucose tolerance (GT) and insulin sensitivity (IS) initially improved with TAC (2 wks) vs SHAM, linked to enhanced insulin signaling in liver and visceral adipose tissue (VAT), a 48% increase in plasma adiponectin, upregulation of oxidative/thermogenic gene expression in subcutaneous adipose (SAT), and downregulated gene expression for lipolysis and lipogenesis in VAT. However, by 6 wks TAC both IS and GT were impaired with reduced insulin signaling in liver and VAT, downregulation of PGC1a and oxidative enzymes in brown adipose tissue and complete reversal of oxidative and lipogenic gene expression in SAT. Metabolic mediators post-TAC included: 1) elevated plasma ANP (TAC=140±16 pg/ml; SHAM=74±7),and brain NP (TAC=850±36 vs SHAM=771±12); 2) elevated blood adiponectin at 2 wks TAC but a reduction at 6 wks persisting to wk 17 that is consistent with IS and GT shifts. These findings demonstrate multiphasic changes in extra-cardiac metabolic responses to pathogenic stress on the heart with changes in insulin signaling, circulating natriuretic peptides and adipokines, and varied gene expression in adipose tissue that are associated with altered insulin response/glucose handling and thermogenesis in mice prior to any functional decline due to cardiac decompensation.
Abstract 12803: Long-term Outcomes After Surgical Pulmonary Arterioplasty: Analysis of Re-intervention Rates and Patient-specific Risk Factors
Authors: Cresalia Nicole M , Armstrong Aimee K , Hirsch-Romano Jennifer C , Norris Mark , Yu Sunkyung , Rocchini Albert P , Zampi Jeffrey D
Published: April 2024

Introduction:
Branch pulmonary artery stenosis (PAS) is common in congenital heart disease. Surgical patch arterioplasty is a conventional therapy, however, limited data exist on long-term outcomes.

Hypothesis:
We examined the incidence of and risk factors for re-intervention after surgical arterioplasty for PAS. We assessed the hypothesis that certain characteristics are associated with increased need for re-intervention.

Methods:
This retrospective cohort study included patients with two-ventricle physiology who underwent patch arterioplasty for PAS at a single high-volume center from 2004-2013. Freedom from surgical or percutaneous re-intervention for recurrent PAS was estimated. Univariate and multivariable Cox regression were performed to determine risk factors for re-intervention.

Results:
Among 116 patients undergoing patch arterioplasty at a median age of 1.2 years, hospital discharge survival was 95%. Of the survivors, 97 (88%) had a median follow-up of 3.6 years (range 15 days to 11 years). PAS re-intervention occurred in 31/97 (32%) at a median time to re-intervention of 1.6 years (range 7 days to 9.3 years). Freedom from re-intervention is shown in Figure 1. In univariate analysis, age less than 30 days at time of arterioplasty, congenital PAS (versus acquired), and bilateral PAS were significantly associated with re-intervention. In multivariate analysis, neonatal age (adjusted hazard ratio [AHR 4.4], p=0.004) and bilateral PAS (AHR 3.3, p=0.003) remained independently associated with re-intervention.

Conclusions:
We present the largest cohort study with the longest follow-up time evaluating outcomes after surgical pulmonary arterioplasty for PAS to date. Re-intervention for recurrent PAS following patch arterioplasty is common. In conclusion, patients at highest risk for re-intervention, such as neonates and patients with bilateral PAS, may benefit from frequent monitoring or novel approaches to repair.
Abstract 12842: Regional Relaxation Abnormality Does Not Precede Regional Contraction Abnormality in the Ischemic Myocardium Immediately After Coronary Occlusion
Authors: Iwagami Erika , Asanuma Toshihiko , Masuda Kasumi , Sakurai Daisuke , Kamimukai Toshiki , Nakatani Satoshi
Published: April 2024

Background:
Although it has been reported that diastolic dysfunction precedes systolic dysfunction in the whole ventricle in the ischemic cascade, it is unclear whether the relaxation abnormality precedes the contraction abnormality in the region of ischemic insult. We investigated the beat-by-beat change of contraction and relaxation parameters after coronary occlusion.

Methods:
In 13 open-chest dogs, left ventricular short-axis images were continuously acquired with high frame rate speckle tracking echocardiography (109.3 fps, GE Vivid E9) along with hemodynamic data before and after left circumflex coronary artery occlusion (20 consecutive heartbeats after occlusion). Circumferential strain and strain rate were analyzed in the ischemic and non-ischemic regions. Peak systolic strain (ε
s
), end-systolic strain (ε
es
), and contraction duration as regional contraction parameters and the first positive peak of the strain rate (SR
first positive peak
) as a regional relaxation parameter were measured.

Results:
Negative dP/dt began to decrease and tau began to prolong after the 15th beat of occlusion. In the ischemic region, ε
es
and contraction duration significantly decreased after the 15th beat, and ε
s
significantly decreased at the 20th beat. However, SR
first positive peak
did not decrease during 20 consecutive heartbeats but rather significantly increased after the 15th beat (0.51 ± 0.10 vs. 1.34 ± 0.15 /s, p<0.05). Because the contraction duration was prolonged in the non-ischemic region after the 15th beat, dyssynchrony during the isovolumic relaxation period became remarkable (figure, arrowheads).

Conclusions:
In the ischemic myocardium immediately after coronary occlusion, the regional relaxation parameter did not become abnormal before the contraction parameter became abnormal. The deterioration of diastolic parameters for the whole ventricle (negative dP/dt and tau) seemed to be due to dyssynchrony during the isovolumic relaxation period.
Abstract 12862: Predictors of Hospitalization and Effects of Dabigatran and Warfarin on Hospitalization Rates: An Analysis From The Re-ly Trial
Authors: Merali Ali-Reza , Alak Aiman , Connolly Stuart J , Fraessdorf Mandy , Brueckmann Martina , Ezekowitz Michael D , Reilly Paul , Yusuf Salim , Wallentin Lars
Published: April 2024

Introduction:
Hospitalization is common in patients with atrial fibrillation (AF), and predicts poor prognosis, but is poorly understood.

Aim:
We evaluated predictors of hospitalization in patients with AF treated with dabigatran etexilate (DE) or warfarin in RE-LY to understand predictors of hospitalization and to further evaluate the effects of anticoagulant choices on hospitalization.

Methods:
A multivariate regression model was developed to determine predictors of hospitalization. Hospitalization due to bleeding events were identified and rates were compared between DE and warfarin.

Results:
Of 18,113 patients in RE-LY, 7,200 (39.8%) were hospitalized at least once during mean follow up of 2 years, with 14,025 total hospitalizations. Compared to patients not hospitalized, patients with hospitalizations were older, more often had coronary artery disease, prior MI, a history of heart failure, moderate renal impairment, hypertension, diabetes and higher CHADS
2
scores. Multivariate analysis identified peripheral artery disease (PAD; HR 1.44, 95% CI 1.22-1.69), a CHADS
2
score of ≥ 3 (HR 1.29, CI 1.11-1.51), VKA-naïve (HR 1.28, CI 1.19-1.37), left ventricular ejection fraction (EF) ≤ 40% (HR 1.24, CI 1.12-1.36), and renal impairment with CrCL ≤ 50mL/min (HR 1.12, CI 1.02-1.23) as predictors of hospitalization. First hospitalization rates were 39.5%, 41.6% and 42.6% for DE 110 mg bid, DE 150 mg bid and warfarin, respectively. The treatment effects of both DE doses compared to warfarin were consistent, between patients hospitalized and those not. Hospitalization occurred less often with DE 110 compared to warfarin (RR = 0.93, CI 0.87-0.99) and compared to DE 150 (RR=0.95, CI 0.89-1.01). Hospitalizations for bleeding events occurred less often with DE 110 (3.5%) compared both to warfarin (4.6%) (p=0.02) and to DE 150 (5.2%) (p<0.001); rates were statistically similar between DE 150 and warfarin (p=0.07).

Conclusion:
Predictors of hospitalization included common comorbidities of an elderly AF population, such as PAD, higher CHADS
2
scores, low EF and renal impairment. DE 110 mg bid was associated with significantly fewer hospitalizations compared to both warfarin and DE 150 bid; in part due to reduction in hospitalizations for bleeding events.
Abstract 12878: The Effect of Advanced Glycation End Products (AGE) Breaker, Alagebrium on the Cardiac Structural and Functional Change in Type I Diabetic Rat Model
Authors: Seo Hye-Sun , Lee Nae-Hee , Cho Youn-Haeng , Choi Hyung Oh , Suh Jon
Published: April 2024

Background:
Chronic hyperglycemia contributes to diabetic complications through the formation of advanced glycation end products (AGEs). The crosslink breaker, 3-phenacyl-4,5-dimethylthiazolium chloride (ALT-711), alagebrium chloride is known to reduce the pathological condition through breaking AGE cross-links. However, there has been little assessment regarding the impact of alagebrium on AGE-dependent signaling or restoring structural molecular physiology as well as the myocardial functional change.

Methods:
We investigated the effect of alagebrium on myocardial functional change using echocardiography as well as structural change in diabetic rat model based on the cellular mechanism.

Results:
AGE enhanced reactive oxygen species (ROS) synthesis dose-dependently in cardiomyocytes. Alagebrium induced decrease in enhanced ROS synthesis by AGE and increased expression of receptor for AGE (RAGE). In western blot and RT-PCR experiments, alagebrium also inhibited AGE-induced activation of MAP Kinase and decreased AGE-induced connective tissue growth factor (CTGF) and extracellular matrix. In echocardiography, the left ventricular (LV) dimension was increased (6.33 ±0.58mm at initial vs. 8.33±0.32mm at 16weeks after diabetes, p=0.003), and systolic contractility in radial and circumferential direction was decreased as diabetes was progressed in diabetic rat model. Diabetic progress also modified collagen structure. However, the alagebrium treatment reversed these LV remodeling (8.33±0.32mm at initial vs. 7.03±0.46mm at 4weeks after medication, p=0.049) and systolic dysfunction. The value of radial strain improved from 15.2±5.8% to 38.7±6.9% at 4weeks after medication. (p=0.032)

Conclusion:
In conclusion, alagebrium treatment in diabetic rat heart improved myocardial systolic dysfunction and LV remodeling by blocking the AGE-induced intracellular ROS synthesis resulting in inhibition of contractile dysfunction induced by AGE. The beneficial effect of alagebrium on diabetic cardiomyopathy was mediated by reduction of extracellular matrix production and this might be mediated by decreased activation of ERK (extracellular signal-regulated kinase) MAP kinase.
Abstract 12943: Assessment of Both Coronary Microvascular Damage and Left Ventricular Chamber Stiffness After Successful Percutaneous Coronary Intervention Predicts Left Ventricular Aneurysm in ST-Segment Elevation Myocardial Infarction
Authors: Yamamuro Atsushi , Tamita Koichi , Yoshikawa Junichi , Kaji Shuichiro , Furukawa Yukaka
Published: April 2024

Background:
In ST-segment elevation myocardial infarction (STEMI), the short deceleration time of left ventricular (LV) early filling by Doppler is a powerful independent predictor of LV remodeling. On the other hand, recent studies have shown that even if successful reperfusion is achieved in epicardial coronary arteries, microvascular obstruction results in insufficient reperfusion of the infarcted myocardium, leading to LV dysfunction. The purpose of this study was to examine the effects of both microvascular damage and LV chamber stiffness on the risk of LV aneurysm after successful percutaneous coronary intervention (PCI) in STEMI patients.

Methods:
Two hundred and twenty-one consecutive patients with first anterior STEMI were studied following successful PCI. Microvascular damage was evaluated on the basis of coronary flow velocity patterns using Doppler guidewires. We defined the presence of microvascular obstruction as diastolic deceleration time of ≤600ms and the presence of systolic flow reversal. LV filling patterns were determined by LV inflow pulsed-wave Doppler examination on day 3 after STEMI. Deceleration time ≤130 ms was defined as restrictive. We classified patients into three categories: without restrictive and microvascular obstruction (group 1, n=125), with restrictive or microvascular obstruction (group 2, n= 43), and with restrictive and microvascular obstruction (group 3, n=53). Left ventriculogram obtained 6 months after the infarction was analyzed to measure the LV volume. True LV aneurysm was defined as a deformity of the infarct segment that was apparent during diastole as well as during systole, and demonstrated diastolic contour abnormality.

Results:
Group 3 was at the highest risk of true LV aneurysm, while group 1 was at the lowest (2/125 [2%], 15/43 [35%], and 30/53 [57%]; P<0.01). The assessment of both examinations was related to the LV volume index at 6 months after the infarction: patients in a poor group had a larger end-diastolic volume index (65±22 vs 91±28 vs 128±31ml/m2; P<0.01).

Conclusions:
Assessment of both microvascular damage and LV chamber stiffness can accurately predict the risk of LV aneurysm in STEMI patients who underwent successful reperfusion, identifying a subset of high risk patients.