bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13485: An Improved Prediction Scoring System To Estimate Survival With Favorable Neurological Outcomes After Out-of-hospital Cardiac Arrest: Evidence From A Nationwide Population-based Cohort Study In Japan
Authors: Funada Akira , Goto Yoshikazu , Maeda Tetsuo , Tada Hayato , Teramoto Ryota , Shimojima Masaya , Hayashi Kenshi , Yamagishi Masakazu
Published: April 2024

Introduction:
Information on probability of survival with favorable neurological outcomes after out-of-hospital cardiac arrest (OHCA) can be useful for physicians when deciding whether to withhold further resuscitation attempts or terminate on-going resuscitation immediately after patient arrival at the emergency department.

Hypothesis:
We hypothesized that a prediction scoring system integrated with prehospital variables could identify patients who are unlikely to survive with a favorable neurological outcome.

Methods:
We analyzed the records of 238,174 adult OHCA patients obtained from a prospectively recorded Japanese national Utstein-style database from 2011 to 2012. The primary endpoint was 1-month survival with favorable neurological outcomes (cerebral performance category [CPC] score, 1 or 2 [CPC 1-2]). We developed a prediction scoring system to estimate 1 month CPC 1-2 after OHCA by using 2011 data (n = 118,631) and validating it by using corresponding 2012 data (n = 119,543). We used multivariate methods to select the best independent predictors of 1 month CPC 1-2 and classified patients as having a very low (<1%), low (1%-5%), average (>5%-15%), or higher than average (>15%) probability of 1 month CPC 1-2.

Results:
The rate of 1 month CPC 1-2 was 2.1% (n = 4,897). The best performing model was based on 3 prehospital variables: witness status (YES or NO), initial documented shockable rhythm (YES or NO), and age (categorized as 18 to 64, 65 to 74, 75 to 84, or ≥85 years). The C statistic was 0.88 when applied to the validation set. It identified the probability of 1 month CPC 1-2 as very low, low, average, and above average in 70.3%, 23.0%, 3.3%, and 3.5% of patients, respectively (1 month CPC 1-2 in 0.4%, 2.2%, 11.3%, and 26.9% of patients, respectively). Overall, 90% of patients were identified as having a low or very low probability of 1 month CPC 1-2 after OHCA (1 month CPC 1-2 in 0.8% of patients).

Conclusions:
Our prediction scoring system identifies OHCA patients who are unlikely to benefit from further resuscitation after arrival at the emergency department; this information can aid the decision regarding termination of resuscitation.
Abstract 13495: Ambulatory Blood Pressure Characteristics and Long-Term Risk for Atrial Fibrillation
Authors: Perkiomaki Juha , Nortamo Santeri , Ylitalo Antti , Kesäniemi Antero , Ukkola Olavi , Huikuri Heikki
Published: April 2024

Introduction:
Data on the significance of different ambulatory blood pressure (ABP) characteristics in predicting long-term risk for atrial fibrillation (AF) are limited.

Methods:
Total of 903 subjects with or without hypertension aged from 40 to 59 years, who were recruited to the OPERA (Oulu Project Elucidating Risk of Atherosclerosis) study, had ABP monitoring, underwent thorough clinical examinations and laboratory tests.

Results:
After an average 16.4 ± 3.6 years of follow-up, 91 (10%) of the study subjects had experienced a new-onset AF requiring a hospital visit. Of the components of baseline ABP, the night-time mean systolic blood pressure had the strongest univariate association with the occurrence of AF (120.8 ±15.9 vs. 116.4 ± 14.1 mmHg, p=0.005, in subjects with vs. without the occurrence AF). When the univariate predictors of AF, such as age, sex, body mass index, height, smoking history, alanine aminotransferase and uric acid, were entered in the multivariate Cox hazards model, age (HR=1.1, 95% CIs=1.06-1.15, p<0.001) and body mass index (HR=1.06, 95% CIs=1.015-1.115, p=0.011) retained their significant predictive power. After adjustments in this clinical hazards model, the night-time mean systolic blood pressure still predicted the occurrence of AF (HR=1.014, 95% CIs=1.001-1.028, p=0.038). The blood pressure night-time dipping status was not associated with the occurrence of AF (p=0.41).

Conclusion:
Of the ABP characteristics, the night-time systolic blood pressure is a significant independent contributor to the long-term risk of new-onset AF.
Abstract 13504: Geriatric Nutritional Risk Index Predict Cardiovascular Events in Patients at Risk for Heart Failure
Authors: Minamisawa Masatoshi , Miura Takashi , Motoki Hirohiko , Ueki Yasushi , Mochidome Tomoaki , Oguchi Yasutaka , Nishimura Hitoshi , Ebisawa Soichiro , Koyama Jun , Ikeda Uichi
Published: April 2024

Introduction:
Geriatric nutritional risk index (GNRI) is a simple nutritional assessment tool for elderly patients. Lower GNRI is associated with a worse prognosis in patients with heart failure (HF) with preserved ejection fraction. However, few data are available regarding the prognostic impact of GNRI value for risk stratification in patients at risk for HF, classified as stage A/B according to the ACC/AHA HF guidelines.

Hypothesis:
We hypothesized that GNRI values would predict adverse cardiovascular (CV) events, even in patients without prior HF.

Methods:
We retrospectively enrolled 2258 consecutive patients without prior HF who were hospitalized for CV diseases between 2005 and 2012. GNRI on admission was calculated as follows: 14.89 х serum albumin (g/dL) + 41.7 х body mass index/22. Patients were divided into two groups stratified by GNRI (median value 106.7). The study endpoint was the composite of CV death and hospitalization for worsening HF.

Results:
Over a 4.6-year median follow-up, adverse events were observed in 139 patients (6.2 %). In Kaplan–Meier analysis, patients with low GNRI (< 106.7, n = 1128) showed worse prognoses than those with high GNRI (≥ 106.7, n = 1130) (8.1 % vs. 4.2 %, P < 0.001). In multivariate Cox proportional hazards analysis after the adjustment for age, sex, estimated glomerular filtration rate, B-type natriuretic peptide, and left ventricular ejection fraction, Low GNRI (<106.7) was significantly associated with the incidence of CV events (hazard ratio: 1.72, 95% confidence interval: 1.26–2.35; P = 0.001).

Conclusions:
In patients without prior HF, GNRI is an independent predictor of CV events. Simple assessment of GNRI may be useful for predicting CV events in those patients.
Abstract 13518: Low Skeletal Muscle Mass Index is Associated With Cardiovascular Events in Patients After ST-segment Elevation Myocardial Infarction
Authors: Satou Ryosuke , Matsuzawa Yasushi , Akiyama Eiichi , Suzuki Hiroyuki , Kawashima Chika , Konishi Masaaki , Kimura Yuuichiro , Hashiba Katsutaka , Maejima Nobuhiko , Iwahashi Noriaki , Hibi Kiyoshi , Kosuge Masami , Ebina Toshiaki , Sumita Shinichi , Kimura Kazuo
Published: April 2024

Introduction:
Although it has been implicated the association between low skeletal muscle mass and cardiovascular diseases, the prognostic value of skeletal muscle mass in patients with ST-segment elevation myocardial infarction (STEMI) is unclear.

Hypothesis:
We assessed the hypothesis that low skeletal muscle mass index (SMMI) is associated with an increased risk of secondary cardiovascular events in patients with STEMI.

Methods:
A total of 200 patients with STEMI were enrolled. SMMI was estimated from dual-energy X-ray absorptiometry scan before discharge, and calculated by dividing appendicular skeletal muscle mass (kg) by height squared (m
2
). The patients were divided into low and high SMMI groups using the first tertile of SMMI. Low SMMI was defined as ≤6.843 kg/m
2
for men and ≤5.321 kg/m
2
for women. All patients were followed for cardiovascular events, which consist of cardiovascular deaths, nonfatal myocardial infarctions, nonfatal ischemic strokes, and congestive heart failure.

Results:
During follow-up (median 340 days [interquartile ranges 298 and 389]), 15 patients experienced cardiovascular events (1 cardiovascular death, 6 myocardial infarction, 6 stroke, and 3 congestive heart failure). The event rate at 1 year after STEMI was significantly higher in patients with low SMMI (15.5%) than with high SMMI (2.5%) (log-rank p<0.001) (Figure). Even after adjustment for the propensity score which was calculated with age, gender, height, weight, risk factors and medications, patients with low SMMI had 5.8-fold higher risk of subsequent cardiovascular events compared to those without (Adjusted hazard ratio 5.86, 95% confidence interval 1.18 to 35.28, p=0.03).

Conclusion:
Among patients with STEMI, low SMMI was significantly and independently associated with an increased risk of future cardiovascular events.
Abstract 13741: Neurologic Injury and Cerebral Blood Flow In Single Ventricles Throughout Staged Surgical Reconstruction
Authors: Fogel Mark A , Pawlowski Tom , Li Christine , Schwab Peter , Wilson Felice , Nicolson Susan , Montenegro Lisa , Diaz-Berenstein Laura , Spray Thomas , Gaynor J William , Fuller Stephanie , Mascio Christopher , keller Marc , Harris Matthew , Whitehead Kevin K , Elci Okan , Bethel James , Licht Daniel , Vossough Arastoo
Published: April 2024

Introduction:
Single ventricle pts experience a high rate of brain injury and adverse neurodevelopmental outcome.

Hypothesis:
The incidence of brain abnormalities is different at various surgical stages and is linked with cerebral blood flow (CBF), oxygen delivery and carbon dioxide reactivity.

Methods:
Single ventricle pts were studied with MRI scans immediately prior to bidirectional Glenn (pre-BDG), prior to Fontan and then 3-9 months after Fontan reconstruction.

Results:
168 consecutive subjects recruited into the project underwent 235 scans: 63 pre-BDG (4.8±1.7 months), 118 BDG (2.9±1.4 years) and 54 after Fontan (3.4±1.1 years). Non-acute ischemic white matter changes on T2 weighted imaging, focal tissue loss, punctate microbleeds and ventriculomegaly were all more commonly detected in BDG and Fontans compared to pre-BDG (see figure); punctate microbleeds were also more common in Fontan than pre-BDG (P<0.05). CBF was higher in BDG than Fontan and almost reached statistical significance versus pre-BDG (see graph). The odds of discovering brain injury adjusting for surgical stage as well as 2 or more co-existing lesions within a patient all decreased (63-97% and 44% respectively) with increasing amount of CBF (P<0.05). In general, there was no association of oxygen delivery or carbon dioxide reactivity with neurological injury.

Conclusion:
Significant brain abnormalities are commonly present in single ventricle pts and detection of these lesions increase as children progress through staged surgical reconstruction with multiple co-existing lesions more common earlier than later. Cumulative exposures to surgery may account for increased incidence, though changes in brain maturation may increase detection of white matter injury. In addition, an inverse association of various indices of CBF with these brain lesions is present (CBF highest in BDG stage), however, CO
2
reactivity, oxygen delivery were not associated with brain lesion development.
Abstract 13748: A Disintegrin and Metalloproteinase 17 Deletion in Smooth Muscle Cell Transiently Suppresses Angiotensin II Mediated Hypertension
Authors: Shen Mengcheng , Morton Jude , Davidge Sandra T , Kassiri Zamaneh
Published: April 2024

Introduction:
A disintegrin and metalloproteinase-17 (ADAM17) proteolytically releases membrane-bound growth factors and cytokines. Hypertension is associated with remodeling, hypertrophy and hyperplasia of smooth muscle cells (SMCs). ADAM17 has been reported to mediate Angiotensin II (Ang II)-induced SMC hypertrophy. We investigated the role of smooth muscle cell ADAM17 in Ang II-induced hypertension.

Hypothesis:
Smooth muscle cell ADAM17 deficiency suppresses Ang II-induced hypertension.

Methods:
SMC-specific ADAM17-deficient mice (

Adam17
flx/flx
/SM22Cre

;

Adam17
SMC-Cre

), and littermate controls (

Adam17
flx/flx

) received Ang II or saline (Alzet pumps, 1.5 mg/kg/d; 4 wks). Blood pressure was measured in conscious mice before and 4 wks after Ang II infusion (Telemetry). Vascular function (vasoconstrictor/dilator response), circumferential wall stress/strain were assessed in second order mesenteric arteries
ex vivo
at 2 wks after Ang II/saline infusion.

SMCs were isolated from either genotype (enzyme dispersal method). SMC proliferation (BrdU incorporation), migration (scratch assay) and apoptosis (Annexin V/7-AAD staining, Flow Cytometry) were assessed (±Ang II). Activation of signaling pathways (phospho/total EGFR, Akt and ERK1/2), HB-EGF were assessed by Western blot.

Results:

Adam17
SMC-Cre

mice exhibited suppressed hypertension in the 1
st
week of Ang II infusion (reduced systolic, diastolic & MAP). However, by the 2
nd
week, systolic and diastolic BP rose to similar levels as

Adam17
flx/flx

mice and remained similar.
Ex vivo
analyses revealed similar acute vasoconstrictor/dilator responses, and comparable wall stiffness in both genotypes; but the Ang II-induced increase in wall thickness was not observed in

Adam17
SMC-Cre

group.

ADAM17-deficient SMCs showed reduced Ang II-induced proliferation, migration, and activation of HB-EGF and ERK1/2. A time-course study revealed delayed Ang II-mediated EGFR activation in ADAM17-deficient SMCs (@24 hrs vs 30 min).

End organ damage, hypertrophy and fibrosis in the heart and kidneys, were comparable.

Conclusions:
ADAM17 deficiency in SMCs causes a transient reduction in Ang II-induced hypertensive response, possibly due to delayed activation of the EGFR pathway.
Abstract 13809: Soluble TNFα Receptor 1 Level Predicts Incident Heart Failure: The Multi-Ethnic Study of Atherosclerosis
Authors: Bakhshi Hooman , Ambale-Venkatesh Bharath , Meyghani Zahra , Ostovaneh Mohammad R , Wu Colin O , Cushman Mary , Tracy Russell , Bluemke David A , Lima João A
Published: April 2024

Introduction:
Heart failure(HF) is a common chronic disease with growing incidence and prevalence. Innate and adaptive immunity have important roles in initiation and progression of HF. Therefore we investigated the association of key biomarkers including soluble tumor necrosis α receptor 1 ( sTNFαR1; first-wave cytokine activity) and interleukin-2 receptor(sIL-2R; T cell activation) with incident HF in a population based cohort.

Methods:
The Multi-Ethnic Study of Atherosclerosis (MESA) is a population based study consisting of 6814 men and women free of clinical cardiovascular disease at enrolment recruited from four ethnicities in six US field centers. We included all participants with available sTNFαR1 and sIL-2R level measurements at baseline exam (n=2848). Both probable and definite HF were considered as the endpoint of the study. Cox Proportional Hazard models were used to evaluate the association of inflammatory biomarkers and time to first HF after adjusting for traditional risk factors for HF.

Results:
The mean (SD) age was 61.6 (10.2) years and 46.4% were male. The median (IQR) sTNFαR1 (pg/ml) and sIL-2R (pg/ml) levels were 1292 (1107-1547) and 903 (727-1154). Over a median (IQR) follow up of 12.3 (11.6-12.8) years, 112 participants developed incident HF. Every 100 pg/ml higher sTNFαR1 level was associated with 5% higher risk of incident HF independent of traditional risk factors of HF (Table). The association with sIL-2R level was not statistically significant, although had a trend towards a modest association.

Conclusion:
sTNFαR1 level is associated with future HF in a multi-ethnic population based cohort.
Abstract 13813: Prior β-Blocker Treatment Dampens Immune Cell Responses Following Myocardial Infarction
Authors: Grisanti Laurel A , Gao Erhe , Koch Walter J , Tilley Douglas G
Published: April 2024

Following myocardial infarction (MI), immune cell infiltration initiates and regulates cardiac remodeling and repair. Our previous work has shown the importance of β2-adrenergic receptors (β2AR) in modulating immune cell infiltration to the heart following injury through the regulation of chemokine receptor expression and splenic retention of bone marrow (BM)-derived leukocyte populations. Pharmacological inhibition of βAR is a common strategy for the treatment of many cardiovascular etiologies, however the impact of β-blocker therapy on immune cell responses following acute cardiac injury is unknown. We hypothesized that prior treatment with β-blockers with distinct isoform selectivity would differentially decrease leukocyte infiltration to the heart following MI. Mice were administered either vehicle, a β1AR-selective (Metoprolol; Met), a β2AR-selective (ICI 118,551; ICI) or a βAR non-selective (Carvedilol; Carv) antagonist for two weeks via minipump. Analysis of mice treated with ICI or Carv showed decreased BM expression of CCR2 and CXCR4, as well as elevated levels of leukocyte populations within the spleen. While these effects were not observed in mice infused with a β1AR-selective dose of Met, a higher concentration of Met (equivalent to moderate doses used in humans) also decreased CCR2 and CXCR4 expression in BM and increased splenic leukocyte retention. To determine the impact of β2AR-selective versus non-selective blockade on immune cell responses following acute cardiac injury, mice from each treatment group underwent sham or MI surgery. In addition to decreased CCR2 and CXCR4 expression in the BM, mice administered ICI, Carv and the non-selective dose of Met had impaired recruitment of leukocyte populations to the heart following MI. Toward clinically relevant ends, we assessed CCR2 and CXCR4 expression in leukocytes isolated from blood samples of healthy and heart failure patients and found that levels of each were decreased in patients having taken β-blockers. In all, these results demonstrate that prior β-blocker treatment negatively regulates immune cell responsiveness to acute cardiac injury.
Abstract 13856: Circulating microRNA Differentiates HFpEF and HFrEF Patients
Authors: Lu Min , Hu Xuguang , Cleland John G , Nicholls Rachel , Clark Andrew L , Khakoo Aarif , Dan Fitzpatrick , Wang Xiaozhen
Published: April 2024

Introduction:
Circulating microRNAs (miRNAs) might reflect altered regulation of key pathways that determine the progression of heart failure (HF) and therefore provide therapeutic targets. We explored the feasibility of serum miRNA profiling in patients with HF and whether miRNA profiles are different in i) non-HF control vs. HF and ii) HF with preserved ejection fraction (HFpEF) vs HF with reduced ejection fraction (HFrEF).

Methods:
Serum samples from 124 subjects were obtained from non-HF controls (n=61), patients with HFpEF (n=51), and patients with HFrEF (n=12). miRNAs were isolated, and levels of 84 miRNAs known to exhibit altered expression in cardiovascular disease were assessed using real-time quantitative PCR. Data analyses were carried out using R limma package. Multiple testing was adjusted by Benjamini-Hochberg’s approach.

Results:
57 out of 84 miRNAs had detectable expression in the serum (Ct mean<35), in which 3 miRNAs (miR-122, miR-142, and miR-143) differed significantly between HF and control subjects (adjusted p-value<0.01, absolute fold change >2). These miRNAs negatively regulate expression of pathogenic genes in cardiovascular diseases. Specifically, miR-142 targets acetyltransferase p300 and gp130, key regulators of growth and STAT3-mediated survival signals. miR-143, together with miR-145 (adjusted p-value=0.1, absolute fold change=1.9) are highly expressed in vascular smooth muscle cells (VSMCs). They are required for the transition from proliferative to contractile VSMCs via targeting known repressor genes of the contractile VSMC phenotype such as KLF4, KLF5, and ACE. One miRNA, miR-140 differed between HFpEF and HFrEF (non-adjusted p=0.03, absolute fold change>3). miR-140 targets SUMRF1, an E3 ligase for bone morphogenetic protein receptor II (BMPR2). Mutations of BMPR2 cause pulmonary arterial hypertension and cardiomyopathy in human.

Conclusions:
Circulating miRNA profiles exhibit distinct patterns in control and HF that are plausibly associated with specific pathogenetic pathways in HF which may be useful biomarkers or therapeutic targets.
Abstract 13924: Four-Tier Classification of Pulmonary Artery Metric Severity for Diagnosis and Prognosis of Pulmonary Hypertension
Authors: Bhatia Harpreet S , Szymonifka Jackie , Zhou Qing , Lavender Zachary R , Waxman Aaron B , Semigran Marc J , Malhotra Rajeev , Truong Quynh A
Published: April 2024

Introduction:
Increased main pulmonary artery diameter (mPA) and ratio of mPA to ascending aortic diameter (ratio PA) on computed tomography (CT) are associated with pulmonary hypertension (PH). We aimed to develop a four-tier severity classification of mPA and ratio PA for diagnosis of PH.

Methods:
In 228 patients (136 with PH) undergoing right heart catheterization (RHC) and CT for dyspnea, we measured mPA and ratio PA. Using a derivation cohort (n=114), we determined cutpoints for four tiers of mPA and ratio PA severity to maximize sensitivity and specificity, and confirmed these values in a validation cohort (n=114).

Results:
Figure A shows the 4-tier cutpoints for mPA and ratio PA as Framingham sex-specific normal, mild, moderate, and severe. The 4-tier classification of mPA and ratio PA successfully predicted PH (derivation: both c-stats 0.90; validation: both c-stats 0.85). The sensitivity of the normal tier was 99% for mPA and 93% for ratio PA, while the specificity of the severe tier was 98% for mPA and 100% for ratio PA. With increasing severity of mPA and ratio PA tiers, there was a corresponding increase in the proportion of patients with elevated RHC Mean Pulmonary Artery Pressure (Figure A) and Echo Right Ventricular Systolic Pressure (both p<0.001). Patients with moderate to severely enlarged mPA had worse survival than those with normal or mildly enlarged mPA (Figure B). Similar results were seen with ratio PA.

Conclusions:
Non-invasive CT four-tier classification of mPA and ratio PA has high diagnostic accuracy for PH and can easily be used clinically. Higher severity of mPA and ratio PA are also associated with worse prognosis.
Abstract 13951: Circulating Inactive Matrix Gla-protein, Warfarin Use and Large Artery Stiffness in Heart Failure With Reduced Ejection Fraction
Authors: Chirinos Julio A , Vassim Izzah , Varakantam Swapna , Phan Timothy S , Syed Amer Ahmed , Bhattacharya Priyanka , Beraun Melissa , Soto-Calderon Haideliza , Akers Scott R
Published: April 2024

Background:
large artery stiffness increases pulsatile afterload to the LV and is strongly predictive of adverse outcomes in heart failure and reduced ejection fraction (HFrEF). The identification of pathways related to arterial stiffness may provide novel therapeutic targets. Matrix Gla-protein (MGP) is a vitamin K-dependent protein that inhibits arterial calcification. Vitamin K deficiency leads to production of inactive non-phosphorylated and uncarboxylated MGP (dp-ucMGP). We hypothesized that greater levels of dp-ucMGP, indicating impaired MGP activation, are related to arterial stiffness in human HFrEF.

Methods:
We studied 50 subjects with HFrEF and 279 control subjects without HF. dp-ucMGP MGP was measured with ELISA (VitaK; The Netherlands). In a subgroup of subjects (34 with HFrEF and 146 with no HF), carotid-femoral PWV (a measure of large artery stiffness) was measured with arterial tonometry (Sphygmocor Device). Carotid-radial PWV, a measure of medium-sized muscular artery stiffness, was also measured.

Results:
Subjects with HFrEF demonstrated markedly increased levels of dp-ucMGP (654.7 vs. 426.8; P=0.004). Among subjects with HFrEF, warfarin use (standardized Beta 0.66; P<0.0001) was the main predictor of dp-ucMGP. In turn, dp-ucMGP predicted carotid-femoral PWV (Beta=0.43; P=0.01) in HFrEF, even after adjustment for age, gender, mean arterial pressure and heart rate (Beta=0.43;
P
=0.007). In contrast, dp-ucMGP was not associated with carotid-radial PWV, a measure of muscular artery stiffness.

Conclusions:
HFrEF is associated with reduced levels of inactive dp-ucMGP, particularly in the setting of warfarin use. Circulating dp-ucMGP is independently associated with large artery stiffness in HFrEF, likely due to its role in vascular calcification. This suggests that deficient vitamin-K dependent activation of MGP may contribute to arterial stiffness in HFrEF and could be targeted with vitamin K supplementation and/or the use of anticoagulants other than warfarin. This hypothesis needs to be tested in future trials.
Abstract 13959: SIRT1 Deacetylase Mediates Klotho Gene Deficiency-induced Arterial Remodeling and Stiffness
Authors: Gao Diansa , Zuo Zhong , Tian Jing , Ali Quaisar , Lin Yi , Lei Han , Sun Zhongjie
Published: April 2024

Objective:
Arterial stiffness is an independent risk factor for stroke and myocardial infarction. This study was designed to investigate the potential role of SIRT1, an important deacetylase, and its relationship with Klotho, a kidney-derived aging-suppressor protein, in the pathogenesis of arterial stiffness and hypertension.

Methods and Results:
We found that the serum level of Klotho was decreased by nearly 45% in patients with arterial stiffness and hypertension. Interestingly, Klotho haplodeficiency caused arterial stiffening and hypertension, as evidenced by significant increases in pulse wave velocity (PWV) and blood pressure (BP) in Klotho-haplodeficient (

KL
+/-

) mice. Notably, the expression and activity of SIRT1 were decreased significantly in aortic endothelial and smooth muscle cells in
KL
+/-
mice, suggesting that Klotho deficiency downregulates SIRT1. Treatment with SRT1720 (15 mg/kg/day, IP), a specific SIRT1 activator, abolished Klotho deficiency-induced arterial stiffness and hypertension in

KL
+/-

mice. Klotho deficiency was associated with significant decreases in activities of AMP-activated protein kinase alpha (AMPKα) and endothelial nitric oxide synthase (eNOS) in aortas, which were abolished by SRT1720. Furthermore, Klotho deficiency upregulated NADPH oxidase activity and superoxide production, increased collagen expression, and enhanced elastin fragmentation in the media of aortas. These Klotho deficiency-associated changes were blocked by SRT1720.

Conclusion:
This study provides the first evidence that Klotho deficiency downregulates SIRT1 activity in arterial endothelial and smooth muscle cells contributing to the pathogenesis of arterial remodeling and stiffening. Pharmacological activation of SIRT1 is likely to be an effective therapeutic approach for arterial stiffness and hypertension.
Abstract 13966: Catheter Ablation for Atrial Fibrillation Reduces the Recurrence of Ischemic Stroke
Authors: Hama Yoshiyuki , Ishimura Masayuki , Kuwahara Taishi , Ueda Marehiko , Miyazaki Akira , Yamanouchi Masato , Kanda Junji , Yamamoto Masashi , Himi Toshiharu , Kobayashi Yoshio
Published: April 2024

Introduction:
Cardioembolic stroke related to atrial fibrillation (AF) is associated with a high recurrence rate and high mortality and morbidity. Catheter ablation for AF is effective in reducing AF burden, while the impact of AF ablation on a recurrence of stroke remains to be elucidated.

Methods:
We performed a retrospective multicenter cohort study of patients who were diagnosed with AF. A total of 1792 patients with AF (age 67±10, male 67%, 47% paroxysmal AF) were analyzed. Six hundred thirty-three patients underwent AF ablation. Patients with a history of transient ischemic attack (TIA) or ischemic stroke (IS) were listed. The association between a recurrence of TIA/IS, and AF ablation was evaluated.

Results:
There were 282 patients with a history of TIA/IS (104 ablation, 178 no-ablation). Ablation group had more patients with heart failure than no-ablation group. Besides this, there were similar about CHADS2 score in both group. Fifty-six recurrences were observed. AF ablation was associated with a lower incidence of recurrences (Hazard ratio 0.30; 95% CI 0.11 - 0.85; p=0.02). Independent predictors of recurrences of TIA/IS were, not undergoing AF ablation, aging, and a presence of hypertension.

Conclusion:
Our results suggested that AF ablation could reduce the recurrence of TIA/IS.
Abstract 13995: Decreased Circulating Omega-6 Fatty Acid Levels Are Associated With Total Mortality in Patients Admitted to Cardiac Intensive Care Unit
Authors: Ouchi Shohei , Miyazaki Tetsuro , Shimada Kazunori , Sugita Yurina , Shimizu Megumi , Murata Azusa , Kato Takao , Aikawa Tatsuro , Suda Shoko , Shiozawa Tomoyuki , Hiki Masaru , Takahashi Shuuhei , Kasai Takatoshi , Miyauchi Katsumi , Daida Hiroyuki
Published: April 2024

Introduction:
Polyunsaturated fatty acids (PUFAs), especially omega-3 fatty acids, have several important roles in the pathogenesis of cardiovascular diseases. Several studies have reported the anti-inflammatory and anti-atherogenic effects of omega-6 and omega-3 fatty acids. However, the clinical significance of PUFAs metabolism in the acute phase of cardiovascular diseases remains unknown. Therefore, we investigated the association between circulating PUFAs levels and clinical prognosis in patients admitted to the cardiac intensive care unit.

Methods:
We recruited 414 consecutive patients (acute decompensated heart failure: 36.0%, acute coronary syndrome: 38.4%) admitted to the cardiac intensive care unit in our University Hospital from April 2012 to October 2013. Fasting plasma PUFAs levels, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and dihomo-gamma-linolenic acid (DGLA), were measured within 24 h after admission. After excluding patients with malignant diseases, end stage kidney disease, and received EPA therapy, 328 patients were followed up until December 2015.

Results:
During the 2.4 year mean follow-up period, 51 patients died. The levels of DGLA (31.3 ± 12.2 vs. 23.6 ± 11.3 μg/mL, P < 0.01) and AA (171.6 ± 51.9 vs. 147.8 ± 44.2 μg/mL, P < 0.01), but not EPA (53.6 ± 34.8 vs. 47.5 ± 26.4 μg/mL, NS) and DHA (127.2 ± 43.1 vs. 116.7 ± 36.4 μg/mL, NS), were significantly lower in the non-survivor group compared with the survivor group. Kaplan-Meier survival analysis showed that low DGLA, AA levels and DGLA/AA, but not EPA and DHA levels, were associated with all-cause mortality. Furthermore, Kaplan-Meier survival analysis showed that low DGLA, AA levels and DGLA/AA were associated with all-cause mortality in 114 patients with acute decompensated heart failure (ADHF), whereas each PUFAs levels were not significantly associated with all-cause mortality in 137 patients with acute coronary syndrome.

Conclusion:
Decreased levels of circulating DGLA and AA in patients admitted to the cardiac intensive care unit were significantly associated with total mortality, especially patients with ADHF. The present study showed it is possible DGLA levels predict long-term mortality.
Abstract 14003: Prognosis Value of Aortic Valve Calcium Scoring After Transcatheter Aortic Valve Implantation performed With New Generation Prosthesis
Authors: Leclercq Florence , Akodad Myriam , Agullo Audrey , Macia Jean Christophe , Marin Gregory , Lattuca Benoit , Gandet Thomas , Schmutz Laurent , Albat Bernard , Cayla Guillaume
Published: April 2024

Introduction:
The degree of aortic valve calcification has been shown to be associated with paravalvular aortic regurgitation (AR) and mortality after transcatheter aortic valve implantation (TAVI).

Hypothesis:
Calcium scoring of the aortic valve might no longer be a prognosis factor of adverse events after implantation of new devices designed to reduce paravalvular leaks.

Methods:
In a prospective monocentric study, Agatson calcium score (CS) was evaluated on multislice computed tomography (MSCT) before TAVI in consecutive patients who had TAVI with balloon expandable SAPIEN XT (n=61) or self expandable CoreValve (n=57) (group 1, n=118), and in patients who received the new generation balloon expandable SAPIEN 3 valve (n=142). Major adverse clinical events were evaluated at 1-month follow-up (VARC-2 criteria)

Results:
Main clinical characteristics did not significantly differ between the 2 groups excepted concerning logistic Euroscore (20.1% in group 1 vs 15.1% in group 2; p=0.001). Pre procedural CS value was 4092+/- 2176 in group 1 vs 4209+/- 2204 in group 2 (p=0.9). At follow-up incidence of more-than-mild AR was significantly higher in group 1 vs group 2 (n=27; 22.9% and n=10; 7.1 % respectively, p <0.01). CS was associated with occurrence of AR in group 1 (3429 +/- 1505 without AR vs 6234 +/- 2711 with AR; p<0.001), but not in group 2 (4663+/- 3057 vs 4176+/- 2149 respectively; p=0.9). Similarly, CS was associated with adverse clinical events only in group 1 (table 1). A CS value > 6000 was a major predictor of adverse events in group 1 (OR: 106; IC 95: 15.5-727.6; p<0.0001) but not in group 2 (p=0.4).

Conclusions:
Severe calcifications of the aortic valve evaluated on MSCT appear to be an major prognostic parameter after TAVI performed with the second generation prosthesis but not with the new designed SAPIEN 3 valves. Impact of CS on patient selection before TAVI need probably to be reconsidered with the new generation devices .
Abstract 14004: Role of Inflammation in the Pathogenesis of Hypertension a 9-year Repeated-measures Data Analysis in a Prospective Cohort Study
Authors: Tomiyama Hirofumi , Matsumoto Chisa , Komatsu Shunsuke , Kimura Kazutaka , Shiina Kazuki , Yamashina Akira
Published: April 2024

Introduction:
The underlying mechanisms of the association of inflammation with the development of hypertension has not been clarified.

Hypothesis:
Inflammation affect the development of hypertension via vascular and/or renal abnormalities.

Methods:
The association of inflammation with vascular and/or renal abnormalities, and the association of such abnormalities with elevation of the blood pressure were examined by analyzing longitudinal repeated-measures data using a linear mixed model (LMM) approach in a 9-year prospective observational study. 3908 middle-aged Japanese employees of the construction company (aged 41 ± 9 years old) without hypertension at the study baseline. The blood pressure, brachial-ankle pulse wave velocity (baPWV), radial augmentation index (rAI), estimated glomerular filtration rate (eGFR; based on the serum creatinine) and serum C-reactive protein (CRP) levels were measured annually in the subjects from year 2007 to year 2015.

Results:
During this study period, 520 subjects (13%) developed hypertension. LMM analysis of the obtained repeated-measures data after adjustments for covariates revealed the following: 1) At each annual measurement, higher annual values of the log-transformed CRP were associated with a higher annual increase of the baPWV (beta = 62.647 ± 26.017, p < 0.001), but not the annual increase of the rAI or annual decrease of the eGFR; 2) higher annual values of the baPWV were associated with a higher annual elevation of the blood pressure (beta = 0.032 ± 0.001, p < 0.001).

Conclusions:
In middle-aged Japanese subjects without hypertension at the study baseline, the presence of inflammation, as reflected by serum CRP levels, appears to be associated with the longitudinal increase of the arterial stiffness, but not with abnormal progression of the central hemodynamics or decline of the glomerular filtration rate. In turn, this longitudinal increase in the arterial stiffness appears to be associated with the longitudinal elevation of the blood pressure to hypertensive range. Thus, inflammation may play a role in the pathogenesis of hypertension via the accelerated progression of arterial stiffness.
Abstract 14017: Prognostic Impact of Peak Heart Rate During Exercise in Atrial Fibrillation
Authors: Aihara Kazufumi , Kato Yuko , Suzuki Shinya , Uejima Tokuhisa , Semba Hiroaki , Kano Hiroto , Matsuno Shunsuke , Takai Hideaki , Otsuka Takayuki , Oikawa Yuji , Nagashima Kazuyuki , Kirigaya Hajime , Sagara Koichi , Kunihara Takashi , Yajima Junji , Sawada Hitoshi , Aizawa Tadanori , Yamashita Takeshi
Published: April 2024

Background and Aim:
Heart rate (HR) during exercise is known to be associated with cardiovascular morbidity/mortality in sinus rhythm (SR). However, the relationship between HR profile during exercise and cardiovascular prognosis remain unknown well in patients with atrial fibrillation (AF). We previously reported that peak VO2 but not resting HR is an independent predictor for future heart failure (HF) events in patients with AF. The aim of this study was to investigate the relationships between HR profile during exercise and future heart failure (HF) events in patients with AF and those with SR simultaneously.

Methods:
We used the cohort from the single-hospital database between 2004 and 2013 (N=22,230). Of the total, 2,231 patients (AF; N=321, SR; N=1910) who underwent symptom-limited cardiopulmonary exercise testing were analyzed. HF events were defined as either hospitalization for HF or death from HF. They were categorized according to the quartiles of peak HR in each rhythm.

Results:
Significant positive relationships between peak HR quartiles and peak VO2 were observed in both groups (AF: p for trend <0.001, SR: p for trend <0.001). Peak HR quartiles were also apparently negatively associated with the incidence of HF events in both groups (Figure). In univariate analysis for HF events, peak HR was significantly related to HF events in both rhythms. Multivariate analysis showed that peak HR was a statistically significant predictor for HF events in the AF group even after adjusted for age, use of HR lowering drugs, left ventricular ejection fraction, organic heart disease and eGFR. However, in the SR group, predictive power of peak HR was weakened after the same adjustment.

Conclusion:
It was suggested that peak HR is an independently strong predictor for future HF events in patients with AF.
Abstract 14021: Increased Cardiac Conduction Abnormalities After Tricuspid Annuloplasty During Cardiac Transplantation: A Single Center 3 Year Retrospective Review
Authors: Rubin Geoffrey , Bayne Joseph , Givens Raymond , Noonavath Meghana , Takayama Hiroo , Takeda Koji , Naka Yoshifumi , Garan Hasan , Farr Maryjane , Wan Elaine
Published: April 2024

Introduction:
Tricuspid annuloplasty (TA) performed in donor hearts at time of orthotopic cardiac transplantation to reduce tricuspid regurgitation and preserve right ventricular function in transplant recipients has been shown to improve transplant outcomes. However, after incorporation of TA into our surgical protocol, we have observed an increased incidence of conduction abnormalities including right bundle branch block and heart block suggestive of AV nodal injury after incorporation of TA into the transplant surgical protocol.

Methods:
We conducted a retrospective review of medical charts of 97 adult cardiac transplantation recipients, as well as, information available on the donor hearts over a three year time period from 2014 to 2016 at Columbia University Medical Center, New York, NY.

Results:
No donor hearts had RBBB prior to harvest. Before vs. after incorporation of the TA procedure into the transplant protocol: the mean age of transplant recipients was 52 ± 1.7 s.e.m years of age vs. 57 ± 1.3 s.e.m years of age. 6 patients (11.8%, n=51) vs. 19 TA patients (42.2%, n=45) had RBBB postoperatively (p<0.005). Development of RBBB was increased in 27 mm (52%) vs 25 mm TA (35%), p=NS. Only 1 recipient (1.9%, n=51) vs. 4 TA recipients (8.8 %, n=45) had complete heart block within 30 days postoperatively (p=0.19), two of whom went on to receive implantation of permanent pacemakers. One of the two patients ultimately recovered AV conduction.

Conclusions:
There was a 3.6 fold increase in RBBB and 4.6 fold increase in incidence of AV block after incorporation of TA to the transplant surgical protocol at our center. Our results suggest that TA may cause injury to the conduction system of the donor heart. This is the first retrospective study demonstrating significant conduction abnormalities after incorporation of TA into the transplant surgical protocol.
Abstract 14025: Mild QTc Prolongation was Associated With Cardiovascular Events in Japanese Male Patients With Cardiovascular Risk Japan Morning Surge Home Blood Pressure (J-HOP) Study
Authors: Arima Seigo , Kabutoya Tomoyuki , Hoshide Satoshi , Kario Kazuomi
Published: April 2024

Introduction:
The relationships between QTc intervals and the risk of cardiovascular (CV) events could differ among ethnicities or between subjects with/without left ventricular hypertrophy (LVH).

Hypothesis:
We hypothesized that mild QTc prolongation was associated with CV events in Japanese patients with CV risk factors.

Methods:
Subjects were 3,592 patients enrolled in the Japan Morning Surge Home Blood Pressure Study who had one or more CV risk factors. Corrected QT intervals (QTc) were calculated using the Bazett formula. Prolonged QTc interval was defined as ≥440 ms in men and ≥460 ms in women on electrocardiogram (ECG). We divided patients into 3 subgroups according to the percentile of QTc (shortest 10%, middle 80%, and longest 10%). The primary endpoints were fatal/nonfatal CV events (myocardial infarction, stroke, hospitalization for heart failure, aortic dissection). The Sokolow-Lyon criteria (RV5(6)+SV1) ≥35 mm were used to diagnose LVH.

Results:
During the mean follow-up period of 48±39 months, there were 138 CV events. In male patients, those with prolonged QTc (N=57) were more likely to suffer CV events than those without prolonged QTc (N=1523) (log rank 6.22, p=0.013). A Cox proportional hazards model including age, hypertension, dyslipidemia and diabetes revealed that prolonged QTc was a significant independent predictor of CV events in male patients (hazard ratio 2.21, 95%CI 1.01-4.82, p=0.047). In female patients, CV events were similar in prolonged QTc (N=33) and non- prolonged QTc patients (N=1766, p=0.73). In male patients, the longest 10% of QTc patients (QTc≥406ms, N=157) were more likely to suffer CV events than those in the middle 80% of QTc patients (QTc 332-405ms, N=1265) and shortest 10% of QTc patients (QTc<332ms, N=157) (log rank 16.57, p<0.001). In the absence of LVH (N=1308), male patients in longest 10% of QTc suffered more CV events than those in the other groups (log rank 6.61, p=0.037), and in the presence of LVH (N=272), males in the longest 10% of QTc also suffered more CV events than those in the other groups (log rank 13.73, p=0.001).In female patients, CV events were similar in three subgroups.

Conclusions:
Mild QTc prolongation was associated with CV events in Japanese male patients with a CV risk with or without ECG-LVH.
Abstract 16627: Predictors of Response to Exercise Training in Patients With Hypertrophic Cardiomyopathy
Authors: Kolevar Matthew , Bragg-Gresham Jennifer , Hornsby Whitney , Helms Adam S , Day Sharlene M , Saberi Sara
Published: April 2024

Introduction:
RESET-HCM was a randomized clinical trial of 16 weeks of moderate-intensity exercise training (ExT) in patients with hypertrophic cardiomyopathy (HCM). Compared with usual activity (UA), ExT resulted in a modest but significant 6% improvement in mean peak oxygen consumption (VO
2peak
), the best measure of cardiorespiratory fitness (CRF). Studies of heart failure populations have shown that ≥15% improvement in VO
2peak
can be achieved with ExT.

Hypothesis:
We hypothesize that intervention-, disease-, and patient-specific factors differentially influence VO
2peak
response to ExT.

Methods:
Data from 113 subjects were analyzed. Those who achieved ≥ 15% improvement in VO
2peak
in response to ExT were categorized as high responders (HR), while low responders (LR) were those who did not. Baseline characteristics and activity log data were compared between HR and LR. Logistic regression investigated associations between VO
2peak
response and these measures.

Results:
Twenty-two subjects were HR (16/57 [28.1%] in the ExT group vs. 6/56 [10.7%] in the UA group, p=0.02). HR had fewer comorbidities such as hypertension (9.1% vs 26.4%, p=0.03) and diabetes mellitus (0% vs 7.7%, p=0.01). Ejection fraction (EF) was lower among HR than LR (68.6% vs 71%, p=0.02), but other measures of cardiac remodeling, including hypertrophy and fibrosis burden, resting left ventricular outflow obstruction, and diastolic function did not differ. HR had lower baseline VO
2peak
(18.4 vs 22.6 mL/kg/min, p=0.01). Although adherence to the frequency element of exercise prescriptions decreased over time in both groups, HR were 25% more adherent (p=0.02), exercising an average of 1 more day per week (3.8 vs 2.8, p=0.02). On multivariate analysis, baseline VO
2peak
(OR: 0.79; 95% CI: 0.68-0.92) and EF (OR: 0.85; 95% CI: 0.74-0.98) were independent predictors of ≥15% improvement in VO
2peak
after adjustment for age and sex. Higher exercise frequency (OR: 1.37; 95% CI: 0.97-1.95) was also an important factor.

Conclusions:
Higher exercise frequency, lower CRF at baseline, and lower EF predicted a greater magnitude of response to moderate intensity ExT in HCM patients. Future studies will be necessary to make the response to ExT more uniform across a heterogeneous group of HCM patients.
Abstract 16664: Intrapatient Variability in the Brockenbrough-Braunwald-Morrow Sign and Peak Instantaneous Left Ventricular Outflow Gradients in Obstructive Hypertrophic Cardiomyopathy
Authors: Bauch Terry D , Smith Alexandra J , Watts James A , Rubal Bernard J , Murgo Joseph P
Published: April 2024

Introduction:
Although the variability in left ventricular outflow tract (LVOT) gradients in patients with hypertrophic cardiomyopathy (HCM) is well known, the value of pulse pressure (PP) changes with ectopy for predicting changes in LVOT gradient remains unreported.

Hypothesis:
This study examines the intrapatient variability in peak instantaneous LVOT gradients and aortic pulse pressure (PP) associated with the Brockenbrough-Braunwald-Morrow sign (BBM sign) compared with beat-to-beat variability.

Methods:
Variability in continuously recorded, high-fidelity left ventricular and aortic pressure waveforms were evaluated by computer-aided analysis in the resting state (N = 659 beats) and during supine exercise (N = 379 beats) in a symptomatic patient with a resting LVOT gradient >30 mmHg.

Results:
BBM sign was observed in 92.9% (26/28) of post-PVC beats at rest and the post PVC PP decreased 11.8±8.2% (P<0.001) compared with a 148.3±49.5% (P<0.001) increase in the LVOT gradient. During exercise, BBM sign was noted in 84.2% (32/38) of post-PVCs beats and PP decreased 4.0±6.3% (P<0.001) compared with a 74.2±37.5% (P<0.001) increase in LVOT gradient. PP decreases were also noted in 89.5% (17/19) beats during sinus arrhythmia following prolonged RR intervals. Changes in pulse pressure with ectopy poorly predicted quantitative changes in the LVOT gradient (R
2
≤ 0.198). However, component analysis of the LVOT gradient suggests that beat-to-beat variability provides information similar to ectopic provocation in characterizing gradients in HCM and that rest and exercise changes converge to a common reference value.

Conclusions:
Although caution is suggested when interpreting pulse pressure changes with the BBM sign as surrogate for measuring LVOT gradients, this study suggests that analysis of hemodynamic variability in HCM may prove useful in characterizing the severity of obstruction.