bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9271: Significance of Primary Therapy With Intravenous Immunoglobulin Plus Prednisolone For Severe Kawasaki Disease: Result From Japanese Multicenter Randomized Clinical Trial.
Authors: Kobayashi Tohru , Saji Tsutomu , Otani Tetsuya , Takeuchi Kazuo , Nakamura Tetsuya , Arakawa Hirokazu , Kato Taichi , Hara Toshiro , Hamaoka Kenji , Ogawa Shunichi , Miura Masaru , Nomura Yuichi , Fuse Shigeto , Ichida Fukiko , Seki Mitsuru , Morikawa Akihiro ,   The RAISE Study Investigators
Published: April 2024

Background
Recent re-assessment reports have suggested that primary corticosteroid therapy for severe Kawasaki disease patients might be beneficial.

Methods
We conducted a multicenter, prospective, randomized, open, blinded-endpoints, and parallel-group study to determine whether the addition of prednisolone to conventional intravenous immunoglobulin therapy for severe Kawasaki disease reduces the risk of coronary artery abnormality. Between September 2008 and December 2010, 248 severe Kawasaki disease patients with risk score ≥5 points were randomly assigned to receive either intravenous immunoglobulin (IVIG group; n = 123) or intravenous immunoglobulin plus prednisolone (IVIG+PSL group; n = 125). The primary endpoint was presence of coronary artery abnormality during study period. Secondary endpoints included incidence of coronary artery abnormality at week 4, Z score of coronary arteries, duration of fever after enrollment, need for additional rescue therapy, serum levels of C-reactive protein (CRP) at weeks 1 and 2 after enrollment, and severe adverse events.

Results
Incidence of coronary artery abnormality during study periodt was significantly lower in the IVIG+PSL group than in the IVIG group (3% vs 23%, respectively; P<0.001). Similarly, incidence of coronary artery abnormality at week 4 after enrollment was significantly lower in the IVIG+PSL group than in the IVIG group (3% vs 13%, respectively; P=0.014). Furthermore, IVIG+PSL group had shorter duration of fever after enrollment (P<0.001), lower risk of need for additional rescue therapy (P<0.001), and lower CRP level at weeks 1 and 2 (both P<0.001) compared with IVIG group. Incidence of severe adverse events was similar in the two groups.

Conclusions
Intravenous immunoglobulin plus prednisolone is superior to intravenous immunoglobulin alone to prevent coronary artery abnormality in patients with severe Kawasaki disease. (UMIN-CTR Number, UMIN000000940.)
Abstract 9290: Clinical, Electrocardiographic, and Genetic Characteristics of Patients with Idiopathic Ventricular Fibrillation Associated with Early Repolarization
Authors: Watanabe Hiroshi , Nogami Akihiko , Ohkubo Kimie , Makiyama Takeru , Hayashi Yuka , Shimada Toshio , Nagao Satomi , Yagihara Nobue , Takehara Naofumi , Kawamura Yuichiro , Sato Akinori , Okamura Kazuki , Chinushi Masaomi , Hosaka Yukio , Sato Masahito , Fukae Satoki , Oda Hirotaka , Okabe Masaaki , Maemura Koji , Horie Minoru , Watanabe Ichiro , Aizawa Yoshifusa , Makita Naomasa
Published: April 2024

Background:
Early repolarization or J-wave has generally been considered benign for decades. However, we and others recently reported that early repolarization is associated with idiopathic ventricular fibrillation (VF). This study aimed to investigate its clinical and genetic characteristics and to identify risk factors for arrhythmia events.

Methods and results:
This study included 38 patients (32 men; age, 42±17 years) with idiopathic VF associated with early repolarization. All of the patients had arrhythmia events. The events occurred during sleeping (n=12) or at rest (n=9) in more than half of the patients. An electrical storm defined as ≥3 episodes of VF during 24 hours was observed in 8 patients (21%). A family history of sudden cardiac death was reported in 7 patients (18%). In 12-lead electrocardiograms, early repolarization was present in the inferior leads in 9 patients, in the lateral/precordial leads in 12 patients, and in both of the inferior and lateral/precordial leads in the remaining 17 patients. Conduction disease, mostly prolongation of PR interval, was present in 13 patients (34%). The heart rate was slower, and the PR interval and QRS duration were longer in patients with idiopathic VF compared to 190 age- and sex-matched healthy controls. VF was inducible by programmed electrical stimulation in 15 of 27 patients (55%). We identified loss-of-function mutations in
SCN5A
in 3 unrelated patients, and interestingly, His-ventricular interval was prolonged in all of them. During a follow-up of 6.0±5.7 years, VF recurred in 9 patients. Multivariate analyses revealed that a family history of sudden cardiac death and a history of electrical storm were associated with increased risk of arrhythmia recurrences. The age of arrhythmia onset, gender, lead location of early repolarization, activity at the initial event, conduction disease, or inducibility of VF were not associated with the risk of recurrences.

Conclusions:
This study showed the clinical and genetic characteristics of idiopathic VF associated with early repolarization, suggesting the underlying mechanism for arrhythmia susceptibility. Our data may be useful for risk stratification for arrhythmia events.
Abstract 9297: ST-Segment Category at Acute Presentation is Associated with Time Course of Coronary Artery Disease Progression in Patients with Acute Coronary Syndromes
Authors: Nakachi Tatsuya , Ishii Nao , Kusakawa Yuka , Kato Shingo , Muto Kazuhiro , Ohkusu Yasuo , Nakagawa Takeshi , Fukui Kazuki , Umemura Satoshi , Kimura Kazuo
Published: April 2024

Background:
Acute coronary syndrome (ACS) is categorized, according to the presenting electrocardiogram, into ST-segment elevation ACS (STEACS) and non-ST-segment elevation ACS (NSTEACS). Several studies have shown that early mortality was higher for STEACS, but late mortality remained consistently higher for NSTEACS. However, its underlying mechanism is unclear.

Methods:
We studied 219 patients (179 men, age 64 + 10 years) with STEACS (n= 93) or NSTEACS (n = 126) who underwent percutaneous coronary intervention (PCI) for culprit lesion during initial hospitalization. Estimated glomerular filtration rate (eGFR) was calculated according to MDRD study formula at initial presentation. All patients underwent serial coronary angiograms (CAGs) performed immediately before PCI ,and at 6 + 3 months and 60 + 10 months after presentation. Coronary artery disease progression (CP) was defined as an increase > 15 % in stenosis severity of lesion in nonculprit artery between 2 serial CAGs.

Results:
There were no significant differences in age, sex, coronary risk factors, lipid profiles, eGFR, multivessel disease, follow-up periods and medication between STEACS and NSTEACS. The rate of CP between first and second CAGs did not differ according to ST-segment category at acute presentation. Compared to STEACS, NSTEACS had higher rate of CP between second and final CAGs (Figure). Multivariate analysis revealed that the independent predictors of CP between second and final CAGs were NSTEACS (odds ratio 3.01, 95% CI 1.52 to 5.94, p=0.002), eGFR < 60 ml/min/1.73m
2
(odds ratio 2.32, 95% CI 1.11 to 4.84, p=0.025) , and diabetes mellitus (odds ratio 2.18, 95% CI 1.12 to 4.21, p=0.021).

Conclusion:
ST-segment category at initial presentation is associated with the persistency of the widespread coronary disease activity following presentation in patients with ACS undergoing PCI. This may partly explain the time-dependent differences in outcomes among patients with STEACS and NSTEACS.
Abstract 9309: Benefit of Prasugrel in ST-Elevation Myocardial Infarction According to Timing of Percutaneous Coronary Intervention: Insight from the TRITON-TIMI 38 Study
Authors: Udell Jacob A , Braunwald Eugene , Antman Elliot M , Murphy Sabina A , Montalescot Gilles , Wiviott Stephen D , TRITON-TIMI 38 Investigators
Published: April 2024

Background:
Prasugrel is approved as an alternative to clopidogrel in STEMI. Treatment strategies and outcomes for primary PCI (<12 hours from onset [PPCI]) versus secondary PCI (>12 hours from onset or initial medical therapy [SecPCI]) may differ.

Methods:
We performed a pre-specified analysis within the 3534 STEMI patients in TRITON-TIMI 38. Patients were randomized to prasugrel or clopidogrel on presentation if PPCI was intended or at the time of SecPCI. Since the clinical importance of procedural MI remains controversial, we performed sensitivity analyses excluding these events from the primary endpoint.

Results:
2340 (68%) STEMI patients underwent PPCI. As previously reported, the reduction in the primary endpoint (CV death, MI, or stroke) with prasugrel versus clopidogrel was significant in STEMI patients at 30 days (30d) and 15 months (15m). Efficacy appeared consistent among PPCI patients (30d HR 0.81 [95% CI 0.60-1.09]; 15m HR 0.89 [0.69-1.13]) and SecPCI patients (30d HR 0.51 [0.34-0.76]; 15m HR 0.65 [0.46-0.93]; Figure 1+2). There was no interaction between timing of PCI and randomized treatment with respect to outcome at 30d or 15m (p-interaction>0.05 for both). Reduction in CV death/spontaneous MI/stroke with prasugrel remained consistent among PPCI and SecPCI patients (Figure 1+2) with no interaction with timing of PCI and treatment (p-interaction>0.05 for both). Trends in reduction of spontaneous MI were observed in PPCI (30d HR 0.53 [0.28-1.01]; 15m HR 0.72 [0.48-1.10]) and SecPCI (30d HR 0.26 [0.09-0.80] and 15m HR 0.57 [0.29-1.14]). TIMI major bleeding events were infrequent, however bleeding associated with prasugrel as compared to clopidogrel was consistent in the STEMI cohort, and either PCI subgroup, with the overall trial result (PPCI 15m HR 1.52 [0.87-2.65]; SecPCI 15m HR 0.39 [0.14-1.11]).

Conclusion:
In patients with STEMI, the efficacy and safety of prasugrel as compared to clopidogrel is consistent irrespective of the timing of PCI.
Abstract 9317: Combined Assessment of Flow-Mediated Dilatation of the Brachial Artery and Brachial-Ankle Pulse Wave Velocity Has an Additive Value on Prediction of Future Cardiovascular Events in Patients with Chronic Coronary Artery Disease
Authors: Sugamata Wataru , Uematu Manabu , Deyama Juntarou , Hirano Mitsumasa , Nakamura Takamitsu , Kitta Yoshinobu , Sano Keita , Fujioka Daisuke , Saitou Yukio , Kawabata Ken-ichi , Obata Jun-ei , Kugiyama Kiyotaka
Published: April 2024

Flow-mediated dilatation (FMD) of the brachial artery can assess systemic endothelial dysfunction that is an early phase of atherosclerosis. The brachial-ankle pulse wave velocity (PWV) reflects systemic arterial stiffness. Both are widely used as noninvasive methods for assessment of systemic atherosclerosis. This study examined the hypothesis that the combined assessment of FMD and PWV may have an additive effect on the prediction of cardiovascular (CV) events in patients with chronic coronary artery disease (CAD).

Methods and Results:
FMD and PWV were measured in 625 consecutive patients with chronic CAD. All study patients were prospectively followed up for < 8.5 years or until occurrence of one of the following CV events: cardiac death, non-fatal myocardial infarction (MI), heart failure requiring hospitalization, recurrent or refractory unstable angina pectoris (uAP) requiring coronary revascularization and ischemic stroke. During a mean follow-up of 71 ± 26 months, 79 events occurred (14 cardiac death, 19 MI, 10 heart failure, 31 uAP, 5 stroke). FMD value was not significantly correlated with PWV value, although there was a tendency to have an inverse correlation (r = - 0.11, p = 0.14). Patients with a CV event had lower FMD and higher PWV than those without a CV event (FMD: 3.56 ± 0.28% vs. 5.11± 0.56%, p < 0.01. PWV: 1757 ± 36 cm/sec vs. 1645 ± 38 cm/sec, p = 0.01). In a multivariate Cox hazards analysis, low FMD (< 4.3%, 50
th
percentile of study patients) and high PWV (≥ 1660 cm/sec, 50
th
percentile of study patients) were significant predictors of CV events (HR;1.58 and 1.66, 95% CI 1.01 - 2.48 and 1.05 - 2.61, respectively, both p < 0.05) that were independent of age, LDL-C levels, hypertension, smoking and diabetes. When outcomes were stratified according to low FMD and high PWV in combination or alone, the combination of low FMD and high PWV was the strongest predictor of CV events, followed by low FMD alone or high PWV alone on the basis of the
c
-statistic (area under the ROC curve; 0.75, 0.60 and 0.63, respectively).

Conclusions:
Combined assessment of FMD and PWV has an additive value on the prediction of future cardiovascular events in patients with CAD. This combined assessment may be useful for risk stratification in patients with CAD.
Abstract 9322: Remnant Lipoproteinemia is a Predictor of Coronary Events in Patients with Coronary Artery Disease and Chronic Kidney Disease
Authors: Saito Yukio , Nakamura Takamitsu , Sugamata Wataru , Deyama Juntaro , Uematsu Manabu , Sano Keita , Fujioka Daisuke , Kitta Yoshinobu , Kawabata Ken-ichi , Obata Jun-ei , Kugiyama Kiyotaka
Published: April 2024

Although triglyceride (TG) levels are increased in chronic kidney disease (CKD), the independence of high TG levels as a risk for coronary events remains debatable. We have previously shown that remnant lipoproteins, one of TG-rich lipoproteins, is a strong risk for future coronary events independent of low HDL-C levels and high LDL-C levels in patients with coronary artery disease (CAD). Thus, this study examined predictive value of remnant lipoproteins for coronary events in CAD patients with CKD.

Methods:
Fasting serum levels of remnant lipoproteins (remnant-like lipoprotein particles cholesterol; RLP-C) were measured by an immunoseparation method in 229 patients with CAD and CKD (estimated GFR < 60 ml/min/1.73m
2
, excluding hemodialysis patients). All patients were prospectively followed up for a period of 18 months or until occurrence of one of following events: cardiac death, nonfatal myocardial infarction (MI), unstable angina requiring unplanned coronary revascularization or worsening heart failure requiring hospitalization.

Results:
During follow-up period, events occurred in 28 (37%) patients with higher levels of RLP-C (> 5.0 mg/dL, 75
th
percentile of the distribution) (5 cardiac death, 4 MI, 15 unstable angina, 4 heart failure), while events occurred in 18 (11.7%) patients with lower RLP-C levels (< 5.0 mg/dL) (2 MI, 14 unstable angina, 2 heart failure) (p<0.0001). In Kaplan-Meier analysis, higher RLP-C levels resulted in a higher probability for the development of coronary events than lower RLP-C levels (p < 0.01). In multivariate Cox proportional hazards analysis, higher RLP-C levels were a significant predictor of coronary events (HR 1.8, 95%CI 1.3 - 6.9, p < 0.01), that was independent of TG levels and the Framingham risk variables. In
c
-statistics, RLP-C levels had an incremental effect on the predictive value of the Framingham risk variables for coronary events (area under ROC curve: RLP-C + Framingham risks 0.83 vs. Framingham risks alone 0.75, p < 0.01).

Conclusions:
High remnant lipoprotein levels are an independent predictor of coronary events in CAD patients with CKD. Assessment of remnant lipoprotein levels may be useful for risk stratification for coronary events in patients with CKD.
Abstract 9324: Optimal Acute Plasma Glucose Level for Cardiac Arrest Patients in the Therapeutic Hypothermia Era
Authors: Kagawa Eisuke , Dote Keigo , Kato Masaya , Sasaki Shota , Nakano Yoshinori , Itakura Kiho , Ochiumi Yusuke , Takiguchi Yu
Published: April 2024

Introduction:
Hyperglycemia has adverse outcomes in resuscitated patients who have experienced cardiac arrest. Therapeutic hypothermia has a neuroprotective effect in these patients and improves outcome. However, the optimal acute plasma glucose level for cardiac arrest patients in the therapeutic hypothermia era is still unclear.

Hypothesis:
We assessed the hypothesis that mild to moderately acute hyperglycemia is associated with improved neurological outcome in cardiac arrest patients treated with hypothermia.

Methods:
Between September 2003 and May 2011, comatose survivors of cardiac arrest, who were treated with mild hypothermia, were retrospectively enrolled in this study. Plasma glucose was measured after the indexed cardiac arrest. The study patients were divided into four groups according to plasma glucose levels: Q1 (<11.1 mmol/l), Q2 (11.2-14.5 mmol/l), Q3 (14.6-18.4 mmol/l), and Q4 (>18.5 mmol/l). Neurological outcomes were assessed by cerebral performance categories at discharge. Cox proportional regression analysis was used to estimate independent predictors of favorable neurological outcome and optimal acute plasma glucose levels.

Results:
Median age, rate of ventricular fibrillation, and median time interval from collapse to return of spontaneous circulation in Q1 (N = 36), Q2 (N = 38), Q3 (N = 37), and Q4 (N = 37) patients were 58, 55, 63, and 57 y (P = 0.42); 42%, 76%, 62%, and 54% (P = 0.02); and 40, 23, 33, and 41 min (P = 0.01), respectively. The rates of favorable neurological outcome in Q1 (N = 36), Q2 (N = 38), Q3 (N = 37), and Q4 (N = 37) patients were 25%, 66%, 43%, and 16%, respectively. Q1 [odds ratio (OR) 0.21; 95% confidence interval (CI), 0.05-0.78] and Q4 (OR, 0.14; 95%CI, 0.03-0.56) were significantly associated with an unfavorable neurological outcome after adjusting for baseline characteristics.

Conclusions:
Optimal acute plasma glucose levels for cardiac arrest patients treated with hypothermia ranged from 11.2-18.4 mmol/l, which was usually thought to be hyperglycemia.
Abstract 9330: In-stent Restenotic Tissue with a Microchannel in Patients with Diabetes: Insights from Coronary Optical Coherence Tomography Image Analysis
Authors: Suzuki Nobuaki , Kyono Hiroyuki , Otsuki Shuji , Fu Qiang , Miyagawa Mutsuki , Hosogoe Naoyoshi , Saito Tomohisa , Ishikawa Shuichi , Miyazawa Akiyoshi , Watanabe Hidenori , Kozuma Ken , Isshiki Takaaki
Published: April 2024

Introduction
Coronary optical coherence tomography (OCT) allows the detection of subtle differences in patients with coronary artery disease. To date, OCT can virtually depict the various histological findings that occur at in-stent restenotic tissue. The present study investigated the clinical implications of microchannels located in in-stent restenotic sites.

Methods
We examined 48 consecutive in-stent restenotic (stenosis area, >50%) coronary artery lesions from 44 patients who underwent coronary OCT. OCT images were obtained with a time-domain OCT imaging system. The images were acquired during automatic-pull back (1 mm/s; 20 frames/s). A microchannel was defined as the low signal cavity with a diameter of 50-150 µm (Figure; white arrows) and was evaluated by 2 independent analysts. A third analyst provided the final decision when there was a discrepancy between the first and second analysts. Diabetes was diagnosed in accordance with the guidelines of the Japanese Diabetes Society.

Results
In total, 16,008 frames were evaluated. Microchannels were detected in 464 (2.9%) frames from 24 (50%) lesions in 22 (50%) patients. The kappa statistic on the lesion level between the 2 analysts was 0.875. Diabetes was diagnosed in 23 (52.3%) patients, and 7 (15.9%) patients had insulin therapy. The incidence of microchannels was significantly more frequent in patients with diabetes (65.2% vs. 33.3%, p = 0.03). In contrast, none of the coronary risk factors (hypertension, dyslipidemia, smoking) other than diabetes showed a significant relationship with microchannel formation.

Conclusion
Microchannels were frequently observed at in-stent restenotic tissue sites in patients with diabetes. The results indicated that microvessel formation, which is a common diabetic complication, is a unique pathophysiological factor of in-stent restenosis in patients with diabetes. Neovascular formation may be targeted to prevent in-stent restenosis in patients with diabetes.
Abstract 9348: ROCK2 in Vascular Smooth Muscle Cells Plays a Crucial Role for Hypoxia-Induced Pulmonary Hypertension in Mice
Authors: Shimizu Toru , Satoh Kimio , Tanaka Shin-ichi , Fukumoto Yoshihiro , Shimokawa Hiroaki
Published: April 2024

Background:
Pulmonary hypertension (PH) still remains a fatal disease characterized by progressive increase in pulmonary vascular resistance. We have previously demonstrated that the Rho-kinase (ROCK) pathway in vascular smooth muscle cells (VSMC) plays an important role in the pathogenesis of cardiovascular diseases by enhancing their migration and proliferation. Rho-kinase has 2 isoforms, ROCK1 and ROCK2, with different functions; ROCK1 for circulating inflammatory cells and ROCK2 for the vasculature. In this study, we thus examined whether ROCK2 in VSMC is involved in the pathogenesis of PH.

Methods and Results:
We developed VSMC-specific ROCK2-deficient (ROCK2
+/-
) and VSMC-specific ROCK2-overexpressing (ROCK2-Tg) mice. Both genotypes showed normal growth under physiological conditions. Chronic hypoxia (10% O
2
for 4 weeks) significantly increased ROCK2 expression and ROCK activity in lung tissues from littermates (P<0.05, n=4 each). The extent of the hypoxia-induced PH, as evaluated by the extent of pulmonary vascular remodeling, right ventricular (RV) systolic pressure and RV hypertrophy, was significantly reduced in ROCK2
+/-
mice and was significantly enhanced in ROCK2-Tg mice compared with the littermates (all P<0.05). Immunostaining showed that the number of CD45
+
inflammatory cells in the lung was significantly reduced in the ROCK2
+/-
mice and was increased in the ROCK2-Tg mice compared with the littermates, suggesting the role of vascular ROCK2 in inflammatory cell recruitment. In addition, VSMC proliferation (Ki67
+
cells) significantly correlated with the ROCK2 expression after chronic hypoxia, suggesting the role of ROCK2 in VSMC proliferation. In cultured mouse aortic VSMC, ROCK2 expression was decreased in ROCK2
+/-
VSMC (-21%) and was increased in ROCK2-Tg VSMC (+100%) compared with littermate VSMC. Hypoxia (1% O
2
for 24 hours) significantly increased ROCK activity in littermate VSMC (P<0.05, n=5 each). Scratch assay showed that migration activity was significantly reduced in the ROCK2
+/-
VSMC and was increased in the ROCK2-Tg VSMC compared with littermate VSMC (P<0.01).

Conclusions:
ROCK2 in VSMC plays a crucial role in the pathogenesis of hypoxia-induced PH through enhanced VSMC migration and proliferation.
Abstract 9349: Wave Reflection but Not Arterial Stiffness is Much Highly Correlated with Ambulatory Blood Pressure Parameters Including Blood Pressure Variability and Morning Blood Pressure Surge
Authors: Hsu Pai F , Chuang Shao Y , Cheng Hao M , Sung Shih H , Yu Wen C , Chou Pesus , Chen Chen H
Published: April 2024

Background:
With growing evidences that blood pressure (BP) variability, daily BP peak or morning BP surge are independently related to organ damage and future cardiovascular events. We try to invest the role of arterial stiffness and wave reflection, cardiac output in the association of those ambulatory BP parameters.

Methods:
A sample of 1156 normotensive and untreated hypertensive Taiwanese participants (546 women aged 30-79 years) was drawn from a community-based survey. All participants were recorded with 24 hours ambulatory blood pressure monitors. Besides, serum laboratory data, carotid-femoral pulse wave velocity (PWV, current gold standard for arterial stiffness), amplitude of the backward pressure wave decomposed from a calibrated tonometry-derived carotid pressure waveform (Pb, a transit-time independent index for wave reflections), and hemodynamic data include cardiac output were collected.

Results:
Mean 24 hours, day, and night systolic blood pressure (SBP), diastolic blood pressure (DBP), SBP standard deviation (SBPsd), DBP standard deviation (DBPsd), are all highly correlated to Pb, PWV, cardiac output (CO) and augmented pressure (r=0.506,0.274, 0.167, 0.419, all p<0.01 with regard to 24 hour SBPsd). At multi-variates regression models, Pb remains the strongest predictor for early morning BP surge, SBPsd, and DBPsd even after adjusting possible confounders include age, sex, cholesterol, triglycerides, creatinine, and body weight index.

Conclusion:
Reflective wave Pb is the strongest independent factor for predicting daily BP variability, (SBPsd, DBPsd) and even mean-SBP, DBP, morning BP surge but not central arterial stiffness.
Abstract 9364: MADIT-CRT: Resynchronization Patients Experience More Complications Than ICD-Only Patients but Outcomes are Not Significantly Impacted
Authors: Daubert James P , Hranitzky Patrick M , McNitt Scott , Klein Helmut U , Gold Michael R , Wilber David J , Brown Mary , Cannom David S , Zareba Wojciech , Moss Arthur J ,   Multicenter Automatic Defibrillator Implantation Trial-CRT (MADIT-CRT) Investigators
Published: April 2024

BACKGROUND and METHODS:
MADIT-CRT randomized 1820 patients with mild or asymptomatic heart failure symptoms, ejection fraction below 0.30 and QRS wider than 0.13 s in a 3:2 ratio to cardiac resynchronization therapy (CRT) with an ICD versus ICD alone and demonstrated a 41% reduction in heart failure (HF) events. CRT therapy requires additional lead(s) over a standard ICD. The additional LV (and RA) leads may contribute to an excess of complications with CRT. Lead or procedure-related complications could in turn lead to increased morbidity (such as heart failure (HF) events) and mortality in patients experiencing them. In this MADIT-CRT sub-study we sought to determine if complications were greater in the CRT arm and if patients experiencing a complication had unfavorable outcomes. Complications were classified by timing (0-30 days, > 30 days) and severity (non-severe and severe). HF and mortality events were adjudicated by a blinded events committee.

RESULTS:
Within the first 30 days, severe complications occurred significantly more frequent in the CRT arm than in the ICD-only arm, 5% vs 3% respectively (p=0.033). Between 30 days and end of follow-up, severe complications were similar in frequency in the two arms (p=0.223). Non-severe complications also were more frequent in the CRT arm than the ICD arm both within the first 30 days, 23% vs 9% respectively (p<0.01), and between day 30 and end of follow-up, 24% vs 15% (p,0.01). Patients experiencing either non-severe or severe complications had a similar HF or death event rate compared with patients free from complications (Figure).

CONCLUSIONS:
Severe complications occurred more frequently during the first 30 days in the CRT arm of MADIT-CRT and non-severe complications were more frequent throughout follow-up in the CRT arm. Fortunately, patients experiencing these complications as a group did not suffer more HF or death event rates.
Abstract 9385: Longer History of Diabetes Attenuates Benefit of Low-Dose Aspirin for Primary Prevention of Cardiovascular Events: A subanalysis from the JPAD Trial
Authors: Okada Sadanori , Morimoto Takeshi , Ogawa Hisao , Kanauchi Masao , Sakuma Mio , Soejima Hirofumi , Nakayama Masafumi , Doi Naofumi , Kubo Atsushi , Akai Yasuhiro , Kawano Takahiro , Jinnouchi Hideaki , Waki Masako , Sugiyama Seigo , Uemura Shiro , Saito Yoshihiko ,   the JPAD Trial Investigators
Published: April 2024

Benefit of low-dose aspirin for primary prevention of cardiovascular events remains controversial in patients with diabetes. We have conducted the JPAD trial to evaluate whether low-dose aspirin could prevent cardiovascular events in patients with type 2 diabetes and no history of cardiovascular disease. The JPAD trial randomly assigned 2,539 patients to the aspirin group (81 or 100 mg daily) or the no aspirin group, and followed for 4.4 years. In the JPAD main trial, low-dose aspirin did not reduce cardiovascular events overall. On the other hand, the efficacy of aspirin on primary prevention has been proven in general population at high risk by previous clinical trials. Therefore, we hypothesized that longer history of diabetes attenuates aspirin's benefit for primary prevention. The analysis included 2,301 patients whose onset of diabetes was reported. We stratified patients according to quartile duration of diabetes at baseline, and assessed aspirin's benefit for prevention of cardiovascular events. The hazard ratio of aspirin's benefit was 0.90 (95% confidence interval [CI]: 0.50 to 1.61), 1.05 (95% CI: 0.55 to 2.02), 0.90 (95% CI: 0.44 to 1.80), and 0.34 (95% CI: 0.12 to 0.81) for patients with baseline duration of diabetes of ≥12.3, 7.0 to 12.3, 2.9 to 7.0, and <2.9 years, respectively. Next, we analyzed to identify any threshold duration of diabetes below which aspirin's benefit changed. The longer duration of diabetes gradually decreased aspirin's benefit for prevention of cardiovascular events (Figure). Low-dose aspirin significantly reduced cardiovascular events in the patients with baseline duration of diabetes of ≤8 years. These results suggested that longer history of diabetes diminishes benefit of low-dose aspirin for primary prevention of cardiovascular events. Although further studies are needed, our findings might explain that the aspirin's benefit is proven in general population at high risk but not in all patients with diabetes.
Abstract 9387: The Inverse Association Between the Existence of Coronary Artery Disease and the Progression of Abdominal Aortic Aneurysm
Authors: Nakayama Atsuko , Morita Hiroyuki , Ando Jiro , Fujita Hideo , Nagayama Masatoshi , Takanashi Shuichirou , Sumiyoshi Tetsuya , Miyata Tetsurou , Nagai Ryozo
Published: April 2024

Objectives:
The aims of this study are to clarify the relationship among preoperative CAD (coronary artery disease), clinical manifestation of AAA (abdominal aortic aneurysm) and postoperative MACE (major adverse cardiac events).

Background:
A strong co-existence of CAD and AAA is well-known, however, it remains to be elucidated whether the existence of CAD is associated with the accelerated expansion rate of AAA.

Methods:
We conducted a retrospective cohort study on 823 consecutive patients receiving the coronary angiography before elective surgical repair for infrarenal fusiform AAA in two hospitals from 2003 through 2009. Ruptured, saccular, traumatic or inflammatory aneurysm were excluded in advance and cases with Marfan syndrome and cases with short followed-up period (<3 months) were also excluded. After exclusion, 665 patients were taken into consideration. All patients were underwent coronary angiography before surgery and their AAA size were followed up by CT scan at least more than 3 times until surgery.

Results:
The higher rates of postoperative MACE including cardiovascular death, acute coronary syndrome and cerebral infarction were observed in the CAD cases (n=342) compared with non-CAD cases (n=323) by Kaplan-Meier analysis (P=0.038). The initial follow-up size of AAA was 36.8±5.9 mm and the size at surgery was 52.3±10.8 mm. The existence of CAD cases was inversely associated with the accelerated expansion rate of AAA (CAD 3.8±2.1 mm/yr vs. non-CAD 5.0±3.2 mm/yr, HR 0.24, p<0.01). ECG change or asynergy in echocardiography at surgery were not associated with the expansion rate. Otherwise, only ex-smoker was the risk of the expansion rate (HR 1.67, p=0.037). Coronary risk factors except for ex-smoker, and the administration of antihypertensive drugs and statin weren’t significantly associated with the expansion rate. Multiple analyses indicated the same result.

Conclusions:
Although CAD was the strong risk of MACE after surgical repair for AAA, the counterintuitive inverse association between the existence of CAD and progression of infrarenal AAA was identified. This is the significant study on the relationship between CAD and the expansion rate of AAA.
Abstract 9401: Risk of Acute Kidney Injury is Not Higher in Patients Who Undergo Coronary Angiography and Cardiac Surgery in Close Succession
Authors: Ko Byungsoo , Mithani Salima , Garcia Santiago , Tholakanahalli Venkat , Adabag Selcuk
Published: April 2024

Background
Cardiac surgery and coronary angiography are both associated with higher risk of acute kidney injury (AKI). We hypothesized that the risk of postoperative AKI increases when coronary angiogram and cardiac surgery are performed in close succession, without sufficient time to allow kidney function to recover from the adverse effects of intravenous contrast.

Methods
We included 2133 consecutive patients who underwent cardiac surgery at the Minneapolis Veterans Administration Medical Center from 2004 to 2010. The outcome variable was AKI as defined by the AKI network (increase in creatinine >0.3 mg/dl or >50% from baseline 48 hours after surgery or hemodialysis) and the Risk, Injury, Failure, Loss, End-stage (RIFLE) criteria. Estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease (MDRD) method. Multivariable logistic regression analysis was used. Number of days between coronary angiogram and cardiac surgery was analyzed as a continuous variable.

Results
Patients were 66±10 years old. Mean preoperative creatinine and eGFR were 1.1±0.4 mg/dl and 75±22 ml/min/1.73 m
2
, respectively. Cardiac surgery was performed after a median 14 days (range 0-235) following coronary angiography. Of the 2133 patients, 680 (32%) met the AKI network definition, and 390 (18%) and 111 (5%) met the RIFLE risk and injury criteria of AKI, respectively. Age, body mass index, diabetes mellitus New York Heart Association class III/IV, cardiopulmonary bypass time, and impaired preoperative renal function (eGFR < 60 ml/min/1.73m
2
) were independent predictors of AKI. However, the time between coronary angiogram and cardiac surgery was not associated with AKI in univariable and multivariable analyses. Frequency of AKI was 35% in 433 patients who were operated within 3 days of coronary angiogram vs. 31% in 1700 patients who were operated after 3 days (p=0.17). Results were the same in subgroups of patients with impaired preoperative renal function and those who had contrast-induced nephropathy.

Conclusion
Risk of AKI after cardiac surgery is not influenced by the time between coronary angiogram and cardiac surgery. There is no need to delay cardiac surgery for the sole purpose of renal recovery after coronary angiogram.
Abstract 9430: Right Ventricular Apical and Free Wall Pacing, but Not Ventricular Septal Pacing Leads to Left Ventricular Reverse Rotation
Authors: Nozoe Masatsugu , Nishigami Kazuhiro , Honda Toshihiro , Nakao Koichi
Published: April 2024

Background:
Although left ventricular (LV) twisting has been recognized to play an important role in LV function, the impact of right ventricular (RV) pacing on LV twisting including rotational abnormality has not been fully understood. We investigated the influence of the pacing site on the rotational abnormality in patients underwent pacemaker implantation.

Methods and Results:
We evaluated 21 patients who underwent permanent pacemaker implantation for sick sinus syndrome or atrioventricular block (age 79 years) with preserved systolic function. According to RV pacing site, we divided our patients into septal pacing group (n=10) and non-septal (free wall or apex) pacing group (n=11). Rotation in the apical LV was evaluated using speckle tracking image in echocardiogram and the clockwise rotation of the apical wall or/and the counterclockwise rotation of the basal wall were defined as reverse rotation. We assessed LV rotational abnormality, under own beats or/and RV pacing rhythm.

Results:
During own beats, only one patient (1/21= 5%) with incomplete right branch block and atrial flutter demonstrated reverse rotation. In contrast, during RV pacing rhythm, 9 patients (9/21=43%) exhibited reverse rotation, in whom there were 8 patients in non-septal pacing group and 1 patient in septal pacing group. Reverse rotation was observed more in non-septal pacing group than in septal pacing group.

Conclusions:
RV apical or free wall pacing could induce the reverse rotation of the LV wall while RV septal pacing preserved LV rotation.
Abstract 9437: A Novel Index of Left Ventricular Contractility Loss Due to Mechanical Dyssynchrony, “Strain Rate Dispersion Index”, Predicts Responders to Cardiac Resynchronization Therapy
Authors: Iwano Hiroyuki , Yamada Satoshi , Watanabe Masaya , Mitsuyama Hirofumi , Yokoshiki Hisashi , Nishino Hisao , Yokoyama Shinobu , Kaga Sanae , Onozuka Hisao , Mikami Taisei , Tsutsui Hiroyuki
Published: April 2024

Background:
Echocardiographic time-delay indices of left ventricular (LV) mechanical dyssynchrony cannot accurately predict responders to cardiac resynchronization therapy (CRT). It may be due to the limitation that they cannot reflect LV contractility wasted by dyssynchrony. We thus determined whether a novel index of LV contractility loss caused by dyssynchrony, “strain rate dispersion index (SRDI)”, measured by using speckle tracking method could better predict the response to CRT than time-delay indices.

Methods:
We studied 27 patients with NYHA class III or IV heart failure (HF) and low LV ejection fraction (<35%) before and 6 months after CRT. In the apical 4-chamber view and mid-ventricular short-axis view, the standard deviation of time to segmental peak strain (St) among 6 segments (St-SD) was calculated as a time-delay index. SRDI was calculated as the average of segmental peak systolic strain rate (SR) minus global peak systolic SR, indicating the estimated global LV contractility loss caused by dyssynchrony. Longitudinal and circumferential indices were measured (L-St-SD and C-St-SD, L-SRDI and C-SRDI, respectively). Responder to CRT was defined as decrease of LV end-diastolic volume (ESV) >15% or improvement of HF symptom (NYH A class≥1).

Results:
ESV decreased from 164±108 to 137±99 ml (p<0.05) 6 months after CRT. Seventeen patients were identified as responders (63%). Although QRS duration and C-St-SD at baseline were comparable between responders and nonresponders, L-St-SD, L-SRDI, and C-SRDI were significantly higher in responders (L-St-SD: 153±61 vs 86±41 ms, p<0.01; L-SRDI: 0.21±0.07 vs 0.11±0.06 s
-
1
, p<0.01; C-SRDI: 0.19±0.11 vs 0.10±0.05 s
-
1
, p<0.05). QRS duration did not correlate with the changes in ESV (ΔΕSV) whereas L-St-SD (r=-0.50), C-St-SD (r=-0.53), L-SRDI (r=-0.45), and C-SRDI (r=-0.53) significantly correlated with ΔESV. By multivariate analysis, C-SRDI was the single independent predictor of ΔESV (β=-0.53, p<0.01). During the follow up, adverse events occurred in 8 out of 9 nonresponders; death in 2 patients and readmission due to worsening HF in 6 patients. In contrast, no such events occurred in the responders.

Conclusions:
SRDI could predict the response to CRT better than time-delay indices.
Abstract 9471: Temporal Relationship and Predictive Value of Urinary Acute Kidney Injury Biomarkers After Pediatric Cardiopulmonary Bypass
Authors: Krawczeski Catherine D , Goldstein Stuart L , Woo Jessica G , Wang Yu , Piyaphanee Nuntawan , Ma Qing , Bennett Michael R , Devarajan Prasad
Published: April 2024

Introduction
Acute kidney injury (AKI) occurs commonly after cardiopulmonary bypass (CPB). Serum creatinine (S
Cr
) is an inadequate marker for AKI. Rapidly detectable AKI biomarkers could allow early intervention and improve outcome. We evaluated the temporal pattern and predictive value (alone and in combination) of 4 urinary AKI biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), liver fatty-acid binding protein (L-FABP) and kidney injury molecule-1 (KIM-1) for CPB associated AKI.

Methods
Urine samples were obtained prospectively before and at intervals after CPB in 220 patients. AKI was defined as a ≥50% S
Cr
rise within 48h of CPB. The temporal pattern of biomarker elevation was established and biomarker elevations were correlated with AKI severity and clinical outcomes. Logistic regression was used to assess AKI predictors. Biomarker predictive abilities were evaluated by AUC, net reclassification improvement (NRI) and integrated discrimination improvement (IDI).

Results
AKI occurred in 27% of patients. NGAL increased in AKI patients at 2h after CPB and remained elevated at all timepoints (Figure). IL-18 and L-FABP increased at 6h and KIM-1 increased at 12h. Biomarker elevations correlated with disease severity and clinical outcomes, and improved AKI prediction above a clinical model. At 2h addition of NGAL increased the AUC from 0.74 to 0.85 (
p
<0.0001). At 6h NGAL, IL-18 and L-FABP each improved the AUC from 0.72 to 0.91, 0.84 and 0.77, respectively (all
p
<0.05). At 12h, all biomarkers improved the AUC. The added predictive ability of the biomarkers was supported by NRI and IDI. Biomarker combinations further improved AKI prediction.

Conclusion
Urine NGAL, IL-18, L-FABP and KIM-1 are sequential predictive AKI biomarkers and correlate with clinical outcomes after pediatric CPB. These biomarkers, particularly in combination, may be useful in establishing AKI timing and application of appropriately timed therapy.
Abstract 9485: Fragmented QRS Complexes, Conduction Disorder, and ST Segment Abnormality on Twelve-Lead Electrocardiography Predict Severe Cardiac Manifestation in Sarcoidosis
Authors: Nagao Satomi , Watanabe Hiroshi , Kodama Makoto , Tanaka Junichi , Suzuki Eiichi , Narita Ichiei , Aizawa Yoshifusa
Published: April 2024

Background:
Cardiac Sarcoidosis is a potentially lethal disease, but many patients with cardiac sarcoidosis are asymptomatic and the diagnosis is difficult before severe cardiac manifestation. Therefore, we aimed to identify electrocardiographic predictors of cardiac sarcoidosis.

Methods and Results:
This prospective, observational cohort study included consecutive 227 patients with non-cardiac sarcoidosis who did not have cardiac manifestations including advanced atrioventricular block, ventricular tachycardia, and systolic dysfunction at baseline. We studied the association of baseline electrocardiographic findings with risk of developing cardiac manifestation. In patients with non-cardiac sarcoidosis, the abnormities were frequently found in the baseline electrocardiogram; conduction disorder in 26 patients (11%), ST segment abnormality in 23 patients (10%), and fragmented QRS complex defined as various RSR’ patterns without typical bundle branch block in 19 patients (8%). During a follow-up of 6.3±3.7 years, 11 patients developed severe cardiac involvement including advanced atrioventricular block (4 patients), ventricular tachycardia (4 patients), and systolic dysfunction (3 patients). In multivariate analyses, baseline heart rate and PR interval were associated with the increased risk of developing cardiac manifestation (Table). QRS duration or corrected QT interval were not associated with cardiac manifestation. Multivariate analyses revealed that conduction disorder, ST segment abnormality, and fragmented QRS complex were associated increased the risk of developing cardiac involvement.

Conclusions:
We identified the electrocardiographic predictors of severe cardiac manifestation in patients with non-cardiac sarcoidosis, suggesting that these electrocardiographic abnormalities may reflect the early stage of cardiac involvement.
Abstract 9515: NMR Spectroscopy Uncovers Important Atherogenic Lipoprotein Abnormalities in Nonalcoholic Fatty Liver Disease: The Insulin Resistance Atherosclerosis Study (IRAS).
Authors: Haffner Steven M , Wagenknecht Lynne E , Lorenzo Carlos
Published: April 2024

Introduction:
Nonalcoholic fatty liver disease may be the most frequent cause of chronically elevated transaminase levels in the general population. One of these inexpensive and routinely measured enzymes, alanine aminotransferase (ALT) is an independent predictor of future cardiovascular disease and diabetes. ALT has been associated with dyslipidemia, but the extent of this relationship is not well described.

Hypothesis:
Because to its advantage over conventional methods, we hypothesized that proton nuclear magnetic resonance (NMR) spectroscopy could be better for detecting atherogenic lipoprotein abnormalities in nonalcoholic fatty liver disease. Thus, we analyzed the relation of ALT to lipoproteins measured by NMR spectroscopy and conventional methods in non-diabetic participants in the IRAS.

Methods:
Cross-sectional analysis of lipoproteins and apolipoproteins in 912 non-diabetic participants in the IRAS. In fasting single fresh plasma samples, we measured plasma lipoproteins by conventional methods and NMR spectroscopy and apolipoprotein B (apo B) by immunoprecipitation. Insulin sensitivity was measured by the frequently sampled intravenous glucose tolerance test.

Results:
After adjusting for age, sex, race/ethnicity, and clinic, ALT was associated with triglycerides, LDL and HDL cholesterol, and apo B (
Table
). ALT had significant relationships with large VLDL, total LDL, IDL, small LDL, and large HDL particle concentrations plus VLDL, LDL, and HDL particle sizes. ALT remained associated with total LDL, IDL, and small LDL particle concentrations, LDL particle size, and apo B after the additional adjustment for waist circumference and insulin sensitivity.

Conclusions:
NMR spectroscopy uncovers a more extensive relationship between atherogenic lipoprotein abnormalities and ALT in non-diabetic individuals. These abnormalities could partially explain the relation of ALT to future cardiovascular disease.
Abstract 9519: Acute Myocardial Ischemia Results in Renal Dysfunction via Systemic and Local Inflammation and Oxidant Stress, and LOX-1 Abrogation Attenuates This Phenomenon
Authors: Lu Jingjun , Deshmukh Abhishek , Wang Xianwei , Mitra Sona , Wang Wenze , Muniyappa Harisk , Hu Changping , Das Kumuda , Sawamura Tatsuya , Mehta Jawahar
Published: April 2024

Aims
It is assumed that acute myocardial infarction (MI) affects renal function.We tested this assumption in mice subjected to left coronary artery (LCA) occlusion. We also tested the hypothesis that LOX-1 deletion may inhibit systemic inflammation and oxidant stress and reduce renal dysfunction following MI.

Methods
Wild-type (WT) and LOX-1 KO mice were subjected to total and permanent LCA occlusion resulting in acute and extensive MI.Cardiac function (LVEF) was analyzed by echocardiography at days 3 and 21 post-MI.Renal function (serum BUN and creatinine) and morphology (H&E and trichrome staining) were assessed at same time points.The pro-inflammatory signals and markers of fibrosis were measured by Western blotting in the renal tissues.

Results
On day 3 after LCA ligation, there was a marked rise in pro-inflammatory cytokines in circulation (Multiplex system®). Importantly, there was a decline in renal function in association with >2-fold increase in renal mass,swelling of renal gomeruli and tubules and mild fibrosis in the renal medulla. There was a significant increase in the expression IL- 1β and VCAM-1, LOX-1, NADPH oxidase, and markers of fibrosis (collagen IV, procollagen-I and fibronectin) in renal tissues. On day 21, renal size was smaller, renal function and morphology were improved except for more fibrosis, and signals of inflammation and oxidant stress were less marked (P<0.05 vs. day 3). Deletion of LOX-1 resulted in a marked decline in systemic and renal pro-inflammatory and oxidant stress markers(all P<0.05 vs. wild-type mice) and better renal function. Cardiac function as well as survival were better in LOX-1 KO mice than in the wild-type mice (P<0.01) - all subjected to total LCA occlusion.

Conclusion
We demonstrate that acute MI results in renal dysfunction and histologic abnormalities reminiscent of acute injury to the kidneys. LOX-1 deletion by reducing pro-inflammatory and pro-oxidant signals results in significantly less renal dysfunction.