bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10990: Regulatory Implications of Different Definitions and Outcomes in Worsening Heart Failure
Authors: Kelly Jacob P , Mentz Robert J , Gallup Dianne , Anstrom Kevin J , Redfield Margaret M , Chen Horng H , O'Connor Christopher M , Hernandez Adrian F , Felker G. Michael
Published: July 2021

Introduction:
Despite the use of different definitions for worsening heart failure (WHF) in prior clinical trials and registries, an in-hospital WHF event has consistently been associated with worse patient outcomes. WHF is being considered as a potential endpoint to support drug approval. We combined patients from two acute HF trials conducted by the HF Network (ROSE-AHF and DOSE-AHF) to understand how different WHF definitions are associated with event rates.

Methods:
WHF was defined as persistent or worsening HF requiring rescue therapy including IV vasoactive agents, ultrafiltration, or mechanical support over 72 hours after randomization in ROSE and also included additional open label loop or thiazide diuretic in DOSE. We assessed the relationship between WHF and the composite endpoint (CE) of re-hospitalization, emergency room visits for HF and mortality through 60 days. We also assessed for a differential relationship of WHF from 0-24 hours, 24-48 hours and 48-72 hours post-randomization.

Results:
The overall incidence of WHF was 14.6% (24.1% in DOSE and 6.3% in ROSE). Patients who developed WHF had lower baseline systolic blood pressure, less peripheral edema and higher BUN. In the combined dataset, WHF was associated with an increase in the CE (hazard ratio [HR] 1.64; 95% confidence interval [CI] 1.11-2.42; p-value 0.01). However, the association between WHF and 60-day outcomes was significant in ROSE but not in DOSE (Table). The development of WHF between 48-72 hours compared with 0-24 hours or 24-48 hours was associated with improved outcomes ([HR] 0.48, 95% CI 0.27 - 0.88, p-value 0.02 and [HR] 0.45, 95% CI 0.26 - 0.78, p-value 0.004, respectively).

Conclusions:
A WHF definition that incorporated intensification of diuretics increased the event rate but was not associated with worse 60-day outcomes. The timing of a WHF event also had a differential association with outcomes. These data support the use of a standardized WHF definition in clinical trials.
Abstract 11417: Drug Abuse and Abdominal Pain: A case of Cocaine Induced Renal and Cardiac Infarction
Authors: Malhotra Rohit , Kotwal Anupam , Gore Joel
Published: July 2021

Introduction:
A 35 year old man presented with sudden onset left-sided chest pain and left flank pain. He had known non-ischemic cardiomyopathy (EF of 40-45%), non compliant with treatment. He was in severe pain with left costovertebral angle tenderness. Initial investigations showed a WBC count of 12,000, troponin of 3.72 and a urinalysis significant for 2+ proteins but no RBCs. Initial ECG showed <1 mm ST segment elevations with T wave inversions in inferior leads. Cardiac catheterization, did not demonstrate any flow limiting disease. Serial ECGs demonstrated a resolution of the aforementioned changes and his troponins trended down. Further review revealed an extensive history of cocaine use confirmed with a positive urine drug screen. Due to worsening abdominal pain, a CT abdomen with contrast was done which showed an acute segmental infarct on the upper pole of left kidney, but a CT angiogram did not show any evidence of obstructing vascular lesion or dissection. He was discharged on oral oxycodone, diltiazem and lisinopril.The patient returned in one week with exertional chest pain that was relieved with sublingual nitroglycerin. ECG on admission showed diffuse T wave inversions which improved in 6 hours. A repeat urine drug screen was positive for cocaine. Troponins peaked at 5.03. He then complained of persistent right flank pain and a repeat CT angiogram showed a new moderate-sized segmental infarct in the mid-pole of the
right
kidney. His pain was managed with oxycodone and he was eventually discharged home with isosorbide mononitrate, amlodipine and lisinopril.

Conclusions:
Renal infarcts may be sometimes missed in the absence of imaging, but must be suspected in drug users with flank pain and inferior EKG changes. In this case, it was hypothesized that renal arterial vasospasm led to the infarct; an extension of the known effect of cocaine on coronary vessels. This case highlights the importance of ruling out renal infarction as a cause for persistent abdominal pain. Identification of the cause of infarction is important, so as not to subject patients to long term anticoagulation. Guidelines for the treatment of drug induced renal infarction are lacking and the approach to such patients, as with all substance abusers, is abstinence.
Abstract 11478: Excellent Clinical Courses of Autologous Skeletal Myoblast Sheet Transplantation Compared to a Propensity Score-Matched Cardiac Resynchronization Therapy
(Best of Basic Science Abstract)
Authors: Imamura Teruhiko , Kinugawa Koichiro , Sakata Yasushi , Miyagawa Shigeru , Sawa Yoshiki , Yamazaki Kenji , Ono Minoru
Published: July 2021

Introduction:
We recently reported a multi-center, single-arm, phase II study that evaluated the efficacy and safety of autologous skeletal myoblast sheet (TCD-51073) transplantation. The advantage of this procedure over a control group has not yet been analyzed.

Hypothesis:
TCD-51073 has better clinical outcome compared with background-matched control group.

Methods:
Seven patients with advanced heart failure due to ischemic etiology (TCD-51073 group, New York Heart Association [NYHA] class III; left ventricular ejection fraction (LVEF) <35%) refractory to optimal medical and coronary revascularization therapy, received TCD-51073 at 3 study centers between 2012 and 2013 with a 2-year follow-up period. As previously reported, 112 patients received cardiac resynchronization therapy (CRT) with follow-up at the University of Tokyo Hospital between 2007 and 2014.

Results:
Of them, 21 patients were selected for the control group by propensity score matching. No significant difference in baseline variables between the groups was observed. LVEF and NYHA class improved significantly in the TCD-51073 group during the 6-month study period (p<0.05). During the 2-year follow-up, 7 patients (33%) in the CRT group and no patient in the TCD-51073 group died due to cardiac disease or received VAD implantation (p=0.128 by the log-rank test).

Conclusions:
Transplantation of TCD-51073 is clinically advantageous in facilitating LV reverse remodeling, improving HF symptoms, and preventing cardiac death in patients with ischemic etiology when compared to background-matched patients receiving CRT.
Abstract 11554: Chronic Cenderitide Administration Improves Cardiorenal Function and Remodeling in Experimental Heart Failure
Authors: Ichiki Tomoko , Harty Gail J , Huntley Brenda K , Sangaralingham S Jeson , Harders Gerald E , Burnett John C
Published: July 2021

Introduction:
Heart failure (HF) is a major health burden in which renal impairment worsens prognosis. Targeting the vicious cycle between heart and kidney may be a more optimal therapeutic strategy for HF. The cardiac natriuretic peptides have cardiorenal protective effects through their receptor GC-A and GC-B. We sought to determine the actions of chronic administration of the dual GC-A/GC-B agonist cenderitide (CD-NP) upon cardiorenal function in experimental HF.

Hypothesis:
Chronic cenderitide therapy will improve cardiorenal function in HF.

Methods:
Experimental canine HF was induced by rapid right ventricular pacing at 240 bpm for 10 days which mimics advanced overt HF in humans. Canines (n=5 of each group) were treated with or without cenderitide (Capricor Therapeutics) subcutaneous injection (SQ) twice per day (SQ-BID, 10 ug/kg/day), cenderitide continuous SQ pump (SQ-pump, 5 ng/kg/min), or oral enalapril (ACEi, 0.5 mg/kg/day) for 10 days from the beginning of pacing. We defined hemodynamics, echo parameters, circulating neurohumoral factors at day 11, and global gene profiles using RT-PCR microarrays related to the NP system, fibrosis, growth factors, and inflammation in left atrium which undergoes early remodeling in this model.

Results:
The SQ-pump group showed significantly less atrial and renal weights, higher cardiac output, glomerular filtration rate, and % ejection fraction, and lower systemic vascular resistance and plasma renin activity (all p<0.05) without lowering mean arterial pressure (MAP), whereas SQ-BID and ACEi lacked these effects together with lowering MAP compared to untreated canines. Gene profile analyses showed gene related to inflammatory cytokines such as TNF-alpha, IL-1 beta, and ROCK-2, and apoptosis such as caspase 7, Fas ligand, C-Myc and TP53 were suppressed (all p<0.05) in SQ-pump but not SQ-BID or ACEi compare to un-treated group.

Conclusions:
Continuous SQ administration of cenderitide demonstrated superior beneficial effects on cardiorenal function and remodeling together with inhibition of circulating renin and tissue inflammatory and apoptosis pathways. Our studies suggest that continuous administration of cenderitide may provide cardiorenal protection in the setting of advanced HF.
Abstract 11559: Long-term Outcomes of
in situ
versus Free Right Internal Thoracic Artery Grafting for Multivessel Coronary Artery Bypass Graft Surgery
Authors: Nishigawa Kosaku , Kin Hajime , Yamazaki Masataka , Naito Kazuhiro , Suenaga Etsuro , Takanashi Shuichiro
Published: July 2021

Introduction:
The right internal thoracic artery (RITA) is occasionally used as a free graft when it does not have sufficient length to reach the target vessels. We compared the long-term clinical outcomes in propensity score-matched patients undergoing coronary artery bypass grafting (CABG), using the RITA as an in situ or free graft.

Methods:
From September 2004 to June 2013, 1413 patients underwent isolated CABG using the bilateral internal thoracic artery (ITA) for the revascularization of the left coronary system. Of these, 1365 patients undergoing CABG using the RITA as an in situ graft (n=878) or a free graft (n=487) were retrospectively analyzed, after excluding 48 patients in whom at least 1 ITA was used as the inflow conduit of the other graft. A total of 461 pairs were matched using propensity scores calculated from 28 preoperative variables (C statistic, 0.62). The study end-points were repeat revascularization, cardiac death, and major adverse cardiac and cerebrovascular events (MACCE).

Results:
The average numbers of total distal anastomoses and distal anastomoses of the RITA were significantly higher in patients undergoing free RITA grafting than in those undergoing in situ RITA grafting (4.5±1.1 versus 4.3±1.1, P=0.003 and 1.5±0.6 versus 1.1±0.2, P<0.001, respectively). In patients undergoing free RITA grafting, the RITA was used as an aortocoronary bypass graft in 68 (14.8%) and as a composite graft in 393 (85.2%) patients. There was no significant difference in the postoperative mortality and morbidity between the groups. The mean follow-up period was 4.4 years. The Kaplan-Meier estimated cumulative survival rate free from repeat revascularization, cardiac death, and MACCE at 5 years in patients undergoing in situ versus free RITA grafting, was 89.5±1.6% versus 89.9±1.6% (P=0.519), 97.3±0.9% versus 98.0±0.7% (P=0.736), and 73.7±2.3% versus 75.3±2.4% (P=0.783), respectively.

Conclusions:
The long-term clinical outcomes in patients undergoing free RITA grafting were comparable to those in patients undergoing in situ RITA grafting. Free RITA grafting is the effective surgical alternative to in situ RITA grafting for CABG in patients with multivessel coronary artery disease.
Abstract 11567: A Rare Coincidence of Sitosterolemia and Familial Mediterranean Fever Identified by Whole Exome Sequencing
Authors: Tada Hayato , Kawashiri Masa-aki , Nohara Atsushi , Inazu Akihiro , Mabuchi Hiroshi , Yamagishi Masakazu
Published: July 2021

Background:
Sitosterolemia is an extremely rare inherited disease characterized by increased levels of plant sterols such as sitosterol, the cause of which is ATP-binding cassette (ABC) sub-family G member 5 or member 8 (ABCG5 or ABCG8) gene mutations. Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease characterized by recurrent self-limiting fever and serositis caused by mutations in FEMV gene. Molecular diagnosis for such cases through candidate-gene approaches have required a huge effort for a long time. Whole exome sequencing (WES) technologies have already accelerated genetic studies of Mendelian disorders, yielding approximately ~30 % of success for diagnosing, and there is great interest in extending this approach to this rare phenotype.

Methods and Results:
WES was performed for the proband (14 yr Japanese female, initial LDL cholesterol = 535 mg/dl) with histories of recurrent self-limiting episodes of fever and serositis. Among 206,430 variants found in the individual, we found 18,220 nonsense, missense, or splice site variants, of which 3,087 were rare (minor allele frequency ≤0.01 or not reported) in 1000 Genome (Asian population). Filtering assuming recessive pattern of inheritance successfully narrowed down the candidate to the compound heterozygous mutations in ABCG5 gene (c.1256C>T or p.Arg419His / c.1763-1T>G [splice acceptor site]) and MEFV gene (c.329 A>G or p.Leu110Pro / c.442G>C or p.Glu148Val). She was genetically diagnosed as a coincidence of sitosterolemia and FMF for the first time.

Conclusion:
We report the first case exhibiting rare coincidence of sitosterolemia and FMF identified using WES. Such comprehensive approach is useful to identify causative mutations for multiple unrelated inherited diseases.
Abstract 11591: Physiological CPR Quality Parameters and ROSC Indicators
Authors: Aelen Paul , Ordelman Simone , Woerlee Pierre , Noordergraaf Gerrit-Jan
Published: July 2021

Introduction:
Survival of cardiac arrest depends on CPR quality with blood flow as the main parameter. Blood flow is affected (among others) by compression depth. AHA guidelines advise the same depth range for all patients while their individual optimum may vary widely. An individual and time dependent optimum, guided by a non-invasive measure of blood flow may result in an increased survival chance. We investigated surrogate parameters that reflect invasive blood flow.

Methods:
VF was induced in seven anesthetized pigs of ± 30 kg. CPR was performed at 100 cpm with a proprietary automated CPR device. Compression depth was altered every 2 minutes (sequence: 4.0, 3.25, 4.0, 5.0, 6.0, 5.0 and 4.0 cm) to obtain a large range of blood flows. After 14 minutes of CPR defibrillation was performed. After a stable ROSC period the complete sequence was repeated.

Correlation coefficients between net carotid blood flow and potential surrogate parameters were calculated for the compression period in order to see what parameters could be used to reflect CPR quality. The same analysis was done for a 6 min period around the last compression (see figure 1) to investigate what parameters could be used to detect ROSC.

Results:
Average correlation coefficients between carotid flow and surrogate parameters are shown in figure 1.

Conclusion:
DBP and CPP were the best CPR quality and ROSC indicators. Contrary to CPP, DBP has the potential to be measured non-invasively (e.g. with a cuff) which in the future might be used to steer CPR and detect ROSC.

PPG signals (i.e. a pulse oximetry sensor) had a negative correlation with flow as PPG reflects blood volume inversely. The baseline channels showed some potential to be used as ROSC detector and as CPR surrogate, especially in the infrared channel. The amplitudes of the PPG were not of use to detect ROSC or to steer CPR.

SBP, MAP, PP, ETCO2 and VCO2 have the potential to detect ROSC but are not of great use as a measure of CPR quality. For ETCO2 the low correlation is remarkable.
Abstract 11682: Prognostic Impact of Periodic Leg Movements in Hospitalized Heart Failure Patients
Authors: Kanno Yuki , Yoshihisa Akiomi , Takiguchi Mai , Miura Shunsuke , Sato Akihiko , Shimizu Takeshi , Nakamura Yuichi , Yamauchi Hiroyuki , Owada Takashi , Abe Satoshi , Suzuki Satoshi , Oikawa Masayoshi , Sakamoto Nobuo , Yamaki Takayoshi , Sugimoto Koichi , Kunii Hiroyuki , Nakazato Kazuhiko , Suzuki Hitoshi , Saitoh Shu-ichi , Takeishi Yasuchika
Published: July 2021

Background:
Periodic leg movements during sleep (PLMs) are the disorder characterized by regularly recurring movements of the legs during sleep. Recently, it has been reported that PLMs have a critical association with cardiovascular mortality and morbidity. However, the prevalence and impact of PLMs on cardiac and all-cause mortality still remain unclear in patients with heart failure (HF). Methods and Results: Consecutive 114 patients admitted for treatment of HF and underwent polysomnography were divided into two groups based on PLM index: moderate-severe PLMs group (PLM index ≥ 20/h, n = 24) and non-mild PLMs group (PLM index < 20/h, n = 90). We compared patient characteristics, findings of echocardiography and cardio-pulmonary exercise test between the two groups. Furthermore, we prospectively followed cardiac events including cardiac death and all-cause mortality. The moderate-severe PLMs group, as compared to non-mild PLMs groups, had lower levels of estimated GFR (46.8 vs. 59.5 ml/min/1.73cm
2
, P = 0.032) and tended to have lower peak VO
2
(14.5 vs. 16.3 ml/min/kg, P = 0.09). In contrast, age, body mass index, systolic blood pressure, B-type natriuretic peptide, hemoglobin, sodium, C-reactive protein and left ventricular ejection fraction were similar between the two groups. Importantly, cardiac mortality (log-rank P = 0.005) and all-cause mortality (P = 0.028) were higher in moderate-severe PLMs group than in non-mild PLMs group (Figure). In the multivariable Cox proportional hazard analyses, after adjusting for potential confounding factors, PLM index was an independent predictor of cardiac (HR 1.024, 95% CI 1.006-1.042, P = 0.009) and all-cause mortality (HR 1.016, 95% CI 1.001-1.031, P = 0.045) in HF patients. Conclusions: The PLM index was a novel predictor of cardiac and all-cause mortality in HF patients.
Abstract 11774: Beyond Restenosis - Patients’ Preferences for Drug Eluting versus Bare Metal Stents
Authors: Qintar Mohammed , Chhatriwalla Adnan K , Ashraf Javed M , Buchanan Donna M , Tang Fengming , Jones Philip , Spertus John A
Published: July 2021

Introduction:
Drug eluting stents (DES) reduce the need for target vessel revascularization, and are used in ~80% of percutaneous coronary interventions (PCI) in the US. However, DES also necessitate the use of prolonged dual anti-platelet therapy (DAPT), which is associated with increased bleeding/bruises, can complicate future surgeries and can increase patients’ medication costs (DAPT drawbacks). Patients’ preferences regarding the benefits of DES and DAPT drawbacks have not previously been studied or reported.

Methods:
In a prospective, observational cohort study, consecutive patients undergoing PCI at 2 Kansas City hospitals completed a survey assessing the importance of the following factors related to the decision to receive DES: need for repeat PCI and DAPT drawbacks. Each factor was rated from 1 (not important) to 10 (extremely important). The most important factor, or group of factors, to each patient was then identified.

Results:
Among 317 PCI patients (66% male, 71% white, 45% DM, 80% HTN, 43% with prior PCI), 21% did not consider the need for repeat PCI as the most important factor (Figure). Only 14% considered the need for repeat PCI the single most important factor and 65% considered at least one DAPT drawback as important as repeat PCI. A third (32.8%) ranked minor bleeding/bruising as the most important factor (alone (5.5%) or with other domains (27.3%)).

Conclusions:
While the need for repeat PCI is an important factor to patients considering stent options, 85% of PCI patients regard other factors to be at least as important. Eliciting patients’ preferences is important to better tailor stent choices to the goals and values of individual patients undergoing PCI.
Abstract 11793: Early Detection of Chemo-cardiotoxicity Assessed by Layer Specific Strain: Myocardial Layer is Most Vulnerable to Anthracycline Chemotherapy
Authors: Park Seong-Mi , Kim Mi-Na , Park Kyong-Hwa , Shim Wan-Joo
Published: July 2021

Background:
Anthracycline-based chemotherapy has a progressive dose-dependent toxicity to the myocardium and is related to a poor prognosis. Early detection of subclinical myocardial dysfunction caused by the chemo-cardiotoxicity is thus important for predicting apparent left ventricular (LV) dysfunction and heart failure. Recently, detailed layer-specific analysis of myocardial deformation has been described. This study assessed LV myocardial dysfunction using layer-specific strain in patients who received anthracycline-based chemotherapy.

Methods:
Consecutive 54 patients (50 ± 14 years old, all women) with preserved LV ejection fraction (≥50%) after receiving anthracycline chemotherapy were included. Two-dimensional speckle tracking was used to assess circumferential strains (CS) from the three acquired parasternal short-axis views at basal, midventricular, and apical level. Peak systolic CS was determined for the total wall thickness (CStotal) and for each of three myocardial layers (CSendo, CSmyo and CSepi for endocardial, mid-myocardial, and epicardial layer, respectively) using EchoPAC PC software. Twenty normal controls were studied for comparisons.

Results:
CStotal was worse in patients than in controls (-24.5 ± 7.0% vs -22.0 ± 5.8%, P =0.03) even though LV ejection fraction was not different (P = 0.25). Layer-specific strains showed a decreasing gradient from the endocardium to the epicardium both in controls and patients (P <0.001) and it was more apparent from the endocardium to the myocardium in patients than in controls. CS were significantly different between controls and patients in myocardial and epicardial layers (CSmyo, -23.2 ± 8.0% vs -20.8 ± 7.9%, P =0.01; CSepi, -17.8 ± 6.0% vs -16.0 ± 6.8%, P =0.04), but not significant in endocardial layer (CSendo, -29.4 ± 8.4% vs -28.2 ± 9.2%, P =0.09). CStotal was most related to CSmyo (r = 0.943, P <0.001) and CSmyo correlated with the cumulative doxorubicin dose (r = 0.296, P = 0.03).

Conclusion:
CStotal was reduced and CSmyo was most impaired in patients, which means that myocardial layer is most vulnerable to anthracycline chemotherapy. Layer-specific evaluation of LV may be helpful for early detection of subclinical myocardial dysfunction in these patients.
Abstract 11906: Heart Failure Admissions to General Medicine Services are Associated With Increased 30-day Readmission Rate
Authors: Goyal Parag , Sterling Madeline , Beecy Ashley N , Kochhar Savira , Ruffino John T , Jones Erica C , Horn Evelyn M
Published: July 2021

Introduction:
Hospitalists are increasingly caring for patients with heart failure (HF) at a time when there is need to identify modifiable factors associated with 30-day readmission rates.

Hypothesis:
Patients admitted to General Medicine services (GM) will have higher 30-day readmission rates than those admitted to Cardiology services.

Methods:
This retrospective cohort comprised patients with a principal diagnosis of HF discharged from GM or Cardiology services in 2013-2014 at an urban academic hospital. Patients discharged with hospice were excluded. Index hospitalizations and 30-day readmissions were identified via query of the electronic medical records. Demographics, clinical indices, and hospitalization characteristics were collected by chart review.

Results:
Among 926 patients admitted with HF, 40% were admitted to GM and 60% were admitted to a Cardiology service. Patients on GM were slightly older, more likely female, and more likely to have Medicare (Table). They also had higher LVEF, less RV dysfunction, and less ventricular tachycardia (VT). Rates of non-cardiac comorbidities were comparable between groups. Patients on GM experienced a 1.4-fold increased 30-day readmission rate compared to those on Cardiology services (32% vs. 23%, p=0.023). Multivariate regression analysis showed that admission to GM remained a predictor for 30-day readmission (OR 1.37, [1.01 to 1.87], p=0.048) after controlling for key differences between groups including age, sex, insurance, LVEF, RV dysfunction, VT, and admission blood pressure and hemoglobin.

Conclusions:
HF patients admitted to General Medicine have less structural heart disease, and yet have a higher rate of 30-day readmission compared to those admitted to Cardiology services. This underscores the importance of ensuring that hospitalists obtain adequate heart failure training (related to both inpatient care and optimization of discharge regimens), so as to avoid un-necessary readmissions.
Abstract 11983: Oral Therapies for Type 2 Diabetes in Combination With Long-acting Insulin and the Risks of Myocardial Infarction and Stroke
Authors: Floyd James S , Wiggins Kerri L , Dublin Sascha , Longstreth William T , Smith Nicholas L , McKnight Barbara , Heckbert Susan R , Weiss Noel S , Psaty Bruce M
Published: July 2021

Introduction/Hypothesis:
The use of oral therapies in combination with insulin for the treatment of type 2 diabetes is common, but the cardiovascular risks or benefits are largely unknown. Among users of long-acting insulin, we conducted a population-based case-control study to evaluate the incident myocardial infarction (MI) and incident stroke risks associated with sulfonylurea and metformin use. We hypothesized that sulfonylurea use would be associated with elevated risk and metformin use with decreased risk.

Methods:
Cases were enrollees of Group Health Cooperative (GHC) with type 2 diabetes who used long-acting insulin at the time of diagnosis with a first MI (n=413) or first stroke (n=247) from 1995-2010. Controls (n=443) were randomly sampled GHC enrollees with type 2 diabetes who used long-acting insulin, matched to cases on age, sex, and calendar year. Sulfonylureas and metformin use was classified as current, past, or never using electronic pharmacy records. MI and stroke diagnoses and potential confounding variables were validated by medical record review. Analyses were adjusted for matching variables and cardiovascular risk factors, including smoking, duration of diabetes, blood pressure, and cholesterol.

Results:
Current use of sulfonylureas compared with never use was associated with a higher risk of MI (OR 1.67; 95% CI, 1.10-2.55) but not stroke (OR 1.22; 95% CI, 0.74-2.00). Current use of metformin compared with never use was associated with a lower risk of stroke (OR 0.54; 95% CI, 0.31-0.95) but not MI (OR 0.77; 95% CI 0.44-1.33). Past use of sulfonylureas and past use of metformin were not associated with either outcome. Findings were robust to sensitivity analyses that tested assumptions about eligibility criteria and medication adherence. An unmeasured confounder associated with a 2-fold increased MI risk would have to be present in 70% more current users than never users of sulfonylureas to render the sulfonylurea-MI odds ratio null.

Conclusions:
The use of sulfonylureas in combination with long-acting insulin may increase the risk of MI compared with insulin alone. Our study adds to a growing body of evidence that metformin may be an effective cardiovascular disease prevention therapy, even when used with insulin.
Abstract 11987: Adenoviral Intramyocardial VEGF-D Gene Transfer Increases Myocardial Perfusion in Refractory Angina Patients
Authors: Hassinen Iiro , Hartikainen Juha , Hedman Antti , Kivelä Antti , Saraste Antti , Knuuti Juhani , Husso Minna , Mussalo Hanna , Hedman Marja , Toivanen Pyry , Heikura Tommi , Ylä-Herttuala Seppo
Published: July 2021

Background:
There is a rapidly growing number of refractory angina patients who in spite of the optimal medical therapy are severely symptomatic and who are not suitable for revascularization. Proangiogenic gene therapy is a potential new treatment for these patients. We evaluated for the first time safety, feasibility and efficacy of adenoviral (Ad) gene therapy using a new member of the VEGF family, VEGF-D, in the treatment of refractory angina.

Methods and Results:
KAT301 trial is a randomized, placebo-controlled, single-blinded phase I/II study. A total of 30 patients were randomized to intramyocardial AdVEGF-D gene transfer (VEGF group) or placebo (control group) with a 4:1 ratio. VEGF group underwent transseptal puncture and electroanatomical mapping of left ventricle with NOGA system (Cordis Corp), followed by intramyocardial injection of AdVEFG-D in the ischemic areas. The control group underwent transseptal puncture, left ventricle mapping and intracardiac saline infusion. Vital signs and laboratory assessments were measured at baseline and at 1, 2, 7,14 days and 3 months after the gene therapy to evaluate the safety and feasibility. Twenty patients underwent assessment of myocardial perfusion and blood flow reserve at rest and during adenosine induced exercise with positron emission tomography (15O-PET) at baseline and three months after the procedure.

Mild transient elevation in body temperature and CRP and moderate hypotension was detected in VEGF group after the procedure. Troponine-T was elevated in both groups after the procedure but was normalized in two days. Perfusion reserve at 3 months in the myocardial segment with the lowest perfusion reserve at baseline increased significantly in the VEGF group (0.93±0.30 to 1.21±0.39, p=0.035) but not in the controls (1.21±0.63 to 1.53±0.67, p=0.343). No antibody responses were found against the transgene in the VEGF group after the treatment.

Conclusion:
Intramyocardial AdVEGF-D gene therapy is well tolerated in refractory angina patients. Changes in PET analysis at 3 months indicate that gene therapy can enhance myocardial perfusion in segments with the lowest perfusion reserve. Based on the results a randomized, controlled, blinded phase II/III trial is justified.
Abstract 12006: Renal Sympathetic Denervation Improves Both Progressive Cardiac Remodeling and Renal Damages in Hypertensive Heart Failure Rats: Comparison With β Receptor Blockade
Authors: Watanabe Heitaro , Iwanaga Yoshitaka , Miyaji Yuki , Yamamoto Hiromi , Miyazaki Shunichi
Published: July 2021

Background:
Chronic activation of sympathetic-nervous system (SNS) is triggered and contributes to subsequent cardiac remodeling and the transition to heart failure (HF).

Hypothesis:
Renal sympathetic denervation (RDN) may affect the process by improving the renal damage and suppressing cardiac SNS in rat hypertensive HF model with renal injury. The effects may be comparable to those of chronic β blocker treatment.

Methods and Results:
In Dahl salt-sensitive hypertensive rats, RDN or sham operation was performed at hypertrophic stage (11 weeks). Vehicle (CONT) or β blocker, bisoprolol (BISO) was administrated in rats with sham operation. Both RDN and BISO did not alter blood pressure during the study, but BISO group showed the significantly less heart rate. In RDN and BISO groups, the median survival time was significantly improved from 18.9 (CONT) to 21.4 and 22.5 weeks, respectively (P < 0.01). Echocardiography showed the improvement of LV dilatation and fractional shortening, and histological analysis showed the amelioration of myocyte hypertrophy and fibrosis in RDN and BISO groups at HF stage (17 weeks). β1 adrenergic receptor and tyrosine hydroxylase expression in LV myocardium was significantly increased only in RDN group. In contrast, α1b, α1d, and α2c adrenergic receptor expressions were improved only in BISO group. Furthermore, renal histopathologic damages and function were ameliorated in the both treatment groups. It was accompanied by suppression of local endothelin-1 and renin mRNA expressions.

Conclusions:
Renal sympathetic denervation ameliorated progression of both myocardial and renal damages in the hypertensive rats, independent of blood pressure. The overall effects were similar with those of chronic β receptor blockade having the effects on heart rate and α adrenergic receptors’ expression. The underlying mechanism may be associated with preservation of myocardial sympathetic-nervous system and renal protection.
Abstract 12035: Effect of 10-minute Dispatch-Assisted Cardiopulmonary Resuscitation Training in Addition to a Standard Course: A Simulation Study
Authors: Fukushima Hidetada , Asai Hideki , Norimoto Kazunobu , Seki Tadahiko , Kawai Yasuyuki , Okuchi Kazuo
Published: July 2021

Introduction:
Immediate bystander cardiopulmonary resuscitation (CPR) is essential for the good outcome of sudden cardiac arrest victims. Current guidelines recommend dispatch-assisted CPR (DA-CPR), which can double the frequency of bystander CPR. Laypersons, however, are not familiar with how dispatchers provide CPR instructions. DA-CPR training may be effective at spreading DA-CPR, but this needs to be validated. The aim of this study was to determine the effectiveness of brief DA-CPR training in addition to a standard CPR training course.

Methods:
We conducted a DA-CPR simulation study. Participants with no prior CPR training within 1 year were assigned randomly to one of two 90-min CPR training courses (DA-CPR Group: a standard CPR course with 10-min DA-CPR training or Standard Group: a standard CPR course with a simple introduction to how dispatchers deal with emergency calls). In the DA-CPR Group, the participants practiced the role of a dispatcher and an emergency caller. At 6 months after training, the subjects performed CPR for 2 min under instruction from off-duty dispatchers.

Results:
Of the 66 participants, 59 (DA-CPR Group, 30; Standard Group, 29) completed the simulation at 6 months after training. The median time intervals between call receipt and cardiac arrest recognition or instruction for chest compressions by dispatchers were similar between both groups. However, the subjects in the DA-CPR Group provided the first compression more quickly (median time interval between call receipt and the first dispatch-assisted compression: 108 vs. 129 s, respectively, p < 0.05 Mann-Whitney U test). The quality of chest compressions was, however, similar between both groups.

Conclusions:
All participants could perform DA-CPR at 6 months after training, but those in the DA-CPR Group started chest compressions more quickly. DA-CPR training might be effective for the immediate development of better cooperation between a layperson and a dispatcher.
Abstract 12080: 9-1-1 Caller Descriptions of Gasping During Out-of-Hospital Cardiac Arrest
Authors: Dameff Christian , Tully Jeffrey , Murphy Ryan Anne , Panczyk Micah , Vadeboncoeur Tyler F , Kannan Vijay , Spaite Daniel W , Bobrow Bentley J
Published: July 2021

Background:
Abnormal breathing, or “gasping,” frequently occurs during cardiac arrest and has been associated with increased survival. During 9-1-1 calls, early recognition of gasping may allow dispatchers to identify OHCA and to start CPR instructions promptly. Objective: To characterize lay rescuers’ descriptions of abnormal breathing during OHCA.

Methods:
9-1-1 audio recordings of 4,279 confirmed OHCAs (10/10-7/14) in Arizona were reviewed by program personnel. Terms used by lay rescuers to describe victims’ breathing were recorded in a structured database.

Results:
Abnormal breathing (as opposed to “not breathing”) was described in 542/4279 (13%) calls. There were 623 verbal descriptions. A total of 50 different terms were used. However, the top 8 accounted for 83% and the remaining 42 descriptions (“Other”) comprised only 17% of all terms used. “Gasping” was the most commonly used term (30%; 187/623), followed by “snoring” (15%; 95/623; Figure).

Conclusion:
Lay rescuers used a wide variety of terms to describe abnormal breathing in documented OHCA. However, 8 terms accounted for 83% of descriptions. Familiarizing 9-1-1 telecommunicators with the most commonly used terms may improve the accuracy of recognition and hasten the identification of OHCA.
Abstract 12086: Differences in Risk Factors and Primary Cause of Sudden Unexpected Death by Timing Criteria
Authors: Nwosu Anthony C , Mehta Neil D , Lin Feng-Chang , Oyekunle Taofik , Nanavati Parin P , Lewis Mary E , Osehobo Omoye O , Pursell Irion W , Simpson Ross J , Hodonsky Chani , Mounsey John P , Chung Eugene H
Published: July 2021

Background:
The World Health Organization (WHO) criteria for sudden unexpected death (SUD) describes either witnessed death or unwitnessed death occurring no more than 24 hours after the subject was last seen alive. Sudden Unexpected Death in North Carolina (SUDDEN) is a population-based study of out-of-hospital unexpected deaths using a clinical definition of sudden death without restrictions on the timing of death. Use of time-limiting definitions was found to underestimate the incidence of SUD by 4 to 19 fold. We sought to explore the characteristics and risk factors of this underestimated population.

Methods:
From March 2013 to March 2014, all cases of possible sudden unexpected death were identified from electronic query of the Wake County EMS database. Expected deaths were excluded and independent cardiologists made determination for cohort inclusion by review of medical history. We stratified the cohort by timing of death (less than 24 hours versus above 24 hours and unknown) and analyzed the observed difference in incidence between the two groups.

Results:
Out of 1138 total EMS referrals, 190 were adjudicated as SUD cases into the final cohort. SUDDEN captured 70% more people than studies that used WHO-based criteria. In comparison with cases excluded by WHO criteria, cases meeting WHO criteria were younger (50.1 ± 9.8 years 54.5 ± 8.2 years, p<0.001) and had a higher likelihood of a medical examiner issued death certificate (86.3% vs. 34.9%). WHO-based criteria also include significantly more cases with the primary cause of death listed as unknown (p<0.01). Differences between the groups for BMI, smoking status and dyslipidemia were suggestive. There were no time-based differences in other comorbidities (coronary artery disease, diabetes mellitus, and hypertension) or demographic risk factors (race, gender, marital status, and educational status).

Conclusion:
Time-limiting definitions underestimate SUD incidence. Preliminary study shows trends in some demographic and clinical characteristics between SUDDEN and WHO-recommended criteria. An expanded study sample of a population-based cohort similar to SUDDEN is needed to understand the differences in this often misclassified population.
Abstract 12159: Impact of Varying Onset Timing of Diastolic Tricuspid Annular Movement and Tricuspid Inflow on Predictive Values of Doppler-derived Indices for Clinical Outcomes in Pulmonary Arterial Hypertension
Authors: Takahama Hiroko , Kane Garvan C
Published: July 2021

Background:
In right heart failure, Doppler-derived indices such as RV performance index (RIMP) and tricuspid regurgitant duration (TRD) have been linked to clinical outcomes, but variably. We tested the hypothesis that this variability is based on varying timing and predictive value of the onset of diastolic phase, according to right atrial pressure (RAP) and to whether tissue or flow Doppler is used.

Methods:
We reviewed echocardiograms and catheter examinations for 151 consecutive patients with pulmonary arterial hypertension. Te’ and TE were defined as the time from QRS onset to the onset of early diastolic velocity on tissue Doppler imaging at the tricuspid valve annulus and to TRD terminal indicating the onset of tricuspid inflow. All measurements were corrected for heart rate. The patients were grouped into low (RAP < 10mmHg, n = 84) and high RAP groups (RAP ≧ 10mmHg, n = 67).

Results:
Over 3 years, there were 62 total deaths and 8 lung transplantations. In low RAP group, Te’ was prolonged in association with an increase in Tau (R = 0.51, p = 0.0001) and prolonged Te’ predicted higher mortality (HR = 1.20 / 10ms, p = 0.02). In high RAP group, Te’ was still prolonged as Tau increased (R = 0.43, p = 0.008) independently of RAP, while TE was reversely shortened as RAP rose (R = 0.41, p = 0.0006) and shortened TE predicted higher mortality (HR = 0.86 / 10ms, p = 0.008). An increase in RIMP using tissue Doppler only in low RAP group and shortened TRD only in high RAP group predicted higher mortality (HR = 2.09 / 0.1, p = 0.002 and HR = 0.89 / 10ms, p = 0.02, respectively), keeping in line with Te’ and TE, respectively.

Conclusions:
Both the onset of diastolic tricuspid annular movement and the onset of tricuspid inflow relate to relaxation disorder. As RAP elevates, only the tricuspid inflow onsets early. These observations should be considered when interpreting Doppler-derived indices: they predict clinical outcomes in a limited group of patients according to RAP and to whether tissue or flow is focused on.
Abstract 12168: Risk Stratification for Ventricular Tachyarrhythmias in Patients With Cardiac Sarcoidosis by Cardiac Magnetic Resonance Imaging
Authors: Yasuda Masakazu , Iwanaga Yoshitaka , Kato Takao , Izumi Toshiaki , Inuzuka Yasutaka , Nakamura Takashi , Kawamura Takayuki , Ikeguchi Shigeru , Inoko Moriaki , Kurita Takashi , Miyazaki Shunichi
Published: July 2021

Introduction:
Recently, late gadolinium-enhancement (LGE) cardiac magnetic resonance (CMR) imaging, which has been used to uniquely characterize the myocardial fibrosis, is reported to have a prognostic value in cardiac sarcoidosis (CS)

Hypothesis:
Not only fibrosis mass, but also its localization may help to identify the risk of ventricular tachyarrhythmias (VA) in patients with CS.

Methods:
70 consecutive CS patients underwent CMR (cine and LGE imaging). Left ventricular (LV) mass and fibrosis mass were calculated and the localization was analyzed using 17 segment model. VA was defined as sustained ventricular beats ≥ 3 or ventricular fibrillation. The patients underwent prospective follow-up through 2015 from CMR examinations.

Results:
33.3 % of the patients had a history of VA at the time of CMR examination. During a median follow-up of 15.5 months, 31.9 % had new-onset (11.6 %) or recurrent VA (20.3 %). Increased LV fibrosis mass (LVFM) was associated with the prevalence of VA (P < 0.001) and receiver operating characteristics curve analysis indicated good predictive performance of LVFM for the combined VA (history of VA and new-onset VA) (AUC = 0.788, best cut-off value; 8.28 g). In addition, when localization score (LS) was defined as the summation of LGE enhancement in LV basal anterior, basal anteroseptal, or RV out-flow tract (RVOT) lesion, it was associated with the combined VA (P < 0.001). Kaplan-Meier analysis showed that both LVFM and LS groupings were significantly associated with VA occurrence (Figure A). Furthermore, a combined analysis of LVFM and LS groups showed a better risk stratification for VA (Figure B).

Conclusions:
Not only fibrosis mass, but also its localization of basal anterior, anteroseptal, or RVOT was associated with the history of VA as well as the prognosis for VA in patients with CS. CMR may be a useful tool for risk stratification for ventricular tachyarrhythmias by detecting myocardial fibrosis and localization in CS patients.
Abstract 12200: Blood Pressure Control in Diabetic Patients is Most Effective Between Ages 65 to 75 for Prevention of Atherosclerotic Events
Authors: Soejima Hirofumi , Morimoto Takeshi , Okada Sadanori , Sakuma Mio , Nakayama Masafumi , Uemura Shiro , Masao Kanauchi , Doi Naofumi , Jinnouchi Hideaki , Sugiyama Seigo , Waki Masako , Saito Yoshihiko , Ogawa Hisao
Published: July 2021

Background:
In 2013, the blood pressure (BP) control target for diabetic patients was changed in both Europe and USA; however, there was a paucity of supporting evidence. We investigated whether BP control<140/90 mmHg was effective in any age group in diabetic patients for preventing atherosclerotic events.

Methods:
We performed the Japanese primary prevention of atherosclerosis with aspirin for diabetes (JPAD) trial to examine the efficacy of low-dose aspirin therapy in 2536 type 2 diabetes patients. After completion of the JPAD trial in 2008, we followed up the same subjects until 2013, the JPAD2 cohort.

Primary end points were a composite of ischemic heart disease, stroke, peripheral arterial disease, and sudden death. We divided the patients into either a high age 65 (H65) group (n=1360; age≥65 years) or a low age 65 (L65) group (n=1176; age<65 years). We then re-divided the patients into a high age 75 (H75) group (n=412; age≥75 years) or a low age 75 (L75) group (n=2124; age<75 years).

Results:
Systolic BP was unchanged 131 mmHg in 2009 and 130 mmHg in 2013 in each JPAD patients. Diastolic BP decreased from 73 mmHg in 2009 to 71 mmHg in 2013. The difference of incidence of atherosclerotic events between BP≥140/90 patients and BP<140/90 patients was significant in H65 group (P=0.0026, Figure). During a median of 8.1 years, the difference of incidence of the events between the patient groups was not significant in the L65 group (P=0.4515, Figure). The difference of incidence of the events was not significant in H75 group (P=0.8050, Figure). The difference of incidence of the events was significant in the L75 group (P=0.0034, Figure).

Conclusions:
The difference of incidence of atherosclerotic events between BP≥140/90 patients and BP<140/90 patients was significant only when patients aged 65 to 75 years is included in the analysis. This study then supports a recommendation of the guidelines that better BP control target of age≥75 years patients is not necessary to be BP<140/90 mmHg.
Abstract 12243: Associations Between Physical Activity and Prognostic Biomarkers in Patients With Stable Coronary Heart Disease in the STABILITY Trial
Authors: Held Claes , Stewart Ralph A , Armstrong Paul W , Cannon Christopher P , Hadziosmanovic Nermin , Hagström Emil , Hochman Judith S , Koenig Wolfgang , Lonn Eva , Nicolau Jose , Siegbahn Agneta , Steg Philippe Gabriel , Watson David , White Harvey D , Wallentin Lars
Published: July 2021

Introduction:
Physical activity (PA) reduces the risk of events in patients with stable coronary heart disease (CHD). Biomarkers reflecting myocardial dysfunction, renal function and inflammatory activity are associated with outcomes in stable CHD. It is poorly known to what extent the benefits of PA may be linked to biomarker levels.

Hypothesis:
The association between PA and outcomes may be mediated by processes indicated by changes in the levels of prognostic biomarkers.

Methods:
At baseline, 15,486 patients with stable CHD participating in the global STABILITY trial, completed a baseline lifestyle questionnaire including self-reporting on hours spent each week on mild, moderate and vigorous exercise, corresponding to approximately 2, 4 and 8 METS, respectively. Plasma levels of high-sensitivity (hs) C-reactive protein (hs-CRP), hs-troponin T (hs-TnT), N-terminal pro-B type natriuretic peptide (NT-proBNP), cystatin-C, growth differentiation factor-15 (GDF-15) and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity were assessed from plasma samples obtained at baseline. Associations between PA and biomarker levels were evaluated after multivariable adjustments (age, gender, traditional clinical cardiovascular risk factors and standard biomarkers including cholesterol levels) with sedentary patients as reference.

Results:
Associations between levels of PA and hs-CRP, hs-TnT, NT-proBNP, cystatin C, GDF-15 and activity of Lp-PLA2 are shown in the Table, after adjustments for co-variables. PA was independently and inversely associated with all biomarker levels, except for Lp-PLA2.

Conclusions:
Increasing PA, was independentlyand inversely associated with levels of most clinically important biomarkers, except for Lp-PLA2. The effects of PA on outcomes may partly be explained by disease processes reflected by changes in biomarker levels.