bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 5999: Optical Coherence Tomography Findings At Two Years Follow Up In Fully Biodegradable Everolimus Eluting Stents
Authors: Gonzalo Nieves , Serruys Patrick W , Freire Rafael , Ligthart Jurgen , Giessen Wim vd , Bruining Nico , Regar Evelyn
Published: July 2021

Fully biodegradable stents may avoid the potential long-term complications of metallic drug-eluting stents such as late and very late stent thrombosis. We sought to evaluate the structural changes in a bioabsorbable DES and its interaction with the coronary vessel wall over time using optical coherence tomography (OCT). We investigated 14 consecutive patients undergoing implantation of a bioabsorbable everolimus-eluting coronary stent (BVS: Abbott Laboratories, IL, USA), composed of a poly-L-lactic acid backbone, coated with a degradable polymer/everolimus matrix. OCT (LightLab Imaging, Inc., Westford, MA) was performed immediately after stent implantation, at 6 months and at 24 months follow-up. All patients tolerated OCT imaging without complications. At baseline, OCT could detect the interface between the BVS stent and other tissues or fluid, but the inside of the strut appeared black, giving a unique box appearance. After 6 months, the struts were still clearly visible; however, their optical properties had changed considerably. In patients undergoing two years follow up (n=5, full dataset will be available at time of presentation) the majority of struts was not visible anymore and all visible struts were embedded into the vessel wall with complete tissue coverage. In contrast to 6months follow-up, at 2 years no intraluminal thrombi or dissections were visible. At 2 years follow-up the majority of stent struts were not visible by OCT. All the visible struts were covered and apposed. The lumen surface was smooth without intraluminal thrombi or dissections.
Abstract 6023: The Need for Blood Transfusion Is an Independent Predictor of Incident Cardiovascular Events and All-Cause Mortality among Patients Undergoing Percutaneous Coronary Intervention
Authors: Brugts Jasper Jan , Mercado Nestor , Ix Joachim , Shlipak Michael G , Dixon Simon R , Gersh Bernard J , Lamos Pedro , Guarneri Mimi , Terstein Paul , Wijns Williom , O’Neill William W , Boersma Eric
Published: July 2021

Periprocedural bleeding is one of the most frequent complications of percutaneours coronary interventions. We assessed the relation between blood transfusion and all-cause mortality or incident cardiovascular events (death, MI, stroke) among 6103 patients of the Evaluation of Oral Xemilofiban in Controlling Thrombotic Events (EXCITE)-trial. Subjects were followed for 7 months after enrollment for the occurrence of events. Multivariate Cox-regression analysis evaluated the independent association of blood transfusion with each outcome adjusted for age, gender, race, diabetes mellitus, hypertension, hypercholesterolemia, history of MI, PCI, CABG, heart failure, LVEF<30%, use of beta-blockers, statins, ACE-inhibitors, platelet inhibitors and allocation to treatment with xemolifiban. In addition, propensity score analyses were performed (ROC 0.80). Mean age was 59.2 years, 21.7% were female, and 18.9% had diabetes mellitus. Of the169 patients who received blood transfusion, 14 (8.3%) died and 42 (24.9%) experienced a CVD event. Of the 5934 patients without transfusion, 65 (1.1%) died (p-value: <0.001) and 555 (9,4%) experienced a CVD event (p-value: <0.001) In multivariate analysis, blood transfusion was associated with a 5.3 fold increased risk of mortality (HR 5.3; 95% CI 2.8 –10.2), and a 2.5 fold increased risk of incident CVD (HR 2.5; 95% CI 1.7–3.4.) Noteworthy, patients who were US citizens had a higher transfusion rate then non-US citizens (OR 1.45, 95%CI 1.02–2.06) The need of blood transfusion is a strong and independent predictor of all-cause mortality and incident CVD events among patients undergoing PCI.
Abstract 6073: Dexrazoxane Cardioprotection in Doxorubicin-Treated Children with Acute Lymphoblastic Leukemia: Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia Consortium Protocol 95–01 Randomized Controlled Trial
Authors: Lipshultz Steven E , Scully Rebecca E , Lipsitz Stuart R , Sallan Stephen E , Silverman Lewis B , Miller Tracie L , Barry Elly V , Asselin Barbara L , Athale Uma , Clavell Luis A , Larsen Eric , Moghrabi Albert , Samson Yvan , Schorin Marshall A , Orav E. John , Colan Steven D
Published: July 2021

Background: Doxorubicin (DOX) chemotherapy injures myocardial cells, leading to progressive cardiac dysfunction. Dexrazoxane (DZR), a free-radical scavenger, reduced troponin T (cTnT) elevation during therapy in children with acute lymphoblastic leukemia (ALL) on Dana-Farber Cancer Institute (DFCI) Protocol 95– 01. The long-term cardiac benefits of DZR are not yet known.

Methods: We centrally remeasured echocardiograms from childhood ALL survivors who were randomly assigned to DOX (n =64; 30 mg/m
2
/dose for 10 doses) with or without DZR (n =58; 300 mg/m
2
/dose) during DFCI Protocol 95– 01.

Results: Demographics and follow-up were similar in both arms (median f/u years: DOX 4.0 vs. DZR/DOX 3.7). Mean left ventricular (LV) end-systolic dimension was significantly abnormal for DOX vs. DZR/DOX at 3 years (mean Z-score: DOX 0.637 vs. DZR/DOX −0.0005, P=0.0164) and progressed at 3.5 years (0.800 vs. −0.006, P=0.0028) and 4 years (1.01 vs. 0.005, P=0.0013). DOX-group mean LV end-diastolic (ED) dimension was significantly dilated at 3.5 years (mean Z-score: DOX 0.223 vs. DZR/DOX −0.424, P=0.022) and 4 years (0.428 vs. −0.456, P=0.004). With 3.5 years follow-up, a number of non-significant trends showed DZR/DOX echo measures to be more normal: LV fractional shortening Z-score (DOX −2.092 vs. DZR/DOX −1.00); LV mass Z-score (−0.672 vs. −0.537); LVED posterior wall thickness Z-score (LVEDPWTz; −0.596 vs. −0.395). For DZR/DOX-patients, cTnT elevation (defined as >0.01 ng/ml) during DOX treatment correlated with thinner LVED posterior wall 3.5 years post treatment (mean LVEDPWTz: cTnT− =−0.011 vs. cTnT+= −1.200, P=0.0352).

Conclusions: DZR is protective against late DOX cardiotoxicity with smaller LV dimensions, consistent with less LV remodeling. LV function, thickness, and mass trended to more normal among children who received DZR and all parameters trended toward a greater DZR effect over time. Further, cTnT elevation during therapy predicted late LV wall thinning.

Table 1:

Post-treatment Mean Differences in Dimension Z-Scores
Abstract 6082: Sex Differences in Mortality after Acute Myocardial Infarction: Changes from 1994 to 2006
Authors: Vaccarino Viola , Parsons Lori , Peterson Eric D , Rogers William J , Kiefe Catarina , Canto John
Published: July 2021

Introduction.
In the past 10 years, several studies have shown that younger, but not older, women have a higher hospital mortality than age-matched men. We examined whether such mortality differences have declined in recent years.

Methods.
We investigated temporal tends in the case fatality of MI according to sex and age (in 5 age groups) during a12-year period, 1994 to 2006. The study population included 916,380 MI patients from the National Registry of Myocardial Infarction (NRMI) who had a confirmed diagnosis of MI.

Results.
Hospital mortality declined markedly between 1994 and 2006 in all patients, but more so in women than in men in virtually every age group. The mortality reduction in 2006 relative to 1994 was largest in women <55 years old (53%) and lowest in men <55 years old (33%). In patients <55 years, the absolute decline in mortality was 3 times larger in women than in men (2.7% vs 0.9%). The sex difference in mortality decline became progressively lower in older patients (p=0.002 for the interaction between sex, age and year). As a result, the excess mortality in younger women compared with men was less pronounced in 2004 – 06 than in 1994 –95 (Figure

). Changes in patient characteristics and treatments over time accounted in part for these mortality trends.

Conclusion.
In recent years, women, particularly younger women, experienced larger improvements in hospital mortality after MI than men. As a result, the higher mortality of younger MI women compared with men has narrowed.
Abstract 6101: Cost Effectiveness of Cardiac Computed Tomography Compared to Myocardial Perfusion Imaging (MPI) as an Effective Gatekeeper to Cardiac Catheterization in the Evaluation of Asymptomatic Firefighters with an Abnormal Treadmill Test
Authors: Budoff Matthew , Karwasky Robert , Ahmadi Naser Ahmadi MD , Nasserian Cyrus A , Chang William W , Flores Ferdinand R , Rizzo John , Gunnarsson Candace , McKay Charles R
Published: July 2021

To identify CAD among patients who fail treadmill tests, the traditional clinical care pathway is MPI, then invasive coronary angiography (ICA). In a retrospective cohort study, we compared the direct costs for detecting CAD using the traditional clinical care pathway and an alternative that incorporates MDCT, with coronary calcium score (CCS) followed by computed tomographic angiography (CTA) and ICA. Over a 2-year period, 3,950 Los Angeles, CA Firefighters underwent wellness/fitness exams at 6 contracted medical facilities. A total of 495 cases had abnormal treadmill tests and were referred for follow-up cardiology evaluation. All cases received CCS, followed by CTA for calcium scores >10, and ICA for abnormal CTA (>50% obstruction in at least one vessel). MPI results were estimated based on the prior year’s experience, with abnormal MPI receiving ICA. Costs to detect CAD were calculated for both the MPI and MDCT pathways based on results for the cohort and current Medicare reimbursement costs. Sensitivity analyses were performed by varying each of the clinical and cost components of the model to “low” and “high” levels and computing net costs. Most model inputs were varied by ±50% of baseline values to gauge the robustness of the results. Among 495 cases with abnormal treadmill tests, 146 (29.5%) would have required ICA due to abnormal MPI tests; 131 (26.9%) had abnormal CCS (>10) and went to CTA; 40 (8.1%) had abnormal CTA (>50% stenosis) and went to ICA. ICA showed 38 (7.7%) cases of CAD. The computed cost to detect CAD was $1,376 per case for the traditional route with MPI as gatekeeper and $503 per case for CCS as gatekeeper. All sensitivity analyses showed lower costs for the MDCT compared to MPI pathways. The net cost to ICA-confirmed diagnosis of CAD is substantially lower with MDCT compared to MPI as gatekeeper to ICA.
Abstract 6128: Cardiac Sympathetic Denervation in Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia and Risk of Recurrent Ventricular Tachyarrhythmias
Authors: Paul Matthias , Kies Peter , Schulze-Bahr Eric , Rahbar Kambiz , Schober Otmar , Breithardt Guenter , Wichter Thomas , Schaefers Michael
Published: July 2021

Background:
Patients (pts) with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) typically present with ventricular tachyarrhythmias often provokable by stress or catecholamines thereby indicating an involvement of the cardiac adrenergic system in the arrhythmogenesis. Previous studies demonstrated abnormalities of the presynaptic uptake-1 assessed by 123I-MIBG scintigraphy (MIBG-SPECT). In this study, we investigated the potential role of adrenergic dysfunction on the arrhythmia profile in pts with ARVC/D.

Methods:
In 42 pts with ARVC/D (mean age 43±14 years), MIBG-SPECT was performed. Results were compared to those obtained from 10 control subjects (n=10; mean age 43±12 years) without identifiable structural heart disease. MIBG images were acquired four hours post injection and analysed for regional 123I-MIBG uptake in a standardized 33-segment bull’s eye scheme.

Results:
Overall, an abnormal tracer uptake was detected in 25 pts with ARVC/D (59%). The extent of right ventricular dilatation and regional wall motion abnormalities as well as electrocardiographic markers of re-/depolarisation (e.g. T-wave inversion, epsilon-potential, maximal QRS-duration in right precordial leads) were not significantly different between pts with a normal and an abnormal MIBG-SPECT. However, during long-term follow-up of 9.2±3.4 years, pts with abnormal MIBG-SPECT experienced life-threatening ventricular tachyarrhythmias more often than those with a normal sympathetic innervation (21 of 25 pts (84%) vs. 7 of 17 pts (41%);
P
<0.01).

Conclusions:
An impairment of adrenergic innervation appears to account for a higher risk for VT recurrences in pts with ARVC/D. These results suggest a future role of MIBG-SPECT for individualized risk stratification in pts with ARVC/D.
Abstract 6147: A Tissue Stem Cell Niche Regulates Bicuspid Aortic Valve Disease
Authors: Rajamannan Nalini M
Published: July 2021

Bicuspid aortic valve disease is the most common congenital cardiac malformation and indication for surgery for aortic valve patients. The age of onset for the development of stenosis is earlier in bicuspid aortic valves than tricuspid aortic valves. Understanding the cellular mechanisms of this valve lesion, will help to develop novel approaches towards slowing disease progression. This study hypothesizes that bicuspid aortic valve disease develops secondary to a tissue stem cell niche to activate a cross-talk mechanism which induces Notch1 cleavage and Lrp5 mediated bone formation specific to the bicuspid aortic valve. Human ex vivo bicuspid valves versus control aortic valves were tested for Notch1 expression by RTPCR, Western Blot and Immunohistochemistry. eNOS null bicuspid mice: control (n=20), cholesterol (n=20), cholesterol + Atorvastatin (n=20), were tested for the development of aortic stenosis by Visual Sonics Echo, Immunohistochemistry for Notch1, Wnt, Lrp5, Osteocalcin, PCNA and RTPCR for Notch1, Lrp5, Cbfa1, Osteocalcin. In vitro studies were performed to characterize Wnt secretion from aortic valve endothelial cells and gene expression for Notch1, Lp5 and osteocalcin from the valve myofibroblast cells. This study characterizes the secretion of Wnt3a (>300-fold, p<0.01) from aortic valve endothelium in the presence of abnormal nitric oxide regulation and lipids as measured by eNOS enzymatic activity and tissue nitrite levels. Osteoblastogenesis in the adjacent myofibroblast cell is activated via Notch1 cleavage(p<0.001) and upregulation of the Wnt3a/Lrp5 receptor. Human ex vivo valves express Notch1 cleavage as compared to normal valves from heart transplant(p<0.01). Cholesterol treated eNOS mice develop severe stenosis with cleavage of Notch1, increase in Lrp5, Wnt3a, cyclin, Cbfa1, and Osteopontin,(3-fold increase(p<0.01) which was not present in the controls and normalized in the statin treated valves. Targeting the Notch1/Wnt3a/Lrp5 pathway in bicuspid valvular calcification presents a novel approach towards treating this disease. The importance of this cross talk mechanism is demonstrated in three models of aortic valve disease and will have important clinical implications.

This research has received full or partial funding support from the American Heart Association, AHA National Center.
Abstract 6171: High-dose Epoprostenol Therapy Reverses Pulmonary Hypertension by Inducing Pulmonary Artery Smooth Muscle Cell Apoptosis in Patients with Idiopathic Pulmonary Arterial Hypertension
Authors: Akagi Satoshi , Nakamura Kazufumi , Matsubara Hiromi , Nagase Satoshi , Morita Hiroshi , Kusano Kengo , Ohe Tohru
Published: July 2021

Background: Intravenous epoprostenol has been shown to improve long-term survival in patients with idiopathic pulmonary arterial hypertension (IPAH). Although most experts believe that the appropriate dose range of epoprostenol is between 25 and 40 ng/kg/min, the optimal dose has not been determined. In the present study, we investigated the hemodynamic change induced by high-dose epoprostenol therapy in IPAH patients, and we determined by experiments the reason why high-dose epoprostenol improves hemodynamics.

Methods: We evaluated hemodynamics in 16 IPAH patients (11 females and 5 males, mean epoprostenol dosage was 100.7±35.4 ng/kg/min) treated with high-dose epoprostenol. Lung tissues obtained from 2 IPAH patients and one non-PAH patient were assessed by terminal dUTP nick end-labeling (TUNEL) assays. We examined the induction of apoptosis by epoprostenol in cultured PAH-pulmonary artery smooth muscle cells (PASMCs) and non-PAH-PASMCs. To assess the apoptosis in cultured PASMCs, we performed TUNEL assay, caspase-3,-7 assays and transmission electron microscopy. We also examined the expression of survivin by immunocytochemical analysis.

Results: Compared with the baseline state, there were significant reductions in mean pulmonary artery pressure (26%) and pulmonary vascular resistance (66%). Hemodynamic improvements in the present study were superior to those in previous studies. Apoptotic cells were detected in lung tissues obtained from IPAH patients treated with high-dose epoprostenol. TUNEL-positive and caspase-3,-7-active cells were observed in cultured PAH-PASMCs treated with epoprostenol at a high concentration. Condensation of chromatin along the nuclear membrane and fragmentation of the nucleus were observed by transmission electron microscopy. Epoprostenol at a high concentration significantly induced apoptosis in cultured PAH-PASMCs compared with that in non-PAH-PASMCs (7.69% versus 1.92%; P<0.01). Immunocytochemical analysis revealed that epoprostenol suppressed expression of survivin in cultured PAH-PASMCs.

Conclusions: The results of the present study showed that high-dose epoprostenol therapy reverses pulmonary hypertension by induction of PASMCs apoptosis.
Abstract 6190: Outcomes of Carotid Stenting in Patients with Concomitant Severe Carotid and Aortic Stenosis Prior to Aortic Valve Replacement
Authors: Kar Subrata , Shishehbor Mehdi H , Tuzcu E. Murat , Bhatt Deepak L , Bajzer Christopher , Kapadia Samir R
Published: July 2021

Introduction:
Carotid stenosis increases the risk for perioperative stroke during open heart surgery. Patients with concomitant severe carotid and aortic stenosis (AS) are frequently referred for carotid intervention prior to aortic valve replacement.

Hypothesis:
We hypothesized that carotid stenting can be safe and efficacious in the setting of severe AS.

Methods:
Of the total of 829 consecutive patients that underwent carotid interventions from 1998 –2005 at the Cleveland Clinic, 52 patients (65% male, age 78.82 ± 26.16 years) with severe AS (aortic valve area ≤ 1.0 cm
2
, 0.71 ± 0.15 cm
2
) were included. Demographic, echocardiographic, and angiographic data were obtained prospectively. Our primary endpoints were stroke, transient ischemic attacks (TIAs), or death.

Results:
The mean STS Mortality scores for all groups were 6.85 ± 4.53% (n=46), six patient scores were immeasurable. There were no procedural strokes or mortality. TIA occurred in 1 patient during carotid stenting. Thirty day mortality was 6% (2 patients with LV-EF <20% died from heart failure and arrhythmia and 1 died from pulmonary embolism). Two other patients with depressed EF expired >30 days after carotid stenting prior to planned aortic valve replacement (AVR). AVR was performed in 29 of the 52 patients (26 patients ≥ 30 days post carotid stenting and 3 patients <15 days post carotid stenting). Of the remaining 23 patients, AVR was not performed due to death (n=5), high surgical risk from medical comorbidities (n=7), and patient refusal (n=3). Close monitoring and reassessment was recommended in 8 patients with asymptomatic AS. The mean STS mortality scores for patients who underwent AVR and who did not have AVR were 6.88 ± 5.05% and 6.81 ± 4.08% respectively (p=ns).

Conclusions:
Carotid interventions can be safely accomplished in patients with severe AS prior to AVR.
Abstract 1183: Longitudinal Assessment of Dyslipidemia in a Representative Sample of US Adults: Prevalence and Attainment of Goal/Recommended Levels
Authors: Ambegaonkar Baishali M , Kim Jaewhan , Biskupiak Joseph , Sazonov Vasilisa
Published: July 2021

Elevated low density lipoprotein cholesterol (LDL-C), low high density lipoprotein cholesterol (HDL-C) and elevated triglycerides (TG) are cardiovascular (CV) risk factors. The objective of this study was to evaluate attainment of goal/recommended lipid levels and predictors thereof post initiation of lipid modifying therapy (LMT) in a representative sample of US adults with commercial and government health insurance. Among 111,623 patients age >35 from GE Centricity Electronic Medical Records with ≥1 abnormal lipid value (before June 2004), we extracted 51,891 patients who initiated LMT between June 2004 and December 2006 (index date), continued therapy for 1 year, and had full lipid panels (LDL-C, HDL-C and TG) pre and post index date. LDL-C goals were defined according to NCEP ATP III guidelines. Recommended level for TG was <200 mg/dL, and for HDL-C >40mg/dL for men and >50mg/dL for women. Patients with history of coronary heart disease (CHD), diabetes and 10 year CHD risk>20% were classified as high CV risk. Multiple logistic regressions evaluated predictors of lipid level attainment (individual and ≥2). Among 51,891 patients, 53% had elevated LDL-C, 60% had low HDL-C, 37% had elevated TG and 73% had low HDL-C and/or elevated TG prior to LMT initiation. Despite 1 year therapy - with over 80% initiating statin therapy - 34% had elevated LDL-C (29% for high risk), 56% had low HDL-C (67% for high risk), 30% had elevated TG (32% for high risk) and 65% had low HDL-C and/or elevated TG (75% for high risk). CHD and diabetes were associated with better attainment of LDL-C goal and TG recommended levels. Females (Odds Ratio=0.24, 95% Confidence Interval [0.16 – 0.34]), patients with 10 year CHD risk>20% (OR=0.22, 95% CI [0.12– 0.40]) and those with higher baseline total cholesterol (OR=0.98, 95% CI [0.97– 0.99]) were less likely to attain ≥2 recommended lipid levels. In this cohort of insured US adults, additional 19% attained LDL-C goal following LMT for 1 year but few improved in terms of HDL-C (4%), TG (7%) and HDL-C and/or TG (8%). Additionally, dyslipidemia persisted among high risk patients despite higher likelihood of reaching LDL-C goal with presence of CHD or diabetes. Control of multiple lipid parameters remained poor.
Abstract 1189: Changes in the Prevalence of Abnormal Lipid Fractions among US Adults: Results from the National Health and Nutrition Examination Survey II, III, and 1999–2006
Authors: Cohen Jerome D , Cziraky Mark J , Jacobson Terry A , Wallace Anna , Cai Cassie
Published: July 2021

Objective
To examine the prevalence of abnormal lipid fractions among US adults from 1976 through 2006, with a focus on the relationship of dyslipidemia and obesity.

Methods
Adults aged 20 to 74 years who took the blood lipid examination were selected from the National Health and Nutrition Examination Surveys (NHANES): NHANES II (1976 –1980), NHANES III (1988 –1994), and NHANES 1999 –2006. Obesity was defined as BMI ≥ 30 kg/m
2
. Dyslipidemia was defined as presence of one or more abnormal lipid fractions: low density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL, high density lipoprotein cholesterol (HDL-C) < 40 mg/dL, and triglycerides (TG) ≥ 150 mg/dL. Crude and age-stratified proportions of abnormal lipid fractions for US adults and for those with obesity were estimated. Multivariate analysis was used to assess the association between dyslipidemia and obesity, controlling for age, gender, race/ethnicity, NHANES wave, and comorbidities (heart attack, diabetes and smoking status).

Results
The prevalence of abnormal LDL-C decreased from 43.5% in NHANES II to 36.3% in NHANES 1999–2006; however, during this period, the prevalence of abnormal TG and HDL-C combined doubled from 2.1% to 4.8% and the abnormal TG more than tripled within the elderly population (from 1.8% to 11.3%). It was estimated that antidyslipidemic medication use was less than 2.6% for adults with dyslipidemia throughout study period. With the increased prevalence of obesity between NHANES II and NHANES 1999 –2006, the prevalence of abnormal TG and HDL-C combined increased from 3.8% in NHANES II to 6.5% in NHANES 1999 –2006 within obese adults. Multivariate analyses of BMI with dyslipidemia were significant (p< 0.001). Adults with obesity were more likely to have dyslipidemia than those with BMI < 25 kg/m
2
[OR=2.9, (95% CI: 2.7–3.2)].

Conclusions
Prevalence of abnormal TG and/or HDL-C increased between NHANES II and NHANES 1999–2006 although the abnormal LDL-C shows an optimistic trend. This was paralleled by a shift in the distribution of BMI toward the obese category. As the US population is aging and becoming more obese, this analysis underscores the need for renewed public health efforts with focus on treating multiple abnormal lipid fractions and preventing dyslipidemia via body mass control.
Abstract 1190: Association of Smoking Status with Incidental Metabolic Syndrome in Men; a 3-year Follow-up Study
Authors: Kim Byung Jin , Sung Ki Chul , Kim Bum Soo , Kang Jin Ho , Lee Man Ho
Published: July 2021

Although cigarette smoking has been known to be a risk factor for increased insulin resistance and other metabolic abnormalities, there is no data to assess the association of smoking status with incidental metabolic syndrome (MS). We investigated the incidence of MS and assessed the effect of smoking status on incidental MS. The subjects were 4542 men (median age of 44 years) without MS who were followed for an average of 3 years. For analysis, smoking status was divided into 4 groups, non-smokers, new-smokers, ex-smokers, or sustained-smokers, according to smoking status at baseline and 3-year follow-up. The overall incidence of MS was 10.6%; the incidence of MS in each group was 8.0% in the non-smokers, 7.1% in the new-smokers, 17.1% in the ex-smokers, and 13.9% in sustained-smokers (p<0.0001). In a multivariate logistic regression model (Model 1) adjusting for age, baseline weight, alcohol consumption, exercise, and baseline number of MS components, sustained-smokers and ex-smokers predicted a significant increased odds for incidental MS of 1.68 (95% CI 1.33–2.12) and 2.43 (95% CI 1.80 –3.29), respectively, as compared with non-smokers. When weight change is included (Model 2), the odds ratios were attenuated (1.54[1.21–1.95] ; 1.87[1.37–2.56], respectively). Among sustained-smokers, the odds ratio for incidental MS increased according to the amount or the duration of smoking. Furthermore, ex-smokers had a significant increased odds for incidental MS of 1.45 (95% CI 1.06 –1.98), compared with continuous-smokers (model 1). This was no longer significant after including weight change (model 2). In conclusion, either sustained smoking or smoking cessation in 3 years is a risk factor for incidental metabolic syndrome in men, independent of weight change, as compared with non-smoking. Also smoking cessation in 3 years might be a higher risk factor for incidental MS than sustained smoking. Our study indicates that weight control in men, especially with smoking cessation is critical to attenuate the additional risk for incidental MS.
Abstract 1199: Low Serum Magnesium Concentrations Predict Increase in Left Ventricular Mass Over Five Years Independently of Common Cardiovascular Risk Factors: Study of Health in Pomerania
Authors: Reffelmann Thorsten , Dörr Marcus , Ittermann Till , Völzke Henry , Ruppert Jörg , Robinson Daniel , Felix Stephan B
Published: July 2021

Increased cardiac left ventricular mass (LVM) is a significant predictor of adverse cardiovascular events. Experimental studies suggest a pathophysiological role of magnesium (Mg
++
) in the development of arterial hypertension and left ventricular hypertrophy (LVH). Subjects, aged 45 – 79 years, from the population-based, epidemiological, longitudinal “Study of Health in Pomerania” with complete echocardiographic data (n = 1 348 after exclusion of aortic valve disease) were grouped into five quintiles according to serum Mg
++
at baseline (0.790±0.003 mmol/l, mean±SEM). In the lowest Mg
++
-quintile (Mg
++
<<26>0.73 mmol/l), LVM (187.4±3.1 g at baseline) increased by 14.9±1.2 g over the following five years, while in the highest Mg
++
-quintile (Mg
++
<<0.85 mmol/l) LVM (186.7±3.4 g at baseline) decreased by −0.5±2.8 g (p<0.0001 between quintiles). After five years, LVM was significantly higher in the lowest Mg
++
-quintile (LVM: 202.2±3.4 g) in comparison to the highest Mg
++
-quintile (187.2±3.5 g, p<0.003 between quintiles). Mg
++
inversely correlated with the difference in LVM over five years (p<0.0001, females: p<0.002, males: p<0.024) and also with differences in Sokolow-Lyon-index over five years (p<0.01). Unlike age, gender, presence of hypertension or diabetes mellitus, body mass index, smoking status, renal function, high-sensitive C-reactive protein and use of various antihypertensive drugs including diuretics, only Mg
++
(p<0.0001), pulse pressure (p<0.002) and use of β-blockers (p<0.04) were identified as independent predictors of difference in LVM over five years. Hypomagnesemia is one of the strongest predictors of increase in LVM over the following five years. It should initiate decisive preventive measures in subjects prone to developing LVH.
Abstract 1252: A Multimarker Strategy for Risk Prediction in Heart Failure: Application of Novel Methods in a Community Cohort
Authors: Dunlay Shannon M , Gerber Yariv , Weston Susan A , Killian Jill M , Redfield Margaret M
Published: July 2021

Introduction:
Mortality among patients with heart failure (HF) is high. Though individual biomarkers have been studied to determine their value in risk prediction, the role of a multimarker strategy in predicting mortality above established risk indicators requires evaluation in a relevant cohort using robust analytical methods.

Objective:
To determine whether adding C-reactive protein (CRP), B-type natriuretic peptide (BNP), and troponin T (TnT) to established risk indicators improved HF mortality risk prediction.

Methods:
Olmsted County residents presenting with HF from July 2004 to September 2007 were prospectively recruited to undergo biomarker measurement. We investigated whether addition of CRP, BNP, and TnT to a model including established risk indicators improved 6-month mortality risk prediction using multiple methods (
c
statistic, net reclassification index, integrated discrimination improvement).

Results:
Of 566 participants (mean age 77±13 years, 48% male), 87(15%) patients died after 6 months follow-up. Patients with CRP (<12.1mg/L), BNP (<341pg/mL), and TnT (≥0.01ng/mL) below the median (n=112) had the lowest mortality (3%), those with one or two biomarkers above the median had intermediate mortality, and those with all biomarkers above the median (n=105) had markedly increased 6-month mortality (33%). After adjustment for other predictors, higher CRP, BNP, and TnT were each associated with increased mortality, with odds ratios (95% confidence intervals) of 1.66(1.24 –2.24), 2.06(1.42–3.07), and 1.45(1.12–1.87), respectively. While adding CRP, BNP, and TnT individually to the model improved mortality risk prediction, the combination of two or more biomarkers offered greater incremental benefit. Using all biomarkers resulted in an increase in the
c
statistic from 0.747 to 0.832 (p<0.001), a net reclassification index of 0.33 (p<0.001), and a 100% relative improvement in risk discrimination (integrated discrimination improvement 0.097, p<0.001).

Conclusions:
The combined use of CRP, BNP, and TnT markedly improved the prediction of 6-month mortality in HF beyond established risk indicators. Implementation of a multimarker strategy including CRP, BNP, and TnT for risk prediction in HF should be considered.

This research has received full or partial funding support from the American Heart Association, AHA Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).
Abstract 3104: Heart Failure: Is there an Epidemic? A 17-Year Longitudinal Study on the Incidence, Prevalence and Survival Outcomes
Authors: Teng Tiew-Hwa K , Finn Judith , Hobbs Michael , Geelhoed Elizabeth , Hung Joseph
Published: July 2021

Background
Despite concerns of a heart failure ‘epidemic’, long term population trends on the incidence, prevalence and survival outcomes of heart failure (HF) are not well characterized.

Methods
The Western Australian Hospital Morbidity Database was used to identify index patients with first-time admissions for HF from 1990 to 2006, with no prior admission for HF since 1 January 1980. Age and gender adjusted temporal trends in HF incidence were examined and Cox-proportional hazards model used to analyse 5-year survival following index admissions, adjusted for significant covariates. Prevalence was calculated at end of each calendar year. Base period used was 1990–1993.

Results
There were 70,967 index heart failure (HF) patients identified during 1990–2006, with almost equal distribution between genders. There was a significant downward trend for age and gender-adjusted incidence of HF with average decline of 1.73% (95% CI 1.5%, 1.9%, p=0.001) per year over the 17-year period. Incidence rate reached a peak in 1993 and thereafter there was a steady decline. Compared to the base period, age and gender-adjusted survival at 5-year after index HF admission improved with an absolute survival gain of 6.9% (95% CI 4.3%, 9.4% p=0.001) for 1994–97 period, 9.3% (95% CI 6.7%, 11.9%, p=0.001) for 1998–2001 period and 7.0% (95% CI 4.1%, 9.8%, p=0.001) for 2002– 05 period respectively. Prevalence of HF increased significantly over the different time periods, with a 2.26 fold higher prevalence in 2002–2006 compared to base period. The increase in prevalence was greatest in the 70–79 year age group, with an increase from 200.3 per 10,000 in the base period to 606.0 per 10,000 in 2002–2006.

Conclusions
In the last 17 years, incidence of hospitalized HF patients has declined steadily in both genders. However, there has been a marked increase in prevalence of HF due in part to an ageing population and improved HF survival. Management of these chronic elderly HF patients remains a major public health problem.
Abstract 3112: Slower Periodic VO
2
Oscillations during Exercise Indicate Worse Clinical Status and Poorer Prognosis of Patients with Heart Failure
Authors: Ibuki Motoaki , Takaki Hiroshi , Oishi Shogo , Taniguchi Takuya , Kawakami Rika , Noguchi Teruo , Goto Yoichi , Sugimachi Masaru
Published: July 2021

Purpose:
It is generally assumed that the cycle length (CL) of periodic VE or VO
2
oscillation, an ominous sign seen during exercise in advanced heart failure (HF), is approximately one minute. However, in our experience, the duration seems to vary substantially among individuals, and the differences in CL may be of clinical and prognostic value. We hypothesized that CL varies substantially among patients with HF and that slower oscillations indicate worse clinical status and prognosis.

Methods:
From a consecutive series of over 4500 symptom-limited bicycle exercise tests with respiratory gas analysis performed for recent 5.5 years, we selected 50 patients (LVEF = 31 ± 13%) with HF exhibiting the most marked exercise VO
2
oscillations that allowed us to accurately measure CL. The patient selection were made by our developed FFT method estimating the ratio of low-frequency power (0.5–1.25 cycle/min) relative to total power (4-min time-window, overlapping every 30sec). After averaging CL of at least 3 periodic VO
2
fluctuations for each patient, patients were evenly divided into two groups according to the median of CL: Group-S (Slower, longer CL, n=25) and Group-F (Faster, shorter CL, n=25). Demographic, clinical, prognostic, and exercise data were compared between the groups.

Results:
We found that CL substantially varied from 45 to 118 sec (median = 67 sec). CL of Group-S was 80 ± 11 sec, while that of Group-F was 59 ± 6 sec. There was no significant difference with respect to age, sex, and etiology of HF between the groups. Compared with Group-F, Group-S showed lower peak VO
2
(15.4 ± 3.6 vs 18.6 ± 4.2 ml/min/kg, p=0.005) and oxygen pulse (7.4 ± 2.5 vs 9.5 ± 2.1 ml, p=0.002), and greater VE/VCO
2
slope (42 ± 12 vs 37 ± 8, p=0.049). Group-S also had higher BNP level (457 ± 348 vs 256 ± 275 pg/ml, p=0.03). Kaplan-Meier mortality rates for cardiac and all-cause death were significantly higher in Group-S than in Group-F (both, p<0.05).

Conclusions:
We demonstrated that cycle length of exercise VO
2
oscillations substantially varies among patients with heart failure, and that the difference is of clinical significance; the slower the cycle length, the worse the clinical status and prognosis.
Abstract 3118: Combined Assessment of Intima-Media Thickness and Echolucency of an Atherosclerotic Plaque in Carotid Artery has an Additive Value on Prediction of Future Coronary Events in Patients with Coronary Artery Disease and Carotid Atherosclerosis
Authors: Hirano Mitsumasa , Nakamura Takamitsu , Kitta Yoshinobu , Takishima Isao , Makino Aritaka , Sano Keita , Kodama Yasushi , Kawabata Ken-ichi , Obata Jun-ei , Kugiyama Kiyotaka
Published: July 2021

Single ultrasound assessment of either intima-media thickness (IMT) or plaque echolucency of carotid artery is considered a surrogate for systemic atherosclerotic burden and provides prognostic information for coronary events. The assessment of IMT and plaque echolucency of carotid artery has the advantage of obtaining structural and compositional information on atherosclerotic plaques in a single session. This study examined the hypothesis that the combined ultrasound assessment of IMT and echolucency in a carotid artery may have an additive effect on the prediction of coronary events in patients with coronary artery disease (CAD). Ultrasound assessment of carotid IMT and plaque echolucency with integrated backscatter (IBS) analysis (intima-media IBS value minus adventitia IBS) was performed in 411 patients with CAD and carotid plaques (IMT ≥ 1.1 mm). The plaque with the greatest axial thickness in carotid arteries was the target for measurement of maximum IMT (plaque-IMTmax) and echolucency (lower IBS reflects echolucent plaque). All patients were prospectively followed up for 70 months or until the occurrence of one of the following coronary events: cardiac death, nonfatal myocardial infarction, or unstable angina pectoris requiring revascularization. During follow-up, 49 coronary events occurred (cardiac death in 2, myocardial infarction in 10, unstable angina in 37). In a multivariate Cox hazards analysis, plaque-IMTmax and plaque echolucency (lower IBS value) were significant predictors of coronary events (HR; 1.82 and 0.85, 95% CI 1.2 – 2.9 and 0.80 – 0.91, respectively, both p < 0.01) independently of age, LDL-C levels, and diabetes. When outcomes were stratified according to plaque-IMTmax and plaque echolucency in combination or alone, the combination of plaque-IMTmax and plaque echolucency was the strongest predictor of events, followed by plaque echolucency and plaque-IMTmax, on the basis of the
c
-statistic (area under the ROC curve; 0.80, 0.73, and 0.71, respectively). Combined ultrasound assessment of IMT and echolucency of carotid plaque had an additive value on the prediction of coronary events, and these simultaneous ultrasound measurements may be useful for risk stratification in CAD.
Abstract 3126: Coronary Artery Calcification as a Predictor of Subsequent Coronary Artery Disease Events
Authors: Costacou Tina , Orchard Trevor J
Published: July 2021

Coronary artery calcification (CAC) as measured by electron beam computed tomography (EBCT) can be used as an indicator of atherosclerotic burden. We have previously reported a cross sectional association between the presence of CAC and history of clinical coronary artery disease (CAD) in type 1 diabetes. In this analysis, we assessed the ability of CAC to predict the incidence of CAD events. Participants from the Pittsburgh Epidemiology of Diabetes Complications Study of childhood onset type 1 diabetes who underwent an EBCT screening (1996–98) and were free of clinical CAD were selected for study (n=236). Mean age at EBCT screening was 36.6 years and diabetes duration 28 years. CAC was calculated using the Agatston score and was used both as a continuous variable (after log transformation) and as a categorical variable. CAD was defined as non-fatal MI (n=4), ischemic ECG changes (Minnesota codes 1.3, 4.1, 4.2, 4.3, 5.1, 5.2, 5.3, 7.1) (n=9), hospitalized unstable angina (n=1), new onset angina leading to revascularization (n=2) or fatal CAD (n=4). Glucose disposal rate (eGDR-insulin sensitivity) was estimated by a regression equation derived from hyperinsulinemic euglycemic clamp studies with terms for waist to hip ratio, HbA
1c
, and hypertension. During a mean follow-up of 7.4 years, 20 (8.5%) individuals had an incident event. Individuals who had an event were older, with a greater diabetes duration, systolic blood pressure, HbA
1c
, and WBC count, a lower eGDR (all p-values <0.05), and a higher CAC score (p<0.0001). Thus, approximately 24% of persons with CAC ≥200 had a subsequent CAD event compared to only 3% of those with a zero score. In multivariable Cox proportional hazard models with backward elimination, a CAC score greater than zero was a significant predictor of CAD incidence (HR=4.07, 95% CI=1.38–11.96). Other significant predictors comprised diabetes duration (HR=1.07, 95% CI=1.01–1.14) and HbA
1c
(HR=1.39, 95% CI=1.10–1.76). The area under the ROC curve increased from 0.720 to 0.784 with the inclusion of CAC score. In this cohort of individuals with type 1 diabetes, CAC is a significant predictor of subsequent CAD status and adds to the prediction beyond standard risk factors. Thus, CAC may be used as a screening tool for CAD risk in type 1 diabetes.
Abstract 3164: Combined Antithrombotic Therapy in Atrial Fibrillation. Role of different Antiplatelet Strategies
Authors: Pérez-Gómez Francisco , Bover Ramón , Salvador Antonio , Maluenda María Paz , Asenjo Susana , Pérez-Saldaña Rosario , Igea Angel , Suarez Marta , Coleto Dulcenombre , Fernández Cristina
Published: July 2021

The NASPEAF trial showed that combined anticoagulant plus antiplatelet therapy was more effective than anticoagulant alone at reducing vascular events in atrial fibrillation (AF) patients. We planned both to validate this benefit during a longer follow-up of patients included in that trial and to assess the hypothesis that combination of anticoagulation plus different antiplatelets could be differently effective and/or safe in patients from that trial and new ones followed-up for at least one year. Methods: Five hundred and seventy-four AF patients were included. Anticoagulation alone therapy (INR 2.0 –3.0) was used as control group (g) 1 to compare with anticoagulation (1.9 –2.5) plus either trifusal 600 mg/d (g2), trifusal 300 mg/d (g3) or aspirin 100 mg/d (g4). Median follow-up was 50, 32, 50 and 37 months respectively. The primary outcome was a composite of ischemic/haemorrhagic stroke, systemic/coronary ischemic events and cardiovascular death. The incidence of severe bleeding was also collected. Anticoagulation was regularly controlled in dedicated units. Results: Long-term follow-up showed benefit of combined anticoagulant plus trifusal 600 mg/d vs anticoagulant alone (primary outcome 2.86% pt/years in g1 vs 1.36% in g2, P=0.014). Combined therapy using other antiplatelet strategies was less effective or safe due to higher incidence of ischemic events when using trifusal 300 mg/d (2.44% pt/years in g3 vs 0.61% in g2, P=0.031) as well as more severe bleeding events with aspirin 100 mg/d (6.60% pt/years in g4 vs 1.51% in g2, P=0.008). Groups g1, g3 and g4 had similar primary outcome (2.86% pt/years, 2.67% and 2.83% respectively). Mean INR and other anticoagulation parameters were similar in the three combined therapy groups. Non-gastric severe bleeding incidence during combined therapy with trifusal 600 mg/d (0.3% pt/years) was lower than that observed in either anticoagulant alone therapy (2.1%, P=0.012) or combined with aspirin (6.60%, P=0.008). In conclusion, long-term follow-up of the NASPEAF trial confirmed the benefit of combined antithrombotic therapy over anticoagulant alone therapy. Combined therapy with aspirin 100 mg/d instead of trifusal 600 mg/d caused higher incidence of severe bleeding.
Abstract 3175: Factors Associated with Longer Delays from Symptom Onset to Hospital Presentation in Patients with Acute Myocardial Infarction
Authors: Chan Paul S , Nallamothu Brahmajee K , Ting Henry H , Tang Fengming , Krumholz Harlan M , Spertus John A
Published: July 2021

Delayed contact with the medical system may lead to worse patient outcomes in acute myocardial infarction (AMI), particularly ST-elevation myocardial infarction (STEMI). We examined the effect of previously unstudied aspects of patients’ characteristics on delays to presentation, including health status, depressive symptoms, and socioeconomic status. Within the Translational Research Investigating Underlying disparities in acute Myocardial infarction Patients’ Health status (TRIUMPH) study, we examined predictors of delays to hospital presentation in 1,476 patients with AMI from 26 sites using multivariable hierarchical ordinal models. Time from symptom onset to hospital presentation was categorized as ≤2 hours, >2 to 6 hours, and >6 hours. Time to hospital presentation was ≤2 hours in 540 (36.6%) patients, between 2– 6 hours in 354 (24.0%) patients, and >6 hours in 582 (39.4%) patients. Factors associated with longer delays to presentation included frequent angina (compared to no angina: daily angina, Odds Ratio [OR] of 3.48 [95% CI: 1.53–7.88]; weekly angina, 2.46 [1.64 –3.67]; and monthly angina, 1.26 [0.96 –1.64]; p for trend<.001), presentation during weekday work hours (8am to 5pm) (compared to weekend: weekday, 1.40 [1.06, 1.85]; weeknight, 1.15 [0.85,1.54]; p for trend = 0.05), cost barriers (1.39 [1.05 to 1.85]; p=0.02), and no healthcare insurance (1.56 [1.15–2.12]; p=0.005). In contrast, patients with STEMI (0.55 [0.43– 0.70]; p<.001), prior coronary revascularization (0.67 [0.48 – 0.92]; p=0.01) and prior AMI (0.68 [0.48 – 0.97]; p=0.03) were more likely to present earlier. No relationship was found for depression, educational level, social support, or marital status. More frequent angina, cost barriers, no healthcare insurance, and time of day are associated with longer delays to hospital presentation, while those with prior AMIs and coronary revascularization were more likely to present earlier. Efforts to reduce delays should address patient issues related to health status (like angina), cost burden, and healthcare access.