bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P444: Long-Term Prognosis of Stress Cardiomyopathy in Women
Authors: Salmoirago-Blotcher Elena , Reddy Sandhya , Goldberg Robert J , Lessard Darleen M , Fitzgibbons Timothy , Bouchard Joseph , Crawford Sybil , Ockene Ira S , Aurigemma Gerard P
Published: July 2021

Background:
Transient Stress Cardiomyopathy (TSC) is a reversible condition mimicking acute myocardial infarction that frequently affects postmenopausal women and is often triggered by emotional or physical stress. Limited information is available about the long-term prognosis of this condition as previous studies were mostly case series and/or were unable to adjust for several confounding variables. The aim of this retrospective cohort study was to assess the post-hospital discharge prognosis of women diagnosed with TSC compared with historical ST-elevation myocardial infarction (STEMI) female controls. The principal study outcome was a composite of cardiovascular (CV) hospital readmissions and death from any cause.

Methods:
Cases were identified by reviewing the charts of consecutive women hospitalized at UMass Memorial Medical Center in Worcester, MA, with an ICD-9 code of 429.83 (Takotsubo cardiomyopathy) from 01/2002 until 06/2012. To be eligible, cases had to fulfill all Mayo clinic criteria for TSC. Controls were randomly selected (2:1 ratio) among women with a validated diagnosis of STEMI enrolled in the Worcester Heart Attack Study during the same period. Clinical characteristics and information about CV readmissions and death were abstracted from the medical record. Survival curves were generated by the Kaplan-Meier method. Log-rank statistics was used to compare survival curves. Risk of death or CV readmissions (with the STEMI category as the referent) was estimated from multivariate Cox proportional hazard regression models adjusted for variables associated with the composite outcome.

Results:
Out of 356 consecutive women hospitalized with an ICD-9 code of 429.83 (Takotsubo cardiomyopathy), 50 met Mayo diagnostic criteria. Baseline age was 65±14 years in TSC cases and 71 ±15 in STEMI controls (n=100). The prevalence of coronary risk factors, and of a history of angina, stroke and heart failure, was lower among TSC cases vs. controls. At admission, TSC women had lower peak CK, troponin I levels and SBP values; mean (angiogram) ejection fraction was 0.32 in TSC and 0.47 in STEMI women. TSC cases were less frequently prescribed aspirin, beta-blockers, lipid lowering agents and ACE inhibitors at hospital discharge. Over an overall average follow-up of 2 years, incidence rates of the composite outcome were 140/1,000 person-years among women with TSC and 347/1,000 person-years among those with STEMI. In multivariate adjusted models, the hazard ratio for the composite endpoint in TSC vs. STEMI women was 0.50 (CI: 0.26,0.98).

Conclusion:
Women diagnosed with TSC had a significantly better post-discharge prognosis than women with STEMI. However, mortality and CV readmissions rates among TSC women were relatively high, indicating that TSC is not a benign condition.
Abstract P450: Young Women with Increased Cardiovascular Disease Risk Burden have Poor Health Literacy
Authors: Paul Tracy K , Sciacca Robert R , Rodriguez Juviza K , Giardina Elsa-Grace V
Published: July 2021

Introduction:
Young women are thought to have low cardiovascular disease (CVD) risk; however, mortality due to ischemic heart disease has actually risen among women aged 35-44 years. We hypothesized that young women with increased CVD risk burden are more likely to misperceive body image and less likely to practice healthful behaviors.

Methods:
To determine CVD risk burden among young women (aged 18-49 years) of a primarily urban population, 569 women visiting outpatient medical clinics were assessed. Anthropometric measures [height, weight, waist, body mass index (BMI)], attitudes towards weight, and lifestyle behavior were determined. Body image self-perception was assessed using validated silhouette scales. Increased CVD risk burden was defined as presence of hypertension, diabetes mellitus, tobacco use, hyperlipidemia, and/or obesity.

Results:
Participants were Hispanic (62.7%; 357/569); non-Hispanic White (20.7%; 118/569); non-Hispanic Black (8.9%; 51/569) and Asian/other ethnicity (7.5%; 43/569); mean age was 35.9 years ± 8.1 and income $39,828 ± $20,229. BMI categories were: obese (BMI ≥ 30 kg/m
2
, 27.4%; 155/569); overweight (BMI 25.0 - 29.9 kg/m
2
, 29.0%; 164/569); normal (BMI 18.5 - 24.9, 41.2%; 233/569); and underweight (BMI ≤ 18.4; 2.3%; 13/569). Women without CVD risk burden were the reference standard.

Nearly half (47.7%; 271/569) had increased CVD risk burden; and 33.5% (190/569) had ≥ 1 CVD risk factor, exclusive of obesity, including hypertension (18.0%), hyperlipidemia (11.5%), current tobacco use (10.2%), and diabetes mellitus (5.8%).

Women with increased CVD risk were less likely to correctly identify body size (48.3% vs. 69.4%, p<0.0001). They were more likely to be concerned about weight (82.0% vs. 65.8%, p =0.01) and actively trying to lose weight (77.3% vs. 65.4%, p=0.03). But, they were less likely to read nutrition labels when making food choices (29.4% vs. 17.9%, p=0.03) and more likely to cite cost (18.7% vs. 12.1%, p=0.03) and difficulty implementing a weight loss regimen (22.2% vs. 15.6%, p=0.05) as barriers to losing weight. Most, regardless of CVD risk burden, knew blood pressure, cholesterol, and blood sugar status. However, women with increased CVD risk burden were less likely to know cholesterol level (81.4% vs. 88.8%, p=0.02). Fewer obese women knew that tobacco contributes to CVD risk compared to non-obese women (92.3% vs. 96.6%, p=0.04).

Conclusion:
Paradoxically, though aware of their CVD risk factors and with heightened weight concerns, young women with increased CVD risk burden misperceive their body size and lack healthy behavior knowledge. A disconnect exists between this group’s recognition of their underlying risk and ability to modify their lifestyle to decrease CVD risk burden.
Abstract 101: Top Quality of Ventilation During Out-of-Hospital Cardiac Arrest Is Hard to Reach
Authors: Datler Philip , Sulzgruber Patrick , Poppe Michael , Keferböck Markus , Zeiner Sebastian , Lobmeyr Elisabeth , Nürnberger Alexander , Van Tulder Raphael , Krammel Mario , Sterz Fritz
Published: July 2021

INTRODUCTION:
With an incidence of ~45patients with out-of hospital cardiac arrest (OHCA) /100.000 inhabitants per year and thus over 700 cases annually, but a survival rate as low as 10%, OHCA remains still a challenge the chain of survival. Recently ventilation has gained less importance for BLS and thus the question arises, if this attitude was mirrored during ALS measures provided by ambulance crews. Therefore our analysis assessed the quality of ventilation during out of hospital cardiac arrests.

METHODS:
Over a period of 9 months, from August 1st 2013 until April 30th 2014, all patients suffering from an OHCA, aged 18 years and above and treated by the emergency medical service crews in Vienna, Austria were included in this study. A collective of 701 consecutive cases have been analyzed using the ECG- and impedance data recorded by the defibrillators used. On the basis of this data, the abidance of the quality standards of ventilation was examined using the current guidelines of the European Resuscitation Council of 2010 as gold standard. After the evaluation of each case, the responding EMS-teams were informed about the quality of the resuscitation via a feedback form.

RESULTS:
Endotracheal intubation was accomplished in 338 patients (47%). Ventilation was performed in accordance to the ERC guidelines in 49% (CI: 46-52) of total recorded ventilation minutes. Patients who had restoration of spontaneous circulation (ROSC) (n=135) after being intubated were ventilated with 9 (CI: 9-11; variance: 11) ventilations per minute. In patients not achieving ROSC (n=203) 10 (CI: 9-11; variance: 25) ventilations per minute were administered. Patients that were ventilated with a supraglottic airway device or a bag valve and mask received 6(SD±4) ventilations per minute.

CONCLUSION:
The high ventilation rate standard deviations within the compliance to guidelines suggest that there are numerous cases in which ventilation standards are not met. Therefore further analysis will be necessary to find out, what influence this might have on outcome and if it will be necessary to put more emphasis in upcoming discussions on the quality of ventilation at least during advanced life support.
Abstract 11017: Renin Inhibition Reduces Atherosclerotic Plaque Neovessel Formation and Regresses Advanced Atherosclerotic Plaques
Authors: WU Hongxian , Cheng Xian Wu , Hu Lina , Hao Chang-Ning , Hayashi Mutsuharu , Takeshita Kyosuke , Hamrah Mohammad Shoaib , Shi Guo-Ping , Kuzuya Masafumi , Murohara Toyoaki
Published: July 2021

Background:
The interaction between the renin-angiotensin system and toll-like receptors (TLRs) in the pathogenesis of advanced atherosclerotic plaques is not well understood. We studied the effects of the renin inhibitor aliskiren on the progression of advanced atherosclerotic plaque in apolipoprotein E-deficient (ApoE
–/–
) mice with a special focus on plaque neovessel formation.

Methods and Results:
Four-wk-old ApoE
–/–
mice were fed a high-fat diet for 8 wks, and the mice were randomly assigned to one of three groups and administered a vehicle, hydralazine, or aliskiren for an additional 12 wks. Aliskiren reduced the atherosclerotic plaque area and plaque neovessel density. It increased the plaque collagen and elastin contents, and reduced plasma angiotensin II levels and plaque macrophage infiltration and cathepsin S (CatS) protein. Aliskiren also decreased the levels of AT1R, gp91phox, TLR2, monocyte chemotactic protein-1, and CatS mRNAs in the aortic roots. Hydralazine had no beneficial vascular effects, although its administration resulted in the same degree of blood pressure reduction as aliskiren. CatS deficiency mimicked the aliskiren-mediated vasculoprotective effect in the ApoE
–/–
mice, but aliskiren showed no further benefits in ApoE
–/–
CatS
–/–
mice.
In vitro
, CatS mRNA expressions were induced by angiotensin II, and TLR2 silencing reduced CatS mRNA expression. Moreover, the genetic inhibition of CatS impaired the endothelial cell angiogenic action
in vitro
and
ex vivo
.

Conclusion:
Renin inhibition appears to inhibit advanced plaque neovessel formation in ApoE
–/–
mice and to decrease the vascular inflammatory action and extracellular matrix degradation, partly by reducing AT1R/TLR2-mediated CatS activation and activity, thus regressing advanced atherosclerotic plaques.
Abstract 11056: Hospitals Accepting Greater Proportions of High Risk Transfer-In STEMI Patients Do Not Have Higher Risk-Adjusted Hospital Mortality: A Report From the AHA Mission: Lifeline Program
Authors: Kontos Michael C , Wang Tracy Y , Chen Anita Y , Thomas Laine , Bates Eric , Dauerman Harold , Henry Timothy , Manoukian Stephen V , Roe Matthew T , French William J
Published: July 2021

Background:
Mortality is an important quality measure for acute MI hospital care. There is concern that, despite risk adjustment, PCI receiving hospitals receiving a disproportionate volume of high risk STEMI transfers may have their reported mortality adversely affected.

Methods:
All STEMI patients from April 2011 to December 2013 in the ACTION Registry®-GWTG™ were included. High risk was defined as pts with either cardiogenic shock or cardiac arrest on admission. Hospitals were divided into tertiles based on the proportion of high risk STEMI patients who were transferred relative to the total number of STEMI patients treated. Adjusting for covariates in the ACTION mortality risk model, the differences in risk-adjusted in-hospital mortality in each tertile were determined before and after excluding high risk STEMI transfer pts.

Results:
Among 119,680 STEMI pts treated at 539 primary PCI hospitals, 37,028 (31%) pts were transfers, of whom 4,500 (4%) were high risk. The proportion of high risk STEMI transfers ranged from 0-12% across hospitals. Times from initial hospital presentation to PCI were similar across tertiles: Low 107 min; Middle, 100 min; High 106 min. The ACTION mortality risk model, which includes cardiogenic shock but not cardiac arrest, slightly underestimated mortality for high-risk STEMI transfer pts (observed in-hospital mortality rate: 26%, predicted mortality rate: 24%). While differences in observed hospital mortality were present among hospitals with a greater proportion of high-risk transfers, risk-adjusted mortality was unaffected by the inclusion or exclusion of high-risk transfer patients across all tertiles (TABLE).

Conclusions:
Receiving PCI hospitals accepting greater proportions of high risk STEMI transfer pts did not have a higher risk-adjusted in-hospital mortality when a clinical mortality risk model was used for risk adjustment.
Abstract 11065: Paradoxical Impact of Overweightness on Mortality in Lung Transplantation
Authors: Chaikriangkrai Kongkiat , Jhun Hye Yeon , Jyothula Soma
Published: July 2021

Background:
Prognostic value of body mass index (BMI) and cardiorespiratory fitness (CRF) has been described extensively in various populations. The objective of this study was to examine impact of BMI and CRF on all-cause mortality in isolated lung transplant recipients.

Methods:
Consecutive isolated lung transplant recipients from 2008 to 2013 were identified. Pre-transplant cardio-metabolic risk factors were collected. The cohort was categorized using BMI into normal (BMI 18.5-24.9 kg/m
2
), underweight (BMI < 18.5 kg/m
2
), overweight (BMI 25.0-29.9 kg/m
2
) and obese (BMI ≥ 30 kg/m
2
). Fit patient was defined as those who had pre-transplant six-minute-walk distance > 300 m.

Results:
The study comprised of 324 patients with mean age of 57 ± 13 years. Fifty eight percent were male. Primary lung pathologies were 26.9% obstructive, 2.5% vascular, 6.5% cystic fibrosis and 64.2% restrictive lung diseases. Pertinent cardio-metabolic risk factors included 36.7% normal weight, 9.9% underweight, 33.6% overweight, 19.8% obese, 21.9% unfit, 13.9% coronary artery disease, 55.6% hypertension, 29.6% diabetes mellitus, 42.3% hyperlipidemia, 42.9% smoking history. Annualized mortality rate stratified by BMI exhibited J-shaped distribution with lowest mortality in overweight group (p 0.005). Kaplan Meier analysis correspondingly showed highest survival in overweight strata (p 0.006). In subgroup analysis by CRF, paradoxical impact of overweightness on mortality was diminished in fit patients (p>0.05) but not in those who were unfit (p<0.05) as shown in figure 1.

Conclusion:
In our lung transplant cohort, BMI and mortality had J-shaped relationship with highest survival in overweight group. This paradoxical impact was diminished in patients who were fit. Our findings extend the paradigm of obesity paradox into lung transplantation arena.
Abstract 11089: Hepatic Abnormalities are Present Before and Early After the Fontan Operation
Authors: Schwartz Matthew , Glatz Andrew C , Daniels Kaitlyn , Goldberg David J , Rand Elizabeth , Epelman Monica , Cohen Meryl S
Published: July 2021

Objectives:
Progressive hepatic fibrosis is common after the Fontan operation, but little is known about its onset. We sought to determine if there is non-invasive evidence of hepatic injury prior to the Fontan operation, and if further injury is seen soon after the procedure.

Methods:
Patients undergoing the Fontan operation at our institution were prospectively enrolled and underwent hepatic ultrasound with Doppler and serum testing immediately before and 3 to 6 months after the operation.

Results:
Thirty patients were enrolled at a median age at time of the Fontan operation of 3.1 yrs (range: 2.2-8.1 yrs). An extracardiac Fontan operation was performed in 67% and nearly all (97%) underwent fenestration. Three patients (10%) had abnormal hepatic echotexture prior to the Fontan operation. At the post-Fontan study, mean liver length increased (9.9 vs. 10.9 cm, p<0.0001) and mean hepatic artery end diastolic velocity decreased (18.8 vs. 14.5 cm/sec, p=0.03). One patient showed new, abnormal hepatic echotexture after surgery. Among serum indices, mean aspartate aminotransferase (56.7 vs. 60.7 IU, p=0.04), mean alanine transaminase (ALT) (18.9 vs. 33.9 IU, p=0.0002), and mean gamma-glutamyl transferase (GGT) (18.7 vs. 46.1 IU, p=0.002) increased at the post-Fontan assessment compared to the pre-operative values. By linear regression, hospital length of stay and duration with chest tube after Fontan operation were both significantly associated with an increase in GGT (p< 0.001 for both) and ALT (p=0.008, p=0.04) 3 to 6 months after surgery. There were no associations found between change in ultrasound or serum markers of liver function and pre-Fontan hemodynamic variables as measured by echocardiogram, catheterization, and/or magnetic resonance imaging.

Conclusions:
Hepatic ultrasound abnormalities were seen prior to the Fontan operation in some patients. Early after the Fontan operation, liver length and serum hepatic markers were increased relative to pre-Fontan values. Post-operative morbidity was associated with an increase in these serum markers. In total, these findings suggest that liver insult may occur prior to the Fontan operation and further insult likely begins soon after the Fontan circulation is created.
Abstract 11167: Effects of Conversion to Everolimus With Low-Dose Calcineurin Inhibitors From Mycophenolate Mofetil on Cardiac Allograft Vasculopathy in Maintenance Heart Transplant Recipient: Serial Three-Dimensional Intravascular Ultrasound Analysis at 2 Years
Authors: Watanabe Takuya , Seguchi Osamu , Nishimura Kunihiro , Yanase Masanobu , Sato Takuma , Sunami Haruki , Nakajima Seiko , Hisamatsu Eriko , Sato Takamasa , Kuroda Kensuke , Kobayashi Takashi , Nakao Yoko , Nakai MIchikazu , Takegami Misa , Higashiyama Aya , Watanabe Makoto , Kokubo Yoshihiro , Hata Hiroki , Fujita Tomoyuki , Miyamoto Yoshihiro , Nakatani Takeshi
Published: July 2021

Introduction:
Everolimus (EVL) has been shown to reduce the severity of CAV in de novo heart transplant (HTx) recipients. However, there is still little knowledge about the effects of conversion from mycophenolate mofetil (MMF) to EVL with reducing calcineurin inhibitor (CNI) dose on cardiac allograft vasculopathy (CAV) in maintenance HTx recipients. To evaluate this hypothesis, we performed a retrospective study.

Methods:
We examined 63 consecutive HTx recipients who were investigated with three-dimensional intravascular ultrasound (3D-IVUS) analysis every year. 24 recipients were converted to EVL with low-dose CNI from MMF with standard-dose CNI (EVL group) while the others maintained on MMF with standard-dose CNI (MMF group). 3D-IVUS analyses in a year after conversions to EVL with low-dose CNI was compared with those just before the conversions in EVL group, while recent two 3D-IVUS analyses at one year interval were compared in the control group.

Results:
At the former analyses, plaque volume (PVI) and %plaque volume (%PVI, PVI/vessel volume percent) were significantly greater and lumen volume (LVI) was smaller in the EVL group in comparison with those in the MMF group. %PVI increased (10.37±7.53 versus 12.95±9.83, P=0.008) and LVI (10.57±2.63 versus 9.52±2.42 mm
3
/mm, P<0.001) reduced significantly in the control group but not in the EVL group. The increase in %PVI during one year was suppressed and the decrease in LVI preserved in the EVL group compared with the control group (2.60±0.92 vs -0.66±1.14 %, p=0.031, -1.05±0.26 vs 0.05±0.19 mm
3
/mm, p=0.007, respectively). These effects were sustained at 2 years (p=0.042 and p=0.005).

Conclusions:
Compared with persistent MMF therapy, EVL conversion with low-dose CNI significantly reduce the severity of luminal narrowing in maintenance HTx recipients.
Abstract 11254: Association of Sleep Disordered Breathing and Sleep Architecture With Atrial Fibrillation: The MESA Study
Authors: Kwon Younghoon , Gharib Sina A , Biggs Mary Lou , Jacobs David R , Alonso Alvaro , Duprez Daniel , Lima Joao , Lin Gen-Min , Soliman Elsayed Z , Mehra Reena , Redline Susan , Heckbert Susan
Published: July 2021

Background:
Sleep disordered breathing (SDB) has been associated with nocturnal atrial fibrillation (AF). However, the association of SDB and other important sleep characteristics with prevalent AF (beyond nocturnal AF) is unclear. We explored the cross-sectional association of SDB and other objectively measured sleep characteristics with AF.

Methods:
Prevalence of AF was examined among MESA (Multi-Ethnic Study of Atherosclerosis) study participants who underwent polysomnography (PSG) (n=2048) (MESA Sleep Study). Presence or a history of AF was determined if AF or atrial flutter was identified by at least one of the following measures: (i) 12-lead ECG during study examination; (ii) PSG; (iii) ICD-9 codes from hospital discharge diagnosis; (IV) inpatient and outpatient Medicare claims data.

Results:
Overall prevalence of AF was 4.9 % (n=100). Prevalence of AF was significantly higher at 6.7% in subjects with moderate to severe SDB (n = 691, apnea hypopnea index (AHI) ≥15/h) compared with a prevalence of 4.0% in participants without SDB (n = 707, AHI < 5/h) (p=0.02). After accounting for demographics, body habitus, cardiovascular disease (CVD) risk factors and prevalent CVD, participants with higher values of AHI were more likely to have AF, although the result was not statistically significant (OR: 1.22 [0.99-1.49] per SD [17/hr], p = 0.06). Exploratory analyses of the association of sleep architecture with AF using the same model found significantly lower odds of AF associated with longer duration of slow wave sleep (SWS) (OR: 0.66 [0.5-0.89] per SD [34 min], p = 0.01). Results from a multivariable model that included 3 key sleep characteristics (AHI, SWS time and arousal index (AI)) suggested that all were independently associated with AF (AHI: OR 1.45 [1.13-1.87] per SD, p = 0.004; SWS time: OR 0.65 [0.49-0.87] per SD, p = 0.004; AI: OR 0.65 [0.50-0.86] per SD (12/hr), p = 0.002).

Conclusion:
In a cross-sectional study of a large multi-ethnic population, the prevalence of AF was associated with more severe SDB, shorter SWS time, and lower AI. This finding highlights sleep architecture’s implication, potentially via autonomic balance, in the association between sleep and AF.
Abstract 11273: Caveolae-Specific Phosphorylation of L-type Calcium Channel β2a Subunit Exacerbates Cardiac Hypertrophy
Authors: Kumagai Shohei , Hayamizu Nao , Matsunami Sachi , Otsuka Wataru , Sakata Yasushi , Fujio Yasushi , Nakayama Hiroyuki
Published: July 2021

Background:
L-type calcium channel (LTCC) localizes at T-tubules and caveolae in cardiomyocytes, and plays major roles in excitation-contraction coupling and cardiac hypertrophy. The expression of β2a subunit of LTCC (β2a) is increased in human failing heart. Recently, it was reported that phosphorylation of β2a by CaMKII enhanced LTCC activity. However, the functional role of β2a phosphorylation in heart failure remains to be elucidated.

Objective:
To make clear the functional role of β2a phosphorylation in cardiomyocytes.

Methods and Results:
Adenoviral overexpression of β2a demonstrated its constitutive phosphorylation by CaMKII and induced neonatal cardiomyocyte hypertrophy. Interestingly, phosphorylated β2a was co-localized with caveolin3. To assess caveolae-specific activation of CaMKII, we generated a fusion protein composed of phospholamban and caveolin3 (PLN-Cav3). This protein localized at caveolae, and caveolae-specific activation of CaMKII was detected using phospho-specific antibody for PLN (Thr17). In addition, to inhibit caveolae-specific CaMKII activity, we developed a GFP fusion protein with caveolin binding domain fused to CaMKII inhibitory peptide (CBD-GFP-AIP). We identified that this protein co-localized with caveolin3, and inhibited activation of CaMKII specifically at caveolae using PLN-Cav3 method. Moreover, CBD-GFP-AIP abolished β2a phosphorylation and attenuated β2a-induced cardiac hypertrophy. We found that phenylephrine (PE) stimulation activated caveolae-CaMKII and β2a in vitro and in vivo. Finally, we generated transgenic mice overexpressing wild-type (w-TG) or non-phospho mutant β2a (m-TG) in cardiomyocyte and evaluated cardiac hypertrophy after two weeks of chronic PE stimulation. The expression of β2a in both TG increased approximately 2.5 fold compared to control mice. PE-induced cardiac hypertrophy was attenuated in m-DTG compared to w-DTG mice (heart weight-body weight ratio: control; 4.8±0.2, *w-TG; 5.5±0.3, m-TG; 4.8±0.4, n=5-6, *p<0.05 vs others).

Conclusion:
We developed novel methods to evaluate and inhibit caveolae-specific activation of CaMKII. Using these methods, we revealed that phosphorylated β2a localized at caveolae, and exaggerates cardiac hypertrophy.
Abstract 11292: Impact of Chronic Obstructive Pulmonary Disease on Cardiovascular Function and Prognosis in Heart Failure Patients
Authors: Shimizu Takeshi , Yoshihisa Akiomi , Takiguchi Mai , Nodera Minoru , Miura Shunsuke , Nakamura Yuichi , Yamauchi Hiroyuki , Owada Takashi , Abe Satoshi , Suzuki Satoshi , Oikawa Masayoshi , Kobayashi Atsushi , Yamaki Takayoshi , Sugimoto Koichi , Kunii Hiroyuki , Nakazato Kazuhiko , Suzuki Hitoshi , Saitoh Shu-ichi , Takeishi Yasuchika
Published: July 2021

Background:
Chronic obstructive pulmonary disease (COPD) often coexists with heart failure (HF), and is thought to have a critical association with mortality and morbidity in HF patients. However, the impact of COPD on cardiovascular function and the detailed all-cause mortality of HF remain unclear.

Methods and Results:
Consecutive 378 patients admitted for HF who underwent spirometry were divided into 3 groups: HF without COPD (Non-COPD group, n = 272), HF with mild COPD (GOLD I group, n = 82), and HF with moderate COPD (GOLD II group, n = 24). We compared echocardiographic findings, vascular function including flow mediated dilatation (FMD) and cardio-ankle vascular index and circulating levels of troponin T, BNP, CRP, and estimated GFR among the three groups. The GOLD II group, as compared to Non-COPD group, had 1) higher troponin T (0.030 vs. 0.020 ng/ml, P = 0.009), 2) greater cardio-ankle vascular index (8.99 vs. 8.29, P = 0.032), 3) similar levels of FMD, BNP, CRP, and estimated GFR, and 4) similar cardiac systolic and diastolic function of the right and left ventricle. In addition, rates of cardiac (P = 0.049), non-cardiac (P = 0.001), and all-cause mortality (P = 0.002) were higher in GOLD II group than in Non-COPD and GOLD I groups. Importantly, in the Cox proportional hazard analyses, the GOLD stage II was an independent predictor of cardiac (P = 0.038), non-cardiac (P = 0.036), and all-cause mortality (P = 0.015) in HF patients.

Conclusions:
HF patients with coexistent moderate COPD (GOLD stage II) have greater myocardial damage, greater arterial stiffness, and higher cardiac and non-cardiac mortality. Thus, taking appropriate management to control COPD may improve the prognosis of HF patients with COPD.
Abstract 11320: Long-Term Stent-Related and Patient-Related Outcomes of Second-Generation Everolimus-Eluting Xience V Stents versus Zotarolimus-Eluting Resolute Stents in Real-World Practice: Three Year Results From the Multicenter Prospective EXCELLENT and RESOLUTE-Korea Registries
Authors: Park Jonghanne , Lee Joo Myung , Park Kyung Woo , Han Jung-Kyu , Yang Han-Mo , Kang Hyun-Jae , Koo Bon-Kwon , Bae Jang-Whan , Woo Sung-Il , Park Jin Sik , Jin Dong-Kyu , Jeon Dong Woon , Oh Seok Kyu , Park Jong-Seon , Kim Doo-Il , Hyon Min Su , Jeon Hui-Kyung , Lim Do-Sun , Kim Myeong-Gon , Rha Seung-Woon , Her Sung-Ho , Hwang Jin-Yong , Kim Sanghyun , Choi Young Jin , Kang Jin Ho , Moon Keon-Woong , Jang Yangsoo , Kim Hyo-Soo
Published: July 2021

Background:
Long term outcomes are imperative to confirm safety of drug-eluting stents. There have been two randomized controlled trials comparing everolimus-eluting stents (EES) and Resolute zotarolimus-eluting stents (ZES-R). To date, long-term clinical outcomes of these stents were limited to only one report which has recently reported 4-year comparisons of these stents. Therefore, more evidences are needed regarding long-term clinical outcomes of the second generation stents. This study compared the long-term clinical outcomes of EES with ZES-R in “all-comer” cohorts up to 3-year follow-up.

Methods:
The EXCELLENT and RESOLUTE-Korea registries prospectively enrolled 3,056 patients treated with EES and 1,998 with ZES-R. Target lesion failure and patient-related composite events were compared in crude and propensity score matched analyses.

Results:
Of 5054 patients, 3830 patients (75.8%) had off label indication (2217 with EES and 1613 with ZES-R). The stent-related outcome (189 [6.2%] vs. 127 [6.4%], p=0.812) and the patient-related outcome (420 [13.7%] vs. 250 [12.5%], p=0.581) did not differ between EES and ZES-R respectively at 3 year, which was corroborated by similar results from the propensity score-matched cohort (HR 0.92, 95% CI 0.70-1.20, p=0.523 and 0.85, 95% CI 0.70-1.02, p=0.081, for stent and patient related outcomes, respectively). The rate of definite or probable stent thrombosis up to 3 years (22 [0.7%] vs. 10 [0.5%], p=0.370) was also similar. The rate of stent thrombosis was very low and comparable between the two stents (3 [0.1%] vs. 1 [0.1%], p=0.657). In multivariate analysis, chronic renal failure (adjusted HR 3.615, 95% CI 2.440-5.354, p<0.001) and off label indication (adjusted HR 1.782, 95% CI 1.169-2.718, p=0.007) were the strongest predictors of target lesion failure.

Conclusion:
In this robust real world registry with unrestricted use of EES and ZES-R, both stents showed comparable safety and efficacy at 3-year follow-up. Overall incidences of target lesion failure and definite stent thrombosis, including very late stent thrombosis, were low, even in the patients with off label indications, suggesting excellent long term safety and sustained efficacy of both types of second generation drug-eluting stents.
Abstract 11345: Resource Demands and the Incidence of Cardiopulmonary Resuscitation Within a Pediatric Cardiac Intensive Care Unit
Authors: Bacon Matthew K , Conrad Stephanie J , Hatch Brittney C , Hughes John D , Terrell Michelle K , Maynord Patrick O , Smith Andrew H
Published: July 2021

Background:
Econometric evidence suggests exponential declines in the ability to provide critical care services as variable demands exceed a relatively fixed supply of available critical care resources. We hypothesized that increasing demands upon resources within a pediatric cardiac intensive care unit (CICU) is also associated with increases in the incidence and rate of cardiopulmonary resuscitation.

Methods and Results:
Records from each twelve-hour nursing shift within an eighteen-bed pediatric CICU from 1 July 2010 through 30 April 2014 were retrospectively reviewed. There were 2716 reports available for review from 2769 shifts (97%). During the study period, there were 1,803 surgical and 1,215 medical admissions, accounting for a median census of 15 (interquartile range [IQR] 13-17) patients per shift, and a total of 20,269 patient days (40,538 patient-shifts) over the 44-month study period. Median bed capacity was 83% (IQR 72-94%), and median patient to nursing assignment ratio was 1.5 (IQR 1.4-1.6 patients per nurse assignment). Cardiac arrest (defined as administration of chest compressions) was identified in 138 occasions in 134 shifts, an arrest rate of 3.4 arrests per 1000 patient-shifts. Arrests were no more frequent during night versus day shifts (3.2 v. 3.6 per 1000 patient shifts, p=0.40), nor were they greater during weekend versus weekday shifts (2.9 v. 3.9 per 100 patient-shifts, p=0.14). There was a trend toward an increase in the incidence of cardiac arrest with patient to nurse assignment ratios of less than 1.5 (2.8 v. 3.9 arrests per 1000 patient shifts, p=0.06). Unit occupancy exceeding 85% was associated with a 45% greater rate of cardiac arrest (2.6 v 4.1 arrests per 1000 patient-shifts, 95%CI 0.3 to 2.6 increase, p=0.01).

Conclusions:
We report a significant increase in the incidence of cardiopulmonary resuscitation at times of greater resource consumption within a pediatric CICU as defined by unit capacity. Multi-institutional studies are necessary to identify generalizable organizational characteristics that may promote efficient allocation of resources and optimize delivery of care to a population of patients at greater risk for significant hospital morbidity.
Abstract 11409: Comparison of National Cardiovascular Data Registry to an Administrative Database
Authors: Pentakota Sri Ram , Swerdel Joel N , Kostis William J , Cabrera Javier , Cosgrove Nora M , Moreyra Abel E , Kostis John B ,   For the Myocardial Infarction Data Acquisition System (MIDAS) Study Group
Published: July 2021

Introduction:
Public reporting of cardiovascular outcomes from registries has been useful in monitoring and improving quality of care. However, participation in registries such as National Cardiovascular Data Registry (NCDR) is voluntary and information could be biased due to self-selection of the participating hospitals thus limiting the external validity. Administrative databases usually do not include detailed information, but include all patients.

Hypothesis:
To compare in-hospital mortality following admission for acute myocardial infarction (AMI) between NCDR and a statewide database of all admissions to nonfederal hospitals in New Jersey (Myocardial Infarction Data Acquisition System, MIDAS) for the year 2011.

Methods:
We compared the proportion of in-hospital deaths for patients admitted for AMI between NCDR (published data) and MIDAS (unadjusted and adjusted for age, gender and cardiac catheterization (CATH) or percutaneous coronary intervention (PCI). MIDAS data were derived by direct standardization using the 2011 National Inpatient Sample (NIS) as the standard population.

Results:
The in-hospital mortality rates were lower in NCDR than MIDAS (4.56% vs. 6.37% crude, 5.92 adjusted). NCDR patients were younger and received more CATH (84.97% vs. 62.07%) PCI (64.17% vs. 41.67%). Adjustment for demographics and PCI explained 33% (1.36 vs. 1.81) of the mortality difference between NCDR and MIDAS. Similar findings were obtained when mortality was adjusted for demographics and CATH (40%, 1.81 vs. 1.29, of the mortality difference explained).

Conclusions:
Prospective registries and administrative databases provide complementary information. The significant differences in patient profiles, frequency of procedures and in-hospital mortality rates between NCDR and MIDAS imply that the care in NCDR hospitals is better. The magnitude of the differences warrants caution in generalizing the NCDR data to the entire nation.
Abstract 11452: Are Patients With Caseous Calcification of the Mitral Annulus But Without Atrial Fibrillation at Increased Risk of Cerebral Embolization?
Authors: Dietl Charles A , Hawthorn Christopher M , Raizada Veena
Published: July 2021

Background:
Caseous calcification of the mitral annulus (CCMA) is very uncommon, and is frequently misdiagnosed as an intracardiac tumor, thrombus, abscess, or simply as mitral annular calcification (MAC). These masses are generally believed to have a benign prognosis. The aims of this study are to increase the awareness of this unusual variant of MAC, and to determine whether patients with CCMA are at increased risk of cerebral embolization in patients with or without atrial fibrillation (AF).

Methods:
A comprehensive literature search was done to determine whether patients with CCMA are at increased risk of cerebral embolization, using the following search modules: caseous calcification of the mitral annulus, mitral annular calcification, cerebral embolization with mitral annulus calcification, risk of stroke with mitral annular calcification.

Results:
Among the 496 articles listed in PubMed.gov, ScienceDirect.com, and Google Scholar, a total of 129 patients with CCMA were identified in 85 publications, and 31 articles were reviewed to evaluate the incidence of stroke in 1800 patients with MAC. Literature review revealed that the incidence of cerebrovascular events (CVE) associated with CCMA is 18.6% (24 of 129) which is even higher than the risk of embolic CVE reported in patients with MAC, 11.6% (209 of 1800) (range 4.8% to 24.1%). Only 2 of 24 patients (8.3%) with CCMA who suffered a CVE had history of AF, whereas the majority (22 of 24, or 91.7%) of CCMA patients with a CVE did not have AF.

Conclusions:
Despite the fact that several reports suggest that CCMA is a benign condition, CCMA may be potentially serious, because of the increased risk of cerebral embolization, even in patients without atrial fibrillation.
Abstract 11471: Peripheral Arterial Disease and Risk of Atrial Fibrillation and Stroke: The Multi-Ethnic Study of Atherosclerosis
Authors: O’Neal Wesley T , Efird Jimmy T , Nazarian Saman , Alonso Alvaro , Heckbert Susan R , Soliman Elsayed Z
Published: July 2021

Introduction:
Peripheral arterial disease (PAD) shares several risk factors with atrial fibrillation (AF) and persons with PAD have an increased risk of stroke. It is unclear if PAD is associated with an increased risk for AF and whether such an association explains the increased risk of stroke associated with PAD.

Methods:
We examined the association between PAD, as measured by the ankle-brachial index (ABI), and incident AF and incident stroke, separately, in 6,568 participants (mean age 62 ± 10; 53% women; 62% non-white) from the Multi-Ethnic Study of Atherosclerosis (MESA). ABI values <1.0 or >1.4 defined PAD in this analysis. Participants were free of baseline clinical cardiovascular disease and AF. AF was ascertained by review of hospital discharge records and from Medicare claims data until December 31, 2010. An independent adjudication committee ascertained stroke events. Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95%CI) for the association between PAD and AF and stroke.

Results:
A total of 774 (12%) participants had baseline PAD. Over a median follow-up of 8.5 years, 301 (4.6%) participants developed AF and 140 (2.1%) developed stroke. In a model adjusted for socio-demographics, cardiovascular risk factors, and potential confounders, PAD was associated with an increased risk of AF (HR=1.5, 95%CI=1.1, 2.0). In a similar model, PAD was associated with incident stroke (HR=1.7, 95%CI=1.1, 2.5) and the magnitude of risk was not different after inclusion of AF as a time-dependent covariate (HR=1.7, 95%CI=1.1, 2.5). Similar results were obtained in subgroup analyses stratified by age, sex, and race/ethnicity.

Conclusions:
PAD is independently associated with an increased risk of AF and stroke in the MESA study. The relationship between PAD and stroke is not mediated by AF.
Abstract 11530: Age-Specific Differences Between Conventional and Ambulatory Daytime Blood Pressure Values
Authors: Conen David , Aeschbacher Stefanie , Thijs Lutgarde , Li Yan , Boggia José , Asayama Kei , Hansen Tine W , Kikuya Masahiro , Björklund-Bodegård Kristina , Ohkubo Takayoshi , Jeppesen Jørgen , Gu Yu-Mei , Torp-Pedersen Christian , Dolan Eamon , Kuznetsova Tatiana , Stolarz-Skrzypek Katarzyna , Tikhonoff Valérie , Schoen Tobias , Malyutina Sofia , Casiglia Edoardo , Nikitin Yuri , Lind Lars , Sandoya Edgardo , Kawecka-Jaszcz Kalina , Mena Luis , Maestre Gladys E , Filipovsky Jan , Imai Yutaka , O’Brien Eoin , Wang Ji-Guang , Risch Lorenz , Staessen Jan A
Published: July 2021

Introduction:
Mean daytime ambulatory blood pressure (ABP) values are considered to be lower than conventional BP (CBP) values, but data on this relation among younger individuals <50 years are scarce. To address this issue, we performed a collaborative analysis in a large group of participants representing a wide age range.

Methods:
CBP and 24-hour ABP were measured in 9550 individuals not taking BP lowering treatment from 13 population based cohorts. We compared the individual differences between daytime ABP and CBP according to 10-year age categories. Age-specific prevalences of white-coat hypertension and masked hypertension were calculated based on guideline-recommended thresholds.

Results:
Among individuals aged 18-30, 30-40 and 40-50 years, mean daytime systolic and diastolic ABP were significantly higher than the corresponding CBP (6.0, 5.2 and 4.7 mmHg for systolic BP; 2.5, 2.7 and 1.7 mmHg for diastolic BP, all p<0.0001) (Figure). Systolic and diastolic BP indices were similar in participants aged 50-60 years (p=0.20 and 0.11, respectively). In individuals aged 60-70 and ≥70 years, CBP was significantly higher than daytime ABP (5.0 and 13.0 mmHg for systolic BP; 2.0 and 4.2 mmHg for diastolic BP, all p<0.0001) (Figure). Accordingly, the prevalence of white coat hypertension exponentially increased from 2.2% to 19.5% from those aged 18-30 years to those aged ≥70 years, with some variation between men and women (prevalence 8.0% versus 6.1%, p=0.0003). Masked hypertension was more prevalent among men (21.1% versus 11.4%, p<0.0001). The age-specific prevalence of masked hypertension was 18.2%, 27.3%, 27.8%, 20.1% 13.6% and 10.2% in men, and 9.0%, 9.9%, 12.2%, 11.9%, 14.7% and 12.1% in women.

Conclusions:
In this large collaborative analysis we found that the relation between daytime ABP and CBP strongly varies by age. These findings may have important implications for the diagnosis of hypertension and its subtypes in clinical practice.
Abstract 11543: Resolution of Mitochondrial Oxidant Stress Improves Aged-Cardiac Performance
Authors: Owada Takashi , Yamauchi Hiroyuki , Saitoh Shu-ichi , Machii Hirofumi , Takeishi Yasuchika
Published: July 2021

Senescence is a major factor to increase mitochondrial oxidant stress, which contributes to the pathogenesis of heart disease. However, the effect of antioxidant therapy on cardiac mitochondria in aged-cardiac performance remains elusive. We postulated that mitochondrial targeting of superoxide scavenging would have benefit in the aged heart. Increased levels of superoxide and NADPH oxidase activity were appeared in cardiac myocytes isolated from old mice (52W) compared to those from young mice (8W) (Superoxide: 2.6±0.4 vs. 1.2±0.2 nmol/mg protein; NADPH oxidase activity: 2654±282 vs. 1124±156 RLU, P<0.01, n=12, respectively). In old mice treated with the mitochondria-targeted antioxidant MitoTEMPO (180 μg/kg/day, 28 days) coinfusion using subcutaneously implanted minipump, levels of superoxide and NADPH oxidase activity markedly decreased (0.2±0.2 nmol/mg protein and 342±45 RLU, respectively, P<0.01) and eliminated fluorescence intensity of MitoSox Red in cardiomyocytes (from 11.2±2.1 to 0.4±1.1 arbitrary unit, P<0.01). Treatment with MitoTEMPO in old mice improved left ventricle ejection fraction (from 48±5% to 62±5%, P<0.01) and diastolic dysfunction assessed by echocardiography. Endothelium-dependent vasodilation in isolated coronary arterioles was impaired in old mice compared to that in young mice, which was improved by MitoTEMPO treatment (Figure). Mitochondria from the old mouse myocardium exhibited lower rate in complex I (-38±5%) and complex II (-34±6%) -dependent respiration compared with young mice. Supplementation of MitoTEMPO in old mice improved the respiration rates in mitochondria to the level similar to those in young mice. Resolution of mitochondrial oxidant stress by MitoTEMPO in old mice restored cardiac function and coronary vasodilative capacity to the same magnitude observed in young mice. Therefore, antioxidant strategy targeting mitochondria could have therapeutic benefit in heart diseases with senescence.
Abstract 11552: Statin Therapy in Patients With Type 2 Diabetes: Development and Validation of a Model to Predict Individualized Treatment Effects Based on the ASCOT, ALLHAT and CARDS Trials
Authors: Kaasenbrood Lotte , Poulter Neil R , Sever Peter S , Colhoun Helen , Livingstone Shona J , Pressel Sara L , Davis Barry R , van der Graaf Yolanda , Boekholdt S. Matthijs , Visseren Frank L
Published: July 2021

Introduction:
Clinicians need to translate results from randomized clinical trials to individual patients with type 2 diabetes mellitus (T2DM). In this study we aim to develop and validate a model for the prediction of absolute risk reductions (ARR) for major cardiovascular events by usual-dose statin therapy for individuals with T2DM.

Methods:
Data from the ASCOT-LLA trial (atorvastatin 10 mg versus placebo) of 2,725 T2DM patients were used to predict 10-year individualized ARR on major cardiovascular events (myocardial infarction, stroke or cardiovascular death). Predictions were based on a newly developed model of 8 predictors: age, sex, current smoking, systolic blood pressure, non-HDL cholesterol, fasting glucose, history of cardiovascular events and treatment allocation (statin or placebo). External validation was performed in ALLHAT-LLT (3,878 T2DM patients) and CARDS (2,838 T2DM patients). Possible effect modification of statin therapy was evaluated for baseline cardiovascular risk and single interactions between predictors and treatment allocation.

Results:
The predicted 10-year ARR for cardiovascular events was low (<2%) for 13% of the T2DM patients, translating in 10-year NNT >50 (Figure 1). About 30% of the T2DM patients had an ARR of >4% (10-year NNT <25). The addition of treatment interactions did not significantly improve model performance. The developed model showed adequate calibration and moderate discrimination in both external validation sets (concordance statistic 0.64 in ALLHAT and 0.68 in CARDS).

Conclusion:
Absolute risk reductions by statin therapy can be estimated for individual patients with T2DM using a model based on trial data. There is a wide distribution in absolute risk reduction by statin therapy in T2DM patients due to a distribution in cardiovascular risk. Individualized treatment effects are more informative for patients and clinicians than relative average effects and can be used to guide clinical decision-making.
Abstract 11566: Beyond LDL Cholesterol: Carriers of the PCSK9 R46L Variant Are Characterized by an Anti-Atherogenic Lipoprotein Profile Assessed by Nuclear Magnetic Resonance Spectroscopy
Authors: Arsenault Benoit J , Boekholdt S. Matthijs , Hovingh G. Kees , Kastelein John J , Wareham Nicholas J , Khaw Kay-Tee
Published: July 2021

Background:
Carriers of the PCSK9 R46L genetic variant are characterized by low levels of low-density lipoprotein (LDL) cholesterol and a decreased risk of cardiovascular disease (CVD). Whether these individuals are characterized by other features of a more beneficial lipoprotein-lipid profile is unknown.

Methods and Results:
We measured the lipoprotein-lipid profile of 2373 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study by nuclear magnetic resonance spectroscopy. Among them, 77 participants carried at least one allele of the R46L genetic variant. Carriers and non-carriers had comparable clinical characteristics (age, body mass index, blood pressure, smoking and diabetes prevalence). As expected, carriers had lower LDL cholesterol levels compared to non-carriers (3,75±0,99 vs. 4,16±1,01 mmol/L, p<0.001 in carriers vs. non-carriers, respectively). Carriers were characterized by a lower very low-density lipoprotein (VLDL) particle concentration and a lower LDL particle concentration of any size (Table). Total high-density lipoprotein (HDL) particle concentration was not different in carriers vs. non-carriers. However, carriers had a higher concentration of large HDL particles and a higher mean HDL particle size. We also found that carriers were characterized by a lower secretory phospholipase A2 (sPLA2) activity (4,21±0,88 vs. 4,61±1,26, nmol/ml/min p=0.004 in carriers vs. non-carriers, respectively) and a lower lipoprotein-associated phospholipase A2 (Lp-PLA2) activity (47,5±14,1 vs. 52,4±16,2 nmol/ml/min, p=0.008 in carriers vs. non-carriers, respectively).

Conclusions:
Results of this study suggest that on top of having low LDL cholesterol levels, carriers of the PCSK9 R46L genetic variant have a lower VLDL and LDL particle concentration, a higher concentration of large HDL particles and lower sPLA2 and Lp-PLA2 activity. This anti-atherogenic profile may explain to a certain extent the reduced CVD risk observed in carriers of the PCSK9 R46L genetic variant.