bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3600: An Obesity Paradox Among Apparently Healthy Male Veterans
Authors: McAuley Paul , Myers Jonathan , Abella Joshua , Oliveira Ricardo , Hsu Leon , Froelicher Victor F
Published: July 2021

Background:
Body mass index (BMI) is inversely related to mortality in patients with cardiovascular disease (CVD), the so-called obesity paradox. We studied a group of male veterans referred to exercise testing for clinical reasons, but determined to be free of CVD, to evaluate whether this occurs in such individuals.

Methods:
After excluding 40 patients with BMI <20 kg/m
2
, we evaluated a total of 3317 consecutive men (mean age 57 ± 12 years) referred for exercise testing between 1992 and 2004. Patients were classified according to three predetermined BMI groups: 20.0 –24.9, 25.0 –29.9, and ≥30.0 kg/m
2
. The association of BMI and all-cause mortality was assessed by Cox proportional hazards analysis.

Results:
During a mean follow-up of 5.8 ± 3.3 years, a total of 212 patients (6.4%) died. After adjusting for age, ethnicity, smoking and fitness level, subjects with BMI-defined normal weight were 60% more likely to die (HR [95% CI] 1.63 [1.21–2.19]; Figure

) than overweight or obese men. Further adjustment for hypertension, hypercholesterolemia and diabetes did not appreciably alter these results.

Conclusions:
Veterans are a select group in that they must meet weight criteria to qualify for military service. In this cohort of apparently healthy male veterans, we observed a strong inverse relation of BMI to mortality. This warrants further investigation into the extent and nature of the obesity paradox.
Abstract 483: Prevention of Aneurysm Formation using Ribbon-type Decoy Oligodeoxynucleotides against NFκB and Ets in a Rat Model
Authors: Miyake Takashi , Aoki Motokuni , Makino Hirofumi , Morishita Ryuichi
Published: July 2021

Current therapy to treat abdominal aortic aneurysm (AAA) is limited to elective surgical repair. Especially, there is no well-defined treatment strategy for small AAAs. Therefore, the development of a novel therapeutic approach to treat AAA is awaited. We focused on the simultaneous inhibition of the transcription factors, NFκB and ets. Indeed, we previously reported the preventive and regressive effects of chimeric decoy oligodeoxynucleotides (ODN) against NFκB and ets. However, local application of ODN is necessary due to easily degradation. To overcome this limitation, we developed novel chimeric decoy ODN with a ribbon-shaped circular structure (ribbon-type chimeric decoy ODN, RC-ODN) to stabilize decoy ODN against nucleases. First, we examined the stability of RC-ODN. RC-ODN was more stable than the conventional phosphorothioated chimeric decoy ODN (PC-ODN) after incubation in the presence of exonuclease or serum. In addition, the inhibitory effect of RC-ODN on MMP-9 expression in cultured THP-1 cells was more potent than that of PC-ODN (n=8, P<0.005). To achieve a minimally invasive molecular therapy, intra-peritoneal application of RC-ODN was performed in a rat AAA model. One week after injection of FITC-labeled RC-ODN, FITC-positive macrophages, migrated from peritoneal space, could be detected in the aneurismal wall. In addition, EMSA showed that both NFκB and ets activity were inhibited by RC-ODN. 4 weeks after treatment, transfection of RC-ODN inhibited the aortic dilatation as compared to control or ribbon-type scrambled decoy ODN transfer (n=6 per group, RC-ODN 5.66±1.08 mm
2
, Scrambled 13.89±3.55 mm
2
, P<0.05). Interestingly, a significant preservation of elastic fibers was observed with RC-ODN treatment, accompanied by a reduction of MMP-9 activity (P<0.0005) and MMP-12 expression (P<0.0005), while the recruitment of macrophages was not inhibited. The expression of cysteine proteases, cathepsin B and K, was also suppressed by RC-ODN treatment (P<0.05). Here, the present study provided a novel strategy to treat AAA by the simultaneous inhibition of NFκB and ets using intra-peritoneal application of RC-ODN in a rat model. Minimally invasive molecular therapy using this strategy is expected to be useful for treating AAA.
Abstract 3622: End of Trial Period for Randomized Controlled Cardiology Trials: Is patient safety monitored and protected?
Authors: Zia Mohammad I , Heslegrave Ronald , Newton Gary E
Published: July 2021

Background:
The post trial period is the period after the end of study drug administration. The Declaration of Helsinki (DOH) states that “at the conclusion of the study, every patient entered into the study should be assured of access to the best proven prophylactic, diagnostic and therapeutic methods identified by the study.” It further adds that “post trial access arrangements or other care must be described in the study protocol so the ethical review committee may consider such arrangements during its review.” Therefore our objectives were:

to determine whether research trial protocols systematically consider post trial period issues including planned follow-up and patient surveillance in the post trial period; and

to assess if consent forms addressed end of trial issues.

Methods:
We searched the research ethics board (REB) databases at 2 academic institutions in Toronto from 1995 to 2006 to identify approved randomized clinical trials of chronic medical therapies for cardiac conditions.

Results:
Fourty-two studies were identified including 18 heart failure and 15 coronary artery disease trials. Thirty-eight of these trials were industry funded. Almost all trials (n=37) ended study drug abruptly at the last clinic visit, while only 4 studies offered a clinical visit post trial termination, and an additional 3 reported a telephone contact after trial completion. Only 5 trials submitted consent forms to the REB with a discussion of the post trial period. After REB review, no additional consent forms addressed the post trial period. When comparing the time period before and after the updated version of the DOH in 2000, there was a trend towards a decline in addressing post trial care (p=0.08).

Conclusion:
The majority of cardiac trials end study drug abruptly with unknown and potentially negative consequences, and most patients have no systematic post trial follow up from trial investigators. Study patients are also not made aware of the post trial period, as the majority of study consent forms do not discuss post trial care. Therefore, an important aspect of clinical trial design, the post trial period, could be improved by systematic follow-up described in the protocol, and full discussion of this aspect of trial participation in the consent form.
Abstract 3625: Do Patients Who Meet SCD-HeFT Criteria in Clinical Practice Differ from Patients Enrolled in SCD-HeFT?
Authors: Al-Khatib Sana M , Wang Yongfei , Lee Kerry L , Mark Daniel B , Poole Jeanne E , Sanders Gillian D , Peterson Eric , Curtis Jeptha , Bardy Gust H
Published: July 2021

Background:
Many studies have demonstrated the lack of generalizability of randomized clinical trials’ findings to clinical practice. We conducted this study to determine whether the baseline characteristics of patients meeting SCD-HeFT criteria in the ACC-NCDR ICD Registry are similar to those of patients enrolled in SCD-HeFT.

Methods:
Of the 1,438 US hospitals participating in the ICD Registry, 85% submit data on all ICD implants. We identified patients with NYHA class II or III symptoms and an LVEF ≤ 35%. We excluded patients with an MI within 40 days, CABG within 1 month, and PCI within 3 months prior to ICD implantation. We also excluded patients who received an ICD for secondary prevention or an ICD with cardiac resynchronization therapy. Baseline characteristics were compared using the t-test for continuous variables and the chi-square test for categorical variables.

Results:
Patients in the ICD Registry are significantly older and have more co-morbidities than patients enrolled in SCD-HeFT (Table

). The rates of use of ACE-inhibitors and digoxin were significantly lower in the Registry than in the trial (p <0.01 for both). The rates of use of beta-blockers, aspirin and statins were significantly higher in the Registry than in the trial (p <0.01 for all)

Conclusions:
The baseline characteristics and medical management of patients who receive an ICD in clinical practice are significantly different from those of patients enrolled in SCD-HeFT. Future studies should investigate whether these differences translate into differences in ICD effectiveness.
Abstract 3630: Sex Differences in the Characteristics of Patients Receiving ICD Therapy for Primary Prevention
Authors: Daugherty Stacie L , Peterson Pamela N , Wang Yongfei , Curtis Jeptha P , Heidenreich Paul A , Krumholz Harlan M , Vidaillet Humberto J , Masoudi Frederick A
Published: July 2021

Background:
Prior studies suggest that women are less likely than men to be referred for ICD implantation for the primary prevention of sudden cardiac death. We hypothesized that women who undergo primary prevention ICD implantation would be more likely to meet strict evidence-based criteria for this therapy.

Methods:
We studied 59,833 patients in the NCDR ICD national registry who underwent first-time primary prevention ICD placement between January 2005 and April 2007. Patients were classified according to whether or not they met enrollment criteria of either of two primary prevention trials (MADIT-II: prior MI, LVEF ≤ 30% and MI>40 days or SCD-HeFT: prior heart failure; LVEF≤ 35%, and NYHA class II or III, unless receiving a biventricular pacemaker/ICD (BiV ICD), in which case NYHA IV was considered acceptable). Multivariable analyses assessed the association between sex and concordance with trial enrollment criteria after adjustment for demographic, clinical and health system characteristics.

Results:
Among the primary prevention cohort, 27% (n=16,079) were women. Compared with men, women were more often non-white (23.5% vs. 16.8%, p<0.01) had higher NYHA classifications (62.9% vs. 54.7% in class III or IV, p<0.01), and more frequently had a history of heart failure (88.3% vs. 83.2%, p<0.01) and non-ischemic cardiomyopathy (47.0% vs. 28.1%, p<0.01). Women were also more likely to receive a BiV ICD than men (49.4% vs. 42.2%, p<0.01). Overall, 86.1% of women and 85.6% of men met the major primary prevention trials enrollment criteria (p=0.08). Men more often failed to meet trial criteria due to LVEF above cutoff (9.5% vs. 6.7%, p<0.01) or having an MI≤ 40 days before implant (5.7% vs. 4.5%, p<0.01). In multivariable analyses, women were significantly more likely to meet either trial enrollment criteria (OR 1.09, 95% CI 1.03–1.15) than men.

Conclusions
: In a large national registry of patients undergoing primary prevention ICD implantation, women were slightly more likely than men to meet the enrollment criteria for MADIT II or SCD-HeFT. As it is not known if patients who fail to meet these criteria benefit from ICD implantation, the implications of this differential pattern of use on outcomes should be investigated.
Abstract 3635: Weight Loss Reverses Left Ventricular Structural Changes In Subjects With Severe Uncomplicated Obesity. A One year Follow Up Study.
Authors: Rider Oliver J , Francis Jane M , Ali Mohammed K , Robinson Monique R , Neubauer Stefan
Published: July 2021

Objective
Obesity has been linked to a spectrum of cardiovascular abnormalities from subclinical changes in cardiac structure to overt heart failure. Uncomplicated obesity (i.e. obesity without any other co-morbidity or cardiovascular risk factors) has been shown to cause increased LV mass and LV dilatation. Our hypothesis was that these changes are, at least in part, reversible following significant weight loss over one year.

Method
Forty-one obese (BMI 37.7 ± 7.4 SD) and 12 age, sex matched controls (BMI 21.6 ± 1.8 SD) with no identifiable cardiac risk factors underwent cardiac MR imaging for the assessment of LV Mass (g), LV end-diastolic volume (EDV; ml), stroke volume (SV; ml) and LV EF (%). Fourteen obese subjects underwent repeat imaging after a one year period of weight loss, averaging 14.6 ± 11.5 % total body weight.

Results
Obesity per se was associated with elevated LV mass (125 ± 27 vs 89 ± 23g; p<0.001), LV mass indexed to height (74.4 ± 14.3 vs 52.3 ± 11.4g/m; p<0.001) and EDV (147 ± 28 vs 119 ± 24 ml; p<0.001). ESV and SV were also elevated in obesity (47 ± 12 vs 39 ± 12ml; p=0.05, and 100 ± 14 vs 80 ± 18 ml; p<0.001, respectively). LV EF was similar between groups (p=0.83). After weight loss, there was a significant reduction in LV mass (by 16 ± 11g; 135 ± 31 vs 119 ± 28g; p<0.001), LV mass indexed to height (76.4 ± 15.7 vs 68.9 ± 12 g/m; p<0.001). EDV and ESV were significantly smaller after weight loss (146 ± 25 vs 133 ± 23 ml; p<0.001, and 43 ± 12 vs 41 ± 10 ml; p<0.001 respectively). LV EF and SV did not change significantly.

Conclusion
In subjects with obesity in the absence of identifiable cardiac risk factors, LV hypertrophy and LV dilatation were partially reversible after a one year period of weight loss.
Abstract 3643: Consciousness of Reduced Salt Diet and Actual Achievement of Salt Reduction Estimated from 24hr Urinary Na Excretions in General Populations in Japan, PRC, UK and US: The INTERMAP Study
Authors: Okuda Nagako , Ueshima Hirotsugu , Okayama Akira , Saitoh Shigeyuki , Nakagawa Hideaki , Sakata Kiyomi , Kadowaki Takashi , Curb J. David , Zhao Liancheng , Elliott Paul , Stamler Jeremiah
Published: July 2021

OBJECTIVES: Assess the percentage of persons with consciousness of reduced salt diet (RSD) in general population samples and estimate actual differences in Na intake between RSD participants and others based on two timed 24hr urinary (24hr-U) Na excretions.

METHODS: Data from 4680 men and women ages 40 –59yr randomly selected from 17 general populations in four countries, Japan (n=1145), PRC (n=839), UK (n=501) and US (n=2195), in the International Study of Macro- and Micro-nutrients and Blood Pressure (INTERMAP). Awareness of RSD was surveyed by questionnaire. Participants provided timed 24hr-U samples twice; Na and K were measured. Means of 24hr-U Na, K excretions and Na/K ratio were compared between RSD and non-RSD participants. Values were also estimated adjusted for body weight, age and sex (multiple regression analysis).

RESULTS: RSD participants were few, 3.1% (Japan), 1.3% (PRC), 4.8% (UK) and 7.2% (US). Similarly among hypertensive (HTN) participants, 9.0% (Japan), 5.8% (PRC), 10.3% (UK) and 14.7% (US). Mean 24hr-U Na excretions (SE)(mmol) for RSD and non-RSD participants were 184.3(7.8) vs. 198.8(1.7)(p=0.129) (Japan); 191.2(19.3) vs. 228.0(3.5)(p=0.228) (PRC); 167.3(14.0) vs. 144.1(2.2)(p=0.114) (UK); and 150.9(4.7) vs. 163.5(1.3)(p=0.010) (US); adjusted Na excretions, 180.0(8.6) vs. 198.9(1.5)(p=0.031) (Japan); 172.4(27.4) vs. 228.2(3.1)(p=0.043) (PRC); 156.3(9.2) vs. 144.6(2.0)(p=0.217) (UK); 149.9(4.2) vs. 163.6(1.2)(p=0.002) (US). There were no significant differences in adjusted K excretions; Na/K ratios gave results similar to those for Na for all four countries. Adjusted Na excretions for HTN participants were significantly lower than for non-HTN participants in Japan (186.5(4.0) vs. 200.3(1.6)(p=0.002)); significant differences were not observed for other countries.

CONCLUSIONS: Only a small percent of all and of HTN participants reported following consciously RSD. While 24hr-U Na excretions tended to be significantly lower for RSD participants, total salt intakes were still high. To prevent CVD, it is important to implement salt reduction guidelines more aggressively.
Abstract 3661: “Energy Drink” Consumption Causes Increases in Blood Pressure and Heart Rate
Authors: Steinke Leah , Kalus James S , Dhanapal Vishnuprabha , Lanfear David E , Berlie Helen D
Published: July 2021

Introduction: “Energy drinks” are very popular and are used frequently, especially by young adults. Most marketed energy drinks contain high levels of caffeine and taurine. Both caffeine and taurine have been shown to have direct effects on cardiac function and hemodynamic status.

Hypothesis: We assessed the hypothesis that a commonly used energy drink alters blood pressure, heart rate and EKG parameters in healthy volunteers.

Methods: Healthy volunteers (n = 15, 53% female, 25.9 ± 5.9 years, 69.8 ± 14.8 kg) abstained from caffeine for 48 hours prior to and throughout the study period. On study day 1 (D1), blood pressure (BP), heart rate (HR) and an EKG were measured at baseline. Participants then consumed 500 mL (2 cans) of an energy drink containing caffeine (80 mg) and taurine (1000 mg) and BP, HR and EKG measurements were repeated at 30 minutes, 1, 2, 3, and 4 hours after consumption. Participants then consumed 2 cans of energy drink daily for the next 5 days (D2–D6). On day 7 (D7) the procedures followed on D1 were repeated. Average baseline measurements on days 1 and 7 were compared to maximum values during that observation period.

Results: On both D1 and D7, maximum mean systolic BP, HR and corrected QT-interval (QTc) occurred at 4 hours. Maximum diastolic BP occurred at 2 hours on D1 and D7. Baseline and maximum mean values are presented in Table 1

. Within 4 hours of energy drink consumption on D1 and D7 respectively, systolic BP increased by 7.9% (p = 0.006) and 9.6% (p < 0.001), HR increased by 7.8% (p = 0.009) and 11.0% (p < 0.001) and QTc increased by 4.5% (p = 0.368) and 5.5% (p = 0.052). Diastolic BP increased by 7.0% (p = 0.046) and 7.8% (p = 0.063) within 2 hours of energy drink consumption.

Conclusions: In conclusion, although no significant EKG changes were observed, subjects’ HR increased 5–7 bpm and systolic BP increased 10mmHg after consuming an “energy drink”. This level of change is likely clinically significant in patients with cardiac disease or those who consume such drinks regularly.

Table 1.

Baseline and Maximum Values (mean ± SD)
Abstract 3702: Anemia as an Independent Predictor of Perioperative and Long Term Cardiovascular Outcome in Patients Scheduled for Elective Vascular Surgery
Authors: Dunkelgrun Martin , Hoeks Sanne , Goei Dustin , Welten Gijs , Vidakovic Radosav , van Gestel Yvette , Schouten Olaf , van Domburg Ron , Poldermans Don
Published: July 2021

BACKGROUND: Anemia has been shown to be an independent risk factor for adverse cardiac outcome in various populations. This study evaluated the predictive value of anemia in patients scheduled for elective vascular surgery.

METHODS: In total, 1211 patients (76% male, age 68 ± 11 yrs) were enrolled. Anemia was defined as serum hemoglobin < 13 g/dL for men and < 12 g/dL for women, as defined by WHO. Anemia was divided into tertiles to compare mild, moderate and severe anemia with non-anemic patients. Outcome measures were 30-day and 5-year cardiac events (CE) (cardiac death or myocardial infarction). Mean follow up was 3.4 ± 3.2 years. Multivariable linear and Cox regression analysis was used, adjusting for age, sex, type of surgery and baseline characteristics, including angina, myocardial infarction, heart failure, diabetes and renal failure. Data are presented as HRs, with 95% confidence intervals.

RESULTS: In total, 74 (6%) patients experienced a 30-day CE and 199 (16%) a 5-year CE. Anemia was present in 399 (33%) patients, of which 133 were mild, 133 moderate, and 133 severe anemia. The presence of anemia was associated with renal failure, diabetes and heart failure. CE free survival at 30 days and 5 years was worse for patients with anemia (Figure

). After adjustment for all clinical risk factors, the 30-day HRs for a CE per anemia group were; mild 1.8, 1.0 – 4.1, moderate 2.9, 1.4 – 6.2, and severe 7.6, 4.1–13.1, and 5-year HRs for CE per anemia group were; mild 2.2, 1.3–3.8, moderate 3.6, 2.4 –5.6, and severe 6.6, 4.6 –9.6.

CONCLUSION: The presence and severity of preoperative anemia are significant predictors of 30-day and 5-year cardiac events in patients undergoing elective vascular surgery.
Abstract 3715: Inflammatory and Thrombotic Changes in Bereavement: A Potential Mechanism of Increased Cardiovascular Risk
Authors: Buckley Thomas , Morel-Kopp Marie-Christine , Bartrop Roger , McKinley Sharon , Ward Christopher , Mihailidou Anastasia S , Goldstone Kerrie , Bramwell Margaret , Hocking Belinda , Roche Dianne , Spinaze Monica , Tennant Christopher , Tofler Geoffrey
Published: July 2021

Background:
Bereavement is associated with increased risk of cardiovascular disease (CVD) especially in early bereavement. The mechanism of increased risk has not been well studied. This prospective study evaluated inflammatory and thrombotic measures in bereaved spouses and parents, within 2 weeks of bereavement and again at 6 months.

Methods:
Fifty-one subjects (35F/17M; aged 65.2 ± 13.1 years (mean ± SD) were prospectively studied within 2 weeks of bereavement and at 6 months, and compared to 43 non-bereaved relatives of discharged patients; age 61.1 ± 11.1 years). All participants had haemostatic measures obtained between 8 –11 am and processed within one hour. White cell subpopulations and activation marker levels were obtained using flow cytometry. Group results were analysed using ANOVA controlling for age.

Results:
Acute bereavement versus controls:
Compared to controls, acutely bereaved had a higher white cell count (WBC) 7.1 vs 6.2 10
9
/L (p<0.001), higher neutrophil count 4.4 vs 3.5 10
9
/L (p=0.001) and a trend towards higher monocyte count 468 vs 525/uL (p=0.06). Acutely bereaved subjects also had a reduced T suppressor cell number (CD8
+
) (406 vs 496 MFI, p=0.02), increased activation marker CD26 on CD4 T cells (541 vs 496 MFI, p =0.02) and increased NK cells positive for CD57 (46.5% vs 39.8%, p=0.05). Acutely bereaved subjects had higher levels of vWF-Ag than controls 126% vs 116% (p=0.04), and higher cortisol levels (340 vs 277 nmol/L (p=0.007).
Bereavement - acute versus 6 months:
Compared to acute assessment results shown above, the bereaved at 6 months showed reduced WBC count (6.2 10
9
/L; p=0.003), neutrophil count (3.7 10
9
/L; p<0.001), monocyte count (486, p=0.009) and CD57
+
NK cells (p <0.001). vWF-Ag was also lower (114%; p=0.02) as was factor VIII-ac (1.33 vs 1.17, p = 0.001). Fibrinogen and C-reactive protein did not change significantly from acute to 6 months.

Conclusion:
Acute bereavement is associated with increased inflammatory and prothrombotic changes. These findings provide insight into potential mechanisms for the increased CVD risk with bereavement and clues to potential preventive measures.
Abstract 3722: Multimodality Cardiovascular Imaging Detects Improvment Of Subclinical Microvascular Dysfunction With Continuous Positive Airway Pressure Therapy In Obstructive Sleep Apnea Patients: A Prospective, Randomized, Double-blinded Study
Authors: Katikireddy Chandra , Nguyen Patricia , Won Christine , Cardell Chia-Yu , Nichols Deborah , Leary Eileen , McConnell Michael , Holmes Tyson H , Kushida Clete A , Yang Phillip
Published: July 2021

Background:
Several observational studies suggest that obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease. However, there is little data on early subclinical development of cardiovascular disease in OSA patients.

Hypothesis:
We tested the hypothesis that continuous positive airway pressure (CPAP) improves subclinical cardiovascular disease in OSA patients.

Methods:
Sixteen consecutive patients diagnosed with moderate to severe OSA were recruited into a double-blinded, prospective study. Multimodality cardiovascular imaging (CVI) studies (cardiac MRI, echocardiography, and vascular ultrasound) were performed to assess LV mass, LV and RV ejection fraction (EF), adenosine stress myocardial perfusion reserve (MPR), nitroglycerin mediated coronary vasoreactivity, and flow-mediated vasodilatation (FMD) of the brachial artery. Patients were randomized to either CPAP or sham CPAP therapy and monitored for compliance during the entire period of treatment. After 3 months of therapy, they underwent follow-up CVI studies to assess development of subclinical cardiovascular disease.

Results:
MPR significantly improved (p=0.02) in patients with CPAP therapy compared to those without. Similarly, FMD of brachial artery improved significantly (p=0.04) following CPAP therapy. No significant differences were observed in LV mass (p=0.31), LV EF (p=0.17), RV EF (p=0.09), LV diastolic function (E/A) (p=0.67), and coronary vasoreactivity (p=0.25) between the two groups.

Conclusions:
Impairment of endothelial dependent FMD, and MPR, surrogate markers of microvascualr function, has been shown to be the subclinical cardiovascular effects in OSA patients. Our findings suggest that CPAP therapy may prevent the progression of subclinical cardiovascular disease in OSA patients.
Abstract 3772: Alternate Listing Transplantation is a Cost-Effective Treatment for End-Stage Heart Failure Patients
Authors: Russo Mark J , Chen Jonathan M , Hong Kimberly N , Argenziano Michael , Davies Ryan R , George Isaac , Ascheim Deborah D , Moskowitz Alan , Gelijns Annetine , Oz Mehmet C , Naka Yoshifumi
Published: July 2021

BACKGROUND:
In order to offer the benefit of heart transplantation to a greater number of patients some centers match high-risk recipients (HR) with non-standard or ”marginal” donors (MD) in a strategy known as Alternate Listing Transplantation (ALT). However, pairing sicker recipients with lower quality donor organs remains both clinically and ethically controversial. The purpose of this study was to determine the cost-effectiveness of this strategy.

METHODS:
The United Network of Organ Sharing provided deidentified patient-level data. UNOS data was used to determine clinical outcomes, including waiting time, post-transplant survival, length of stay, re-hospitalizations, episodes of rejection, and infection, based on all adult heart transplant candidates (age [gt] 18 yo) and listed between 1995–2005 (n=35,049). Through a systematic literature review of randomized controlled trials and case series that estimated related costs, a cost model (see Table

) using an intention-to-treat assumption was developed to calculate the incremental cost-effectiveness ratio (ICER) for HR candidates who subsequently received marginal donor hearts (HTR) compared with candidates who were not transplanted (NTXP). High-risk recipient criteria included age [gt] 65yo, retransplantation, HepC+, HIV+, CrCl <30 ml/min, DM with PVD, DM with Crcl <40 ml/min. MD criteria included age [gt] 55yo, DM, HIV+, HepC+, EF<45%, and donor:recipient weight <0.7.

RESULTS:
Median survival from listing was 0.55 yrs and 5.1 yrs in the HTR and NTXP groups, respectively. The estimated ICER was $66,645($34,046–$127,491) ICER varied by HR recipient criteria.

CONCLUSIONS:
The ICER for ALT falls at the upper limits acceptability for being cost-effective. However, stratified analysis by HR group suggests that this strategy is not appropriate for all groups.

Cost Model Assumptions
Abstract 3775: Average Blood Glucose and Mortality in Patients Hospitalized with Acute Myocardial Infarction
Authors: Kosiborod Mikhail , Inzucchi Silvio , Krumholz Harlan M , Xiao Lan , Jones Phillip G , Fiske Suzanne , Masoudi Frederick A , Marso Steven P , Spertus John A
Published: July 2021

Background: Elevated blood glucose (BG) on admission is associated with higher mortality risk in patients (pts) hospitalized with AMI. However, the prognostic value of average BG, which reflects overall glycemic exposure much better than admission BG, is unknown. Furthermore, the nature of the relationship between average BG and mortality has not been determined.

Methods: We evaluated a cohort of 16,871 AMI pts hospitalized from January 2000-December 2005, using Cerner Corporation’s Health Facts® database from 40 hospitals, which contains demographics, clinical and comprehensive laboratory data. Logistic regression models evaluated the nature of the relationship between mean BG during the entire AMI hospitalization and in-hospital mortality, after adjusting for multiple patient factors and confounders. Similar analyses were performed in subgroups of pts with and without diabetes (DM).

Results: A J-shaped relationship was observed between mean BG and in-hospital mortality, which persisted after multivariable adjustment (Figure

). Mortality increased with each 10 mg/dL incremental rise in mean BG over >120 mg/dL, and with incremental decline in mean BG <80 mg/dL. The slope of these relationships was much steeper in pts without DM.

Conclusions: Average BG during the entire AMI hospitalization is a powerful independent predictor of in-hospital mortality. Both persistent hyper- and hypoglycemia are associated with adverse prognosis. Whether strategies directed at optimizing BG control will improve survival remains to be established.

Association Between Mean BG and In-Hospital Mortality After Multivariable Adjustment (Reference: Mean BG 100 to <110)
Abstract 512: Cardiac Metabolic Adaptation during Chronic Exercise is Independent of PGC-1 Signaling
Authors: Schwarzer Michael , Pytel Gracjan , Bugger Heiko , Schrepper Andrea , Schoepe Maria , Riehle Christian , Doenst Torsten
Published: July 2021

PGC-1alpha is a transcriptional coactivator that regulates gene expression of mitochondrial proteins and energy metabolic enzymes. In skeletal muscle, PGC-1alpha is induced by endurance training and thought to mediate the energy metabolic adaptation to exercise. We investigated the role of PGC-1alpha signaling in metabolic adaptation of the heart in response to exercise. Male Sprague Dawley rats were trained on treadmills for 10 weeks, resulting in increased left ventricular posterior wall diameter (1.84±0.13 vs. 2.35±0.15 mm, p<0.05), indicating physiological hypertrophy. Gene expression of PGC-1alpha and beta and their transcription factors (NRF1&2, ERRalpha, TFAm) was not different compared to controls. Similarly, expression of OXPHOS genes (Ndufa10, Uqcrc2, COXIV) was unchanged in treadmill-trained hearts. In accordance with gene expression, state 3 respiration of isolated mitochondria was not different from controls, using palmitoyl-carnitine, pyruvate, or glutamate as substrates (natomsO/min/mg protein: Control PC 121±30, Pyr 58±6, Glu 203±42). In contrast, mitochondrial state 3 respiration of the oxidative soleus muscle was tripled with all substrates (natomsO/min/mg protein: PC 150±18 vs. 453±125, Pyr 95±23 vs. 310±37, Glu 115±12 vs. 280±23, p<0.05). Since PGC-1alpha signaling may also regulate substrate oxidation, we investigated oxidation of fatty acids (FAO) and glucose (GO) in the isolated working rat heart using 0.4mM oleate and 5mM glucose. FAO was not different between groups (μmol/min/gdw: 0.99±0.07 vs. 0.92±1.10). While expression of PPARalpha was increased in treadmill trained rats (+49%, p<0.05), FAO genes were not differentially expressed (MCAD, LCAD, CPT1). GO was 40% lower in trained hearts (0.38±0.08 vs. 0.23±0.06 μmol/min/g dry, n.s.) and was accompanied by a trend towards increased PDK4 expression (+90%, p=0.059). The response to insulin was normal. Cardiac power in trained working hearts was also normal. We conclude that PGC-1 signaling may not mediate the cardiac hypertrophic response to exercise. In contrast to skeletal muscle, respiratory capacity is not increased in heart muscle after exercise. The metabolic phenotype of hypertrophied hearts in response to exercise is surprisingly normal.
Abstract 18: Can Schoolchildren provide Life Supporting First Aid sufficiently?
Authors: Fleischhackl Roman , Nuernberger Alexander , Schoenberg Christina , Urso Tanja , Habart Tanja , Mittlboeck Martina , Sterz Fritz
Published: July 2021

Aims:
We investigated possible relationships between body constitution, age and sex of school children and their intellectual and physical abilities to provide effective life supporting first aid.

Methods:
Our observational study was carried out at the end of a school year, after first aid training had been provided by local teachers. As primary outcomes we measured CPR effectiveness parameters (depth of chest-compressions, number of chest-compressions, ventilation volume). As secondary outcomes we rated emergency calls, guideline adherence when checking signs of life and recovery position according to predefined checklists. Possible inter-dependencies between age, sex, body mass index (BMI) and physical or intellectual performance were calculated. Correlations between continuous data were assessed by Spearman rank correlation coefficient and differences between groups were tested by Wilcoxon’s rank-sum test. A p-value < 0.05 was considered significant.

Results:
We included 147 pupils at the age from 9 to 18 years. The median depth of chest-compressions was calculated at 35 mm (IQR 31– 41 mm), median number of compressions per minute was 129 bpm (IQR 108 ndash;143 bpm). Median volume applicated during mouth-to-mouth ventilation was 540 ml (IQR 0 –750 ml). Secondary outcomes are displayed in table 1

. BMI (r=0.35; p<0.0001), body weight (r=0.38; p=<0.0001) and body height (0.31; p=0.0002) showed statistically highly significant dependencies with chest-compression depth and ventilation volume. All other outcomes were not related to sex, age or body constitution.

Conclusions:
Children above the age of 9 years showed high quality overall performance after beeing trained in life supporting techniques. Effectivness parameters obtained from adults previously seem to be comparable. Even if physical strength could limit CPR effectiveness, children should not be withheld from first aid education.

Sec. Outcomes: Check f. vital signs, recovery position, emergency call, chestcompr/ventilation ratio
Abstract 22: Systemic Nitrite (NO2-) Levels are Depleted in a Mouse Model of Asystolic Cardiac Arrest and Therapeutic Repletion Improves Survival and Functional Neurological Recovery
Authors: Dezfulian Cameron , Alekseyenko Aleksey , Jeffries Kenneth R , Gladwin Mark T
Published: July 2021

Nitrite (NO2) represents a circulating reservoir of nitric oxide (NO) that is reduced to NO during ischemia. In pre-clinical studies, NO2 therapy was cytoprotective following focal heart, brain and liver ischemia-reperfusion. We hypothesized that systemic NO2 is depleted during global ischemia (cardiac arrest) and its early repletion could protect the heart and brain from reperfusion injury. C57BL/6 mice were rendered asystolic using a KCl bolus. After 12 min of warm ischemia (36.5C), paired mice were randomized to IV nitrite (blinded) or saline placebo given just prior to epinephrine, mechanical ventilation and chest compressions. All mice received identical pre- and post-CPR care until euthanasia and had similar physiologic parameters. NO2-treated mice had improved survival 22 hours post-CPR compared to saline-treated controls (HR 2.75 [95% CI:1.1– 6.8]; Table 1

). Deaths occurred 1– 6 h post-CPR and were associated with worsened cardiac ejection fraction 1.5h post-CPR. Neurologic function and thermoregulation were significantly improved in NO2-treated 22h survivors vs. paired controls. Cardiac arrest depleted whole blood and plasma NO2 (Table 2

). NO2 therapy restored levels near pre-arrest baseline with associated improvements in post-CPR oxygenation, ventilation and pH, without altering metabolic acidosis. Intravenous NO2 as adjunctive therapy to epinephrine early in CPR shows promise in improving cardiac and neurologic outcomes in a mouse model of cardiac arrest. The ease of NO2 delivery (vs. hypothermia), its approval and known safety profile in humans and its efficacy against reperfusion injury after prolonged asystole make NO2 an excellent drug candidate.

Survival, Cardiac and Neurologic Function After Resuscitation from Cardiac Arrest

Arterial Nitrite Levels and Blood Gases 5 minutes After Resuscitation from Cardiac Arrest
Abstract 25: Effect of Thrombolytics on the Immediate Prognosis for Out-of-Hospital Cardiac Arrest
Authors: Renard Aurelien , Jost Daniel , Verret Catherine , Briche Frederique , Fontaine David , Banville Isabelle L , Martin Anne-Celine , Val-de-Grâce Ecole du , Benner Patrick , Spiegel Andre , Fuilla Claude
Published: July 2021

Immediate care of out-of-hospital cardiac arrest (CA) is standardized by the established ILCOR ACLS Guidelines. Studies concerning the impact of thrombolysis, generally for CA of cardiac etiology have not shown a benefit. We sought to evaluate the rate of hospital admission for all CA patients treated with pre-hospital thrombolytics.

Methods: Non-randomized retrospective study was conducted from 09/1/2005 to 02/15/2007 of non-traumatic CA patients treated with (T+) or without (T-) thrombolysis. The protocol for administration of thrombolytics was at the discretion of the field physician, aiming for within 20 minutes of collapse in almost all cases, and prior to return of spontaneous circulation. The primary endpoint was admission alive to the hospital. We performed multivariate analysis by logistic regression to identify risk factors independently associated with outcome: age, gender, response time, defibrillation, witnessed arrest, bystander CPR.

Results: We reviewed 1331 consecutive patient records, of which 116 (8.7%) received thrombolytics. Both T+ and T- groups had comparable response times, witnessed arrest, and bystander CPR. Patients in T+ were significantly younger (59±14 vs 67±19 years old), predominantly males (81% vs 61%), and received more defibrillation shocks (61% vs 26 %). Significantly more patients T+ arrived alive to hospital for admission (45% vs 24%). Risk factors independently associated with hospital admissions were thrombolysis, age, response time, witnessed arrest, and bystander CPR. The impact of thrombolysis was different whether or not the patient was defibrillated (odds ratio with shocks 1.1 [95%CI: 0.2–5.0] vs without shocks 3.6 [95%CI: 1.9 – 6.9]), despite a greater overall rate of hospital admission for shocked patients.

Conclusion: Thrombolysis appears to improve the rate of admission alive to the hospital in patients that were not defibrillated with adjustment for age, gender, response time, witnessed arrest, and bystander CPR. These preliminary results should be confirmed by a prospective randomized study. This analysis can help determine appropriate inclusion criteria for a future study.
Abstract 30: Incomplete Chest Recoil During Piglet CPR Worsens Hemodynamics
Authors: Zuercher Mathias , Hilwig Ronald W , Nysaether Jon , Nadkarni Vinay M , Berg Marc D , Ewy Gordon A , Kern Karl B , Berg Robert A
Published: July 2021

Background
: Incomplete chest recoil during cardiopulmonary resuscitation (CPR) (ie, leaning on the chest during the decompression phase) is purported to decrease venous return, and thereby decrease forward blood flow.

Aim
To determine the effect of 10% and 20% lean on hemodynamics during piglet CPR.

Methods
: 10 piglets (10.7±1.2 kg) were anesthetized with isoflurane and instrumented with micromanometer-tipped catheters in the right atrium (RA) and aorta (Ao). After induction of ventricular fibrillation, CPR was provided in three-minute epochs with no lean, 10% lean, or 20% lean while aortic systolic pressure (AoS) was targeted at 80–90 mmHg. Because the mean force to attain 80 –90 mm Hg AoS was 18 kg in preliminary studies, 10% and 20% lean were provided as 1.8 and 3.6 kg weights on the chest, respectively. Left ventricular myocardial blood flow (MBF) and cardiac index (CI) were determined by fluorescent, color-microsphere technique. Statistics: paired
t
-test and repeated measurement ANOVA for parametric, Wilcoxon Rank Sum Test and Friedman’s ANOVA for non-parametric data.

Results
: 10% and 20% lean resulted in higher right atrial diastolic pressure (RAD) and lower coronary perfusion pressure (CPP) than no lean. Hemodynamics were not different with 10% lean vs. 20% lean. Mean 10%–20% lean resulted in substantially lower MBF and CI than no lean (Table

).

Conclusions
: 10–20% leaning during CPR increases RAD, decreases CPP, and substantially decreases MBF and CI.

Table
Abstract 37: The Impact Of Bodyweight On Early And Late Mortality And ICD Shocks In Ventricular Fibrillation Out-of-hospital Cardiac Arrest Survivors
Authors: Bunch T. J , White Roger D , Lopez-Jimenez Francisco , Thomas Randal J
Published: July 2021

Background
: Studies have shown an association between obesity and total mortality in patients with and without coronary artery disease. Less is known regarding the impact of obesity after cardiac arrest. Obese survivors of ventricular fibrillation (VF) out-of-hospital cardiac arrest (OHCA) may have worse outcomes than nonobese patients due to resuscitation challenges, long-term risks of cardiovascular disease, and other comorbidities.

Methods
: All patients who presented with a VF OHCA in Rochester Minnesota from November 1990-September 2006 were included. Patients were classified by weight (BMI <25, 25–30, >30). ICD shocks for VF/VT were determined by review of subsequent device interrogations.

Results
: 226 patients (age 63.7±13.5) were treated for VF OHCA with an average call-to-shock time of 6.3±1.8 minutes. 99 patients (44%) survived to hospital discharge with neurologic recovery. Data to calculate BMI were available in 213(95%). There was no difference between the relative distribution of body weight between the hospital survivors [<25(32%), 25–30(37%), >30(31%)] and nonsurvivors [<25(32%), 25–30(44%), >30(28%)], p=0.711. There was no difference in ICD implantation rates between weight groups (p=0.251). The patients were followed for an average of 5.8±4.4 years. The 5-year survival was 80±5%. 5-year survival was lower in underweight/normal patients [<25, 71% (63–79) compared to heavier patients (25–30:88% (82–94), p=0.001]. The survival difference persisted after adjustment for age (p=0.02). Malignancy was the most common cause of death in the underweight group. The 5-year survival free of ICD shocks was 61±7% with no weight-based difference in shocks.

Conclusion
: There was no apparent weight-based influence on resuscitation survival after VF OHCA. Patients who are under to normal weight had a lower long-term survival and represent a high-risk population primarily due to noncardiac diseases.
Abstract 45: A Mathematical Model of Ventilation, Perfusion, and Oxygenation in Low-Flow States
Authors: Davis Daniel P , Davis Paul W
Published: July 2021

Background: Recent investigations underscore the critical importance of ventilation strategies on resuscitation outcomes. In low perfusion states, such as cardiac arrest and traumatic shock, the rise in intrathoracic pressure that accompanies positive-pressure ventilation (PPV) can significantly impede venous return and lead to a decrease in cardiac output. The optimal ventilation strategy in these “low-flow” states remains unclear.

Objectives: To create a mathematical model of perfusion and oxygenation to predict the effects of PPV with both normotension and hypotension.

Methods: The lung pressure-volume relationship was modeled using a novel formula allowing manipulation of various lung characteristics, including vital capacity, compliance, and the upper and lower inflection points. A separate formula was then derived to predict mean intrathoracic pressure for a given minute ventilation using the pressure-volume formula. The addition of positive end-expiratory pressure was also modeled. Finally, a formula was derived to model oxygen absorbance as a function of alveolar surface area and flow based on ventilation rate and mean intrathoracic pressure.

Results: Mathematical models of the lung pressure-volume relationship, mean intrathoracic pressure, and absorbance were successfully derived. Manipulation of vital capacity, compliance, upper and lower inflection points, positive end-expiratory pressure, and minute ventilation allowed prediction of optimal ventilation rate and tidal volume for a normal and an ARDS lung. For a normal lung, optimal values for both mean intrathoracic pressure and absorption were achieved with a ventilation rate of 4 breaths/min. A decrease in the upper inflection point or increase in minute ventilation resulted in faster optimal ventilation rates, although none exceeded 14 breaths/min.

Conclusions: A mathematical model of ventilation was successfully created allowing manipulation of multiple variables related to lung compliance and ventilation strategy. This model suggests the use of lower ventilation rates with larger tidal volumes to minimize the hemodynamic effects of PPV and maximize oxygen absorbance.
Abstract 48: Reduction of Histological Damage with Mild Therapeutic Hypothermia after Prolonged Cardiac Arrest
Authors: Springler Gregor , Janata Andreas , Weihs Wolfgang , Bayegan Keywan , Schratter Alexandra , Robak Oliver , Holzer Michael , Frossard Martin , Behringer Wilhelm , Schock Robert B , Coté Marc , Freedman Robert J , Losert Udo M , Schmidt Peter , Laggner Anton N , Sterz Fritz
Published: July 2021

Purpose: The aim of our study was to assess the effect of hypothermia on histological damage in 19 brain regions after prolonged cardiac arrest in pigs.

Methods: Pigs were anaesthetized and mechanically ventilated. After stabilisation of pulmonary artery temperature (Tpa) at 38.5±0.2 °C, ventricular fibrillation (VF) was induced and 10 min of untreated VF were followed by 8 min of cardiopulmonary resuscitation (mechanical chest compressions, two doses of vasopressin 0.4 IE/kg). At 8 min of CPR, up to 3 countershocks were delivered. Pigs that had return of spontaneous circulation (ROSC) were randomized to one of 2 groups (control, hypothermia). Pigs in the hypothermia group were cooled to Tpa 33.0±1.0 °C with a surface cooling device (LRS Thermosuit™) circulating ice water over most of the skin surface. Pigs in the control group were kept at 38.5±1.0 °C throughout the experiment. After 14 hours of hypothermia, pigs were rewarmed, weaned and brought to the stable. At day 9 of the experiment, final neurologic examination was performed. After that the animals were sacrificed and perfused with 4 liters of saline, followed by 1 liter of paraformaldehyde (3%, pH 7.4). The brain was removed and 19 different regions of the brain were examined by means of lightmicroscopy using a histopathologic damage score that was used in previous studies. Following damage qualities were considered: edema, eosinophilic necrosis (oncosis), vacuolar degeneration and malacia. The total numeric histological damage score (HDS) was the sum of all area scores. Data are presented as median and interquartile range, group comparison was done with a Mann-Whitney-U test.

Results: 16 (29 –35 kg) pigs were randomized. The time to reach target temperature in the hypothermia group (n = 8) was 9.0 (5.3; 11.9) min. Total HDS in the hypothermia group was 71 (61; 84), in the control group 132 (124; 174; p<0.001). Significant (p<0.05) improvements in damage were found in hippocampus, temporal, parietal, frontal and occipital cortex.

Conclusions: Histological damage after prolonged cardiac arrest was improved significantly in cooled animals compared to control animals. Not all brain regions could benefit to the same extent.
Abstract 55: Ventricular Fibrillation remains the Primary Presenting Rhythm: Results from the Wearable Cardioverter Defibrillator Human Study
Authors: Wang Hao , Tang Wanchun , Tsai Min-Shan , Li Yongqin , Weil Max H
Published: July 2021

Background.
Clinical studies during the last 2 decades have demonstrated a progressive decrease in the incidence of ventricular fibrillation (VF) as the presenting rhythm in settings of out-of-hospital sudden cardiac arrest (SCA). In the present study, we investigated the initial rhythm of SCA from data recorded in a wearable cardioverter defibrillator (WCD) which collected these events in real time.

Hypothesis.
In settings of out-of-hospital SCA, VF remains the leading cause.

Methods and Results.
The incidence and the type of arrhythmias were determined by reviewing stored electrocardiograms in the WCDs. Seventy-four consecutive WCD recipients and 108 events were analyzed. Patients with a previously implanted ICD that required change due to infection were the most prevalent recipients of WCDs. Fifty-one percent were VF/VT patients and 43.8% were pulseless electrical activity (PEA) patients. VF/VT was the initial rhythm of SCA in 79.7% of patients and 86.1% of events while the PEA occurred in 20.3% of patients and 13.9% of events. 84.5% of patients survived VF/VT and 18.8% of patients survived PEA. There was no difference in the characteristics of patients with different initial rhythms.

Conclusions.
In out-of-hospital settings, VF remains the predominant initial rhythm when recorded immediately following SCA. .