bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2832: Papillary Muscle Infarction is a Predictor of Ischemic Mitral Regurgitation: Novel Insights from Cardiac Magnetic Resonance Study
Authors: Boonyasirinant Thananya , Buakhamsri Adisai , Curtin Ronan , Setser Randolph M , Flamm Scott D
Published: July 2021

Introduction
Ischemic mitral regurgitation (MR) bodes worsened prognosis and increased mortality in patients with ischemic cardiomyopathy. Various mechanisms of ischemic MR have been purposed, resulting in a spectrum of surgical strategies with varying success rates. Papillary muscle infarction may contribute to ischemic MR, but could not be identified non-invasively until the recent development of chronic infarction specific imaging (delayed-enhancement, or DE-MRI).

Hypothesis
We hypothesized that papillary muscle infarction, determined by DE-MRI, was correlated with the presence of ischemic MR.

Methods
Contrast-enhanced cardiac MRI for viability assessment was performed in 100 patients with ischemic cardiomyopathy (67 male, mean age 65 years). Papillary muscle infarction was determined from DE-MRI, and left ventricular (LV) functional parameters were calculated from contiguous short-axis cine-MRI images using the disc-summation technique.

Results
MR by echocardiography was present in 67%: 30% with mild MR (1+), 27% moderate MR (2+), and 10% severe MR (3– 4+). In patients with no, mild, moderate, and severe MR, there was a positive correlation with the prevalence of posterior papillary muscle infarction (15%, 40%, 52%, and 70%, respectively), but there was no association with anterior papillary muscle infarction (p=NS). There was a significant inverse relationship with LV ejection fraction (LVEF) (29%, 26%, 24%, and 20%, respectively). Both LVEF (p=0.013) and posterior papillary muscle infarction (p=0.006) were significantly associated with ischemic MR on univariate analysis. Using multiple logistic regression analysis, both posterior papillary muscle infarction and LVEF remained independent determinants of MR presence and severity (p<0.001 for both).

Conclusions
Patients with ischemic cardiomyopathy demonstrate a significant and positive correlation between the severity of MR and prevalence of posterior, but not anterior papillary muscle infarction identified by DE-MRI, and an inverse relationship with LVEF. The identification of papillary muscle infarction may provide insights into alternative approaches for repair of ischemic MR.
Abstract 2845: Differential Impact of Left Ventricular Remodeling on Septal and Lateral E/Ea Ratio in Predicting Diastolic Staging in Chronic Systolic Heart Failure
Authors: Tang W. H. Wilson , Shrestha Kevin , Mullens Wilfried , Borowski Allen , Troughton Richard W , Klein Allan L
Published: July 2021

Background:
The ratio of peak transmitral pulsed Doppler early velocity to early diastolic tissue Doppler velocity of the lateral or septal mitral annulus (E/Ea) is considered a reliable estimation of diastolic dysfunction, and their average has been incorporated as clinical determinant of diastolic heart failure. Their relative relaibility in the setting pf left ventricular volumes has not been established.

Methods:
We performed comprehensive 2D echocardiography in 214 ambulatory patients with chronic systolic heart failure (LVEF ≤35%, NYHA II-III). Diastolic staging was determined from patterns of transmitral and pulmonary vein flows.

Results:
In our study population (mean age 57 years, 73% male mean left ventricular end-diastolic volume [LVEDV] 228 ml, mean LVEF 25%)
,
the median lateral and septal Ea were 6.9 cm/s and 4.5 cm/s, respectively. The median E/lateral Ea, E/septal Ea, and E/average Ea [inter-quartile range] were 10.8 [7.1–15.1], 16.1 [11.1–23.0], and 12.7 [8.8–17.7], respectively. In the first two tertiles of indexed LVEDV (LVEDVi<92.6 ml/m
2
and 92.6–129.5 ml/m
2
), all three E/Ea indices increased with increasing diastolic stages (all p<0.001). However, in the highest tertile of LVEDVi (>129.5 ml/m
2
), E/septal Ea (but not E/lateral Ea) increased with increasing diastolic stages (Figure

).

Conclusions:
Unlike E/septal Ea, E/lateral Ea did not increase with increasing diastolic stage in patients with chronic systolic heart failure presenting with LV dilatation. These observations may suggest that the E/septal Ea measurements may be more reliable than E/lateral Ea to assess diastolic dysfunction in patients with enlarged ventricles.
Abstract 2871: Saddle-Shaped Annuloplasty Reduces Mitral Leaflet Stress: A Real-Time 3D Echocardiographic Study
Authors: Blom Aaron S , Xu Chun , Ryan Liam P , Jackson Benjamin , Parish Landi M , Eperjesi Thomas J , Gorman Joseph H , Gorman Robert C
Published: July 2021

Objectives: High leaflet and chordal stresses contribute to recurrent mitral regurgitation after repair procedures. We hypothesized that a saddle-shaped annuloplasty ring would reduce leaflet stress compared to a similarly sized flat annuloplasty ring. To test this hypothesis we used a novel 3D echocardiographically-based finite element modeling (FEM) technique for quantifying regional mitral valve stress.

Methods: Real-time 3D echocardiography was performed in 8 sheep before and after placement of either a 30mm flat annuloplasty (n=4) or a 30mm saddle-shaped annuloplasty. Full-volume data sets of the MV were obtained using an IE33 platform(Philips Medical Systems, Andover, Massachusetts) and exported to Cardio-View (Tomtec Imaging Systems, Munich, Germany) for image analysis. Individual leaflet data were then interpolated using Matlab (The Mathworks, Natick, Massachusetts). Triangulated leaflet surfaces were extracted and the data imported into a commercial finite element program (ABAQUS/Explicit 6.3, HKS Inc. Pawtucket, RI) to quantify regional stress distributions in all segments (P1, P2, P3 and A1, A2, A3) of the MV.

Results: Peak anterior and posterior leaflet stresses after flat annuloplasty placement were 0.20±0.001MPa and 21±0.02MPa. Peak anterior and posterior leaflet stress after saddle-shaped annuloplasty placement was 0.19±0.02MPa and 13±0.01MPa (p<0.05 for the posterior leaflet stresses)

Conclusions: Saddle-shaped annuloplasty design results in greater stress reduction in the posterior leaflet than standard flat annuloplasty rings and may, therefore, result in more durable repairs.

This research has received full or partial funding support from the American Heart Association, AHA Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania & West Virginia).
Abstract 2877: A Combined Cell Therapy and In Situ Tissue Engineering Approach for Myocardial Repair
Authors: Habib Manhal , Shapira Keren , Caspi Oren , Arbel Gil , Gepstein Amira , Seliktar Dror , Gepstein Lior
Published: July 2021

Cell replacement and tissue engineering strategies are emerging as novel therapeutic paradigms for myocardial repair. Here we tested the hypothesis that a combined
in situ
tissue engineering and cell delivery strategy utilizing transplantable hydrogel-embedded cardiomyocytes [either neonatal rat ventricular cardiomyocytes (NRVCMs) or human embryonic stem cell-derived cardiomyocytes (hESC-CMs)] will improve functional performance in the rat infarction model.

Methods and results
: A novel liquid biodegradable PEGylated fibrinogen was developed, which was proved to be compatible with cardiomyocyte survival and maturation
in vitro
. Photopolymerization using UV beam results in a rapid liquid to hydrogel transformation. Animals were randomized to injection of saline, NRVCMs alone, the biopolymer alone, or the combined delivery of the biopolymer and the NRVCMs. Histological studies demonstrated the presence of the hydrogel-embedded cardiomyocytes within the scar tissue. The biopolymer was fully absorbed one month following delivery. Echocardiography revealed typical post-infarction remodeling in the control group (saline injection) as manifested by the deterioration of ejection fraction (EF) by 28±3% (from 43±2% at post-injury baseline to 30±2% at 4 weeks). Injection of the biopolymer or NRVCMs alone prevented this remodeling process (39±2% to 39±2% and 43±3% to 43±2% respectively; p<0.05 when compared to controls). Co-injection of the biopolymer and NRVCMs resulted in the best functional outcome with EF improving by 22±8% from 40±4% to 48±4% (p<0.05 when compared to the saline or biopolymer groups and p=0.07 when compared to NRVCM group). Finally, initial studies also demonstrated a favorable effect following the co-injection of the biopolymer together with hESC-CMs (from a baseline value of 45±1% to 47±1%). Similar improvements in all groups were also noted for other remodeling parameters (LV diastolic area and wall motion score)

Conclusions:
We describe a novel injectable in-situ-forming hydrogel that functions as an efficient cardiomyocyte carrier for both NRVCM and hESC-CMs and acts synergistically with the grafted cells to prevent the unfavorable post-infarction cardiac remodeling and improve ventricular function in rats.
Abstract 2954: Short-term Effects of High Dose Idebenone on Left Ventricular Mass and Function in a Pediatric Cohort with Friedreich’s Ataxia
Authors: Plehn Jonathan F , Hasbani Keren , Horton Ken , Ernst Inez , Arai Andrew E , Di Prospero Nicholas A
Published: July 2021

Background:
Early mortality in Friedreich’s Ataxia (FA) is believed to commonly result from an underlying hypertrophic cardiomyopathy which may be caused by increases in reactive oxygen species. Antioxidant therapy could result in slowing of disease progression or regression of left ventricular mass (LVM).

Methods:
We tested the hypothesis that high dose idebenone could lead to regression of LVM and LV functional improvement in 48 pediatric subjects with genetically-confirmed FA (23 females, 25 males, mean age=13.4 years) randomly assigned to weight-stratified low (4 – 8 mg/kg), medium (10–20 mg/kg) or high (30–50 mg/kg) doses of idebenone or placebo. Cardiac magnetic resonance imaging (MRI) and echocardiographic (echo) two-dimensional and Doppler analysis blinded to treatment assignment were performed at baseline and after 6 months of therapy.

Results:
At baseline, increased LVM indexed by height
2.7
was observed in 44%, LV concentric remodeling (relative wall thickness >0.39) in 83% and impaired early relaxation by Doppler tissue velocity (E’) in 88% of subjects as determined by age-adjusted, normative echo data. MRI-determined LVM (n=45 subjects) was inversely related to measures of LV relaxation including E’ (p<0.0001), color Doppler flow propagation (p<0.007) and isovolumic relaxation time (p<0.005) but not mitral deceleration time. LVM also correlated with peak lateral systolic tissue velocity (p=0.002) but not LV ejection fraction. At 6 months combined, idebenone-assigned subjects demonstrated a 1.3 ± 1.6 % reduction of LVM vs. baseline which compared to an 8.9 ± 4.0% LVM increase in placebo subjects (p=.007). By Fisher’s test, LVM regression was observed only in the high and intermediate dose groups (p≤0.05 and p≤0.01) with a trend toward regression in the low dose group (p=0.056). No effects on diastolic relaxation or systolic functional parameters were observed after 6 months of idebenone treatment.

Conclusions:
Hypertrophic cardiomyopathy and associated diastolic functional impairment is highly prevalent in pediatric FA patients with moderate neurologic impairment. Short term treatment with high dose idebenone appears to result primarily in blunting of LV mass progression but not to detectable improvements in LV function.
Abstract 2962: Donor-specific Antibodies Correlate with Events in Heart Transplant Patients
Authors: Pavlovic-Surjancev Biljana , Patel Nilamkumar , Sinacore James , Neuswanger Norma , Susskind Brian , Heroux Alain
Published: July 2021

Antibodies (ab) against human leukocyte antigens (HLA) in transplant (tx) recipients are associated with poor outcome. Flow PRA (panel reactive ab) detects non-specific ab against Class I & II HLA (%). New technology detects ab against donor HLA = Donor-Specific Ab (DSA). Experience with DSA in heart tx patients (pts) is limited.

Purpose:
To evaluate presence of non-specific ab & DSA and to correlate it with events in heart tx pts.

Methods
: We included all pts with heart tx done Feb 1986-Feb 2008 followed at our ctr with post-tx flow PRA drawn March 2006-Feb 2008 on random sample or event-related sample, ordered at clinician’s discretion. Random sample was drawn during clinic visit or hospital admission not related to graft rejection. Event is defined as hospital admission for suspected graft rejection. There were 277 samples drawn for flow PRA from 93 pts. To reduce bias related to multiple samples from 1 pt we included only 1 sample with highest PRA %. Pts were categorized in 2 groups: PRA ≥ 10% (high) and PRA < 10% (low). Low titer DSA was < 100,000 molecules of equivalent soluble fluorescence units (MESF).

Results
: Among 93 pts, 27 pts had PRA ≥10% (29%), among which 13 pts had event (14% of 93 pts) and 66 pts had PRA < 10% (71%) among which 3 pts had event (3% of 93 pts). Low PRA Group: Among 66 pts with PRA < 10%, 63 pts had no events (95.5%). Among 66 pts with PRA < 10%, 42 pts had no DSA tested and 24 pts had DSA tested. Among 24 pts with DSA tested, 23 pts had negative DSA and 1 pt had positive low titer DSA (this pt had no event). Three pts with negative DSA had an event; one of them had cross-reactive ab. High PRA Group: 27 pts with PRA≥10% were subcategorized in 2 groups based on the presence or the absence of the event. Group 1(N = 14 (52%)) had no event:8 pts did not have DSA drawn, 5 pts were DSA negative and 1 pt was positive with low titer DSA. Group 2(N = 13 (48%)) had an event:10 pts were DSA positive with high-titer, whereas 3 pts were DSA negative (1 pt had cross-reactive ab to donor-specific antigen). Difference between Groups 1 and 2 was significant by Fisher’s exact test (p < 0.05).

Conclusions
: Majority of pts hospitalized for suspected rejection (75%) had high-titer positive DSA (62.5%) or cross-reactive ab to donor-specific antigen (12.5%). This study will be basis for future prospective DSA monitoring.
Abstract 3000: Blood Pressure Imposes Different Cardiovascular Morbidity On Renal Transplant Candidates Depending On The Presence Of Concomitant Cardiovascular Disease Regardless Of Left Ventricular Function
Authors: Gowdak Luis Henrique W , de Paula Flavio J , Cesar Luiz Antonio M , Krieger Eduardo M , De Lima Jose Jayme G
Published: July 2021

Background:
Renal transplant candidates (RTC) are at risk of cardiovascular disease (CVD) and events (MACE). We compared the impact of blood pressure on the incidence of MACE in RTC according to left ventricular (LV) function and the presence of CVD.

Methods:
956 RTC (62% men, 53 ± 11 years) were divided according to the presence of CVD (CAD, heart failure, peripheral arterial disease, and/or stroke). LV ejection fraction (EF) was obtained by echo and the mean arterial pressure (MAP) calculated during the baseline visit. The composite incidence of fatal/non-fatal MACE was determined during a median follow-up of 24 months and its rate plotted for each MAP level for RTC with and without CVD; the best curve to fit the regression model was determined by the regression coefficient (R
2
).

Results:
The incidence of MACE was 18.4% in the overall population. RTC with concomitant CVD had a 3-fold increase in the endpoint (31.9%) compared with RTC without CVD (11.3%) (P < 0.0001). As shown by the dark lines, in RTC with (
“J-shape”
curve; R
2
= 0.91; P < 0.0001) or without CVD (linear; R
2
= 0.88; P < 0.0001), the MAP was associated with MACE. In the graph, the mean LVEF for each MAP level is represented by the bars (CVD[−]= white; CVD[+]= gray). There was no difference in the mean LVEF in RTC without CVD (P = 0.57), whereas in the group with CVD, the mean LVEF was lower in those with lower MAP (P = 0.014). Even so, in RTC with CVD and similar LVEF, those with a MAP between 101–120mmHg had the lowest rate of events.

Conclusions:
In RTC, blood pressure has a different impact on the occurrence of MACE depending on the presence of CVD. In RTC with CVD, this effect seems to be stronger at extreme levels of MAP, regardless of the LV function.
Abstract 3045: Procedural and 30-day Outcomes Following Transcatheter Aortic Valve Implantation using the Third Generation (18F) CoreValve Revalving® System - Results from the Multicenter, Expanded Evaluation Registry 1 year after Being CE Mark Approved, on Behalf of all Actively Participating Centers
Authors: Piazza Nicolo , Grube Eberhard , Gerckens Ulrich , den Heijer Peter , Linke Alex , Luha Olev , Raimondo Angelo , Ussia Giampaolo , Wenaweser Peter , Laborde Jean-Claude , de Jaegere Peter , Serruys Patrick W.
Published: July 2021

Background: Over 2000 transcatheter aortic valve implantations (TAVI) have been performed worldwide by means of two differing technologies. Initial reports, limited by the initial learning curve and small sample size, documented rates of procedural success and 30-day mortality in three-quarters and more than one-tenth of patients, respectively.

Objective: To describe the procedural performance and 30-day outcomes following implantation using the 18F CoreValve Revalving System (CRS) as part of the multicenter, expanded evaluation registry, 1-year after obtaining CE mark approval.

Methods: Patients with symptomatic severe aortic stenosis and logistic EuroSCORE ≥ 15%, or age ≥ 75 years, or age ≥ 65 years associated with pre-defined risk factors, and for whom a physician proctor and a clinical specialist were in attendance during the implantation and who collected the clinical data, were included.

Results: From April 2007, to April 2008, 646 patients with a mean age of 81± 6.6 years, mean aortic valve area 0.6 ± 0.2 cm2, and logistic EuroSCORE of 23.1± 13.8% were recruited. After valve implantation, the mean transaortic valve gradient decreased from 50.4 ± 16.8 to 3.2 ± 5.2 mmHg. Only one percent of patients had paravalvular aortic regurgitation ≥ grade 2. The rate of procedural success was 97%. The procedural mortality rate was 1.5%. At 30 days, the all-cause mortality rate (i.e. including procedural mortality) was 8% and the combined rate of death, stroke and myocardial infarction was 9.3%.

Conclusion: The results of this study demonstrate a high rate of procedural success and low rate of 30-day mortality in a large cohort of high-risk patients undergoing TAVI with the CRS self-expanding aortic valve prosthesis.
Abstract 3047: Management Of Procedural Complications Associated With Transcatheter Aortic Valve Implantation
Authors: Lange Ruediger , Bleiziffer Sabine , Ruge Hendrik , Mazzitelli Domenico , Schreiber Christian , Hutter Andrea , Tassani-Prell Peter , Bauernschmitt Robert
Published: July 2021

Objective The transcatheter aortic valve implantation (TAVI) technology is rapidly evolving. The complications related to these procedures are different from those seen after conventional aortic valve replacement. Herein, we report our experience on the incidence and management of procedure-related complications in the first series of TAVI.

Methods Between 6/2007 and 6/2008, 112 patients (n=62 female, mean age 81.3±7y, mean logistic EuroScore 25.0±15.6%) underwent TAVI through either a retrograde (n=92 transfemoral, n=3 via subclavian artery, n=1 ascending aorta) or antegrade (n=16 transapical) approach at our institution. 95 CoreValve and 17 Edwards Sapien (n=17) prostheses were implanted.

Results 30-day mortality was 8.9% (n=10). Major vascular complications occurred in 19 patients (16,9%). 2 patients with iliac or femoral rupture were treated with covered stent. 14 patients with bleeding from vascular site were treated with surgical suture or prosthesis implantation. Three patients had lethal aortic root (n=2) or abdominal (n=1) aortic rupture. Cardiac tamponade occurred in 8 patients (7.1%); among these 3 were treated conservatively, 4 underwent subxyphoid puncture and one patient had thoracotomy. Valve displacement could be treated interventionally in 5 out of 6 patients, 1 patient underwent conventional surgery. In 2 patients, with extremely poor LV function, emergent institution of cardiopulmonary bypass was required during the procedure. 5 patients underwent interventional re-valving (n=2) or surgical re-replacement (n=3) due to high-grade regurgitation (n=5) or valve displacement (n=1). Pacemaker implantation due to postprocedural AV block was required in 23 patients (20.7%). Despite these complications, the overall initial procedural success was 98 % (n= 110/112).

Conclusions A significant number of complications after TAVI requires surgical treatment. Therefore, TAVI procedures should be performed in a hybrid operating room which allows for immediate surgical intervention and the rapid institution of cardiopulmonary bypass if necessary.
Abstract 3078: The Poor Prognosis of Diabetic Patients with High Ankle-Brachial Index Depends on the Presence of Masked Peripheral Arterial Disease
Authors: Aboyans Victor , Tran Minh Hoang , Salamagne Claire , Archambeaud Francoise , Criqui Michael H , Laskar Marc , Lacroix Philippe
Published: July 2021

Background: A high ankle-brachial index (ABI >1.40) is associated with poor prognosis. An underlying peripheral arterial disease (PAD) is frequent in diabetic patients with high ABI, although it cannot be adequately diagnosed by the ankle pressure measurement, due to stiff arteries. We hypothesized that in diabetic patients, the poor cardiovascular disease (CVD) prognosis associated with high ABI would depend on the coexistence of masked PAD.

Methods: We reviewed the data of 403 consecutive diabetic patients who had a Doppler assessment of their lower limbs between 1999 and 2000. They were classified as “normal” when Doppler waveform patterns (DWP) were normal and ABI within the 0.91–1.39 range, “PAD only” in case of ABI ≤0.90, “stiff only” if ABI ≥1.40 with normal DWP, and “mixed disease” when ABI ≥1.40 with abnormal DWP. Patients were followed until 04/2008. The primary endpoint was the occurrence of any of the following events: death, stroke or myocardial infarction.

Results: The patients (age: 65.6 ± 13.2 yrs, 54.6% females; 90.2% type-2 diabetes) were classified as “normal” (14.4%), “PAD only” (48.4%), “stiff only” (16.4%) and “mixed disease” (20.8%). During a mean follow-up of 6.5 years, the event-free survival curves of “PAD only” and “mixed disease” groups showed poorer prognosis than the “stiff only” and “normal” groups (figure

). In a model adjusted for age, sex, diabetes type and duration, traditional CVD risk factors, renal failure and CVD history, only the presence of PAD was significantly associated with the primary endpoint (OR: 3.36 (1.25 – 4.44), p=0.008).

Conclusions: In diabetic patients with high ABI (>1.40), only those with an associated PAD have a poorer prognosis.
Abstract 3092: Risk Associated with Sports Competition: Is Lacrosse Really a Uniquely Dangerous Sport?
Authors: Maron Barry , Doerer Joseph J , Haas Tammy S , Hodges James S , Estes N. A , Link Mark S
Published: July 2021

Background. Sudden deaths in young competitive athletes are tragic events having great personal impact on physicians and lay communities. These deaths occur in a wide variety of sports due largely to unsuspected cardiovascular disease or commotio cordis. Lacrosse is now the most rapidly growing sport in the U.S., presently with 500,000 competitors. The risks specifically associated with participation in lacrosse have been the subject of substantial media attention, implying that this sport may be unsafe relative to other youth sports. However, systematically assembled data in this regard are not available.

Methods. The U.S. Sudden Death in Young Athletes Registry, 1980 –2008, was accessed and 22 sudden deaths (including 4 survivors of cardiac arrest) were identified in high school and college competitive lacrosse participants.

Results. Ages were 13–22 years (mean 17±2y); all were male. Nineteen athletes died on the athletic field and 3 during sedentary activities. Ten of the 22 athletes died of non-penetrating blunt blows to the chest (i.e., commotio cordis), including 4 goalies who were wearing standard chest protectors. Another 10 athletes collapsed suddenly due to either documented or presumed cardiovascular disease (e.g., most commonly hypertrophic cardiomyopathy, long QT syndrome, mitral valve prolapse), and 2 incurred subarachnoid hemorrhage from blows to the head. The overall mortality rate associated with lacrosse was 1.39 deaths/100,000 person-years, and lower than a variety of other sports including baseball, basketball, and football (p=0.07), as well as hockey (p=0.1). Deaths due to commotio cordis were more frequent in lacrosse (0.63 deaths/100,000 person years) than in all other competitive sports (p<0.0001) with the exception of hockey (p=0.7).

Conclusions. Sudden deaths in young high school and college lacrosse participants are rare relative to the number of athletes involved, and are caused disproportionately by commotio cordis. These findings underscore the importance of (and represent an impetus to) developing more effective chest protection for young people in this popular and growing competitive sport.
Abstract 4013: The Impact of Atrial Fibrillation on the outcomes of patients suffering a second Myocardial Infarction
Authors: Deng Yingzi , Kostis William J , Wilson Alan C , Cosgrove Nora , Shao Yu-Hsuan , Moreyra Abel , Kostis John B
Published: July 2021

In the past 20 years, significant increases in hospital admissions for atrial fibrillation (AF) and in survival of acute myocardial infarction (MI) have been observed. We examined the occurrence of AF and its effect on short and long term outcomes of first MI(FMI) and second MI(SMI). Hospitalized MIs from MIDAS (Myocardial Infarction Data Acquisition System, N=269,110) in New Jersey from 1986 to 2005 were included in the analysis. The rate of the co-exiting MI and AF and 30-day and 1 year mortality were investigated. Approximately 11 %( N=26,631) of FMI patients had a second event. The rate of co-existing AF for the FMI was 9.6% in 1986 and 16.2% in 2005, a 40.9% increase; while AF increased 60.4%, from 7.7% to 20.5% for SMI. Patients with AF were older (76.5 vs 69.3), more likely to be female (43.6% vs 39.4%), to have subendocardial infarction (58.5% vs 49.2%). Patients AF were less likely to be black in racial (4.2% vs 8.4%) and to receive percutaneous coronary interventions (PCI) (6.1% vs 10.4 %). There were more strokes (2% vs 0.9%) and heart failure hospitalizations (HF, 58% vs 39%) in the AF group(p<0.0001). Thirty-day mortality rates (AF vs non-AF) were 20.9% and 13.8% for the FMIs; and 21.5% vs 14.2% for SMIs. One-year mortality rates were 37.4% and 20.5% at FMI, and 43.3% and 28.1% at the SMI, respectively. When adjusting for age, gender, race, MI site, PCI, year of MI, diabetes, stroke and HF, AF increased the 30 day mortality by 36%( OR1.36 95% CI 1.32–1.41) for FMI, and by 33% (OR 1.33(1.22–1.46)] for SMI. The effect of AF on mortality was more pronounced at 1 year [FMI 1.54(1.50 –1.58), SMI:1.44(1.34 –1.55)]. Current AF as well as the history of AF increased both 30-day [OR for current AF: 1.35(1.22–1.50), history of AF: 1.17(1.04 –1.32)] and 1-year mortality [current AF: 1.5(1.4 –1.6), history of AF: 1.21(1.11–1.33)]. The rate of AF in MI patients has increased, especially SMIs. AF remains as a strong predictor of worse outcome for patients suffering a second MI. Both the history of AF and current AF were associated with higher mortality in MI patients.
Abstract 4015: Validity of the Combined Efficacy plus Safety Composite Endpoint (Net Clinical Benefit) in TRITON-TIMI 38
Authors: Kaul Sanjay , Shah Prediman K , Diamond George A
Published: July 2021

BACKGROUND:
Composite endpoints (CE) are frequently used in clinical trials for parsimonious summarization of treatment effects. The construction of the CE is generally based on the premise that each component endpoint is interchangeable. However, for this assumption to be valid, each component should be of equal or comparable clinical importance, occur with similar frequency, and be equally responsive to treatment intervention.

OBJECTIVE:
To examine the validity of the combined efficacy plus safety “quadruple” CE of Net Clinical Benefit utilized in TRITON.

METHODS:
A hierarchical (excluding double counting) CE analysis was performed using all-cause death, nonfatal MI, nonfatal stroke and TIMI Major or TIMI Major plus Minor bleeding. A formal assessment of heterogeneity was also conducted using the Cochran’s Q and I
2
tests.

RESULTS:
Figure

(top panel) shows a wide variability in the contribution of each component to the CE (death 23%, MI 55%, stroke 7%, major bleeding 15%). There was significant heterogeneity of treatment effect across the components (P=0.0006) with treatment differences primarily attributable to nonfatal MI and bleeding with little or no impact on death or nonfatal stroke. Similar observations are seen with TIMI major plus minor bleeding (bottom panel).

CONCLUSIONS:
The benefit of prasugrel is driven by nonfatal MI, the most prevalent but arguably not the most important component of the CE. A large gradient in clinical importance, prevalence, and treatment effect across components challenges the validity of “net clinical benefit” CE in TRITON. Furthermore, lack of information about the type of MI prevented precludes an informed benefit-risk assessment.
Abstract 4017: Reduced Anti-Platelet Response to Clopidogrel in Diabetic Patients Undergoing Percutaneous Coronary Intervention
Authors: Saucedo Jorge , Singla Anand , Mauer Karin , Bliden Kevin P , Antonino Mark J , Yadav Sunny , Hamed Miruais , Hennebry Thomas , Gurbel Paul A
Published: July 2021

Despite dual antiplatelet therapy with aspirin and clopidogrel, patients with diabetes mellitus (DM) suffer from frequent recurrent ischemic events. Previous studies have shown that DM patients have a higher prevalence of aspirin resistance than non-DM patients. The aim of this analysis was to determine if DM patients have a decreased antiplatelet response to either maintenance or high loading clopidogrel administration when compared to non-DM patients. One hundred and thirty eight patients that underwent percutaneous coronary intervention (PCI) in the Clear Platelets-2 Study were included in this analysis. Patients were grouped according to clopidogrel dose use and presence of DM. Subjects were either on maintenance therapy with 75mg of clopidogrel (C75 group; n=72) or received a loading dose of 600mg of clopidogrel immediately after PCI (C600 group; n=66). All patients received 325-mg aspirin. Platelet function was measured by Light Transmission Aggregometry using ADP (5 and 20μM), TRAP (15 μM), and collagen (2μg/ml). Overall, DM patients in the C75 group had higher platelet aggregation using 5 and 20μM ADP and 2μg/ml collagen. DM patients had lower relative platelet inhibition at 24hrs with 5 μM ADP and 2μg/ml collagen in the C600 group when compared to non-DM patients (Table

). DM patients undergoing PCI exhibit higher platelet aggregation when receiving standard clopidogrel maintenance dose and lower relative platelet inhibition with high clopidogrel loading dose. Higher doses of clopidogrel or more potent P2Y12 receptor antagonists may be needed in DM patients to obtain comparable platelet inhibition to non-DM patients.
Abstract 4031: Nitric Oxide Synthase 3 Deficiency Worsens Myocardial Dysfunction and Survival in Murine Polymicrobial Sepsis
Authors: Bougaki Masahiko , Searles Robert J , Yu Jia D , Volpate Gian Paolo , Ichinose Fumito
Published: July 2021

Background:
Myocardial dysfunction during sepsis contributes to the high mortality of patients with septic shock. The role of NOS3 on cardiac function during sepsis remains incompletely understood. Here, we examined impact of NOS3 deficiency on myocardial function and survival during peritonitis-induced polymicrobial sepsis.

Methods:
Severe polymicrobial sepsis was induced by colon ascendens stent peritonitis (CASP) in wild-type (WT) and NOS3 deficient (KO) mice. Cardiac function was examined both in vivo hemodynamic study and in isolated left ventricular cardiomyocytes, where sarcomere length (SL) and intracellular calcium transients ([Ca
2+
]
i
) were measured by video-edge detection and Fura-2 fluorescence, respectively. Mitochondrial function was assessed by measuring the ATP production rate in isolated mitochondria from left ventricle.

Results:
Mortality at 24 hours after CASP was higher in KO (15/15, 100%) than in WT (13/20, 65%, P<0.05 vs KO). In vivo hemodynamic study 22 hours after CASP revealed both systolic and diastolic cardiac functions were impaired to a greater extent in KO than in WT. In isolated cardiomyocytes, CASP induced-reduction in percent SL shortening and the peak amplitude of [Ca
2+
]
i
was more marked in NOS3KO than in WT. The time constants for SL relengthening and diastolic [Ca
2+
]
i
decay were prolonged to a greater extent in KO than in WT after CASP. Cardiac inflammation estimated by expression levels of inflammatory cytokines (TNF-α, IL-1β, IL-6) was more pronounced in KO than in WT. CASP-induced reduction in ATP production rate of myocardial mitochondria was more marked in KO than in WT, which was associated with reduction in mitochondrial complex I activity.

Conclusions:
These results suggest that NOS3 deficiency aggravates myocardial dysfunction through mitochondrial dysfunction and decreases survival after peritonitis-induced polymicrobial sepsis in mice.

Table

Hemodynamic and myocyte study 22 hours after CASP or sham
Abstract 4065: Concrete Symptom Clusters are Identifiable and Identical in Women and Men with Heart Failure, and Predict Health Outcome
Authors: Lee Kyoung Suk , Lennie Terry A , Riegel Barbara , Heo Seongkum , Wu Jia-Rong , Chung Misook , Rayens Mary Kay , Moser Debra K
Published: July 2021

Background:
Although symptoms in patients (pts) with heart failure (HF) are often viewed in isolation, pts usually have multiple, concurrent symptoms. Identification of symptom clusters could improve pts’ recognition of worsening HF, and enhance pt care. Given gender differences in outcomes in HF, examination of potential differences in clusters and their impact on outcomes is reasonable.

Purpose:
To identify HF symptom clusters in women and men and examine the impact of clusters on total number of all-cause hospitalizations per pt during 12 month follow-up.

Methods:
Data from 513 pts with HF (61 ± 12 yrs, 31.7% female, 53.6% NYHA III/IV) were used. Seven symptoms (i.e., edema, dyspnea, fatigue, trouble sleeping, worry, depression, and memory problems) were analyzed for clustering using an agglomerative hierarchical clustering approach and Ward’s method. Validity of cluster solution was assessed with split-sample replication. Symptoms were clustered, and pts were grouped based on symptom burden in clusters.

Results:
Two symptom clusters were identified in both men and women:

physical symptom cluster - dyspnea, fatigue, trouble sleeping; and

emotional/cognitive symptom cluster - worry, memory problems, depression.

Pts were grouped into 4 based on their symptom burden in each of the 2 clusters:

low burden related to both clusters;

burden from physical cluster > than that from emotional cluster;

burden from the emotional cluster > than that from physical cluster; and

high and equal burden from both clusters.

ANOVA revealed a difference in number of hospitalizations in both men and women based on the groups (p=.002); there were no gender differences. Pts in group 3 (emotional symptoms > than physical) were most frequently hospitalized (1.8 ± 2.8 hospitalizations/pt in group 3 compared to 1.7 ± 2.5/pt in group 4 vs .88 ± 1.6/pt in group 2 vs .66 ± 1.3/pt in group 1; post hoc Tukey indicates p <.05 for all comparisons except group 3 with 4).

Conclusion:
HF symptoms cluster in two identifiable groups: a physical and an emotional/cognitive cluster. Pts with the most burden from the emotional cluster have the worst outcomes, suggesting that increased attention needs to be paid by clinicians to emotional symptoms and the fact that they occur in clusters.
Abstract 4069: Refusal to Seek Medical Care for Symptoms Prior to Sudden Cardiac Death
Authors: Rosenfeld Anne G , Daya Mohamud , Christensen Vivian , Rawson Rebecca
Published: July 2021

Sudden cardiac death (SCD) is accompanied by preceding symptoms in a significant proportion of victims, with a median duration of up to 2 hours in some cases. The purpose of this study was to describe the characteristics of SCD victims with heralding symptoms who refused medical care. We conducted a secondary data analysis of interview data from witnesses of 99 cases of out-of-hospital presumed myocardial infarction death with known symptoms. Qualitative description methods were used to analyze qualitative data. Logistic regression was used to test the influence of type of symptoms (chest pain vs. non-chest pain), history of heart disease, and age on refusal of medical care. Categorization as refusal of medical care required conversation with someone where refusal was expressed verbally by the victim. There were 19 cases (19%) that refused medical care; their mean age was 72. The majority were male (16/19, 84%). Fifteen cases involved persistent refusal, defined as refusing care until collapse (range of <15 minutes to 60 hours). Four victims initially refused care and then permitted access to medical care. The suggestion for seeking medical care came from someone else in all but one case, and usually included multiple attempts. The care options offered but refused included calling 911 or a doctor, as well as going to the hospital, emergency department or a doctor’s office. Reasons for refusal of medical care (more than one reason in some cases) included stating the symptoms were due to something not urgent (n=10), other obligations (n=3), expressed dislike of hospitals or doctors (n=4), or recent medical reassurance of health status (n=7). Controlling for age, victims with chest pain vs. non-chest pain symptoms were more likely (OR = 3.56, p = .036, 95% CI = 1.09 –11.66) to refuse medical care and those with a history of heart disease were less likely (OR = .16, p = .004, 95% CI = .05–.55) to refuse medical care. Patients with chest pain and no history of heart disease are more likely to refuse advice to seek medical care. Public health messages about how to respond to cardiac symptoms should include strategies to overcome the reasons people refuse medical care.

This research has received full or partial funding support from the American Heart Association, AHA Pacific/Mountain Affiliate (Alaska, Arizona, Colorado, Hawaii, Idaho, Montana, Oregon, Washington & Wyoming).
Abstract 4091: Characteristics of the Electroanatomical Substrate in Patients with Fast and Slow Ventricular Tachycardias Late after Myocardial Infarction
Authors: Wijnmaalen Adrianus P , Schalij Martin J , Zeppenfeld Katja
Published: July 2021

Ventricular tachycardias (VT) in patients after myocardial infarction (MI) may be unstable prohibiting catheter mapping due to short VT cycle lengths (CL). Linear radiofrequency lesions applied at the scar borderzone can be effective to eliminate these VTs. This study used voltage mapping to assess characteristics of the electroanatomical substrate for fast and slow VTs in post MI patients. The study population consisted of 34 consecutive patients referred for radiofrequency ablation of sustained VT after MI. Group A (12 patients, 12 male, age 60±12yr, 67% anterior MI) with documented spontaneous or inducible fast VT (CL<250ms) were compared to 22 patients (18 male, age 65±16yr, 73% anterior MI) with slow VT (CL>250ms, group B). All patients underwent programmed electrical stimulation and left ventricular electroanatomical sinus rhythm voltage mapping. Bipolar electrogram amplitudes >0.5mV were defined as dense scar, >0.5mV and ≤1.5mV as borderzone and a ‘patchy pattern’ as multiple low voltage areas separated by areas of normal voltage (>1.5mV). VT occurred 10±11yr (group A) and 14±8yr (group B), respectively after the index MI (p=ns). Mean LV ejection fraction was comparable in both groups (A 31±14% vs. B 26±10%, p=ns). The mean VT CL was 236±12ms in group A and 318±55ms in group B (p<0.01). In group A 42% had underwent early reperfusion with an angiographically documented patent infarct related artery (IRA) directly and at the time of VT occurrence compared to 9% in group B (p=0.03). A patchy pattern of LV scar in the IRA supplied area was present in 83% of group A compared to 5% in group B (p<0.01) and the proportion of dense scar was significant smaller in group A than in group B (20±15% vs. 49±19%, p<0.01). The characteristics of low voltage scars after MI are different in patients with and without fast VT’s. Less confluent scars are associated with early reperfusion with a patent IRA and give rise to faster VTs. These findings have implications for VT ablation strategies that target the infarct border zones.
Abstract 4098: Epicardial Amiodarone-Releasing Hydrogel Reduces Inducibility of Atrial Fibrillation in Goats
Authors: Bolderman Robert W , Hermans Rob J , Rademakers Leonard M , Jansen Tim S , De Jong Monique M , Bruin Peter , Dias Aylvin A , Van der Veen Frederik H , Maessen Jos G
Published: July 2021

Amiodarone (AM) is one of the most effective anti-arrhythmic drugs to prevent postoperative atrial fibrillation (AF). However, due to systemic side effects, prophylactic AM therapy is only appropriate for patients at high risk for postoperative AF. This study addressed the hypothesis that local epicardial delivery of AM produces therapeutic myocardial drug concentrations, while systemic levels remain low. Goats (n=14) were instrumented with right atrial epicardial patch electrodes, and a PEG-based hydrogel with AM (1 mg/kg bw) (n=9) or without drug (n=5) was applied to the right atrial epicardium. AF inducibility was assessed up to 28 days in awake goats by applying burst stimuli. Myocardial and plasma AM concentrations were analysed by HPLC. AM-hydrogel produced higher subepicardial than subendocardial drug concentrations, which both remained therapeutic up to 21 days after hydrogel application (fig. 1a

). In this period, AF inducibility was significantly lower in the AM-hydrogel group compared to hydrogel alone (fig. 1b

; p<0.05). Plasma AM and metabolite levels were below detection limits (<30 ng/L) during the 28-day follow-up. Epicardial AM-releasing hydrogel produces sufficient myocardial drug concentrations to reduce AF inducibility up to 3 weeks, whereas plasma drug levels remain undetectably low. This study demonstrates that local delivery of anti-arrhythmic drugs is a feasible approach to obtain therapeutically effective myocardial drug concentrations, while minimizing risk for systemic side effects. Locally applied AM-releasing hydrogel may be a novel strategy to prevent postoperative AF.

Figure 1a.

Amiodarone Distribution in Right Atrium (n=5)

Figure 1b.

AF Inducibility After Hydrogel Application (mean + SD)
Abstract 4102: Preoperative Angiotensin Blocking Drug Therapy Does Not Reduce Atrial Fibrillation After Cardiac Surgery
Authors: Rader Florian , Blackstone Eugene H
Published: July 2021

Introduction:
Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery. Angiotensin blocking drug therapy (ABDT) with Angiotensin converting enzyme (ACE) inhibitors and Angiotensin II receptor blockers (ARBs) has been shown to have anti-arrhythmic effects in animal models. However, data from small observational studies of ABDT use in patients undergoing cardiac surgery had discordant results and did not sufficiently adjust for selection bias. Therefore, we performed the largest study to date examining the association between preoperative use of ABDT and postoperative atrial fibrillation.

Methods and Results:
A consecutive series of 10,552 patients underwent coronary artery bypass graft (CABG) surgery with or without valvular surgery at Cleveland Clinic between 1997 through 2002. Of these 4,795 (45%) patients were on ABDT within 30 days prior to surgery and 3,633 (34%) patients developed POAF prior to discharge. Without adjusting for patient co-morbidities, ABDT had an Odds Ratio (OR) of 1.13 (95% Confidence Interval (CI) 1.05–1.25, p<0.01). A propensity score matched sample was developed, adjusting for 68 potential confounders. In the 6874 matched patients, who had a well balanced co-morbidity profile, ABDT was not associated with POAF (OR 1.03, CI 0.93–1.12, p=0.67). A subsequent propensity score matched analysis of 3227 patients, who underwent isolated valvular surgery in the same timeframe, also demonstrated ineffectiveness of preoperative ABDT (OR 0.91, CI 0.74 –1.09, p=0.33), irrespective of valve location. Stratified analysis by linear propensity score quintiles and propensity-adjusted logistic multivariable regression analysis of all patients in the CABG and the valvular surgery cohort confirmed these findings.

Conclusions:
In this large observational study preoperative use of ACE inhibitors or ARBs did not reduce postoperative occurrence of atrial fibrillation in patients undergoing cardiac surgery. Although withdrawal from ABDT prior to surgery is common practice and could account for this result, we cannot recommend such therapy for primary prophylaxis without larger randomized controlled trials.
Abstract 4105: Increasing Contact Force Increases Lesion Size during Cryo-Ablation
Authors: Ikeda Atsushi , Nakagawa Hiroshi , Pitha Jan V , Swank Steven , Barold Helen S , Sharma Tushar , Jackman Warren M
Published: July 2021

The purpose of this study was to determine the relationship between electrode-tissue (ET) contact force and lesion size during cryo ablation for two cryo electrode lengths in both perpendicular and parallel orientations using the canine thigh muscle preparation. In 3 anesthetized dogs, the skin over the thigh muscle was incised and raised to form a cradle which was superfused with heparinized blood at 37°C. 10F catheters with 6.5 mm and 10 mm (8.5 mm exposed) cryo electrodes (CryoCor) were held perpendicular and parallel to the thigh muscle at 3 ET contact forces:

0 g (1mm above tissue with only ice ball contact);

2)10 –15g (Low Contact); and

30 –35 g (High Contact). Pulsatile blood flow (0.5 m/sec) was directed at the ablation site.

Two cryo applications (− 90°C for 2 min) were delivered per dog for each of the 3 contact forces, at parallel and perpendicular orientations, for 6.5 and 10 mm electrodes (total 72 cryo). Temperatures were measured at the electrode and within the tissue at depths of 2, 4 and 6 mm. Lesion size was measured using nitroblue tetrazolium. Lesion depth and diameter increased with increasing ET contact force in both electrode orientations and both electrode sizes (

Fig

). Tissue temperatures (2 mm, 4 mm and 6 mm depths) were significantly lower with ET contact (low and high), compared to no contact (0 g). Compared to 6.5 mm, the 10 mm electrode produced slightly greater lesion diameter in parallel orientation, but did not increase lesion depth. Cryo ablation without ET contact (only ice ball contact) produced little or no lesion. ET contact force facilitates cryo ablation. Ice ball contact alone is insufficient for lesion formation.