bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 178: Long-Term Benefit of Using Dual Dispatch in Out-of-Hospital Cardiac Arrest: The Salsa (Saving Lives in Stockholm Area) Trial
Authors: Nordberg Per , Hollenberg Jacob , Dahlkvist Tobias , Pettersson Hans , Ringh Mattias , Dillenbeck Emelie , Rosenqvist Mårten , Svensson Leif
Published: April 2024

Introduction:
Out-of-hospital cardiac arrest (OHCA) afflicts around 275,000 victims per year across Europe and is accountable for more than 60% of deaths from coronary heart disease. In 2005, a dual dispatch system in OHCA was implemented in Stockholm, Sweden, using CPR-trained fire fighters with automatic external defibrillators as first responders in addition to the emergency medical services (EMS). The pilot study from 2006 showed promising results on improving time intervals and survival rates.

Hypothesis:
We assessed the hypothesis that reduced pre-hospital response times to shorten the time to CPR and defibrillation and to optimize the quality of CPR would improve survival rates in OHCA.

Methods
Included in the trial were witnessed out-of-hospital cardiac arrest patients, where resuscitation attempts was initiated, irrespective of first rhythm, from the years 2004 (historical controls) and 2007-2009 (intervention period). In 2007-2009 fire-fighters were dispatched in suspected OHCA in parallel with the EMS.

Results and Conclusions
In total, 2060 patients were included, 427 controls and 1633 in the intervention group. During the intervention period 2007-2009, fire fighters were first on scene in 39% of cases with dual dispatch. The median time from call to arrival of first responder shortened from 7.5 minutes during the control period to 6.8 minutes among dual dispatch cases in the intervention group. The proportion of patients admitted alive to hospital increased from 27.4% among controls to 33.5% in the intervention group (OR 1.3, p=0.02). The proportion of patients alive after 1 month increased from 5.9% to 12.3 % (OR 2.3, p<0.001). In conclusion, the implementation of a dual dispatch system using fire-fighters as first responders have shortened response times and significantly increased the survival to 1 month, irrespective of the first rhythm in witnessed OHCA. The increase in survival is mainly believed to be associated with improved CPR and shortened time intervals.
Abstract 17842: Relationship Between Novel Angiographic Endpoint of Endovascular Therapy and Clinical Result of Patients with Critical Limb Ischemia
Authors: Utsunomiya Makoto , Nakamura Masato , Sugi Kaoru
Published: April 2024

Objectives
Several reports have been published of the acceptable patency and limb salvage rates following infra-popliteal interventions for the treatment of critical limb ischemia (CLI). However, the optimal angiographic endpoint of endovascular therapy (EVT) remains unclear. The aim of this study was to assess the relationship between the appearance of wound blush as an angiographic endpoint and the limb salvage rate in patients with CLI.

Methods
“Wound blush” was defined as contrast opacification of the vessels around the wound in digital subtraction angiograms obtained immediately after the EVT through the catheter introduced into the popliteal artery. We analyzed the data of 77 consecutive patients (93 limbs) with ischemic ulcerations classified as Rutherford category 5 or 6, who underwent EVT alone, without bypass surgery. Patients were divided into two groups depending on whether or not wound blush was obtained in the angiogram obtained immediately after the procedure, and the ‘freedom from amputation’ rate was compared between the two groups.

Results
The overall limb salvage rate was 81.7%. The limb salvage rate was significantly higher in the wound blush-positive group than in the wound blush-negative group, and remained so for at least 3 years after the EVT (96.4% vs. 56.8%, P<0.001).

Conclusion
Presence of wound blush after EVT is associated with higher SPP, both of which are associated with higher rates of limb salvage. Wound blush as an angiographic endpoint in EVT may be a novel predictor of limb salvage in patients with CLI.
Abstract 17843: Comparison of IVUS Findings Using Different Tissue Characterization System; VH-IVUS vs. iMAP-IVUS in Patients with Acute Coronary Syndrome
Authors: Lee Sung-Yun , Doh Joon Hyung , Kim Sang wook , Choe Hyunmin , Kwon Sung Uk
Published: April 2024

Background:
Two different tissue characterization techniques are available in the real world IUVS-guided percutaneous coronary intervention, VH-IVUS gave clinical implication especially identification of thin-cap fibroatheroma (TCFA) that can predict clinical event. The iMAP-IVUS system is relatively new technology available since last year in Korea. Limited data associated with iMAP-IVUS and no systemized report for comparison of two different systems.

Methods:
We performed pre-PCI IVUS using both VH-IVUS and iMAP-IVUS system consecutively for 20 patients with acute coronary syndrom treated with stent implantation. We excluded the 4 patients who had lesions with acoustic shadow on grey scale IVUS; because iMAP read the all shadows as necrotic core, then we selected and compared 30 pairs of cross-sectional tissue characterization IVUS images without acoustic shadow.

Results:
The VH-IVUS interpreted as less fibrotic (10.7 ± 7.9 vs 64.0 ± 5.9 %, p=0.001) when compared to iMAP-fibrotic components and much more fibro-fatty tissue components (64.4 ± 7.0 vs 9.0 ± 1.8 %,
p
=0.001) when compared to iMAP-lipid pool components for similar cross-sectional pairs. Necrotic core (22.7 ± 6.9 vs 26.9 ± 7.5 %,
p
=0.342) and calcified (2.1 ± 1.4 vs 6.8 ± 10.9 %,
p
=0.474) tissue components was similar between two systems. VH-IVUS detected 2 TCFAs but iMAP-IVUS could not fulfill the VH-definition of TCFA. Exact concordant level of cross-sectional IVUS image could not compared in few cases because VH-IVUS images were captured by EKG gating whereas iMAP IVUS by 2 frames/mm interval.

Conclusion:
Large necrotic core components were detected in two tissue characterization IVUS systems, but there were significant discrepancies in discriminations between fibrotic and lipid tissue components in patients with ACS who had lesions without acoustic shadow. We need more detailed study such as pathology study to verify the accuracy of these tissue characterization system.
Abstract 17883: Neutrophil Extracellular Traps as an Interface Between Inflammation and Thrombosis in DVT
Authors: Stark Konstantin , von Brühl Marie-Luise , Steinhart Alexander , Chandraratne Sue , Köllnberger Maria , Lorenz Michael , Pfeiler Susanne , Manukyan Davit , Bergmeier Wolfgang , Wagner Denisa , Engelmann Bernd , Massberg Steffen
Published: April 2024

Objective:
Neutrophil extracellular traps (NET) have mainly been implicated in antimicrobial host defense, but recently their contribution to arterial and microcirculatory thrombosis has been identified. These extracellular DNA structures also have been found in deep venous thrombosis (DVT), but how they participate in thrombus formation in vivo is unclear. In this study we wanted to assess the dynamics of NET formation and their impact on DVT development in vivo in a murine flow reduction model of the inferior vena cava (IVC).

Methods:
Thrombosis was induced in C57Bl6 mice by placing a narrowing ligature around the IVC, resulting in a reduction of blood flow velocity (n=16). NET formation in vivo was visualized by intravital epifluorescence microscopy. The IVC was harvested 48h after flow reduction, weighed and stained by immunofluorescence. Thrombogenesis and NET formation were quantified in DNase, anti-H2A-H2B-DNA antibody, and heparin treated animals as well as in GPIb-/- mice.

Results:
Extracellular DNA could be detected in vivo as early as 3h after flow reduction (n=3). These DNA structures were positive for neutrophil elastase, myeloperoxidase, and histones, confirming that they are indeed NETs. In the IVC harvested 48 hours after the flow restricting procedure, we found that NETs were binding platelets, tissue factor, and fibrinogen. The functional impact of NETs for DVT formation is indicated by the finding that disruption of NETs by DNase (n=5) or anti-H2A-H2B-DNA antibody (n=5) treatment resulted not only in a reduced number of NETs, but also in a significantly reduced thrombus weight compared to wt control. Surprisingly, injection of heparin resulted in a diminished number of NETs inside the IVC, which could add to its antithrombotic effect (n=3). In addition, in the IVC of GPIb-/- mice only very few NETs could be identified, suggesting that platelets trigger NET formation during DVT (n=3).

Conclusion:
Here we show, that neutrophils contribute to DVT by NET formation. This provides a platform for platelet adhesion and concentration of procoagulatory factors on their surface, linking inflammation and thrombosis at the cellular level. Thus, disruption of NETs could be an interesting new therapeutic approach for prophylaxis and treatment of DVT.
Abstract 17889: Sequential Side-Main-Side Branch Balloon Dilation - Sms Technique - As an Alternative to Final Kissing Balloon Inflation in Bifurcation Lesions Treated with Provisional Stenting
Authors: Medina Alfonso , Martín Pedro , Suarez de Lezo Javier , Pan Manuel , Nóvoa Jose , Suárez de Lezo Jose , Melián Francisco , Mazuelos Francisco , Caballero Eduardo , Segura Jose
Published: April 2024

Introduction.
Final kissing balloon inflation is recommended in provisional stenting in order to accommodate the stent to the bifurcation anatomy. However KBI induces an asymmetry in the proximal stent and does not totally correct the deformation induced under the side branch origin after isolated SB dilation.

Objective.
To evaluate with IVUS the scaffolding and changes in stent geometry with a new sequential balloon dilation technique which we named SMS-technique.

Methods.
63 patients with a true bifurcation coronary lesion (LM 4, LAD 47, LCx 10 and RCA 2) were treated with the SMS technique (Figure). The stent diameter was selected using the distal main branch (MB) reference, then (S) side branch balloon angioplasty was performed with a balloon selected according to its diameter. (M) another balloon, selected according to the proximal main branch reference diameter, was inflated proximally and at the carinal region. (S) final balloon angioplasty of the side branch (SB). An IVUS study was performed at each step.

Results.
Primary success was obtained in all lesions. Two patients needed a second stent. The table shows the quantitative IVUS findings at each step (*p<0,01). After SMS technique, complete apposition at the proximal stent segment was achieved in all cases. No cases of stent thrombosis were recorded.

Conclusion.
The SMS technique provides optimal apposition of the stent at the proximal segment of the MB and correction of the stent deformation under the SB origin.
Abstract 17917: Is Small Change Significant? Association of Small Differences in Life's Simple 7 and Mortality: the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort
Authors: Cushman Mary , Judd Suzanne E , Howard Virginia J , Zakai Neil A , Kissela Brett , Kleindorfer Dawn , Safford Monika M , Howard George
Published: April 2024

Background.
The AHA 2020 Goal includes improving cardiovascular health, defined using a metric consisting of 7 health factors, Life's Simple 7. A central concept of the goal is that small improvements in behavior / lifestyle factors at the population level will lead to large risk reductions over the life course. We developed a simple score to quantify Life's Simple 7 and evaluated the association of small differences in this score with all-cause mortality in REGARDS, a biracial national cohort.

Methods.
We studied 17,820 REGARDS participants without vascular diseases; black and white men and women aged 45-98 from across the US, enrolled in 2003-7, when extensive risk factor data were measured in participants' homes. The 7 components of Life's Simple 7 (blood pressure, cholesterol, glucose, BMI, smoking, physical activity, diet) were each scored in AHA-defined categories of poor (1 point), intermediate (2 points) and ideal (3 points), and were summed to yield scores ranging from poor for all (7) to ideal for all (21). With 4.6 years follow up there were 2319 deaths.

Results.
The score was normally distributed with mean (SD) of 13.5 (2.6). The age, sex and race-hazard ratio (HR) of death for a 1-unit increase in Simple 7 Score was 0.86 (95% CI 0.84, 0.87). There was no impact of further adjustment for income and education. Considering only the 4 behavior/lifestyle score components (BMI, smoking, physical activity, diet), the adjusted HR per 1 unit higher score was 0.79 (95% CI 0.77, 0.81).

Conclusions.
A small incremental difference, corresponding to improvement of 1 category (poor to intermediate or intermediate to ideal) for 1 component of Life's Simple 7 Score was associated with substantial reduction in 4.6-year all cause mortality. The association was larger considering only the 4 behavioral/lifestyle components. Results suggest profound implications of achieving the 2020 Goal that 20% of people improve by 1 level of this metric.
Abstract 17945: Abnormal Left Ventricular Torsion Assessed by Speckle Tracking Echocardiography in Orthotopic Heart Transplant Patients as Early Predictor of the Acute Myocardial Rejection
Authors: Kalra Nishant , Sorrell Vincent L , KC Dipak B , Abidov Aiden
Published: April 2024

Background
LV torsion is a critical aspect of cardiac biomechanics and hold promise for better understanding the ventricular dysfunction. The aim of this study was to determine whether LV torsion assessed by 2D-speckle tracking imaging can predict rejection in transplanted hearts.

Methods
From Oct 2010 to Feb 2011, patients who had transplant and underwent echocardiogram as well as RV biopsies in our Center, were analyzed. The echocardiograms and RV biopsies were done within 3 days of each other. Patients who did not have any prior cardiac surgeries or valvular heart disease were analyzed for comparison (controls). Torsion measurements were performed off-line using commercially available software. Basal and apical short-axis views were used for measurement of torsion. LV torsion was calculated as (apical LV rotation minus basal LV rotation)/LV diastolic longitudinal length. By speckle tracking echocardiography, global longitudinal strain was also calculated in all the patients. LVEF was assessed using modified Simpson's method. Patients with incomplete data were excluded.

Results
14 transplant patients were compared with 6 matching controls. 4 transplanted patients had a biopsy-confirmed rejection. Torsion, global strain and LVEF were all reduced in patients with rejection as compared to those without rejection and with controls. When mean value of torsion in controls was applied as a normal threshold to the study population, 75% (3/4) of the patients with rejection had an abnormal torsion despite normal LVEF. Torsion analysis provided a sensitivity and specificity of 75% and 70% for detecting rejection in transplant patients.

Conclusion
To our knowledge this is the first study to demonstrate the value of LV torsion in predicting rejection in patients post heart transplant. In patients with rejection, abnormal LV torsion at initial presentation can be utilized as an early non-invasive predictive marker to help in identification of these patients.
Abstract 17948: In-vivo Visualization of Increased and Persistent Vascular Lipid Deposition by Nirs and Ivus Predicts Subsequent Development of High-Risk Atherosclerotic Lesions
Authors: Patel Dhavalkumar , Hamamdzic Damir , Llano Raul , Patel Daivesh , Cheng Lan , Fenning Robert , Bannan Khalid , Wilensky Robert L
Published: April 2024

Introduction:
Thin-cap fibroatheromas are the pathologic cause of acute coronary syndromes and ischemic sudden death. Near infrared spectroscopy (NIRS) detects lipid concentration in the arterial wall and intravascular ultrasound (IVUS) identifies necrotic cores and vascular remodeling. We hypothesized that concurrent use of these two invasive technologies could predict development and progression of high-risk fibroatheromas as determined by histology.

Methods:
Multi-vessel coronary angiography, IVUS and NIRS were performed 3, 6 and 9 months (m) after induction of diabetes (DM) and hypercholesterolemia (HC) in 21 pigs. Five animals died of ischemic sudden death and 3 of other causes. The remaining animals were sacrificed at 9-m.

Results:
Longitudinal IVUS data demonstrated a progressive increase in plaque + media and necrotic core areas and positive remodeling. At 9-m NIRS positivity predicted the presence of TCFAs and ThFCAs (both p=0.0001 vs NIRS negative), greater plaque (p<0.0001) and necrotic core (p<0.0019) areas and thinner fibrous caps (p=0.04) by histology. Importantly, NIRS positive fibroatheromas possessed a higher number of activated macrophages (p=0.006), as well as greater number of proliferating (p=0.016) and apoptotic cells (p=0.04) in the fibrous cap. NIRS positivity also predicted greater necrotic core size on IVUS scan at the subsequent time point. Moreover, 88% of arterial segments which were NIRS positive at 3 and 6-m developed into a fibroatheroma at 9-m by histology compared to 35% of persistently NIRS negative segments (p<0.01).

Conclusion:
Results from IVUS and NIRS predicted the subsequent development of high-risk coronary fibroatheromas with greater plaque and larger necrotic core areas possessing characteristics of increased plaque instability.
Abstract 17970: Metabolic Support of Mitochondrial Complex I with Yeast Ndi1 Evokes Significant Cardioprotection in the i
n vivo
Rat Model of Acute Myocardial Infarction
Authors: Przyklenk Karin , Whittaker Peter , Wider Joseph , Undyala Vishnu V , Gottlieb Roberta A , Mentzer Robert M
Published: April 2024

Lethal myocardial ischemia-reperfusion injury has been attributed in part to mitochondrial respiratory dysfunction (including damage to Complex I) and the resultant excessive production of reactive oxygen species. Recent evidence has shown that Ndi1 (the single-subunit protein that serves as the surrogate for Complex I in yeast), transduced by addition of the TAT-conjugated protein to culture media and buffer, can preserve mitochondrial function and attenuate ischemia-reperfusion injury in isolated cardiomyocytes and isolated buffer-perfused hearts. However, the
in vivo
efficacy of this novel metabolic strategy to salvage ischemic-reperfused myocardium has, to date, not been explored. To address this issue, TAT-conjugated Ndi1 and TAT-conjugated placebo control protein were synthesized using a cell-free (non-bacterial) system. After confirming the identity of the proteins by immunoblotting, rats were randomly assigned to receive intraperitoneal injection of either TAT-Ndi1 or TAT-placebo. Two hours post-treatment, all animals underwent 45 min coronary artery occlusion followed by 2 hours of reperfusion. Infarct size was delineated by tetrazolium staining and normalized to the volume of at-risk myocardium (the primary determinant of infarct size in this model), with all analysis conducted in a blinded manner. Risk region was comparable in the two cohorts, averaging 28-32% of the total left ventricular weight (p=ns). Pre-ischemic administration of TAT-Ndi1 was, however, associated with profound cardioprotection: infarct size in TAT-Ndi1-treated rats was 25+7%* of the myocardium at risk, significantly smaller than the value of 63+5% seen in the TAT-placebo control group (mean + SEM; *p<0.01
versus
control). These results provide the first
in vivo
evidence that yeast Ndi1 can provide metabolic support to ischemic-reperfused myocardium and reduce myocardial infarct size. Moreover, these data suggest that metabolic support of mitochondrial proteins may provide a novel molecular strategy to protect the human heart against planned ischemia-reperfusion events.
Abstract 17987: Association of Cardiovascular Events and Apolipoprotein CIII - A Systematic Review and Meta-Analysis
Authors: Wyler von Ballmoos Moritz , Haring Bernhard
Published: April 2024

BACKGROUND:
Apolipoprotein CIII (apoCIII) is an 8.8-kDa apolipoprotein peptide found on HDL, VLDL and LDL.

OBJECTIVE:
To systematically review current evidence on the association of blood apoCIII level with cardiovascular events, and to evaluate whether the current literature suggests a dose-response relationship for this association.

DATA SOURCES
: MEDLINE, EMBASE, BIOSIS, CINAHL, Clinicaltrials.gov, grey-literature sources, contact with investigators, and reference lists of studies, without language restrictions.

STUDY SELECTION:
Publications were selected if they investigated the association between blood apoCIII level and coronary heart disease, myocardial infarction, stroke, or sudden death from stroke or myocardial infarction. Data including study and patient characteristics, apoCIII level, and outcomes were extracted independently by two investigators.

DATA SYNTHESIS AND RESULTS:
10 studies (6 case-control, 4 cohort studies) with a total of 1469 cases of cardiovascular events met inclusion criteria. Four studies compared apoCIII levels and showed higher blood levels in subjects with a cardiovascular event. The other six studies calculated adjusted estimates of relative risks of 1.82-3.88 (total apoCIII), 2.25-8.87 (non-HDL apoCIII), and 0.64-2.57 (HDL apoCIII) for cardiovascular events. Random-effects meta-analyses were performed with summarized dose-response data where applicable. All studies showed a positive, significant association of apoCIII with cardiovascular disease. Risk estimates demonstrate a monotonous, graded increase in risk of cardiovascular disease with increasing levels of apoCIII and are beyond what could reasonably be explained by residual confounding alone.

CONCLUSION:
The current body of literature includes several methodologically sound studies that together provide consistent evidence for an independent association of cardiovascular events with blood apoCIII level. Available data suggest that apoCIII is an independent risk factor for cardiovascular events. Further data is needed in order to determine the significance of the location and amount of apoCIII on specific lipoproteins in cardiovascular risk management.
Abstract 17993: Bystander-Initiated Cardiopulmonary Resuscitation Can Maintain Regional Cerebral Oxygen Saturation Levels on Hospital Arrival in Patients with Refractory Out-of-Hospital Cardiac Arrest
Authors: Ito Noritoshi , Nanto Shinsuke , Nagao Ken , Hatanaka Tetsuo , Nishiyama Kei , Doi Yasuji , Kurozumi Yuma , Natsukawa Tomoaki , Morita Masaya , Kawata Atsushi , Tsuruoka Ayumu , Sawano Hirotaka , Shibata Hiroyuki , Yamada Noriaki , Okada Ken-ichiro , Hayashi Yasuyuki , Kai Tatsuro , Hayashi Toru
Published: April 2024

Background:
Bystander-initiated cardiopulmonary resuscitation (B-CPR) plays a key role in the chain of survival for out-of-hospital cardiac arrest (OHCA) patients. We have previously reported that a low regional cerebral oxygen saturation (rSO2) level is a strong predictor of poor neurological outcome in OHCA patients.

Objectives:
To assess the association between B-CPR and rSO2 levels measured immediately on hospital arrival.

Methods:
This study was a prospective cohort study. Of 418 OHCA patients, 186 consecutive non-traumatic, cardiac arrest on arrival (CAOA) patients were prospectively registered. The rSO2 levels were measured with sensors placed on either side of their forehead using a near-infrared spectroscopy (NIRS) device (INVOS, Covidien, US) within 3 minutes after hospital arrival. We monitored rSO2 levels at least for more than one minute and used the lower of the 2 measured rSO2 levels for analysis. Clinical staff performed ordinary post-cardiac-arrest interventions (PCAIs) regardless of rSO2 levels. Primary outcome measure was good neurological outcome (CPC 1/2) at hospital discharge according to the “Utstein-style”. After dividing the eligible 186 patients into the two groups (B-CPR group (n=76) and no B-CPR group (n=110)), we compared the rSO2 levels on hospital arrival and the neurological outcome between the two groups.

Results:
Among 186 CAOA patients in PCAIs era, 18 patients (9.7%) had good neurological outcome. The B-CPR group patients had more maintained rSO2 levels on hospital arrival with a much higher proportion of good neurological outcome as compared with the no B-CPR group patients (33±20% vs. 22±13%, p=0.00003; 21% vs. 2%, p=0.00005, respectively).

Conclusion:
The findings suggest that B-CPR for CAOA patients after OHCA contributes to maintaining the rSO2 levels on hospital arrival and improving neurological outcome at hospital discharge even in the PCAIs era.
Abstract 18: Coronary Perfusion Pressure in VF and in PEA/A Cardiac Arrest Animals
Authors: Walcott Gregory , Melnick Sharon , Killingsworth Cheryl
Published: April 2024

We hypothesized that equivalent chest compressions are less effective at perfusing the heart in pulseless electrical activity/asystole (PEA/A) cardiac arrest than in ventricular fibrillation (VF) cardiac arrest. We tested this hypothesis in two swine models of cardiac arrest. Two groups of pigs (33+4 kg) were anesthetized and instrumented to measure coronary perfusion pressure (CPP). CPP was calculated as aortic minus right atrial pressure measured just before the initiation of a chest compression. Group 1 underwent 5 minutes of unsupported electrically induced ventricular fibrillation. Group 2 animals were ventilated with a 12% oxygen and balance nitrogen mixture until aortic pulsations were less than 2 mmHg. Animals remained unsupported for an additional 6 minutes. Both groups were resuscitated with chest compressions (100/min) and ventilations (100% O2, 10/min). After 7 minutes, Group 1 animals were defibrillated. Resuscitation continued until either return of spontaneous circulation occurred or 20 minutes elapsed. Return of spontaneous circulation occurred in 6 of 7 Group 1 and 2 of 6 Group 2 pigs. CPP during resuscitation started at ~5 mmHg for both groups. Group 1 CPP increased to 13 mmHg in the first 3 minutes of chest compressions while the CPP in Group 2 remained at 5 mmHg. Decompression central venous pressure was the same for both groups (7 mmHg). CPP correlated with decompression aortic pressure in both groups. CPP was lower in Group 2 animals than in Group 1 animals and this difference was reflected in the number of animals who had return of spontaneous circulation. This data would suggest that one reason why PEA/A patients survive cardiac arrest less frequently than VF patients is that chest compressions perfuse the heart less effectively in PEA/A patients than in VF patients.
Abstract 18034: Clinical, Angiographic and Genetic Determinants of Early Coronary Stent Thrombosis: the ONASSIST Study
Authors: Cayla Gullaume , Scott Stuart , O'Connor Stephen , Hulot Jean-Sebastien , Silvain Johanne , Beygui Farzin , Barthelemy Olivier , Allanic Frederick , Montalescot Gilles , Collet Jean-Phlippe
Published: April 2024

OBJECTIVES:
To perform a comprehensive analysis of all determinants of definite early stent thrombosis (ST) to identify the risk and the modifiable factors of early EST.

Methods:
Using a web-based case collection and reporting system, 123 patients with definite early ST on dual antiplatelet therapy were matched 2:1 according to age and gender with 246 controls. All patients were genotyped for 23 genetic variants involved in clopidogrel metabolism (
CYP2C19
,
CYP2C9, CYP2B6, CYP3A5, POR, ABCB1, PON1
), platelet receptor function (
P2Y12, ITGB3
), and the coagulation and fibrinolytic system (
MTHFR
, Factor V, Fibrinogen, Prothrombin,
PAI1
and
VKORC1
).

Results:
CYP2C19*2
(OR
und
=2.53, 95% CI [1.61-3.97], p<0.0001) and
ABCB1 TT3435
(OR
und
=2.01, 95% CI [1.22-3.30], p=0.006) carriers were more frequent among patients with EST than controls while
CYP2C19*17
(OR
und
=0.53, 95% CI [0.31-0.88], p=0.01) and
ITGB3 PlA2
(OR
und
=0.50, 95% CI [0.29-0.87], p=0.01) carriers were less frequent. Percutaneous coronary intervention in acute setting, complex lesions, impaired left ventricular function < 35%, high clopidogrel loading doses and use of proton pump inhibitor were non genetic independent correlates of early ST. The accuracy of the clinical model to discriminate between early ST and controls (AUC 0.72, 95% CI [0.66-0.77] did not differ significantly from the genetic model (AUC 0.68, 95% CI [0.62-0.73] (p=0.34), although combining both led to a significant improvement in the discriminatory power of the model (AUC 0.78, 95% CI [0.73-0.83], p=0.004). Among all independent predictors of early ST, the use of high clopidogrel loading doses (OR=0.73, 95% CI[0.57-0.94], p=0.01) and proton pump inhibitors (OR=2.19, 95% CI [1.28-3.72], p=0.004) were the only modifiable factors.

Conclusion:
In addition to established clinical and angiographic factors, three genes involved in clopidogrel metabolism and platelet receptor function
(CYP2C19, ABCB1, ITGB3)
significantly improved the ability to predict early ST. PPI use and clopidogrel dose were both independently correlated with the risk of early ST, suggesting that the final amount of active metabolite generated is a major factor of prevention.
Abstract 18111: Significance of Delayed Gadolinium Enhancement Cardiac Magnetic Resonance in Patients with Brugada Syndrome
Authors: Murakami Masato , Nagase Satoshi , Morita Hiroshi , Nakamura Kazufumi , Kohno Kunihisa , Kusano Kengo F , Suenaga Hidetaka , Ito Hiroshi , Ohe Tohru , Saito Shigeru
Published: April 2024

Introduction-
Gadlinium-enhanced Cardiac magnetic resonance (CMR) is a useful diagnostic tool for evaluating myocardial abnormality in several diseases. However, the prevalence of delyed Gadlinium enhancement (DGE) in CMR has not been yet reported in patients with Brugada syndrome (BrS).

Methods-
Seventy consecutive patients with BrS who underwent Gadlinium-enhanced CMR were evaluated in this study. All patients underwent echocardiography and signal-averaged electrocardiography (SAECG). Forty six patients underwent both ventriculography and electrophysiologic study, and 26 patients received mutation analysis of SCN5A.

Results-
DGE was found in five patients (7.1 %). All patients with DGE were symptomatic. Early repolarization (ER) in inferolateral leads was significantly highly detected in patients with DGE than without DGE (80.0% vs 16.9%, P<0.01). Late potentials examined with SAECG were present in all patients with DGE and in 42 of 65 patients without DGE (64.6%). The value of RMS40 evaluated with SAECG was significantly smaller in patients with DGE than in patients without DGE (p<0.0001). CMR, echocardiography, and both ventriculography failed to show apparent abnormalities of chamber dimensions and wall motion in any patients. In electrophysiologic study, VF was induced with programmed ventricular stimulation in four of five patients with DGE (80.0%) and in 21 of 41 patients without DGE (51.2%). Mutation analysis revealed that DGE was present in one patient with SCN5A mutation and in 2 patients without SCN5A mutation.

Conclusions-
This is the first report that CMR with DGE can identify abnormal myocardium which is undetectable with other methods in some cases with BrS. Depolarization abnormality is prominent in BrS patients with DGE. Because the positive predictive value of DGE is high, CMR with DGE might be a useful tool for evaluating high risk patient with BrS.
Abstract 18126: Attenuations in Serum Albumin Over Time Powerfully Predict an Amplified Risk of Death in Chronic Heart Failure
Authors: Jabbour Richard , Husain Syed , Zaman Nabeela , Aung Nay , Zen Ling Hua , Baruah Resham , Cole Graham , Manisty Charlotte , Barron Antony , Mayet Jamil , Francis Darrel , Thomas Martin , Woldman Simon , Okonko Darlington O
Published: April 2024

Background:
Worsening heart failure is typically accompanied by diffuse inflammation, plasma volume expansion, diminished nutritional status and blunted liver biosynthetic function due to hepatic congestion. Because attenuations in serum albumin over time reliably reflects these derangements, we hypothesized that it would be predictive of death in patients (pts) with chronic heart failure (CHF) and that its prognostic power would supercede that of static single measures of albumin at baseline.

Methods:
We analysed the relation of serum albumin on first consultation and over time with mortality in 246 outpatients with CHF (mean [±SD] age 68±12y, LVEF 29±8%, albumin 42±5 g/L, 48% NYHA class >2, 55% ischemic).

Results:
On initial consultation, 12 (5%) pts had an albumin < 35g/L. Over a median (±IQR) follow-up of 13±18 months, 51 (21%) pts died, 132 (54%) pts had a fall in albumin, and 46 (19%) pts harboured attenuations > 6g/L. On Cox proportional hazards analyses, a lower albumin at baseline predicted increased mortality (HR 0.89, CI 0.84 - 0.94, χ
2
:18, P<0.0001) independently of all covariates. However, a falling albumin over time (unadjusted HR 0.89, CI 0.84 - 0.92, χ
2
53, P<0.0001) was even more predictive (Difference in ROC AUC for baseline vs Δalbumin 0.16, P<0.001) and did so independently of baseline albumin, NYHA class and changes in urea and hemoglobin (Δalbumin adjusted HR 0.84, CI 0.81 - 0.88, χ
2
54, P<0.0001). A reduction in albumin > 6 g/L optimally predicted death (ROC AUC 0.82, CI 0.76 - 0.86, P<0.0001, Fig A) and conferred a 6-fold escalated risk of mortality (HR 6.42, CI: 3.67 - 11.22, P<0.0001, Fig B). In incremental prognostic analyses, the addition of Δalbumin to the strongest 4 variable model dramatically augmented the χ
2
value (Fig C).

Conclusions:
Attenuations in serum albumin over time strongly correlate to an enhanced risk of death in chronic heart failure and could be utilised to further refine risk stratification.
Abstract 18156: Donor Specific Alloantibodies to HLA II Antigens Result in Accelerated Cardiac Allograft Vasculopathy Assessed by 3d Volumetric Ivus
Authors: topilsky yan , Gandhi Manish J , Hasin Tal , Raichlin Eugenia , Boilson Barry A , Schirger John A , Edwards Brooks S , Clavell Alfredo L , Rodeheffer Richard J , Frantz Robert P , Joyce Lyle , Park Soon J , Daly Richard C , Lerman Amir , Kushwaha Sudhir S , Pereira Naveen L
Published: April 2024

BACKGROUND:
The immunologic risk associated with preformed donor-specific allo-antibodies (DSA) against human leukocyte antigens (HLA) in heart transplant (HTX) recipients is unclear. The goal of this study was to evaluate potential role of DSA on the progression of cardiac allograft vasculopathy (CAV) in HTX recipients.

METHODS:
The presence of DSA against HLA was evaluated using solid phase Single Antigen Bead assay (One Lambda, Inc., Canoga Park, CA; Luminex platform) before transplant in 35 HTX recipients. Using alloantibody specification analysis, 11% (4/35) and 20% (7/35) had DSA against donor Class I and II HLA respectively including the one patient who had both (DSA I & II+) . 71% (25/35) of patients had no demonstrable DSA (DSA-). All patients had negative cytotoxicity cross match. Baseline three-dimensional intravascular ultrasound studies (3D IVUS) were performed at 1.0 [0.18, 1.4] year after transplant. Follow up 3D IVUS exams were performed 0.92 [0.85, 1.04] years after the baseline exam.

RESULTS:
The increase in mean plaque (media and intima) volume (PV) was accelerated in the DSA II+ group as compared to the DSA- group (0.87±1.9 mm (3)/mm vs. 0.16±1.8 mm (3)/mm) but the vessel volume index (follow up vessel volume/ baseline vessel volume) was similar between groups (1.08±0.5 vs. 1.09± 0.4; p=0.9). Plaque index (PI) (PV/vessel volume x 100 [%]) increased significantly in the DSA II+ group (17.9±6.3%) but not in the DSA- group (-13.6±13.2%, P=0.02). None of these values were significant in the DSA I+ only group. Treatment with Sirolimus did not affect PI progression between the DSA II+ and DSA- groups (PI progression: 15.9±8.7% vs. -11.7±7.1%, P=0.03). Age, gender, lipid and uric acid levels, prevalence of diabetes, ischemic time, time between IVUS examinations, the use of steroids, mycophenolate vs. azathioprine or calcineurin inhibitors vs. sirolimus were not different between the groups (P>0.4 for all).

CONCLUSIONS:
Heart transplant recipients with clearly defined anti-Class II DSA are at risk for accelerated cardiac allograft vasculopathy. Whether interventions to minimize the risk of DSA such as virtual crossmatch, desensitization and complement inhibition will retard CAV remains to be proven.
Abstract 18187: Shone's Complex: Single Center Experience Over 22 Years
Authors: de la Uz Caridad M , Ayres Nancy A , Payne William A , Pignatelli Ricardo H , Petit Christopher J
Published: April 2024

Background:
Children with Shone's Complex (SC) have multiple levels of left heart obstruction and often require a number of left heart interventions. They are at risk of long-term morbidity and mortality. However, long-term outcomes in children with SC are limited.

Methods:
SC was defined as a mitral valve (MV) anomaly and ≥ 1 other left heart obstructive lesion including coarctation of the aorta (CoA), subvalvar, supravalvar and aortic valvar stenosis (AS). MV morphology type was classified as typical (MVtyp) - hypoplastic annulus, thickened leaflets; mitral ring (MVr); arcade or other papillary muscle anomaly (MVarc); parachute (MVpap); and other including double-orifice (MVo). Pts who underwent Norwood palliation were excluded. We reviewed overall outcomes and focused on the impact of pulmonary hypertension (PH) and pre-existing atrial septal defect (ASD) on left heart growth, number of interventions, and death/transplant (OHT).

Results:
A total of 129 SC pts presented at 35d (0d - 18yrs) of age and were followed for 7.0 ± 6.8 years. MV morphology included MVtyp (n=89, 68%), MVr (n=23, 18%), MVpap (n=21, 16%), MVarc (n=25, 19%). A total of 113 pts underwent 232 (median 2, 0-5) interventions including ASD closure (n=49), VSD closure (n=30), AVR (n=8), MVR (n=10), MV repair (n=39), AS repair (n=37), balloon valvuloplasty (n=36) and CoA dilation/repair (n=60). Pre-intervention, ASD was associated with lower mean LA pressure 11.7±5.6 vs 18.5±6.5 mmHg (p=0.02) and lower mitral gradient 5.3 ± 5.6 vs 10.9 ± 10.6 mmHg (p<0.01) on catheterization. Following first surgical intervention, residual ASD was associated with decreased annular growth of AV (p=0.042) and MV (p=0.01), smaller increase in LVEDD (p=0.001) and LVESD (p=0.018). MVpap was associated with smaller MV (p<0.001) and less MV annular growth by latest follow-up (p=0.001). Twenty-year OHT-free survival was 87%. By multivariate analysis, PH was associated with death/OHT (OR 6.8, 1.7-27.8). Survival in pts without residual ASD was 88% vs 77% with an ASD (p=0.017).

Conclusions:
SC pts with residual ASD have a higher rate of interventions. Left heart growth is optimized with ASD closure, while MVpap is associated with decreased growth. Pts who develop PH and have residual ASDs are at higher risk of mortality.
Abstract 182: Risk of Cardiac Arrest by Location Type to Guide Future AED Placement in a Large Urban Center
Authors: Brooks Steven C , Hsu Jonathan , Tang Sabrina K , Jeyakumar Roshanthakumar , Chan Timothy C
Published: April 2024

Introduction:
Public access defibrillation (PAD) programs can improve survival from out-of-hospital cardiac arrest (OHCA). We aimed to identify high risk public locations which should be prioritized for automated external defibrillator (AED) placement.

Objectives:
1) To determine the average annual incidence of cardiac arrest by location type within the study area, 2) To describe current registered PAD deployment by location type.

Methods:
An observational cohort study using the Resuscitation Outcomes Consortium Epistry database. We included all public location, non-traumatic, EMS-treated OHCAs from January 1, 2006 to June 30, 2010 in the City of Toronto. The total site counts in each location category were derived from a city planning database and used as the denominator in calculating average annual per site cardiac arrest incidence. AED locations were obtained from an EMS registry. Two investigators independently categorized each OHCA and AED location. Disagreements were resolved by consensus.

Results:
There were 1297 OHCAs, of which 571 occurred on streets and could not be associated with a specific location type, leaving 726 eligible cases. The average age was 58±17.5 years, 82.7% were male and 13.9% survived to hospital discharge. Of all included patients, 44.9% had bystander CPR attempted and 9.5% had a bystander apply a defibrillator. Table 1 contains data from the top 15 location types ranked on average annual OHCAs per individual site. There were 1616 AED covered locations in the City of Toronto. 57.3% of the registered AED sites were elementary and secondary schools, 16.0% were post secondary schools, 7.8% were offices and 4% were community or recreation centres.

Conclusions:
We have identified location types with highest risk for cardiac arrest. Most registered AEDs have been placed at Elementary and Secondary Schools which are relatively low risk for OHCA. Our data can guide future AED deployment to increase availability for use in public location OHCA.
Abstract 18224: Patient and Caregiver Perceptions of Living with a Left Ventricular Assist Device as Destination Therapy
Authors: Kitko Lisa A , Boehmer John P , Hupcey Judith E
Published: April 2024

LVADs have been shown to improve survival in patients with end-stage heart failure. Initially developed as a bridge to transplantation, LVADs are now implanted permanently as destination treatment (DT) or end of life treatment. While the number of LVAD-DT implants is increasing, there remains a paucity of research on the experiences of patients and their caregivers and the impact of living with this device. The objective of this study was to examine changes in the perception of burden of treatment for patients and caregivers prior to and following the LVAD implant.

Methods:
A sample of 25 patients and caregivers one month to 2-years post-LVAD implant were surveyed using a one item (rating 0-100) visual analog scale (VAS) with “0” being “not at all burdened” to “100” being “extremely burdened.” Patients and caregivers were asked to rate their perceptions of the burden of treatment (eg, medications, diet, daily weights, appointments) prior to the implant and their present perceptions post-LVAD implant.

Findings:
For the majority of patients, the perceptions of the burden of treatment dramatically decreased post-LVAD implant, with no trend based on time since implant. Conversely, caregivers continued to rate their perceptions of the burden of treatment post-LVAD implant at pre-implant levels or higher.

Conclusions:
A disparity exists in the perception of burden post-LVAD implant between patients and caregivers. Patients post-LVAD-DT implant rate the burden of treatment lower than caregivers. Caregivers continue to perceive increased rates of the burden of treatment related to general care (eg., diet, medications) and the care required to maintain the LVAD-DT such as battery support, uncertainty related to device failure, and drive line care.

Implications:
The incongruent perceptions of the burden of treatment post-LVAD-DT between patients and caregivers has important practice implications. Caregivers are the main source of support for these patients and need to be considered as both co-providers and co-recipients of care. Thus caregivers’ needs must also be assessed and interventions targeted to improve the experiences of both patients and caregivers as they live through this end-of-life trajectory.
Abstract 18233: Association of Circulating Levels of Asymmetric Dimethylarginine with Carotid Intima-Media Thickness: Evidence From 5269 Participants
Authors: Sun Lan , Bai Yongyi , Xin Wenyu , Du Guanhua
Published: April 2024

Backgrounds:
Epidemiologic investigations have linked the circulating levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), to carotid intima-media thickness (IMT). However, these studies result in various extent of relation between ADMA and IMT, the conclusions were inconsistent, and the precise relationship is therefore under debate. The objective of this systematic review and meta-analysis is to provide an overview of the relevant studies evaluating the association of levels of ADMA with carotid IMT and to gain more robust estimate of the relationship.

Methods and results:
Studies were identified through PubMed, Cochrane Library, Embase, reviews, and reference lists of relevant papers. Weighted mean differences (WMDs) of the correlation coefficient (R) and partial correlation coefficient (PR) were calculated for relations by using random-effect models. Eleven studies with a total of 5269 subjects were included in our meta-analysis. In an overall pooled estimate of correlation coefficient (R), levels of ADMA were significantly related to carotid IMT (pooled R: 0.25; 95% confidence interval [CI]: 0.146 to 0.363, P<0.001). Pooled estimate of partial correlation coefficient (PR) also resulted in a significant association of ADMA with carotid IMT (pooled PR: 0.15; 95% CI: 0.07 to 0.23; P <0.001). Furthermore, subgroup analysis found that the relation between ADMA and IMT was stronger in patients with Chronic Kidney Diseases (CKDs) than that in subject with normal renal function.

Conclusions:
Circulating levels of ADMA were positively related to carotid IMT, especially in patients with CKDs. These findings indicate that elevation of plasma ADMA levels is an indicator of early-onset atherosclerosis and a predictor of atherosclerotic disease, especially in patients with CKDs. The findings of this meta-analysis need confirmation in longitudinal studies. Furthermore, future research efforts should be concentrated on higher quality, longer follow-up and more rigorous prospective and interventional studies to determine the causal relationships between the associations.
Abstract 18251: Sirt1 Mediates Pressure Overload-Induced Cardiac Hypertrophy and Failure in vivo
Authors: Oka Shinichi , Alcendor Ralph , Zablocki Daniela , Zhai Peiyong , Yamamoto Takanobu , Sadoshima Junichi
Published: April 2024

Mitochondrial dysfunction is a hallmark of the failing heart. Sirt1, a class III histone deacetylase, plays an important role in mediating transcriptional regulation of metabolic genes in response to stress. The function of endogenous Sirt1 during heart failure is poorly understood. Here we investigated the role of Sirt1 in pressure overload-induced cardiac hypertrophy and failure using genetically altered mouse models, namely cardiac specific Sirt1 heterozygous (Sirt1
+/-
) and homozygous (Sirt1
-/-
) knockout (KO) (C57BL/6) and Sirt1 overexpression (Tg-Sirt1) mice (FVB). These mice were subjected to pressure overload with transverse aortic constriction (TAC). Notably, C57BL/6 mice are more susceptible to TAC-induced cardiac hypertrophy and failure than FVB mice. Cardiac hypertrophy induced by 4 weeks of TAC was exacerbated in Tg-Sirt1 (heart weight/body weight (HW/BW, mg/g), Wild type (WT) 6.0, Tg-Sirt1 8.4*, p<0.05 vs WT), whereas it was ameliorated in Sirt1 KO mice (HW/BW, (mg/g), WT 7.9, Sirt1
+/-
6.9*, Sirt1
-/-
6.0*, * p<0.05 vs WT). TAC-induced systolic dysfunction was also exacerbated in Tg-Sirt1 (ejection fraction (EF) (%), WT 71, Tg-Sirt1 48*, p<0.05 vs WT), whereas it was ameliorated in Sirt1 KO mice (EF (%), WT 55, Sirt1
+/-
65*, Sirt1
-/-
63*, * p<0.05 vs WT). The expression of nuclear encoded mitochondrial genes, such as Cpt2, Sdha, Fh1 and Ndufv1, was downregulated by TAC in WT mice, an effect that was normalized in Sirt1
-/-
mice (relative mRNA levels vs WT sham, Sdha: WT TAC 0.56, Sirt1
-/-
sham 1.2, Sirt1
-/-
TAC 0.81*, Ndufv1: WT TAC 0.59, Sirt1
-/-
sham 0.84, Sirt1
-/-
TAC 1.1*, * p<0.05 vs WT TAC). On the other hand, ATP content was decreased in Tg-Sirt1 mice after TAC (45% reduction vs WT). Chromatin immunoprecipitation assays revealed that pressure overload induces recruitment of Sirt1 to the promoter region of these mitochondrial genes (relative promoter occupancy after 4 weeks of TAC, Cpt2 2.6*, Sdha 7.4*, Fh1 5.4*, Ndufv1 5.6*, * p<0.05 vs sham), indicating that endogenous Sirt1 interacts with mitochondrial genes, thereby negatively regulating their expression during TAC. These results suggest that Sirt1 mediates pressure overload-induced cardiac hypertrophy and failure, possibly through attenuation of mitochondrial function.