bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19548: Detection, Correlation and Prediction of Systemic Vascular Disease using 3D volumetric Carotid Ultrasound: Results from the High Risk Plaque Initiative
Authors: Baber Usman , Sartori Samantha , Mehran Roxana , Muntendam Pieter , Garcia Mario J , Sillesen Henrik , Falk Erling , Fuster Valentin
Published: April 2024

Purpose
We sought to determine the prevalence and clinical correlates of carotid atherosclerosis using novel 3D ultrasound imaging.

Methods
In the High-Risk Plaque (HRP) Initiative, 3690 asymptomatic, at-risk adults underwent non-invasive imaging for evaluation of subclinical atherosclerosis in the carotid arteries using duplex ultrasound for measurement of plaque volume (3D) and intima-media thickness (IMT). Coronary artery calcification (CAC) was assessed using computed tomography (CT). Plaque volume in the right and left carotid arteries was averaged and patients were categorized by tertiles of increasing plaque volume. The prevalence and clinical correlates of carotid atherosclerosis were compared across groups. Discrimination for CAC detection using 3D carotid ultrasound versus IMT was also assessed with receiver operating curve (ROC) analysis.

Results
Any carotid atherosclerosis was common, detectable in 70% of participants using 3D carotid ultrasound. Greater carotid atherosclerotic burden was associated with increasing age, lower high-density lipoprotein cholesterol, smoking, white race and male gender (p<0.05 for all comparisons). Carotid atherosclerosis was also strongly associated with CAC as the prevalence of CAC > 100 was 20.3%, 34.6%, 50.1% and 62.2% across groups (p<0.001). Discrimination for detection of CAC was also higher using 3D carotid ultrasound compared to IMT with c-statistics of 0.69 and 0.59 for CAC > 100; and 0.71 and 0.59 for CAC > 400, respectively (Figure).

Conclusion
In this large observational study, carotid atherosclerosis as detected by 3D volumetric ultrasound is highly prevalent and associated with traditional risk factors. Compared to IMT, carotid atherosclerosis as visualized by 3D ultrasound is a better predictor of CAC, suggesting that this novel modality may be superior to IMT in detection of systemic vascular disease.
Abstract 19556: The Beneficial Effects of Statin Therapy on Total and Composition-Specific Plaque Volumes Measured by Computed Tomography Angiography
Authors: Ahmadi Naser , Nabavi Vahid , Malpeso Jennifer , Ebrahimi Ramin , Budoff Matthew
Published: April 2024

Background:
Coronary plaque volume and its progression is an independent predictor of cardiovascular mortality. This study evaluates the overall and composition-specific (noncalcified, mixed or calcified) change in plaque volume measured by computed tomography angiography (CTA) in response to statin therapy.

Methods:
One hundred and seven consecutive subjects (age 67±9 years, 80.7% men) who underwent serial clinically indicated CTAs with median interval of 1.2 year, were studied. clinical and demogrpahic findings of 31 with statin therapy and 75 without statin therapy were evaluated. Total and composition-specific plaque volume of target segment with luminal stenosis0.05). At follow-up, there were -38.2% decrease in plaque volume in individuals with statin therapy as compared to those without statin therapy (p=0.0001), and remained significant even after adjustment for age, gender and conventional risk factors. Similarly, significant decrease in noncalcified and mixed plaque as well as lack of progression of calcified plaque in statin therapy group was noted (p<0.05). Risk factor adjusted median decrease in overall, mixed, calcified and noncalcified plaque volumes were 56%, 12%, 43% and 144% more in statin therapy group as compared to those without statin therapy, which was more robust in women(p<0.05).

Conclusion:
Statin therapy was associated with significant decrease in plaque volume, especially noncalcified plaques, prominently in women. CTA accurately measures the overall and composition-specific change in plaque volume in response to statin therapy; highlighting its important role as a non-invasive modality, to monitor response to anti-atherosclerosis therapy and its management.
Abstract 19578: Title: Natural Killer T cells Play a More Critical Role in Reperfusion Injury Than in the Hyperglycemic Exacerbation of Infarct Size
Authors: Xu Yaqin , Smith Robert S , Yang Zequan , Laubach Victor E , Kron Irving L , French Brent A
Published: April 2024

Introduction:
Invariant Natural Killer T (iNKT) cells express a T cell receptor encoded by the Jalpha18 gene that recognizes glycolipid antigens presented by CD1d. These same iNKT cells have recently been implicated in the hyperglycemic exacerbation of lung ischemia/reperfusion injury. Thus, we hypothesized that Jalpha18-/- mice, which lack iNKT cells, would similarly be protected against the hyperglycemic exacerbation of cardiac injury in the mouse model of reperfused myocardial infarction (MI).

Methods:
Reperfused MI was performed in euglycemic (n=8) and hyperglycemic (n=7) C57Bl/6 wild-type (WT) mice, as well as in congenic euglycemic (n=11) and hyperglycemic (n=8) Jalpha18-/- mice. MI consisted of 30 min coronary occlusions followed by 2 h reperfusion. Infarct size was determined by digital planimetry after TTC and Phthalo blue staining, and was reported as infarct size as percent area-at-risk (%A@R).

Results:
Infarct size was reduced by 56% in euglycemic Jalpha18-/- mice compared to euglycemic WT mice (18±3% vs. 41±5%, mean±SEM, p<0.05). Infarct size was also reduced in hyperglycemic Jalpha18-/- mice compared to hyperglycemic WT mice, albeit to a much lesser extent (52±3% vs. 63±3%, p<0.05). Further, the areas at risk as percent of the left ventricular (LV) mass were similar for all groups (p=NS).

Conclusions:
With regard to mechanism, these results clearly demonstrate that iNKT cells and innate immune responses contribute importantly to reperfusion injury. From a translational perspective, the results predict that interventions focused on suppressing the innate immune response during reperfusion will be significantly more effective in euglycemic patients than in those suffering from stress hyperglycemia.
Abstract 19579: The Incidence of Stroke and Pericardial Effusion after Pericardial Suture Ligation of the Left Atrial Appendage
Authors: Gangireddy Sandeep R , Coffey James O , Viles-Gonzalez Juan , Koruth Jakob S , Miller Marc A , d'Avila Andre , Dukkipati Srinivas , Reddy Vivek Y
Published: April 2024

Introduction:
Left atrial appendage closure (LAAC) is an effective alternative to warfarin in nonvalvular AF patients who are intolerant to oral anticoagulation. Our aim was to determine the incidence of stroke and pericardial effusion following pericardial suture ligation of the left atrial appendage.

Methods:
Retropspective analysis of 16 patients who underwent LAAC with an epicardial suture delivery system (LARIAT) at single center. Pericardial access was obtained using an anterior approach, followed by transeptal puncture. Epicardial and endovascular magnetic-tipped guidewires were then aligned, and the epicardial snare and suture were advanced over the left atrial appendage. After snare closure and suture deployment, TEE and fluoroscopy were used to confirm left atrial appendage exclusion. Patients were discharged on aspirin. Reported stroke or TIA events were confirmed by CT or MRI.

Results:
Of the 16 patients included, the mean age was 74.2 ±9.1, 56% of patients (9/16) were male, and the mean CHADS2 score was 3.6 ± 1.2; 11 patients (69%) had a prior stroke or TIA. These patients accumulated a total of 9.6 person-years of follow up (5.3 months ±7.7). LAAC was confirmed by repeat TEE at 1.95 ± 3.0 months, and 7/16 patients (44%, 95% CI 10-77%) experienced any size left atrial appendage leak, and 1/16 (6%, 95% CI 0-20%) experienced a large leak (≥3mm). After LAAC, 1/16 patients experienced a stroke. A 71 year old male (CHADS2 = 3) who was not on anticoagulation developed a central retinal artery occlusion 5 months post-procedure. The overall incidence of stroke or TIA was 6%, (95% CI 0-20%). After LAAC, 3/16 patients developed a pericardial effusion (19%, 95% CI 0-40%), of which 2 required pericardiocentesis.

Conclusion:
We observed a significant rate of pericardial effusion and symptomatic ischemic events after LAAC with an epicardial suture ligation system; further study is needed to assess its relative safety compared to alternate LAAC devices in patients intolerant to oral anticoagulation.
Abstract 19610: Role of Hypoglycemic Agents on Ischemic Preconditioning in Diabetic Patients with Stable Multivessel Coronary Artery Disease
Authors: Garcia Rosa M , Hueb Whady , Uchida Augusto H , Rezende Paulo C , Lima Eduardo G , Garzillo Cibele L , Segre Carlos A , Favarato Desiderio , Ramires Jose A , Kalil Filho Roberto
Published: April 2024

Background:
Ischemic preconditioning (IPC) protects the heart from irreversible injury and some hypoglycemic drugs can abolish IPC, affecting infarct size and contractile function and contributing to a worse prognosis. We aimed to evaluate the effect of 2 hypoglycemic agents on myocardial IPC in patients with type 2 diabetes and symptomatic coronary artery disease.

Methods:
We evaluated 81 patients, consecutively included, with type 2 diabetes, previous positive exercise test and multivessel coronary disease confirmed by coronary angiography. In phase I, without drug, all patients underwent 2 consecutive treadmill exercise tests (T1 and T2). After that, we started the phase II: 42 patients received repaglinide 6 mg per day (group R) and 38 pacients received Vildagliptin 100 mg per day ( group V), during one week and underwent 2 sequential tests (T3 and T4). The time interval between the exercise tests was 30 minutes.

Results:
In phase 1, IPC was demonstrated, in all patients, by improvement in the time to 1.0 mm of ST segment depression (T-1.0mm) in second of two sequential tests. All patients developed ischemia in T3; however, 83.3% of patients in group R experienced ischemia earlier in T4, indicating the cessation of IPC (
P
<0.0001). In group V, only 28% of patients demonstrated IPC cessation, with 72% still preserving the protective effect (
P
<0.0069).

Conclusions:
Repaglinide eliminated myocardial IPC, probably by its effect on the ATP-K channel. Vildagliptin did not affect this protective mechanism in a relevant way in patients with type 2 diabetes and coronary artery disease, suggesting a good alternative treatment in this population.
Abstract 19645: Cardiac Effects of Physiological Hypertrophy in a Murine Model of Calcium Channel Overexpression
Authors: Barr Larry , Zhang Hongyu , Berretta Remus , Molkentin Jeffery D , Houser Steven R
Published: April 2024

Background —

 The L-type calcium channel (LTCC) is integral for calcium entrance into the cardiomyocyte to induce CICR from the SR. We have developed a mouse model with inducible, cardiac-specific expression of the β2a subunit of the LTCC (β2a), leading to pathological hypertrophy akin to post-MI heart failure. Chronic exercise is known to cause physiological hypertrophy in normal hearts, leading to enhanced contractile state and thickened heart tissue, without a pathological phenotype. We administered chronic physiological hypertrophy in the form of swim training on the β2a line and its WT counterpart, analyzing the cardiac changes.

Methods and Results —

 β2a (n=8) and WT (n=16) FVB mice aged 4 months were swam twice a day, four hours apart, for 21 days. They swam for 10min sessions on Day 1, with each subsequent day increasing the session time by 10 min until 90min sessions were reached. ECHO was performed at beginning and end of swim training, then terminal HW/BW ratio was determined. EF and FS increased significantly with swimming in WT (EF [%] pre-swim: 57.21±2.02 vs. post-swim: 69.98±2.88; FS [%] pre-swim: 29.53±1.34 vs. post-swim: 39.27±2.42) and from sedentary counterparts. β2a mice showed no significant change after swimming (EF [%] pre-swim: 69.8±1.75 vs. post-swim: 74.06±2.72; FS [%] pre-swim: 38.24±2.38 vs. post-swim: 42.40±2.22) and no change from sedentary β2a mice. Both ECHO parameters were significantly greater in β2a mice versus WT before swimming, but not after. There was a significant difference in HW/BW ratio in WT exercised mice versus sedentary (HW/BW [mg/g] swim: 4.63±0.2 vs. sed: 5.75±0.19) that was not present in exercised versus sedentary β2a mice (HW/BW [mg/g] swim: 5.98±0.31 vs. sed: 5.96±0.25).

Conclusions —

 Chronic exercise may not affect mice with pathological hypertrophy through overexpressed LTCC but causes physiological hypertrophy in their wild type counterparts.
Abstract 19653: Therapeutic Potential of Long Ultrasound Tone Bursts in Microbubble-Ultrasound Mediated Therapeutics: Mechanistic Insights Using High Speed Imaging
Authors: Wang Jianjun , Chen Xucai , Pacella John , Villanueva Flordeliza
Published: April 2024

Background:
Microbubble (MB)-Ultrasound (US) assisted therapy has been shown to restore perfusion in myocardial infarction (sonothrombolysis). Due to a presumption that MBs under high acoustic pressure do not persist after long acoustic cycles, most schemes of US-assisted therapy utilize a very short US pulse (a few acoustic cycles) when a high US pressure is used. However, we have recently observed enhanced in vitro sonothrombolytic effect using MBs and very long US pulses, at high acoustic pressures. We therefore sought to explore the actual fate of MBs during a long acoustic cycle exposure by visual observation of MB acoustic behaviors at varying pulse lengths.

Methods:
MB behaviors were optically observed during long US tone burst excitation using an ultra-high speed imaging system that allows microscopic visualization of MB cavitation. The system is capable of capturing 128 frames at up to 25 million frames per second (Mfps). Long US tone bursts (up to 5,000 acoustic cycles) at 1 MHz and various pressures (0.25, 0.5, 1.0, and 1.5 MPa) were used to study the dynamic behavior of both lipid and polymer MBs in a 200-µm diameter cellulose tubing.

Results:
High speed movies of the MBs during long tone burst excitation showed that MBs first underwent inertial cavitation then formed gas-filled aggregates that continued to oscillate. The locations of the aggregates were random due to the dynamic nature of MB destruction. Figure 1 shows still frames of a high speed movie (5 Mpfs) of polymer MBs 1,000 acoustic cycles into a long tone burst at 1.5 MPa: MB aggregates continued to oscillate, break up, and new aggregates were formed.

Conclusion:
These data show for the first time that MBs survive as aggregates that continue to oscillate with large amplitude during a long tone burst, demonstrating the therapeutic potential for US-assisted therapy. This discovery suggests that long acoustic cycles have additional therapeutic effect for MB-US assisted therapies such as sonothrombolysis.
Abstract 19695: Platelet TSC1 is an Important Mediator of Arterial Thrombosis
Authors: Ahn Yong-Joo , Kim Hyung-Hwan
Published: April 2024

Background
: Arterial thrombosis is responsible for peripheral vascular disease, myocardial infarction, and stroke. Mammalian target of rapamycin (mTOR) inhibition promotes arterial thrombosis. To determine the contributions of platelet specific Tuberous sclerosis 1 (TSC1) deficiency to arterial thrombosis, we generated PF4Cre-TSC1

flox/+

mice. Because the effect of mTOR activation on thrombus formation
in vivo
has not yet been studied, we hypothesize that mTORC1 signaling pathway in platelets may play an important role in arterial thrombosis.

Methods and Results
: To determine the role of platelet TSC1 in arterial thrombosis, we generated a mouse strain with platelet-specific TSC1 deficiency (PF4Cre-TSC1

flox/+

) using conditional TSC1

flox/flox

mice and platelet-specific PF4-Cre mice. PF4Cre-TSC1

flox/+

mice did not show any obvious phenotypic abnormalities. Arterial thrombus formation was investigated using
in vivo
ferric chloride induced thrombosis model. Ferric Chloride (5% FeCl
3
) induced thrombotic occlusion. Compared to PF4-Cre mice, PF4Cre-TSC1

flox/+

mice exhibited elongated thrombotic occlusion time by 21.7%. Platelet specific TSC1 deficiency promotes arterial thrombosis
via
activation of mTOR and S6, a downstream target of mTORC1.

Conclusion
: These finding indicate that platelet specific TSC1 deficiency promotes arterial thrombosis
in vivo
. These results suggest that activation of mTORC1 may have therapeutic benefits in arterial thrombosis.
Abstract 19697: Left Ventricular Unloading by Impella® Microaxial Flow Pump for Treatment of Left Ventricular Overload in Venoarterial Ecmo Supported Cardiogenic Shock Patients
Authors: Roentgen Philipp , Kuehn Christan , Warnecke Gregor , Tongers Joern , Schäfer Andreas , Haverich Axel , Bauersachs Johann , Schieffer Bernhard
Published: April 2024

Background
Venoarterial (VA)-ECMO is an established support for refractory cardiogenic shock (CS), but may be complicated by an increase of cardiac afterload leading to left ventricular (LV) distension with consecutive pulmonary edema and deterioration of left ventricular function.

Methods
VA-ECMO was instituted in patients with refractory CS of different etiology. Progressive LV overload was detected by clinical signs of pulmonary edema and critical elevated LV end diastolic pressure (LVEDP). LV unloading by Impella
®
2.5 via femoral access was established. Patients were followed up for heart rate, catecholamine demand, white blood cell count (WBC) and serum lactate levels before and after 24 hours (h). Fatal bleeding complications, signs of limb ischemia and 28-day mortality were assessed. Data are presented as mean±SD.

Results
Six patients, SAPS II-Score on admission 56±15, age 61±18 yrs are presented. Three MI patients complicated with refractory CS. One patient with myocarditis, one due to acute heart failure complicated by septic shock and one due to acute heart transplant rejection. Five/6 patients were on mechanical ventilation and all showed clinical and radiologic signs of pulmonary edema (LVEDP before LV unloading 35±15 mmHg). Under Impella
®
support (5±2 days) heart rate decreased after 24 h from 120±15 to 104±20/min. After 24h catecholamine demand decreased (dobutamine and epinephrine p=n.s.; norepinephrine 0.44±0.38 to 0.20±0.19 µg/kg/min, p=0.04). Serum lactate levels declined from 5.5±4.8 to 2.5±1 mmol/l at 24 h and 1.3±0.3 mmol/l at 72 h. WBC declined from 22±6 to 18±6 thd/µl (p=0.004) after 24 h. No fatal bleeding complications or limb ischemia occurred. 28-day mortality was 17 %. One patient with myocarditis died in multiorgan failure.

Conclusion
VA-ECMO treatment of CS complicated by LV overload can safely and efficiently be treated by LV unloading using microaxial flow pump Impella
®
2.5. This biventricular decompression rapidly reduces catecholamine demand and lactate levels indicating an improved organ function followed by a resolution of SIRS due to cardiac shock (reduced WBC).
Abstract 19702: Bending Flexibility of Stents: Comparison among Four DES Platforms with Different Design and Materials Deployed in in-vivo Simulated Cyclically-Bending Coronary Artery Model
Authors: Iwasaki Kiyotaka , Kishigami Sho , Arai Jun , Ohba Takafumi , Yamamoto Tadashi , Hikichi Yutaka , Kasanuki Hiroshi , Umezu Mitsuo
Published: April 2024

Objective:
Deployment of coronary stents in bending coronary artery often provokes changes in cyclic bending angles during cardiac contraction and relaxation. We investigated cyclic bending flexibility of four drug eluting stents consisted from different design and materials, using a novel methodology using in-vivo simulated cyclically-bending and mechanically-matched coronary artery model.

Methods:
Based on angiographic data of bending angles of proximal right coronary artery (RCA) in end-systole and end-diastole of 63 patients, the angle data matched to type-B according to ACC/AHA guideline were used to fabricate a RCA model. Because the average angles in end-systole and end-diastole were 105° and 125°, stents were deployed in the coronary artery models which are cyclically bended between 105° and 125°. Mechanical stiffness of the coronary artery model was adjusted to that of referenced human coronary artery. Promus Element PtCr stents (3×20mm), Resolute Integrity MP35N CoCr stents (3×18mm), Xience Prime L605 CoCr stents (3×18mm), Cypher SUS 316L stents (3×18mm) were deployed in the transparent elastic bending coronary artery mode at each nominal balloon inflation pressure (n=6 each). Bending angles of stents were analyzed using digital microscope.

Results:
Bending flexibility was clearly differentiated among four DES platforms as shown in the figure. These data indicated that Promus Element PtCr stents was most flexible among the four stents in response to cyclic deformation of the coronary artery model. There were significant differences in the bending angles both in end-systole and end-diastole as well as in the traveling angles.

Conclusion:
Cyclic bending flexibility of four DES consisted from different design and materials was quantitatively revealed using a novel methodology.
Abstract 19716: Role of Aldose Reductase in Perivascular Adipose Tissue and Vascular Dysfunction in Short-Term Diet-Induced Obesity
Authors: Conklin Daniel J , MacKinlay Kenneth G , Murphy Daniel A , Haberzettl Petra , Bhatnagar Aruni
Published: April 2024

Obesity is a risk factor for diabetes and cardiovascular (CVD) disease, and the quantity of perivascular adipose tissue (PVAT) associates with CVD risk. To test the hypothesis that changes in PVAT are causal in diet-induced vascular dysfunction, mice (wild type, WT and aldose reductase-null, ARKO, an obesity-sensitive model) were fed a low fat chow diet (10% kcal fat) or high fat chow diet (HFD; 60% kcal fat) for 4 weeks (short-term) in either 8 weeks old or 18 weeks old C57 mice (n=4-6/group). After 4 weeks, body weight and lean and fat mass was measured (DexaScan). Vascular, endothelial and PVAT function and structure were measured in isolated thoracic aorta without and with PVAT in response high potassium solution (100 mM HIK), phenylephrine (PE), acetylcholine (ACh), thromboxane A2 analog (U46619) and sodium nitroprusside (SNP). As expected, HFD increased body weight in all groups although ARKO mice (young and old) gained significantly more body weight, fat grams (whole body, epididymal), and % body fat when compared with age-matched WT mice. Similarly, aortic PVAT mass increased in ARKO mice indicating that PVAT growth mirrored visceral adiposity induced by short-term HFD feeding and enhanced in ARKO mice. PVAT significantly enhanced HIK-induced contractions and SNP-stimulated relaxations (%), decreased U46619-induced tension but neither altered PE-stimulated contraction nor ACh-induced relaxation (%) in isolated aorta of LFD-fed WT. Several of these PVAT effects were altered by age, AR deletion and 4-weeks of HFD feeding. For example, PVAT rescued endothelial dysfunction (ACh, -84.0±7.7%) detected as decreased ACh-induced relaxation in aorta without PVAT (ACh, -43.6±6.8%, p<0.05) of 22-week WT mice fed HFD, indicating that short-term HFD induces compensatory PVAT changes that counteract deleterious endothelium changes -- a novel finding. Effects of PVAT were only slightly modified in ARKO mice despite a greater mass of PVAT, indicating a complicated role of AR deletion in PVAT. These data add to a growing literature that reveals a complex, integrative vascular function of PVAT that is modulated during obesity and metabolic syndrome.
Abstract 19722: Cardiac Deletion of miRNA-17-92 Cluster Augments Acute Myocardial Ischemia-Reperfusion Injury
Authors: Zhou Mi , Chen Lijuan , Zhao Qiang , Wang Yingjie , Jiang Ming , Pan Yaohua , Ashraf Muhammad , Weintraub Neal , Rubinstein Jack , Tang Yaoliang
Published: April 2024

Objective:
MicroRNAs (miRNA) are small, endogenous, conserved, noncoding RNAs that down-regulate protein production by translational repression. The miR-17-92 cluster (encoding miR-17, -18a, -19a/b, -20a, and miR-92a) is highly expressed in stem cells and is up-regulated by ischemia, but little is known about the postnatal role of miR-17-92 in myocardial ischemia-reperfusion injury (I/R).

Methods and Results:
We established a transgenic mouse model with cardiac-specific deletion of miR-17-92 by crossing miR-17-92 flox/flox (F/F) mice with myh6-MerCreMer (MCM) via tamoxifen dependent Cre-loxP mediated DNA recombination. Two weeks after tamoxifen induced miRNA-17-92 inactivation, no significant differences in histology were observed between tamoxifen and corn oil treated animals despite downregulation of miR-17, -18a, -19a/b, -20a, and miR-92a in the heart. However, in response to 45min ischemia by LAD ligation followed by 24hrs reperfusion in vivo, cardiac miR-17-92 knockout resulted in increased I/R injury, and TTC and phthalocyanine blue staining revealed significantly larger infarct size as compared with control (63.6%±3.9%, n=10 vs. 41.0%±3.1%, n=7, P<0.05). Consistent with increased infarct size, cardiac miR-17-92 inactivation led to increased cardiomyocyte apoptosis after I/R injury, as identified by TUNEL staining. Furthermore, PTEN levels were increased while Phospho-Akt levels were significantly decreased in miR-17-92 inactivated hearts.

Conclusions:
We conclude that cardiac deletion of miR-17-92 augments the ischemia-reperfusion injury by inhibiting survival signaling. .
Abstract 19807: Increased Triacylglycerol Synthesis in the Heart Improves Functional Recovery After Ischemia
Authors: Kolwicz Stephen C , Liu Li , Goldberg Ira J , Tian Rong
Published: April 2024

Accumulation of cardiac lipids has been associated with cardiac dysfunction in diabetes and obesity while increased muscle lipid storage in athletes is associated with improved function. We have previously shown that cardiac specific overexpression of diacylglycerol acyltransferase 1 (MHC-DGAT1), the rate limiting enzyme for triacylglycerol (TAG) synthesis, enhances TAG synthesis, reduces ceramide formation, and rescues lipotoxic cardiomyopathy. Using MHC-DGAT1 mice, we tested whether increased TAG synthesis and storage affected cardiac responses to ischemia-reperfusion. A doubling of cardiac TAG content in MHC-DGAT1 (P<0.05; n=4) was not associated with in-vivo cardiac dysfunction or heart size. With dynamic 13C NMR spectroscopy we found a 70% increase of incorporation of 13C labeled fatty acids (FA) into the cardiac TAG pool in MHC-DGAT1 hearts. In isolated Langendorff perfused hearts, rate pressure product (RPP), was similar in MHC-DGAT1 and control (CON) hearts at baseline (BL). When subjected to 25min of no-flow ischemia (ISC), end diastolic pressure rose equivalently in both groups. However, recovery of RPP during reperfusion (REP) was significantly improved in MHC-DGAT1 compared to CON (51±6% vs 28±6%; n=5-6). At the end of REP, 13C NMR spectroscopy of heart extracts suggested decreased exogenous FA oxidation with no change in glucose oxidation in MHC-DGAT1 hearts. Cardiac TAGs, measured in freeze-clamped hearts, remained unchanged in CON during BL, at end ISC, and at end REP (n=3 per time point). Interestingly, despite ~2-fold increase in TAG in MHC-DGAT1 at BL, TAG content depleted to levels similar to CON at end ISC and REP, inferring accelerated TAG lipolysis in MHC-DGAT1 during the ischemic period. Non-esterified fatty acid (NEFA) concentration was not different between the groups at any time point. In conclusion, these results suggest that ischemia-induced activation of lipolysis in MHC-DGAT1 hearts improves functional recovery, in part, by increasing the oxidation of endogenous lipids during reperfusion. These data also suggest a potential secondary role of endogenous lipids to act as signaling molecules to modulate cardiac function.
Abstract 19822: Ldlr Splice-Site Mutation (ivs9-1g>A) Identified by Whole-Exome Sequencing in an Extended Family with Myocardial Infarction
Authors: Brænne Ingrid , Medack Anja , Stark Klaus , Field Sarah , Tuna Salih ,   Cardiogenics Consortium, Deloukas Panos , Samani Nilesh J , Schunkert Heribert , Hengstenberg Christian , Erdmann Jeanette
Published: April 2024

Introduction:
Large genome-wide association studies have identified a number of chromosomal loci for CAD and MI, which display clear significance yet weak absolute effects for disease manifestation. Combined, these loci explain only a small fraction of the expected heritability. Aim: Here we analyzed a rare extended family with clustering of MI/CAD by means of whole-exome-sequencing (WES) to reveal rare disease-causing variants, which may provide new insights in the cause of the disease.

Methods:
Primarily, we analyzed three affected cousins of a German MI family with 13 affected and 56 unaffected family members by WES using the Agilent SureSelect 38 Mb Kit. Variants were validated by Sanger re-sequencing.

Results
and Discussion: We identified 19,870 variants shared by all three sequenced family members. Of these, 17,268 variants were found in dbSNP with a frequency >1%. Of the remaining 2,602 variants, 935 are conserved (46 Way) and again 728 are located outside of regions of segmental duplication. To identify function-altering variants we filtered all variants based on avsift score >0.05 and ,,HIGH“ effect predicted by Annovar and SNPEFF, respectively. Due to the relative large number of potentially disease causing variants, we focused on the variants not known in dbSNP. This approach left three variants. One variant, a single base-pair substitution (G>A) in intron 9 of the LDLR gene, was validated by Sanger re-sequencing. This variant lies in the acceptor splice-site of exon 10 (c.855-1G>A) and leads the loss of exon 10 (loss of 76 AA) in the LDLR domain class B repeat. We sequenced all family members available for genetic analysis and found that the variant co-segregates with MI. Mutation carriers had -on average- elevated LDL cholesterol (LDLC) levels (211 vs 141mg/dL), but with variable plasma levels (116-274mg/dL), such that severe hypercholesterolaemia was not observed in our index patient.

Conclusion:
Using WES we identified the disease-causing variant for this familial form of MI in the LDLR . Interestingly, highly varying LDLC levels initially impeded the diagnosis of heterozygous familial hypercholesterolaemia. This work clearly show the power of systematic WES approaches for identification of disease causing variants within families.
Abstract 202: Elevated Plasma Levels of Interleukin 6 Are Associated with Risk of Sudden Death in the Community Even When Measured During the Acute Cardiac Arrest Event
Authors: Havmoeller Rasmus , Uy-Evanado Audrey , Teodorescu Carmen , Jerger Katherine , Kwok Dorothy , Ayala Jo , Huertas-Vazquez Adriana , Chen Ida , Reinier Kyndraron , Gunson Karen , Jui Jonathan , Chugh Sumeet S
Published: April 2024

Introduction:
Elevated plasma levels of interleukin 6 (IL6) reflect plaque vulnerability and have been associated with sudden death in a cohort study but samples were drawn many years prior to the event. We sought to confirm this relationship by evaluating IL6 at the time of the sudden cardiac arrest (SCA) in a group of men and women in the community.

Hypothesis:
Elevated IL6 is a determinant of SCA in the community.

Methods:
In an ongoing, prospective, community-based study of SCA in Northwest US, we compared levels of plasma IL6 in 143 adult cases of adjudicated SCA and 149 gender- and age-matched controls with coronary artery disease (73 vs 73% male, age 64.0±11.9 vs. 64.2±11.6 y). Cases with cancer, non-cardiac causes of arrest, or terminal illnesses were excluded. Plasma was obtained from blood drawn at the time of arrest (cases) and at a routine visit (controls), and analyzed using Quantikine Immunoassay (CV <7.8%, normal range 0.4-8.9 pg/ml). IL6 levels were log transformed and compared (T-test and Chi-square test) per quartiles (based on controls). Logistic regression was used to predict the adjusted odds of SCA associated with IL6 levels (per increase in quartile).

Results:
IL6 was significantly higher in SCA cases vs controls (median 13.2 [IQR 5.4-25.8] vs 5.3 [1.5-4.6] pg/ml, P<0.0001). Cases and controls did not differ regarding BMI, smoking, diabetes or obesity (all P>0.05). Median CRP levels were below clinical levels of significance and similar between cases and controls (2.5 [1.0-5.4] vs 1.9 [1.0-6.2] ug/ml, P=0.56). In a logistic regression model IL6 was independently associated with increased risk of SCA (OR/increased quartile of IL6: 2.4, 95% CI 1.7 - 3.5, P<0.001) also after adjusting for other risk factors (Table).

Conclusions:
Elevated levels of IL6 in plasma are associated with SCA in this community-based study. Further evaluations are needed to elucidate the background of this finding and the potential role of this biomarker in risk stratification of SCA.
Abstract 204: Incidence Rate of Shockable Cardiac Arrest Varies Considerably Among Facilities
Authors: Kaneko Hiroshi , Hatanaka Tetsuo , Nagase Aki , Sakamoto Tetsuya , Marukawa Seishiro
Published: April 2024

Introduction: Despite wide proliferation of AEDs in public facilities in Japan, only ∼1% of patients with out-of-hospital cardiac arrest receive defibrillation attempts using on-site AEDs. In the decision-making process as to what specific facilities may merit the placement of on-site AEDs, each facility needs to estimate a site-specific incidence rate of cardiac arrest. We hypothesized that the incidence of cardiac arrest per person-year differs significantly across types of facilities.

Methods: Locations of cardiac arrest from 2003 through 2010 were abstracted from the database of the Fire Department of Nagoya City (population of 2.2 million; ∼2,000 cardiac arrests annually). The locations of cardiac arrests were tallied and grouped into 36 facility categories consistent with the Fire Service Act, and the number of cardiac arrests within each category was determined. Data on the number of visitors/workers/residents for each category were obtained from governmental databases and annual financial reports. The incidence rate was calculated as the number of cardiac arrest per 1 billion person-years.

Results: In 18 facility categories, the database for cardiac arrest and the database for numbers of visitors/workers/residents coincided in the categorization rules. For each of the categories, the incidence rate of cardiac arrest with initial shockable rhythm was calculated (the top 7 categories are shown in the table).

Conclusions: The incidence rate of shockable cardiac arrest varies considerably among facilities. Such variation in the incidence rate may reflect divergence among facilities in terms of characteristics of visitors/workers/residents, average duration of stay, intensity of physical or emotional activities, etc. These incidence rates, combined with the expected numbers of visitors/workers/residents, may be used to estimate anticipated numbers of shockable cardiac arrests per facility and the need for placing on-site AEDs.
Abstract 208: Innovative Web-Based e-Registry Enhances Survival After Out-of-Hospital Cardiac Arrest
Authors: Ko Patrick Chow-In , Chiang Wen-Chu , Chiu Allen Wen-Hsiang , Lin Chi-Hung , Lin Hsien-Tang , Chen Qing-Mei , Xiong Guang-Hua , Hsiao Ying-Wen , Ma Matthew Heui-Ming
Published: April 2024

Introduction:

Patient and prehospital predictors of survival after OHCA include ventricular fibrillation, witnessed arrest, and receiving bystander cardiopulmonary resuscitation. Whether systems-based approaches on Emergency Medical Service (EMS) such as new registry or reform could improve survival have not been well studied.

Hypothesis:

An innovative web-based e-registry may enhance survival after OHCA.

Methods:

An urban EMS with 2.62 million residents in 272 squared km was studied. Traditionally the EMS operated an OHCA Registry by manual-traced paper archives that coordinated data collections across dispatch center, ambulance teams and receiving hospitals. After a 2-year redesign, a computerized Web e-Registry in 2010 was established. The ambulance team initiated an individual patient data block right after an OHCA event, and that data block was immediately pushed to the customized webpage of receiving hospital so that they could easily upload patient outcomes anytime online, and periodically update patient status to the Web system. Health Bureau tracked the compliance with data uploading among receiving hospitals. Fire Department staff reviewed and uploaded prehospital and defibrillator data to the Web. The outcomes of 2-hour sustained return of spontaneous circulation (2hr ROSC), survival to discharge, and favorable Cerebral Performance Category 1 and 2 at discharge (fCPC), and data-missing rate for 4 years before the e-Registry (n=7,499) were compared to those 1 year after (n=1,777).

Results:

After e-Registry, for arrest of shockable rhythm, fCPC increased by 9.5% (95% CI: 4.2-16.1%); for non-shockable arrest, 2hr ROSC (4.2%, 95% CI: 1.4-7.1%) and fCPC (0.7%, 95% CI: 0.2-1.4%) increased significantly. After adjusting for patient and EMS variables, e-Registry was associated with fCPC (adjusted odds ratio: 1.9, 95% CI: 1.1-3.6) for shockable arrest, 2hr ROSC (adjusted OR: 1.2, 95% CI: 1.1-1.4) and fCPC (adjusted OR: 2.3, 95% CI: 1.1-5.1) for non-shockable arrest. Outcomes data-missing rate was significantly reduced by 5.3% (95% CI: 2.8-7.9%).

Conclusions:

Compared to paper archives, systems-based intervention by launching web-based e-registry may enhance favorable CPC after OHCA and reduce outcomes data-missing rate.
Abstract 245: Clinical Use of Miniaturized Chest Compressor for Cardiopulmonary Resuscitation
Authors: Wang Xiuhua , Zhang Chao , Chen Wei
Published: April 2024

Introduction: During cardiopulmonary resuscitation (CPR), high quality chest compression is the most important factor for successful resuscitation. In the present study, we investigated the effectiveness of a mechanical miniaturized chest compressor (MCC) on successful resuscitation in human patients.

Hypothesis: We hypothesized that MCC is safe and equally as effective for CPR when compared with conventional manual chest compression.

Methods: This is a retrospective study comparing the effectiveness of MCC between 2 separate cohorts of patients. From May 2011 - April 2012, MCC was used in all out of hospital cardiac arrest (CA) patients brought to our emergency room, except those who were 18 years old or under and patients of trauma and terminal stage diseases. A total of 25 patients were included in MCC group. Another 22 patients with similar conditions received conventional manual chest compression from May 2010 - April 2011 that were included as the control group. MCC device was used with a fixed compression rate of 100/min and compression depth between 3.8 and 5 cm. Manual chest compression was performed based on the current CPR guidelines. ACLS guideline procedures were followed in all patients. The protocol was continued until successful resuscitation or for a total of 30 mins. Successful resuscitation was defined as return of spontaneous circulation with blood pressure > 90/60 mmHg for more than 30 mins.

Results: Mean age, gender and duration from CA to CPR did not differ significantly between MCC and manual groups. The success of resuscitation was numerically greater in MCC group when compared with the manual group (Table). There was no single incidence of rib fracture in patients treated with MCC.

Conclusion: MCC is safe and as effective as manual chest compression. It may, therefore, provide a new option for CPR.
Abstract 252: Critical Incident Debriefing After Cardiopulmonary Resuscitation in Pediatric Cardiac ICU: Effect on Patient Safety, Performance Improvement and Survey
Authors: Kane Janie , Swearingen Christopher , Dyamenahalli Umesh
Published: April 2024

Background:
Critical incident debriefing has been established in many industries, including healthcare. To our knowledge, there have not been any published data about debriefing in the pediatric cardiac ICU (PCICU) setting.

Objective:
The goal of this initiative was to test the feasibility of debriefing and to establish a multidisciplinary team process after CPR for the purpose of improvements.

Methods:
This qualitative process as part of rapid cycle improvement was initiated as a method to improve patient management, and included assimilation of pertinent information, provision of immediate team feedback, safety and system improvement. After every CPR, we involved frontline staff in an informative, non-punitive, continuous quality improvement process. Debriefings lasting 10 to 15 minutes were led by the attending physicians. Issues related to communication, response time, effectiveness of the resuscitation, and support of family members was included. Participants were encouraged to express concerns and questions related to pre-code and code events to improve patient management and enhance unit safety culture. A survey of team members assessed effectiveness of the debriefing process using REDCap web application.

Results:
From 2008 to 2011, 68/71 consecutive debriefings were performed. As a result, there have been several rapid cycle improvements in patient care, including preventative and anticipatory patient management, timely notification of team members, comprehensive team training via simulation training, restructuring of supply availability, family support during acute events and hospital-wide revision of the code record. One hundred twenty-three PCICU personnel were invited to complete the survey. Sixty [49%] responses were received: 100% from patient care nurse managers, 36%bedside nurses, 50% APNs, 63%physicians and 100%respiratory therapists. The beneficial aspects of the debriefing included the examination of opportunities to improve (88%), asking questions, reviewing performance (85%), and receiving education (80%).

Conclusion:
Clinical debriefing in a PCICU is feasible. It positively affected the quality of patient care, enhanced the safety culture, improved occurrence reporting, and staff felt empowered.
Abstract 253: Accuracy of Detecting Chest Compression Rate from the Thoracic Impedance Data Recorded Through Chest Pads
Authors: Firoozabadi Reza , Helfenbein Eric , Babaeizadeh Saeed
Published: April 2024

Background

To assist healthcare providers in performing quality CPR, devices such as Q-CPR
TM
measurement and feedback tool can be used with defibrillators. However, such devices are not always present, but almost every defibrillator records impedance signal through chest pads. Therefore, being able to detect the chest compression (CC) rate from the thoracic impedance signal in real-time can be valuable in practice. The real-time rate, for example, can be used to provide feedback to the rescuer or to remove compression artifact from ECG during CPR to shorten the time between last compression and the defibrillation shock.

Objective

To detect the chest compression rate from thoracic impedance signal and compare it to the true rate from compression signal.

Methods

Recordings of 175 out of hospital cardiac arrest (OHCA) patients older than 18 years were used. The database was collected using Laerdal HeartStart 4000 defibrillators in 6 ambulances in 3 European regions between March 2002 and October 2003 for prospective study of OHCA patients. The defibrillators had an extra chest pad mounted on the lower part of the sternum with an accelerometer and a pressure sensor to record the compression signal which by analyzing it the true compression rate was determined. The thoracic impedance signal from the chest pads was also recorded and analyzed to calculate the compression rate.

Results

At the end of each 10-second segment of the data the compression rate was calculated from the thoracic impedance and was compared to the true rate in the same interval. The difference between the true and calculated rate was 2±13 compression per minute (cpm). For 95% of the data segments the difference was lower than 20 cpm, and only 9% of the segments had a rate difference larger than 10 cpm.

Conclusion

In the absence of CPR measurement and feedback tools, it is possible to accurately detect the chest compression rate using only the thoracic impedance signal which is usually recorded through the defibrillator chest pads. This can potentially be used as a software-only CPR feedback tool to help improve the quality of CPR delivery. However, unlike devices such as Q-CPR
TM
, this method does not give any feedback on the compression depth or ventilation volume and rate.
Abstract 256: Novel Universal Field Termination-of-Resuscitation Decision Rules for Predicting Nonsurvivors After Refractory Out-of-Hospital Cardiac Arrest
Authors: Goto Yoshikazu , Maeda Tetsuo , Goto Yumiko , Ohta Keisuke
Published: April 2024

Introduction
: Pre-hospital termination-of-resuscitation (TOR) decision rules have been introduced for emergency medical services personnel to identify non-survivors after refractory out-of-hospital cardiac arrest (OHCA) according to their life support care levels.

Hypothesis
: We assessed the hypothesis that our newly developed universal TOR rules for mixed levels of providers can predict non-survivors with an appropriate positive predictive value (PPV).

Methods
: We analyzed 495607 OHCA adult patients with all causes, using a prospectively recorded nationwide Utstein-style database in Japan over 5 years (2005-2009). Main outcome measures were specificity and PPV of newly developed TOR rules for predicting 1-month survival with unfavorable neurological outcome (cerebral performance category = 3-5). Secondary outcome measures were specificity and PPV of new rules for predicting 1-month death. We developed new TOR rules using data from 4 years (2005-2008,
n
= 390577), with validation using external data from 2009 (
n
= 105030).

Results
: Multivariate logistic regression analysis showed that no return of spontaneous circulation had the strongest association with outcome (odds ratio [OR] 38.3; 95% confidence interval [CI] 35.9-41.0). Unshockable initial rhythm (OR 3.38; 95%CI 2.98-3.84) and witnessed by bystanders (OR 2.01; 95%CI 1.87-2.17) were also independently associated with neurological outcomes. Three variables were incorporated into new TOR rules. New rules showed 0.939 specificity (95%CI 0.933-0.945) and 0.998 PPV (95%CI 0.998-0.999) for identifying survivors with unfavorable outcome, and had a c-statistic of 0.922. The specificity, PPV, and c-statistic for external validation data were 0.966 (95%CI 0.958-0.973), 0.999 (95%CI 0.999-0.999), and 0.942, respectively. The specificity and PPV in developing group for predicting 1-month death were 0.875 (95%CI 0.870-0.881) and 0.992 (95%CI 0.991-0.992), respectively, and those in validation group were 0.903 (95%CI 0.894-0.911) and 0.993 (95%CI 0.992-0.993), respectively.

Conclusions
: Novel developed universal field TOR decision rules for mixed levels of providers can predict non-survivors after refractory out-of-hospital cardiac arrest with appropriate PPV.