bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18430: Human Molecular Genetic and Functional Studies Identify TRIM63, Encoding Muscle RING Finger Protein 1, as a Novel Gene for Human Hypertrophic Cardiomyopathy
Authors: Chen Suet Nee , Czernuszewicz Grazyna , Lombardi Raffaella , Jin Jianping , Willerson James , Marian Ali J
Published: April 2024

Rationale: A delicate balance between protein synthesis and degradation maintains cardiac size and function. TRIM63 encoding Muscle RING Finger 1 (MuRF1) maintains muscle protein homeostasis by tagging the sarcomere proteins with ubiquitin for subsequent degradation by the Ubiquitin-Proteasome System (UPS).

Objectives:
To determine the pathogenic role of TRIM63 in human hypertrophic cardiomyopathy (HCM).

Methods and Results:
Sequencing of TRIM63 gene in 302 HCM probands (250 Caucasians) and 339 controls (262 Caucasians) led to identification of two missense (p.A48V and p.I130M) and a deletion (p.Q247X) variants exclusively in the HCM probands. These three variants were absent in 751 additional controls screened by TaqMan assays. Likewise, rare variants were enriched in the Caucasian HCM population (11/250, 4.4% vs. 3/262, 1.1%, respectively, p=0.024). Expression of the mutant TRIM63 was associated with mislocalization of TRIM63 to sarcomere Z disks, impaired auto-ubiquitination, reduced ubiquitinylation and UPS-mediated degradation of myosin heavy chain 6, cardiac myosin binding protein C, calcineurin (PPP3CB), and p-mTOR in adult cardiac myocytes. Induced expression of the mutant TRIM63 in the mouse heart was associated with cardiac hypertrophy, activation of the mTOR-S6K and calcineurin pathways and expression of the hypertrophic markers, which were normalized upon turning off expression of the mutant protein.

Conclusions:
TRIM63 mutations, identified in patients with HCM, impart loss-of-function effects on E3 ligase activity and are likely causal mutations in HCM. The findings implicate impaired protein degradation in the pathogenesis of HCM.
Abstract 18437: B-type Natriuretic Peptide and Subclinical Atherosclerosis in Healthy Population
Authors: Mizuno Yoshiko , Suzuki Toru , Kohro Takahide , Iimuro Satoshi , Yamazaki Tsutomu
Published: April 2024

Background:
B-type natriuretic peptide (BNP) is associated with both coronary artery calcium, a marker of subclinical atherosclerosis, as well as myocardial ischemia and cardiac events. We examined the correlation of BNP with carotid intima-media thickness (IMT) in healthy asymptomatic population.

Methods:
The population of this study included 425 asymptomatic subjects (mean age 61 years, 53% male) free of cardiovascular disease who underwent IMT measurements by high-resolution carotid duplex Doppler studies. BNP levels were measured using the immune enzymometric assay (E test TOSOH II assay kit TOSHO, Japan). To reduce skewness, BNP levels were log transformed before regression analyses. Multivariate regression analyses adjusted for age, sex, smoking, blood pressure, eGFR, and other cardiovascular risk factors were performed. IMT was also categorized into two groups, increased and normal IMT, according to the age-modified IMT criteria. After the categorization, Student's t test was applied to evaluate the correlation between BNP and IMT.

Results:
In our study population, there were no significant differences in BNP levels between the two IMT categories. However, higher levels of BNP was observed amongst female subjects with increased IMT (BNP=27.25±1.36mm vs. 19.31±3.02mm for increased IMT vs. normal IMT, p=0.0171). Although there was no statistical difference in the levels of IMT between the sex (male 1.71±0.03pg/ml vs. female 1.61±0.03pg/ml, p=0.0595), higher IMT remained independently associated with higher BNP in female subjects. In multivariate models, log BNP (p=0.0302) was the second greatest estimator of IMT in females, while age (p=0.0002) and blood pressure (p=0.0314) were also statistically significant estimators. BNP, however, did not show any significant impact on IMT in males.

Conclusions:
Elevated BNP identifies a substantially increased likelihood of IMT progression. Therefore, BNP may serve as a marker of subclinical atherosclerosis. However its utility may be limited to female subjects.
Abstract 18441: Adenosine-Free Functional Assessment of Coronary Stenosis Severity by Contrast-Induced Submaximal Hyperemia
Authors: Nolte Froukje , van de Hoef Tim P , de Klerk Wouter , Baan Jr. Jan , Lockie Tim P , Spaan Jos A , Piek Jan J , Siebes Maria
Published: April 2024

Background
Detection of clinically significant stenoses by fractional flow reserve (FFR) or hyperemic stenosis resistance (HSR) requires maximal vasodilation, which varies with the amount of adenosine (ADO) given. However, the hemodynamic effect of a coronary artery stenosis is uniquely determined by its quadratic pressure gradient-velocity (ΔP-
v
) relationship over a range of physiological flow velocities.

Hypothesis
Functional stenosis severity can be defined from the ΔP-
v
relationship in terms of the mean pressure gradient at a fixed submaximal velocity (dP
v
). Since contrast medium (CM) induces reactive hyperemia, it provides a convenient means to increase flow for this purpose.

Methods
In 64 patients, aortic pressure (P
a
) and intracoronary pressure (P
d
) and
v
distal to an intermediate stenosis were recorded throughout the response to an i.c. ADO injection (30-60 µg). The curve fit (ΔP=A
v
+B
v
2
) of each ΔP-v relationship was used to obtain the mean dP
v
at 20, 25, 30, and 40 cm/s. Ischemic cut-off values for each dP
v
were defined with respect to FFR (=P
d
/P
a
) <0.75 and HSR (=ΔP/
v
) >0.80 mmHg/cm/s. The dP
v
with the least discordance was used to assess diagnostic performance. Measurements were repeated after i.c. CM injection (3 ml) in 20 patients. Similarity between ADO and CM-derived ΔP-
v
relationships was evaluated by comparing the dP
v
at all fixed velocities.

Results
ADO-based FFR ranged from 0.27 to 0.97 and HSR from 0.08 to 9.12 mmHg/cm/s. Maximal
v
after CM was 17 ± 16% lower (p<0.01) and P
d
was 9 ± 11% higher (p<0.001) compared to ADO. Corresponding ADO and CM ΔP-v relationships showed good agreement; no significant differences were found for dP
v
at any of the tested velocities. Diagnostic performance was highest for dP
v
at a velocity of 25 cm/s (dP
v25
), with a cut-off >15.8 mmHg. Sensitivity, specificity, and accuracy compared to FFR were 84%, 92% and 87% for ADO and 88%, 92% and 90% for CM-based dP
v25
, respectively. Sensitivity, specificity and accuracy

were 100% compared to HSR for both ADO and CM-based dP
v25
.

Conclusion
dP
v25
is a promising new index of functional stenosis severity that is based on stenosis hemodynamics and yields a high diagnostic accuracy. This index can be obtained from CM injections and obviates problems associated with the use of adenosine.
Abstract 18466: Anemia is Associated with an Adverse Outcome in Patients with Atrial Fibrillation: Insights Form the Re-ly Trial
Authors: Westenbrink B. Daan , Alings Marco , Connolly Stuart , Eikelboom John , Ezekowitz Michael D , Oldgren Jonas , Yang Sean , Pogue Janice , Yusuf Salim , Wallentin Lars , van Gilst Wiek H
Published: April 2024

Background:
Anemia may predispose to cardiovascular events. While patients with atrial fibrillation (AF) may be particularly prone to anemia, the impact of anemia on outcome in patients with AF is unclear.

Methods:
We retrospectively analyzed the RE-LY trial that randomized 18,113 patients with AF to receive dabigatran or warfarin for a median follow-up of 2 years.The association between anemia (Hb <13.0 g/dL in men and <12.0 g/dL in women) and the incidence of cardiovascular and bleeding events was assessed with multivariable Cox regression analysis.

Results:
Anemia was present in 12% of the population at baseline and the presence of anemia was associated with an increased incidence of all cause mortality or myocardial infarction (adjusted hazard ratio (adj. HR) 1.50, 95% confidence interval (CI) 1.32-1.71). Anemia was also associated with an increased incidence of the primary RE-LY endpoints of stroke or systemic embolism (adj. HR 1.41 95% CI (1.12-1.78)) and major bleeding (adj. HR 2.14, 95% CI 1.87-2.46). The association between anemia and outcome did not differ according to major cardiovascular comorbidities, treatment allocation or prior use of warfarin. After 6 months, anemia had resolved in 35% of anemic patients, while anemia had developed in 10% of patients without prior anemia. Resolution of anemia was associated with a more favorable outcome than sustained anemia (adj HR. 0.71, 95%CI 0.97-0.52), or new onset anemia (adj HR. 0.68, 95%CI 0.50-0.93)

Conclusions:
Anemia is associated with an increased risk of cardiovascular events and bleeding complications in patients with AF. Accordingly, resolution of anemia is associated with a more favourable outcome than sustained anemia.
Abstract 18474: Risk Factors for Long Term Morbidity After Pediatric Heart Retransplantation : Analysis from the International Society of Heart and Lung Transplantation Registry
Authors: Conway Jennifer , Edwards Leah B , McCrindle Brian W , Kirk Richard , Manlhiot Cedric , Dipchand Anne I
Published: April 2024

Recent detailed analysis of the ISHLT registry has shown that retransplantation [ReTx] following pediatric primary heart transplantation [PTx] has inferior outcomes. Little is known about long-term morbidities following ReTx. Data from the ISHLT registry (1998-2010) were used to examine risk factors for long-term morbidities in all ReTx patients with a PTx at age < 18 y. 9,966 transplants were reviewed: 9,248 PTx, 602 first ReTx and 32 second ReTx. Long term morbidities were significantly (p<0.001) more common after ReTx than PTx including allograft vasculopathy [AV] (HR 2.8), late rejection (HR 2.0) and late renal dysfunction (HR 2.6); but not PTLD (HR 1.2, p=0.52). Factors associated with development of AV after ReTx included history of hypertension [HTN] pre-ReTx (HR 1.8, p=0.003), AV as the indication for ReTx (HR 1.96, p=0.003) , donor factors including HTN (HR 5.7, p=0.001) , diabetes (HR 5.7, p=0.005), cocaine use (HR 2.6, p=0.02), male donor to female recipient (HR 1.5, p=0.02); and post-ReTx factors including renal dysfunction (HR 1.8, p=0.002), hospitalization for infection (HR 2.7, p=0.04) and drug treated HTN (HR 1.6, p=0.05). Risk for late rejection after ReTx included CMV+ serology pre-ReTx (HR 1.7, p=0.03), donor CMV+ serology (HR 1.8, p=0.007), early rejection post-ReTx (HR 1.6, p=0.03), documented non-compliance (HR 3.6, p<0.001), and later year of ReTx (HR 1.3, p<0.001). Risk factors for late renal dysfunction included higher pre-ReTx creatinine (HR 1.3, p<0.001), later year of ReTx (HR 1.1, p<0.001), dialysis post-ReTx (HR 4.0, p<0.001), drug treated HTN in follow-up (HR 3.4, p<0.001), development of AV (HR 1.7, p=0.003) and hospitalization for infection (HR 4.1, p=0.008). In a multivariate model, no associations were found between duration of PTx (e.g. cumulative health burden) and any of the ReTx morbidities. ReTx following PTx in the pediatric age range is associated not only with inferior outcomes but also with a significant risk of long term morbidities. Further study of the key risk factors identified may help in patient and donor selection for ReTx with the goal to improve outcomes.
Abstract 18475: Association of Plasma Omega-3 to Omega-6 Polyunsaturated Fatty Acid Ratio with Apical Ballooning Syndrome (Tako-Tsubo cardiomyopathy -TTC)
Authors: Katoh Youichi , Nagamine Sho , Wada Takeshi , Isogai Hiroyuki , Yuu Hiroshige , Ozaki Dai , Shimai Ryota , Yamase Miki , Yaginuma Kenji , Yokoyama Ken , Oigawa Tetsuya , Enjyoji Toshihisa , Nakazato Yuji
Published: April 2024

Background:
Eicosapentaenoic acid (EPA) of the omega-3 polyunsaturated fatty acids (ω-3 PUFA) family plays important roles in the prevention of cardiovascular disease (CVD), while arachidonic acid (AA) of the ω-6 PUFA family promotes inflammatory and prothrombotic influences. Tako-Tsubo cardiomyopathy (TTC, also reffered as apical balloning syndrome) is a heart syndrome associated with transient myocardial contractile dysfunction. Decreased endothelial function in response to acute mental stress has been reported in patients with a prior episode of TTC. However, the pathogenesis of TTC remains unclear and the relationship between TTC and EPA/AA ratio has not been elucidated.

Methods and Results:
This study consisted of 10 consecutive patients with clinically diagnosed TTC. The aim of this study was to investigate the association between the plasma EPA/AA ratio and the early stage of clinically diagnosed TTC. To examine the plasma fatty acid level, blood samples were obtained from control, old myocardial infarction, and clinically diagnosed TTC patients. A clinically diagnosed TTC patients revealed a lower plasma EPA/AA ratio [Control patients, 0.58 (n=18) vs Old myocardial infarction patients, 0.38 (n=22) vs TTC patients, 0.15 (n=10), p=0.011]. High-sensitivity CRP levels and a low plasma EPA/AA ratio could independently predict the prevalence of TTC on multivariate logistic regression analysis [odds ratio 1.83 (95%CI 1.03-3.25), p=0.036 and odds ratio 2.05 (95%CI 1.12-3.92), p=0.02)].

Conclusion:
In patients with TTC, a low plasma EPA/AA ratio was significantly associated with the early stage of clinically diagnosed TTC. The findings implicate lower EPA/AA ratio and the following endothelial dysfunction as a potential mechanism involved in the pathogenesis of this unique cardiomyopathy.
Abstract 18481: Genetic Polymorphisms Associated with Response to Intraoperative Heparin Anticoagulation and Thrombosis Risk in Pediatric Patients Undergoing Cardiac Surgery
Authors: Manlhiot Cedric , Mital Seema , Gruenwald Colleen E , Brandao Leonardo R , Manickaraj Ashok K , Caldarone Christopher A , Russell Jennifer L , Sivarajan VB , Schwartz Steven M , Holtby Helen M , McCrindle Brian W
Published: April 2024

Introduction:
Thrombosis is an important and widespread post-operative complication of pediatric cardiac surgery. Prophylaxis intraoperative anticoagulation in this context is obtained by using heparin which requires a bond with antithrombin to achieve anticoagulant effect. We sought to identify SNPs associated with blood antithrombin levels, response to heparin and post-operative thrombosis risk in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass (CPB).

Methods:
A total of 625 cardiac operations with CPB in 383 patients were reviewed. Ninety-six SNPs on 53 genes in the coagulation/fibrinolysis pathways were assayed using the the Illumina GoldenGate custom SNP panel. Genotyping was successful for >99% of SNPs. Regression models adjusted for repeated measures and bootstrap resampling (1,000 samples) were used to offset multiple comparisons bias; SNPs with very low minor allele frequencies were excluded.

Results:
Average preoperative antithrombin activity was 89±18% (normal 100%, adjusted for age and oxygen saturation) and average response to heparin was 1.0±0.3U/ml/100U/kg (blood heparin concentration achieved per 100U/kg of heparin). Post-operative thrombosis was observed after 86 operations (14%) (within 30 days of surgery, risk-adjusted according to a previously published model of post-operative thrombosis risk). SNPs associated with higher antithrombin levels, lower heparin response and higher postoperative thrombosis are listed in the Table.

Conclusions:
Polymorphisms in genes in the coagulation and fibrinolytic systems activity were associated with antithrombin levels, response to heparin and risk of post-operative thrombosis. The association of individual SNPs at the laboratory and clinical levels suggest a mechanism for upstream alteration in the coagulation system that is correlated with undesirable clinical outcome and could be the target for genetically tailored clinical interventions.
Abstract 18485: Relationship Among Pathologic Changes in Patients with Myxomatous Degeneration: Insights from In Vivo Measurement of Mitral Leaflet Geometry Using 3D TEE Data
Authors: Jang Jeong Yoon , Song Jae-Kwan , Jun Dong-Hwan , Kwon Chang Hee , Park Yong Kyu , Sun Byung Joo , Kim Dae Hee , Song Jong-Min , Kang Duk-Hyun
Published: April 2024

Background:
Although pathologic and imaging studies showed mitral valve leaflet elongation, chordal elongation and rupture (CR), and annular dilatation in patients with myxomatous degeneration (MD), in vivo quantitative analysis of these anatomical changes and their potential relationship has not been reported.

Methods:
3D full volume data were obtained during TEE in 20 healthy subjects and 40 patients with severe mitral regurgitation (MR) due to MD confined to a single scallop in posterior mitral leaflet. A customized software (Omni4D) was used to evaluate mitral valve geometry.

Results:
Twenty one patients had typical prolapse without CR, whereas 19 had flail leaflet with CR. Compared to controls, these patients with MD and severe MR showed larger annular area (AA) and total and individual leaflet surface area (LSA) with smaller anterior/posterior LSA. There was no difference in MR severity, AA, total and individual LSA. Positive correlation was observed between LSA and annular area in both controls and patients with MD. Although correlation between posterior LSA and AA was stronger than that between anterior LSA and AA in patients with MD, there was no difference in controls.

Conclusions:
Different mechanisms seem to be associated with leaflet elongation in prolapsing and non-prolapsing mitral leaflet and increase in AA and LSA was not different in patients with and those without CR.
Abstract 18489: Abnormal Coronary Findings on Non-Invasive Computed Tomography Coronary Angiography in Adult Patients with Transposition of the Great Arteries Corrected by Arterial Switch Operation
Authors: Veltman Caroline E. , Beeres Saskia L. M. A. , Kalkman Deborah N. , Hazekamp Mark G. , Bax Jeroen J. , Kroft Lucia J. , Kies Philippine , van der Wall Ernst E. , Schalij Martin J. , Scholte Arthur J. H. A. , Vliegen Hubert W. , Jongbloed Monique R. M.
Published: April 2024

Purpose:
Early mortality and long-term outcome in patients with congenital transposition of the great arteries (TGA) corrected by arterial switch operation (ASO) mainly depend on the perfusion of the myocardium provided by the transferred coronary circulation. This study aimed to assess the prevalence of potential unfavorable coronary findings in adult patients after ASO using non-invasive computed tomography coronary angiography (CTA).

Methods:
The study population consisted of 30 adult patients after ASO (22 male, 22±3 yrs.) referred for non-invasive evaluation of the coronary anatomy by CTA. First, the post-operative coronary anatomy pattern was described using the classification of Gittenberger-de Groot. Furthermore, all scans were reviewed on the presence of (1) significant coronary stenosis, defined as ≥50% luminal narrowing, (2) an inter-arterial coronary course, and (3) an acute angled coronary origin.

Results:
A post-operative anatomy patterns of 1R-2LCx was observed in 24 patients (80%), 1RCx-2L in 5 patients (17%) and 2RLCx in 1 patient (3%). A total of 13 patients (43%) had abnormal coronary findings of which 1 patient (3%) had a significant stenosis in the proximal LAD, 5 patients (17%) had an inter-arterial coronary course (case examples in Figure 1) and 7 patients (23%) had an acute angled coronary origin. All 16 patients with a normal CT results had a post-operative coronary pattern of 1R-2LCx, whereas this pattern was only observed in 8/14 (57%) patients with abnormal coronary findings on CTA (P<0.005).

Conclusions:
The current study demonstrated that abnormal coronary findings are frequently observed in adult patients with TGA corrected by ASO. Moreover, a significant association between the coronary anatomy and the presence of coronary abnormalities on CTA was observed, indicating that patients with a post-operative coronary anatomy pattern other than 1R-2LCx may be at higher risk to have potential malignant coronary findings on CTA.
Abstract 18505: High-sensitive Troponin T Levels Independently Predict Survival in TAVI Patients
Authors: Frank Derk , Stark Sophia , Lutz Matthias , Weissbrodt Anne , Freitag-Wolf Sandra , Petzina Rainer , Rosenberg Mark , Lutter Georg , Frey Norbert
Published: April 2024

TAVI (transcatheter aortic valve implantation) has become a valuable therapeutic tool in the treatment of inoperable or high risk patients with severe aortic stenosis. Several risk scores have been proposed to estimate the perioperative and long-term risk of patients undergoing TAVI. However, exact estimation of perioperative and long term risk remains difficult. We thus sought to investigate whether biomarkers may improve risk stratification in this setting. We included 111 consecutive patients undergoing TAVI (using Edwards Sapien and Sapien XT prostheses) at our institution from February 2011 until May 2012. 109 patients were available for complete follow up. 61% were females, mean age was 80.6 years (+/- 11.0 years), 55% were treated via transfemoral access. Since elevated troponin T levels have been associated with adverse outcome in various forms of cardiac disease, high sensitive troponin T (hsTNT) values and other parameters were measured a day before TAVI (baseline) and 1, 3, and 7 days post-procedure. Mean EF was 48.3% (+/- 10.3%) and mean logistic Euroscore 20.8% (+/- 13.1%). Mean follow-up was 163 days (+/-144 days), The primary endpoint was all-cause mortality and a total of 18 deaths (16.51%) occurred. 30 day mortality was 6.4% (7/109). Median baseline hsTNT values were 22.7 ng/ml with an interquartile range (IQR) of 12-47 ng/ml. Cox regression analyses including age, sex, procedural access site, NYHA class, renal function [creatinine], NTproBNP, STS score, and logistic Euroscore revealed only baseline hsTNT (HR for upper quartile 6.32 vs. quartiles 1-3, CI 2.15-18.55, p=0.001) and the baseline creatinine level (HR=1.89 per quartile, CI 1.02-3.48, p=0.043) as independent prognostic parameters for cumulative mortality. At 72 hours post-TAVI, hsTNT increased to a median of 178 ng/ml, IQR 88.7-361.52 ng/ml. hsTNT levels at day 3 were associated with adverse outcome, but did not offer additional prognostic information when compared to preprocedural hsTNT levels. However, the individual raise in hsTNT at day 3 is associated with the incidence of cumulative death (p=0.034). In conclusion, elevated hsTNT the day before TAVI is an independent risk predictor of all-cause death in TAVI patients.
Abstract 18543: Impaired Coronary Metabolic Dilation Leads to Heart Failure During Pressure Overload
Authors: Ohanyan Vahagn A , Luther Dan , Kolz Christopher , Logan Suzanna , Enrick Molly , Stevanov Kelly , Yin Liya , Chilian William
Published: April 2024

The coupling of myocardial blood flow to cardiac work (metabolic dilation) is critical for proper cardiac function. If this coupling is altered, the imbalance could lead micro-areas of hypoxia, ischemia, and fibrosis culminating in heart failure. Accordingly we hypothesized, that when subjected to an extreme metabolic challenge (pressure overload), insufficient dilation of the coronary circulation leads to micro-areas of ischemia and infarction (diffuse fibrosis) and compromised cardiac function. To test this, we studied cardiac function and pathology in Wild Type (WT) and Kv1.5
-/-
mice, which have impaired metabolic dilation. To impose a metabolic challenge, transaortic constriction (TAC) was done in Kv1.5
-/-
male (n=12), female (n=12) and WT (n=12) mice. TAC increased mean aortic pressure from 98±5 to 142±8 mmHg. Transthoracic echocardiography was performed for evaluation of cardiac function at 7, 28 days after TAC. Masson’s Trichrome and Hypoxyprobe (HP) staining was done at day 28 for evaluation myocardial fibrosis and areas of hypoxia, respectively. After TAC survival rate of Kv 1.5
-/-
females was lower (P<0.05) than in males and WT (Panel A). Ejection fraction (EF) was lower (P<0.05) in Kv1.5
-/-
(male and female) than WT at all times after TAC (Panel B). In WT, EF was decreased 7 days after TAC, but the reduction was moderate compared to Kv 1.5
-/-
. After 28 days of TAC, myocardial fibrosis was markedly higher in Kv1.5
-/-
compared to WT (Panel C). In Kv1.5
-/-
, fibrosis was in endocardial and perivascular regions, but in WT it was transmural and less developed. HP and DAPI (to locate nuclei) revealed that the number of cells positive for hypoxyprobe was 222% greater in Kv1.5
-/-
than in WT, suggesting impaired oxygen delivery. Taken together, we conclude that the absence of Kv1.5 channels, which uncouples myocardial blood flow from cardiac work, compromises coronary and cardiac adaptations to TAC leading to diffuse ischemia, micro-areas of infarction and heart failure. .
Abstract 18591: Anatomically- Versus Clinically-derived Risk Scores Have Markedly Differing Predictive Abilities Following PCI For Multivessel CAD: The “TLR Paradox”
Authors: Kovacic Jason C , Limaye Atul M , Gukathasan Nilusha , Sartori Samantha , Lee Paul , Trost Biana , Narechania Birju , Roy Swathi , Sayeneni Swapna , Kim Michael C , Moreno Pedro Moreno , Baber Usman , Mehran Roxana , Dangas George , Kini Annapoorna S , Sharma Samin K
Published: April 2024

Objectives:
Risk scores for predicting events after PCI vary widely in their calculation, ranging from purely anatomical (SYNTAX risk score [SRS]) to purely clinical (ACEF, modified ACEF [ACEFmod], NCDR), while other scores combine both elements (Clinical SYNTAX score [CSS], New York State Risk Score [NYSRS]). We sought to clarify the utility of these scores for predicting clinical events in pts with triple vessel CAD undergoing PCI.

Methods:
Patients with triple vessel and/or LM disease with 12 month follow-up were studied from our single center PCI registry. Exclusion criteria included STEMI presentation, prior revascularization and shock. Clinical events at 12 months were compared to baseline risk scores, based on score tertiles and area under the receiver operating characteristic curves (AUC).

Results:
We identified 584 eligible patients (69.8±12.3yrs, 405 males). All scores were predictive of mortality, with the SRS being least predictive (AUC=0.66) (Figure). The most accurate scores for mortality were the CSS and ACEF (AUC=0.76 for both: p=0.019 and 0.08 vs. SRS, respectively). In contrast, the SRS and CSS were the only scores predictive of MI (both p<0.05). For TLR, while the SRS trended toward being positively predictive (p=0.075), several scores trended towards a negative association, which reached significance for the NCDR (p=0.045) (Figure). No score was particularly accurate for predicting MACE (death+MI+TLR), with AUCs ranging from 0.53 (NCDR) to 0.63 (SRS).

Conclusions:
Competing factors influence mortality, MI and TLR after PCI. An increasing burden of comorbidities is associated with mortality, but a paradoxically reduced likelihood of TLR. On the other hand, anatomical complexity predicts MI. By combining these outcomes to predict MACE, all scores show reduced utility.
Abstract 18595: Efficacy of Vorapaxar is not Modified by Thienopyridine Therapy: Results from TRA 2°P-TIMI 50 Trial
Authors: Bonaca Marc P , Scirica Benjamin M , Braunwald Eugene , White Harvey D , Aylward Philip E , Grande Peer , Murphy Sabina A , Morrow David A
Published: April 2024

Vorapaxar antagonizes the platelet protease-activated receptor (PAR)-1,the primary receptor for thrombin on human platelets. The addition of vorapaxar to standard therapy has been shown to reduce thrombotic events in patients with stable atherosclerosis. We investigated whether the efficacy and safety of vorapaxar in stable atherosclerosis were modified by thienopyridine therapy. METHODS: The TRA2P-TIMI 50 trial was a randomized, double-blind, placebo controlled trial of vorapaxar 2.5 mg daily in 26,449 patients with established atherosclerotic vascular disease. Patients were stratified at randomization based on planned use of thienopyridine therapy. The first efficacy endpoint was a composite of cardiovascular death (CVD), MI, or stroke and the primary safety endpoint was GUSTO moderate or severe bleeding. Analyses were adjusted for qualifying disease state (MI, stroke, PAD). Treatment with ASA ≤ 162 mg was recommended. RESULTS: Thienopyridine was planned in 15,356 (58%) and ASA was used in 24,734 (94%) overall. Patients randomized to vorapaxar had similar significant reductions in the primary endpoint regardless of planned thienopyridine therapy (Figure, p-interaction 0.64) and after adjustment for qualifying disease state (MI, stroke, PAD). Findings were similar when patients were stratified by actual thienopyridine use at baseline (Figure, p-interaction 0.76) and at 18 months (p-interaction 0.99). GUSTO moderate or severe bleeding was increased with vorapaxar with no significant interaction in those planned for thienopyridine therapy (p-interaction 0.29) or those receiving thienopyridines through 18 months (p-interaction 0.71). CONCLUSIONS: Vorapaxar reduced CVD, MI, or stroke in stable patients with a history of atherothrombotic events and this effect was present whether or not vorapaxar was used with a thienopyridine. The increased risk of bleeding with vorapaxar was also similar regardless of thienopyridine therapy.
Abstract 18597: How Accurate is the ‰Eyeball Test? A Comparison of Physicians' Subjective Assessment Versus Statistical Methods in Estimating Mortality Risk after Cardiac Surgery
Authors: Jain Renuka , Kuskowski Michael , Selcuk Adabag
Published: April 2024

Introduction:
In the era of increasing percutaneous options for ischemic and valvular heart disease, estimation of surgical risk has become a key factor in selecting optimal treatment strategies. Surgical risk has historically been estimated by physicians' subjective assessment and more recently by validated statistical risk scores. The aim of this study was to compare the performance of these two methods of risk estimation in cardiac surgery.

Methods:
We studied 5099 consecutive patients who underwent cardiac surgery at the Minneapolis VA Medical Center between 1993 and 2010. Perioperative mortality risk was estimated statistically by the national VA mortality risk score, and subjectively by cardiac surgeons. These surgeons were blinded to the statistical estimate. All estimates were recorded prior to surgery. Perioperative (30-day) and long-term mortality were ascertained.

Results:
Mean age was 65 +9 years and 75% of the pts underwent CABG only. Both methods overestimated mortality risk (Physician's estimate 5.6 + 4.4%; statistical estimate 4.3 + 5.1%; observed mortality 3.3%). Correlation between the two methods was modest (C = 0.56, P<0.01). Physician estimate was higher than the statistical estimate and observed mortality in all pts except those in the highest risk category (>10% mortality). Statistical estimate was significantly better than physician’s estimate in discriminating operative death vs. survival (C-index = 0.78 vs. 0.73; p=0.003) and in the long-term (C-index = 0.72 vs. 0.61; p<0.001) (Figure).

Conclusions:
In patients undergoing cardiac surgery, statistical risk estimate is a more accurate discriminator of operative and long-term mortality than physician’s subjective assessment. However, both methods generally overestimated observed mortality.
Abstract 18625: Preemptive Continuous Renal Replacement Therapy in Pediatric Cardiac Patients Requiring Extracorporeal Support is Associated with Increased Mortality
Authors: Wolf Michael J , Chanani Nikhil K , Heard Micheal L , Mahle William T
Published: April 2024

Objective:
Acute kidney injury (AKI) is a common co-morbidity for children placed on ECMO because of primary cardiac disease; AKI can impact both length of ECMO support and adversely affect clinical outcomes. Continuous veno-venous hemofiltration (CVVH) is thought to optimize fluid status and lessen inflammatory response during pediatric ECMO support, leading some centers to use it as a standard adjunct to ECMO support. However, published data are derived primarily from the children without primary cardiac disease. Therefore, we reviewed our experience for pediatric cardiac patients receiving CVVH while on ECMO support.

Methods:
A retrospective analysis of the Children's Healthcare of Atlanta CICU ECMO database from 2002-2011 was performed. In order to limit the bias that CVVH would be instituted only after evidence of end-organ injury, we considered “pre-emptive CVVH” to be CVVH instituted with 48 hours of ECMO initiation. Multivariate logistic regression was undertaken to adjust for covariates.

Results:
Of 153 total cardiac ECMO patients, 59 (39%) received CVVH at the discretion of the attending physician. The time from ECMO initiation to CVVH initiation was 1.7 ± 2.9 days (median 1 day). Pre- and post-ECMO serum creatinine levels were similar between patients on ECMO who received CVVH with those that did not receive CVVH. However, peak serum creatinine was 1.1 ± 0.4 mg/dL (median 1.0 mg/dL) in the CVVH group and 0.9 ± 0.4 mg/dL (median 0.8 mg/dL) in the non CVVH group (p=0.003). Patients on ECMO who received CVVH had a higher mortality (p<0.0001), were less likely to have had ECPR (p=0.004), and had a longer duration on ECMO (p<0.0001). In multivariate analysis subjects receiving CVVH support within 48 hours of ECMO cannulation were three times more likely to die during their hospitalization (OR 3.02; 95% CI 1.32-6.9, p=0.009) even after adjusting for other risk factors such as ECPR, indication (post-operative support), and pre-ECMO serum creatinine.

Conclusion:
Preemptive CVVH support in pediatric cardiac patients requiring ECMO support is associated with increased in-hospital mortality. A strategy of pre-emptive CVVH in the cardiac ECMO population does not appear justified.
Abstract 18627: Cellular Encapsulation of Mesenchymal Stem Cells Enhances Cardiac Repair in a Rat Model of Myocardial Infarction
Authors: Levit Rebecca D , Landazuri Natalia , Phelps Edward A , Brown Milton E , Garcia Andres , Davis Michael E , Joseph Gigi , Long Robert , Weber Collin J , Safley Susan A , Suever Jonathan D , Lyle Alicia N , Taylor W. Robert
Published: April 2024

Stem cell therapies for myocardial repair have shown promise in preclinical trials, but lower than expected retention and viability of transplanted cells. In an effort to improve this, we employed an alginate encapsulation strategy for human mesenchymal stem cells (hMSCs) and attached them to the heart with a biocompatible PEG hydrogel patch in a rat MI model. Encapsulation allows for diffusion of pro-angiogenic cytokines and growth factors made by the hMSCs while maintaining them at the site of implantation. Animals were treated as follows: (1) MI only, (2) MI + gel, (3) MI + gel + empty capsules, (4) MI + gel + 1x106 non-encapsulated hMSCs or (5) MI + gel + 1x106 hMSCs encapsulated in alginate. Cells were tracked using bioluminescence (BLI) and cardiac function measured by echo and CMR. Animals treated with encapsulated hMSCs in the patch had a large increase in microvascular density in the peri-infarct area (828 ± 56 vessels/mm2; n = 6; p < 0.01) compared to other groups (MI: 121 ± 10, MI + gel: 153 ± 26, MI + gel + MSC: 198 ± 18, MI + gel + empty capsules: 215 ± 55; n = 6-9). Scar size at 28 days was also significantly reduced in encapsulated hMSC treated animals (7 ± 1 %; n = 6; p < 0.05) compared to control hearts (MI: 12 ± 1 %, MI + gel: 14 ± 2%, MI + gel + MSC: 14 ± 1%, MI + gel + empty capsules: 12 ± 2%; n = 4-8). Longitudinal BLI showed greatest hMSC retention when the cells were encapsulated. Post MI cardiac fractional shortening and ejection fraction, as measured by echo and CMR, were improved in encapsulated hMSC treated hearts (Table 1). Alginate encapsulated hMSCs attached to the heart with a hydrogel patch resulted in a highly significant improvement in left ventricular function after acute myocardial infarction. The mechanism for this markedly enhanced effect appears to be increased cell survival and retention, resulting in improved vascularization of the peri-infarct area. Cellular encapsulation may represent a new translatable strategy applicable to many cell types for regenerative therapy for CVD.
Abstract 18633: Prevalemce and Clinical Outcomes of Stent Fracture and Stent Recoil After Drug-eluting Stent Implantation at the Right Coronary Artery Ostial Site at Mid and Late Term
Authors: Ozaki Masatomo , Kadota Kazushige , Goto Tsuyoshi , Fujii Satoki , Yamamoto Hiroyuki , Kato Harumi , Oka Naoki , Fuku Yasushi , Hirono Akitoshi , Maruo Takeshi , Tanaka Hiroyuki , Tada Takeshi , Habara Seiji , Shigemoto Yoshikazu , Hasegawa Daiji , Tasaka Hiroshi , Okamoto Yoji , Otsuru Suguru , Saito Naoki , Hayakawa Yuki , Ohashi Noriyuki , Miyake Koshi , Eguchi Haruki , Yoshino Mitsuru , Hyodo Yusuke , Kubo Syunsuke , Ichinohe Tahei , Amano Hideo , Izawa Yu , Nakamura Michitaka , Mitsudo Kazuaki
Published: April 2024

Background: After stent implantation at the right coronary artery (RCA) ostial site, in-stent restenosis (ISR) often occurs and target lesion revascularization (TLR) is required. But at the RCA ostial site, the impact of stent fracture(SF) or stent recoil(SR) on midterm and especially late term restenosis is unknown.

Methods: From March 2004 to June 2010, 129 RCA ostial sites were successfully treated with 3 types of drug-eluting stent: sirolimus-eluting stent (SES), n=74; paclitaxel-eluting stent (PES), 39; everolimus-eluting stent (EES), 16. Mid and late term follow-up coronary angiography(CAG) was performed at 8 months and after 20 months. And SF and SR were assessed. We defined SF as apparent strut separation and SR as axial recoil less than 80% in the stent diameter, both analyzed by coronary angiography.

Results: We found 41 SF lesions (31.8%) and 24 SR lesions (18.6%) at the 8months follow up CAG. Out of the 102 patients without ISR at the 8months CAG, we were able to follow up 86 patients until the late term. The data of ISR and TLR at 8month and ISR at late term are shown in the table.

Conclusion: At the RCA ostial site, SF and SR have an effect on the ISR and TLR at 8month. Furthermore SF and SR have impact on late term ISR consecutively.
Abstract 18635: G Protein-Coupled Receptor Kinase 2 Regulates Cellular Oxidative Stress and Survival
Authors: Theccanat Tiju , Ludmer Nicolas , Akhter Shahab A
Published: April 2024

Cardiac myocyte oxidative stress and apoptosis are considered important mechanisms for the development of heart failure (HF). Chronic HF is characterized by increased levels of circulating catecholamines to augment cardiac output. Long-term stimulation of myocardial β-adrenergic receptors (β-ARs) is known to be deleterious in cardiac myocytes, however, the potential mechanisms underlying increased cell death are unclear. We hypothesize that G protein-coupled receptor kinase-2 (GRK2), a critical regulator of myocardial β-AR signaling and function, plays an important role in mediating cellular oxidative stress and apoptotic cell death in response to β-agonist stimulation. Stimulation of H9c2 cells with a non-selective β-agonist, isoproterenol (ISO) [10
-5
M] led to a 3-fold increase in oxidative stress/reactive oxygen species (ROS) generation as quantified by Mitosox staining and a significant increase in apoptosis measured by TUNEL and caspase-3 activity compared to PBS-treated controls. There was also a 2.5-fold increase in NADPH oxidase-4 (Nox4) expression but no change in Nox2, the primary NADPH isoforms and major sources of ROS generation in cardiac myocytes. ISO stimulation led to a 3-fold increase in GRK2 activity, similar to the myocardial GRK2 activity present in chronic HF. A 3-fold adenoviral-mediated overexpression of GRK2 led to similar increases in ROS production and apoptosis as seen with ISO stimulation. The increases in oxidative stress by either ISO stimulation or GRK2 overexpression were abolished by pre-treatment with apocynin, a non-specific Nox inhibitor, or siRNA-mediated knockdown of Nox4. Direct activation of adenylyl cyclase with forskolin did not lead to increased ROS production suggesting that β-agonist-induced oxidative stress is likely mediated by activation of GRK2 and increased Nox4 activity and not cAMP/PKA. Adenoviral-mediated expression of the GRK2 inhibitor, βARKct, inhibited Nox4 upregulation, ROS production and apoptosis in response to ISO stimulation. These data demonstrate that GRK2 may play an important role in regulating oxidative stress and apoptosis in the heart and provides another mechanism for the beneficial effects of cardiac-targeted GRK2 inhibition.
Abstract 18643: Longterm Mortality in 272 Women with Peripartum Cardiomyopathy
Authors: Barasa Anders , Rosengren Annika , Ladfors Lars , Swedberg Karl , Schaufelberger Maria
Published: April 2024

Introduction:
Peripartum cardiomyopathy (PPCM) is new-onset unexplained dilated cardiomyopathy with heart failure (HF) during the last months of pregnancy and the months following delivery. Prognosis and clinical course is highly variable and overall mortality in hospitalized cases unknown. Purpose: To determine long term mortality and predictors of outcome in women with PPCM in Sweden.

Methods:
Through linking records from the Hospital Discharge Registry and Medical Birth Registry (MBR), cases eligible for inclusion were identified from subjects with a pregnancy associated HF or PPCM diagnosis. To determine time and mode of death, these were further linked to the Cause of Death Registry. Controls (5:1) matched for age and year of diagnosis were allocated from the MBR.

Results:
From 1987 to 2010, we included 272 PPCM cases (1341 controls) with an average incidence rate of 1 in 9,191 live births (1 in 18,142 (1987-1991), and 1 in 6,549 (1996-2010)). A total of 22 cases and 5 controls died during the study period. Mean follow-up was 16.4 years. One-, 3-, 5- and 10-year all cause mortality was 4.0%, 5.9%, 5.9% and 7.0% among cases, and 0%, 0%, 0.15% and 0.22% among controls respectively (fig). The odds ratio (OR) of a fatal outcome in women with PPCM compared to controls was 23.5 (95%CI = 8.8; 62.6). Mortality among cases declined from 22.6% (1987-1996) to 3.8% (1997-2010), OR 5.93 (95%CI = 2.37; 14.78) for the first compared to the last period.

Conclusions:
PPCM mortality was lower than indicated in previous reports from USA, but still much higher than in healthy controls. Deaths leveled off after 3 years from diagnosis. Though incidence more than doubled, mortality continued to decline.
Abstract 18650: Impact of Severity of Aortic Stenosis on Left Ventricular Apical Rotation
Authors: Najib Mohammad , Ganji Jhansi , Chaliki Hari
Published: April 2024

Introduction-

Two dimensional speckle tracking echocardiography is a novel non-invasive method to assess subtle changes in left ventricular (LV) function such as strain and rotational dynamics. Limited data exists for assessing the impact of severity of aortic stenosis (AS) on LV apical rotation

Objective-

To determine the impact of severity of AS on LV longitudinal strain as well as LV apical rotation in patients with preserved LV ejection fraction and various degrees of AS.

Methods-

We prospectively measured longitudinal LV strain and apical rotation in 74patients with preserved LV ejection fraction but no (n= 22), mild (MG 10-25 mmHg; n= 20), moderate (MG 25-40 mmHg; n= 18), or severe (MG >40 mmHg; n= 14) AS who were undergoing echocardiographic examination at our institution. Two dimensional speckle tracking method was used to obtain average peak longitudinal strain using apical 4, 2-chamber and long-axis views while apical short axis view was used to obtain the LV apical rotation.

Results-

Mean age between no vs. mild vs. mod vs. severe AS groups (73±11yrs; 70±13yrs; 77±6yrs; 76±14 yrs) was not different (p=0.26). Presence of hypertension (64%, 65%, 78%, 71%) and coronary artery disease (14%, 6%, 25%, 29%) were also not different between the groups (p = 0.76 and p = 0.23 respectively). Average LV peak global longitudinal strain was not different between groups (-17.5±3%; -17.5±5%;-16.6±4%; -16.6±3% (p=0.82). However LV peak apical rotation was higher with worsening severity of aortic stenosis (14.8±8°; 14.7±9°; 21.3±11°; 23.7±12°) (overall p=0.02) (Figure).

Conclusions-

1) LV peak longitudinal strain was not different between patients with no stenosis when compared to patients with various levels of aortic stenosis. 2) However, LV apical rotation increases with worsening levels of AS probably to maintain the LV stroke volume. Further studies are needed to evaluate the role of LV apical rotation in deciding the timing of surgery in patients with severe AS.
Abstract 18674: Effects of Erythropoietin during Hemorrhagic Shock in a Swine Model
Authors: Whitehouse Kasen , Borovnik Lesjak Vesna , Miao Yang , Baetiong Alvin , Velmurugan Sathya , Currie Brian , Radhakrishnan Jeejabai , Gazmuri Raúl J
Published: April 2024

Background:
Erythropoietin (EPO) has recently been shown to activate cell survival mechanisms in a broad array of organs and tissues including the heart, brain, kidney, liver, and skin. We developed a swine model of hemorrhagic shock (HS) of increasing severity to investigate whether erythropoietin - through these mechanisms - could help attenuate tissue injury and improve survival.

Methods:
Two HS protocols were developed in two series of 24 male pigs each. In an initial series, 50% of the estimated blood volume (BV) was withdrawn (BW) over 30 minutes (
Series-50%
); in a subsequent series an additional 15% BV was withdrawn over an additional 30 minutes to a total of 65% BV removal (
Series-65%
). At 90 minutes, normal saline - threefold the BV withdrawn - was given over 240 minutes in both series followed by blood reinfusion (BR). Within each group, pigs were randomized to receive EPO (5,000 U/kg) or NaCl intraosseously after having withdrawn 10% of the BV.

Results:
Overall survival measured at the end of BR was 87.5% in
Series-50%
and 25% in
Series-65%
with no differences between EPO and NaCl (Table). The greater HS severity in
Series-65%
was evidenced by a lower mean aortic pressure, development of lactic acidosis, and lower oxygen consumption (VO2) at the end of HS. However, these manifestations of increased shock severity appeared to have been attenuated by EPO (Table).

Conclusions:
Despite comparable survival outcomes, the present study supports the possibility that EPO could exert beneficial hemodynamic effects under conditions of anaerobic metabolism; a possibility currently being investigated by examining whether EPO could be effective in reducing organ dysfunction in combination with therapies able to increase survival.