bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2039: Urinary 8-Hydroxy-2′-Deoxyguanosine Levels Decrease After Cardioversion in Atrial Fibrillation
Authors: Uemura Takashi , Yamabe Hiroshige , Nagayoshi Yasuhiro , Tanaka Yasuaki , Morihisa Kenji , Ogawa Hisao
Published: July 2021

Background
: Atrial fibrillation (AF) has been shown to be associated with increased oxidative stress mediated by reactive oxygen species (ROS). Previous studies have proposed that there is a link between oxidative stress and AF, and thus oxidative stress may contribute to the pathological consequences of AF such as thrombosis, inflammation, and atrial tissue remodeling. Urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) which is a product of deoxyribonucleic acid (DNA) damage by ROS has become to be regarded as a putative biomarker of oxidative DNA damage. Also, biopyrrins which are oxdative metabolites of bilirubin (an important scavenger of ROS) are considered as the potential marker of oxdative stress. In the present study, we assessed serial changes in oxidative stress in patients with AF after cardioversion by measuring urinary 8-OHdG and urinary biopyrrin excretion.

Methods and Results
: The study subjects consisted of 15 patients with persistent or chronic AF, who underwent electrical or pharmacological cardioversion. We measured urinary 8-OHdG and biopyrrin levels obtained before cardioversion and 24 hours after cardioversion using enzyme-linked immunosorbent assay. There was no significant difference in the biopyrrin/creatinine levels before and 24 hours after cardioversion (3.2±2.6 vs. 3.3±2.4 mU/mg, P=NS). However, 8-OHdG/creatinine levels decreased significantly 24 hours after cardioversion (18.4±9.1 vs. 14.7±8.5 ng/mg, P=0.0012). There was no significant correlation between urinary 8-OHdG/creatinine and biopyrrin/creatinine levels. This discrepancy may be related to the difference in the time course between urinary 8-OHdG/creatinine and biopyrrin/creatinine levels. Thus, measurement of 8-OHdG/creatinine levels seemed to be a more useful marker which reflects the oxidative stress than biopyrrin/creatinine levels at the time 24 hours after cardioversion.

Conclusions
: These findings suggest that the restoration of sinus rhythm by cardioversion decreases oxidative DNA damage in AF patients, and urinary 8-OHdG may be useful for the estimation of oxidative stress in AF patients. The increase of oxidative stress may play an important role in the pathogenesis of AF, and persist AF and result in the perpetuation of AF.
Abstract 2051: Recombinant Factor VIIa Affects Vein Graft Patency and Flow in Rabbits
Authors: Mazer David , Leong-Poi Howard , Alfardan Zuhair , Wang Zhilan , Qiang Beiping , Mahoney James , Latter David , Strauss Bradley , Teitel Jerry
Published: July 2021

INTRODUCTION: Recombinant factor VIIa (rVIIa) has been used to decrease postoperative bleeding in cardiac surgical patients. However, there is potential for rVIIa to interact with tissue factor expression at the site of new anastomoses resulting in early graft occlusion. This safety study tested the hypothesis that the administration of rVIIa dose-dependently reduces graft patency at the site of new vascular anastomoses comparable in size to human coronaries, in a rabbit model.

METHODS: After ACC approval, a reversed venous graft was fashioned in the right carotid artery using autologous right jugular vein with 9 – 0 sutures in 64 anesthetized and heparinized rabbits. Animals were then given either one of three doses of rVIIa (300 ug/kg, 90 ug/kg or 20 ug/kg IV) or placebo (n=16/group). The primary outcome was graft patency, measured by a blinded observer 24 hours postoperatively using vascular ultrasound (HDI 5000cv, 15 MHz probe) and/or direct inspection. Factor VII activity levels were measured from citrated plasma samples with a 1-stage prothrombin time-based assay using rabbit thromboplastin. Data was analyzed using chi-square, fishers exact test, or ANOVA where appropriate, with p<0.05 considered significant.

RESULTS: Physiologic variables (ACT, hemoglobin, pH, pCO2) and vessel diameter were similar between groups. Graft patency and flow were significantly reduced, and plasma factor VII levels significantly increased in the rVIIa treated rabbits in a dose-dependent fashion.

DISCUSSION: The study suggests that high doses of rVIIa (300 and 90 ug/kg) are associated with an increased incidence of occlusion of new vascular grafts. A clear dose-response effect was observed, suggesting that higher doses may be associated with increased thrombotic outcomes.
Abstract 2062: Predictors Of Outcome In Low Flow, Low Gradient Aortic Stenosis. Result Of The Multicenter Topas Study
Authors: Clavel Marie-Annick , Fuchs Christina , Burwash Ian G , Mundigler Gerald , Dumesnil Jean G , Baumgartner Helmut , Bergler-Klein Jutta , Beanlands Rob S , Pibarot Philippe
Published: July 2021

Background:
Patients with low flow aortic stenosis (AS) have a poor prognosis and a high operative mortality. Dobutamine stress echocardiography (DSE) has been used to assess LV contractile reserve and determine the “actual” severity of the stenosis. Recently, we proposed the projected aortic valve area at a normal flow rate (AVA
proj
) to better differentiate true-severe from pseudo-severe AS. The objective of this study was to identify the independent predictors of survival in low flow, low gradient AS.

Methods and results:
101 patients with low flow, low gradient AS (AVA≤1.2cm
2
, LV Ejection Fraction (LVEF) ≤40% and mean gradient (MG) ≤40 mmHg) underwent DSE and an assessment of functional capacity using the Duke Activity Status Index (DASI). A subgroup of 74 patients underwent a 6-minute walk test (6MWT). Overall survival was 70±5% at 1 year and 61±5% at 2 years. On univariate analysis, predictors of mortality were 6MWT ≤320m (p<0.0001), DASI ≤20 (p=0.0001), rest AVA ≤1cm
2
p=(0.006), peak DSE LVEF (LVEF
peak
) ≤35% (p=0.02), AVA
proj
≤1.2cm
2
(p=0.04). After adjusting for age, gender, and the type of treatment (surgical vs. medical), significant predictors of mortality were DASI ≤20 (HR: 1.79, 95%CI: 1.28 –2.53 p=0.0006) and AVA
proj
≤1.2cm
2
(HR:1.64, 95%CI: 1.04 –2.87 p=0.03). In the subgroup of patients undergoing a 6MWT (n=74), independent predictors of mortality were: 6MWT ≤320m (HR: 2.49, 95%CI: 1.55– 4.30 p<0.0001), AVA
proj
≤1.2cm
2
(HR: 2.07, 95%CI: 1.18 – 4.08 p=0.01), and LVEF
peak
≤35% (HR: 1.64, 95%CI: 1.10 –2.51 p=0.016). In the subset of patients undergoing valve replacement (n=44), unvariate predictors of operative mortality (18%) were: 6MWT ≤180m (OR: 9.8, 95%CI: 3.7–35, p=0.0002), DASI ≤15 (OR: 3.21, 95%CI: 1.67– 6.48, p=0.011) and LVEF
peak
≤20% (HR:5.83, 95%CI: 2.6 –16.7 p=0.001).

Conclusion:
In low flow, low gradient AS, the most significant risk factors for poor outcome were:

Impaired functional capacity documented by a reduced DASI or 6MWT,

More severe valve stenosis as documented by a smaller AVA
proj
, and

Reduced peak stress LVEF, a composite accounting for resting LV function and contractile reserve.

This new knowledge may assist in predicting the prognosis of patients with low flow AS and improve operative risk stratification.
Abstract 2073: Use of Diastolic Tissue Velocity and Standard Parameters to Assess Treatment Response in Subclinical Myocardial Disease - A Randomized Trial of Lifestyle Intervention in Type 2 Diabetes
Authors: Hordern Matthew D , Smith Louise M , Short Leanne , Downey Melodie , Prins Johannes B , Coombes Jeff S , Marwick Thomas H
Published: July 2021

Background.
Myocardial dysfunction is common in type 2 diabetes (T2DM), but the best markers of treatment response are undefined. We sought the effects of a 1 year lifestyle intervention (LI) on myocardial function and left ventricular (LV) characteristics, and to determine the predictors of this improvement.

Methods.
Pts with uncomplicated T2DM (223), no known cardiac disease and a negative stress echo were randomized into usual care (n=112) or LI groups (n=111). The LI involved individualized home-based training (150min/wk of moderate exercise) and caloric restriction. Myocardial function (diastolic (E′) tissue velocity, strain and strain rate), LV characteristics (EF, E/A, LVMI and E/E′), metabolic control (HbA
1c
, blood glucose, insulin resistance (HOMA), BMI, fat mass) and VO
2max
were assessed at baseline and follow-up in 159 pts (LI n=74) who remained in the study for 1 year.

Results.
Compared with usual care, LI was associated with significant (p<0.05) increases in E′ but not in strain, strain rate, EF, E/A, LVMI and E/E′ (Table

). Changes in E′ tissue velocity were significantly correlated with baseline E′ (r=−0.59, p<0.01), baseline metabolic status (BMI (r=0.23, p<0.01), insulin (r=0.22, p<0.01), HDL (r=−0.18, p<0.03)) and metabolic improvement (BMI (r=−0.17, p<0.04), insulin (r=−0.22, p<0.01), HbA
1c
(r=−0.24, p<0.01) and HOMA (r=−0.24, p<0.01)). Multivariate analysis revealed that age (beta=−0.33, p<0.01), baseline E′ (beta=−0.68, p<0.01) and changes in HbA
1c
(beta=−0.21, p<0.01) were independent predictors of changes in E′ and together accounted for 52% of the change in E′ (p<0.01).

Conclusions.
Diastolic myocardial properties, but not systolic deformation or standard LV characteristics respond to a 1 year individualized lifestyle intervention in T2DM. Improved diastolic myocardial function were associated with poor metabolic and myocardial health at baseline and greater improvements in metabolism over the intervention period.

Comparison between Intervention and Control Groups
Abstract 2085: Increased Regional Coronary Vascular Resistance During Hyperemia in Hypertrophic Cardiomyopathy Is Associated with Reduced Myocardial Blood Volume
Authors: Komatsu Hiroshi , Yamada Satoshi , Naya Masanao , Onozuka Hisao , Mikami Taisei , Tamaki Nagara , Tsutsui Hiroyuki
Published: July 2021

Introduction:
In patients with hypertrophic cardiomyopathy (
HCM
), myocardial blood flow (
MBF
) is decreased during hyperemia because of high coronary vascular resistance. Recently myocardial blood volume (
MBV
) can be estimated in vivo using myocardial contrast echocardiography (
MCE
) with the compensation for acoustic field inhomogeneity. The relationship between MBV and coronary resistance, however, has not been investigated. We thus assessed the hypothesis that increased regional coronary vascular resistance during hyperemia in HCM is associated with reduced MBV.

Methods:
In 13 patients with HCM (
H
, 53±16 years) with asymmetric septal hypertrophy and 9 normal volunteers (
N
, 54±11 years), MCE was performed under infusion of Levovist at rest and during hyperemia induced by ATP. Apical 4-chamber views of intermittent harmonic power Doppler imaging were acquired at end-diastole of every sixth beat. MBV was calculated as 10
X/10
×100%, where X was myocardial contrast intensity minus contrast intensity of the adjacent intracavity blood pool in dB.
15
O-water PET was performed to measure regional MBF. These parameters were measured in the interventricular septum (
IVS
) and LV posterolateral (
PL
) wall. Regional coronary vascular resistance was calculated as (mean blood pressure)/MBF.

Results:
Wall thickness was significantly greater in H than in N (IVS: 19±4 vs 10±1 mm, p<0.0001; PL: 10±1 vs 9±1 mm, p<0.05). MBV of IVS was lower in H than in N (rest: 2.1±0.7 vs 3.5±1.1%, p<0.01; hyperemia: 2.1±1.3 vs 4.3±1.7%, p<0.01), whereas MBV of PL wall did not differ between groups. Coronary resistance at rest did not differ between groups, but the resistance during hyperemia was significantly greater in H than in N (IVS: 59±16 vs 31±14 mmHg·min·g·ml
−1
, p<0.001; PL: 40±10 vs 30±11 mmHg·min·g·ml
−1
, p<0.05). Coronary resistance at rest did not correlate with MBV, whereas that during hyperemia inversely correlated with MBV during hyperemia (r=−0.77, p<0.0001) as well as MBV at rest (r=−0.65, p<0.0001).

Conclusions:
Increased coronary vascular resistance during hyperemia in HCM was significantly associated with reduced MBV. MCE is useful for assessing the dynamic function of coronary circulation in the clinical setting.
Abstract 2093: Myocardial Upregulation of mRNA Angiotensin II Receptor Subtype 1 (AGTR1) at One Year of Heart Transplantation is Associated with Worse Long-term Clinical Outcome Including Skin Cancer.
Authors: Yamani Mohamad H , Haire Christinna , Taylor David O , Young James B , Starling Randall C
Published: July 2021

Background:
We have previously shown that myocardial upregulation of mRNA gene expression of angiotensin II receptor subtype 1 (AGTR1) is associated with transplant vasculopathy evidenced by coronary intravascular ultrasound at one year following heart transplantation.

Objectives:
This study was undertaken to evaluate the long-term clinical outcome of heart transplant patients in relation to upregulation of mRNA AGTR1.

Methods:
A total of 45 heart transplant patients, mean age 55±12 years (78% male) had heart biopsy analysis for mRNA AGTR1 (Taqman PCR) at one year of transplantation. Dual Immunofluorescence staining for AGTR1 and vWF was also performed. Patients were divided into 2 groups according to the mRNA AGTR1 expression: Group I (n= 24), AGTR1 ≤2.0 and Group II (n=21), AGTR1 > 2.0. Patients underwent annual coronary angiography and were followed up for a mean period of 7.6±2.1 years. Transplant coronary vasculopathy was defined as angiographic evidence of coronary obstruction greater than 30% in the absence of donor coronary artery disease.

Results:
The 2 groups had similar baseline characteristics. During follow up, Group II patients tended to have increased risk of diabetes mellitus (57.1% versus 29.2%, P= 0.058) and renal insufficiency (61.9% versus 33.3%, P= 0.055) defined by serum creatinine greater than 1.5 mg/dl. Group II patients had a worse survival (10 year K-M survival: 61% versus 86%, log-rank P= 0.061) and increased vasculopathy (10 year K-M freedom from vasculopathy: 19% versus 66%, log-rank P= 0.036). Since the renin-angiotensin system has been implicated in the development of various cancers, we also evaluated the clinical outcome of malignancy in relation to mRNA AGTR1. Interestingly, the 10 year K-M freedom from any malignancy tended to be worse in Group II patients (46% versus 77%, log-rank P= 0.063) and statistically significantly different in skin cancer (57% versus 86%, log-rank P= 0.034).

Conclusions:
Myocardial upregulation of mRNA AGTR1 at one year of heart transplantation is associated with worse clinical outcome including skin cancer. These findings may call for the need of prospective randomized trials to evaluate if the natural course of these patients could be altered with the use of angiotensin receptor blockers.
Abstract 2099: Pretransplant Toxoplasma Gondii Seropositivity Amongst Heart Transplant Recipients Is Associated With An Increased Risk Of All-cause And Cardiac Mortality
Authors: Arora Satish , Jenum Pål , Aukrust Pål , Rollag Halvor , Andreassen Arne , Simonsen Svein , Gude Einar , Fiane Arnt , Geiran Odd , Gullestad Lars
Published: July 2021

Chronic
Toxoplasma gondii (T. gondii
) infection is known to trigger potentially adverse immuno-regulatory changes, but the long-term implication for heart transplant (HTx) recipients has not been assessed previously. Hence, we evaluated the risk of mortality, development of cardiac allograft vasculopathy (CAV) and acute cellular rejection amongst
T. gondii
seropositive HTx recipients and the four donor/recipient seropairing groups.

Methods:
Frozen pre-HTx serum samples of 288 recipients and 246 donors were evaluated for
T. gondii
serostatus using Platelia IgG immunoassay method. All patients had also undergone prospective serostatus evaluation using alternative assays and results determined by the two methods were compared. Follow-up data regarding mortality, CAV development and acute cellular rejection was available for all patients.

Results:
Overall, 211 (73%) recipients were seronegative and 77 (27%) were seropositive. In total, 82 recipients died, 76 developed CAV and 82 had significant cellular rejection. Recipient seropositivity was associated with a significantly higher risk of all-cause mortality (hazard ratio [HR], 1.9; 95% CI, 1.1–3.4; p= 0.02) and CAV mortality (HR=4.4; 95% CI, 1.3–15.6, p=0.02), but was not associated with earlier CAV development or higher rejection score. Donor/recipient seropairing status was not a risk factor for any endpoint.

Conclusions: T. gondii
seropositivity amongst HTx recipients is associated with a significantly increased risk of long-term total, and in particular CAV-related, mortality. This may be mediated via immunoregulatory changes triggered by chronic
T. gondii
infection and needs to be explored further.
Abstract 322: Role of T-Type Calcium Current in Cardiac Remodeling Probed with Genetically Engineered Knockout Mice
Authors: Le Quang Khai , Poulin F , Gillis Marc-Antoine , Comtois Philippe , Coutu Pierre , Tardif Jean-Claude , Li Danshi , Levesque Paul , Charpentier F. , Nattel Stanley
Published: July 2021

Background:
Previous studies suggested that T-type Ca
2+
-current (I
CaT
) blockers suppress disease-related cardiac remodeling, but all available I
CaT
-blockers have non-specific actions on other currents and/or functions. To obtain a clearer sense of the role of I
CaT
in cardiac remodeling, we studied mice with the principal cardiac I
CaT
subunit (Cav3.1) knocked out.

Methods:
Adult male Cav3.1 knockout mice (KO) were compared with wild type (WT). LAD-ligation was performed to create anterior-wall myocardial infarction (MI). Echocardiography was used to evaluate cardiac performance at baseline, 2-w and 4-w post-MI. Intracardiac programmed stimulation was performed 4-w post-MI. Standard pacing protocols were used to determine atrial and ventricular electrophysiological properties and to induce arrhythmias.

Results:
Surface ECG parameters were examined in 10 KO and 10 WT mice prior to LAD ligation. At baseline, PQ interval was significantly longer in KO mice than in WT animals (44 ± 1 ms vs 40 ± 1 ms, respectively; p < 0.05); no significant differences were observed in RR, QRS or QTc intervals. At 10 minutes post-MI, WT (but not KO) mice showed increased heart rate (p = 0.002). Baseline echocardiography showed smaller LV fractional shortening (FS) and ejection fraction (EF) in KO mice compared with WT (34 ± 1% KO vs 42 ± 3% WT; 69 ± 2% KO vs 77 ± 3% WT; respectively, p < 0.05). At 4-w post-MI, FS and EF of KO mice were still smaller than WT mice (15.5 ± 1.6% vs 21.0 ± 1.5%; 37.4 ± 3.2% vs 48.1 ± 2.8%, respectively; p < 0.05). At baseline and 4-w post-MI, the contractility index (pressure-volume curves) was decreased in KO mice (p < 0.05). Intracardiac electrophysiological recordings revealed no differences in atrial and ventricular ERP or sinus node recovery time for WT vs KO. At 4-w post-MI, extrastimuli induced sustained atrial fibrillation (> 2 s) in 60% (6/10) KO mice, versus 17% (1/6) in WT (p = 0.05) and ventricular tachyarrhythmias in 82% (9/11) of KO mice versus 17% (1/6) of WT (p < 0.01).

Conclusion:
Contrary to previous studies with (imperfectly selective) pharmacological agents having T-type Ca
2+
channel blocking actions, our findings suggests that reductions in I
CaT
do not favorably alter post-MI remodeling and may negatively affect cardiac function and arrhythmias.
Abstract 2123: Gadolinium-DTPA-Exposure-Induced Systemic Inflammatory Response (GEISIR) in Patients with Chronic Renal Insufficiency
Authors: Steen Henning , Giannitsis Evangelos , Zeier Martin , Schwenger Vecat , Katus Hugo A
Published: July 2021

Background
Cardiovascular morbidity is extraordinarily high in patients with chronic kidney disease (CKD) and accurate cardiovascular assessment is necessary. Due to the renal toxicity of certain contrast agents, this assessment has often been avoided. MRI contrast agents, such as gadolinium-DTPA, were originally thought to be a non-nephrotoxic alternative to iodinated contrast agents. The purpose of this study was to evaluate the safety of gadolinium-DTPA and to assess side effects in CKD patients who received gadolinium-DTPA during cardiovascular MRI.

Methods
Between August 2004 and December 2006, we longitudinally investigated 76 end-stage renal disease (ESRD) patients (70 haemodialysis=HD, 6 peritoneal dialysis=PD) who received gadolinium-DTPA during cardiovascular MRI.

Results
We report for the first time that 8% of ESRD patients experienced a gadolinium-DTPA-exposure-induced systemic inflammatory response (GEISIR). Furthermore, two of them previously not dialyzed CKD patients - rapidly progressed to end-stage renal failure.

Conclusion
Exposure to gadolinium-DTPA is not as harmless as was initially assumed. In ESRD patients, gadolinium-DTPA may induce severe adverse events, such as GEISIR. Therefore, short-term re-administration of gadolinium should be avoided in ESRD patients. Due to the extremely long half-life of gadolinium-DPTA, especially in PD patients, careful consideration should be given as to whether or not gadolinium-exposed patients require hemodialysis. Further data are imperative to determine optimal measures after gadolinium exposure in CKD patients
Abstract 2143: Improved Long-Term Survival in a High Risk Population Following Drug Eluting Stent Availability
Authors: Gandhavadi Maheer , Shunk Kendrick A , McNulty Edward J
Published: July 2021

Background
Data regarding the impact of drug eluting stent (DES) use on long-term outcomes outside trial populations are limited.

Methods
1,547 consecutive patients underwent stent implantation from January 2000 until December 2006 at the San Francisco Veterans Affairs Medical Center. To assess the impact of DES availability on mortality, that population was partitioned into a pre-DES cohort (N=591) and a post-DES availability cohort (N=956). Kaplan-Meier survival curves for the two cohorts were compared.

Results
The entire population was relatively high risk: 37% had diabetes, 38% a reduced ejection fraction, and 53% a prior MI or elevated troponin prior to the procedure. Median follow up was 4.7 years for the pre-DES cohort and 1.8 years for the post-DES cohort. DES were used in 83% of procedures in the post-DES cohort. Survival improved significantly in the post-DES cohort (P = .04, Log Rank)(see Figure

). Baseline characteristics, procedural variables and discharge medications were analyzed in a Cox proportional hazards model (see Table

). DES use was an independent predictor of improved survival (Hazard Ratio for death 0.52, 95% CI .28–.95).

Conclusions
In an unselected, high risk population, long-term survival improved following the availability of drug eluting stents. After adjusting for potential confounding factors, DES use was an independent predictor of improved survival.

Independent Predictors of Death in all 1,547 Patients
Abstract 2193: Genetically-mediated Torsades De Pointes During Complete Heart Block
Authors: Subbiah Rajesh N , Gollob Michael H , Klein George J , Chihrin Stephen M , Skanes Allan C , Gula Lorne J , Leong-Sit Peter , Krahn Andrew
Published: July 2021

Background:
Torsades de pointes (TdP) is a well known arrhythmic sequela in congenital and acquired long QT syndromes (LQTS). Less frequently, bradyarrhythmias are associated with QT prolongation and TdP. Although some observations have been made on the predictors of TdP in bradyarrhythmias, there is limited data on cellular mechanisms or genetic predisposition to bradycardia-induced TdP.

Methods:
In a retrospective case-control study, we identified 11 patients who were referred with CHB and TdP. Comprehensive assessment was performed in these patients, including, history, examination, ECG parameters (baseline, in CHB and pre-TdP) and genetic testing of repolarization related ion channel genes. 33 control patients with CHB and no TdP were selected for comparison of ECG parameters. All patients received either a pacemaker or implantable cardioverter defibrillator, with outpatient follow-up.

Results:
Four out of 11 patients with CHB and TdP had a genetic mutation identified involving ion channels responsible for cardiac repolarization (36%), involving hERG (n=3) and SCN5A (n=1). The key observations were that Tpeak to Tend interval was significantly longer in patients with a genetic abnormality at baseline, in CHB and pre-TdP (see Table 1

). Compared to controls, patients who had TdP complicating CHB had significantly longer QTc and Tpeak to Tend intervals in CHB.

Conclusion:
TdP in the setting of CHB appears to identify patients who have an underlying genetic predisposition to reduced repolarization reserve. In particular, the terminal phase of repolarization (Tpeak to Tend) appears to be a marker for patients who have a cardiac ion channel abnormality. Given these findings, genetic testing should be considered in patients with TdP in the setting of CHB.
Abstract 2207: Significant Impact of the Total Cavopulmonary Connection Resistance on Cardiac Output and Exercise Performance in Single Ventricles
Authors: Sundareswaran Kartik S , Pekkan Kerem , Dasi Lakshmi Prasad , Kitajima Hiroumi D , Whitehead Kevin , Fogel Mark A , Yoganathan Ajit P
Published: July 2021

Introduction:
The resistance of the total cavopulmonary connection (TCPC) in single ventricle (SV) circulation has long been hypothesized as a critical contributing factor to their diminished exercise capacity. We investigate this hypothesis using a lumped parameter (LP) model coupled with cardiac catheterization (cath) and computational fluid dynamics (CFD).

Methods:
SV pulmonary vascular resistance (1.80 ± 0.83 WU) and systemic vascular resistance (18.4 ± 7.2 WU) were obtained from cath data on 48 pts with a TCPC. TCPC resistances (0.55 ± .24 WU, min=0.24, max = 0.93) were established from CFD simulations (n=13) and in vitro experiments (n=8) conducted on anatomically accurate TCPC models from MRI. Resistance and compliance values for the normal pediatric circulation were obtained from the literature. These values were then used in a LP model developed for both the normal and SV circulation.

Results:
For a biventricular circulation, the cardiac output (CO) dependence on resistance is negligible, but not for the SV circulation (Fig 1a

). Capacity to increase CO with heart rate is also severely reduced for the SV. At a simulated exercise HR of 140 beats per minute, the SV patient with the highest resistance (0.93 WU) had a significantly lower increase in cardiac output (22%) when compared to an SV patient with the lowest resistance (26%) and the normal circulation (67%) (Fig 1b

).

Conclusion:
Hemodynamic energy cascade in a SV circulation should not be judged by stereotypes of biventricular circulation. The impact of TCPC surgical pathway resistance on cardiac output at rest and exercise was significantly higher on SVs compared to biventricular circulation.

Figure 1.

Impact of TCPC resistance in single ventricle vs. normal circulation, specifically (a) resting cardiac output, and (b) exercise cardiac output
Abstract 2223: Shear Induced Platelet Function Is Highly Increased In Patients With Cardiac Arrest Undergoing Cardio-pulmonary Resuscitation (CPR)
Authors: Spiel Alexander O , Mayr Florian B , Frossard Martin , Kliegel Andreas , Losert Heidrun , Sterz Fritz , Laggner Anton N , Jilma Bernd
Published: July 2021

Background: The prognosis of patients with cardiac arrest is still poor, and hardly any specific therapeutic options exist to improve outcome. Platelet activation has been observed in patients undergoing cardiopulmonary resuscitation (CPR). This may contribute to impairment of microcirculatory function and overall poor outcome despite return of spontaneous circulation. Data on direct platelet function in cardiac arrest are scarce. Platelets of patients with myocardial infarction are hyperfunctional, which predicts the degree of myocardial necrosis. Thus, we hypothesized that platelets may be even more hyper-functional in patients whose myocardial infarction causes cardiac arrest. We determined platelet function under high shear rates of patients with cardiac arrest and were further interested whether this may be related to the cause of cardiac arrest.

Methods: We conducted a prospective study in 77 cardiac arrest patients at the Emergency Department of a tertiary care hospital. Collagen adenosine diphosphate closure time (CADP-CT) was assessed by the FDA-approved platelet function analyzer (PFA-100). In addition, plasma levels of von Willebrand factor (vWf:RiCo) were measured by turbidometry. Independent staff members of the emergency department not otherwise involved in this trial diagnosed the origin of cardiac arrest.

Results: More than half of cardiac arrests were caused by myocardial ischemia. CADP-CT values (54s; 95%CI: 48–60s in 3.8% citrate) were much shorter in these patients as compared to patients with other causes of cardiac arrest (110s; 95%CI: 84–135s, p<0.001). This is substantially less than the 87s (95%CI: 80–94s) in patients with ST-elevation myocardial infarction as previously published. vWf:RiCo levels were substantially increased above the upper normal limit (180 U/dL) in all patient groups.

Conclusion: Patients with myocardial ischemia triggered cardiac arrest displayed the highest degree of platelet hyper-function under high shear rates, which was not solely due to increased vWF. Those patients may benefit from a rapid, more aggressive anti-platelet therapy than currently performed or an anti-vWF targeted therapy.
Abstract 2247: Feasibility of Long Ventricular Transmural Linear Lesions Created with a New Novel Saline-Injection Needle Catheter: Utility for Ablating Scar Related VT
Authors: Henz Benhur , Okumura Yasuo , Curley Michael G , Johnson Susan B , Packer Douglas L
Published: July 2021

Introduction:
Unstable scar related ventricular tachycardia (VT) is a common problem after myocardial infarction. Aggressive ablation may be limited, however, by incomplete scar penetration with available RF energy delivery technologies. The purpose of this study was to test the feasibility of full thickness linear ablation of infarcted ventricular substrate with a high penetration virtual electrode needle based electrode system.

Methods:
Chronic infarcted (> 2months) mongrel dogs (35–40 kg) underwent percutaneous catheter ablation of the LV with a saline-injection needle catheter employing an 8 mm 20-GA tip. Constant power at 40W was delivered for 90 sec via the virtual electrode needle during infusion of saline 10 ml/h at 50°C. The lines were created under electroanatomic map guidance and intracardiac ultrasound (ICE). The ejection fraction was monitored immediately before and after the ablation. One week after ablation, the dogs where restudied using CARTO epicardial and endocardial voltage mapping and hemodynamic testing.

Results:
The ablation lines created by a virtual electrode energy delivery made in the antero-lateral wall showed mean length of 4.4±1.4 cm. The mean area of ablation per lesion in the endocardium, mid myocardium and epicardium was 1.1±1.0, 2.6±1.3 and 1.9±1.3 cm
2
(p<0.05) respectively, with a mean ablation depth of 1.5±0.5 cm. Sixty-four percent of the length of lesions were transmural and in non-transmural areas had an average depth of 90±16% of wall thickness. The mean number of gaps/line was 0.5±0.7 with a length of 0.6 cm. Ejection fraction was 50±14, 52±17 and 52±13% before, after and 1 week post ablation respectively. At one week the epicardial and endocardial areas of low bipolar voltage < 1.5mV and dense scar < 0.5mV in the Carto map were 11.4±1.2 and 7.9±6.1cm
2
respectively which measurements were confirmed at necropsy by macroscopic scar in the epicardium and endocardium of 11.8±4.3 and 6.6±4.1 cm
2
respectively.

Conclusion:
This new novel saline-injection needle catheter effectively creates continuous long transmural lines in the infarcted LV. These data also confirm that the macroscopic ablation lesions can be consistently and accurately monitored by 3D electroanatomical mapping in both endocardium and epicardium.
Abstract 335: Deletion Of Bmper In Mice Identifies A Novel Bmp-dependent Pathway For Regulating Cardiomyocyte Hypertrophy
Authors: Ren Rongqin , Willis Monte , McDonough Holly , Kelley Rusty , Wu Yaxu , Patterson Cam
Published: July 2021

Bone morphogenetic proteins (BMP) are members of the TGF-β superfamily that regulate numerous cellular functions during development and in adulthood. We recently reported that Bmper (BMP-binding endothelial precursor-derived regulator) is an extracellular protein that modulates BMP activities. We created knock-in mice in which GFP replaces exons 1 and 2 of the Bmper gene, and found that ventricular cardiomyocytes abundantly expressed Bmper in vivo, especially during late stages of cardiac development in utero. To explore the role of Bmper in cardiomyocyte differentiation, in vitro hypertrophy assays were performed using embryonic day 18.5 cardiomyocytes from Bmper −/− and Bmper +/+ mice and cells were treated with vehicle, BMP2 (100 ng/ml), or the alpha-adrenergic agonist phenylephrine (100 μM) for 48 hours. Phenylephrine treatment induced a ~30% cell size increase in wild-type cardiomyocytes, whereas to our surprise BMP2 elicited an ~80% increase in size, indicating a potent hypertrophic effect of BMP2 on cardiomyocytes. In comparison to wild-type cardiomyocytes, Bmper −/− cells were ~100% larger without any treatment and were not further responsive to BMP2 or phenylephrine. Real-time PCR analysis of BMP2- and phenylephrine-treated wild-type cardiomyocytes revealed up-regulation of cardiac differentiation markers (including atrial natriuretic factor, smooth muscle actin, alpha-myosin heavy chain, and GATA2) and BMP signaling components (including BMP ligands, receptors, and Smad1/5/8). These same markers were upregulated in Bmper −/− cardiomyocytes, even in the absence of treatment. These observations indicate that the BMP pathway has a previously undisclosed role in regulating hypertrophy in cardiomyocytes and that Bmper, as a BMP antagonist, dramatically attenuates BMP-induced cardiomyocyte hypertrophy.
Abstract 2253: The association of Brugada pattern type 1 and fever: a retrospective analysis
Authors: Weiner Shepard D , Healy Kirsten O , Reiffel James A , Coromilas James
Published: July 2021

INTRODUCTION:
Many precipitants of the Brugada pattern ECG have been identified, including fever. However, the association of fever with Brugada pattern type is unknown. We assessed the hypothesis that the Brugada pattern ECGs that occur in the setting of a febrile episode are related to the Brugada pattern type.

METHODS:
This retrospective study examined all ECGs performed at Columbia University Medical Center from October 2004 to March 2007. The ECGs identified as showing possible Brugada pattern were reviewed and classified according to the ECG criteria endorsed by the Heart Rhythm Society and European Heart Rhythm Association. The medical record was then investigated for documentation of fever, defined as a temperature greater than or equal to 38.0 degrees Celsius. The primary outcome was the presence of fever within 48 hours of the Brugada pattern ECG.

RESULTS:
Forty Brugada pattern ECGs were identified (21 type 1 and 19 type 2). Background characteristics of the patients according to Brugada pattern type are shown in the Table

. Eleven patients (27.5%) had fever (median temperature 38.4; temperature range 38.0 – 40.1) and Brugada pattern ECGs. There was a statistically significant association of Brugada pattern type 1 (nine patients) and fever compared to Brugada pattern type 2 (two patients) and fever (p=0.031; OR 6.96, 95% CI 1.26 – 38.44). Seven of nine patients (77.7%) with fever and Brugada pattern type 1 had a normal ECG when afebrile and one of two patients (50.0%) with fever and Brugada pattern type 2 had a normal ECG when afebrile.

CONCLUSIONS:
A significant number of patients with Brugada pattern type 1 had this ECG finding in the context of fever. The majority of these patients had a normal ECG when afebrile. Further investigation is needed to assess the biologic plausibility of this finding as well as the relationship of Brugada pattern type 1 unmasked by fever in asymptomatic patients to the clinical features of Brugada syndrome.

Background Characteristics by Brugada Pattern Type
Abstract 2270: Preoperative Metabolic Therapy Improves Cardiac Surgical Outcomes: A Prospective Randomized Clinical Trial
Authors: Rosenfeldt Franklin L , Leong Jee Y , Pepe Salvatore , Van der Merwe Juliana , Esmore Donald S , Krum Henry
Published: July 2021

In the current era the typical patient presenting for cardiac surgery is elderly with multiple co-morbidities. These high-risk patients contribute disproportionately to postoperative morbidity and mortality. We have shown that metabolic therapy with antioxidants such as coenzyme Q
10
(Co Q
10
) and lipoic acid as well as energy substrate precursors such as orotate have protective effects on the stressed myocardium. We postulated that such therapy would reduce myocardial damage and improve post-operative recovery.

Aim:
To assess the effects of perioperative metabolic therapy on clinical and biochemical outcomes of cardiac surgery.

Methods:
Patients (
n
=117), mean age 65 years, 74% male, undergoing elective coronary artery bypass graft (CABG) or valve surgery were randomised to receive daily for a minimum of 2 weeks before, and 4 weeks after surgery, metabolic therapy consisting of CoQ
10
300mg, magnesium orotate 1.2g, alpha lipoic acid 300mg, fish oil 999 mg and selenium 200 μg or placebo.

Results:
In the whole group, metabolic therapy vs placebo was associated (multivariate analysis) with lower 24-hour postoperative plasma troponin I (1.44 ± 0.25 vs 2.65 ± 0.61 ug/L,
p
=0.003) and reduced postoperative hospital stay (6.9± 0.04 vs 8.1 ± 0.04 days,
p
=0.002). In CABG alone group (n=70), metabolic therapy reduced the incidence of postoperative atrial fibrillation (23% vs 46%,
p
=0.04, multivariate analysis).

Conclusions:
Metabolic therapy before cardiac surgery is associated with:

Reduced myocardial damage (troponin I release);

Shortened postoperative hospital stay;

Reduced incidence of postoperative atrial fibrillation in CABG patients.

Clinical and economic benefits may be expected from general application of this therapy.
Abstract 2274: Remote Ischemic Preconditioning Using Transient Arm Ischemia Reduces Myocardial Injury During Cardiac Surgery
Authors: Hausenloy Derek J , Mwamure Peter K , Venugopal Vinod , Harris Joanne , MacAllister Raymond J , Barnard Matthew , Grundy Ernie , Ashley Elizabeth , Kolvekar Shyam , Hayward Martin , Keogh Bruce , Yellon Derek M
Published: July 2021

Remote ischaemic preconditioning (RIPC) describes the phenomenon in which brief ischemia of one tissue or organ protects remote organs from a sustained episode of ischemia. Studies suggest that myocardial injury sustained during coronary artery bypass graft (CABG) surgery is associated with worse clinical outcomes. We conducted a single-blinded randomized controlled ‘proof-of-concept’ study to determine whether RIPC, using transient upper limb ischemia as the protective stimulus, reduces myocardial injury in patients undergoing CABG surgery. Fifty seven adult patients undergoing elective CABG surgery were randomized to RIPC (n=27) or control (n=30) following induction of anesthesia. RIPC comprised three 5-min cycles of right upper limb ischemia, induced by an automated cuff-inflator placed on the upper arm and inflated to 200 mmHg, with an intervening 5 minutes of reperfusion during which time the cuff was deflated. Serum troponin-T was measured pre-operatively and at 6, 12, 24, 48 and 72 hours post-surgery. Pre-operative troponin-T in all patients was <0.01 μg/L. RIPC significantly reduced serum troponin-T release in patients undergoing elective CABG surgery, at 6, 12, 24 and 48 hours post-surgery, such that the total area under the curve was reduced by 43% with RIPC (20.58±9.58 μg/L over 72 hours in RIPC vs 36.12±26.08 μg/L over 72 hours in control: 95% CI 4.88–26.21 μg/L:P=0.005). This clinical study demonstrates for the first time that remote ischemic preconditioning induced by transient upper limb ischemia reduces myocardial injury in adult patients undergoing elective CABG surgery.
Abstract 2312: Limitations of Molecular Expression Profiling (
Allomap Score
) in Predicting Endomyocardial Biopsy Findings in Cardiac Allograft Recipients: Two Year Follow-Up Surveillance Study
Authors: Nikolaidis Lazaros A , Borzognia Benham , Bove Alfred A
Published: July 2021

Background:
Molecular profiling of immune pathways implicated in cardiac allograft rejection has led to the development of a composite score (Allomap, range: 0 – 40) recently approved for clinical use. The potential for non-invasive monitoring in lieu of invasive biopsies and its reported high negative (NPV) predictive value are offset by low positive predictive value (PPV) and controversy about the threshold score (≥ 30 vs. ≥ 35) consistent with rejection. Nevertheless, the score has not been extensively validated in clinical practice.

Methods
: We obtained blood samples from cardiac allograft recipients (n=242 samples over 2 years) for determination of Allomap8 score at the time of endomyocardial biopsy. We excluded patients with recent transplant, on high dose steroids or recently treated for rejection. Pathologists blinded to AlloMap score interpreted all biopsies.

Results:
The mean Allomap score in the entire cohort was 29.9±0.4 (median: 31). The distribution was non-Gaussian with the majority of samples in the upper quartile [< 24: n=43 (18 %), 25–29: n=49 (20%), 30 –34: n=98 (40 %), > 35: n=52 (22 %)] Only 9 biopsy specimens (3.7%) were consistent with severe rejection (ISHLT 3A/3B or ≥ 2R per amended classification). Scores were not significantly different across the spectrum of ISHLT grades. Allomap scores of non-rejectors (ISHLT 0), mild rejectors (1-R) and significant rejectors (≥ 2R) were not significantly different (29.3±0.6 vs. 30.2±0.5 vs. 30.1±2.2, respectively). In predicting clinically significant (ISHLT ≥ 3A or 2-R) rejection, the NPV of Allomap was 95 %, yet PPV was < 10 %. Sensitivity (30 –55%) and specificity (37–78%) were highly dependent on the threshold used (≥30 vs. ≥35), thus ROC performance was suboptimal.

Conclusions:
Although molecular profiling of candidate genes to predict cardiac allograft rejection remains an attractive, non-invasive and physiologically sound concept, the clinical application of the present assay is still limited
Abstract 2333: Coronary Magnetic Resonance Angiography with Whole Heart Coverage for The Detection of Coronary Arery Stenoses: A Multicenter Study
Authors: Ichikawa Yasutaka , Sakuma Hajime , Kobayashi Yasuyuki , Ishida Masaki , Katahira Kazuhiro , Matsumoto Yuji , Fujita Naoya , Ochiai Reiji
Published: July 2021

Background:
Previous single center studies demonstrated that coronary magnetic resonance angiography (MRA) with whole heart coverage allows for noninvasive detection of coronary artery disease. In this prospective, multicenter study, we investigated the accuracy of whole heart coronary MRA in patients with suspected coronary disease.

Methods:
The subjects were recruited from five institutions. Free-breathing coronary MRA covering the entire heart were obtained in fifty eight patients by using a 3-dimensional, segmented steady-state free precession sequence without contrast injection. Coronary MRA was interpreted by 3 independent observers. Conventional X-ray coronary angiography was analyzed by a separate blinded reviewer. The diagnostic accuracy of coronary MRA was determined in all segments with reference diameter of 2 mm or more on X-ray coronary angiography regardless of the image quality of MRA.

Results:
Acquisition of coronary MRA was completed in all patients with an averaged imaging time of 9.8 ± 4.8 min. On patient based analysis, coronary MRA showed the sensitivity of 79.4% (range 64.7–88.2%), the specificity of 70.1% (65.9–80.5%), and the negative predictive value of 89.6% (84.6–93.1%). The sensitivity, specificity and negative predictive value in the segmental analysis were 60.6% (53.8–65.4%), 95.5% (94.2–97.6%) and 97.7% (97.4–98.1%).

Conclusions:
Coronary MRA with whole heart coverage can provide detection of luminal narrowing of the coronary artery with moderate sensitivity, high specificity and high negative predictive value. The high negative predictive value observed in this multicenter study indicates that noninvasive MRA approach is useful in ruling out significant coronary artery disease.
Abstract 2374: Whole Grain Intake in Relation to Lipids, Apolipoproteins, and Lipoprotein Subclasses in a Multi-ethnic Cohort: The Insulin Resistance Atherosclerosis Study
Authors: Mellen Philip , Liese Angela , Haffner Steven , Goff David
Published: July 2021

Context:
Whole grain intake is inversely associated with LDL-c and the metabolic syndrome, but the relationship of whole grains with other lipid parameters, such as small, dense LDL, is not established. We sought to evaluate the relationship of whole grain intake with lipids, apolipoproteins, and LDL lipoprotein subclasses in a large, multi-ethnic cohort.

Methods:
This cross-sectional study evaluated 975 non-diabetic participants in the Insulin Resistance Atherosclerosis Study. Baseline whole grain intake was estimated based on intake of dark breads, cooked cereals, and high-fiber cereals assessed in a validated food frequency questionnaire. Fasting lipid measurements included apolipoproteins and lipoprotein subclasses quantified by NMR spectroscopy. Linear regression models evaluated lipid parameters across quartile of whole grain intake after adjustment for demographics (age, sex, ethnicity, center), anthropometrics (BMI, waist circumference), lifestyle factors (smoking, alcohol intake), dietary factors (total kcal, fruits, vegetables, dietary fats) and lipid-lowering medication use. Additional models included directly measured insulin sensitivity (Si).

Results:
The cohort was 56% female, had a mean (SD) age of 54.8 (8.5) years, and was 60% non-white, with a median whole grain intake of .73 servings/day. In adjusted models, there was an inverse association between whole grain intake and LDL-c, Apo-B, Apo-B/Apo-A1 ratio, LDL particle concentration (LDL-p), and small LDL-p (Table

). These associations remained significant after adjustment for Si (LDL-c: p=.007; Apo-B: p=.04; Apo-B/Apo-A1: p=.03; LDL-p: p=.03; small LDL-p: p=.03).

Conclusion:
Whole grain intake is inversely associated with multiple lipid risk factors, including total and small LDL particle concentration, independent of insulin sensitivity and other confounders. This demonstrates additional mechanisms for the cardioprotective effects of whole grains.