bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2816: Assessment Of Left Ventricular Mechanical Dyssynchrony With Radial Strain By Speckle-tracking Best Predicts Response To Cardiac Resynchronization Therapy
Authors: Delgado Victoria , Ypenburg Claudia , Tops Laurens F , Mollema Sjoerd A , Marsan Nina Ajmone , Schalij Martin J , van der Wall Ernst E , Bax Jeroen J
Published: July 2021

Background:
Recently, 2-dimensional strain by speckle tracking imaging has emerged as a new technology for assessment of myocardial deformation in three dimensions: radial, circumferential and longitudinal. The current study evaluates which type of deformation study can best identify left ventricular mechanical dyssynchrony (LVMD) and predicts response to cardiac resynchronization therapy (CRT).

Methods:
One-hundred fifty-two consecutive patients underwent echocardiographic study before implantation of the CRT device and at 6 months follow-up. Radial (RS) and circumferential (CS) strains were applied to midventricular short axis views; difference in time to peak systolic strain value between anteroseptal-to-posterior walls was used to study LVMD. Longitudinal strain (LS) was applied to apical 4-chamber views and LVMD was calculated as the difference between basal septum-to-basal lateral walls. Patients with a decrease of LV end-systolic volume ≥15% at 6 months follow-up were considered responders.

Results:
After 6 months of CRT, 85 pts (56%) showed response to CRT. Compared to non-responders, responders had significant more LVMD when it was assessed by RS (212±146 ms vs. 127±108 ms; p<0.001), whereas there were no differences with neither CS nor LS (Table

). With RS, the optimal cut-off value to predict response to CRT was identified at a time-difference value of ≥130 ms yielding a sensitivity of 83% and a specificity of 71%.

Conclusions:
Radial strain by speckle-tracking imaging is a useful tool to assess LVMD and best predicts echocardiographic response to CRT.

Left Ventricular Mechanical Dyssynchrony assessed by radial, circumferential and longitudinal strain
Abstract 2824: Drug Eluting Stents Implantation In Acute Myocardial Infarction Significantly Delays Healing And Increases Stent Thrombosis
Authors: Nakazawa Gaku , Joner Michael , Ladich Elena , Finn Aloke V , Mont Erik K , Kutys Robert , Burke Allen , Kolodgie Frank D , Virmani Renu
Published: July 2021

Background
Although early clinical results of DES implantation for acute myocardial infarction (AMI) show no significant differences in late thrombosis however, long-term safety is still unclear. We evaluated the pathologic responses following DES implantation in AMI patients and compared to stents implanted in non-AMI lesions.

Methods
From CVPath DES autopsy registry of 116 cases, we identified 22 who presented with AMI at the time of DES implantation and had underlying plaque rupture (PR) or thin-cap fibroatheroma (TCFA). Morphometric analysis was performed using calibrated software (IPLab, Scanalytics) in patients who died ≥30 days after DES implantation. The percentage of struts with fibrin deposition, inflammation (>10 cells/strut), and uncovered struts were also recorded. We assessed arterial healing, by comparing culprit to non-culprit sites within each stented section. Furthermore, age and stent duration matched non-AMI patients who had underlying fibroatheroma (FA) lesion were selected as controls.

Results
Of the 22 patients with AMI, 14 died ≥30 days (mean duration: 285±277 days) and stent thrombosis was documented in 7 (50%, mean duration: 333±396 days), whereas in non-AMI patients with underlying FA, thrombosis was significantly less frequent (8%). Morphometric analysis revealed neointimal thickness was significantly less in culprit sites as compared to non-culprit sites in AMI patients. The percentages of uncovered struts, and struts with inflammation were significantly greater in culprit sites as compared to non-culprit sites in AMI lesions. Lesions in non-AMI patients were significantly different from AMI patients with greater neointimal thickness, less fibrin around struts, inflammation and uncovered struts (Table

).

Conclusions
A higher prevalence of stent thrombosis was observed in patients with AMI than those without AMI and is associated with substantial delayed in arterial healing especially at culprit sites.

Pathologic and Morphmetric Analysis, Culprit vs. Non-Culprit and AMI vs. Non-AMI
Abstract 2838: Bone Marrow Mesenchymal Stem Cells Differentiated into Beating Cardiomyocytes In Vivo and Improved Myocardial Function
Authors: Wang Tong , Tang Wanchun , Sun Shijie , Tsai Min-shan , Weil Max Harry
Published: July 2021

Background:
In settings of heart failure, infusion of bone marrow mesenchymal stem cells (MSCs) improves myocardial function both in experimental and clinical studies. The mechanism by which MSCs improve myocardial function remains unknown.

Hypothesis:
MSCs may differentiate into beating myocytes in vivo. The contractility of these cells is comparable with those of myocytes.

Methods:
A thoracotomy was performed in 10 male Sprague-Dawley rats, weighing 350 – 450g. Myocardial infarction was induced by ligation of the left anterior descending artery (LAD). One week later, animals were randomized to receive 5×10
6
MSCs marked with PKH26 in phosphate buffer solution (PBS) or as a PBS bolus injection into local infarcted myocardium. Six weeks after the MSCs or PBS injection, the hearts were harvested and digested with collagease type II and single cardiomyocytes were obtained. PKH26 labeled myocytes differentiating from MSCs were observed with a microscope Olympus I×71. The contractility of labeled and unlabeled beating cells in MSCs-treated animals was compared. The contractility of unlabeled myocytes was compared between MSCs-treated and control groups.

Result:
The beating fluorescent labeled myocytes can be found in MSCs-treated animals [(1.2±0.4) ×10
6
] and contractility of these cells were the same as that of unlabeled beating myocytes (Table 1

). The contractility of unlabeled myocytes, however, was significantly better in MSCs-treated animals.

Conclusion:
MSCs could differentiate into the beating myocytes. However, this may not be the sole mechanism of improved myocardial function. Table 1

Cells contractility (%)
Abstract 2841: Endothelial Selective NF-κB Inhibition Improves Survival and Preserves Host Defense Capacity in Bacterial Model of Sepsis
Authors: Ding Jianqiang , Ye Xiaobing , Liu Shu F
Published: July 2021

NF-κB plays a predominant role in septic pathology and is a desired target for developing therapies for septic shock. However, NF-κB blockade impairs bacterial clearance capability (BCC), which is detrimental. We have demonstrated that endothelial-restricted NF-κB blockade effectively prevents endotoxemic multiple organ injury (Circulation, 114: II-257). In this study, we examined whether endothelial-selective NF-κB blockade preserves BCC and improves survival in bacterial model of sepsis. Wild type (WT) and transgenic mice (TG) that conditionally overexpress a degradation-resistant I-κBα (I-κBαmt) selectively on endothelial cells were intravenously injected with saline (1 ml/kg) or pathogenic bacteria. Bacterial colonies formed in blood and tissue homogenate cultures of lungs, liver, spleen and kidney were counted. TG mice were induced to express I-κBαmt by feeding with doxycycline in drinking water. No bacteria grew in blood and any tissue homogenate culture from WT and TG mice injected with saline. Bacterial colony counts in blood and the 4 tissue homogenate cultures were similar between TW and TG mice 12 hrs after 10
7
CFU
S. pneumoniae
or 10
8
CFU
S. enterica
injection or 24 hrs after 10
8
CFU
L. monocytogenes
injection (Table

). TG mice showed an improved survival in the cecal ligation and puncture model of sepsis. The survival rate was 33% and 67% for WT and TG mice. Our results demonstrate that endothelial-selective blockade of NF-κB activation improves survival and preserves bacterial clearance capacity in bacterial model of sepsis.

Bacterial Colony Counts (CFU per ml blood or gram tissue)
Abstract 2880: Age Cutoff For The Loss Of Benefit From Bilateral Internal Thoracic Artery Grafting
Authors: Mohammadi Siamak , Dagenais Francois , Mathieu Patrick , Doyle Daniel , Baillot Richard , Perron Jean , Charbonneau Eric , Dumont Eric , Voisine Pierre
Published: July 2021

Objectives

: To identify the age-related benefit of single and bilateral internal thoracic artery (ITA) grafting on long-term cardiac-related survival in patients who survived from primary isolated coronary artery bypass grafting (CABG).

Methods

: A unicenter study was conducted on 12198 consecutive survivors from primary isolated CABG who received single (n=9533 patients) or bilateral (n=1388 patients) ITA grafts, or vein grafts only (n=1277 patients) between 1992 and 2005. Data was collected prospectively. The Cox regression model was used to estimate the hazard ratio of each independent variable on cardiac-specific survival over the entire length of follow-up. Age was a significant covariate into the statistical model. The mean follow-up was 5.7 ± 3.7 years and 100% complete as of December 2005.

Results

: After adjustments for different risk factors, the cardiac-related survival benefit in patients undergoing CABG with two ITAs was superior to that of single ITA grafting up to 60 years of age, displaying a constant decrease over time (Fig 1

). The use of a single ITA was beneficial on cardiac-related survival in all age groups, including octogenarians, compared to patients receiving only vein grafts.

Conclusions

: The use of at least one ITA is associated with increased long-term cardiac-specific survival in all age groups compared to venous-only CABG. The additional cardiac-specific survival benefit of using a second ITA decreases gradually with age, and its statistical significance is lost after 60 years of age.
Abstract 2883: Long-term Survival and Cardiac Troponin T Elevation in On- and Off-pump Coronary Artery Bypass Surgery
Authors: Brown Jeremiah R , Hernandez Felix , Klemperer John D , Clough Robert A , DiPierro Francis V , Hofmaster Patricia A , Ross Cathy S , O’Connor Gerald T
Published: July 2021

Introduction: The long-term clinical usefulness of conventional coronary artery bypass graft surgery (CCAB) and off-pump surgery (OPCAB) remains controversial. Long-term survival and cardiac troponin T (cTnT) elevation following CCAB and OPCAB has not been assessed. We tested the hypothesis that long-term survival was similar for CCAB and OPCAB patients when stratified by the presence or absence of cTnT elevation.

Methods: In this prospective cohort, we followed 1511 non-emergent patients with 2 or 3 vessel disease (778 CCAB and 733 OPCAB) from a single hospital in Northern New England by surgeons using both procedures between 2000–2004 to determine if 6-year survival was similar for CCAB and OPCAB patients. Postoperative cTnT elevation was defined at ≥1 (ng/μL). Data was linked to the Social Security Administration Death Master File. Kaplan-Meier and log-rank techniques were used. Cox’s proportional hazard models were used to calculate adjusted hazard ratios (HR) and 95% confidence intervals (95%CI), adjusting baseline patient and disease characteristics.

Results: Patients were similar with regard to baseline disease characteristics, comorbidities, cardiac history, function and anatomy. CCAB was associated with higher 6-year survival compared with OPCAB regardless of troponin elevation (Figure

, p<0.0001). Adjusted HR (CCAB cTnT <1 as referent) were 1.57 (1.05–2.36) for OPCAB cTnT<1, 1.52 (0.95–2.43) for CCAB cTnT ≥1, and 2.50 (1.37–4.58) for OPCAB cTnT≥1.

Conclusion: In summary, CCAB results in better survival over OPCAB in patients presenting with two or three vessel disease undergoing non-emergent cardiac surgery.
Abstract 2895: Targeted Ultrasound Imaging of Apoptosis with Annexin-A5 Microbubbles in Acute Doxorubicin-induced Cardiotoxicity
Authors: Min Pil-Ki , Lim Soyeon , Kang Soo-Jung , Hong Sung-Yu , Hwang Ki-Chul , Chung Kwang-Hoe , Chung Namsik
Published: July 2021

Background
Recently, apoptosis has been suggested as a common mechanism of myocardial loss in doxorubicin-induced cardiomyopathy. The aim of this study was to assess the feasibility of targeted ultrasound imaging of apoptosis with annexin-A5 microbubbles (A5MB) in acute doxorubicin-induced cardiotoxicity.

Method
Avidinated and octafluoropropan-filled phospholipid microbubbles were conjugated with biotinylated annexin-A5. To confirm the specific binding ability of A5MB, flow cytometry was performed with hydrogen peroxide induced apoptosis of rat aorta smooth muscle cells incubated with FITC-labeled annexin-A5 and A5MB. Adult male rats were injected with 5mg/kg doxorubicin IP weekly for 3 weeks (n=5). Control rats were injected with normal saline (n=2). At 24h after the final treatment, triggering imaging was done at a MI of 0.8 using 15MHz linear probe 15 minutes after IV bolus injection of A5MB for wash-out of freely circulating microbubbles. After the contrast echocardiography, the heart was isolated for histological detection of apoptosis (TUNEL assay).

Result
In in vitro test, fluorescence intensity was low for the healthy cells and high for the apoptotic cells when incubated with FITC-labeled annexin A5 and A5MB. Rats treated with doxorubicin showed significant contrast opacification of myocardium in contrast echocardiography using A5MB (Fig A, B

). However, no opacification was observed in control rats (Fig C, D

). Late apoptosis was confirmed by TUNEL assay in doxorubicin treated rats.

Conclusion
Acute doxorubicin induced cardiomyopathy based on early apoptosis can be assessed and imaged with targeted ultrasound imaging using A5MB in rats.
Abstract 2928: Sudden Arrhythmic Death Syndrome-Diagnostic Yield Of Combined Clinical & Genetic Screening In A British Specialist Clinic
Authors: Lambiase Pier D , Kaski Juan C , Firman Eileen , Elliott Perry M , Ahmed Akbar K , Chow Anthony W , Sheppard Mary , Lowe Martin D , Christiansen Michael , McKenna William J
Published: July 2021

Introduction: Sudden arrhythmic death syndrome (SADS) arises through disorders of ion channel function or structural heart disease. It accounts for over 400 deaths in the UK per annum. To date there has been no comprehensive analysis of the diagnostic yield and efficacy of a family screening approach in SADS index cases where the post mortem heart is structurally normal after expert pathological review.

Methods: 118 SADS families where the SADS victim died between 1 and 35 years of age were evaluated in a systematic family screening programme between 2003–2006. All SADS index cases had a structurally normal heart after expert review of all available tissue. All studied relatives underwent resting, signal averaged ECG, 24h Holter, exercise ECG with V0
2
max, transthoracic echocardiography and an ajmaline challenge test after initial clinical screening. Systematic mutation analysis was performed on the known long QT (LQT)genes including SCN5A & ryanodine receptor/ARVC genes when clinically suspected.

Results: The most common modes of death were rest in 28%, sleep in 25% and exercise in 18%. Clinical screening identified an inherited electrical cause of SADS in 41 of the 118 families (35%)-20 Brugada, 18 LQT Syndrome, 3 Catecholiminergic Polymorphic Ventricular Tachycardia (CPVT). Structural heart disease was identified in 5 ARVC & 2 DCM families. 26 ICDs have been implanted in affected family members-4 LQTS, 7 Brugada, 2 CPVT, 2 ARVC, 2 DCM and 9 on clinical grounds without a definitive diagnosis. The ECG (37%) and ajmaline challenge test (49%) had the highest diagnostic yield in families with a positive diagnosis. To date, genetic testing has increased the diagnostic yield by 5% (6/118 families-2 KCNQ1, 1 HERG, 2 SCN5A, 1 ARVC ), confirming a clinical diagnosis in 6.6%–3 KCNQ1, 3 SCN5A, 1 HERG, 1 KCNH2.

Conclusions: Systematic clinical screening in relatives of SADS victims has a diagnostic yield of 35% increasing to 40% with genetic testing. Electrical causes of SADS predominate in these families. These findings demonstrate that a systematic clinical screening programme in SADS families is both achievable and effective. The full impact of gene testing (including RyR mutations) upon diagnostic yield is awaited.
Abstract 2933: Left Ventricular Structure And Functions In Hemodialysis Patients Treated By Strict Volume Control
Authors: Kayikcioglu Meral , Ozdogan Oner , Ozkahya Mehmet , Duman Soner , Toz Huseyin , Asci Gulay , Can Levent H , Ok Ercan
Published: July 2021

Left ventricular hypertrophy (LVH) is reported to be as high as 70 – 80% in hemodialysis (HD) patients from the centers, where blood pressure can be controlled only in 50% of cases despite use of antihypertensive medications up to 90% of the patients. We evaluated LV structure and functions by echocardiography in HD patients treated by strict volume control strategy with rare usage (<10%) of antihypertensive medications, in order to clarify whether volume control could prevent progression of cardiac abnormalities in HD.

METHODS:
All 704 patients, who were on our HD centre for at least 6 months, underwent echocardiography on a nondialysis day. Cardiac dimensions were measured and type of LVH was described according to relative wall thickness (RWT). Systolic function was judged by ejection fraction (EF); diastolic function was assessed from both mitral inflow PW Doppler and Tissue Doppler imaging (TDI).

RESULTS:
Echocardiographic images were available for evaluation in 621 patients. Mean HD duration was 55±46 months, interdialytic weight gain 2.31±0.94 kg, systolic blood pressure (SBP) 125±16 mmHg, diastolic blood pressure (DBP) 75±9 mmHg. Only 7% of patients were receiving antihypertensive agents. LVH (LVMI ≥ 150gr/m in men, ≥120 g/m in women) was present in 42% of patients. LVH was of the concentric type (RWT≥45) in almost all cases (96%). The LVMI was correlated with age (r: 0.15, p: 0.001), diabetes (r:0.097, p:0.001), SBP (r:0.23, p:0.001), DBP (r:0.17, p:0.01), and interdialytic weight gain (r: 0.14, p:0.001). No correlation was found between LVMI and duration of HD. Mean EF was 66±10%. Systolic dysfunction (EF <45%) was present in only 9%. Diastolic dysfunction (by TDI) was observed in 62% of the patients.

CONCLUSION:
This is the largest echocardiographic study on HD patients. In patients under volume control strategy for hypertension, LVH was present in 42% and of the concentric type. No correlation is seen between LVH and duration of dialysis. These data suggest that development and progression of left ventricular abnormalities are not inevitable when strict volume control policy is applied.
Abstract 2935: Blood Pressure Variability At Night Predicts Cardiovascular Events In Type 2 Diabetics
Authors: Eguchi Kazuo , Ishikawa Joji , Hoshide Satoshi , Ishikawa Shizukiyo , Pickering Thomas G , Schwartz Joseph E , Shimada Kazuyuki , Kario Kazuomi
Published: July 2021

Background
It is not known whether BP variability is a risk factor for future incidence of cardiovascular disease (CVD) in type 2 diabetics (DM).

Objective
To test the hypotheses that short-term BP variability, including the morning BP surge, evaluated by ambulatory BP, predicts risk of incident CVD in DM.

Methods
Ambulatory BP monitoring was performed in uncomplicated 300 diabetics without BP medications, and they were followed for 54 ± 20 months. Morning BP was defined as the mean BP during the two hours after awaking, and morning BP surge as morning BP minus mean BP during the 1 hour that included the lowest BP at night. Incident CVD was defined as either myocardial infarction, stroke, or sudden cardiac death, and its relationship to different measures of BP variability, including morning BP surge and the standard deviation (SD) of daytime and nighttime BP was investigated. Cox proportional hazard models were used to estimate hazard ratios (HR) and their 95% CI, before and after controlling for age, sex, BMI, current smoking, antihypertensive medication, total cholesterol, serum creatinine, and 24-h SBP.

Results
The mean age was 67.8±9.6 years, 48% were male, 253 (84%) had a diagnosis of hypertension, and the mean values of the SD of awake SBP/DBP were 18±6/11±4 mmHg, and those of sleep SBP/DBP were 13±5/9±3 mmHg. During follow-up, there were 29 cardiovascular events. In univariable analyses, morning SBP (p=0.001), SD of awake DBP (p=0.002), and SDs of sleep SBP/DBP (both ps<0.01) were positively associated with incident CVD, but the morning surge of SBP/DBP was not. In multivariable analyses, the SDs of sleep SBP (HR=1.08; 95%CI, 1.01–1.16, p<0.05) and sleep DBP (HR=1.16; 1.07–1.26, p<0.001) were independently associated with incident CVD. Morning BP and morning BP surge were not associated with incident CVD. High nighttime variability of SBP and DBP (15.5 and 10.0 mmHg, each 75 percentile of SD) were associated with 1.6 and 3.0 times the risk of incident CVD, compared to individuals at the 25 percentile.

Conclusions
The hypothesis that morning BP surge is a predictor of CVD was not supported in our diabetic patients. However, BP variability at night appears to predict incident CVD, independent of ambulatory BP level and other traditional risk factors, in type 2 diabetics.
Abstract 2948: Evidence of Coronary Microvascular Dysfunction in patients with Systemic Inflammatory Diseases
Authors: Recio-Mayoral Alejandro , Rubens M B , Kaski J C , Harari O , Camici P G
Published: July 2021

Purpose: Accelerated coronary disease is a leading cause of morbidity and mortality in patients (pts) suffering from immune-mediated inflammatory diseases (IMID), such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). We tested the hypothesis that inflammation, in the absence of conventional cardiovascular risk factors, could result in coronary microvascular dysfunction (CMD) which is known to precede atherosclerosis in large vessels in pts with cardiovascular risk factors.

Methods: Myocardial blood flow (MBF, ml/min/g) was measured using positron emission tomography at rest and during i.v. adenosine (140 μg/Kg/min) in 8 SLE and 10 RA pts aged 47 ± 8 years without conventional cardiovascular risk factors and in 18 age and gender matched controls. In pts multislice (64 slices) CT coronary angiography was performed to exclude coronary stenoses.

Results: Mean disease duration was 18 ± 11 and 14 ± 6 years in RA and SLE respectively. There was no difference in resting MBF between pts and controls (1.27 ± 0.25 vs 1.11 ± 0.23; p=0.06). However, adenosine MBF was diffusely reduced in pts compared with controls (2.72 ± 0.84 vs 4.20 ± 0.75; p<0.0001) (Figure

). Coronary flow reserve (CFR; adenosine/resting MBF) was significantly reduced in pts (2.24 ± 0.74) compared with controls (4.00 ± 0.83; p<0.0001). Six pts showed ECG changes during adenosine stress and had a more severe reduction in CFR (1.73 ± 0.88) compared with those without ECG changes (2.49 ± 0.54; p<0.006).

Conclusions: Patients with IMID and without conventional cardiovascular risk factors have evidence of CMD which can result in reductions of CFR severe enough to cause myocardial ischemia.
Abstract 407: Angiotensin Converting Enzyme 2 (ACE2) Overexpression in Myocytes of Stroke Prone Spontaneously Hypertensive Rats (SHRSP) led to Cardiac Fibrosis
Authors: Masson Rachel , Nicklin Stuart A , Work Lorraine M , Gilday Kirsten , Gregorevic Paul , Allen James M , Chamberlain Jeffrey S , Graham Delyth , Dominiczak Anna F , Baker Andrew H
Published: July 2021

Aim:
Assess the effect of ACE2 overexpression
in vivo
on heart function and blood pressure. Identify an efficient cardiac gene delivery vector by comparison and optimisation of adeno-associated virus 6 (AAV6) and AAV9 mediated gene delivery to myocardium
in vivo
in SHRSPs.

Methods:
We administered a single intravenous injection of AAV6CMVlacZ or AAV9CMVlacZ at 3 doses (2x10
11
, 1.5x10
12
and 3x10
12
vp/rat) into 6 week old SHRSP. Animals were sacrificed 14 days post delivery and tissues stained for β-galactosidase (β-gal) expression which was confirmed by immunohistochemistry (IHC). Quantitative PCR compared the presence of lacZ containing genomes between tissues and animals. To assess the effect of ACE2 overexpression in SHRSP, 4 groups of animals (n = 6/group) were included in the study; PBS, Enalapril, AAV6-alkaline phosphatase (control reporter gene) and AAV6-ACE2. Blood pressure was monitored by tail cuff and cardiac function assessed by echocardiography (ECHO). Cardiac structure was assessed by haematoxylin and eosin (H&E) staining and cardiac fibrosis evaluated by Masson’s trichrome and picrosirius red.

Results:
AAV6-mediated gene transfer was high in heart and skeletal muscle and a dose-dependent response was observed. β-gal staining and IHC confirmed transgene expression throughout the musculature but not within other tissues (kidney, liver, spleen and lung). Whilst AAV9 mediated approximately 10 fold (for highest dose) less gene transfer to the heart than AAV6, levels were comparable in skeletal muscle. However, the AAV9 vector accumulated in the kidneys. ACE2 was overexpressed selectively in the AAV6-ACE2-injected animals. ECHO showed substantial systolic dysfunction in ACE2-injected SHRSP’s compared to controls, and H&E revealed abnormal cardiac structure. Masson’s trichrome and picrosirius red indicated severe cardiac fibrosis. Blood pressure was significantly lower (p<0.001) in the ACE2 group in weeks 9, 10 and 11 post infusion compared to PBS and control vector infused animals.

Conclusions:
AAV6 exhibited a more favourable profile for cardiac gene delivery than AAV9, and represents a useful tool for studying mechanisms of cardiovascular disease. Overexpression of ACE2 in SHRSP myocardium led to severe cardiac fibrosis.
Abstract 408: Thioredoxin-1 Gene Delivery Induces Hemeoxygenase-1 Mediated Myocardial Preservation after Chronic Infarction in Spontaneously Hypertensive Rats
Authors: Penumathsa SureshVarma , Koneru Srikanth , Thirunavukkarasu Mahesh , Zhan Lijun , Maulik Nilanjana
Published: July 2021

Hypertension the major risk factor for many cardiovascular diseases is a result of multiple causes along with excessive generation of reactive oxygen species resulting in imbalance of redox status. Thioredoxin-1 (Trx-1) is a redox regulatory multifunctional protein with anti-inflammatory, anti-apoptotic and antioxidant effects. In the present study we investigated the therapeutic potential of Adeno-Trx-1 in spontaneously hypertensive rats (SHR). The rats were assigned to four different groups (n = 24) such as (1) normotensive Wistar Kyoto (WKY) (2) SHR (3) SHR +Adeno-Lac-Z (SHRLac-Z) and (4) SHR +Adeno-Trx-1 (SHRTrx-1). Echo-guided gene delivery to the anterior wall of left ventricle was performed using 1x109 pfu of adenovirus constructed with Trx-1 and Lac-Z. Two days after injection of adeno virus, the hearts were subjected to permanent left anterior descending coronary artery occlusion (MI). Left ventricular functions by Echocardiography were examined after 30 days of MI as the significant changes in left ventricle were observed after 4 weeks of MI. Decreased left ventricular inner diameter (7 vs 9 mm) and increased ejection fraction (52 vs 42 %), fractional shortening (28 vs 22 %) was observed in SHRTrx-1 compared to SHR. Infarct size, cardiomyocyte apoptosis and protein expression profiles (by Confocal and Western blot analysis) were observed at predetermined time points i.e after 24 and 48 hours of MI respectively. Decreased infarct size (52% vs 67%), cardiomyocyte apoptosis by TUNEL assay (161 vs 240) and increased expression of Trx-1 and HO-1 were observed in SHRTrx-1 compared to SHR. Confocal results were also confirmed by Western blot analysis. Results documented increased expression of Trx-1 (1.8 fold) and HO-1 (1.4 fold) in SHRTrx-1 as compared to SHR. In addition, we have also observed increased expression of anti-apoptotic protein Bcl-2 (1.7 fold) in SHRTrx-1 treated group compared SHR. Thus our results demonstrate for the first time that the cardioprotective effect of Adeno-Trx-1 therapy in SHR is Trx-1/HO-1/Bcl-2 mediated and may represent a novel mechanism for therapy against hypertension induced post infarction heart failure.
Abstract 2966: Should a Minimum Corrected QT Interval (QTc) be a Prerequisite for Long QT Syndrome Genetic Testing?
Authors: Tester David J , Salisbury Benjamin A , Carr Janet L , Harris-Kerr Carole , Reed Carol R , Ackerman Michael J
Published: July 2021

Background:
Long QT Syndrome (LQTS) genetic testing has been available clinically since August 2004. In cases of bona fide LQTS, the yield of genetic testing is approximately 75%. Recently (HRS 2007), Priori and colleagues have suggested that referral for LQTS genetic testing should be based on the screening QTc citing a yield of < 2% for cases referred to their research program with a QTc < 440 ms. Here, we analyze the effect of QTc on the yield in two of the largest assembled cohorts of unrelated patients (pts) referred for LQTS genetic testing.

Methods:
From August 1997 to July 2006, 1125 unrelated pts (717 females, average age at diagnosis 23.5 yrs, average QTc 473 ms) were referred to either the Mayo Clinic Windland Smith Rice Sudden Death Genomics Laboratory (N = 541) for research-based LQTS genetic testing or to PGxHealth (N = 574) for the
FAMILION
®
LQTS genetic test. Comprehensive open reading frame and splice site analysis (60 exons) for LQTS-causing mutations involving
KCNQ1
(LQT1),
KCNH2
(LQT2),
SCN5A
(LQT3),
KCNE1
(LQT5), and
KCNE2
(LQT6) was conducted by either dHPLC/DNA sequencing (Mayo), or by direct DNA sequencing (FAMILION).

Results:
The probability of a positive genetic test increased dramatically with increasing QTc, ranging from 5% for the 38 pts referred for genetic testing despite a QTc < 400 ms to 60% for the 168 pts with a QTc > 500 ms (p < 0.00001). Akin to the Priori cohort, the yield of the genetic test was similar among the subset of pts with a QTc < 470 ms (64% Priori, 61% Mayo cohort, and 53% FAMILION, p = NS). However, the yield for those pts with a QTc between 440 and 470 ms was much greater in the Mayo (49%) and FAMILION (36%) cohorts compared to the Priori cohort (14%, p < 0.0005). In contrast to the 2% yield observed in Italy, 22% of pts with QTc < 440 ms referred to Mayo Clinic and 14.5% of the FAMILION referrals had a positive genetic test (p < 0.001).

Conclusions:
Whereas only 2% of patients with a QTc < 440 ms had a positive genetic test in Italy, the yield was ten times greater among those referred to Mayo Clinic despite the same QTc cut-off. The cumulative index of suspicion for LQTS rather than a pre-specified QTc cut-off should guide clinical decision making as to the appropriate utilization of the genetic test.
Abstract 2972: Permanent Atrial Pacing Lead Implantation Route After Fontan Operation
Authors: Takahashi Kazuhiro , Cecchin Frank , Fortescue Elizabeth B , Berul Charles I , Alexander Mark E , Walsh Edward P , Fynn-Thompson Francis Francis , Triedman John K
Published: July 2021

Background:
Atrial pacing is commonly used for sinus node dysfunction (SND) after Fontan surgery. The preferred route of lead implant has been debated. We compare procedural and clinical outcomes of transvenous (TV) and epicardial (Epi) atrial lead implants in this population.

Methods:
All Fontan patients having an atrial lead implant without other associated surgery between 1992 and 2007 were studied. Demographics, pacing lead performance data and procedural outcome were retrospectively analyzed.

Results:
78 patients (22 TV and 56 Epi) had 90 leads implanted (25 TV/ 65 Epi). Mean follow-up was 3.3±4.1 yrs (TV) and 4.4±3.6 yrs (Epi). TV leads were implanted in older patients (mean age: 23.9 vs. 13.8 yrs, p<0.001), at longer interval after Fontan surgery (mean: 15.1 vs. 5.7 yrs, p<0.001). Indication for TV was more likely to be SND, while Epi pacing was indicated for AV block. Pacing modes were exclusively AAI/AAI-T in TV and mostly DDD in Epi leads. Acute complication occurred in 2/25 (8%) of TV (pneumothorax n=1, skin erosion n=1) and 12/65 (19%, p=0.23) of Epi implants (effusions n=5, heart failure n=1, retained foreign body n=1, pneumothorax n=1, hematoma n=1, disconnection n=1, sepsis n=1, blood loss n=1). Median hospital stay was shorter in TV (2.0 vs 4.5 days, p=0.03). All TV patients and 43 Epi (77%) were anticoagulated. At follow-up, pocket infection occurred in one Epi patient. No clinical thromboembolic event was observed in either group. 3 TV leads failed in 2 patients (9%), while 12 Epi leads failed in 10 patients (18%); however, mean duration of freedom from lead failure was not significantly different (TV 9.9 vs. Epi 8.0 yrs, P=ns). The mean energy threshold was lower at implant for TV leads (0.9 vs 2.2 μJ, P=0.049), but similar for both leads on follow-up (1.2 vs 2.6 μJ, P=0.35). Atrial sensing was unchanged over time for TV (2.2 to 2.0 mV, P=ns), but significantly decreased in Epi (3.4 to 2.4 mV, p=0.006).

Conclusions:
Transvenous atrial pacing leads may be placed in Fontan patients with lower procedural morbidity than epicardial leads, and equivalent expectation of lead performance and longevity. Although the thromboembolic event rate appears low in anticoagulated patients with both lead types, the present study design cannot fully address this important issue.
Abstract 2974: Midterm Results Of Resynchronization Therapy In Pediatrics: Do We Need New Guidelines?
Authors: Dubin Anne M , Collins Kathryn K , Van Hare George F , Reddy V. M , Hanisch Debra , Chiesa Nancy , Rosenthal David N
Published: July 2021

Cardiac resynchronization therapy (CRT) is an accepted therapy for adults with dilated cardiomyopathy (DCM) and has been shown to improve ejection fraction and functional capacity. CRT has been used in children for over 4 years with a variety of indications which differ substantially from those commonly used for adult patients. We reviewed the results of CRT in the combined Stanford-UCSF pediatric electrophysiology program over the past 4 years, in order to evaluate efficacy of CRT in different clinical scenarios. We have provided CRT to 31 patients (15 female) between 2003 and 2007. The mean age at implantation was 7.3 ± 6.6 years. 21 patients had congenital heart disease (CHD) of whom 4 had single ventricle physiology. 5 patients had DCM and 5 had congenital complete heart block with reduced LV systolic function (CCHB). All patients with DCM met criteria for CRT in adults (QRS duration < 120 msec and EF > 35%). Implantation in the other patient groups was performed at the discretion of the physician. Mean follow-up was 26 ± 15 months. Ejection Fraction (EF), by echo, was 30 ± 11% at baseline which improved to 41 ± 19% at last follow-up (p < 0.05). EF as well as LV end diastolic volume and LV end systolic volume showed immediate improvement followed by additional continued improvement over the study period. CHD and CCHB patients reported improved symptoms and had improved cardiac indices by echo. DCM patients, however, showed no improvement and instead had a gradual decrease in ejection fraction over the study period (30 ± 11% to 18 ± 11%, p< 0.01). Two of the 5 DCM patients were transplanted, and one died of pump failure.

Conclusions:
CRT is efficacious in selected patients with congenital heart disease, or those with congenital complete heart block. The role of CRT in pediatric patients with dilated cardiomyopathy is less clear, but adult selection criteria may not be applicable to children.

Comparison of EF preCRT and at last follow-up
Abstract 2980: Long-term Outcome Of Unprotected Left Main Coronary Artery Stenting With Drug-eluting Stent: Comparison With Bare-metal Stent
Authors: Kim Young-Hak , Park Duk-Woo , Lee Seung-Whan , Kim Jeong-Soon , Nam Hyo-Jung , Kim Jong-Young , Kim Gyung-Jung , Lee Cheol Whan , Hong Myeong-Ki , Kim Jae-Joong , Park Seong-Wook , Park Seung-Jung
Published: July 2021

Background:
Long-term outcome of drug-eluting stent (DES) implantation for unprotected left main coronary artery stenosis has not been evaluated in detail.

Methods:
This study included 226 patients with de novo coronary lesions at the unprotected left main coronary artery (ULMCA) who were electively treated with DES and eligible for 2-year follow-up. The outcomes of these patients were compared with those of 200 patients treated with bare-metal stent (BMS) in the preceding years using log-rank test. Cox proportional hazard regression analyses were performed to correct for independent predictors of adverse outcomes between the two groups.

Results:
The DES patients were older, had more history of hypertension and diabetes mellitus, had more involvement of right coronary artery and three vessel stenoses, and were treated with more stents and longer stented length than the BMS patients. On the other hand, debulking atherectomy were more frequently used in the BMS patients. Two-year outcomes with adjusted hazard ratios are presented in the table

.

Conclusions:
For ULMCA stenosis, the superiority of DES in reducing target lesion revascularization (TLR) rate compared with BMS was continuously present up to 2 years. Furthermore, DES had a trend towards lower incidences of death, cardiac death, and stent thrombosis compared with BMS.
Abstract 3044: The Preoperative Utilization of Levosimendan (Preoperative Optimization) Reduced Mortality and Low Output Syndrome After Cardiac Surgery in Patients With Low Ejection Fraction (EF<25%).
Authors: Levin Ricardo L , Degrange Marcela A , Porcile Rafael , Salvagio Flavio , Blanco Norberto , Botbol Livio A
Published: July 2021

Background: Patients with low ejection fraction (EF<25%) present high-risk of mortality and development of low output state (LOS) after cardiac surgery. The objective of this research was to evaluate the preoperative use of the calcium sensitizer Levosimendan (Levo) in patients with EF<25%, underwent open heart surgery. Thirty-day mortality and development of postoperative LOS were the primary end-points of the study.

Methods: Patients with EF<25% and hemodynamic parameters of LOS (cardiac index<2.2 L/min/m2 and pulmonary artery occlusion pressure>15 mm Hg), underwent coronary bypass surgery between 12/01/2002 and 02/01/2007 were randomized to: preoperative infusion of Levo 0.1 mcg/Kg/min, 24 hours before surgery (Levo group-preoperative optimization), or placebo (Control group). LOS postoperative was defined for the same hemodynamic variables. A P value < 0.05 was considered significant

Results: Two-hundred and twenty one patients fulfilled the inclusion criteria, being randomized 111 of them to Levo, and 110 patients to placebo. Both groups were comparable in their general and surgical characteristics. No withdrawal of Levo was required during the preoperative administration, with 8 patients showing hypotension episodes which was resolved with fluid infusions. There were not ventricular arrhythmias, supraventricular arrhythmias (with heart rate over 125) or preoperative ischemic events. The 30-day mortality was 3 patients in the Levo group (2.7%) versus 12 patients in the Control group (10.9%, P value 0.001, OR 0.23, IC95 0.05– 0.90). Seven patients in the Levo group developed postoperative LOS (6.3%) against 20 patients in the Control group (18.2%, P value <0.001, OR 0.30, IC95 0.11– 0.80)

Conclusion: The preoperative optimization with Levosimendan reduced the operative mortality and the development of postoperative LOS in patients with EF<25% underwent open heart surgery. The infusion was safety no needing to withdraw it in any case. These findings could represent a new strategy to reduce the operative risk in this group of patients.:
Abstract 3051: Long Term Results Of Open Endovascular Repair For Aortic Dissections
Authors: Shimamura Kazuo , Kuratani Toru , Mastumiya Goro , Shirakawa Yoshiyuki , Takeuchi Mugiho , Kato Masaaki , Takano Hiroshi , Sawa Yoshiki
Published: July 2021

Background
. Complete resection of the intimal tear in aortic arch is one of the most complicated tasks in the treatment of aortic dissections. We introduced open stent grafting technique to complete this task with technical easiness. In this study we evaluated the long term efficacy of this procedure from our 12 years experience.

Patients and Method.
Form January 1994 to December 2004, 59 aortic dissections with intimal tear in aortic arch or proximal descending aorta were operated with open stent grafting technique (age 61.7yrs, 41 type A and 18 type B). Thirty three (55.9%) were in emergency status. All these cases were morphologically excluded from the indication of transluminal endovascular repair. Under deep hypothermic circulatory arrest with antegrade cerebral perfusion, the hybrid prosthesis was inserted into descending aorta through the transected proximal aortic arch in order to achieve intimal tear exclusion.

Results.
Complete exclusion of the aortic arch intimal tear was achieved in all cases. Operative mortality within 30 days was 3.4%. Major postoperative complications included 4(6.8%) cerebral infarctions, 2 (3.4%) paraplegia, 2 (3.4%) transient paraparesis. Median follow up was 71.2 months (maximum 153 months). One patient (1.7%) showed type I endoleak from the distal end. In 6 patients (10.2%) additional endovascular repair for other thoracic lesions were performed, and only one case with Marfan syndrome required open surgical repair for thoracoabdominal aorta because of expansion of the remaining thoracic dissection. CT scan showed shrinkage of the false channel in 78.6% of the patients. There were no rupture of the remaining dissected aorta and the freedom from aortic related death was 94.7%, 94.7%, and 88.8% at 1,5, and 8 years respectively.

Conclusion.
This study suggested that open stent grafting is a safe and effective technique with good long-term results. This procedure could be an alternative and standard method to repair aortic dissections with aortic arch intimal tear.
Abstract 3068: Intra-left Ventricular Contractile Dyssynchrony As An Independent Determinant Of Left Atrial Remodeling In Patients With Atrial Fibrillation Managed by Catheter-based Circumferential Pulmonary Venous Isolation
Authors: CHIU FU-CHUN , Wang Yi-Chih , Yu Chih-Chieh , Lai Ling-Ping , Hwang Juey-Jen , Tsai Chia-Ti , Tseng Chuen-Den , Katra Rodolphe P. , Lin Jiunn-Lee
Published: July 2021

BACKGROUND.
Enlarged left atrial volume (LAV), resulting from multifactorial pathogenesis, carries a poorer prognosis to patients with atrial fibrillation (AF) even under well rhythm control. We hypothesized that the preexistence of intra-left ventricular (LV) contractile dyssynchrony impaired diastolic filling, which contribute to atrial remodeling in AF patients.

METHODS.
We investigated 40 patients (34 men and 6 women, mean age 60 ± 10 years) with paroxysmal or persistent AF who were converted mainly by catheter ablation-based circumferential pulmonary venous isolation and then pharmacologically maintained in sinus rhythm. Exclusion criteria included significant (>moderate) valvular heart disease, LV ejection fraction <55 %, or ischemic heart disease confirmed by positive stress tests or coronary angiography. The LAV was measured by 2D echocardiography [π×D1×D2×D3/6 from parasternal long-axis view (D1) and apical four-chamber view (D2 & D3)]. The peak myocardial systolic velocity (S
M
) and the time to peak S
M
(T
S
) of the 6-basal and 6-mid LV segments were measured by tissue Doppler imaging (TDI).

RESULTS.
With similar AF duration before conversion, patients with LAV >40ml (n = 16) had similar baseline characteristics, cardiovascular medications, QRS width, and LV chamber sizes as those with LAV <40ml (n = 24). However, TDI showed the mean S
M
was borderline lower (6.3 ± 1.2 vs. 7.1 ± 1.2 cm/s,
p <
0.05), and the maximal intersegmental difference in T
S
(77 ± 43 vs. 40 ± 22 ms,
p <
0.003) was greater in patients with larger LAV. The intersegmental difference in T
S
correlated positively with LAV (r = 0.41,
p <
0.009), and LV filling pressure estimated by early transmitral flow velocity/annular diastolic velocity was significantly higher (12.3 ± 7.8 vs. 8.7 ± 2.2,
p <
0.045) in patients with intersegmental difference in T
S
>65 ms. After adjusting for age, gender, and the diastolic parameters, intersegmental difference in T
S
>65ms emerged as an independent determinant of larger LAV in multivariate logistic analysis (OR=17; 95% CI=2–166,
p <
0.016).

CONCLUSIONS.
Intraventricular dyssynchrony, which accompanied with elevated LV filling pressure, contributed independently to LA remodeling in AF patients converted into sinus rhythm by catheter ablation.
Abstract 3069: Reduction of Left Ventricular Dyssynchrony after Catheter Ablation for Isolated Permanent Atrial Fibrillation in Patients with Depressed Left Ventricular Function
Authors: Reant Patricia , Lafitte Stephane , Sacher Frederic , Derval Nicolas , Brette Stephanie , Hocini Meleze , Douard Herve , Clementy Jacques , Haissaguerre Michel , Roudaut Raymond , Jais Pierre
Published: July 2021

Background: Persistent/Permanent atrial fibrillation (Per AF) and electromechanical left ventricular (LV) dyssynchrony are frequently associated in patients with systolic heart failure. Their relationships have not been investigated yet. Objective: We hypothesized that Per AF could induce or worsen ventricular dyssynchrony. The aim of this prospective study was

to evaluate the degree of LV dyssynchrony in patients with Per AF and depressed LV function;

to describe the evolution of dyssynchrony after AF catheter ablation.

Methods: 28 patients with isolated Per AF and depressed LV function were investigated with a VIVID7 (General Electric) before ablation (D-1), at 1 month (M+1) and at 6 month (M+6) after the procedure and compared to 28 controls. LV ejection fraction was evaluated by biplane Simpson rule. LV dyssynchrony was quantified by tissue Doppler imaging in apical views using a triplane 3D/4D acquisition. Maximal difference between times to peak (mdTP) was determined. TP was measured as the delays between the onset of the QRS and the peak velocity of systolic wave on the 6 basal LV segments. Values were averaged on 3 consecutive cardiac cycles. LV dyssynchrony was defined for a mdTP value >65ms. Parameters of dyssynchrony were normalized to RR interval.

Results: Before ablation, mdTP was >65ms for 10 (36%) of the patients (group1) and >65ms for 18 patients (group 2). Ejection fraction was significantly lower in group 1 than in group 2. During the follow-up, the LV ejection fraction increase was similar in the 2 groups (+42%; +41%)(Table

). In the whole population, mdTP decreased from 57.5±35ms to 44.1±35ms (P<0.05). However, the LV dyssynchrony improvement was much more marked in group 1 than in group 2 (−42%; −13%).

Conclusions: In this study, LV dyssynchrony was present in 36% of the patients with permanent AF and impaired LV ejection fraction. Catheter ablation significantly improved both LV ejection fraction and LV dyssynchrony in this population.

Table