bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 1618: Clinical Spectrum of Tako-Tsubo-Cardiomyopathy in a Western Population: Results of the Tako-Tsubo-Registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenkenhausaerzte (ALKK)
Authors: Schneider Birke , Athanasiadis Anastasios , Pistner Wolfgang , Schamberger Rainer , Toepel Wolfgang , Schoeller Ralph , Bublak Angelika , Gerecke Birgit , Stellbrink Christoph , Gottwald Uta , Schwab Johannes , Peters Kay , Stein Jürgen , Sechtem Udo
Published: July 2021

Purpose:
Tako-tsubo-cardiomyopathy (TTC), initially described in Japan, has increasingly been recognized in western countries over the past years. Most studies, however, comprise relatively few patients. A German tako-tsubo-registry has been initiated to further characterize the clinical profile of this syndrome in a western population.

Methods:
So far 119 patients (P) were included according to following criteria:

acute chest symptoms,

ischemic ECG changes with ST-segment elevation ± T-wave inversion,

reversible left ventricular akinesia not corresponding to a single coronary artery territory,

absence of significant coronary artery stenoses.

Results:
Among 119 P (age 68±13 years) 104 were female (87%) and 15 male (13%). Triggering events present in 112 P (94%) consisted of emotional (n=82) or physical stress (n=59); 29 P (24%) experienced combined stress. The admission ECG showed ST-segment elevation (78%), reciprocal ST-segment depression (17%), negative T-waves (47%) and QTc prolongation (498±78 msec). Q-waves present in 27% on admission resolved during follow-up. Cardiac markers were slightly elevated (CK 264±573 U/l, troponin I 15±52 ng/ml). Ejection fraction was reduced (EF 54±15%). Left ventriculography showed apical ballooning in 83 (70%) and mid-ventricular ballooning in 36 P (30%). Except for a lower EF (50±15 vs 56±14%, p<0.05) in mid-ventricular ballooning, both variants had an identical clinical profile. Right ventricular involvement was seen in 30 P (25%). Complications included pulmonary edema (19%), intraventricular pressure gradient (7%), VT (2%), cardiogenic shock (4%), 1 P died. Cardiac MRI performed in 66 P (55%) displayed no late enhancement within the regional wall motion abnormality. Echocardiography showed normalization of LV function within 3 months. ECG changes completely resolved within 6 months. Recurrence of TTC occurred in 4 P (4%) after 2–35 months. Regarding all parameters, no gender difference was observed.

Conclusion:
TTC predominantly occurs in elderly patients after a stressful event. Atypical mid-ventricular ballooning and right ventricular involvement are common. Cardiac MRI typically shows no late enhancement within the wall motion abnormality. The recurrence rate appears to be low.
Abstract 1635: In Vivo Color Mapping Of Shear Stress Along Coronary Arterial Lumen With Multi-detector Computed Tomography
Authors: Fukumoto Yusaku , Hiro Takafumi , Fujii Takashi , Hiromoto Mitsuyuki , Tanaka Masakazu , Yamada Michio , Matsuzaki Masunori
Published: July 2021

Background and Purpose:
Shear stress is one of the important physical factors in the process of atherosclerosis. However, noninvasive and in-vivo visualization of shear stress distribution along the coronary lumen has been technically difficult, because it is not so possible to assess true three-dimensional (3D) geometrical structure as well as local flow profile in coronary artery for each patient. Recent technology of multi-detector computed tomography (MDCT) can provide an accurate representation of 3D architecture of coronary lumen as well as plaque distribution. This study was to develop a noninvasive way of color mapping of shear stress in coronary artery using a 64-row MDCT, and to preliminarily evaluate its clinical feasibility.

Methods:
Three-dimensional geometric architecture from patients with mild coronary artery disease was first obtained to develop a 3D mesh polygon model of each left and right coronary artery architecture. The mesh data was then used to perform a shear stress color mapping with a computational fluid-dynamical simulation of finite element model. The spatial resolution ( mesh size ) was 0.05 mm
2
. The flow was considered to be a constant laminar one, and the pulsatile motion was neglected. The relationship between shear stress and plaque accumulation was then examined.

Results:
According to the MDCT, atherosclerotic plaque formation was frequently observed in the distal potion at the first and second curvature of right coronary artery, and in the outer side of the bifurcation of the left anterior descending and the circumflex coronary artery. The colorized mapping of shear stress revealed that shear stress tended to be lower at the site of plaque accumulation within coronary artery.

Conclusion:
This method of 3D representation of shear stress distribution along coronary lumen with a 64-row MDCT might be useful for assessing the role of shear stress in atherosclerotic plaque formation or its progression / regression.
Abstract 1637: Radiation Dose Measurements on Subjects Undergoing Combined CT Perfusion and CT Angiography Imaging with a Prototype 256-row MDCT Scanner
Authors: George Richard , Lima Joao , Mahesh Mahadevappa
Published: July 2021

Introduction:
The purpose of this study was to directly measure the radiation dose on subjects undergoing combined CT Perfusion (CTP) and CT Angiography (CTA) imaging on a 256-row MDCT scanner.

Methods:
Fifteen patients underwent combined CTP and CTA imaging on a prototype 256 row MDCT scanner (Toshiba, Nasu, Japan). The prototype 256-row MDCT scanner consists of 256 rows of 0.5 mm size detectors with the capability to scan 12.8 cm length in the axial plane per CT gantry rotation in 0.5 secs. The protocol included a scout scan and test bolus scan followed by adenosine stress CTP (120 kVp, 200 mA, gantry rotation speed of 0.5 secs for 3 rotations, 128x1.0 mm) and rest CTA (120 kVp, 350 mA, gantry rotation speed of 0.5 secs for 3 rotations, 256x0.5 mm) in an axial scan mode. Direct dose measurements were performed using a custom vest worn by the patient fitted with 15–25 thermoluminiscent dosimeters (TLDs) (Landauer, IL) placed in AP and lateral locations. An anthropomorphic phantom was also scanned with the same protocol with TLDs positioned on the surface and inside the phantom at various organ locations. Effective doses were estimated based on the maximum surface dose according to previously validated methodology.

Results:
The effective dose from TLD measurements ranged from 22 to 32 mSv for the entire protocol. This is based on direct dose measured on subjects and not based on dose derived from phantom measurements as done routinely.

Conclusions:
The doses reported in this study are comparable to similarly measured doses from 64-slice MDCT coronary angiography alone. This prototype scanner uses 3 gantry rotations and a 1.5 second exposure time in it current configuration. Since, 256-row MDCT can cover the entire heart in a single rotation, it eliminates the need for tissue overlap from low pitch values. Efforts are currently underway to develop a prospective ECG-gated protocol that can limit radiation exposure to a single rotation for both stress and rest CTA scans. With a single rotation, the effective dose can be reduced to nearly one-third of the dose measured with this prototype, or approximately 7–11 mSv for a combined CTP and CTA imaging.
Abstract 1647: Can Left Ventricular Dyssynchrony as evaluated by Phase Analysis on Gated Myocardial Perfusion SPECT predict Response to Cardiac Resynchronization Therapy?
Authors: Henneman Maureen M , Chen Ji , Dibbets-Schneider Petra , Stokkel Marcel P , Bleeker Gabe B , Ypenburg Claudia , van der Wall Ernst E , Schalij Martin J , Garcia Ernest V , Bax Jeroen J
Published: July 2021

Purpose:
Cardiac resynchronization therapy (CRT) is now a well established therapeutic option for patients with end-stage heart failure. However, not all patients respond to CRT, and therefore preimplantation identification of responders is desirable. The purpose of the present study was to investigate whether the degree of left ventricular (LV) dyssynchrony as assessed with phase analysis from gated myocardial perfusion single photon emission computed tomography (GMPS), can predict which patients will respond to CRT.

Methods:
Forty-two patients with severe heart failure, depressed LV ejection fraction and wide QRS complex, were prospectively included for implantation of a CRT device and underwent GMPS and 2D echocardiography as part of clinical protocol. Clinical status was evaluated using New York Heart Association (NYHA) classification, 6-minute walk test and quality-of-life score. The histogram bandwidth and phase standard deviation (SD) (parameters indicating LV dyssynchrony) were assessed from GMPS, and clinical status and echocardiographic variables were re-assessed at 6 months follow-up.

Results:
Responders (71%) and non-responders (29%) had comparable baseline characteristics, except for histogram bandwidth (175±63° vs 117±51°, P <0.01) and phase SD (56.3±19.9° vs 37.1±14.4°, P <0.01) which were significantly larger in responders as compared to non-responders. Moreover, receiver-operator characteristic curve analysis demonstrated an optimal cutoff value of 135° for histogram bandwidth (sensitivity and specificity of 70%) and of 43° for phase SD (sensitivity and specificity of 74%) for the prediction of response to CRT.

Conclusion:
Response to CRT is related to the presence of LV dyssynchrony assessed by phase analysis with GMPS. A cutoff value of 135° for histogram bandwidth and of 43° for phase SD could be used to predict response to CRT. Larger prospective studies are warranted to confirm the present findings.
Abstract 1651: Exercise Improves Aging-associated Myocardial Insulin Resistance by Enhancing Mitochondrial Function in an eNOS Dependent Mechanism
Authors: Li Qiu X , Zhang Quan J , Zhang Hai F , Zhang Kun R , Li Jia , Guo Wen Y , Wang Hai C , Ma Xin L , Gao Feng
Published: July 2021

Objective
. This study sought to determine whether exercise reduces aging-associated myocardial insulin resistance, with a specific focus on the role of eNOS and its relation to mitochondria.

Methods
. Aging male Sprague-Dawley rats (24 months) were subjected to swim training (60 min/d, 5 d/wk, 9 wk) or assigned as sedentary control. The myocardial contraction, myocardial glucose uptake, mitochondrial function, and eNOS signaling were determined.

Results.
Aging rats had myocardial insulin resistance as shown by decreased insulin-induced glucose uptake (0.22±0.05 μmol/min/g in aging heart vs.1.29 ± 0.13 μmol/min/g in adult heart, n=8,
P
<0.01) and attenuated insulin’s positive inotropic role as evidenced by reduced left ventricular developed pressure (90±12 mmHg in aging heart vs. 155±14 mmHg in adult heart,
P
<0.01). Mitochondrial function was decreased in aging hearts as manifested by the attenuated maximum O
2
consumption by FCCP (1.85±0.39 μmol/min/g in aging hearts vs. 3.72±0.40 μmol/min/g in adult hearts,
P
<0.01). This was accompanied with the reduced insulin-induced O
2
consumption (1.37±0.31 μmol/min/g in aging heart vs. 2.35±0.31 μmol/min/g in adult heart,
P
<0.01). In addition, eNOS expression and its phosphorylation by insulin were reduced by 1.2- and 2.3-fold in aging heart, respectively (
P
<0.01). Swim training upregulated eNOS expression by 72% (
P
<0.01), facilitated eNOS phosphorylation by insulin (
P
<0.01), and improved myocardial insulin sensitivity as shown by enhanced glucose uptake by insulin (
P
<0.01). Moreover, mitochondrial function was facilitated as manifested by the enhanced O
2
consumption by insulin (
P
<0.05), and maximum O
2
consumption (
P
<0.01) following swim training. Pretreatment with Cavtratin, an eNOS inhibitor, abolished exercise-improved mitochondrial response to insulin, blocked exercise-improved myocardial insulin sensitivity and the positive inotropic response to insulin in aging heart.

Conclusion
. These results demonstrate that impaired eNOS signaling and subsequent mitochondrial depression is a major mechanism contributes to aging-associated myocardial insulin resistance, and that exercise improves insulin sensitivity by restoring eNOS signaling and enhancing mitochondrial function.
Abstract 1654: Reduced Left Ventricular Diastolic Function Follows Prolonged Strenuous Exercise In Middle-aged Male Athletes
Authors: Ramer Sarah A , Sasson Zion , Busato Gian-Marco , Persaud Joan A , Malik Amrit A , Goodman Jack M
Published: July 2021

Introduction:
A number of studies have demonstrated LV diastolic dysfunction after prolonged strenuous exercise. However, data remain conflicting in part because of uncontrolled and disparate experimental conditions.

Hypothesis:
We assessed the hypothesis that a decline in LV diastolic function follows prolonged exercise among middle aged male athletes.

Methods:
Eight middle aged recreational male athletes (ages 47–59, mean 52.4± 1.3 years) were recruited. On separate days at least one week apart, subjects performed continuous running of 150 min duration at low and high intensities (55% vs 80% VO2 max, respectively). On each day of exercise, subjects underwent echocardiographic assessments immediately before and 60 min following exercise. Diastolic function was assessed by standard pulsed wave Doppler and tissue Doppler techniques. Efforts were made to maintain hydration throughout, and hematocrit was checked with each echocardiographic assessment.

Results:
Sixty minutes following prolonged exercise, the mean resting heart rate was significantly elevated compared to baseline (81±5 vs 63±3 bpm, p<0.01) and a drop in systolic blood pressure was observed (115±4 vs 132±5mmHg, p=0.02). Baseline and post-exercise hematocrit were similar (43.3%±0.8 vs 43.4%±0.8). Mean (±sem) indices of diastolic function are summarized below and included a significant decline in peak mitral inflow E velocity, accompanied by an increase in mitral inflow A velocity which was significant after high intensity exercise. The decline in both the E/A and e’/a’ ratio was significant for both high and low exercise intensities. A significant prolongation in the IVRT and the mitral inflow E wave deceleration time were seen following low intensity exercise.

Conclusions:
In middle aged men, prolonged exercise is associated with diminished resting LV diastolic performance, detectable one hour following exercise. These changes appear to be independent of hydration state.
Abstract 1681: Evaluation of Quantitative Myocardial Perfusion MRI and TIMI myocardial blush grade (Blush score)
Authors: Nakajima Hiroshi , Okamoto Shinya , Sakuma Hajime , Kurita Tairo , Nagata Motonori , Fujimoto Naoki , Masaki Ishida , Takeda Kan , Ito Masaaki
Published: July 2021

Background: The TIMI myocardial blush grade (MBG) has been shown to be a strong angiographic predictor of mortality in patients with TIMI 3 flow after primary angioplasty. This study was conducted to evaluate the relationship between regional myocardial perfusion quantified by cardiac magnetic resonance and angiographic reperfusion score defined by MBG.

Methods: We studied 29 consecutive patients (25 men, age 63±13 years) with ST-segment elevation acute myocardial infarction (LAD lesion: 12, RCA lesion: 16, LCx lesion: 2) who underwent primary angioplasty within 6 hours from the onset and showed TIMI grade 3. MBG was determined on angiography at the end of angioplasty. All patients underwent rest myocardial perfusion MRI during initial hospitalization, and regional MBF (ml/min/g) was quantified by using a Patlak plot method. Myocardial perfusion (MP) ratio was calculated from quantitative perfusion MRI, as MBF in infarction area/MBF in normal area. The optimal cut-off value of MP ratio that can predict MBG 3 on coronary angiography was determined by using a receiver-operating characteristic (ROC) analysis.

Results: In 29 patients with TIMI 3 flow after angioplasty, 4 patients had MBG 0–1, 7 had MBG 2 and 18 had MBG 3. The MP ratio in MBG 3 group calculated from quantitative perfusion MRI was significantly higher than the MP ratios in MBG 0 –1 group and MBG 2 group (0.96±0.18 vs. 0.48±0.25, P<0.001; 0.96±0.18 vs. 0.66±0.19, P=0.003, respectively). There was no significant difference between the MP ratios in MBG 0 –1 group and MBG 2 group. The ROC curve revealed that MP ratio of 0.74 is an optimal threshold to distinguish MBG 3 from MBG 0 –2, with a high area under the curve of 0.90.

Conclusions: The result of this study demonstrates that MP ratio quantified from rest perfusion MRI correlated well with MBG on coronary angiography.
Abstract 1691: Stages of Chronic Kidney Disease Correlate with Major Adverse Cardiac Events as well as Late Lumen Loss Following the Sirolimus Eluting Coronary Stent
Authors: Kawamura Yota , Morino Yoshihiro , Nagaoka Masakazu , Matsukage Takashi , Masuda Naoki , Tanabe Teruhisa , Ikari Yuji
Published: July 2021

Background:
Chronic Kidney Disease (CKD) is considered as a risk factor for development of cardiovascular disease. However, it is unclear whether CKD has association with prognosis following the drug eluting stent implantation.

Methods and Results
: The Cypher coronary stents were implanted to 302 lesions in 249 patients who underwent elective PCI between January 2005 and April 2006. Average age was 66.3 ± 9.7 and male gender was 80.3%. Diabetes was found in 47% of the patients including 16% of insulin treatment. Stages of CKD are shown in the table 1

and 2

. AHA/ACC lesion type B2/C was 62%. Cypher stents were implanted at maximum pressure at 17.3 ± 3.0 atm. Intravascular ultrasound was used in 92% of the procedure. Clinical follow-up data were available in 89.9 % at 1 year although angiographic follow-up was performed in 73.1% at 8 months. Major adverse cardiac events were frequently observed in association with stages of CKD as shown in the table 1

. Stages of CKD have correlation with late lumen loss at 8 months (Table 2

). Furthermore, in-stent late lumen loss inversely correlated with glomerular filtration rate (GFR) (R = −0.18, p = 0.0097).

Conclusion
: Stages of CKD have correlation with major adverse cardiac events as well as late lumen loss following the sirolimus eluting stent implantation.

Clinical follow-up at 1 year of study stratified by stages of CKD

Angiographic data of study stratified by stages of CKD
Abstract 1695: Percutaneous Aortic Valve Replacement for Severe Aortic Stenosis by CoreValve Bioprosthesis: A Single-Center Experience
Authors: Linke Axel , Walther Thomas , Möbius-Winkler Sven , Woinke Michael , Fassl Jens , Mohr Friedrich W , Schuler Gerhard C
Published: July 2021

Treatment of aortic stenosis remains challenging in older individuals, since their perioperative mortality for conventional aortic valve replacement increases due to co-morbidities. Therefore, it was aim of the present study to elucidate whether retrograde, percutaneous aortic valve replacement (PAVR) using the CoreValve system in older patients (pts) with co-morbidities is safe, feasible and associated with an improvement in hemodynamics.

Methods:
Pts with symptomatic aortic stenosis (valve surface area < 0.8 cm
2
), aged ≥ 75 years and/or a Logistic EuroSCORE ≥ 15 % were considered for enrollment. Using a retrograde approach, valvuloplasty was performed either under local or general anesthesia followed by CoreValve implantation. The CoreValve revalving system carries a porcine pericardial bioprosthesis in a self-expandable nitinol frame. Clinical events were recorded at 30 days after PAVR. Transthoracic echocardiography was performed before and at 10 days after CoreValve implantation to evaluate instantaneous changes in hemodynamics and short term follow-up of the prosthesis.

Results:
A total of 30 pts with a mean age of 83±1 years and a Logistic EuroSCORE of 22±3 % were enrolled. The CoreValve prosthesis was successfully implanted in 28 patients (93%), in two patients a conversion to conventional surgery was necessary due to valve misplacement. The mean gradient across the aortic valve markedly declined from 43±3 mmHg before to 10±2 mmHg at 10 days after PAVR. The valve surface area increased from 0.6±0.1 cm
2
before to 1.6±0.2 cm
2
after CoreValve implantation. Twenty-two pts had grade 0 or 1 aortic regurgitation (AR) after PAVR and 6 patients AR up to grade 2+. Three patients died after successful PAVR, two from sepsis and one from cardiac failure resulting in a 30-day-mortality for the entire study population of 10 %. Three patients (10 %) experienced a periprocedural stroke. Among 25 patients surviving to discharge after successful PAVR, no adverse events occurred within 30 days after leaving the hospital.

Conclusion:
These early results suggest that PAVR with the CoreValve prosthesis is feasible, safe, improves hemodynamics and, therefore, might be an alternative in very high-risk patients for conventional aortic valve replacement.
Abstract 1701: Soluble Receptor for Advanced Glycation End Products (RAGE) is a Prognostic Factor for Heart Failure
Authors: Koyama Yo , Takeishi Yasuchika , Niizeki Takeshi , Suzuki Satoshi , Kitahara Tatsuro , Sasaki Toshiki , Kubota Isao
Published: July 2021

Background: It is known that oxidative stress is increased in patients with heart failure. Advanced glycation end products (AGE) are generated nonenzymatically by glycation and oxidation of proteins. We have recently reported that serum level AGE is an independent prognostic factor for heart failure. Receptor for AGE (RAGE) has a secretory isoform of the receptor protein, termed soluble RAGE. In the present study, we measured serum soluble RAGE levels in patients with heart failure.

Methods: Serum soluble RAGE level was measured in 160 patients with heart failure and 40 control subjects. Patients were prospectively followed with endpoints of cardiac death or re-hospitalization.

Results: Serum soluble RAGE level was increased with advancing NYHA functional class (figure 1

). We determined the cut-off value of serum soluble RAGE level to predict cardiac events from ROC curve analysis as 1220 pg/ml (sensitivity 0.60, specificity 0.69). As shown in figure 2

, high serum soluble RAGE groups (>1220 pg/ml) had a significantly lower cardiac event-free rate (P = 0.0004) than low serum soluble RAGE groups (≥ 1220 pg/ml). In the univariate Cox proportional hazard analysis, serum soluble RAGE, age, NYHA functional class, creatinine, B-type natriuretic peptide (BNP), left ventricular end-diastolic diameter (LVEDD) were significantly associated with cardiac events. In the multivariate Cox proportional hazard analysis, serum soluble RAGE and plasma BNP were independent risk factors for cardiac events (soluble RAGE: HR 2.22, 95% CI 1.08 - 4.53, P = 0.029; BNP: HR 2.86, 95% CI 1.11 - 7.37, P = 0.029).

Conclusions: Serum soluble RAGE level is a novel independent prognostic factor for heart failure.
Abstract 1716: Relationship between Coronary Artery Distensibility and Tissue Characteristics Evaluated by Three-dimensional Integrated Backscatter Intravascular Ultrasound (3D IB-IVUS)
Authors: Ishihara Yoshiyuki , Kawasaki Masanori , Okubo Munenori , Takeyama Urara , Kubota Tomoki , Yasuda Shinji , Takasugi Nobuhiro , Tanaka Shinichiro , Yamaki Takahiko , Ojio Shinsuke , Takemura Genzou , Nishigaki Kazuhiko , Fujiwara Hisayoshi , Minatoguchi Shinya
Published: July 2021

Background:
We developed an Integrated Backscatter Intravascular Ultrasound (IB-IVUS) for tissue characterization of coronary plaques. The relationship between the coronary artery distensibility and tissue components has not been investigated.

Methods:
Fourty-seven plaques with moderate stenosis (30 to 50%) in 36 patients were evaluated by three-dimensional (3D) IB-IVUS at every one millimeter. Plaque distensibility, lumen distensibility, vessel area, lumen area (LA) and plaque area (PA) were measured. Plaque distensibility was defined as follows: [In (systolic BP/diastolic BP)]/[(diastolic PA - systolic PA)/diastolic PA]. Lumen distensibility was defined as follows: [In (systolic BP/diastolic BP)]/[(diastolic LA -systolic LA)/diastolic LA]. % lipid area (lipid area/plaque area) were automatically calculated by IB-IVUS.

Results:
As the % lipid area increased, the lumen distensibility also increased (r = 0.32, p = 0.040). There was a tendency that the plaque distensibility increased as the % lipid area increased (r = 0.31, p = 0.056). 3D plaque distensibility map showed the difference in the plaque distensibility of each segment well.

Conclusion:
This is the first clinical demonstration of the relationship between the % lipid area and plaque distensibility of coronary arteries. The plaque area with greater % lipid area were more likely to increase from systolic to diastolic phase. 3D IB-IVUS color-coded mapping is useful for the evaluation of tissue characteristics and dynamics of coronary plaques.
Abstract 1737: A Strategy for Continuous ECG Recording in Patients Post Pulmonary Vein Isolation for Atrial Fibrillation
Authors: Choi Andrew D , Joshi Sandeep , Marrero Daniel , Raiszadeh Farbod , Badheka Apurva , Steinberg Jonathan S , Mittal Suneet
Published: July 2021

Introduction
: Following pulmonary vein isolation (PVI) for management of atrial fibrillation (AF), may centers obtain continuous ECG recordings for several weeks in order to detect early recurrences of AF. However, the implications of early AF following PVI in an
individual
patient are unknown as is the optimal duration of monitoring in these patients.

Methods
: We evaluated 72 pts (60 ± 11 yrs, 67% male, 67% paroxysmal AF) who underwent PVI and were followed for >= 6 months. At hospital discharge, all pts were fitted with an external event loop recorder (LifeWatch AF Express) for 14 weeks for the continuous automatic detection of AF (defined as an episode lasting >= 30 sec). Clinical follow-up occurred at 1, 3 and 6 months post-PVI; procedural success was defined by freedom from AF at the 6 month follow-up.

Results
: During the 14-week loop monitoring period, no AF was observed in 25 (35%) patients. Only 2 of these pts subsequently developed AF; in both cases, AF occurred 3– 6 months post-PVI. In contrast, 47 (65%) patients had at least 1 AF episode, most commonly (39/47 pts, 83%) within the first 2 weeks of PVI. In fact, absence of AF during the first 2-weeks of loop monitoring identified a cohort of patients with high likelihood of procedural success at 6 months (Figure

).

Conclusions
: Our data support a rationale for at least
2-weeks
of continuous automatic loop ECG monitoring in
all
pts post-PVI. Patients without AF during this period can be expected to have excellent long-term outcome. Longer periods of ECG monitoring may be better limited to patients in whom AF is observed during initial 2-week monitoring.
Abstract 1738: Lone Atrial Fibrillation: Long-Term Clinical and Echocardiographic Follow-up from the Canadian Registry of Atrial Fibrillation
Authors: Leong-Sit Peter , Humphries Karin H , Lee May , Klein George J , Sheldon Robert , Connolly Stuart J , Green Martin S , Talajic Mario , Dorian Paul , Kerr Charles R
Published: July 2021

Background: The natural history of lone atrial fibrillation (AF) is unclear with conflicting data in the literature. We aimed to better describe the clinical outcomes and echocardiographic changes associated with lone AF.

Methods: The Canadian Registry of Atrial Fibrillation (CARAF) enrolled 803 non-surgical and non-flutter patients with new onset AF between 1990 and 1996. At enrollment, patients were classified as lone AF (LAF) or not lone AF (Not LAF) based on structural heart disease or hyperthyroidism. Clinical data was prospectively collected with follow-up at 3 months, 1 year, then annually; echocardiograms were performed at enrollment and years 2, 4, and 7.

Results: The LAF group (n=212) had a median age of 57 (1
st
quartile 44, 3
rd
quartile 67) while the Not LAF group (n=591) had a median age of 67 (59, 73), p<0.0001. During the median follow-up of 8 years in the LAF group and 7 years in the Not LAF group, there was a significant difference in survival free from stroke or embolism favoring the LAF group (Figure

). At 8 years, the probability of remaining free of chronic AF was 78.8% vs 69.3% (p=0.02) and free of symptomatic or documented recurrence of AF was 40.1% vs 26.9% (p<0.01) in the LAF vs Not LAF group. The LAF group had smaller LV diastolic and systolic dimensions by 5.5% and 10.2%, respectively, vs the Not LAF group (p<0.0001). The LV mass was smaller at baseline by 21.1% (p<0.0001) vs the Not LAF group, but increased at a greater rate (4.0% vs 0.9%/2 years, p<0.0001).

Conclusions: Lone AF, compared to non-lone AF, is associated with a lower rate of death, stroke or embolism, recurrence and progression to chronic AF. Interestingly, LV mass increased significantly only in the Lone AF group.
Abstract 283: Redox-mediated Regulation of Histone deacetylase4, a Class II HDAC, by Thioredoxin1 through Interaction with DnaJb5, a Heat Shock Protein 40
Authors: Ago Tetsuro , Liu Tong , Li Hong , Molkentin Jeffery , Sadoshima Junichi
Published: July 2021

Thioredoxin1 (Trx1) reduces redox-sensitive proteins and regulates cell growth and death. We previously reported that cardiac hypertrophy induced by pressure-overload is suppressed in mice with cardiac specific overexpression of Trx1 (Tg-Trx1). To elucidate the mechanisms by which Trx1 suppresses cardiac hypertrophy, we performed DNA microarray analysis using Tg-Trx1 mouse hearts. We identified DnaJb5, a heat shock protein 40, as a gene significantly upregulated by Trx1. Immunostaining and immunoblot analyses indicated that Trx1 and DnaJb5 are co-localized in the nucleus of myocytes. Pull-down and immunoprecipitation assays showed that DnaJb5 interacts with TBP-2, a Trx1-binding protein. DnaJb5 did not disturb the interaction between Trx1 and TBP-2, and enhanced the Trx1 reducing activity. Both Trx1 and DnaJb5 attenuated phenylephrine (PE)-induced activation of NFAT and myocyte hypertrophy
in vitro
. Using transgenic mice harboring an NFAT luciferase reporter, we confirmed that Trx1 suppresses both NFAT activation and cardiac hypertrophy induced by PE
in vivo
. We also found that DnaJb5 binds directly to histone deacetylase 4 (HDAC4), a class II HDAC. An HDAC4 mutant lacking the minimal region responsible for the interaction with DnaJb5 (residues 628 – 881) was localized in the cytosol, in contrast to the nuclear localization of the wild-type HDAC4, suggesting the importance of the interaction for the nuclear localization of HDAC4. Overexpression of Trx1 suppressed PE-induced nuclear export of HDAC4 in myocytes. Using mass spectroscopy, we found that HDAC4 forms a disulfide bond between Cys-667 and -669, which was reduced by Trx1. The HDAC4 Cys667/669Ser mutant was localized in the cytosol, and its nuclear export was suppressed by leptomycin B, an inhibitor of exportin, suggesting that the redox modification induces nuclear export regardless of phosphorylation. Consistently, the Cys667/669Ser substitution abolished the suppressive effect of HDAC4 on NFAT activity and cardiac hypertrophy. Collectively, these results show that Trx1 upregulates DnaJb5, which recruits HDAC4 into the complex formed by Trx1-TBP-2-DnaJb5, thereby reducing HDAC4, retaining its nuclear localization, and suppressing NFAT activity and cardiac hypertrophy.
Abstract 285: Granzymes: Major Players in Vascular Remodelling, Atherosclerosis and Longevity
Authors: Cruz Rani P , Boivin Wendy A , Chamberlain Ciara M , Choy Jonathan C , McManus Bruce M , Granville David J
Published: July 2021

Introduction: Granzymes A and B (GrA/GrB) are cytotoxic proteases that are released by immune cells to eliminate target cells. GrB is present in human vessels and its expression corresponds to increased disease severity. In addition to their cytotoxic roles, in conditions of chronic inflammation, GrA and GrB may contribute to the degradation of extracellular matrix (ECM) proteins leading to tissue degeneration.

Hypothesis: GrA and GrB levels are elevated in atherosclerotic patients and play a key role in the degradation of ECM and atherosclerosis.

Methods: ApoE −/− x GrB −/− double knockout (apoE/GrB-DKO) mice were generated. C57-wt, GrB-KO, apoE-KO or apoE/GrB-DKO mice were fed a high fat diet for 30 weeks, sacrificed, tissues processed and lesion morphology and morphometry assessed. GrA and GrB levels were also measured in human plasma from patients with or without clinically evident atherosclerosis by ELISA. GrA/GrB-mediated ECM proteolytic activity was also assessed.

Results: GrB deficiency significantly reduced the development of xanthomatosis, hair loss and atherosclerosis in the apoE-KO mice. GrB deficiency resulted in a marked reduction of elastin degradation in both the skin and blood vessels. GrB was found to co-localize to elastin fibres in atherosclerotic plaques and was capable of binding to, and cleaving elastin in vitro. ECM cleavage assays demonstrated that GrA and GrB cleave other ECM such as fibronectin. Preliminary studies indicate that GrB deficiency increases the lifespan of the apoE-KO mice as the apoE/GrB-DKO mice can survive up to 60 weeks of age on a high fat diet with no external indication of disease, skin degeneration or hair loss. In humans, preliminary evidence indicates that GrA/GrB levels are elevated in atherosclerosis. Smoking also appears to elevate plasma granzyme levels.

Conclusions: During chronic inflammation, granzymes accumulate extracellularly and exhibit proteolytic activity towards extracellular matrix proteins that results in vascular remodeling and atherosclerosis with age. Attenuation of GrB resulted not only in a significant reduction of atherosclerosis, but also prolonged the lifespan of apoE-KO mice.
Abstract 1759: A 27 year-old Man from ’the Valley’ with Shortness of Breath
Authors: Ho Jennifer E , Yeghiazarians Yerem
Published: July 2021

A 27 year-old man with no significant past medical history was admitted with shortness of breath and subjective fevers. He was diagnosed with Valley fever based on pulmonary infiltrates on chest x-ray and elevated
Coccidiomycosis immitis
IgG and IgM titers and was treated with antifungal therapy. He subsequently developed worsening dyspnea, orthopnea, and lower extremity swelling. On exam his jugular venous pressure was elevated and he had bilateral pleural effusions, lower extremity edema, and a positive Kussmaul sign. The electrocardiogram showed sinus tachycardia with diffuse T-wave inversions. Echocardiography demonstrated thickened adhesive pericardium, exaggerated respirophasic variation of the tricuspid and mitral inflow Doppler patterns and a prominent septal bounce. Cardiac MRI showed markedly thickened enhancing pericardium with an associated small pericardial effusion and prominent septal bounce. There was no delayed enhancement to suggest myocarditis. Cardiac catheterization showed equalization of diastolic pressures in all four chambers, low cardiac output, and simultaneous right and left ventricular pressures showed respirophasic discordance suggestive of increased ventricular interdependence. All of the above findings were consistent with constrictive pericarditis in the setting of disseminated coccidioidomycosis, and the patient underwent urgent surgical pericardiectomy with improvement in his symptoms. Pathology specimens demonstrated fungal spherules and active inflammation consistent with
Coccidiomycosis immitis
infection of the pericardium. This case illustrates the multi-disciplinary diagnostic approach that is often needed to distinguish constrictive pericarditis from restrictive cardiomyopathy. It highlights classic features of constrictive physiology seen on imaging and cardiac catheterization in a unique case of fungal pericarditis. Pericardial involvement in disseminated coccidioidomycosis is rare, and constrictive pericarditis treated with pericardiectomy has been described in only two prior cases in the literature.
Abstract 1761: An Uncommon Cause of Stroke in a 41-Year-old Female
Authors: Merchant Faisal M , Cury Ricardo C , Houser Stuart , Mamuya Wilfred
Published: July 2021

A healthy 41-year-old female experienced sudden onset of right hand weakness, right facial droop and garbled speech. The symptoms lasted for several minutes and then resolved spontaneously. Neurologic exam and head CT were unremarkable. Brain magnetic resonance (MR) imaging demonstrated an infarct in the left frontoparietal operculum; head and neck MR angiogram was unremarkable. A trans-thoracic echocardiogram (TTE) was obtained to evaluate for a patent foramen ovale (PFO) as a cause of paradoxical embolus. Although there was no evidence of PFO, the TTE revealed a 7 × 8 mm pedunculated mass attached to the aortic valve. Trans-esophageal echocardiogram (TEE) confirmed the finding of a highly mobile, echo lucent mass most suggestive of a papillary fibroelastoma (PFE). However, valvular vegetation, thrombus and other primary intra-cardiac tumor could not be excluded. A cardiac MR scan was obtained to further characterize the mass. T2-weighted images demonstrated increased signal within the core of the mass, making tumor more likely than infectious vegetation. The mass also more than doubled in signal intensity after intravenous administration of gadolinium confirming the presence of a vascular source and making thrombus unlikely. The results of non-invasive imaging strongly suggested PFE. In the absence of other stroke source, surgical resection was recommended. Histology of the mass demonstrated a typical budding pattern of fibrous and elastic tissue, confirming the diagnosis of PFE. Papillary fibroelastomas are rare, accounting for less than 10% of primary cardiac tumors; however, they are the most common tumor associated with heart valves. Most PFE are asymptomatic and discovered incidentally. However, due to the risk of embolism, surgical resection is recommended for symptomatic or large left-sided tumors. This case illustrates the importance of a broad differential diagnosis when evaluating a common syndrome (ischemic stroke) in an uncommon circumstance (young patient). It also demonstrates the complimentary nature of echocardiography and cardiac MR in confirming the diagnosis of a cardiac mass prior to invasive therapy. As such, multi-modality imaging has become integral in the evaluation and management of cardiovascular disease.
Abstract 1764: Coapsys
®
Leads to Global Reversal of Left Ventricular Remodeling: Expanded TRACE Study Analysis
Authors: Mittal Sanjay , Mishra Yugal , Trehan Naresh
Published: July 2021

Background:
. We have previously reported as a part of the TRACE study that patients with LV dysfunction undergoing CABG and surgical implantation of Coapsys had significant reductions in LV size and MR at 1 year. Echo data of patients who recieved CABG with and without Coapsys, were retrospectively analyzed to determine the extent and pattern of LV reverse remodeling related to the LV shape change properties of Coapsys.

Methods:
Coapsys consists of anterior and posterior epicardial pads connected by a flexible chord, drawn together to affect change in valvular and ventricular geometry. Coapsys was implanted in patients whose MR remained ≥ grade 2 after CABG (Coapsys + CABG group, n=32). Patients whose MR grade reduced to 1 or less after CABG (CABG Alone group, n=35) received CABG only. Baseline age, ejection fraction, graft number, and MR grade in the Coapsys + CABG group and the CABG Alone group were 58, 35, 2.7, 3.0 and 59, 37 2.8, 2.7 respectively. Detailed echocardiographic measurements of diastolic left ventricular dimensions in 3 echo planes, 4 Chamber (4 Ch), 2 Chamber (2 Ch), and Long Axis (LAX), along with LV length and anterolateral papillary muscle (ALPM) depth were serially collected up to 12 months after surgery.

Results:
Comparison of baseline, 3 month and 12 month dimensions between Coapsys + CABG and CABG Alone groups are displayed in Figure 1

.

Conclusions:
In patients with MR and LV dysfunction undergoing implantation of Coapsys along with CABG, there is significant, global and progressive reversal of LV remodeling. This may to be related to the LV shape change properties of Coapsys and could benefit patients with heart failure.
Abstract 1767: Feasibility of
In Vivo
Cardiac Stem Cell Tracking, by SPECT and PET Imaging, Using the Sodium-iodide Symporter as Reporter Gene
Authors: Terrovitis John , Kwok Keng Fai , Läutamaki Riikka , Engles James M , Barth Andreas S , Miake Junichiro , Leppo Michelle K , Fox James , Seidel Jurgen , Wahl Richard L , Tsui Benjamin , Bengel Frank , Marbán Eduardo , Abraham M. Roselle
Published: July 2021

Background.
Stem cells offer the promise of cardiac repair. Stem cell labeling is a prerequisite to tracking cell fate
in vivo
.

Aim.
To develop a reporter gene that permits
in vivo
stem cell labeling. We examined the sodium-iodide symporter (NIS), a protein that is not expressed in the heart, but promotes cellular uptake of
99m
Tc or
124
I, thus permitting cell tracking by SPECT or PET imaging, respectively.

Methods.
The human NIS gene (
h
NIS) was expressed in rat cardiac derived stem cells (rCDCs) using lentivirus driven by the CAG or CMV promoter. NIS function in transduced cells was confirmed by
in vitro
99m
Tc uptake. Eleven rats were injected with 1 or 2 million rCDCs intramyocardially immediately after LAD ligation; 6 with CMV-NIS and 5 with CAG-NIS cells. Dual isotope SPECT imaging was performed on a small animal SPECT/CT system, using
99m
Tc for cell detection and
201
Tl for myocardial delineation, 24 hrs after cell injection. PET was performed on a small animal PET scanner using
124
I for cell tracking and
13
NH
3
for myocardial delineation, 48hrs after cell injection. Contrast Ratio (CR) was defined as [(signal in the cells)-(signal in blood pool)]/signal in blood pool. High resolution
ex vivo
SPECT scans of explanted hearts (n=3) were obtained to confirm that
in vivo
signal was derived from the cell injection site. The presence of
h
NIS mRNA was confirmed in injected hearts after animal sacrifice (n=2), by real-time RT-PCR.

Results.
NIS expression in rCDCs did not affect cell viability/proliferation (p=0.718, ctr vs NIS). In vitro
99m
Tc uptake was 6.0±0.9% vs 0.07±0.05, without and with perchlorate (specific NIS blocker), respectively. NIS-transduced rCDCs were easily visualized as spots of
99m
Tc or
124
I uptake within a perfusion deficit in the SPECT and PET images. CR was considerably higher when cells were transduced by the CMV-NIS virus in comparison to the CAG-NIS virus (70±40% vs 28±29%, p=0.085). Ex vivo small animal SPECT imaging confirmed that
in vivo
99m
Tc signals were localized to the injection sites. PCR confirmed the presence of
h
NIS mRNA in injected hearts.

Conclusion.
NIS expression allows non invasive
in vivo
stem cell tracking in the myocardium, using both SPECT and PET. This reporter gene has great potential for translation in future clinical applications.
Abstract 1769: Multidetector Computed Tomography allows accurate non-invasive Diagnosis of Etiology of Heart failure as compared with Coronary Angiography and contrast-enhanced MRI
Authors: le Polain de Waroux Jean-Benoit , Pouleur Anne-Catherine , Goffinet Céline , Pasquet Agnès , Vanoverschelde Jean-Louis , Gerber Bernhard L
Published: July 2021

Background:

The distinction of ischemic vs. non-ischemic origin is essential for prognosis and treatment of patients (pts) with congestive heart failure (CHF). To determine etiology, pts typically undergo invasive coronary angiography (CA). Additional information can be obtained by detecting necrosis or fibrosis on delayed enhanced (DE) magnetic resonance (cMR). Recently, we and others have demonstrated that detection of myocardial necrosis is also feasible by multidetector CT (MDCT) at the time of non-invasive coronary imaging. We therefore evaluated whether such a combined and comprehensive evaluation of coronary anatomy and infarct characterization by MDCT might be useful for determining the etiology of CHF.

Methods:

Sixty-one consecutive pts (44 males, 60 ± 16 years) with CHF (mean ejection fraction: 26 ± 11%) of undetermined etiology underwent MDCT, DE-MR and CA. Presence of coronary artery disease (CAD) and patterns of DE on MDCT were compared to CA and DE-MR.

Results:

According to CA, 27 pts (44%) had significant CAD (>50% stenosis in at least one major coronary artery). DE-cMR demonstrated transmural or subendocardial DE in 21 of these 27 pts. These 21 pts were considered to have definite ischemic CHF (group 1). Among the 34 pts without CAD on CA, 23 had no DE on cMR, while 7 (11%) presented midventricular or sub-epicardial DE. These 30 pts were considered to have definite non-ischemic CHF (group 2). Four pts had transmural DE but no CAD and were considered to have probable ischemic CHF (group 3). Finally, 6 pts with CAD on CA, but without DE on cMR were considered to have probable non-ischemic CHF (group 4). Pts were also classified into the same 4 groups using coronary and DE-MDCT. On a per patient basis, agreement between coronary and DE-MDCT and CA/DE-cMR for the diagnosis of patients was excellent (κ=0.87; p<0.001). Coronary and DE-MDCT had 96% sensitivity, 92% specificity and 93% accuracy for detecting definite (group 1) or probable (group 3) ischemic CHF as compared to DE-cMR and CA.

Conclusion:

Combined coronary and DE-MDCT allows for the accurate differentiation of ischemic vs non ischemic etiology of CHF as compared to CA and DE-cMR. Using this single test is however cheaper and faster than combined use of DE-cMR and CA for establishing etiology of CHF.
Abstract 1770: Left Ventricular Filling Curve Variables are Superior to Resting Lung to Heart Ratios in Predicting Left Ventricular End-diastolic Pressure in Patients with Preserved Systolic Function Undergoing Gated Myocardial Perfusion Imaging
Authors: Patel Dineshkumar , Robinson Vincent J , Arteaga Roque B , Thornton John W , Norman Laura K , Carpenter Jimel , Mandawat Mahendra K
Published: July 2021

Introduction:
There is a 4–5 fold increase in morbidity and mortality when diastolic dysfunction is present in patients with coronary artery disease (CAD). Thallium-201 lung/heart ratio (TLHR) at stress has been proven to capture this increased risk. Most laboratories however use technetium-99m agents for stress myocardial perfusion imaging (MPI) which prevents access to stress TLHR.

Method:
This is a retrospective study of 52 consecutive patients (age 58±11 years, 73% had CAD) who underwent MPI and cardiac catheterization within 15 days, without interval change in medication or intervention. All patients had ejection fraction ≥45% and normal sinus rhythm. Left ventricular end-diastolic pressure (LVEDP) at cardiac catheterization was recorded. From MPI, peak filling rate (PFR), time to peak filling rate (TPFR), filling rate during first 1/3 of diastole (1/3FR) were obtained using 4D-MSPECT (University of Michigan) and rest TLHR was calculated manually.

Results:
PFR, TPFR and 1/3FR correlated significantly with LVEDP (r= −0.53, 0.45, −0.45 and
p
=0.00005, 0.0008, 0.0009 respectively). Rest TLHR did not correlate with PFR, TPFR and 1/3FR (r=0.11, 0.06, 0.09 and
p
=0.47, 0.68, 0.55 respectively) or with LVEDP (r=0.10,
p
=0.49). These variables had excellent negative predictive value (NPV) of ≥90% but modest positive predictive value (PPV) of ≥54%. Since PFR did not correlate with 1/3FR (r=0.18,
p
=0.19), we combined these 2 variables. This combination had a NPV of 84% and improved PPV to 86% and specificity to 94%.

Conclusions:
Our study validates diastolic filling variables from 4D-MSPECT showing excellent correlation with LVEDP at cardiac catheterization (
p
≤0.0009). PFR, TPFR and 1/3FR are superior to rest TLHR and they have excellent sensitivity (≥82%) and specificity (≥63%) for detecting LVEDP ≥18mmHg. Hence, a valid methodology of combining the risk of perfusion defects with diastolic impairment can be achieved by adding PFR, TPFR and 1/3FR to MPI results.

Receiver Operated Characteristic Curve Analysis