bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2137: Bicuspid Aortic Valve, Aortic Dissection And Sudden Death In The Young: Just A Matter Of Ascending Aorta Diameters?
Authors: Basso Cristina , Nistri Stefano , Rizzo Stefania , Abudureheman Aierkeen , Thiene Gaetano
Published: July 2021

Background.
Although bicuspid aortic valve (BAV) may remain silent during life, it can announce dramatically with aortic dissection and sudden death. The aim of the study was to determine the aortic diameters and histopathologic background in young people with BAV and aortic dissection.

Design.
Among 449 cardiovascular sudden deaths in the young (<35 years), 15 (3.3%), mean age 27±6.6, 14 M/1F, had a mechanical cardiac arrest due to aortic dissection (type I: 7, type II: 6, type III: 2): 6 had isolated BAV, 2 BAV associated with coarctation, 2 Marfan syndrome, 1 coarctation, 1 pregnancy, 1 hypertension and 2 were idiopathic. Ten young BAV patients who died suddenly without aortic dissection and 10 sex and age-matched controls were considered for comparison. Aortic root was measured at 4 levels (A1, annulus; A2, sinuses of Valsalva, A3, supraaortic ridge and A4, proximal ascending aorta). Histopathologic evaluation of the aortic tunica media was performed to assess elastic fragmentation, disarray, medial necrosis, proteoglycans deposits and fibrosis.

Results.
Aortic diameter values in dissected BAV vs normal BAV vs controls were: A1, 30.7±2.0 vs 27.4±2.3 (p=0.05) vs 26.3±1.6 (p<0.001); A2, 35.0±5.2 vs 28.9±1.8 (p=0.01) vs 27.3±1.5 (p=0.003); A3, 32.5±5.8 vs 26.7±2.5 (p=0.03) vs 24.5±1.5 (p=0.003); and A4, 38.7±7.0 vs 26.6±3.4 (p=0.002) vs 23.9±1.8 (p<0.001). Aortic diameters were significantly higher in Marfan patients (A1, 34.4±2.7; A2, 44.9±4.0; A3, 45.8±5.4; A4, 46.4±1.9). When comparing BAVs with and without dissection, higher scores of medial necrosis (1.2±0.4 vs 0.2±0.5, p=0.01), elastic fragmentation (2.4±0.5 vs 0.7±0.5, p=0.001) and fibrosis (1.6±0.5 vs 0.2±0.5, p=0.004) were found. Moreover, when comparing dissected BAVs and Marfan patients, similar structural abnormalities were found except lower medial necrosis (1.2±0.4 vs 2±0.0, p=0.002).

Conclusions.
Aortic root diameters are lower in dissected BAV than Marfan patients. However, structural abnormalities of the tunica media in terms of elastic fragmentation and fibrosis are similar. Imaging techniques able to assess not only a progressive increase of aortic diameters, but also abnormal aortic elasticity and stiffness are warranted to indentify patients at risk of aortic dissection.
Abstract 2148: Sirolimus-eluting Stent Versus Bare-metal Stent In Diabetic Patients: Results Of The Italian Multicenter, Randomized “Dessert” Study.
Authors: Maresta Aleardo , Varani Elisabetta , Balducelli Marco , Aquilina Matteo , Vecchi Giuseppe
Published: July 2021

Background:
The real benefit of DES in diabetic patients is still debated since few studies have performed a direct randomized comparison between DES and BMS in such a population.

Methods
: The “Dessert” study is a multicenter, randomized trial conducted in Italy to demonstrate the efficacy of sirolimus-eluting stents (SES) compared to BMS in de novo lesions in native coronary arteries of diabetic patients, treated with insulin and/or oral antidiabetics for at least 3 months. Intraprocedural abciximab or pre-procedural tirofiban were administered to all patients. The primary end point was in-stent late loss as assessed by centralized quantitative coronary angiography at 8-month follow up. Centrally adjudicated composite MACE (death, Q wave and non-Q wave myocardial infarction, emergent bypass surgery or repeat target lesion revascularization) and target vessel failure (TVF: death, treated vessel related AMI, TLR) at 30 days, 9 and 12 months, and binary restenosis 8 months post-procedure were the secondary endpoints.

Results:
One hundred fifty patients were randomized to SES (75 patients, 109 lesions) or BMS (75 patients, 109 lesions). The two groups were well balanced for clinical, anatomic and procedural characteristics. On average, 45% of patients had multivessel or multilesion PCI, reference diameter was 2.66±0.43 mm and lesion length was 14.9±7.1 mm. In-stent late lumen loss was reduced from 0.96±0.61 mm for BMS to 0.14±0.33 mm for SES (p<0.001); in-segment binary restenosis resulted 38.8% vs 3.6% respectively (p<0.001). Twelve-month clinical events were significantly lower in the sirolimus group: MACE 22.1% vs 38.6%, p=0.035; TLR 5.9% vs 30%, p<0.001; TVF 14.7% vs 34.3%, p=0.008. One case of subacute stent thrombosis occurred in sirolimus group, and one late stent thrombosis in bare-metal group. At multivariable analysis, stent type confirmed as independent predictor of in-segment late loss (p<0.001), binary restenosis (p<0.001), 12 month TVF (p=0.010) and 12-month MACE (p=0.037).

Conclusions:
The randomized “Dessert” study demonstrated that SES are safe and efficacious in reducing both angiographic and clinical parameters of restenosis compared with BMS in diabetic patients with de novo 1 or 2 vessel coronary stenoses.
Abstract 2151: Long-Term Outcome in Patients Treated with Sirolimus Eluting Stents in Complex Coronary Artery Lesions. Analysis of 3-year Results of the Randomized SCANDSTENT Trial
Authors: Kelbćk Henning , Thuesen Leif , Sygehus Skejby , Kløvgaard Lene , Helqvist Steffen , Krussel Lars R , Sygehus Skejby , Saunamäki Kari , Lassen Jens F , Sygehus Skejby , Jørgensen Erik
Published: July 2021

Background

- The long-term outcome of patients with complex coronary artery lesions treated with drug-eluting stents is unknown. This study evaluated the 3-year clinical outcome of patients randomized in the SCANDSTENT study to have sirolimus-eluting stents (SES) or bare metal stents (BMS) implanted in their complex lesions.

Methods and Results

- We randomly assigned 322 patients with symptomatic coronary artery disease and either a total coronary occlusion, a lesion located in a bifurcation, in an ostial or in an angulated segment of the coronary artery to have SES or BMS implanted. At 3 years, major adverse cardiac events had occurred in 24 patients (15%) in the SES group and in 59 patients (37%) in the BMS group (
P
<0.001). Four versus 2 patients suffered a cardiac death (NS), and 5 versus 1 died of a non-cardiac disease (NS). Six patients in the SES group versus 15 patients in the BMS group suffered a myocardial infarction (
P
<0.05), and target lesion revascularization was performed in 8 patients (4.9%) versus 53 patients (33.8%), respectively (
P
<0.001); of these 4 in the SES versus 7 in the BMS group was performed between 1 and 3 years after the index treatment (NS). According to revised definitions, stent thrombosis occurred in 5 patients (3.1%) in the SES group and in 7 patients (4.4%) in the BMS group (NS); very late stent thromboses were observed in 4 versus 1 patient.

Conclusions

- A continued benefit was observed out to 3 years after implantation of SES in patients with complex coronary artery lesions. Late adverse events occurred less frequently in the SES group, and stent thromboses occurred rarely after 1 year.
Abstract 2164: Impact of Sirolimus-Eluting Stent and Paclitaxel-Eluting Stent on the Outcome of Patients with Sirolimus-Eluting Stent Failure: Multicenter Registry in Asia
Authors: Nakamura Sunao , Hirose Mizuki , Bae Jang-Ho , Cahyadi Yeo H , Udayachalerm Wasan , Tresukosol Damras , Tansuphaswadikul Sudaratana
Published: July 2021

Purpose:
To evaluate the Sirolimus-eluting stent (SES) and Paclitaxel-eluting stent (PES) on the outcome of patients with SES failure (SES-F).

Methods:
A total of 520 patients with 609 SES-F lesions (male 74.8%, mean age 72.1 yrs, LMT 7.1%, LAD 47.6%, LCX 25.0%, RCA 16.2%, SVG 4.1%) were treated with SES (mean lesion length 26.1±12.6 mm, mean stent length 31.3±15.9mm) and PES (mean lesion length 28.3±12.2 mm, mean stent length 32.9±19.3 mm). We evaluate immediate and long-term clinical results by 6 and 12 months angiography.

Results:
The baseline clinical characteristics between 2 groups were similar. See table for clinical results.

Conclusion:
The use of SES and PES in patients with restenosis after SES implantation was safe with low complications. Patients treated with SES showed lesser rate of restenosis compared with PES.
Abstract 2198: Rhythmic Risk in Idiopathic Dilated Cardiomyopathy Depending on the Evolution of Left Ventricular Ejection Fraction in Patients with Implantable Cardioverter Defibrillators
Authors: Kouakam Claude , Theodore Guillaume , Marquie Christelle , Klug Didier , Guedon-Moreau Laurence , Brigadeau François , Marechaux Sylvestre , de Groote Pascal , Lacroix Dominique , Kacet Salem
Published: July 2021

Background

: Patients with idiopathic dilated cardiomyopathy (DCM) receiving an ICD often improve their left ventricular dysfunction in the year following implantation due to reverse remodelling and/or optimization of concomitant drug therapy. We examined whether this improvement impacts the benefit of ICD in terms of appropriate therapy.

Methods

: The study comprised 93 consecutive DCM patients with LVEF <35% and an indication for ICD (primary prevention = 37, secondary prevention = 56). Follow-up duration was 12 to 42 (median 25) months. LVEF was reassessed 5 to 13 (median 7) months after implantation and compared with baseline value at implantation. Concomitant drug therapy with ACE inhibitors and beta blockers was optimized during the same period, according to recent guidelines. All arrhythmic events were assessed by ICD memory interrogation during follow-up. Major (MaAE) and minor (MiAE) arrhythmic events were defined as appropriate shock or ATP for sustained ventricular tachyarrhythmias >200 bpm or <200 bpm respectively. Early events (before LVEF evaluation) were separated from late events (after LVEF evaluation).

Results

: Overall the mean LVEF increased by 7.2 % from 24.6±7% at baseline to 31.8±12% at revaluation. Two patterns were observed: 23 patients had a >14% LVEF increase (group 1) whereas 70 others had an increase <14% in LVEF (group 2). In group 1, 3 MaAE and 1 MiAE occurred in the early period but no event in the late period. In contrast, MaAE were observed in 15 and MiAE in 31 patients from group 2 during the late period. On multivariate analysis, changes in LVEF was an independent predictor of MaAE (OR=0.85; 95% CI 0.77 to 0.95; p=0.005) and MiAE (OR=0.91; 95% CI 0.84 to 0.99; p=0.02) during the late period. On multivariate analysis LVEF improvement was negatively correlated to diuretic use and QRS duration at baseline and to the absence of moderate or severe mitral regurgitation.

Conclusions

: In DCM, rhythmic risk is dynamic and inversely related to the improvement in LVEF. Reverse remodelling under optimal therapy is associated with a late favourable outcome, but 17% of these patients however benefit from ICD therapy in the early period.
Abstract 2225: A Blinded, Randomized Controlled Evaluation Of An Impedance Threshold Device During Cardiopulmonary Resuscitation In Swine
Authors: Mader Timothy J , Kellogg Adam , Smith Jeremy , Murphy Brett , Hynds-Decoteau Rachael , Gaudet Claudia , Caron John , Paquette Allie
Published: July 2021

Background: An impedance threshold device (ITD) has been designed to enhance circulation during CPR. A recent study suggests that the ITD does not improve hemodynamics and that it may worsen outcomes. We sought to determine, in a blinded fashion, the effect of the ITD on coronary perfusion pressure (CPP), passive ventilation (paO2 & paCO2), and return of spontaneous circulation (ROSC), in a porcine model of prolonged ventricular fibrillation (VF). We hypothesized that, when compared to sham, the active device would have no significant impact on these variables.

Methods: Thirty devices (15 active/15 sham) were purchased from the Resuscitation Outcomes Consortium. Thirty male Yorkshire swine were instrumented under anesthesia. VF was electrically induced. After 8” of untreated VF, baseline characteristics were documented and CPR was begun (chest compressions rate 100/minute and ventilations at a ratio of 30:2). The device used on a given animal (active or sham) was randomly assigned. After 3 cycles of basic CPR, a second ABG was drawn and a drug cocktail was given followed by 6 CPR cycles. We recorded CPP continuously. The first 150J rescue shock (RS) was delivered after 9 complete cycles (3 minutes) of CPR. A third ABG was drawn just prior to the first RS. ROSC was defined as systolic blood pressure >80 mmHg for >60s continuously. The randomization code was revealed once preliminary data analysis was completed. Group comparisons were assessed using descriptive statistics, Student’s
t
-test for continuous variables and Fisher’s Exact Test for dichotomous variables. Proportions with 95% confidence intervals were calculated for the rate of ROSC.

Results: Baseline characteristics between the two groups were the same. ROSC occurred in 14/15 animals in both active and sham. The table

summarizes the results (mean) by group after each event/intervention (CPP in mmHg, paO2 & paCO2 in torr).

Conclusions: Use of the active device had no impact on CPP, paO2 & paCO2 or ROSC compared to sham.
Abstract 2230: Lower Extremity Counterpulsation During The Decompression Phase of CPR Improves Hemodynamics And Provides Continuous Forward Carotid Blood Flow.
Authors: Yannopoulos Demetris , Halperin Henry R , Hopkins Johns , Lurie Keith G
Published: July 2021

Background:
We hypothesize that lower extremity counterpulsations (LECP) during the decompression phase of CPR will increase diastolic aortic pressure without raising the intracranial pressure (ICP) and significantly increase forward carotid blood flow.

Methods:
In 6 (24±4Kg) pigs, 4 minutes of untreated VF were followed by 2 minutes epochs of standard (STD) CPR, STD +LECP, active compression decompression (ACD) +ITD and ACD + inspiratory impedance threshold device (ITD)+LECP. Compressions and ventilations were performed according to the 2005 AHA guidelines. A large blood pressure cuff that was circumferentially placed around the pig’s thighs avoiding the abdominal cavity was inflated with air to the point that manometer pressure started to rise. Compressions over the cuff were performed manually and synchronized with the thoracic decompression phase. The cuff was compressed up to 200mmHg. Basic hemodynamic parameters and common carotid blood flow (CCBF) (ml/min) were continuously measured. Cerebral perfusion pressure (CerPP) (mean arterial pressure - mean ICP) and CPP (diastolic AoP - diastolic RAP) were calculated at the end of the 2 minute epochs. Statistical analysis was performed with ANOVA.

Results:
LECP significantly increased diastolic aortic pressure, CPP and CerPP both when added on STD and on ACD+ITD CPR. The largest benefit was observed with ACD+ITD+LECP were there was a 2-fold increase in CPP and CerPP with a 2.5-fold increase in common carotid blood flow compared to STD CPR. LECP did not alter ICP. (Table 1

). Decompression phase CCBF during ACD+ITD+LECP CPR was

positive

and reached pre cardiac arrest levels.

Conclusion:
LECP during thoracic decompression significantly augmented aortic diastolic pressure, CPP and CerPP

without increasing the ICP

. LECP led to a continuous positive cerebral perfusion pressure gradient during CPR cycles and in combination with ACD + ITD CPR common carotid blood flow reached pre-arrest levels.

Hemodynamic Parameters
Abstract 2244: A Novel Micropace-Ablate Protocol Eliminates Coagulum Formation in Radiofrequency Ablation
Authors: Lim Bernard , Venkatachalam K.l. , Johnson Susan , Jahangir Arshad , Asirvatham Samuel
Published: July 2021

Radiofrequency (RF) ablation for cardiac arrythmias is an established curative therapy. However, catheter-tip coagulum formation leading to thromboembolic stroke is a persistent problem despite heparinization. Recent studies demonstrated an up to 70% incidence of thrombus formation on the catheter tip during ablation and a 10 % incidence of thromboembolic events. Catheter tip thrombus can impede the delivery of RF energy to the tissue, resulting in reduced efficacy and longer procedure times. Here we report on a novel method to prevent coagulum formation on ablation catheters by delivering a negative charge to the catheter tip to repel negatively charged fibrinogen molecules during RF ablation. A novel circuit was built with a charge delivery unit using a 9 voltage battery to deliver a fixed offset direct current charge, placed in parallel to the RF delivery unit for negative charge placement during RF delivery. In
in-vivo
canine experiments (n=50) standard 6/4, 8/5 ablation catheters and catheters with abraded tips were advanced from right femoral veins into atria and ventricles under intra-cardiac echo (ICE) and biplane fluoroscopic guidance. The dogs received 1 of 2 therapies:

no RF energy delivered with and without negative charge delivery,

RF energy delivery with and without negative charge delivery.

The presence of thrombus was identified with ICE. The catheter tips were examined also macroscopically with visual inspection and also with field emission scanning electron microscopy (FESEM). FESEM of the catheter tips showed surface coverage of fibrin clot of the catheter tip to be 90 % for non-charged catheters compared to 0 % (p< 0.01) in negatively-charged catheters. There was no significant difference in surface coverage of fibrin clot between negatively-charged catheters with the abraded tips (98.8%) and non-charged catheters with smooth tips (90.7 %, p=ns). Clot volume formed on the catheter tip decreased with increased amount of charge. Application of a negative charge did not affect the quality of the intracardiac electrograms or induce malignant ventricular arrhythmias. Negative charge delivery during RF ablation is feasible and safe and can eliminate coagulum formation, potentially reducing thromboembolic complications.
Abstract 2280: Urine Albumin/creatinine Ratio, Cardiac Structure And Diastolic Function In Patients With Hypertension And Diastolic Dysfunction: The Validd Study
Authors: Verma Anil , Janardhanan Rajesh , Daley William L , Ritter Susan , Kaye William A , Naqvi Tasneem , Lacourcier Yves , Aurigemma Gerard , Thomas James D , Zile Michael , Solomon Scott D
Published: July 2021

Background:
Increasing urine albumin/creatinine ratio (ACR) is associated with systemic microvascular damage and increased cardiovascular morbidity and mortality. However, the relationship between albuminuria and left ventricular (LV) diastolic function, an early measure of myocardial end-organ damage in hypertension, has not been well defined.

Methods:
Urine ACR and echocardiographic measures of LV structure and function were assessed in 384 patients enrolled in the VALsartan In Diastolic Dysfunction (VALIDD) trial with mild hypertension and no heart failure and evidence of diastolic dysfunction based on Doppler assessment of myocardial relaxation velocities.

Results:
Urine ACR was undetected in 151 (39.3%) subjects, between 1 to 30 mg/g in 194 (50.5%), and > 30mg/g in 39 (10.2%). The mean blood pressure in the cohort was 143.8 ± 16.1/86.2 ± 10.3 mmHg and LV hypertrophy was present in < 4% of enrolled patients. Higher urine ACR was associated with lower annular relaxation velocity (E′), higher E/E′ (Figure

), higher prevalence of concentric LV remodeling and higher NT-ProBNP even after adjusting for age, diabetes, systolic BP, eGFR and LV mass index (LVMi) (p < 0.02 for all associations).

Conclusion:
Albuminuria is associated with worsening diastolic function in patients with hypertension, and both measures may represent important and modifiable markers of early end-organ damage even in patients with mild blood pressure elevation.

E′ stratified by urine albumin creatinine ratio

E/E′ stratified by urine albumin creatinine ratio
Abstract 2288: Does Perioperative Diastolic Dysfunction Affect Postoperative Outcome ?
Authors: Matyal Robina , Mahmood Feroze , Subramaniam Balachundar , Panzica Peter , Karthik Swaminathan , Pomposelli Frank , Hess Philip
Published: July 2021

Objective:
To assess the presence of perioperative diastolic dysfunction (DD) in patients undergoing vascular surgery with transesophageal echo (TEE) and its association with postoperative morbidity and mortality.

Methods:
We conducted TEE examinations on 282 patients undergoing high-risk vascular surgery under general anesthesia (GA). All TEE examinations were conducted after induction of GA and endotracheal intubation. We used transmitral flow propagation velocity (Vp); a validated echocardiographic index of left ventricular filling and DD, for assessment of perioperative DD. A Vp value of < 0.45m/sec is considered diagnostic of DD. We used Fisher’s Exact Test and Pearson’s Chi-Square to compare the incidence of postoperative complications i.e. congestive heart failure (CHF), myocardial infarction (MI), arrhythmias, prolonged intubation and death in patients with and without DD. Statistical significance was set at a p-value of ≤ 0.05.

Results:
There were 176 males and 102 females. The mean age in males was 68.6 and 72 years in females. We were able to assess Vp in all these patients. A total of 184 (66%) patients had Vp < 0.45 m/sec. Of these patients with DD, 60 patients (32.6%) had at least one adverse outcome. Ejection fraction (EF) was comparable between the patients with and without adverse outcomes. A Vp value of <0.45m/sec was associated with a statistically significant increase in the incidence of postoperative CHF and arrhythmias and a trend towards higher incidence of postoperative prolonged intubation but not that of MI or death (Table 1

).

Conclusion:
Vp is an easily obtained index of left ventricular filling. Almost 2/3
rd
(66%) of the patients presenting for vascular surgery were diagnosed to have DD by an abnormal Vp. Presence of perioperative DD is associated with a higher incidence of postoperative complications (CHF, Arrhythmias, Prolonged Intubation).

Table 1

Vp: Transmitral Flow Propagation Velocity
Abstract 2290: Assessment of Left Ventricular Torsion Using Two Dimensional Speckle Tracking Echocardiography: Comparison with Tagged Cardiac Magnetic Resonance.
Authors: Goffinet Celine , Chenot Fabien , Montant Patrick , Vancraeynest David , Pouleur Anne-Catherine , le Polain de Waroux Jean-Benoît , Pasquet Agnès , Gerber Bernhard , Vanoverschelde Jean-Louis
Published: July 2021

Background.
LV torsion from helically oriented myofibers is a key parameter of cardiac performance. Until now, LV torsion could only be assessed using tagged cardiac magnetic resonance (cMR). Because of its high spatial and temporal resolution, speckle tracking echocardiography (STE) could be an alternative to cMR. STE offers the opportunity to track myocardial motion independently of both cardiac translation and angle-dependency. The aim of this study was to evaluate the accuracy and reproducibility of STE for the estimation of LV torsion using cMR as the reference standard.

Methods
. Ten controls and 43 patients with a variety of cardiac disease underwent cMR and STE on the same day. STE datasets were analyzed using a prototype version of the 2DQ QLab software that allows to track speckles on a frame by frame basis in the endocardium and epicardium, and to derive LV torsion and twisting velocities. Care was taken to analyze cMR and STE data on similar short-axis slices, matched on basis of their end-diastolic internal dimensions. Inter- and intraobserver variabilities were estimated by two blinded observers for 20 patients. In 5 volunteers STE and cMR were repeated twice to assess test-retest reproducibility.

Results
. Measurements of endocardial, midwall and epicardial torsion by cMR and STE did not differ significantly from each other (12.6 ± 5.9° vs. 12.5 ± 5.6°, 10.7 ± 4.7° vs. 9.7 ± 4.1°, and 8.9 ± 4.1° vs. 8.5 ± 3.8°, all p=ns) and were highly correlated (r=0.96, 0.88 and 0.79), with only small intertechniques biases (0.11 ± 3.4°, 0.98 ± 4.7° and 0.4 ± 5.28°). Peak twisting velocities, obtained by deriving systolic torsion over time, were also similar between cMR and STE (54 ± 18°/s and 63 ± 23°/s, p=ns) and were highly correlated (r=0.74). The intra- and interobserver agreement for peak LV torsion measurements, assessed by the intraclass correlation coefficient, was equally good for cMR (ICC=0.98 and 0.96; bias 0.3 ± 2.9 and 0.65 ± 3.1°) and for STE (ICC=0.98 and 0.96; bias 0.05 ± 2.8 and 0.13 ± 4.7°). Test-retest reproducibility was also excellent.

Conclusions
. Our data show that, compared to cMR, STE allows LV torsion to be accurately and reproducibly measured. This should make LV torsion assessment more available in clinical and research cardiology.
Abstract 2300: Selective Serotonin Reuptake Inhibitor Use is Associated with Decreased Mortality in Pulmonary Hypertension
Authors: Shah Sanjiv J , Gomberg-Maitland Mardi , Thenappan Thenappan , Archer Stephen L , Rich Stuart
Published: July 2021

Introduction:
The serotonergic pathway appears to be involved in pulmonary hypertension (PH) and selective serotonin reuptake inhibitors (SSRIs) prevent development of PH in animal models. We hypothesized that SSRIs would decrease development of PH and would be associated with decreased mortality in PH patients (pts).

Methods:
In a case-control study of the Surveillance of PH in America (SOPHIA) registry, we first tested whether pts without PH had increased SSRI exposure compared to those with PH. In SOPHIA, 1335 pts underwent invasive hemodynamic study and were classified as no-PH (N=155) or confirmed-PH (N=1180). We used logistic regression to see if the no-PH group had increased exposure to SSRIs. Next, we studied baseline SSRI use in the Pulmonary Hypertension Connections (PHC) cohort, a referral-based registry of adults with PH (N=542). A Cox proportional hazards analysis was used to see if SSRI use was associated with decreased mortality.

Results:
In SOPHIA, the no-PH group had a 1.8-fold increased odds of being exposed to SSRIs compared to the confirmed-PH group (p<0.05). In PHC, 69/542 (13%) were taking SSRIs at time of referral. Pts taking SSRIs were more often obese, but otherwise had similar to those not taking SSRIs. During mean follow-up of 4.0±3.1 yrs, 12% of pts taking SSRI vs. 23% of pts not taking SSRI died (hazard ratio [HR] 0.35; p=0.023). The association between SSRI and decreased mortality persisted after adjusting for age, gender, etiology of PH, and obesity (HR 0.36; p=0.026).

Conclusions:
SSRI use appears to be associated with decreased development of PH and decreased mortality in PH. These findings provide rationale for a randomized trial of SSRIs in PH.
Abstract 2301: Agonistic Autoantibodies Against the Endothelin 1 ETA - and α1-Adrenergic- Receptor in the Sera of Patients with Idiopathic Pulmonary Arterial Hypertension.
Authors: Wallukat Gerd , Dandel Michael , Müller Johannes , Bartel Sabine , Schulze Wolfgang , Hetzer Roland
Published: July 2021

Background:
Idiopathic pulmonary arterial hypertension (IPAH) is a progressive fatal disease of unknown cause. This disease is accompanied by an massive increase of pulmonary vascular resistance (remodelling and increase of vascular tonus) inducing right heart failure. It was shown that the synthesis of vasoconstrictors (endothelin 1, thromboxane A2, serotonine) is elevated in patients with IPAH.

Methods:
We analyzed sera of patients with PH with regards to functional autoantibodies (AABs) against G-protein coupled receptors using spontaneously beating rat cardiomyocytes as bioassay. Moreover, we investigated the effect of the AAB on the translocation of the transcription factors NFκB and AP-1.

Results:
The sera of patients with IPAH contain functional AABs against the α1-adrenergic (α1-AR) and the endothelin1 ETA receptor. We purified the AABs by affinity chromatography. AABs against the α1-AR exert a positive chronotropic effect. AABs against the ETA receptor induce like endothelin 1 a negative chronotropic effect. The agonistic effect of the AABs was dose-dependent and blocked by prazosine (α1-AR blocker) and BQ610 (ETA antagonist), respectively. Moreover, the agonistic effect of the AABs was neutralized by peptides corresponding to the second extracellular loop of both receptors. Therefore, the epitopes of the AABs are localized on the second extracellular loops of the receptors. The α1-AR AABs as well as the ETA-receptor AABs induce a permanent stimulation without desensitization of the receptor mediated signal cascade. The α1-adrenergic agonist phenylephrine and endothelin1 as ET receptor agonist cause a translocation of the transcription factor NFκB and AP-1 from the cytosol into the nucleus in cultured neonatal rat cardiomyocytes. The same translocation was observed using the AABs against the α1-AR and ETA receptor.

Conclusion:
The agonist-like AABs against the α1-AR and the ETA receptor influence in vitro the signalling of cultured cells. Moreover, the AABs prevent the desensitization of the receptor mediated signal cascade normally seen by ongoing receptor stimulation. Therefore, we assumed that the functional AABs against the α1-AR and the ETA receptor may be involved in the pathogenesis of IPAH.
Abstract 2316: Myocardial PAI-1 Over-expression Mediates Graft Sclerosis in Cardiac Transplant Recipients with Idiopathic Dilated Cardiomyopathy
Authors: Aharinejad Seyedhossein , Krenn Katharina , Schäfer Romana , Zuckermann Andreas , Paulus Patrick , Grimm Michael
Published: July 2021

Idiopathic dilated cardiomyopathy (DCM) is associated with reduced myocardial vascular density and increased collagen deposition with subsequent myocardial fibrosis and heart failure. The urokinase plasminogen activator (uPA)/plasminogen activator inhibitor (PAI) system plays an important role in extracellular matrix homeostasis as well as in preserving the integrity of the vascular endothelial cell (EC) intimal layer and EC regeneration, proliferation and motility. However, the involvement of the uPA/PAI system in DCM and graft remodeling following cardiac transplantation remains unclear. Gene expression of uPA, the uPA receptor uPAR and PAI-1 was examined in left ventricular (LV) biopsies of explanted hearts in 24 ischemic cardiomyopathy (ICM) and 60 DCM patients and 12 controls by real time RT-PCR and Western blotting. Vascular endothelial growth factor (VEGF) and uPA/PAI interplay was examined in stimulated DCM and ICM myocardium in vitro. Expression of uPA and PAI-1 mRNA was evaluated in endomyocardial biopsies (EMB) at 1, 2, 3, 4, 7, 12, 24 and 52 weeks post-transplant. The mRNA levels of uPA and uPAR were unchanged in both ICM and DCM patients compared to controls. PAI-1 mRNA and protein were up-regulated in DCM compared to ICM and controls (p<0.01). Active and inactive uPA protein was down-regulated in DCM and ICM compared to controls (p<0.05). VEGF stimulation
in vitro
did not affect uPA, uPAR or PAI-1 expression. Following transplantation, PAI-1 expression returned to baseline control levels in EMB from both patient groups, although PAI-1 expression increased at 24 and 52 weeks post-transplant in DCM patients (p<0.01 compared to post-transplant weeks 6 and 12). These data indicate a significant PAI-1 up-regulation associated with uPA down-regulation in DCM, independent of VEGF, which was temporarily corrected by cardiac transplantation. However, recurring up-regulation of myocardial PAI-1 levels at 6 and 12 months post-transplant suggest a persistent PAI-1-related molecular pathology in DCM. We have previously shown increased endothelin-1 expression and collagen deposition in grafts of DCM patients at 1 year post-transplant. The present data point to a previously unknown role of PAI-1 in mediating graft sclerosis.
Abstract 2378: The MinK G38S Polymorphism Associates with Atrial Arrhythmias after Subarachnoid Hemorrhage
Authors: Frangiskakis J M , Tanabe Masaki , Hravnak Marilyn , Crago Elizabeth A , Gorcsan John , Horowitz Michael B , London Barry
Published: July 2021

Background: Subarachnoid hemorrhage (SAH) leads to significant death and disability. Cardiac abnormalities after SAH include atrial arrhythmias (AAs). The MinK (KCNE1) G38S polymorphism has been associated with atrial fibrillation, with the G38 allele being linked to increased action potential duration in heterologous expression systems. The relationship of AAs and ion channel polymorphisms after SAH is not known.

Methods: In 148 patients admitted for acute, aneurysmal SAH, EKG parameters, 24-hour Holter monitors, serum troponin (TnI), potassium (K), magnesium (Mg), and echocardiograms (ejection fraction [EF] and left atrial diameter [LA D]) were examined. MinK G38S was genotyped using fluorescent primers and analyzed with an ABI Prism 7000.

Results: No patient had AAs on presentation, but AAs developed in 101 (68%) patients: SVT (95; 64%); fibrillation (9; 6%); flutter (4; 3%); idioventricular rhythm (2; 1%); and 3° block (1; 1%). AAs were not associated with PR or QTc intervals, TnI, K, Mg, EF, LA D, or stroke severity. AAs were associated with older age (58±9 vs 51±10yrs; p<0.001), lower heart rate (HR; 80±10 vs 84±14bpm; p=0.02), and higher HR variability (SDNN; 97±34 vs 85±32; p=0.05). The MinK S38 allele was associated with AAs (Figure

; GS & SS 70% vs GG 51%; p=0.02), but not LA D.

Conclusions: Atrial arrhythmias are common following SAH and the MinK S38 allele is associated with an increased frequency of atrial arrhythmias. The SAH-induced catecholamine surge, followed by increased parasympathetic activity, may enhance the shortening of the atrial effective refractory period in patients carrying the MinK S38 allele and increase susceptibility to atrial arrhythmias.
Abstract 2399: Low Hospital Mortality Of Acute Myocardial Infarction In Cslinical Practice Due To Optimized Guideline Oriented Treatment: Results Of The Optami-registry
Authors: Gitt Anselm K , Wienbergen Harm , Zeymer Uwe , Towae Frank , Gottwik Martin G , Breithardt Guenter , Senges Jochen
Published: July 2021

Background: Hospital mortality of STEMI in recent randomized trials as ASSENT IV ranges between 3.5 and 6.0%. Although registry data have shown a constant improvement of myocardial infarction outcome over the past years due to better implementation of guidelines for the management of acute myocardial infarction, hospital mortality in clinical practice still was much higher than in the selected patient population of randomized trials. Can ongoing registries in clinical practice as quality assurance programmes further reduce hospital mortality of acute myocardial infarction?

Methods: The OPTAMI Register (Optimized Therapy of Acute Myocardial Infarction) enrols consecutive patients with STEMI or NSTEMI in 33 Centres (27 with cathlab facilities) in Germany to document patient characteristics, acute therapy as well as hospital outcome. All centres are provided benchmark reports for internal quality control.

Results: Out of 1139 enrolled patients, 629 (55%) presented with STEMI and 510 (45%) with NSTEMI. Patients with NSTEMI were older, more often female and had a significantly higher prevalence of relevant comorbidities. OPTAMI documented an extraordinary high rate of primary PCI in STEMI as well as a high rate of early invasive strategy with PCI <48h in NSTEMI. In both groups, adherence to guidelines for the acute adjunctive medical treatment including antiplatelet therapy, betablockers, ACE-inhibitors and statins was higher than ever documented in any German MI registry. Hospital mortality was 4.0% in consecutive patients with STEMI and 3.9% in consecutive patients with NSTEMI.

Conclusion: Preliminary data of the ongoing OPTAMI Registry demonstrate that in selected cnetres (mainly with cath lab facilities) hospital mortality in clinical practice can be reduced to levels of randomised controlled trials by adherence to practice guidelines for the management of acute myocardial infarctions.
Abstract 355: Modulation of Cardiac L-type Calcium Channels by Phospholemman
Authors: Wang Xianming , Gao Guofeng , Peterson Blaise Z
Published: July 2021

Ca
2+
entry through L-type Ca
2+
channels plays a critical role in shaping the action potential and is the initial trigger for EC-coupling. The gating, expression and targeting Ca
2+
channels are tightly regulated by auxiliary subunits and second messenger signaling mechanisms. Here, we report that cardiac Ca
2+
channels are directly modulated by phospholemman (PLM), a single transmembrane protein that is important for regulating ion homeostasis in the heart through its interactions with the Na,K-ATPase and Na/Ca Exchanger (NCX). Experiments using confocal immunofluorescence microscopy indiate that PLM and the Ca
2+
channel alpha-1 subunit, Ca
V
1.2, co-localize to the plasma membranes of HEK 293 and COS-7 cells. Recipricol co-immunoprecipitation studies demonstrate that PLM and Ca
V
1.2 are specifically associated in the mouse heart (see Figure

) and HEK 293 cells expressing the two proteins (not shown). Whole-cell patch-clamp was used to assess the functional consequences of the interaction between PLM and the Ca
V
1.2 subunit using HEK 293 cells transfected with PLM ((+)PLM) or empty PLM vector ((−)PLM). These studies demonstrate that PLM substantially slows the activation kinetics of Ca
V
1.2 channels (see Figure

), but has no effect on neuronal Ca
V
2.1 Ca
2+
channels (not shown). As a result, the level of Ca
2+
entry during the first 50 msec of channel activation is decreased by up to 32%. Since PLM is upregulated in post-ischemic rat hearts and due to the tight functional coupling between the cardiac Ca
2+
channel and NCX, we propose that PLM-induced slowing channel activation and PLM-dependent inhibition of NCX combine synergistically to reduce peak [Ca
2+
]i in infacted myocytes.
Abstract 2461: Low Thromboembolism and Pump Thrombosis Potential of the HeartMate II (HM) LVAD
Authors: Boyle Andrew J , Russell Stuart D , Teuteberg Jeffrey J , Moazami Nader , Moore Stephanie A , Slaughter Mark , Farrar David J , John Ranjit
Published: July 2021

Introduction: The HM continuous flow LVAD has been shown to have good reliability and an excellent safety profile when used as a bridge to transplantation (BTT). Initially, there were concerns that the continuous flow and design of the HM might pre-dispose patients to thromboembolic events or pump thrombosis and therefore oral anticoagulation with coumadin was recommended. Our study evaluates the risk of thromboembolism and pump thrombosis related to the degree of anticoagulation as reflected by the International Normalized Ratio (INR).

Methods: We evaluated all patients enrolled in the HM BTT pivotal trial from 1 to 6 months post-implant in order to eliminate perioperative events unrelated to anticoagulation. All patients were on aspirin and some also on persantine. An INR was measured monthly per protocol. Each individual INR sample from each time interval was assigned to ranges of INR values. Adverse events analyzed were ischemic (I) and hemorrhagic (H) stroke, pump thrombosis (T), and GI bleeding (G). Patients with adverse events were associated with the most recent INR at the start of the time interval.

Results: The median duration of support for 189 patients was 132 days (range: 1–672 days) (cumulative: 96.9 patient years). There were 7 (3.7 %) patients with thrombotic events and 11 (5.8 %) patients with hemorrhagic events. The only pump thrombosis occurred with an INR > 2.5 (0.5 %).

Conclusions: The rates of thromboembolism, including stroke and pump thrombosis appear to be low with the HM as BTT. The thrombotic events appear to be offset by an equivalent number of hemorrhagic events. There appears to be no correlation between the degree of anticoagulation with warfarin, as reflected by the INR, and the frequency of thrombotic or hemorrhagic events. Therefore, particularly in patients having recurrent episodes of bleeding, the risk of lowering the target INR appears to be small.
Abstract 2464: Increase in N-Terminal Fragment of the Prohormone Brain-Type Natriuretic Peptide after Eurotransplant Urgency Listing as a Measure for Predicting Outcome after Heart Transplantation
Authors: Komoda Takeshi , Lehmkuhl Hans B , Knosalla Christoph , Potapov Evgenij , Dandel Michael , Grauhan Onnen , Hetzer Roland
Published: July 2021

Background
When candidates for heart transplantation (HTx) show high levels of N-terminal brain-type natriuretic peptide (NT-proBNP), the prognosis of the patients is poor. However, identification of these high-risk patients is a matter for discussion. We investigated increase of NT-proBNP after listing with Eurotransplant for urgent HTx as a measure to predict outcome after HTx.

Methods
Plasma NT-proBNP was measured in 59 HTx candidates without mechanical circulatory support before and after urgency listing. Complications and mortality after HTx in relation to changes in plasma NT-proBNP levels before and after urgency listing were studied. Percentile increases of maximal NT-proBNP values after urgency listing were compared with values prior to urgency listing and defined as delta-max NT-proBNP.

Results
Area under the receiver operating characteristic (ROC) curve of delta-max NT-proBNP predicting mortality was 0.67. When the cut-off value for delta-max NT-proBNP was determined as 20%, 16 patients were in the group of increase in max NT-proBNP after urgency listing (Group INC) and the rest were in Group NON (n=43). Thirty-day mortality rate after HTx in Group INC was 37.5 % compared to 14.0 % in Group NON. Actuarial survival in Group INC was significantly worse than in the total of 180 patients who underwent HTx between 2004 and 2006 (p < 0.05, log-rank test). Incidence of infection was significantly higher (p < 0.001, Fisher’s exact probability test) in Group INC (68.8 %) than in Group NON (16.3 %). Long-term mechanical respiratory support (longer than 4 days) was more frequent (p < 0.05) in Group INC (87.5%) than in Group NON (55.8 %).

Conclusions
Patients with an increase of NT-proBNP of greater than 20% during urgency listing are at higher risk for post-HTx mortality and complications. VAD implantation may be a valid approach in these patients, but this needs to be addressed in future studies.
Abstract 2482: Fate of Targeted Ultrasound Contrast Agents After Endothelial Adhesion: A Time Course Study
Authors: Bowry Shivani , Wang Jianjun , Ottoboni Sue , Ottoboni Tom , Wagner William R , Villanueva Flordeliza
Published: July 2021

Background:
Targeted microsphere (μSPH) adhesion to endothelial epitopes forms the basis for ultrasound molecular imaging. The fate of targeted μSPH, once bound to the endothelial target, is unknown. This has limited the optimization of ultrasound imaging strategies; for example, the appropriate time to commence imaging after μSPH injection is uncertain, and in part depends on the time course and duration of μSPH binding. We therefore sought to characterize the behavior of adhered μSPH as a function of time using serial observations of rat cremaster microcirculation after μSPH injection.

Methods:
Fluorescent nitrogen-encapsulated polymer μSPH (diameter 3.0 ± 1.4 μm) bearing control non-specific IgG (μSPH
CTL
) or monoclonal antibody against VCAM (μSPH
VCAM
) or ICAM (μSPH
ICAM
) were prepared. Inflamed cremaster muscle of 21 anesthetized Wistar rats was exteriorized for intravital microscopy 4 hours after intrascrotal injection of TNF-α (5μg). Each rat received 1 venous injection of a single μSPH species (n=7 rats/μSPH; 10
8
μSPH/injection). An index venule was identified for serial microscopic observation every 5 min starting 10 min after μSPH injection.

Results:
The cumulative sum of adhered μSPH during 1 hr observation was higher for μSPH
ICAM
(24±11) and μSPH
VCAM
(18±1) than μSPH
CTL
(3±2, p=0.005). The number of μSPH
ICAM
adherent to the index venule was stable over time (10 min: 2 ± 3; 30 min: 3±2; 80 min: 3 ± 5, ANOVA p=0.9). The number of adhered μSPH
VCAM
trended downwards (10 min: 5±4; 30 min: 2±2; 80 min: 1±2; ANOVA p=0.08). By 1 hr, adhered μSPH appeared altered in shape; no μSPH transmigration was seen.

Conclusions:
Nitrogen-filled polymer μSPH targeted to leukocyte adhesion molecules adhere to inflamed endothelium. The extent of μSPH adhesion remains relatively constant over a time period relevant for imaging applications, although beyond 1hr, the μSPH appear morphologically altered and could have different acoustic properties. These data provide a useful and broad time window for effective ultrasound imaging of molecular targets. The time course of μSPH attachment to endothelium is an important consideration when devising strategies for ultrasound molecular imaging and should be characterized in a μSPH- and target- specific manner.
Abstract 2498: Minor Myocardial Damage and LV Dysfunction in Patients with Duchenne Muscular Dystrophy-The Preventive Efficacy of Carvedilol on Plasma Cardiac Troponin I-
Authors: Nishizawa Takao , Yasuma Fumihiko , Sakai Motoko , Kuru Satoshi , Kimura Seigo , Shibata Rei , Ohashi Taiki , Noda Akiko , Izawa Hideo , Nagata Kohzo , Yokota Mitsuhiro , Konagaya Masaaki , Murohara Toyoaki
Published: July 2021

Background:
Cardiac dysfunction is one of the major prognostic factors in patients with Duchenne muscular dystrophy (DMD). Minor myocardial damage assessed by plasma cardiac troponin I (cTnI) is often observed in patients with DMD. However, it is unclear that how the minor myocardial damage occurs to which patient with DMD and how it relates to LV dysfunction. Therefore, we assessed the hypothesis that minor myocardial damage is associated with LV dysfunction, the evaluation of plasma cTnI helps the prediction of LV functional deterioration, and carvedilol prevents elevation of plasma cTnI in patients with DMD.

Methods:
Plasma cTnI were repeatedly (every 3 months) measured for 2 years and LV function was assessed by echocardiography in 58 patients with DMD. Carvedilol (2.5–5 mg/day) was orally administered for a year to the patients who have shown plasma cTnI elevation (positive cTnI, cut off 0.06ng/mL).

Results:
There were 3 differential groups regarding the progression rate of LV systolic dysfunction, i.e. rapid (19% of total, LVEF < 50% in their 10
th
), slow (50% of total, LVEF > 50% in their 20 –30
th
), and unchanged group (31% of total, LVEF < 50% in their 20 –30
th
). The episode of positive cTnI was observed in 27 (46%) of total patients with DMD. LVEF was lower in patients with positive cTnI than that with negative cTnI (42 ± 2 vs. 52 ± 2%,
p <
0.05). Positive cTnI was observed in all patients in rapid group, 84% of patients in slow group, and only 6% of patients in unchanged group. Fourteen differential dystrophin gene mutations were recognized in 48 patients but they were not associated with those 3 differential groups or patients with positive cTnI. Administration of carvedilol in 13 patients (LVEF 40 ± 3) decreased the cTnI detection rate (from 44 ± 5% to 26 ± 10%,
p <
0.05), while it was unchanged in 14 patients (LVEF 41 ± 3) without carvedilol treatment (from 44 ± 7% to 39 ± 6%) during same observation period.

Conclusions:
The elevation of plasma cTnI was associated with LV systolic dysfunction in patients with DMD. The prediction of LV dysfunction in patients with DMD may be feasible with combinations of age, LVEF, and plasma cTnI elevation. Carvedilol could be a new therapeutic strategy to prevent minor myocardial damage in patients with DMD.