bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2068: Systematic Undersized Rigid Ring Decreases Recurrence Rate Following Repair of Ischemic Mitral Valve
Authors: Fontaine Raphaël , Bouchard Denis , Demers Philippe , Cartier Raymond , Carrier Michel , Perrault Louis P
Published: July 2021

Introduction:
Chronic ischemic mitral regurgitation (MR) has been associated with poor long-term survival. Suboptimal midterm results have been a growing concern in the surgical community. In recent years, our approach to repair those valves has evolved to a standardized technique using complete, rigid and small annuloplasty rings. This study aims to compare this systematic approach with our prior experience from 1996 –2001 where recurrent MR rate was high.

Methods:
129 patients underwent repair for pure ischemic mitral valve regurgitation between 2002 and 2005 at our institution. Of these patients, 99 had clinical and echographic follow-up. These patients were compared to the 1996 –2001 cohort of 73 patients.

Results:
Preoperatively, 84% of patients were in NYHA class III or IV, 17% had moderate MR, 83% had moderate-severe to severe MR. Sixteen were redo operations, mostly of previous CABG. All patients except one were treated with a complete rigid ring (Annuloflo 46.5%, Physioring 34.9%, Etlogix 13.9%, others 3.8%). Ring size was: 24 (0.8%); 26 (55.8%); 28 (38%); or 30 (4.5%). Mortality was 8.5% at 30 days, 14.7% at 1 year and 17.8% at 2 years. Immediate postoperative regurgitation was absent or trace in all patients. Freedom from reoperation was 97%. Mean postoperative NYHA class was 1.15 at a mean follow-up of 28 months. Recurrent moderate mitral regurgitation (2+) was 15.34%, severe mitral regurgitation (3+ to 4+) was 13.4% at a mean follow-up of 16 months. In the 73 patients from the period 1996 –2001 at the same echo follow-up time, the moderate and severe recurrence were: 37% and 21%. The decrease in the recurrence rate was highly significant (p=0.001).

Conclusion:
A more standardized approach to ischemic mitral valve repair has improved the high recurrence rate previously reported by our group. Long-term follow-up is necessary to confirm these findings.
Abstract 2081: The Effect Of Left Atrial Volume On Prognostic Value Of Dobutamine-atropine Stress Echocardiography In Patients With Suspected Or Known Coronary Artery Disease.
Authors: Tsutsui Jeane , Dourado Paulo M , Falcão Sandra N , Chagas Antonio C , daLuz Protásio L , Mathias-Jr Wilson
Published: July 2021

Although dobutamine-atropine stress echocardiography (DSE) is an established technique for detecting coronary artery disease (CAD), new echocardiographic parameters have been recently described to influence the prognostic value of this test.

Objective:
To determine the influence of left atrial anatomical evaluation on the prognostic value of DSE in patients with known or suspected CAD.

Methods:
From January 2000 to October 2004 we studied 981 pts (61±12 years, 536 men) who underwent DSE with early-atropine injection protocol. Primary end-point was major cardiovascular events, defined as non-fatal myocardial infarction (MI) and cardiac death (CD). Secondary end-point was major cardiovascular events plus revascularization (surgical and percutaneous). Left atrial diameter was determined by two-dimensional echocardiography in longitudinal paraesternal view and left atrial volume in apical 4-chamber view, at rest. Abnormal DSE was defined as fixed or inducible wall motion abnormalities. Pts were followed for a mean of 18 months (6 to 47 months).

Results:
DSE was abnormal in 330(34%) pts. Mean left atrial diameter was 3.9±0.6 cm (2.2±0.4 cm/m2) while mean left atrial volume was 54.4±18.9 ml (30.7±11.2 ml/m2). Major cardiovascular events occurred in 39(4%) pts (29 CD and 10 non-fatal MI). A total of 120(12%) pts achieved secondary end-point. By univariate analysis the predictors of CD or non-fatal MI were left atrial diameter (p=0.0013), left atrial volume (p<0.001), male sex (p=0.007), diabetes mellitus (p=0.013), previous MI (p=0.013), left ventricular ejection fraction (p<0.001), and abnormal DSE (p<0.001). By multivariate analysis, the independent predictors of CD and MI were left atrial volume (RR=1.02; 95%CI =1.01–1.03; p<0.001) and abnormal DSE (RR=6.38; 95%CI =3.1–13.2; p<0.001). When considering secondary end-point, independent predictors of combined events were left atrial volume (RR=1.01; 95%CI =1.01–1.02; p<0.001), male sex (RR=1.7; 95%CI =1.1–2.5; p=0.017), and abnormal DSE (RR=4.4; 95%CI =2.9 – 6.6; p<0.001).

Conclusion:
Resting left atrial volume is an independent predictor of major cardiovascular events and combined events and can be used as an incremental tool for prognostic evaluation of patients who underwent DSE.
Abstract 2083: Improvement in Coronary Flow Reserve is Associated With Late Recovery of Left Ventricular Function After Carvedilol Therapy in Patients with Idiopathic Dilated Cardiomyopathy
Authors: Sugioka Kenichi , Hozumi Takeshi , Takemoto Yasuhiko , Ehara Shoichi , Kono Yasushi , Ogawa Keitaro , Oe Hiroki , Matsumura Yoshiki , Otsuka Ryo , Yoshitani Hidetoshi , Yoshikawa Junichi , Yoshiyama Minoru
Published: July 2021

Background:
Beta-blocker therapy reverses left ventricular (LV) remodeling in patients with idiopathic dilated cardiomyopathy (IDC). Improvement in coronary circulation by beta-blocker could play a role in theses circumstances. This study investigated the relationship between change in coronary flow reserve (CFR), as a marker of coronary circulation, and subsequent improvement in LV ejection fraction (LVEF) at follow-up during carvedilol therapy in IDC patients.

Methods:
We studied 20 patients with IDC (mean age 56 ± 15 years, NYHA I–II) who were scheduled to receive carvedilol therapy. All patients were stabilized using an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker and diuretic treatment. Transthoracic Doppler echocardiography with intravenous infusion of adenosine triphosphate was used to assess CFR in the left anterior descending artery at baseline and after 1 month of treatment with carvedilol. A follow-up echocardiographic assessment of LVEF was done at 12 ± 6 months of treatment. The patients were classified by the degree of improvement in LVEF in the follow-up study, as Group A (LVEF change ≥10%) and Group B (LVEF change <10%).

Results:
Although there was no significant difference in CFR between the 2 groups at baseline (Group A vs. Group B, 2.4 ± 1.0 vs. 2.2 ± 0.8;
P
=NS), CFR was significantly higher in Group A than in Group B at 1 month of therapy (3.7 ± 0.5 vs. 2.5 ± 0.9;
P
<0.01). The magnitude of CFR change after 1 month of therapy was significantly greater in Group A than in Group B (1.3 ± 0.6 vs. 0.4 ± 0.5;
P
<0.01). Logistic regression analysis revealed that CFR change predicted a significant improvement in LVEF at follow-up (
P
<0.05). Furthermore, a significant correlation was found between the change in CFR after 1 month and that in LVEF on follow-up (r=0.65,
P
<0.01).

Conclusions:
This study demonstrated that early change in CFR is associated with subsequent improvement in LVEF, suggesting the potential predictive value of coronary circulation for subsequent LV reverse remodeling after beta-blocker therapy in patients with IDC.
Abstract 2086: Usefulness of Pneumatic Lower Extremity Compression During Dobutamine Stress Echocardiography
Authors: Kim Hyung-Kwan , Chang Sung-A , Park Jin-Shik , Kim Yong-Jin , Zo Joo-Hee , Oh Hyung-Hee , Park Young-Bae , Choi Yun-Shik , Sohn Dae-Won
Published: July 2021

Background

Afterload is expected to increase with pneumatic compression of the lower extremities. Therefore, left ventricular (LV) wall stress which is the most important factor determining myocardial oxygen demand will also increase, leading to an increase in sensitivity of dobutamine stress echocardiography (DSE) or shortened time to positive response.The purpose of this study was to evaluate the effect of pneumatic compression of lower extremities on the diagnostic accuracy of DSE.

Methods

In 40 patients who underwent DSE and were anticipating coronary angiography, DSE was repeated with the pneumatic compression (100mmHg) of lower extremities (DSEcomp) prior to coronary angiography. Sensitivity and specificity of DSE and DSEcomp were determined based on the coronary angiographic finding.

Results

All patients tolerated pneumatic compression of the lower extremities during the tests. LV end-systolic volume (p=0.042) and end-systolic wall stress (p=0.036) were significantly greater in the DSEcomp than DSE. In 3 patients with false negative results in DSE, DSEcomp showed positive responses, demonstrating a significant increase in sensitivity from 75% to 94% (p=0.045). Only 1 patient with true negative result in DSE was interpreted as showing positive response in DSEcomp, resulting in a decrease in specificity from 88% to 83% (p=NS). In 11 of 13 patients with true positive results both in DSE and DSEcomp, positive responses were seen at least 1 stage earlier in DSEcomp compared to DSE.

Conclusions

Pneumatic compression of lower extremities increases the sensitivity of DSE and shortens the time to positive response.
Abstract 2116: The presence of Type 2 Diabetes mellitus is strongly associated with essential hypertension
Authors: Movahed Mohamnad Reza , Hashemzadeh Mehrtash , Jamal Mazen
Published: July 2021

Background: Diabetes (DM) and hypertension (HTN) are common risk factors for heart disease in the population. Independent association between DM and HTN has not been studied in large populations. The goal of this study was to evaluate independent association between DM and HTN using a very large data base.

Method: We used ICD-9 Codes for type 2 DM (250.00, 250.02) and HTN (401.0, 401.1, 401.9) from the Nationwide Inpatient Sample (NIS) database. We randomly selected the years 1992 and 2002 databases which are 10 years apart as two independent samples. NIS involves approximate a 20-percent sample of U.S. community hospitals and specialty hospitals. We used uni- and multivariate analysis to evaluate any association between type 2 DM and HTN adjusting for comorbid conditions.

Results: 1992 database contained a total of 6,195,744 patients. Type 2 DM occurred in 37.5% of patients with HTN vs. 11.4% of the control group (OR: 4.63, CI 4.61– 4.693, p<0.001). 2002 database contained a total of 7,853,982 patients. Type 2 DM occurred in 57.2% of patients with HTN vs. 22.9% of the control group (OR: 4.49 CI 4.47– 4.52, p<0.001). Using Multivariate analysis adjusting for age, gender, hyperlipidemia, obesity, smoking, and chronic renal failure, DM remained independently associated with HTN in both database. (for the year 1992: OR: 2.49, CI:2.47–2.51, p<0.001 and for the year 2002 OR: 2.19, CI: 2.18 –2.20, p<0.001)

Conclusion: The presence of type 2 DM is strongly associated with HTN. This association is independent of comorbid conditions and has been persistent with no significant changes in the odds ratios over a period of 10 years.
Abstract 2118: A Population-based Comparison of the Cardiovascular Protective Effects of Hydrochlorothiazide and Chlorthalidone
Authors: Nagge Jeff , Juurlink David N
Published: July 2021

Background
Clinical practice guidelines for the treatment of hypertension recommend a thiazide diuretic as initial therapy for the majority of patients. Most clinicians consider chlorthalidone (CHL) and hydrochlorothiazide (HCTZ), the two most commonly prescribed thiazides, to be interchangeable, despite evidence suggesting these drugs are not equivalent.

Methods
We constructed a population-based retrospective cohort study by linking the health records of 1.4 million residents of Ontario, Canada aged 66 or older between July 1, 1993 and March 1, 2002. The index event for entry into the cohort was a new prescription for either HCTZ or CHL. The primary outcome was the time from the index event to a composite outcome of acute myocardial infarction (AMI), stroke, or all-cause mortality. Secondary analyses explored each outcome individually. Analysis was done using Cox proportional hazards regression with the HCTZ group as the reference.

Results
During 218,360 person-years of follow-up in the HCTZ group, there were 10 025 events (death, AMI or stroke), compared to 113 events during 4,214 person-years of follow-up in the CHL group. The unadjusted hazard ratio for the primary outcome was 0.73 (95% confidence interval 0.61 to 0.88), suggesting a substantially lower risk of events during CHL therapy. After adjustment for differences in baseline demographic and clinical characteristics, there was no statistically significant difference between the groups for the primary outcome (adjusted hazard ratio 0.85; 95% confidence interval 0.71 to 1.03). The hazard ratios for each component of the primary composite outcome all trended in the direction of a lower risk of events in users of CHL.

Conclusion
In a large cohort of older patients treated with thiazide diuretics, the use of CHL was not associated with a statistically significant reduction in the risk of AMI, stroke, or death. However, treatment effects favored CHL for every outcome, raising the hypothesis that CHL is superior to HCTZ. Further research is needed to confirm or refute this hypothesis.
Abstract 2125: Severity of Left Ventricular Dyssynchrony in Patients with Ischemic and Non-Ischemic Cardiomyopathy: a Cardiovascular Magnetic Resonance Tissue Synchronization Mapping Study
Authors: Khadjooi Kayvan , Foley Paul W , Chalil Shajil , Dyer Beatrice A , Stegemann Berthold , Smith Russell E , Frenneaux Michael , Leyva Francisco
Published: July 2021

Aims:
Studies on cardiac resynchronization therapy (CRT) for heart failure have shown a differential response in patients with ischemic (ICM) and non-ischemic cardiomyopathy (NICM). Increasing dyssynchrony has been shown to relate to a poor prognosis in patients with heart failure. We hypothesized that ICM and NICM have varying effects on left ventricular (LV) synchrony.

Methods:
The recently described cardiovascular magnetic resonance tissue synchronization index (CMR-TSI), which predicts benefit from CRT, was quantified in 181 patients (age: 66.4 ± 10.6 yrs, NYHA class III or IV, LVEF: 23.5 ± 10.8%, QRS = 139.8 ± 32.0 ms) with ICM (n=105) or NICM (n=76) and age-matched, healthy controls (n=24). The maximum time-to-peak radial wall motion in a short axis stack of LV images (steady-steady free precession imaging) was fitted to an empirical sine wave [y = a + b * sin (t/RR + c)]. The CMR-TSI was calculated as the SD of all segmental phase shifts of the radial wall motion extracted from this wave (see Figure

for bull’s eye maps).

Results:
CMR-TSI was higher in ICM (105.8 ± 44.2, ANOVA p<0.0001) and in NICM (68.1 ± 30.5, p<0.0001) than in controls (22.5 ± 8.6) (see Figure

). In multivariate analyses including ICM and NICM patients only, ischemic aetiology emerged as a positive predictor of CMR-TSI, independent of QRS duration, LV end-systolic and end-diastolic volumes, and LVEF (all p<0.0001).

Conclusions:
ICM is associated with a greater degree of dyssynchrony than NICM, independently of QRS duration, LV volumes and LVEF. These findings may account for the differential response to CRT observed with patients with ICM and NICM.
Abstract 2130: Long-term Outcomes of Adult Atrial Septal Defect With Severe Pulmonary Hypertension After Surgical Closure
Authors: Kim Jeong-Hoon , Kang Duk-Hyun , Lee Jong-Young , Song Jong-Min , Yun Tae-Jin , Choi Kee-Joon , Hong Myeong-Ki , Song Jae-Kwan , Park Seong-Wook , Park Seung-Jung
Published: July 2021

The benefits of surgical closure has been unclear in adult atrial septal defect (ASD) with severe pulmonary hypertension (PHT), and we tried to evaluate improvement of PHT and long-term survival after surgical closure compared to medical follow-up.

Methods:
From 1996 to 2006, we included a total of 71 adult ASD patients (age; 43±15 years) with severe PHT documented by echocardiography. The inclusion criteria were defined as ASD diameter > 15 mm, enlarged right ventricle, and the baseline peak velocity of tricuspid regurgitation (TR) ≥ 4.0 m/sec. We excluded 5 patients with Eisenmenger syndrome documented by cardiac catheterization. Surgical closure was performed on 55 patients (OP group) and the remaining 16 patients were followed up medically (MED group). The improvement of PHT was defined as TR velocity ≤ 3.5 m/sec on follow-up echo.

Results:
Baseline characteristics and clinical results were compared between the two groups in table

. There were no significant differences in terms of gender, ASD diameter, cardiac rhythm, and TR velocity, but the MED group was significantly older. During follow-up of 46±33 months, there were 5 deaths in the MED group and no operative or late death in the OP group, and the 5-year actuarial survival rate of the OP group was significantly higher than the MED group (58±15%, p<0.05). On subgroup analysis according to age, the OP group showed significantly better survival rates than the MED group (p<0.05) in elderly patients (age > 50). In the OP group, TR velocity was significantly decreased from 4.5±0.4 to 3.0±0.7 m/sec on follow-up echo, and improvement of PHT was observed in 47 (85%) patients. On multivariate analysis, female gender and lower baseline TR velocity were the significant independent predictors of improved PHT after surgery.

Conclusions:
In adult ASD with severe PHT, surgical closure can be safely performed and improve PHT effectively. Especially in elderly patients, ASD closure is significantly related with the better survival rates.
Abstract 2139: Pregnancy-related Hospitalizations Among Women With Congenital Heart Disease In California: A Population-based Analysis
Authors: Gurvitz Michelle , Stout Karen K , Canobbio Mary , Richardson Andrea , Chang Ruey Kang
Published: July 2021

Objective: To evaluate pregnancy-related hospitalizations of women with congenital heart disease (CHD) in California

Background: It is recommended that women with complex CHD receive specialty care during pregnancy. There is a perception that these women require cesarean section (CS) for cardiac reasons, but hemodynamic changes are often less with a vaginal delivery. There are no population based studies evaluating pregnancy in CHD.

Methods: California hospital discharge data from the years 2000–2003 were analyzed. Subjects were chosen by age (12–44 years), diagnosis code for CHD and diagnosis or procedure code related to pregnancy. Among the hospitals, there were 7 self-identified specialized adult CHD centers. Descriptive statistics were used to characterize the population by age, CHD diagnosis (complex or non-complex), insurance, hospital (adult CHD center or not), and outcome (delivery, ante-partum, post-partum condition). Multivariate regression was used to determine predictors for CS.

Results: There were 1032 hospitalizations among women age 14–44 years (mean 27.7 years). Hospitalizations occurred at 210 different hospitals, with only 14% at the 7 adult CHD centers. CHD diagnoses were complex in 52% and non-complex in 48%. Among the hospitalization outcomes, 77% were deliveries (66% vaginal, 34% CS), 2% abortive and 21% ante or post partum conditions. CS rates were not statistically different between CHD centers (32%) and non-centers (34%) but were higher than the general population (21%). Women with complex CHD were more likely to have a CS (p=0.005) or an abortive outcome (p<0.001) than those with non-complex CHD. Women with complex CHD were less likely to have a CS at an adult CHD center than those women delivered at non-CHD centers (p=0.005). In regression analyses, complex CHD was the only variable associated with CS.

Conclusion: Most data on pregnancy in CHD are from single center studies, however, the majority of women with CHD delivered at non-CHD centers. Overall pregnancy outcomes did not appear different by hospital type, but the rates of CS in women with complex CHD suggests specialty care may affect mode of delivery. Understanding of the outcomes of pregnancy in women with CHD would be enhanced by detailed population-based studies.
Abstract 2140: Differential Efficacy and Safety of Drug-Eluting Stents With Short Versus Long Term Follow-up: A Meta-Analysis of Randomized Clinical Trials
Authors: Roukoz Henri , Bavry Anthony A , Sarkees Michael L , Kumbhani Dharam J , Rabbat Mark G , Bhatt Deepak L
Published: July 2021

Introduction:
Drug eluting stents (DES) significantly reduce target lesion revascularization (TLR) compared to bare metal stents (BMS) within 1 year of follow-up, however they increase late stent thrombosis. The effect of DES on the need for late revascularization is unclear.

Hypothesis:
We sought to evaluate the safety and efficacy of DES compared to BMS early after intervention (< 1 year) and late (> 1 year) among both stable patients and acute coronary syndromes.

Methods:
We searched the Medline database for randomized clinical trials with long-term follow-up, from 2000 to 2007. We also searched relevant journal supplements for abstracts and obtained trial presentations from cardiology meetings.

Results:
We identified 24 trials (17% acute coronary syndrome patients) with a total of 10,278 patients. The weighted mean duration of follow-up was 28 months. For early outcomes (< 1 year); the incidence of all-cause mortality for DES vs. BMS was 2% vs. 2.1%, RR=0.95, 95%CI (0.70–1.27), p=0.7, cardiovascular mortality was 1.4% vs. 1.5%, RR=0.95 (0.73–1.24), p=0.72, Q-wave myocardial infarction (MI) was 0.8% vs. 0.6%, RR= 1.24 (0.7–2.2), p=0.45, non-Q-wave MI was 3% vs. 4%, RR=0.73 (0.55–0.96), p=0.024, TLR was 5.9% vs. 17.8%, RR=0.29 (0.24–0.34), p<0.001, and stent thrombosis was 0.94% vs. 1.1%, RR=0.83 (0.55–1.27), p=0.4. For late outcomes (>1 year); the incidence of all-cause mortality for DES vs. BMS was 3.9% vs. 3.8%, RR=1.04 (0.79–1.38), p=0.7, cardiovascular mortality 1.4% vs. 1.5%, RR=0.95 (0.73–1.24), p=0.72, Q-wave MI was 0.7% vs.0.6%, RR=1.05 (0.54–2.05), p=0.87, non-Q-wave MI was 1.6% vs. 1.2%, RR=1.39 (0.87–2.21), p=0.16, TLR was 2.6% vs. 3.2%, RR=0.82 (0.59–1.13), p=0.23, and stent thrombosis was 0.59% vs. 0.15%, RR=3.2 (1.22–8.36), p=0.018.

Conclusions:
Within 1 year of follow-up, DES appears to be safe and efficacious with similar mortality, similar stent thrombosis, decreased TLR, and decreased non-Q-wave MI compared to BMS. After 1 year, DES still has similar mortality compared to BMS, however TLR, while low, is no longer reduced, stent thrombosis is increased, and there is a numerical excess of non-Q-wave MI.
Abstract 2155: One year clinical outcomes associated with the use of a Zotarolimus eluting stent: A Single-Center Canadian Experience
Authors: Drzymala Luke , Ha Andrew , So Derek , Glover Chris
Published: July 2021

Background:

The use of drug eluting stents (DES) has improved clinical and angiographic outcomes by reducing the need for target vessel revascularization (TVR). Clinical outcomes associated with the use a novel DES, the Zotarolimus-eluting phosphorylcholine-coated (Endeavor®) stent are less well established. A randomized clinical trial examining the benefits of the Endeavor® stent the rates of target vessel revascularization (TVR), target lesion revascularization (TLR) and stent thrombosis (ST) rates at 9 months in a select “study population” were reported as 7.9%, 4.6% and 0.5% respectively. These studies examined the outcomes of the Endeavor® stents in patients with single and non-complex lesions, while excluding patients with Acute Coronary Syndrome (ACS), Left Main (LM) lesions or In-stent restenosis (ISR). The outcomes of the Endeavor® stents in a “real-world” population have not been studied. The objective of this study was to evaluate the safety and efficacy of Endeavor® stents in consecutive patients from a single, high volume Canadian center.

Methods & Results:

The charts and angiogram reports of consecutive pts between June 2005 and June 2006, who received ≥ 1 Endeavor® stents were reviewed (n=462). In total, 667 Endeavor® stents were deployed in 462 patients. These patients were: 71% male, 65+/−9.1 year-old, 45% DM, 51% smokers, 62% HTN, 73% with dyslipidemia, and 5% with previous bypass surgery. The indications for stenting were: stable CAD 47.7%, ACS 47.1% and STEMI 5.1%. Endeavor® stents were utilized for ISR in 9% of cases. Average stent size was 19.7 +/− 5.8 × 2.9 +/− 0.3mm. At 12 month follow-up, TLR and TVR rates of 6.9% and 8.9% were observed, along with 2 cases of acute ST. There were no cases of late ST (>1 month post stent implantation). Myocardial Infarction occurred in 3.5% patients over 12 months.

Discussion:

In a Canadian interventional cardiology center, TLR, TVR and ST rates of 6.9%, 8.9% and 0.6% were observed at 12 months post-implantation. Despite including patients with multiple lesions, complex lesions, ACS and ISR, the rates observed at our center were comparable to those observed in a select study population. Most importantly there were no late stent thrombosis.
Abstract 2159: Medial Necrosis Due to Sirolimus-Eluting Stent Implantation in Human Coronary Arteries
Authors: Inoue Katsumi , Mitsudo Kazuaki , Nobuyoshi Masakiyo
Published: July 2021

Background: Sirolimus-eluting stents (SES) have been proven to reduce the rates of restenosis by a striking inhibition of neointimal hyperplasia. However, unusual vessel responses to SES, such as late-acquired incomplete stent apposition (ISA) have been observed, and the precise mechanism of late ISA has not been clarified.

Methods and Results: To examine the mechanism of late ISA, the temporal mode of vascular responses after SES (3 days (D) to 12 months (M), 14 lesions) and bare metal stent (BMS; 2 D to 12 M, 24 lesions) implantation was investigated histopathologically in necropsied coronary arteries. In arteries that had been implanted with SES for 4 M, the stent struts were focally covered by thin membranous tissue mainly composed of fibrin deposition. Complete coverage of BMS by neointimal tissue composed of smooth muscle cells (SMC) and extracellular matrix (ECM) was documented after 1.5 M. Only mild neointimal thickening with focal endothelialization was observed around the circumference of the lumen at the stented site of atherosclerotic plaque-free segment in 4 of 9 lesions after 4 to 12 M. In these lesions, expansion of the stent strut forced the struts contiguous to the medial layer. Remarkable loss of medial SMCs was evident not only at the sites of the stent struts that had contacted and focally compressed the medial layer, but also at the sites where there was bowing of the media into the intima between the struts. In contrast, only restricted and incomplete medial SMC depletion was observed in the BMS segments where struts compressed the medial layer. We could observe that the medial SMC depletion was present only in the portions where SES struts directly contacted the medial wall layers. Depletion of medial SMC was not clearly observed even in DES segment between 3 D and 1 M.

Conclusions: Therefore, it is possible that these phenomena concerning elimination of medial SMCs were elicited by not only mechanical injury due to stent expansion but also by the pharmacological effect of sirolimus itself. The cytostatic effects of sirolimus on neointimal formation could be complicated by these local cytotoxic effects followed by a decrease in arterial wall tension, causing stent malapposition.
Abstract 2163: Long-term Follow-up (>3 Years) of Patients Treated With Sirolimus-Eluting Stents for In-stent Restenosis. Results of a Randomized Study.
Authors: Alfonso Fernando , Perez-Vizcayno Maria J , Bethencourt Armando , Martí Vicens , Lopez-Minguez Jose R , Angel Juan , Iñiguez Andres , Moris Cesar , Cequier Angel , Fernandez Cristina
Published: July 2021

Background:
The value of drug-eluting stents in patients (P) with in-stent restenosis (ISR) has been established. However, the long-term results of this strategy in P with ISR remains unknown.

Objective:
We sought to determine the long-term clinical outcome of P treated with sirolimus-eluting stents (SES) for ISR.

Methods:
A systematic, pre-specified, long-term clinical follow-up (FU) was performed in all P included in the RIBS II (Restenosis Intra-stent: Balloon angioplasty [BA] vs elective SES implantation) randomized trial. In RIBS II 150 P with ISR after bare-metal stent implantation were included: 74 allocated to BA and 76 to SES. Late angiography was obtained in 96% of eligible P. A structured clinical questionnaire (cardiac/non cardiac death, myocardial infarction [MI], target vessel revascularization [TVR], thrombosis [TH], and medical therapy) was used during FU.

Results:
Angiographic restenosis (primary end-point) was more frequently found in the BA arm (39% vs 11%, p<0.001). Clinical FU at 1-year was obtained in 150 P (100%). During this time period 6 P died (3 SES, 3 BA), 4 P suffered a MI (2 SES, 2 BA), 2 P experienced TH (1 P in each arm) and 30 required TVR (8 SES, 22 BA, p<0.01). A complete clinical FU >3 years was obtained in 145 P (97%) (mean 38±9 months, median 40 months [IQR 37–42]). Late events (after 1 year, non-exclusive) included: 3 deaths (1 SES, 2 BA), 3 MI (3 SES, 2 due to late TH) and 7 late TVR (5 SES, 2 BA). At 4 years, event-free survival was 76% in the SES arm and 65% in the BA arm (p=0.03). Survival free from TVR at 4 years was 80% in the SES arm and 67% in the BA arm (p=0.02).

Conclusion:
In P with ISR SES implantation improve the long-term clinical outcome as compared with BA treatment.
Abstract 324: Genetically Mediated Increases in Myocyte Contractility after Myocardial Infarction Exacerbate Cardiac Dysfunction
Authors: Zhang Hongyu , Chen Xiongwen , Gao Erhe , Harris David , Nakayama Hiroyuki , Zhang Xiaoying , Macdonnell scott , Eckhart Andrea , Koch Walter , Molkentin Jeffery , Houser steven
Published: July 2021

Myocyte death induced by ischemia or infarction can lead to depressed cardiac pump function and + inotropic drugs are often employed as therapy. The increased myocyte [Ca
2+
] required to increase myocyte contractility can also induce cardiac hypertrophy, arrhythmias and cell death. Our hypothesis is that + inotropic therapies after MI, while they will increase myocyte contractility, will ultimately exacerbate pump dysfunction by increasing myocyte death.

METHODS
: Double transgenic (TG) mouse lines with inducible (Tet-off system; tTA-TG) and cardiac myocyte specific (αMHC promoter) overexpression of the β2a subunit of the L-type Ca
2+
channel (Cav1.2 β2a (β2a-TG)) were used. Littermates having only one or none trangene (only β2a or tTA or WT) served as controls (CTR). Myocardial infarction (MI) was produced by permanent ligation of the left anterior descending coronary artery and animals were sacrificed 6 weeks later. Ischemia/reperfusion (I/R) was produced by ligating the LAD for 30 minutes followed by reperfusion for 3 hours (I/R) and then animals were sacrificed. In-vivo cardiac function was measured with the Visual Sonics Velvo 770 system.

RESULTS
: Myocytes isolated from β2a-TG mice had increased Ca
2+
current (CTR: 13.7 ± 0.7pA/pF, n = 6 vs. TG: 24.3 ± 2.6pA/pF, n = 6; p < 0.05) and contractility (CTR vs. TG VM: 8.0 ± 0.5%, n = 16 vs. 11.9 ± 1.1%, n = 11). Acute I/R resulted into greater Infarct size (the infarcted area vs. total area) in β2a-TG with I/R (62.4 ± 8.4%) than in CTR mice (49.2 ± 2.5%; p < 0.05). Before MI, β2a-TG mice had greater ejection fraction (EF) (73.8 ± 1.2%) than CTRs (68.9 ± 1.3%; p < 0.05). EF was decreased after MI in all mice (β2a-TG: 42.2 ± 7.5% vs. control: 45.2 ± 5.8%, p < ns). However, in β2a-TG mice, EF continued to decrease (27.8 ± 8.0%) at 6 weeks post MI but remained stable in CTRs (40.3 ± 2.9%; p < 0.05). The 6-week post MI survival rate was significantly lower in β2a-TG mice (16.6%) than in CTRs (50.0%; p < 0.05). Infarct size 6 weeks after MI was smaller than in acute I/R, but was still greater in β2a-DTG (45.8 ± 11.8%) than in CTRs (21.7 ± 9.8%; p < 0.05).

CONCLUSION
: These results suggest that increasing the contractility of myocytes after MI contributes to infarct expansion and CHF progression, possibly by increasing Ca
2+
-mediated myocyte death.
Abstract 327: NADPH Oxidase-dependent Signaling Involved In Endothelial Cell Survival And Proliferation: Role Of Nox2 And Nox4
Authors: Peshavariya Hitesh , Selemidis Stavros , Drummond Grant , Jiang Fan , Dusting Gregory J
Published: July 2021

Objective:

Endothelial cells (EC) produce a variety of reactive oxygen species (ROS) which act as mediators of signaling for proliferation, migration, differentiation and cell death. The major source of ROS in EC at rest is the NADPH oxidase enzyme complex. We aimed to determine the roles of the Nox2 and Nox4 catalytic subunits of NADPH oxidase in proliferation and survival of human microvascular endothelial cells (HMEC-1).

Methods:

Intracellular superoxide was measured by dihydroethidium fluorescence and lucigenin chemiluminescence, and total ROS by dichlorodihydrofluorescein-diacetate assay. Nox4 and Nox2 protein expression was measured by Western blot, and cell proliferation was quantitated by trypan blue exclusion and a tetrazolium-based MTS assay. EC survival was measured by caspase3/7 activity.

Results:

The expression of Nox4 (but not Nox2) protein, superoxide and total ROS, were all significantly higher (P < 0.05, N = 4) under proliferative conditions (sparse culture or serum addition) than in quiescent (dense culture or serum-starved) cells. Suppression of NADPH oxidase-derived ROS with specific siRNA significantly reduced cell proliferation as shown below. Under proliferative conditions phosphorylation of ERK and Akt were increased. Suppression of Nox4-derived ROS production reduced the phosphorylation of both ERK and Akt, whereas suppression of Nox2 reduced only Akt phosphorylation. Further, suppression of Nox2, but not Nox4, significantly activated caspase3/7 (P < 0.05, N = 4). Thus Nox4-derived ROS act to promote proliferation of EC via ERK and Akt signaling, whereas Nox2 prevents apoptotic signaling via Akt and caspase3/7.

Conclusion:

Nox isoform-derived ROS act via distinct signaling pathways to promote EC proliferation and survival. Selective modulation of Nox-type NADPH oxidase could be a useful approach for blocking angiogenesis or for therapeutic angiogenesis in chronic ischemia or tissue engineering.
Abstract 2175: Magnitude and Time Course of Platelet Inhibition with Extended Release Dipyridamole with or without Aspirin in Healthy Japanese Volunteers: The AGgrenox versus Aspirin Therapy Evaluation (AGATE-Japan)
Authors: Serebruany Victor L , Malinin Alex , Hanley Dan
Published: July 2021

Background: Randomized trials showed greater stroke prevention with extended release dipyridamole in combination with low dose aspirin than either with aspirin or dipyridamole alone. However, most studies with this formulation (Aggrenox®) were done in Europe and North America. Considering potential inter-racial differences in drug response, we conducted a small randomized study in healthy Japanese volunteers to compare antiplatelet regimens with regard to the changes in the platelet biomarkers.

Methods: Thirty healthy volunteers (18–40 years old, 15 male and 15 female) of Japanese descend were randomized to Aggrenox® (n=17) or aspirin 81 mg (n=13 volunteers) for 30 days. Platelet function was assessed at baseline, and days 15, and 30 by conventional aggregometry, whole blood flow cytometry, and cartridge-based analyzer.

Results: Both Aggrenox® and aspirin provided sustained platelet inhibition at Day 15 and Day 30. Therapy with Aggrenox®, however, was associated with more prominent and significant inhibition of collagen-induced aggregation (p=0.08, Day 15), as well as prolongation of the closure time (p=0.001, Day 30); diminished expression of platelet endothelial cell adhesion molecule-1 (PECAM-1) (p=0.02, Day 30), glycoprotein IIb (GPIIb) antigen (p=0.001 and 0.024 for Day 15 and Day 30), and GPIIb/IIIa activity by PAC-1 antibody (p = 0.014 and 0.03), CD62 (P-selectin) (p = 0.03 for Day 15 and Day 30), as well as inhibition of protease activated receptors (PAR-1) associated with intact WEDE-15 (p = 0.002 and 0.003) and SPAN-12 (p = 0.002 and 0.04) thrombin receptors when compared with aspirin.

Conclusion: The magnitude and durability of platelet response after Aggrenox in healthy Japanese is similar to those effects observed in Caucasians and African-Americans. Larger study to assess drug efficacy and safety in the Japanese post-stroke patients is warranted.
Abstract 2187: The Balance Of Pro-inflammatory And Ant-inflammatory Circulating Cytokine mRNA Gene Expression In CHF Patients With And Without Cachexia Compared To Healthy Control Subjects.
Authors: Sandek Anja , Wüst Joe , Bauditz Juergen , von Haehling Stephan , Swidsinski Alexander , Doehner Wolfram , Rauchhaus Mathias , Lochs Herbert , Volk Hans D , Anker Stefan D
Published: July 2021

Background: Chronic heart failure (CHF) is a state of chronic inflammation. High serum levels of TNF alpha and the presence of cardiac cachexia are known to predict poor survival in CHF. Abnormal balance of pro- and anti-inflammatory circulating cytokine mRNA gene expression is thought to contribute to cachexia in humans, but has never been studied in CHF patients.

Methods and Results: We studied 7 patients with cardiac cachexia (age 70±4 years, LVEF 28±2%, peak VO2 12.7±1.6 mL/kg/min, all >6% weight loss in previous 6–24 months), 19 noncachectic CHF patients (age 68±2 years, LVEF 31±2%, peak VO2 14.7±1.1 mL/kg/min) and 17 control subjects of similar age and gender (peak VO2 25.1±1.7 mL/kg/min, LVEF 71±2%). The mRNA gene expression of circulating mononuclear blood cells for pro-inflammatory mediators that have been implicated in the wasting process of ageing (TNF, STAT-1, STAT-3, SOCS-1 and SOCS-3) as well as anti-inflammatory cytokines (IL-10, tumor growth factor (TGF) beta were investigated by real time polymerase chain reaction. Values for the house keeping gene and genes of interest were calculated from double determinations within 40 cycles. We found higher TNF expression in cachectic compared to noncachectic CHF patients (log mean −0.5±0.17 vs. −1.2±0.12, p=0.002, ANOVA-p=0.0071) and control subjects (log mean −1.2±0.1, p=0.006). In contrast, there was no change in IL-10 gene expression in cachectic patients compared to noncachectic patients and controls (log mean −2.6±0.2 vs. −3.0±0.09 vs. −2.9±0.1, all p>0.13). Consequently TNF/IL-10 expression ratio was highest in cachectic patients (308±138 vs. 132±55 in noncachectic CHF patients vs. 101±37 in controls, p<0.004). There were no differences in gene expression of STAT-1, STAT-3, SOCS-1, SOCS-3 between cachectic and noncachectic individuals (all p>0.17). Similarly, no differences were found for gene expression of TGF beta (p>0.15).

Conclusion: The balance between the pro-inflammatory cytokine TNF and the anti-inflammatory cytokine IL-10 on the level of mRNA expression of circulating mononuclear cells is significantly disturbed. Proinflammatory cytokine imbalance in cardiac cachexia may be important for the pathophysiology of body wasting and may represent the activated immune reflex.
Abstract 2188: Imbalance In The Mmp timp-system And Myocardial Fibrosis In Patients With Inflammatory Cardiomyopathy
Authors: Rutschow Susanne , Lettau Olga , Jaeger Sebastian , Bock Matthias , Puhl Kerstin , Kuehl Uwe , Noutsias Michael , Schultheiss Heinz P , Pauschinger Matthias
Published: July 2021

Introduction: Inflammation and/or viral infection are both relevant for extracellular matrix remodeling. Therefore the effects of myocardial inflammation on ECM remodeling are analyzed in this study.

# Methods and results: Endomyocardial biopsies were obtained from 20 patients with established DCM (2.11±0.44 CD3 cells/mm
2
) and 29 DCMi patients (18.91±6.41 CD3 cells/mm
2
) comparable in age (51.45±3.15 vs. 48.48±2.39 years), LVEDD (72.7±2.2 vs. 69.76±1.06mm) and EF (26±2.99 vs. 25.86±2.0%). Total collagen content was quantified by picosiriusredstaining while the MMP2, MMP3 and TIMP1 expression was evaluated by immunohistochemistry. The MMP1, MMP3 and TIMP1 and ICTP expression in the serum was quantified by Elisa. and levels of IL6 and IL8 were measured by BioPlexAssays. Furthermore various cytokines and proteases were evaluated by real-time-PCR. In DCMi patients both CD3-lymphocyte infiltration (8.95fold, p<0.001) and IL6 expression (2.93fold, p=0.0067) were significantly increased vs. DCM as well as the mRNA-expression of TNF-alpha (p<0,049). The cellular inflammation correlated with the grade of fibrosis (p<0.01) which is 2.43fold elevated in DCMi (p<0.01). This may be caused by the increased MMP expression in DCMi, demonstrated by elevated MMP1 serum level (1.64fold increased, p<0.01 vs. DCM) and slightly increased MMP-2 (1.41fold) and MMP-3 (1.6fold) expression in biopsies. In contrast, the serum levels of TIMP1 were reduced to 83.14% in DCMi (p=0.06 vs. DCM) and correlated negatively to the serum MMP3 expression (p<0.01) indicating an imbalance in the proteasessystem. The transcripts amount of collagen type I (ρ = −0.80;
P
<0.0091) and III (ρ = −0.80;
P
<0.0091), inflammatory cytokines TGF beta (ρ =−0.67;
P
<0.044) and INF beta (ρ = −0.47;
P
<0.05) as well amount of ICTP (ρ = −0.89;
P
<0.0011) was positively correlated with decreased LVEF from DCMi patients. The increased number of CD3 active cells in DCM biopsies was positively linked to the protein amount of TIMP1 as well to the mRNA amount of MMP9.

Conclusion: Myocardial inflammation in patients with DCMi leads to an imbalance in the MMP/TIMP-system, which attributes to the development of myocardial fibrosis.
Abstract 332: Circulating CCN1 Promotes Angiogenesis via Interaction with Blood CD34
+
Cells
Authors: Grote Karsten , Salguero Gustavo , Dangers Marc , Ballmaier Matthias , Schieffer Bernhard
Published: July 2021

Introduction:
CCN1 is so far known as a protein of the extracellular matrix mediating proliferation, adhesion, migration and angiogenesis in an integrin-dependent manner. We recently reported that CCN1 is up-regulated under pathophysiological conditions in the cardiovascular system. Since blood CD34
+
progenitor cells have been shown to promote tissue regeneration, we investigated if CCN1 induces angiogenesis by stimulating blood CD34
+
cells.

Methods and Results:
Circulating CCN1 was detected for the first time in human serum samples (Western blot). Rekombinant CCN1 (100 ng/mL) and supernatants from CCN1-stimulated human CD34
+
progenitor cells promoted tube-formation (Matrigel-Assay; P < 0.05; n = 4) and proliferation of endothelial cells (BrdU-incorporation; P < 0.05; n = 4). Moreover, CCN1 significantly induced angiogenesis in the context of blood CD34
+
cells in vivo determined in Matrigel implanted into C57/BL6 mice as measured by the hemoglobin content (Drabkin’s reagent) and by CD31 staining (immunohistochemistry). In addition, CCN1 induced migration (Transwell cell culture inserts; 7.3 ± 1.3; P < 0.05; n = 4), transendothelial invasion (Transwell cell culture inserts; 2.3 ± 0.7; P < 0.05; n = 3) of CD34
+
progenitor cells and release of various growth factors, chemokines (protein array; e.g. G-CSF, GM-CSF, CCL2, TGF-β1) and matrix metalloproteinase-9 (zymography; 2.5 ± 0.5-fold; P < 0.05; n = 6) from these cells. CD34
+
progenitor cells expressed the CCN1-specific integrins α
M
β
2
and α
V
β
3
(flow cytometry) and binding of CCN1 to CD34
+
progenitor cells was diminished by integrin antagonizing RGD peptides. Furthermore, CCN1 stimulated integrin-dependent signaling in CD34
+
progenitor cells as shown by enhanced phosphorylation of focal adhesion kinase (immunofluorescence) and promoted their adhesion to endothelial cells which could be inhibited with RGD peptides (P < 0.01; n = 4).

Conclusion:
Circulating CCN1 binds integrin-specific to CD34
+
blood cells and thereby induces migration, adhesion and the release of chemokines and MMPs. Moreover, CCN1-dependent stimulation of blood CD34
+
cells promotes endothelial cell proliferation and angiogenesis known to be important for tissue regeneration.
Abstract 2212: Computational Model of Exercise Effects on Fontan Hemodynamics Demonstrates Favorable Energetics In Extracardiac Fontans When Compared to Lateral Tunnel
Authors: Whitehead Kevin K , Pekkan Kerem , Doddasomayajula Ravi , Kitajima Hiroumi D , Sundareswaran Kartik S , Paridon Stephen M , Yoganathan Ajit P , Fogel Mark A
Published: July 2021

Background:
Previous computational experiments using anatomically correct Fontan geometries have suggested that extracardiac Fontans (EC) have lower power loss compared to lateral tunnel intracardiac (IC) Fontans. Differences in exercise performance may also be important in the long term morbidity of Fontan patients. We have previously developed a computational model for studying exercise conditions.

Hypothesis:
It is our hypothesis that the EC total cavopulmonary connection (TCPC) is more hemodynamically favorable and demonstrates significantly lower resistance at exercise.

Methods:
We performed steady flow CFD simulations on 3-D anatomical reconstructions of TCPC from 9 Fontan patients using cardiac magnetic resonance imaging (CMR) data, 5 with EC and 4 with IC. Caval flows were determined using CMR velocimetry and outlet pulmonary artery pressures tuned to obtain flow splits corresponding to equal vascular lung resistance (EVLR) of 2 Woods units for each lung. Simulated exercise conditions of twice (2x) and three times (3x) baseline MRI flow were performed by increasing IVC flow. Power loss calculations using control volume analysis were performed for each TCPC and each flow condition studied. Power losses were normalized to calculate a resistance index and the two groups compared using the Student t-test for independent groups.

Results:
Resistance index was significantly greater in IC compared to EC Fontans for all three flow conditions. This difference was magnified at exercise flow conditions. At baseline flow, EC TCPC resistance index was 0.14 compared to 0.49 Woods units for IC (p = 0.001). This rose to 0.29 and 0.81 for EC and IC TCPC respectively for the 2x exercise condition (p = 0.002), and to 0.44 and 1.2 for the 3x condition (p = 0.008). There was no significant difference in cardiac output between EC and IC pts, but the EC pts were significantly younger.

Conclusions:
CFD modeling of 3-D anatomical reconstructions demonstrates significant differences in power loss between EC and IC TCPC which are magnified at exercise conditions. The differences are hemodynamically significant, as high as 0.76 Woods units at the highest exercise flow condition, and are thus likely important in the long-term survival and quality of life of patients with TCPC.