bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2278: Long Term Clinical Follow-up and Graft Patency of Off-pump vs On-pump Coronary Artery Surgery in Patients with ST-Segment Elevation Myocardial Infarction
Authors: Fattouch Khalil , Runza Giuseppe , Sampognaro Roberta , Midiri Massimo , Ruvolo Giovanni
Published: July 2021

Off-pump coronary artery bypass grafting is better than on-pump in patients with STEMI underwent surgery within 2 days from onset of symptoms. Surgeons may be reluctant to use OPCAB due to concerns about completeness of myocardial revascularization and graft patency. The aim of this study was to assess long-term clinical outcomes and graft patency in this kind of patients. Participants in two previous randomized studies performed in our institution including 207 STEMI patients underwent emergent or urgent CABG within 48 hours from onset of symptoms were followed after surgery to assess graft patency and major adverse cardiac-related events (MACE). There were 145 patients operated in on-pump and 62 patients in off-pump. Patency was assessed by multidetector computed tomography coronary angiography (MDCTA) with a 64-slice scanner. Two blinded observers classified proximal, body and distal segments of each graft as occluded or not, or grade of stenosis. Clinical follow-up was obtained by our cardiologists. Overall early mortality was 5.3% (11 pts). Percentage of early mortality were 6.7% and 1.6% in on- and off-pump group respectively (p<0.05). Follow-up was obtained in all 196 survivors and was 100% complete. Overall late deaths occurred in 14 patients (7%) without statistical significant difference between both groups; of the remaining 182, 168 (92.3 %) had MDCTA scans (108 pts in on-pump vs 60 pts in off-pump). Patency was studied in 335 grafts in on-pump and 156 grafts in off-pump. Mean duration of follow-up were 38±16 months and 37±14 months for on- and off-pump, respectively. Overall, 449/491 (91.5%) of grafts were patent. Percentages of overall grafts classified as patent were similar in on-pump and off-pump groups (307/335, 91.6% and 142/156, 91% respectively) and for arterial and vein grafts separately. There were also no differences between groups in the incidence of late death and MACE. Long term graft patency and MACE are similar with on-pump vs off-pump CABG in high risk STEMI patients when operation was performed by experienced surgeons. Supported by this results and by low early mortality in off-pump group, we suggests strictly the use of off-pump CABG in this type of patients.
Abstract 2279: A Comparison of Early and Long-Term Outcomes Following Off-Pump and On-Pump Coronary Artery Bypass Surgery: Variation by Renal Function
Authors: Li Yan , Zheng Zhe , Zhang Shiju , Lin Ye , Wang Xianqiang , Zhang Peng , Gao Huawei , Li Wei , Hu Shengshou
Published: July 2021

Background:
The two surgical strategies for coronary artery bypass graft (CABG) surgery are on-pump CABG and off-pump CABG (OPCAB). Earlier studies comparing these two strategies have shown only small differences in clinical outcomes. In light of the growing interest in tailored therapy, the identification of patient subset in which major differences in outcomes exist based on surgical strategy is highly important. Patients with impaired renal function may be a potential target because this patient subset is at increased risk for adverse cardiovascular outcomes.

Methods:
We analyzed data from 5550 consecutive patients undergoing isolated CABG surgery between 1999 and 2005 according to the surgical strategy and the estimated glomerular filtration rate (eGFR), which was calculated with the 4-point Modification of Diet in Renal Disease equation. Early outcomes were in-hospital mortality and postoperative morbidities; and long-term outcomes included total mortality, repeated revascularization, myocardial infarction (MI), and major adverse cardiac events (MACEs=total mortality or repeated revascularization or MI). These outcomes were compared after adjustment for differences in baseline risk factors among the patients.

Results:
1543 (27.8%) patients had impaired renal function (eGFR<60ml/min/1.73 m
2
). In this patient subset, OPCAB was associated with lower rates of 2 postoperative morbidities and comparable in-hospital mortality rate, but long-term outcomes appeared to be inferior for OPCAB with regard to total mortality [hazard ratio (HR) 1.662, 95%CI 1.037 to 2.664], repeated revascularization (HR 2.099, 95%CI 1.177 to 3.743), MI (HR 2.046, 95%CI 1.110 to 3.774), and MACEs (HR 1.834, 95%CI 1.236 to 2.722). Among patients with preserved renal function (eGFR≥60 ml/min/1.73 m
2
), the analysis showed no significant differences in clinical outcomes between the two surgical strategies.

Conclusions:
We observed a significant heterogeneity in treatment effect of surgical strategy (off-pump/on-pump surgery) in relation to renal function. These data suggest that impaired renal function may identify a target patient subset that would be most likely to benefit from on-pump strategy.
Abstract 2286: Short- and Long-Term Survival of Mitral Valve Repair Versus Mitral Valve Replacement in Patients with Functional Mitral Regurgitation
Authors: Magne Julien , Senechal Mario , Mathieu Patrick , Dagenais François , Dumesnil Jean G , Pibarot Philippe
Published: July 2021

Mitral valve repair (MVRp) is associated with better survival in patients with organic mitral regurgitation (MR) when compared to mitral valve replacement (MVR). However, there is an important controversy about the type of surgical treatment that should be used in patients with functional MR (FMR). The aim of this study was to compare MVRp (i.e. restrictive annuloplasty) and MVR in patients with FMR. Pre- and operative demographic and clinical data of 392 patients (64% of male, mean age: 65±10 years) with FMR who underwent mitral surgery between 1992 and 2007 were prospectively collected in a computerized database. MVRp was performed in 52% of patients (n=204) and MVR in 48% (n=188). Compared to patients undergoing MVRp, those with MVR were significantly more frequently symptomatic (77% vs. 59%, p=0.0002), had lower left ventricular ejection fraction (LVEF) (40±15%, vs. 46±15%, p=0.0003) and had higher prevalence of pulmonary hypertension (36% vs. 24%, p=0.01) preoperatively. However, there was no significant difference between the 2 groups with regards to age, gender, MR severity, diabetes, obesity, systemic hypertension and atrial fibrillation (p>0.3). Although operative mortality was significantly lower after MVRp compared to MVR (9% vs. 17%, p=0.02), long-term survival was not statistically different between procedures (6 years: 74±4% vs. 72±4%; 12 years: 54±5% vs. 52±7%; p=0.58). After adjusting for other risk factors, the type of procedure (MVRp vs. MVR) did not come out as an independent predictor of either operative (Odds-ratio=1.7, 95% confidence interval [CI]: 0.8 –3.8, p=0.15) or long-term mortality (Hazard-ratio [HR]=1.1, 95%CI: 0.9 –1.4, p=0.29). The independent predictors of long-term mortality were age (HR= 1.04, 95%CI: 1.01–1.07, p=0.003), NYHA class ≥III (HR=1.4, 95%CI: 1.1–2, p=0.02) and LVEF (HR=1.02, 95%CI: 1.01–1.04, p=0.0009). As opposed to what has been reported in patients with organic MR, there is no evidence that MVRp provides any benefit in terms of survival compared to MVR in patients with FMR. These findings suggest that MVRp is not an optimal surgical treatment for FMR and provide an impetus toward the development of new surgical approaches for these patients.
Abstract 2299: Post-CABG Patients with Non-Revascularizable Coronary Artery Disease - A Population Based Study from Olmsted County, Minnesota
Authors: Kiernan Thomas J , Boilson Barry A , Sandhu Gurpreet S , Barsness Gregory W , Rihal Charanjit S , Simari Robert D
Published: July 2021

Advances in molecular and cellular biology have supported the development of new therapeutic approaches to limiting ischemia. Most often these approaches target patients with ischemia post coronary artery bypass grafting (CABG). Currently, there are few data available on the incidence and outcomes of such patients. To understand this important patient cohort and to estimate the potential need for new therapies, we performed a population-based study of post CABG patients who underwent coronary and graft angiography for angina from 2001 – 2005. Patients who underwent coronary artery and bypass graft angiography at Mayo Clinic from 2001 – 2005 were identified. Medical records were reviewed to determine indication for angiography, and angiographic analysis was performed in all patients. The study cohort was then followed prospectively until March 1 2008. Among 133,000 residents of Olmsted County, Minnesota, 347 post bypass patients with angina underwent coronary angiography from 2001 – 2005. Of those, 51% (177 patients) received further revascularization (endovascular and surgical) and the remaining 170 patients were managed medically. There was no statistical difference in terms of all cause mortality and cardiac mortality between the group that received further revascularization and the group that did not. Adjusting for age and sex for differences between the Olmsted County population and the US white 2000 population yields a yearly incidence rate of 17.9 (95% CI 14.2–21.6) to 33.2 (95% CI 28.2 – 38.3) patients with non-revascularizable angina following CABG per 100,000 population. There was no difference in all cause or cardiac mortality in post-CABG patients presenting with angina whether they received further endovascular/surgical revascularization or not. We estimate that non-revascularizable coronary artery disease post CABG arises in approximately 50,000 (95% CI 40,000 – 61,000) to 93,000 (95% CI 79,000 – 110,000) patients per year extrapolating to the entire US population as a whole.
Abstract 2304: Impact of Papillary Muscle Relocation as Adjunct Procedure to Mitral Ring Annuloplasty in Functional Ischemic Mitral Regurgitation
Authors: Jensen Henrik , Jensen Morten O , Smerup Morten H , Vind-Kezunovic Stefan , Ringgaard Steffen , Vestergaard Rikke , Wierup Per , Hasenkam J M , Nielsen Sten L
Published: July 2021

The optimal surgical treatment in functional ischemic mitral regurgitation (FIMR) remains controversial. Recently, a posterior papillary muscle relocation (PMR) technique as adjunct procedure to ring annuloplasty has been proposed to prevent recurrent FIMR. We assessed the hypothesis that relocating both papillary muscles as adjunct procedure to down-sized ring annuloplasty improves mitral leaflet coaptation geometry in FIMR pigs. Eleven FIMR pigs were randomized to down-sized ring annuloplasty (RA, N=6) or RA combined with PMR (RA+PMR, N=5). In the RA+PMR group a 2– 0 Goretex suture was attached to each trigone, exteriorized through the corresponding papillary muscle, mounted on an epicardial pad and tightened to relocate the myocardium adjacent to the anterior and posterior papillary muscles 5 and 15 mm, respectively. Using 3D magnetic resonance imaging the impact from these interventions on leaflet geometry was assessed. Statistically significant (p<0.05) differences in postoperative leaflet geometry were observed at end-systole (RA vs. RA+PMR, mean ±SEM): Occlusional leaflet area (877 ±36 vs. 666 ±52 mm
2
), tenting volume (1620 ±132 vs. 1064 ±198 mm
3
), mean tenting height (5.9 ±0.2 vs. 4.9 ±0.3 mm), mean coaptation length (6.5 ±0.2 vs. 7.6 ±0.3 mm). Figure 1

shows coaptation length and tenting height of leaflet segments A1-P1, A2-P2 and A3-P3 at end-systole. Adding papillary muscle relocation to down-sized ring annuloplasty reduced leaflet tethering and improved coaptation geometry and therefore holds promise for reducing the prevalence of recurrent FIMR in patients.
Abstract 2314: Insulin is the Protective Component of Glucose-Insulin-Potassium Solutions during Coronary Artery Bypass Graft Surgery in Patients with Diabetes
Authors: Lazar Harold L , McDonnell Marie , Chipkin Stuart , Bao Yusheng , Fitzgerald Carmel , Hunter Curtis , Shapira Oz , Shemin Richard , Cabral Howard
Published: July 2021

Maintaining glycemic control(120 –180mg/dl)with GIK solutions in patients with diabetes undergoing CABG decreases perioperative morbidity and enhances long-term survival. The mechanism by which GIK exerts its protective effects is unknown. This study was undertaken to determine whether it is substrate enhancement with glucose, glycemic control with insulin, or the combination of glucose + insulin + potassium which contributes to improved outcomes with GIK in CABG patients with diabetes. One hundred-twenty diabetic patients undergoing isolated CABG surgery were prospectively randomized to achieve glycemic control(120 –180mg/dl)using an INSULIN infusion(100units/100mlNS),LOW GIK(500mlD5W + 80units insulin + 40mEqKCL), and HIGH GIK(D20W + 200units insulin + 80mEqKCL) beginning on anesthetic induction and continuing for 18 hours after surgery. Variables assessed included Major Adverse Events(MAE=death, MI, CVA, atrial fibrillation, infection, ventilation > 24 hours, inotropic usage > 24hours,lenght of stay > 7days), serum glucose, the amount of insulin infused, and serum free fatty acids(ffa).Values are mean+/− standard deviation. HIGH GIK delivered more insulin and resulted in significantly lower levels of glucose and ffa. However, it had no effect on the incidence of MAEs compared to INSULIN infusions without glucose and potassium. Insulin, rather than substrate enhancement with glucose and potassium, is the key element in GIK used in CABG patients with diabetes. Augmenting insulin delivery results in lower levels of glucose and ffa, but has no effect on clinical outcomes as long as gylcemic control(120 –180mg/dl) is achieved.

This research has received full or partial funding support from the American Heart Association, AHA National Center.

RESULTS
Abstract 2318: Selective Mitochondrial Translocation of Phosphorylated PKCε in Viable Myocytes Overexpressing Urocortin after Cardioplegic Arrest and Reperfusion: Physical Interaction of Phosphorylated PKCε with the Kir6.1 Cardiac Potassium Channel Subunit as a Potential Mechanism of Cardioprotection
Authors: Chen-Scarabelli Carol , Faggian Giuseppe , Tessari Maddalena , Yuan Zhaokan , Di Rezze Justin , Saravolatz Louis , Mazzucco Alessandro , Scarabelli Tiziano M
Published: July 2021

Cardioplegic arrest and subsequent reperfusion inevitably expose the heart to an iatrogenic ischemia/reperfusion injury (iIRI). We previously reported that iIRI caused myocyte induction of urocortin, an endogenous cardioprotective peptide. This study investigates in patients undergoing cardiac surgery the cardioprotective role and the mechanism of action of Ucn, with respect to PKCε expression, activation and relocation. Two sequential biopsies were obtained from the right atrium of 25 patients undergoing coronary artery bypass grafting at the start of grafting (internal control) and 10 minutes after release of the aortic clamp. In hearts exposed to iIRI, induction of Ucn was documented both at the mRNA (255% of basic levels; p < 0.05) and protein level (four-fold increase; p < 0.01). iIRI also induced a selective increase of PKC-ε mRNA (225% of internal control; p < 0.05) and a two-fold overexpression of total PKCε (p < 0.05), which paralleled a 2.9-fold increase in PKCε phosphorylation (p < 0.01). Mitochondrial translocation of activated PKCε was only observed in post-cardioplegic samples, using both subcellular fractionation (p < 0.05) and immunostaining techniques (p < 0.05). Importantly, enhanced PKCε/mitochondria colocalization was selectively observed in viable myocytes, showing concurrently positive staining for urocortin (p < 0.05). Finally, co-immunoprecipitation experiments documented an iIRI-enhanced physical interaction of phosphorylated PKCε with the Kir6.1 subunit of the K
ATP
channels (p < 0.05). Following iIRI, urocortin expression in viable cells selectively colocalized with enhanced phosphorylation and mitochondrial relocation of PKCε, suggesting a cardioprotective role for endogenous Ucn. The physical interaction of activated PKCε with Kir6.1, enhanced by cardioplegic arrest, may represent a conjectural mechanism of urocortin-mediated cardioprotection.
Abstract 2323: Protection of Diabetic Heart with Glutaredoxin Gene Therapy
Authors: Lekli Istvan , Mukherjee Subhendu , Ray Diptarka , Gurusamy Narasimman , Das Dipak
Published: July 2021

Glutaredoxin-1 [Grx1], a redox regulator of thioredoxin superfamily has been implicated in myocardial ischemia reperfusion injury. Diabetes is a well-recognized cardiovascular risk factor. Grx1 has been shown to protect the heart from ischemia reperfusion induced injuries. The present study examined whether Grx1 gene therapy could render the diabetic hearts resistant to ischemia reperfusion injury. Diabetes was induced with streptozotocin, and after the diabetes was confirmed, male C57B1/J6 mice were assigned to one of the two groups and open heart surgery was performed. The mice received an intra-myocardial injection of 109 p.f.u. adenovirus encoding Grx1 or injected with empty vector or adenovirus with LacZ. Three days later, the animals were sacrificed and isolated hearts were subjected to 30 min ischemia followed by 2 hours of reperfusion. Ventricular function was examined, and myocardial infarct size and cardiomyocyte apoptosis were determined. Hemodynamic parameters of the Grx1 overexpressed hearts exhibited improved function compared to those treated with either empty vector or LacZ. Grx1 overexpressed hearts also exhibited reduced myocardial infarct size and cardiomyocyte apoptosis. We examined the protein level of ASK1 and the activation of its downstream target JNK, P38MAPK and the level of procaspase 3 as well as the activities of Akt, and c-Src. Grx1 gene therapy inhibited the phosphorylation of c-Src, as well as suppressed the activities of the ASK1 and JNK indicating a reduction of overall death signal. Grx1 overexpression restored the procaspase 3 level. Akt phosphorylation was significantly higher compared to control hearts. The expression of phase II enzyme heme oxygenase-1 was higher after GRX1 gene therapy. Interestingly thioredoxin (Trx)-1 and Trx-2 protein levels were also slightly higher after GRX-1 treatment. The results of this study indicate cardioprotection with Grx1 gene therapy in diabetic hearts as evidenced by improved post ischemic cardiac performance, reduction of myocardial infarct size and cardiomyocite apoptosis as well as significant reduction of ischemia-reperfusion induced death signal.
Abstract 2329: Donor Pretreatment with Hypertonic Saline Attenuates Primary Cardiac Allograft Dysfunction
Authors: Badiwala Mitesh V , Ramzy Danny , Tumiati Laura C , Tepperman Elissa D , Sheshgiri Rohit , Prodger Jessica L , Feindel Christopher M , Rao Vivek
Published: July 2021

Objective:
Hypertonic saline (HTS) has been previously demonstrated to have immune modulatory and vascular protective effects. We assessed the effect of donor pretreatment with HTS on allograft myocardial function in a porcine model of orthotopic heart transplantation. We hypothesized that HTS infusion prior to donor heart arrest and storage would limit ischemia-reperfusion injury and improve myocardial performance following transplantation.

Methods:
Orthotopic transplants were performed after 6 hours of ischemic allograft storage. Donor pigs were randomly assigned to pretreatment with (n = 7) or without (n = 6) HTS (4.5 ml/kg of 7.5% NaCl) administered 1 hour prior to donor heart arrest. Left ventricular performance was determined after caval occlusion using a Millar micromanometer and conductance catheter. Hemodynamic measurements were obtained using a Swan-Ganz catheter.

Results:
Administration of hypertonic saline increased serum sodium level from 138 ± 2 mmol/L to 154 ± 4 mmol/L, which normalized to 144 ± 3 mmol/L 1 hour post-infusion. Weaning from CPB and LV performance after transplantation was improved after donor HTS treatment. Successful weaning from CPB was significantly greater in HTS treated hearts (6/7 versus 1/6, p < 0.05). Preload recruitable stroke work post-transplantation was improved compared to control (88 ± 21% versus 35 ± 8% of baseline, p < 0.01). Similarly, maximal elastance was improved compared to control (85 ± 17% versus 42 ± 12% of baseline, p = 0.03). No significant differences in post-transplant central venous, pulmonary artery or pulmonary capillary wedge pressures were observed between groups. However, post-transplant systolic blood pressure was significantly higher in the donor HTS group (60 ± 9 mmHg versus 35 ± 6 mmHg, p = 0.04).

Conculsions:
Donor HTS pretreatment attenuates post-transplant cardiac allograft myocardial function and improves post-transplant systemic hemodynamic function. HTS may be a novel organ donor intervention to prevent primary graft dysfunction. Further clinical evaluation of this simple and potentially cost-effective intervention is warranted.
Abstract 2386: Asymptomatic Left Ventricular Systolic Dysfunction as a Predictor of Incident Heart Failure and Mortality in the Elderly: The Cardiovascular Health Study
Authors: Pandhi Jay , Kop Willem J , Gottdiener John S
Published: July 2021

Left ventricular systolic dysfunction (LVSD) is an important predictor of outcomes in heart failure (HF) patients. Adverse effects of LVSD in individuals without heart failure, also known as asymptomatic LVSD (ALVSD), are not well established in the elderly. This study reports outcomes and evaluates the impact of LVSD in elderly subjects with ALVSD. The Cardiovascular Health Study is a multicenter longitudinal cohort study designed to assess cardiac risk factors and outcomes in a community-based population 65 years and older. The incidence of HF and mortality was evaluated in those with ALVSD with a median follow-up of 11.9 years. Cox regression was used, adjusting for demographics and cardiac risk factors, and stratified by severity of LVSD. Incident HF occurred in 39.2% of those with ALVSD vs. 22.8% in those without LVSD (RR = 1.51, CI = 1.25–1.84). Impaired ejection fraction (EF) (< 45%) was associated with more than twice the risk of incident HF than normal systolic function (RR = 2.21; CI 1.67–2.91). Individuals with borderline EF (45–55%) did not have an increased risk of incident HF (RR = 1.21; CI 0.94–1.56). The severity of LVSD was also predictive of mortality: borderline LVSD RR = 1.23 (CI 1.04–1.47) for all-cause mortality and 1.60 (CI 1.26–2.03) for cardiac death; impaired LVSD RR = 1.54 (CI 1.24–1.92) for all-cause mortality and RR = 2.12 (CI 1.60–2.81) for cardiac death. ALVSD is associated with increased risk of heart failure, death, and cardiac death when compared to normal systolic function. Furthermore, the degree of systolic dysfunction has a significant impact in predicting these outcomes in elderly individuals with ALVSD.
Abstract 2391: Impact of Therapies for Anemia on Outcomes in Patients with Heart Failure in Randomized Clinical Trials
Authors: Julien Howard M , Muthukrishnan Preetika , Lewis Eldrin F
Published: July 2021

Anemia is common in heart failure (HF) patients and has been well-established as a risk factor for increased risk of HF hospitalization and mortality. Treatment with erythropoietin stimulating agents (ESA) has increased hemoglobin, but outcomes trials are limited and use of ESA has been controversial given disparate results in other populations. This meta-analysis aimed to evaluate the impact of ESA and iron on outcomes in HF patients. A systematic review of four databases was conducted in April 2008 (n = 95 unique trials). Analysis inclusion criteria included randomized controlled trial to ESA/iron with clinically defined HF, yielding 10 eligible trials published between 6/01–3/08. Data was independently extracted and cross-checked for accuracy and reliability (2 investigators). A total of 768 subjects (421 treated and 338 controls) are included (Characteristics in Table 1

). Randomization to ESA produced a significant improvement in exercise capacity 0.39 standard units [95% CI 0.1– 0.6, p = 0.001], a 5.72% [95% CI 1.2–10.3, p = 0.014] increase in left ventricle ejection fraction and a 0.23 mg/dL [95% CI 0.4 – 0.1 p = 0.001] reduction in serum creatinine. There was no difference in all-cause mortality - RR 0.79 [95% CI 0.49, 1.26, p = 0.320]. Trends were noted in reduced hospitalization rates, decreased brain natriuretic peptide, and improved quality of life. Meta-analysis of randomized studies of treatment of anemia in HF patients suggests significant benefit in exercise capacity, left ventricular ejection fraction, and serum creatinine. There does not appear to be excess mortality with ESA/iron treatment. Despite favorable findings, definitive randomized clinical trials are needed to assess the role of this treatment modality in HF management.

Table 1.

Baseline Patient and Study Characteristics
Abstract 2412: Chronic Vagus Nerve Stimulation in Patients with Chronic Heart Failure is Feasible and Appears Beneficial
Authors: De Ferrari Gaetano M , Sanzo Antonio , Borggrefe Martin , Wolpert Christian , Kuschyk Jürgen , Schöne Antonina , Crijns Harry J , Dennert Robert , Milasinovic Goran , Raspopovic Srdjan , Klein Helmut , Smid Jan , Gavazzi Antonello , Iacovoni Attilio , Riuniti Ospedali , Zabel Markus , Schwartz Peter J
Published: July 2021

Introduction
Enhancement of vagal nerve activity has a strong experimental rationale as a potential therapeutic approach to patients with severe Congestive Heart Failure (CHF). The CardioFit (BioControl Medical, Ltd.) is an implantable system capable of delivering chronic vagus nerve stimulation (CVNS) synchronized with the heart beat via a multipolar stimulation lead.

Methods
Twenty-nine patients with stable CHF, NYHA class II–IV, LVEF ≤ 35% on optimal medical therapy were enrolled and successfully implanted in a 7-site international 6-month safety and efficacy pilot study. Optimization of CVNS parameters occurred during a four week run-in period, two to four weeks post-implantation.

Results
Twenty subjects (mean age 57 years, range 30 –75; ischemic etiology in 70%; prior ICD in 50%) completed six-month follow-up; one NYHA class IV subject died due to worsening HF two months after implantation. At 6-months, 14 subjects had improved their NYHA class, and 6 remained stable. A significant improvement (p < 0.05) was found in the subjects’ quality of life (MLwHF® questionnaire); exercise capacity (6-minute walk test; see graph); and blindly evaluated LV ejection fraction (from 24 ± 2% to 29 ± 2%). The most commonly reported transient adverse events were expected side-effects of CVNS such as pain at cuff site (n = 6), cough (n = 7), and voice alteration (n = 5), which were resolved by optimizing stimulation parameters.

Conclusions
Chronic Vagus Nerve Stimulation in patients with advanced heart failure is feasible and appears to be well tolerated and safe. Initial data suggest a favorable trend of clinical outcomes. At this point a large scale randomized controlled study is warranted.
Abstract 2434: Contractility Augmentation Induced by Refractory Period Stimulation Depends upon Pacing-Site and Diminishes Over Time
Authors: Cornelussen Richard , Mills Robert , Stegemann Berthold , Wodzig Will , Prinzen Frits
Published: July 2021

Purpose
: Refractory period stimulation (RPS) is proposed as a novel, clinically useful method to improve left (LV) and right ventricular (RV) contractility and might be attributed to local para-vascular sympathetic nerve stimulation. We hypothesize that during RPS contractility is largest during proximal (nerve) stimulation, is related to noradrenaline (NA) release and accompanied by disturbed relaxation.

Methods
: RPS was delivered with unipolar, epicardial leads on 3 locations (proximal (p), median (m) and distal (d)) along LAD, LCX, and RCA in open thorax, healthy canines (n=7). RPS consisted of 3 pulses (amplitude 8V, width 1.6 ms) at 40 ms interval, delivered ~40 ms after the R-wave. LV/RV pressures were measured. +dP/dt was used to quantify contractility and −dP/dt used to quantify relaxation. Each site was stimulated for 2 min followed by 5-min baseline. During prolonged RPS-delivery (60 min with 30 min recovery), coronary sinus NA was also measured.

Results
: The highest increase in LV+dP/dt was achieved during LADp stimulation (14±7% (mean±sem) increase
vs
baseline) and lowest during LADd stimulation (9±2%). Delivering RPS along the different LCX locations displayed similar increases in +dP/dt (LCXp; 6%±2%, LCXm; 8±2%, LCXd; 7±2%), but significantly less than the LAD-locations, thus pointing toward a nonuniform sympathetic nerve distribution in the LV wall. RPS at the 3 RCA sites had no effect on LV+dP/dt but greatly enhanced RV+dP/dt (RCAp; 21±6%, RCAm; 22±5%,RCAd; 15±5%, respectively), indicating the localized effect of RPS application. The degree of improvement in LV+dP/dt when using the LAD or LCX was accompanied by similar degree of impairment of LV relaxation (eg for LADp −dP/dt decreased by11±7%). During prolonged RPS delivery, the contractility augmentation significantly decreased from 12±5% to 6±2%. This was accompanied by a similar drop in NA-release into the coronary sinus from 1.08±0.38 to 0.47±0.06 nmol/l (baseline 0.24±0.07 nmol/l).

Conclusion
: RPS-induced increase in myocardial contractility depends on the ventricular localization, diminishes over time and most likely involves noradrenalin release from nerve endings. The depression in relaxation is presumably due to regional differences in adrenergic stimulation.
Abstract 2436: Tricuspid E/Ea is a Powerful Predictor of Cardiac Events in Patients with Chronic Pulmonary Hypertension
Authors: Utsunomiya Hiroto , Nakatani Satoshi , Okada Takenori , Kanzaki Hideaki , Kyotani Shingo , Yamamoto Hideya , Nakanishi Norifumi , Kihara Yasuki , Kitakaze Masafumi
Published: July 2021

Background:
Right ventricular (RV) filling pressure can be estimated using tissue Doppler imaging (TDI) from the tricuspid lateral annulus. There are sparse data on the significance of estimated RV filling pressure in predicting the prognosis of chronic pulmonary hypertension (PH).

Methods:
In 50 consecutive patients with chronic PH undergoing right heart catheterization, early diastolic myocardial velocity (E
a
) at the tricuspid lateral annulus and early diastolic tricuspid inflow (E) were obtained from 4-chamber view using TDI. The tricuspid E/E
a
ratio was calculated and compared with the invasive hemodynamic variables including pulmonary arterial systolic pressure (PASP), mean right atrial pressure (RAP) and RV end-diastolic pressure (RVEDP). Cardiac events including cardiac death or rehospitalization due to RV failure were assessed at long-term follow-up (mean 14.0±1.4 months).

Results:
The tricuspid E/E
a
ratio was significantly positively correlated with RAP (r=0.80, p<0.001) and RVEDP (r=0.72, p<0.001), irrespective of RV systolic function (depressed RV systolic function, n=32, r=0.81; preserved RV systolic function, n=18, r=0.75; both p<0.001). An E/Ea ratio > 7.3 had a sensitivity of 87% and a specificity of 97% for mean RAP ≥ 10mmHg. We divided patients into group A with cardiac events (n=19) and group B without events (n=31). There was no significant difference in PASP between the groups. However, serum brain natriuretic peptide and E/Ea ratio were significantly higher in group A than in group B (349±310 vs 129±136 pg/dl, p=0.001; 7.0±3.2 vs 4.5±.9, p=0.004, respectively). Multivariate Cox’s analysis using TDI and conventional echocardiographic variables showed that the tricuspid E/E
a
ratio (relative risk 1.226, 95%CI 1.011–1.486, p = 0.039) and RA area index (relative risk 1.078, 95%CI 1.002–1.159, p = 0.043) were predictive for cardiac events. Kaplan-Meier analysis showed patients with E/E
a
> 7.3 had a significantly worse outcome than those with E/E
a
≤ 7.3 (log-lank: 10.5, p = 0.0012).

Conclusion:
RV filling pressure can be well estimated using the tricuspid E/Ea ratio. This index and RA size are powerful predictors of cardiac events in patients with chronic PH, suggesting the prognostic importance of RV diastolic dysfunction.
Abstract 2451: Chronic Kidney Disease as an Independent Risk Factor for New-Onset Atrial Fibrillation in Patients with Essential Hypertension
Authors: Horio Takeshi , Iwashima Yoshio , Kamide Kei , Tokudome Takeshi , Nakata Hiroto , Yoshihara Fumiki , Nakamura Satoko , Nakahama Hajime , Kawano Yuhei
Published: July 2021

Atrial fibrillation (AF) is frequently observed in hypertensive heart disease. Older age, increased left ventricular (LV) mass, and left atrial (LA) dilatation are known to be risk factors for the occurrence of AF in hypertensive patients. Chronic kidney disease (CKD) has recently been recognized to be a powerful risk for cardiovascular events. However, no study has revealed the association between CKD and the onset of AF. Thus, the present study assessed the hypothesis that CKD may influence the onset of AF in hypertensives. A total of 1,118 essential hypertensive patients (mean age, 63 years) without previous paroxysmal AF, heart failure, myocardial infarction, valvular disease, or LV asynergy were enrolled. In echocardiographic examinations, LA dimension and LV mass index (LVMI) were determined. Estimated glomerular filtration rate (eGFR) was calculated by the modified MDRD formula. During follow-up periods (mean, 4.7 years), fifty-seven cases of new onset AF (including paroxysmal AF) were found (1.1% /year). Cumulative event-free rates by the Kaplan-Meier method were decreased according to the decrease in basal eGFR (≥60, 30 – 60, 15–30, and <15 mL/min) and the increase in proteinuria (−/±, 1+/2+, and ≥3+) (log-rank test P<0.001, respectively). When CKD was defined as decreased eGFR (<60 mL/min) and/or the presence of proteinuria, the prevalence of new-onset AF was significantly higher in subjects with CKD (n=420) than without CKD (n=698) (7.9% vs 3.4%, P=0.001). Kaplan-Meier curves also revealed the increase in event rates in the CKD group (log-rank test P<0.001). By univariate Cox regression analysis, age, smoking, LA dimension, LVMI, and the presence of CKD were significantly associated with the occurrence of AF during follow-up. Among these possible predictors, older age (HR 1.63 /10 years, P<0.001) and the presence of CKD (HR 2.25, P=0.004) were independent determinants for the onset of AF in multivariate analysis. The present study demonstrated that the complication of CKD in hypertensive patients was a powerful predictor of new-onset AF, independently of LV hypertrophy and LA dilatation. Our findings may provide a new aspect in considering the cardiorenal association in hypertensive diseases.
Abstract 2458: Atorvastatin Reduces Sympathetic Activity in Hypertensive Patients
Authors: Gomes Marc E , Tack Cees J , Verheugt Freek W , Smits Paul , Lenders Jacques W
Published: July 2021

Background
In hypertension, a state of increased (central) sympathetic activity exists. This high sympathetic activity is associated with worse prognosis and refractoriness to pharmacological interventions. Animal experimental data suggest that HMG CoA reductase inhibitors (statins) can reduce sympathetic activity at a central level. We hypothesized that atorvastatin 80 mg/day could reduce sympathetic activity in human patients with hypertension.

Methods
Using a prospective, randomized, placebo-controlled, double-blind, cross-over design, patients were randomly assigned to atorvastatin 80 mg/day or placebo, for 3 weeks. Sympathetic nervous system activity was measured at the end of each treatment period, in 13 patients with mild to moderate hypertension by microneurography for direct muscle sympathetic nerve recording (MSNA) and plasma norepinephrine concentrations. Effects on blood pressure were assessed by 24 hour ambulatory blood pressure measurement.

Results
Atorvastatin significantly reduced MSNA (atorvastatin: 58.5±2.0 vs. placebo: 64.7±3.0 bursts/100 beats, P=0.02). Although MSNA values and plasma cholesterol levels were correlated, reduction in MSNA was independent of the degree of reduction in plasma cholesterol. Atorvastatin had no effect on plasma norepinephrine levels nor on daytime and night time blood pressure.

Conclusion:
In patients with mild to moderate hypertension, atorvastatin treatment reduces central sympathetic nervous outflow. This finding supports the concept that HMG CoA reductase regulates sympathetic nervous system activity at the central level and indicates a sympathoinhibitory role for atorvastatin in human hypertensive patients.
Abstract 2476: Regular Physical Activity Prevents the Development of Left Ventricular Hypertrophy in Young Stage 1 Hypertensive Subjects: Results of the Harvest Study
Authors: Mos Lucio , Visentin Pier Alberto , Mormino Paolo , Dorigatti Francesca , Vriz Olga , Dusi Veronica , Palatini Paolo
Published: July 2021

A beneficial effect of physical activity on left ventricular mass( LVM) in the short term has been described in hypertension. Aim of this study was to investigate the long-term effect of regular physical activity on development of left ventricular hypertrophy (LVH) in a cohort of young hypertensive subjects. We studied 454 participants (317 men, mean age 33±8 years) without LVH at baseline whose physical activity status was consistent throughout the follow-up. BP was 146±11/94±5 mm Hg at baseline and 141±/90±8 mmHg after 3 months of non-pharmacological measures. Subjects were divided into 3 categories of physical activity (sedentary, n=281;leisure-time activities, n=140; competitive sports, n=33). Patients were seen every six months until they developed hypertension. Echocardiographic LVM was measured at entry, every 5 years, and/or at the time of hypertension development. Active subjects were younger (31±8 versus 34±8 years, p=.000) and leaner (24.4±3.0 vs 25.2±3.7 Kg/m2, p=.006) than sedentary ones, and were more frequently male (45% versus 22%, p=.000). During a median follow-up of 8.2 years, 32 subjects(7.3%) developed LVH (sedentary=10.3%, leisure-time activities=2.1%, competitive sports= 0%, p=.002). In a logistic regression, physically active groups combined (n=173) were less likely to develop LVH than the sedentary group with a crude OR=0.16 (CI, 0.05– 0.55). After controlling for sex, age, family history for hypertension, body weight, smoking, alcohol and coffee use, blood pressure, LVM, and follow-up time, the OR was 0.22 (CI, 0.06 – 0.77). BP declined over time in physically active subjects (−5.1±17.0/−0.5±10.2 mmHg) and slightly increased in sedentary ones (0.0±15.3/0.9±9.7 mmHg, adjusted p versus active=0.04/0.06). Inclusion of changes in BP over time into the logistic model slightly decreased the strength of the association between physical activity status and LVH development (OR=0.24,CI, 0.07– 0.85). Regular physical activity prevents the development of LVH in young stage 1 hypertensive subjects. Leisure-time and competitive sports activities seem to have both a beneficial effect on LVM. This effect is only partially dependent on the reduction in BP caused by exercise.
Abstract 2514: Endovascular Imaging Causes Significant But Temporary Endothelial Injury
Authors: Van Der Giessen Willem J , Krabbendam Stefan C , van Beusekom Heleen M
Published: July 2021

Coronary Imaging e.g. IVUS and OCT to assess vascular size, plaque morphology and composition are useful tools in clinical trials as well as in routine practice. It is unclear whether imaging catheters induce acute endothelial cell damage (ECD) and how this heals over time.

Methods. Normal porcine coronary arteries were subjected to intravascular imaging (Raman, IVUS, OCT), guidewire-only placement or no manipulation (control). ECD was assessed acute or at 5 days (chronic) with an Evans Blue dye-exclusion test and planimetry followed by scanning electron microscopy (SEM).

Results. Acute injury (% staining of the area exposed to imaging) was considerable, but similar for the 3 imaging catheters. Guidewire-only induced less ECD. One-way ANOVA showed that only OCT- and RAMAN induced more ECD than control. Analysis with SEM showed that staining was associated with either EC denudation or injured but present EC. At 5 days staining was reduced to background levels.

Conclusion. Vascular imaging and guide wire manipulation both induce acute ECD, but this injury heals within 5 days following imaging. Planimetry of endothelial injury
Abstract 2535: The Adverse Long-Term Impact of Renal Impairment on Patients undergoing Percutaneous Coronary Intervention in the DES Era
Authors: Appleby Clare , Ivanov Joan , Mackie Karen , Lavi Shahar , Ing Doug , Overgaard Chris , Seidelin Peter , Dzavik Vlad
Published: July 2021

Renal impairment (RI) is known to be associated with poor in-hospital outcomes following percutaneous coronary intervention (PCI) but its effect on outcomes beyond one year, particularly in the drug eluting stent (DES) era has not been reported. We undertook an observational study to determine the long-term impact of renal impairment on patients undergoing PCI at a large, tertiary cardiac referral centre. Baseline creatinine was available for 11,969 of the 15,012 consecutive patients undergoing PCI at our institution between April 2000 and Sept 2007. Patients were stratified into those with or without at least moderate RI, defined as a creatinine clearance <60ml/min (CKD class ≤ 3). In-hospital mortality and morbidity were calculated for each cohort. Follow up data was obtained through linkage to a provincial registry. Kaplan-Meier analysis was performed and Cox multiple regression analysis was used to identify independent predictors of late mortality and MACE (major adverse cardiovascular events), and to examine the association between DES use and late outcomes in the presence or absence of RI. Of the 11,953 patients with available long-term follow-up, 3070 had RI (25.7%). In hospital mortality and MACE were significantly increased in those patients (3.34% vs 0.44%, p<0.001, and 5.73% vs 2.2%, p<0.001, respectively). At 7 year follow-up, survival and MACE-free survival were both reduced (64.5 ± 1.4% vs 89.4 ± 0.5%, p<0.001, and 44.0 ± 1.4% vs 63.4 ± 0.8%, p<0.001). RI was identified as an independent predictor of both late mortality and cardiovascular events (HR 2.2, p<0.0001 and HR 1.4, p<0.0001) but DES use was associated with a significant risk reduction for these events (HR 0.7, p<0.0001). In patients with RI, DES use, rather than bare metal stents, was associated with a reduction in mortality (HR 0.83, CI 0.66 –1.0, p=0.1) and reduced subsequent CABG (HR 0.46, CI 0.22– 0.97, p=0.041) but had no effect on repeat PCI (p=0.63). In a large registry of “all-comers” for PCI, RI was an independent predictor of adverse late outcomes at 7 year follow-up. DES use however was associated with improved long-term outcomes in this high risk cohort.
Abstract 2571: Long-Term Endothelial Dysfunction after Coronary Artery Stenting with Drug-Eluting Stent Associated with Local Inflammatory Response
Authors: Wakatsuki Tetsuzo , Yamaguchi Koji , Niki Toshiyuki , Kusunose Kenya , Koshiba Kunihiko , Yamada Hirotsugu , Soeki Takeshi , Yagi Syusuke , Iwase Takashi , Akaike Masashi , Sata Masataka
Published: July 2021

Endothelial function remains chronically abnormal after vascular injury associated with coronary intervention. The long-term effects of drug-eluting stent (DES) on endothelial function are not known. We evaluated the endothelial-dependent vasomotor function and local release of pentraxin3 (PTX3) as a local inflammatory marker in nonrestenotic coronary arteries more than six months following DES and bare metal stent (BMS) implantation. Fifty-two patients treated six months earlier with a coronary stenting for isolated proximal left anterior descending (LAD) stenosis, with no evidence of restenosis, were studied. Twenty patients had been stented with BMS, and 32 had been with DES. Changes in diameter at distal site of the stented LAD in response to intracoronary acetylcholine (Ach) infusions (1,3,10,30 μg/min) were assessed by quantitative angiography. At the completion of the protocol, a 2mg bolus of isosorbide dinitrate (ISDN) was injected into the LAD. We also measured serum PTX3 levels sampled in coronary sinus (CS) and sinus of Valsalva (V).

Results:
The two groups had similar risk factors for endothelial dysfunction. The mean percent change in the diameter of the stented LAD by Ach injection was significantly more in the DES group than in the BMS group (−38.9±6.1 vs. −19.2±6.7 %, p<0.01). There was no significant difference in maximal dilation achieved by ISDN infusion between the two groups (34.6±6.6 vs. 31.2±4.6 %, NS). The translesional PTX3 gradient (CS-PTX3 minus V-PTX3) was higher in the DES group than in the BMS group (+0.11±0.05 vs. −0.01±0.05 ng/ml, p<0.01). More severe endothelial dysfunction was observed long term after DES implantation as compared to BMS. These findings were associated with an increased local inflammatory response to DES stenting.
Abstract 2632: Stroke Protection Is Largely Related To Cholesterol-lowering In Lipid-lowering Intervention Trials: A Meta-analysis And Meta-regression
Authors: De Caterina Raffaele , Scarano Marco , Palma Francesco , Marfisi Rosamaria , Di Napoli Pericle , Borrelli Giovanna , Marchioli Roberto
Published: July 2021

Background:
In clinical trials, statins reduce the incidence of strokes. It has been proposed that such effect is independent of cholesterol lowering and best explained by alternative mechanisms. We tested whether the effects of statins on stroke is qualitatively similar to that of other cholesterol-lowering interventions, and explained by cholesterol lowering.

Methods:
We reviewed the literature of randomized lipid-lowering trials reporting the stroke incidence, for a total of 176,974 patients investigated and a cumulative 627,117 patients/year exposure. Strokes incidence was related to treatments tested in the trials, and a meta-regression related the extent of stroke reduction as a function of the reduction in total cholesterol.

Results:
The odds ratio and 95% confidence interval (95% CI) for the total incidence of stroke in the actively-treated group compared with controls were 0.86 (0.81– 0.91, p<0.001). Statins decreased the risk of total stroke significantly (0.83, 0.78 – 0.89, p<0.001). The benefit of non-statin interventions on total stroke was small and not statistically significant (OR 0.95, 95% CI 0.85–1.08, p=N.S.). In the meta-regression, however, we found a significant relationship between the percent reduction of total cholesterol obtained in both statin and non-statin trials and the percent reduction of the relative risk of total stroke (p=0.0471). Neither statins nor other cholesterol-lowering interventions reduced the risk of fatal stroke.

Conclusions:
Among lipid-lowering interventions, statins are effective in decreasing the risk of total stroke, but their benefit appears associated with the extent of reduction of blood cholesterol, and is in line with their greater cholesterol-lowering potency compared with non-statin interventions.