Sex difference and outcome trends following surgical aortic valve replacement from the National Inpatient Sample (NIS) Database.

BACKGROUND: Based on worldwide registries, approximately 50% of patients who underwent aortic valve replacement (AVR) via surgical aortic valve replacement are females. Although AVR procedures have improved greatly in recent years, differences in outcome including mortality between sexes remain. We aimed to investigate the trends in SAVR outcomes in females versus males. METHODS: Using the 2011-2017 National Inpatient Sample (NIS) database, we identified hospitalizations for patients with diagnosis of aortic stenosis during which SAVR was performed. Patients' sociodemographic and clinical characteristics, procedure complications, and mortality were analyzed. Piecewise regression analyses were performed to assess temporal trends in SAVR utilization in females versus males. Multivariable analyses were performed to identify predictors of in-hospital mortality. RESULTS: A total of 392,087 hospitalizations for SAVR across the USA were analyzed. Utilization of SAVR in both sex patients decreased significantly during the years 2011-2017. Males compared to females had significantly higher rates of hyperlipidemia, chronic renal disease, peripheral artery disease, coronary artery disease and tended to be smokers. Differences in mortality rates among sexes were observed for SAVR procedures. Women had higher in-hospital mortality with 3.7% compared to men with 2.5% (OR 1.38 [95% CI 1.33-1.43, P<0.001]). In a multivariable regression model analysis adjusted for potential confounders, women had higher mortality risk with odd ratio (OR 1.38 [95% CI 1.33-1.43], P<0.001). Women had significantly higher rates of vascular complications (5.1% compared to men with 4.6%, P=0.002). CONCLUSIONS: Utilization of SAVR showed a downward trend during the study period. Higher in-hospital mortality was recorded in females compared to males.

The DNA methylome of human vascular endothelium and its use in liquid biopsies.

BACKGROUND: Vascular endothelial cells (VECs) are an essential component of each tissue, contribute to multiple pathologies, and are targeted by important drugs. Yet, there is a shortage of biomarkers to assess VEC turnover. METHODS: To develop DNA methylation-based liquid biopsies for VECs, we determined the methylome of VECs isolated from freshly dissociated human tissues. FINDINGS: A comparison with a human cell-type methylome atlas yielded thousands of loci that are uniquely unmethylated in VECs. These sites are typically gene enhancers, often residing adjacent to VEC-specific genes. We also identified hundreds of genomic loci that are differentially methylated in organotypic VECs, indicating that VECs feeding specific organs are distinct cell types with a stable epigenetic identity. We established universal and lung-specific VEC markers and evaluated their presence in circulating cell-free DNA (cfDNA). Nearly 2.5% of cfDNA in the plasma of healthy individuals originates from VECs. Sepsis, graft versus host disease, and cardiac catheterization are associated with elevated levels of VEC-derived cfDNA, indicative of vascular damage. Lung-specific VEC cfDNA is selectively elevated in patients with chronic obstructive pulmonary disease (COPD) or lung cancer, revealing tissue-specific vascular turnover. CONCLUSIONS: VEC cfDNA biomarkers inform vascular dynamics in health and disease, potentially contributing to early diagnosis and monitoring of pathologies, and assessment of drug activity. FUNDING: This work was supported by the Beutler Research Program, Helmsley Charitable Trust, JDRF, Grail and the DON Foundation (to Y.D.). Y.D holds the Walter & Greta Stiel Chair in heart studies. B.G., R.S., J.M., D.N., T.K., and Y.D. filed patents on cfDNA analysis.

NEXUS Arch: A Multicenter Study Evaluating the Initial Experience With a Novel Aortic Arch Stent Graft System.

OBJECTIVE: To assess the initial clinical experience with a novel endograft system (NEXUS Aortic Arch Stent Graft System) designed to treat aortic arch pathologies and address the morphology and hemodynamic challenges of the aortic arch. SUMMARY BACKGROUND DATA: The aortic arch remains the most challenging part of the aorta for both open and endovascular repair. Transcatheter aortic arch repair has the potential to significantly reduce surgical risks. METHODS: Patients underwent transcatheter aortic arch repair with a single branch, 2 stent graft system, implanted over a through-and-through guidewire from the brachiocephalic trunk, to the descending aorta with an ascending aorta stent graft. The ascending aorta stent graft is deployed into a designated docking sleeve to connect the 2 stent grafts and isolate the aortic arch pathology. Proximal landing zone in all cases was in Zone 0. Anatomical inclusion criteria included adequate landing zone in the ascending aorta, brachiocephalic trunk, and descending thoracic aorta. Preparatory debranching procedure was performed in all patients with carotid-carotid crossover bypass and left carotid to left subclavian bypass, or parallel graft from descending aorta to left subclavian artery. Safety and performance were evaluated through 1 year. Survival analysis used the Kaplan-Meier method. RESULTS: Twenty-eight patients, 79% males, with a mean age of 72.2 ± 6.2 years were treated with 100% procedural success. Isolated aortic arch aneurysm was the principle pathology in 17 (60.7%) of patients, while chronic aortic dissection was the principle pathology in 6 (21.4%) of patients. The remaining 5 (17.8%) had combined or other pathologies. At 1 month, the vascular pathology was excluded in 25 of 26 alive patients (96.1%). The 30 days mortality rate was 7.1%, stroke rate was 3.6% (all nondisabling), and combined mortality/stroke rate was 10.7%. One-year mortality was 10.7%, without device or aneurysm-related death. Two patients (7.1%) reported stroke or transient ischemic attack at 1 year that recovered completely. One year combined mortality/stroke rate was 17.8%. There were 3 patients (10.7%) that had device-related unplanned reinterventions through 1 year. CONCLUSIONS: The NEXUS Aortic Arch Stent Graft System, a novel single branch, 2 stent graft system used for endovascular aortic arch repair that requires landing in the ascending aorta, demonstrates a high success rate with excellent 1 year safety and performance.

Three-year follow-up of aortic arch endovascular stent grafting with the Nexus device: results from a prospective multicentre study.

OBJECTIVES: Endovascular aortic arch stent grafting with branched devices has shown initial promising results. The aim of this prospective, multicentre study was to evaluate 3-year outcomes of aortic arch stent grafting with NEXUS® Aortic Arch Stent Graft System (Nexus), a single-branch, bi-modular, off-the-shelf aortic arch stent graft system in high-risk patients. METHODS: Patients treated with Nexus, either under the feasibility clinical study or as compassionate use procedures in 5 centres, were included in this study. The primary end point was overall survival. The secondary end points included the incidence of procedure-related unplanned intervention, stroke, paraplegia and endoleak. Clinical and radiologic follow-up was performed at each study site at 30 days, 6 months and on a yearly basis thereafter up to 3 years postoperatively. RESULTS: We analysed data from a total of 28 patients. The overall median follow-up was 1132 (interquartile range: 809-1537). There were no device or procedure-related deaths between 1 and 3 years. Overall survival at 1 and 3 years was 89% and 71%, respectively. The cumulative incidence of unplanned reintervention at 1 and 3 years was 11% and 29%, respectively. There were no reports of stroke, paraplegia, aneurysm rupture, myocardial infarction or new aortic valve insufficiency. In this study's 1-3 year follow-up period, 1 type Ib (4%), 1 type II (4%) and 2 type III (8%; between Nexus' distal end and Thoracic endovascular aortic repair (TEVAR) extensions) endoleak were detected. CONCLUSIONS: Endovascular aortic arch exclusion with the single-branch, off-the-shelf Nexus system provides promising clinical and radiologic results at 3-year follow-up in a high-risk patient cohort.

Left atrial appendage exclusion in atrial fibrillation.

Although oral anticoagulants (OACs) are first-line therapy for stroke prevention in patients with atrial fibrillation (AF), some patients cannot be treated with OACs due to absolute or relative contraindications. Left atrial appendage (LAA) exclusion techniques have been developed over the years as a therapeutic alternative for stroke prevention. In this paper, we review the evolution of surgical techniques, employed as an adjunct to cardiac surgery or as a stand-alone procedure, as well as the recently introduced and widely utilized percutaneous LAA occlusion techniques. Until recently, data on surgical LAAO were limited and based on non-randomized studies. We focus on recently published randomized data which strongly support an add-on surgical LAAO in eligible patients during cardiac surgery and could potentially change current practice guidelines. In recent years, the trans-catheter techniques for LAA occlusion have emerged as another, less invasive alternative for patients who cannot tolerate oral anticoagulation. We review the growing body of evidence from prospective studies and registries, focusing on the two systems which are in widespread clinical use nowadays: the Watchman and Amulet type devices. These data show favorable results for both Watchman and Amulet devices, setting them as an important tool in our arsenal for stroke reduction in AF patients, especially in those who have contraindications for OACs. A better understanding of the different therapeutic alternatives, their specific benefits, and downfalls in different patient populations can guide us in tailoring the optimal therapeutic approach for stroke reduction in our AF patients.

Mass to voltage ratio index predicts mortality following TAVI.

Transcatheter aortic valve implantation (TAVI) is commonly performed in elderly patients with aortic stenosis. Better methods of risk stratification are needed in this population with high morbidity. There is a relatively high incidence of cardiac amyloidosis in this population and high LV mass index (LVMI) to QRS voltage may help identify patients with worse prognosis following TAVI. This retrospective study enrolled consecutive patients who underwent TAVI in our institution between the years 2008-2019. Mass voltage ratio index (MVRi) was calculated as the ratio of LV mass index on echocardiogram to voltage using the Sokolow-Lyon criteria on 12 lead ECG performed within 3 months before the intervention. Two hundred and fifty-one patients (mean age 80.8 years, 49% men) were enrolled. One hundred and sixty-eight (67%) patients were alive at 3 years follow up. MVRi was a statistically significant predictor of 3 year mortality (p < 0.005). Patients were divided categorically into tertiles based on MVRi score; the "high" group had significantly higher 3-year mortality (p < 0.001). In the multivariate model only Euroscore (p < 0.009) and MVRi (p < 0.011; OR: 2.32; CI: 1.15-4.964) were statistically significant predictors of mortality. The "high" group had a significantly lower survival rate after 3 years follow up on Kaplan-Meier analysis (p < 0.001). Our findings suggest that MVRi is a strong, independent predictor of increased post-TAVI mortality. This may be a simple clinical tool to assist in the assessment of patients prior to before TAVI.

The Relationship Between Body Mass Index and In-Hospital Mortality in Patients Following Coronary Artery Bypass Grafting Surgery.

Background: The association between Body Mass Index (BMI) and clinical outcomes following coronary artery bypass grafting (CABG) remains controversial. Our objective was to investigate the real-world relationship between BMI and in-hospital clinical course and mortality, in patients who underwent CABG. Methods: A sampled cohort of patients who underwent CABG between October 2015 and December 2016 was identified in the National Inpatient Sample (NIS) database. Outcomes of interest included in-hospital mortality, peri-procedural complications and length of stay. Patients were divided into 6 BMI (kg/m2) subgroups; (1) under-weight ≤19, (2) normal-weight 20-25, (3) over-weight 26-30, (4) obese I 31-35, (5) obese II 36-39, and (6) extremely obese ≥40. Multivariable logistic regression model was used to identify predictors of in-hospital mortality. Linear regression model was used to identify predictors of length of stay (LOS). Results: An estimated total of 48,710 hospitalizations for CABG across the U.S. were analyzed. The crude data showed a U-shaped relationship between BMI and study population outcomes with higher mortality and longer LOS in patients with BMI ≤ 19 kg/m2 and in patients with BMI ≥40 kg/m2 compared to patients with BMI 20-39 kg/m2. In the multivariable regression model, BMI subgroups of ≤19 kg/m2 and ≥40 kg/m2 were found to be independent predictors of mortality. Conclusions: A complex, U-shaped relationship between BMI and mortality was documented, confirming the "obesity paradox" in the real-world setting, in patients hospitalized for CABG.

ChIP-seq of plasma cell-free nucleosomes identifies gene expression programs of the cells of origin.

Cell-free DNA (cfDNA) in human plasma provides access to molecular information about the pathological processes in the organs or tumors from which it originates. These DNA fragments are derived from fragmented chromatin in dying cells and retain some of the cell-of-origin histone modifications. In this study, we applied chromatin immunoprecipitation of cell-free nucleosomes carrying active chromatin modifications followed by sequencing (cfChIP-seq) to 268 human samples. In healthy donors, we identified bone marrow megakaryocytes, but not erythroblasts, as major contributors to the cfDNA pool. In patients with a range of liver diseases, we showed that we can identify pathology-related changes in hepatocyte transcriptional programs. In patients with metastatic colorectal carcinoma, we detected clinically relevant and patient-specific information, including transcriptionally active human epidermal growth factor receptor 2 (HER2) amplifications. Altogether, cfChIP-seq, using low sequencing depth, provides systemic and genome-wide information and can inform diagnosis and facilitate interrogation of physiological and pathological processes using blood samples.

Update in carcinoid heart disease - the heart of the matter.

Carcinoid heart disease (CHD) is a paraneoplastic cardiac manifestation occurring in patients with carcinoid syndrome (CS) and advanced neuroendocrine malignancy. In about 20-40% of patients with CS, chronic exposure to tumor-released circulating vasoactive peptides typically results in right-sided valvular fibrosis leading to valve dysfunction and right heart failure. CHD remains a significant cause of morbidity and mortality. The management of patients with CHD is complex, as both the systemic malignant disease and the heart involvement have to be addressed. Early diagnosis and timely surgical intervention in selected patients are of utmost importance and offer a survival benefit. In patients with advanced carcinoid heart disease, valve replacement surgery is the most effective option to alleviate cardiac symptoms and contribute to survival outcomes. A collaboration of a multidisciplinary team in centers with experience is required to provide optimal patient management. Here, we review the current literature regarding CHD presentation, pathophysiology, diagnostic tools, and available treatment strategies.

Trends in Utilization and Safety of In-Hospital Coronary Artery Bypass Grafting During a Non-ST-Segment Elevation Myocardial Infarction.

Up to 10% of non-ST-segment elevation myocardial infarction (NSTEMI) patients require coronary artery bypass graft (CABG) surgery during their hospitalization. Contemporary, real-world, data regarding CABG utilization and safety in NSTEMI patients are lacking. Our objectives were to investigate the contemporary trends in utilization and outcomes of CABG in patients admitted for NSTEMI. Using the 2003 to 2015 National Inpatient Sample data, we identified hospitalizations for NSTEMI, during which a CABG was performed. Patients' sociodemographic and clinical characteristics, incidence of surgical complications, length of stay, and mortality were analyzed. Multivariate analyses were performed to identify predictors of in-hospital complications and mortality. An estimated total of 440,371 CABG surgeries, during a hospitalization for NSTEMI, were analyzed. The utilization of CABG was steady over the years. The data show increasing prevalence of individual co-morbidities as well as cases with Deyo Co-morbidity Index ≥2 (p <0.001). High, 26.4%, complication rate was driven mainly by cardiac and pulmonary complications. The mortality rate declined from 3.6% in 2003 to an average of 2.4% during 2010 to 2015. Older age, female gender, heart failure, and delayed CABG timing were independent predictors of adverse outcomes. In conclusion, utilization of in-hospital CABG as the primary revascularization strategy in patients with NSTEMI remained steady over the years. These data reveal the raising prevalence of co-morbidities during the study. High complication rate was recorded; however, the mortality declined over the years to about 2.4%. Delaying CABG was associated with small but statistically significant worsening in outcomes.

Endovascular brachytherapy for extensive right-heart and pulmonary artery sarcoma - a case report.

PURPOSE: Primary sarcoma of the heart is a rare but devastating tumor. Median survival with conventional treatment is 8-12 months. When resection is not feasible, patients often succumb to heart failure secondary to obstruction of blood flow, valve dysfunction, chamber compression or conduction abnormalities. Palliative treatment options include systemic chemotherapy and external beam irradiation. We herein describe a novel technique using endovascular brachytherapy, aiming at reducing tumor mass, alleviating right ventricular pressure overload and at the same time keeping the option of R0 resection viable. MATERIAL AND METHODS: A 35-year-old man was diagnosed with a non-resectable high-grade intimal sarcoma of the right ventricle (RV), main pulmonary artery (PA) and right PA. After three cycles of doxorubicin and ifosfamide, the patient's symptoms of right heart failure worsened. Imaging documented tumor progression and supra-systemic pulmonary artery pressure. Through a trans-femoral venous access, a brachytherapy sleeve was placed in the RV and main and right PA. A dose of 20 Gy was delivered over a period of ten minutes. RESULTS: The patient had an uneventful course and was discharged home 24 hours after the procedure. Ten months after brachytherapy, repeat imaging demonstrated a significant reduction in tumor volume and an increase in pulmonary artery cross-sectional area with a marked reduction of pulmonary artery pressure, leading to a complete resolution of heart failure symptoms. CONCLUSIONS: Endovascular brachytherapy is a novel, safe and effective therapeutic modality for non-resectable primary cardiac sarcomas either for palliation of obstruction, or tumor mass reduction to allow complete resection.

Early outcomes with a single-sided access endovascular stent.

OBJECTIVE: The objective of this study was to report the 1-year follow-up study results of the new Horizon stent graft (Endospan, Herzliya, Israel) from two different prospective consecutive trials. The Horizon abdominal aortic aneurysm stent graft system is a 14F profile system requiring only a single access site. It consists of three modules, introduced separately: base limb (iliac to iliac limb); distal aortic limb; and proximal aortic limb with a bare suprarenal crown and active fixation. METHODS: Data from the first in man (FIM) clinical study with 10 patients enrolled and the pivotal study with 30 patients were analyzed. Outcomes measured were freedom from major adverse events (MAEs) including all-cause mortality, myocardial infarction, renal failure, respiratory failure, paraplegia, stroke, bowel ischemia, and procedural blood loss ≥1000 mL. Performance end points included successful delivery and deployment of the device, freedom from aneurysm growth ≥5 mm, type I or type III endoleak, stent graft occlusion, conversion to open surgery, rupture, and stent graft migration. RESULTS: In the FIM study, one conversion to open surgery with >1000 mL of blood loss was registered perioperatively. In the pivotal study, no perioperative MAE was registered. Overall, at 1-year follow-up, two deaths and one aneurysm growth unrelated to endoleak were registered. CONCLUSIONS: The results of both the FIM and pivotal studies demonstrated that 39 of 40 procedures were successful for delivery and deployment of the Horizon stent graft. No MAE was registered during the follow-up. The primary safety and performance end points were met in both studies.

The effect of prolonged physical activity performed during extreme caloric deprivation on cardiac function.

BACKGROUND: Endurance exercise may induce transient cardiac dysfunction. Data regarding the effect of caloric restriction on cardiac function is limited. We studied the effect of physical activity performed during extreme caloric deprivation on cardiac function. METHODS: Thirty-nine healthy male soldiers (mean age 20 ± 0.3 years) were studied during a field training exercise lasted 85-103 hours, with negligible food intake and unlimited water supply. Anthropometric measurements, echocardiographic examinations and blood and urine tests were performed before and after the training exercise. RESULTS: Baseline VO(2) max was 59 ± 5.5 ml/kg/min. Participants' mean weight reduction was 5.7 ± 0.9 kg. There was an increase in plasma urea (11.6 ± 2.6 to 15.8 ± 3.8 mmol/L, p<0.001) and urine osmolarity (692 ± 212 to 1094 ± 140 mmol/kg, p<0.001) and a decrease in sodium levels (140.5 ± 1.0 to 136.6 ± 2.1 mmol/L, p<0.001) at the end of the study. Significant alterations in diastolic parameters included a decrease in mitral E wave (93.6 to 83.5 cm/s; p = 0.003), without change in E/A and E/E' ratios, and an increase in iso-volumic relaxation time (73.9 to 82.9 ms, p = 0.006). There was no change in left or right ventricular systolic function, or pulmonary arterial pressure. Brain natriuretic peptide (BNP) levels were significantly reduced post-training (median 9 to 0 pg/ml, p<0.001). There was no elevation in Troponin T or CRP levels. On multivariate analysis, BNP reduction correlated with sodium levels and weight reduction (R = 0.8, p<0.001). CONCLUSIONS: Exposure to prolonged physical activity performed under caloric deprivation resulted in minor alterations of left ventricular diastolic function. BNP levels were significantly reduced due to negative water and sodium balance.

Comparison of everolimus- and paclitaxel-eluting stents in patients with acute and stable coronary syndromes: pooled results from the SPIRIT (A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) and COMPARE (A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice) Trials.

OBJECTIVES: This study sought to compare the clinical outcomes of everolimus-eluting stents (EES) versus paclitaxel-eluting stents (PES) in patients with acute coronary syndromes (ACS) and stable coronary artery disease (CAD). BACKGROUND: Although randomized trials have shown superiority of EES to PES, the safety and efficacy of EES in ACS is unknown. METHODS: We performed a patient-level pooled analysis from the prospective, randomized SPIRIT (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) II, III, IV, and COMPARE (A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice) trials in which 2,381 patients with ACS and 4,404 patients with stable CAD were randomized to EES or to PES. Kaplan-Meier estimates of death, myocardial infarction (MI), ischemia-driven target lesion revascularization, and stent thrombosis were assessed at 2 years and stratified by clinical presentation (ACS vs. stable CAD). RESULTS: At 2 years, patients with ACS compared with stable CAD had higher rates of death (3.2% vs. 2.4%, hazard ratio [HR]: 1.37 [95% confidence interval (CI): 1.02 to 1.85], p = 0.04) and MI (4.9% vs. 3.4%, HR: 1.45 [95% CI: 1.14 to 1.85], p = 0.02). In patients with ACS, EES versus PES reduced the rate of death or MI (6.6% vs. 9.3%, HR: 0.70 [95% CI: 0.52 to 0.94], p = 0.02), stent thrombosis (0.7% vs. 2.9%, HR: 0.25 [95% CI: 0.12 to 0.52], p = 0.0002), and ischemia-driven target lesion revascularization (4.7% vs. 6.2%, HR: 0.69 [95% CI: 0.48 to 0.99], p = 0.04). In patients with stable CAD, EES reduced the rate of death or MI (4.5% vs. 7.1%, HR: 0.62 [95% CI: 0.48 to 0.80], p = 0.0002), stent thrombosis (0.7% vs. 1.8%, HR: 0.34 [95% CI: 0.19 to 0.62], p = 0.0002), and ischemia-driven target lesion revascularization (3.9% vs. 6.9%, HR: 0.55 [95% CI: 0.42 to 0.73], p < 0.0001). CONCLUSIONS: Treatment with EES versus PES provides enhanced safety and efficacy regardless of the acuity of the clinical syndrome being treated and appears to mitigate the increased risk of stent thrombosis associated with ACS. (A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions [SPIRIT II]; NCT00180310; SPIRIT III: A Clinical Evaluation of the Investigational Device XIENCE V Everolimus Eluting Coronary Stent System [EECSS] in the Treatment of Subjects With de Novo Native Coronary Artery Lesions [SPIRIT III]; NCT00180479; SPIRIT IV Clinical Trial: Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Subjects With de Novo Native Coronary Artery Lesions [SPIRIT IV]; NCT00307047; A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice: the COMPARE Trial [COMPARE]; NCT01016041).

Redo thoracic endovascular aortic repair due to endoleak with celiac artery snorkeling.

Reintervention due to endoleak of aortic endograft repair is often challenging. Herein, we report endovascular endoleak repair in a patient with previous thoracic and abdominal endovascular grafts with extensive coverage of the aorta. The present technique included snorkeling of the celiac trunk to preserve antegrade flow in the celiac artery and to maintain future options for reintervention.

Bupropion for smoking cessation in patients with acute coronary syndrome.

BACKGROUND: Smokers hospitalized with acute coronary syndrome (ACS) are at high risk for subsequent ischemic events. Nevertheless, over two-thirds of patients continue to smoke after an acute myocardial infarction. Bupropion hydrochloride has proven efficacy as a smoking cessation aid, but data regarding its safety and efficacy in ACS patients are limited. METHODS: In a double-blind, randomized controlled trial, we compared the safety and efficacy of 8 weeks of treatment with bupropion slow-release (SR) or placebo for smokers hospitalized with ACS as an adjunct to nurse-led hospital- and telephone-based support. Primary efficacy outcome was smoking abstinence at 1 year. Primary safety outcome was clinical events at 1 year. RESULTS: A total of 151 patients were enrolled; all but 2 completed follow-up. Abstinence rates at 3 months were 45% and 44% in the bupropion SR and placebo groups, respectively (P = .99); 37% vs 42% (P = .61) at 6 months; and 31% vs 33% (P = .86) at 1 year. On multivariate analysis, an invasive procedure performed during index hospitalization was an independent predictor for smoking abstinence at 1 year (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.22-14.19). Presence of adverse effects attributed to treatment was a negative predictor for smoking cessation (OR, 0.23; 95% CI, 0.07-0.78). Treatment with bupropion SR was not associated with an increase in clinical events or change in blood pressure or body mass index, but dizziness was more common compared with placebo (14% vs 1.4%; P = .005). CONCLUSION: In hospitalized patients with ACS who received continuous, intensive nurse counseling about smoking cessation, bupropion did not increase the rates of smoking abstinence.

Serum cytokine tumor necrosis factor-alpha and interleukin-6 associated with the severity of coronary artery disease: indicators of an active inflammatory burden?

BACKGROUND: Atherosclerosis is a chronic inflammatory process resulting in coronary artery disease. OBJECTIVES: To determine the relationship between inflammatory markers and the angiographic severity of CAD. METHODS: We measured inflammatory markers in consecutive patients undergoing coronary angiography. This included C-reactive protein, fibrinogen, serum cytokines (interleukin-1 beta, IL-1 receptor antagonist, IL-6, IL-8, IL-10) and tumor necrosis factor-alpha), all measured by high sensitivity enzyme-linked immunoabsorbent assay. RESULTS: There was a significant correlation between TNFalpha and the severity of CAD as assessed by the number of obstructed coronary vessels and the Gensini severity score, which is based on the proximity and severity of the lesions. Patients had more coronary vessel disease (> 70% stenosis) with increasing tertiles of serum TNFalpha; the mean number of vessels affected was 1.15, 1.33, and 2.00 respectively (P< 0.001). IL-6 correlated with the Gensini severity score and coronary vessel disease (> 70% stenosis). A weaker correlation was present with IL-1 receptor antagonist. A significant correlation was not found with the other inflammatory markers. After adjustment for major risk factors, multivariate analyses showed that significant independent predictors of CAD vessel disease were TNFalpha (P< 0.05) and combined levels of TNFalpha and IL-6 (P< 0.05). IL-6 levels were independently predictive of Gensini coronary score (P< 0.05). CONCLUSION: TNFalpha and IL-6 are significant predictors of the severity of coronary artery disease. This association is likely an indicator of the chronic inflammatory burden and an important marker of increased atherosclerosis risk.

Uraemic hyperparathyroidism causes a reversible inflammatory process of aortic valve calcification in rats.

AIMS: Renal failure is associated with aortic valve calcification (AVC). Our aim was to develop an animal model for exploring the pathophysiology and reversibility of AVC, utilizing rats with diet-induced kidney disease. METHODS AND RESULTS: Sprague-Dawley rats (n = 23) were fed a phosphate-enriched, uraemia-inducing diet for 7 weeks followed by a normal diet for 2 weeks ('diet group'). These rats were compared with normal controls (n = 10) and with uraemic controls fed with phosphate-depleted diet ('low-phosphate group', n = 10). Clinical investigations included serum creatinine, phosphate and parathyroid hormone (PTH) levels, echocardiography, and multislice computed tomography. Pathological examinations of the valves included histological characterization, Von Kossa staining, and antigen and gene expression analyses. Eight diet group rats were further assessed for reversibility of valve calcification following normalization of their kidney function. At 4 weeks, all diet group rats developed renal failure and hyperparathyroidism. At week 9, renal failure resolved with improvement in the hyperparathyroid state. Echocardiography demonstrated valve calcifications only in diet group rats. Tomographic calcium scores were significantly higher in the diet group compared with controls. Von Kossa stain in diet group valves revealed calcium deposits, positive staining for osteopontin, and CD68. Gene expression analyses revealed overexpression of osteoblast genes and nuclear factor kappaB activation. Valve calcification resolved after diet cessation in parallel with normalization of PTH levels. Resolution was associated with down-regulation of inflammation and osteoblastic features. Low-phosphate group rats developed kidney dysfunction similar to that of the diet group but with normal levels of PTH. Calcium scores and histology showed only minimal valve calcification. CONCLUSION: We developed an animal model for AVC. The process is related to disturbed mineral metabolism. It is associated with inflammation and osteoblastic features. Furthermore, the process is reversible upon normalization of the mineral homeostasis. Thus, our model constitutes a convenient platform for studying AVC and potential remedies.

Long-term (>3 Years) outcome and predictors of clinical events after insertion of sirolimus-eluting stent in one or more native coronary arteries (from the Israeli arm of the e-Cypher registry).

The aim of this study was to evaluate long-term (3.4 years) outcomes and predictors of clinical events in patients treated with sirolimus-eluting stents in the Israeli arm of the e-Cypher registry. From July 2002 to October 2003, 488 patients from 8 medical centers in Israel were enrolled in the e-Cypher registry. Nineteen patients with interventions in venous grafts were excluded from the final analysis. Long-term follow-up was completed for 98% of the remaining patients. There were 29 cases (6.3%) of death (3.9% cardiac and 2.4% noncardiac deaths). According to the broad academic research consortium definition of stent thrombosis, there were 19 cases (4%) of stent thrombosis (incidence density 0.9 cases/100 patient-years). There were 46 cases (9.9%) of target lesion revascularization and 76 cases (16.3%) of major adverse cardiac events (combination of death, myocardial infarction, and target lesion revascularization). Independent predictors of stent thrombosis were renal failure (hazard ratio 9.6, 95% confidence interval 1.9 to 47), stent length (hazard ratio 1.1, 95% confidence interval 1 to 1.2), and the off-label use of sirolimus-eluting stents (hazard ratio 5.3, 95% confidence interval 1.2 to 24). In conclusion, during >3 years of follow-up, stent thrombosis, major adverse cardiac events, and target lesion revascularization continued at constant rates over time. Clinical parameters such as renal failure and procedural parameters such as off-label use and stent length were independent predictors of stent thrombosis.