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Introduction: The effects of bone marrow cell (BMC) therapy in patients with chronic ischemic heart disease (CIHD) remain controversial. Hypothesis: We hypothesized that injection of BMCs in patients with CIHD would improve left ventricular (LV) structure and function. We also hypothesized that BMC therapy would improve clinical outcomes in CIHD patients. Methods: We performed a systemic review and meta-analysis of pooled data from published randomized controlled trials (RCTs) that evaluated the efficacy of BMC administration in patients with CIHD. The effects of BMC injection on LV ejection fraction (LVEF), LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV), infarct size, and patient outcomes were analyzed using random-effects meta-analysis. Results: The literature search yielded 30 RCTs enrolling 1,548 patients. Transplantation of BMCs resulted in an improvement in LVEF in cell-treated patients compared with controls (2.89%; 95% confidence interval (CI): 1.80 to 3.97; P P = 0.14) and LVEDV (-5.95 ml; 95% CI: -12.09 to 0.18 ml; P =0.06). The improvement in LVEDV was more pronounced (-7.42 ml; 95% CI: -13.68 to -1.17ml; P =0.02) in patients with baseline LVEF Conclusions: BMC injection improves cardiac function and remodeling in patients with CIHD. These benefits are more pronounced in patients with LVEF

Background: Implantable cardioverter-defibrillator (ICD) therapy prevents sudden cardiac death in selected patients with heart failure. When a primary prevention ICD arrives at elective replacement interval (ERI), conventional management is to replace the device. However, the effectiveness of ICDs in patients with nonischemic and ischemic cardiomyopathy (NICM and ICM, respectively) whose left ventricular ejection fraction (LVEF) improved to ≥50% before replacement is unclear. Hypothesis: The therapeutic benefit of primary prevention ICD for NICM is attenuated by the recovery of LVEF at the time of ERI. Methods: Consecutive patients presenting for first time primary prevention ICD battery change-out at a single quaternary care center between 1/1/2008 and 6/27/2019 were included. The primary endpoint was the rate of ICD therapy (ICD discharge and anti-tachycardia pacing) according to LVEF recovery at ERI. Results: During the study period 6851 ICDs were placed, of which 310 underwent battery change-out, of whom 100 did not receive therapy from the first ICD, of whom 44 had NICM. The demographics of the NICM cohort are in the table. Following ERI, 0 (0%) with NICM and recovered LVEF had received ICD therapy, whereas 13 (30%) with persistently low LVEF had received therapy (p = 0.07). Furthermore, among patients without recovered LVEF, the NICM group had a lower rate of therapy (4, 12%) than the ICM group (12, 32%) (p=0.04). Conclusion: Rates of ICD therapy provided by primary prevention ICD after first battery change out trended towards a significantly lower rate in NICM patients with LVEF that recovered to ≥50% than those without LVEF recovery. No other patient demographic significantly predicted therapy-free survival but the analysis was limited by sample size. A prospective study with a larger cohort would be necessary to better estimate therapy-free survival.

Introduction: Patients with end stage renal disease (ESRD) often progress to hemodialysis (HD), where permanent access such as arteriovenous fistula (AVF) is needed. Due to associated cardiovascular comorbidities, several of these patients also require cardiac implantable electronic devices (CIEDs) for pacing or defibrillation needs. HD vascular access is their lifeline, yet prolonged use is fraught with complications which often necessitate the eventual use of both upper extremities. Conventional CIEDs require placement of leads through subclavian veins which limits the ability to use that extremity for AVF. Novel devices such as subcutaneous defibrillator and leadless pacemakers do not require placement of leads in the upper extremity and may offer an advantage in HD patients to preserve both upper extremities for AVF. Objective: To compare the incidence of successful use of contralateral upper extremity for AVF following HD access failure in patients with novel and conventional devices. Methods: This study included all patients who underwent placement of novel leadless and conventional devices during the last 10 years at the Ohio State University. Incidence of successful use of contralateral upper extremity for AVF following HD access failure was assessed as the primary outcome. Incidence of initial HD access failure was assessed as a secondary outcome. Results: A total of 58 patients with novel devices (subcutaneous defibrillator: 30 and leadless pacemaker: 28) comprised the interventional group, while a total of 25 patients with conventional devices comprised the control group. The primary outcome occurred in 18% of the interventional group and 0% of the control group (p < 0.01). Incidence of initial access failure was 46% in the interventional group and 40% in the control group (p= 0.2). Conclusion: Patients on HD have a high incidence of access failure and often require use of the contralateral upper extremity for AVF. Presence of novel devices provides the option for contralateral access compared to conventional transvenous devices. Where possible and clinically indicated, novel devices should be preferred over conventional transvenous devices in ESRD and HD patients.

Background: Recent enhancements have been introduced to the Abbott Confirm Rx™ insertable cardiac monitor (ICM) arrhythmia detection algorithms (SharpSense™). This study aims to characterize the real-world performance of SharpSense™ algorithms, in the upgraded ICM devices by comparing device detected pause and bradycardia (brady) episodes before and after the SharpSense™ upgrade. Methods: Confirm Rx™ devices with at least 90 days monitoring each before and after SharpSense™ upgrade were included in the study. Brady and pause episodes were extracted from Merlin.net™ patient care network for evaluation and adjudicated by expert adjudicators. Results: A total of 197 devices were included in the analysis. Devices were implanted for syncope (35%), AF management (33%), and other indications, including cryptogenic stroke and palpitations (32%). The SharpSense™ upgrade significantly reduced the total number of detected episodes by 92% (pause: 93%, brady: 87%) and the rate of transmitted episodes by 73.6% from 50.3 to 13.3 (pause: 34.9 to 6.0, brady: 7.8 to 1.5) episodes per patient-week (p < 0.001). SharpSense™ reduced false positive episodes by 82.8% and 91.5% for pause and brady, respectively. The percentage of devices with at least one false positive episode was reduced from 52% to 35% for pause and from 39% for 20% for brady. The number of devices with false positive rate greater than 1 episode per week was reduced from 39% to 20% for pause and from 23% to 8% for brady. Conclusion: SharpSense™ upgrade resulted in substantial reduction of pause and bradycardia episode detections, false positive detections, and frequency of transmitted episodes for clinic review.

The lifetime risk (LTR) articulates the probability of disease in the residual lifetime for an index age. These estimates can be useful for general audience-targeted knowledge translation activities against hypertension. There are only a few reports on lifetime of impact of hypertension on stroke events in Asians in whom stroke incidence is higher than Westerners.The Suita Study, a cohort study of cardiovascular diseases in Japan, was established in 1989. We included all participants who were stroke free at baseline. Age (in years) was used as the time scale. Age-specific incidence rates were calculated with person-year method within 10-year bands. We estimated the sex and index-age specific LTR of first-ever stroke with taking the competing risk of death into account.We followed 5783 men and women during 1989-2007 for 74 933 person-years. During the follow-up period, 276 (149 men and 127 women) participants had incident stroke. Of them, majority were cerebral infarction; 166 (102 men and 64 women). The LTR of stroke, accounted for competing risk of death, at 45 years of age for men without hypertension was 17.21% and it was 32.79% for hypertensive men. Among the hypertensive patients, participants with stage 2 or greater hypertension had higher LTR of stroke than the participants with stage 1 hypertension. This increased LTR of stroke for hypertensive patients were also observed among women and across all index ages for stroke.In this urban community-based population, we observed that hypertension has significant effect on the residual LTR of stroke among both men and women of middle age, specifically for ischemic stroke.

Background— Ventricular tachycardia (VT) radiofrequency ablation has been associated with reduced VT recurrence and mortality, although it is typically not considered among New York Heart Association class IV (NYHA IV) heart failure patients. We compared characteristics and VT radiofrequency ablation outcomes of those with and without NYHA IV in the International VT Ablation Center Collaboration. Methods and Results— NYHA II–IV patients undergoing VT radiofrequency ablation at 12 international centers were included. Clinical variables, VT recurrence, and mortality were analyzed by NYHA IV status using Kaplan–Meier analysis and Cox proportional hazard models. There were significant differences between NYHA IV (n=111) and NYHA II and III (n=1254) patients: NYHA IV had lower left ventricular ejection fraction; more had diabetes mellitus, kidney disease, cardiac resynchronization implantable cardioverter–defibrillator, and VT storm despite greater antiarrhythmic drug use ( P Conclusions— Despite greater baseline comorbidities, VT radiofrequency ablation can be safely performed among NYHA IV patients. Early VT recurrence is significantly associated with subsequent mortality regardless of NYHA status. Elimination of recurrent VT in NYHA IV patients may reduce mortality to a level comparable to NYHA II and III with arrhythmia recurrence.

Background: Patients with polycystic kidney disease (PKD) have a high incidence of intracranial aneurysms. Patterns of surgical and endovascular treatments and their associated outcomes are largely unknown in this patient population. Methods: We used the National Inpatient Sample (NIS, years 2002-2012) to compare the in-hospital outcomes of aneurysm treatments between PKD and non PKD patients. In our cohort, we included all adult patients (18 years or older) with the primary discharge diagnoses of ruptured and unruptured aneurysms with or without a secondary diagnosis of PKD. We analyzed the following comparative outcomes of PKD patients: 1) rates of endovascular and surgical treatments; 2) in-hospital complications; 3) length of hospital stay; 4) moderate-to severe-disability; and 5) mortality. Results: Of all the admitted patients (n=182,012) for aneurysmal treatment, 1105 (0.61%) patients had PKD. Rates of surgical treatment were higher in the PKD cohort (64.23 % versus 51.63 %, p= 0.0008) while fewer of the PKD patients underwent endovascular treatment (35.7 % versus 48.3 %, p= 0.0008). Lower rates of in-hospital complications such as: myocardial infarction, pneumonia, deep venous thrombosis, hyponatremia, cerebral vasospasm, hydrocephalus, were seen in the PKD group PKD patients were also less likely to receive intubation, mechanical ventilation, ventriculostomy, gastrostomy and ventriculoperitoneal shunt as compared to patients with no PKD. There was no significant difference in the mean length of hospital stay (9.4 versus 10.7 days, p=0.0873) between the two groups. Mean hospital charges in the US dollars (118209 versus 140003, p=0.0179) were also lower in the PKD group. Rates of moderate-to-severe disability and in-hospital mortality were also significantly lower in the PKD cohort- 17.2 % versus 23.2 %; P= 0.0442 and 3.5% versus 6.3%; P=0.0276 respectively. Conclusions: In patients admitted for treatment of ruptured or unruptured intracranial aneurysms, PKD status is associated with significantly lower rates of certain in-hospital complications, moderate-to-severe disability and mortality in comparison with non-PKD patients.

Background: The Carotid revascularization for primary prevention of stroke assessed in CREST trial (year 2010) revealed risk of the composite outcome of stroke, myocardial infarction, or death were almost similar in carotid artery stenting (CAS) and carotid artery endarterectomy (CEA) group. This study analyzed such current clinical practice and outcome (year 2011 to 2013) from multicenter national registry described below. Methods: Cohort of non-high risk patients who underwent targeted CAS or CEA were collected from American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) Registry in post CREST era. This registry prospectively collects around more than 300 variables across the nation pertaining to patient characteristics, co-morbid conditions, operative details, and 30-day postoperative outcomes. Frequency analysis of such outcome was performed to assess the re-validation of CREST trial in current clinical practice. Results: In Post CREST NSQIP Registry we identified 142 (CAS) and 7834 (CEA) patients. In Post CREST era (current clinical practice) the rates of any stroke among CEA patients (1.9%, 95% CI 1.57-2.17, CREST Ref 2.3%) (p=0.25) and CAS patients (2.1%, 95% CI 0.54-5.75, CREST Ref 4.1%) (p=0.25) observed in clinical practice were comparable to those observed in CREST trial. The rates of MI/arrhythmia among CEA patients (1.7%, 95% CI 1.47-2.06, CREST Ref 2.3%) (p=0.22) and CAS patients (2.8%, 95% CI 0.89-6.79, CREST Ref 1.1%) (p=0.13) are comparable from CREST trial. The rates of 1 month mortality among CEA patients (0.6%, 95% CI 0.42-0.76, CREST Ref 0.3%) (p=0.27) and CAS patients (0.7%, 95% CI 0.04-3.47, CREST Ref 0.7%) (p=0.92) were also similar. The rate of cranial nerve injury in CEA patients has declined (2.1%, CI 1.83-2.47, CREST Ref 4.7 %) (p Conclusions: Our results support reproducibility of CREST procedural outcomes for both CEA and CAS in general practice in post-trial period.

Background and Purpose: Hemicraniectomy is carefully selected for patients with acute ischemic stroke in whom endovascular treatment has failed to prevent adverse outcomes of large hemispheric stroke. We evaluated trends in the utilization of hemicraniectomy in patients who underwent endovascular therapy according to the availability of three generations of thrombectomy devices and analyzed the associated rates of death and disability among them over a nine year period. Methods: We obtained data for patients admitted to hospitals in the United States from 2004 to 2012 with a primary diagnosis of ischemic stroke using a large national database. We determined the rate and pattern of hemicraniectomy utilization, and associated in-hospital outcomes of endovascular treatment among ischemic stroke patients. Outcomes were compared between three time periods: 2004-2006 (post MERCI), 2007-2009 (post Penumbra) and 2010-2012 (post Solitaire stent retriever) approvals. Results: Of the 6,021,636 patients admitted with ischemic stroke, 28,956 (0.48%) underwent endovascular treatment. Of the patients who underwent endovascular therapy, 2,219 (7.6%) required subsequent hemicraniectomy. There was a 7 fold decrease in the utilization of hemicraniectomy in these patients between 2004 and 2009 (25.6% in 2004 vs. 3.5% in 2009, p < 0.001) with a yearly trend towards decreased utilization of hemicraniectomy [OR 0.7, 95% CI 0.6- 0.8, p In multivariate logistic regression analysis there was a reduction in the rate of in hospital mortality of the 2007-2009 and the 2010-2012 groups when compared to the 2004-2006 interval group (2007-2009, odds ratio (OR) 0.9, 95% confidence interval (CI) (0.7- 1.2) and 2010-2012, [OR 0.9, 95%CI 0.7- 1.1]). The rate of moderate to severe disability increased for patients treated during 2007-2009 and 2010-2012. Conclusion: In the last 9 years there has been a significant decrease in the utilization of hemicraniectomy in acute ischemic stroke patients who underwent endovascular treatment. Despite reduction in use of hemicraniectomy, the mortality rate in endovascularly treated patients have shown a reduction, but there was an increase in rate of moderate to severe disability.

Background and Purpose— Atherosclerosis is a progressive inflammatory disease and can develop in large arteries such as carotid and femoral arteries or medium-sized muscular arteries of the heart. Previous predominantly experimental studies suggested an important role of chemokines in the development of atherosclerosis. The main aim of this study was to examine potential effect of the CCR5-del32 mutation on systemic inflammation, intima-media thickness in carotid and femoral arteries, and on the indices of cardiovascular disease. Methods— In the present study, we have examined the association of a common functional 32-bp frameshift deletion mutation in a chemokine receptor (CCR5) in relation to inflammation and atherosclerosis. CCR5 is a G protein-coupled receptor involved in inflammatory response and regulation of leukocytes activation and migration. Genetic screening of this mutation was carried out on a well-known and previously described cohort of Bruneck (n=826) using polymerase chain reaction. Results— Screening was successful in 810 subjects of whom 7 were homozygous, 102 were heterozygous, and 701 were normal. The mutation was associated with significantly lower levels of C-reactive protein in a dose-dependent manner. Moreover, CCR5-del32 was associated with a significantly lower carotid intima-media thickness in the common carotid artery (del32/del32, 837±8 μm; wt/del32, 909±21 μm; wt/wt, 958±8 μm; P =0.007 after multivariable adjustment). Furthermore, incident cardiovascular disease (1995 to 2005) was markedly reduced in del32 homozygotes and heterozygotes subjects compared with wild-type homozygotes (del32/del32=0%, wt/del32=7.8%, wt/wt=14.8%, P =0.020). Findings equally applied to coronary artery and cerebrovascular disease. Conclusions— The chemokine receptor CCR5-del32 frameshift mutation is associated with low levels of C-reactive protein, decreased intima-media thickness, and cardiovascular disease risk. These findings are consistent with the hypothesis that the chemokine receptor CCR5 is involved in the mediation of low-grade systemic inflammation and may play a role in human atherosclerosis and cardiovascular disease.

Introduction: Results from randomized controlled trials (RCTs) of bone marrow cell (BMC) therapy for cardiac repair have been discordant. The true impact of BMC therapy in patients with chronic ischemic heart disease (CIHD) and ischemic heart failure remain unclear. Hypothesis: We hypothesized that BMC injection would improve clinical outcomes and left ventricular (LV) parameters in patients with CIHD. Methods: We performed a systematic review and meta-analysis of data from RCTs of BMC therapy on LV ejection fraction (LVEF), LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV), infarct scar size, and clinical outcomes in patients with CIHD. Database searches based on specified criteria identified 15 eligible RCTs (enrolling 648 CIHD patients). Changes in predefined parameters were analyzed with random-effects meta-analysis. Peto odds ratio (OR) was calculated for clinical outcomes. Results: Compared with standard therapy, BMC transplantation improved LVEF (3.84%; 95% confidence interval [CI], 2.30 to 5.38; P Conclusions: BMC therapy improves LVEF, LVESV, and infarct scar size in patients with CIHD. The improvement in LVEF was also confirmed in meta-analysis of RCTs using MRI. Importantly, these numerically small benefits translated into improved clinical outcomes in BMC-treated CIHD patients.

Background: Epicardial ligation of left atrial appendage (LAA) is an attractive alternative to oral anticoagulation for patients with atrial fibrillation and high risk of bleeding. Objectives: To delineate the safety of epicardial ligation of the LAA for stroke prevention in atrial fibrillation Methods: This is a retrospective, multicenter registry of consecutive patients undergoing LAA ligation with the LARIAT device at 14 U.S. sites. The primary endpoint was procedural success, defined as device success (suture deployment and Results: A total of 610 patients underwent LARIAT exclusion of LAA. The mean age of the participants was 71 (SD: ± 10) years. The mean CHADs2VASc and HASBLED score was 2.74(±1.33) and 3.87 (±1.8) respectively. Epicardial access was obtained using micro-puncture needle in 60 percent of the cases. The acute closure was achieved in 554 (91 %) patients. Cardiac perforation needing continued drainage and transfusion occurred in 12 patients (1.96 %). Perforation of epigastric artery occurred in 2 patients (0.3 %). Eight patients (1.3 %) required open heart surgery. Five patients required > 2 weeks of treatment for pericarditis. No myocardial infarction or stroke happened in the peri-procedural period. One patient died as complication of the procedure. A follow up transesophageal echocardiogram (TEE) was performed in 76 % of the patients that showed a leak of < 5 mm and thrombus in 49 (8 %) and 12 (1.96 %) patients respectively. Conclusions: In this largest multicenter experience of LAA ligation with the LARIAT device, the rate of acute closure was high with significantly fewer complications compared to limited contemporary data. The use of micro-puncture is probably safer approach to avoid cardiac injury during epicardial access. A prospective randomized trial is required to adequately define clinical efficacy, optimal post-procedure medical therapy, and the effect of operator experience on procedural safety.

Introduction: The results from clinical trials of bone marrow cell (BMC) therapy in ischemic heart disease (IHD) have been discordant with regard to left ventricular (LV) functional improvement. This discrepancy has been attributed, in part, to the use of dissimilar cardiac imaging modalities. MRI is the gold standard for assessment of cardiac structure/function. Hypothesis: We hypothesized that BMC therapy will improve LV parameters in patients with IHD when assessed by cardiac MRI. Methods: We performed a systematic review and meta-analysis of data from randomized controlled trials (RCTs) of BMC therapy in patients with IHD that used cardiac MRI. Database searches through May 30, 2015 identified 27 eligible RCTs (enrolling 1826 patients). The MRI data on LV ejection fraction (EF), infarct size, LV end-systolic volume (LVESV), and LV end-diastolic volume (LVEDV) were analyzed with random-effects meta-analysis. Clinical outcomes were analyzed using Peto odds ratio (OR). Results: Compared with standard therapy, BMC therapy improved LVEF (1.62%; 95% confidence interval [CI]: 0.49 to 2.75; P=0.005) and reduced LVESV (-2.00 ml; 95% CI: -3.19 to -0.82; P=0.0009). The improvement in LVEF was similar in patients with acute myocardial infarction (MI) and chronic IHD. Perhaps more importantly, BMC therapy was associated with reduced incidence of recurrent MI (OR: 0.39; 95% CI: 0.20 to 0.78; P=0.007) along with substantial improvement in other outcome parameters, including mortality (Table). However, these changes did not reach statistical significance perhaps due to smaller patient numbers. Conclusions: These results from meta-analysis of RCTs using cardiac MRI indicate that BMC therapy improves LV function and outcomes in patients with IHD. These data may help resolve the controversy regarding whether the reported benefits of BMC therapy are dependent on the selection of imaging modalities.

Background— Accumulating evidence established a positive association of anti–heat shock protein 60 (HSP60) autoantibodies and the presence of atherosclerosis in humans. However, whether these autoantibodies play a causal role in the development of atherosclerosis is unknown. Methods and Results— In the present study, anti-HSP60 autoantibodies from blood of patients with coronary heart disease were isolated by affinity chromatography and injected into the tail vein of apolipoprotein E–deficient mice. Atherosclerotic lesions in aortas were significantly increased 8 weeks after injection. Furthermore, administration of a specific mouse monoclonal antibody (II-13) recognizing amino acid residues 288 to 366 of HSP60 effectively induced atherosclerotic lesions in apolipoprotein E–deficient mice. II-13 injection resulted in endothelial cell damage, followed by increased leukocyte attachment and accumulation of macrophages and smooth muscle cells in lesions. Interestingly, II-13–induced atherosclerosis was blocked by pretreatment of animals with F(ab) 2 segments derived from the antibody, but not mouse IgG F(ab) 2. . Conclusions— Autoantibodies recognizing amino acid residues 288 to 366 of HSP60 induce atherosclerosis via the mechanisms of autoimmune reactions to HSP60 expressed on arterial endothelial cells, which can be prevented by F(ab) 2 segments derived from these antibodies.

Background: Use of aldosterone antagonist (AA) therapy is a class I recommendation in moderate to severe heart failure (HF). Multiple studies have reported the underutilization of AA in eligible patients. We wished to analyze determining factors for this ongoing underutilization using the AHA’s Get With the Guidelines (GWTG) HF database from American Heart Association (AHA). We hypothesized that elevated creatinine is a major barrier to use of AA. Methods: A comprehensive HF program utilizing the GWTG measures was recently established at our institution. Outcome data utilizing the GWTG registry from January 2009 to June 2012 was analyzed. Given ACC/AHA guidelines that creatinine should be < 2.5 mg/dL in men or < 2.0 mg/dL in women, we chose to analyze genders separately. To analyze effect of degree of creatinine elevation on AA therapy at discharge, two subcategories of creatinine levels were analyzed. Creatinine levels above 2.0 mg/dL in women and 2.5 mg/dL in men were excluded, as AAs are contraindicated in these patients. Categorical variables were compared using the chi-square test. Results: Our total compliance rate with AA therapy at discharge during the study period was 26% (149 of 565) for females and 31% (199 of 640) for males. There was no significant decline in compliance when creatinine levels were >1 mg/dL. Additionally, when comparing rates of compliance according to creatinine level across gender, there was no statistically significant difference in the use of AAs (see Table). Conclusion: Overall, AA therapy compliance at discharge at our center, as well as a majority of nationally recognized HF center participating in GWTG-HF registry remains suboptimal, irrespective of gender. This is despite known data that has clearly shown AAs significantly reduce mortality, cardiovascular death, HF hospitalizations and the composite endpoints. In contrast to prior studies, mild creatinine elevation does not seem to be a significant barrier to presciption of AAs. It is possible that other variables such as polypharmacy, hyperkalemia and effects of dual blockade of the renin-angiotensin-aldosterone system and the possibility of endocrine side effects associated with the non-selective AAs may be playing a role. More aggressive and consistent use of AA therapy for HF is warranted.

Background: Administrative datasetsare used frequently without risk adjustment to determine regional and national level characteristics pertaining to performance of carotid endarterectomy (CEA). We developed and validated a new index to provide risk adjustment and to predict patient mortality or other outcomes in the hospital in patients undergoing CEA. Methods: The primary end point was occurrence of stroke, cardiac complications, or death during the post procedural period of CEA derived from the Nationwide Inpatient Sample (NIS) which is representative of all admissions in the United States. Multivariate logistic regression was performed to identify the effect of clinical and demographic factors associated with the composite (stroke, death, or cardiac event) end point. Data from 2005-2006 (study period 1) was used to derive the risk index score (weights used to define risk adjustment were identified from the logistic regression model) while data from 2007-2009 (study period 2) was used for validation of the risk index. Results: A total 120,633 patients with mean age in yrs [±SD] of 71.1 [±9.5] and 42.4% females underwent CEA during the study period. The composite endpoint during study period 1 was 3.02%; cardiac event 1.77%, stroke 0.99% and in-hopital mortality 0.47%. Predictors of the composite endpoint were (odds ratio [OR], P value) as follows: age≥70 years (1.15, 0.013), atrial fibrillation (3.18, Conclusion: A new risk index is developed to assist in risk adjustment in the logistic regression model and is meant to be used with large administrative data sets to provide appropriate adjustment for comparative studies.

Background: Hedgehog signaling effects endothelial and fibroblast cell migration and vascularization of various tissues during embryonic development. We propose here that stem cell based Shh gene delivery to the heart promotes neovascularization and enhances regional blood flow (RBF) in the infartced heart. Methods and Results: The pCMVShh plasmid was constructed and used for non-viral transfection of primary mesenchymal stem cell (MSC) culture. Successful transfection and expression of Shh in transfected MSCs ( Shh MSCs) was confirmed by immunoflourescence, real-time PCR and Western blotting. Real-time PCR based array showed upregulation of angiogenic factors in Shh MSCs including netrin (>62-fold) and iNOS (>100-fold). The expression of netrin and iNOS was PKC dependent and was abolished in the presence of 2.5 μ M chelerythrin. Transduction of iNOS gene into MSCs increased netrin expression implying a role for iNOS downstream of PKC. Western blot showed that 45-KDa PKM proteolytic subunit of PKC was involved in this activity. Shh MSCs conditioned medium was biologically active and caused greater migration and tube formation of human vascular endothelial in vitro in comparison with untransfected MSCs ( non-Shh MSCs) conditioned medium. For in vivo studies, 70 μ l DMEM without cells (group-1) or containing 1x10 6 male non-Shh MSC (group-2), or Shh MSCs (group-3) were transplanted into female rat model of acute coronary artery ligation. S ry -gene studies on day-4 after cell engraftment showed higher survival of Shh MSCs ( p < 0.05 vs non-Shh MSC). Immunostaining for vWillebrand Factor-VIII and smooth muscle actin showed robust angiogenesis with distinctly large vessels in group-3 ( p < 0.001 vs group-2). RBF measured by fluorescent microspheres was increased ( p < 0.01 ) and infarction size was attenuated ( p < 0.05 ) in group-3 as compared with control groups. Left ventricle ejection fraction (52.3±2.6%) and fractional shortening (21.8±1.2%) were more preserved in group-3 as compared with control groups. Conclusions: Ex-vivo Shh gene delivery improves angiogenesis and RBF in the infarcted heart to preserve global heart function through the upregulation of multiple angiogenic cytokines including iNOS and netrin.