Administration of Interleukin-15 Peptide Improves Cardiac Function in a Mouse Model of Myocardial Infarction.

Interleukin-15 is a pleotropic factor, capable of modulating metabolism, survival, proliferation, and differentiation in many different cell types. The rationale behind this study relates to previous work demonstrating that IL-15 is a major factor present in stem cell extracts, which protects cardiomyocytes subjected to hypoxic stress in vitro. The objective of this current study was to assess whether administration of IL-15 peptide will also show protective effects in vivo. The data indicate that administration of IL-15 reduces cell death, increases vascularity, decreases scar size, and significantly improves left ventricular ejection fraction in a mouse model of myocardial infarction.

Angiographic success and procedural complications in patients undergoing retrograde percutaneous coronary chronic total occlusion interventions: a weighted meta-analysis of 3,482 patients from 26 studies.

BACKGROUND: The efficacy and safety profile of retrograde chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. We sought to perform a weighted meta-analysis of the success and complication rates of retrograde CTO PCI. METHODS: We conducted a meta-analysis of 26 studies published between 2006 and April 2013 reporting in-hospital outcomes of retrograde CTO PCI. Data on procedural success, frequency of death, emergent coronary artery bypass graft surgery (CABG), stroke, myocardial infarction (MI), perforation, tamponade, stent thrombosis, major vascular or bleeding events, contrast nephropathy, and radiation skin injury were collected. RESULTS: A total of 26 studies with 3482 patients and 3493 target CTO lesions were included. Primary retrograde CTO PCI was attempted in 52.4%. Pooled estimates of outcomes were as follows: procedural success 83.3% [95% confidence interval (CI): 79.0% to 87.7%]; death 0.7% (95% CI: 0.5% to 1.2%); urgent CABG 0.7% (95% CI: 0.4% to 1.2%); tamponade 1.4% (95% CI: 1.0% to 2.2%); collateral perforation 6.9% (95% CI: 4.6% to 10.4%); coronary perforation 4.3% (95% CI: 1.2% to 15.4%); donor vessel dissection 2% (95% CI: 0.9% to 4.5%); stroke 0.5% (95% CI: 0.2% to 1.0%); MI 3.1% (95% CI: 0.2% to 5.0%); Q wave MI 0.6% (95% CI: 0.4% to 1.1%); vascular access complications 2% (95% CI: 0.9% to 4.5%); contrast nephropathy 1.8% (95% CI: 0.8% to 3.7%); and wire fracture and equipment entrapment 1.2% (95% CI: 0.6% to 2.5%). CONCLUSIONS: Retrograde CTO PCI is associated with high procedural success rate and acceptable risk for procedural complications.

Clinical, angiographic, and procedural predictors of periprocedural complications during chronic total occlusion percutaneous coronary intervention.

OBJECTIVES: To identify clinical, angiographic, and procedural factors associated with increased risk of periprocedural complications during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). BACKGROUND: Successful CTO PCI can provide significant clinical benefit; however, procedural risks have received limited study. We sought to identify factors associated with increased CTO PCI periprocedural risk that could be utilized to guide patient and lesion selection. METHODS: The clinical, angiographic, and procedural records of 336 consecutive CTO PCI procedures performed at a single center from May 2005 through 2012 were reviewed, and data on periprocedural complications were recorded. Logistic regression was performed to identify independent predictors of periprocedural complications during CTO PCI. RESULTS: The incidence of major and minor complications was 3.9% and 10.4%, respectively. Minor bleeding and vascular events were the most common complications (4.8%), followed by perforation (2.4%), contrast-induced nephropathy (1.8%), and transient hypotension (0.6%). Major complications were uncommon: death (0.3%); emergency coronary artery bypass grafting (0.6%); stroke (0.3%); tamponade (0.3%); clinical myocardial infarction (0.9%); donor vessel injury (0.6%); and major bleeding or vascular events (0.9%). Patients who experienced any complication had higher preprocedure troponin levels and were more likely to undergo treatment using the retrograde approach. In multivariable analysis, use of the retrograde approach was independently associated with increased risk of periprocedural complications (odds ratio, 2.057; 95% confidence interval, 1.045-4.051; P=.04). CONCLUSIONS: Major complications of CTO PCI are infrequent, but are more common with use of the retrograde approach.

Application of the "hybrid approach" to chronic total occlusion interventions: a detailed procedural analysis.

OBJECTIVE: To assess the outcomes of the "hybrid" approach to chronic total occlusion (CTO) percutaneous coronary interventions (PCIs). BACKGROUND: The "hybrid approach" to CTO PCI advocates appropriate and early change of crossing strategy to maximize success, safety, and efficiency. METHODS: We prospectively recorded and analyzed detailed step-by-step procedural data in 73 consecutive CTO PCI cases performed by a single operator between July 2011 and August 2012. RESULTS: Technical success was achieved in 66 of 73 cases (90.4%). Mean patient age was 65 ± 7 years, and 30% had prior coronary artery bypass surgery. Dual injection was used in 78%. The primary approach was retrograde in 9 cases (12.5%) and antegrade in 64 cases (87.5%), of whom 25 cases (39.1%) underwent retrograde attempt after failed antegrade approach. The initial crossing approach was successful in 40 cases (54.8%), but 32 cases (44%) required 3.6 ± 1.4 approach changes (range 2-7). Antegrade wire escalation, antegrade dissection/reentry, and retrograde crossing were utilized in 97.2%, 46.6%, and 46.6% of cases, respectively. Among successful cases, the final CTO crossing technique was antegrade wire escalation in 50.0%, antegrade dissection/reentry in 24.2%, and retrograde in 25.8%. The mean procedure time, fluoroscopy time, and air kerma radiation exposure until CTO crossing or stopping the procedure were 66 ± 55 minutes, 25 ± 23 minutes, and 2.3 ± 1.9 Gray, respectively. Three patients (4.1%) had a major complication. CONCLUSION: In the "hybrid approach" to CTO PCI, changes in crossing strategy were needed in approximately half the cases, resulting in high success and low complication rates.

Prevalence and management of coronary chronic total occlusions in a tertiary Veterans Affairs hospital.

OBJECTIVES: We sought to determine the contemporary prevalence and management of coronary chronic total occlusions (CTO) in a veteran population. BACKGROUND: The prevalence and management of CTOs in various populations has received limited study. METHODS: We collected clinical and angiographic data in consecutive patients that underwent coronary angiography at our institution between January 2011 and December 2012. Coronary artery disease (CAD) was defined as ≥50% diameter stenosis in ≥1 coronary artery. CTO was defined as total coronary artery occlusion of ≥3 month duration. RESULTS: Among 1,699 patients who underwent angiography during the study period, 20% did not have CAD, 20% had CAD and prior coronary artery bypass graft surgery (CABG), and 60% had CAD but no prior CABG. The prevalence of CTO among CAD patients with and without prior CABG was 89 and 31%, respectively. Compared to patients without CTO, CTO patients had more co-morbidities, more extensive CAD and were more frequently referred for CABG. Percutaneous coronary intervention (PCI) to any vessel was performed with similar frequency in patients with and without CTO (50% vs. 53%). CTO PCI was performed in 30% of patients without and 15% of patients with prior CABG with high technical (82 and 75%, respectively) and procedural success rates (80 and 73%, respectively). CONCLUSIONS: In a contemporary veteran population, coronary CTOs are highly prevalent and are associated with more extensive co-morbidities and higher likelihood for CABG referral. PCI was equally likely to be performed in patients with and without CTO.

Long-term outcomes with use of the CrossBoss and stingray coronary CTO crossing and re-entry devices.

BACKGROUND: The Boston Scientific CrossBoss and Stingray Coronary CTO Crossing and Re-Entry devices (formerly the BridgePoint Medical System) can improve success rates in chronic total occlusion (CTO) percutaneous coronary intervention (PCI), but there are no published data on long-term clinical outcomes. METHODS: The acute and long-term outcomes of 170 consecutive patients who underwent CTO PCI at our institution were reviewed, including 60 patients in whom the CrossBoss and Stingray devices were used and 110 patients treated with other crossing strategies. RESULTS: Baseline characteristics were similar between the two cohorts. Patients in whom the CrossBoss/Stingray was utilized had more prior CTO PCI attempts (13.1% vs 1.6%; P=.003), required longer fluoroscopy times (46 ± 22 minutes vs 35 ± 20 minutes; P<.001), higher contrast dose (390 ± 141 mL vs 323 ± 132 mL; P>.99), and more guidewires for lesion crossing (8.0 ± 6.5 vs 4.7 ± 2.3; P<.001), but procedural success (75.8% vs 76.2%; P>.99) and major complication rates (4.8% vs 3.2%; P=.69) were similar. During a median follow-up of 1.81 years, the CrossBoss/Stingray group had no difference in target lesion revascularization (40.9% vs 29.6%; P=.13) and major adverse clinical events (40.3% vs 35.2%; P=.42). CONCLUSIONS: Use of the CrossBoss/Stingray devices for CTO PCI is associated with equally high success and equally low complication rates as other techniques, both immediately post procedure and during long-term follow-up, in spite of its use in higher complexity cases.

Procedural outcomes of revascularization of chronic total occlusion of native coronary arteries (from a multicenter United States registry).

Percutaneous coronary intervention (PCI) of chronic total occlusions (CTOs) is a rapidly evolving area of interventional cardiology. We sought to examine the immediate procedural and in-hospital clinical outcomes of native coronary artery CTO PCI from a multicenter United States (US) registry. We retrospectively examined the procedural outcomes of 1,361 consecutive native coronary artery CTO PCIs performed at 3 US institutions from January 2006 to November 2011. Mean age was 65 ± 11 years, 85% of patients were men, 40% had diabetes, 37% had previous coronary artery bypass graft surgery, and 42% had previous PCI. The CTO target vessel was the right coronary artery (55%), circumflex (23%), left anterior descending artery (21%), and left main or bypass graft (1%). The retrograde approach was used in 34% of all procedures. The technical and procedural success rates were 85.5% and 84.2%, respectively. The mean procedural time, fluoroscopy time, and contrast utilization were 113 ± 61 minutes, 42 ± 29 minutes, and 294 ± 158 ml, respectively. In multivariate analysis, female gender, no previous coronary artery bypass surgery, and years since initiation of CTO PCI at each center were independent predictors of procedural success. Major complications occurred in 24 patients (1.8%). In conclusion, among selected US-based institutions with experienced operators, native coronary artery CTO PCI can be performed with high success and low major complication rates.

Endothelial progenitor cell response to antiproliferative drug exposure.

BACKGROUND: Vascular stent coverage by endothelial cells, derived from endothelial progenitor cells (EPC) is considered a surrogate for healing. However, the effects of antiproliferative drugs used in current drug-eluting stents (DES) on EPC proliferative and antithrombotic function remains poorly defined. METHOD AND RESULTS: Herein, we studied and compared the in vitro and in vivo effects of four antiproliferative drugs - paclitaxel, sirolimus, everolimus, and zotarolimus on several EPC properties including colony forming units (CFU), cell proliferation, apoptosis, antithrombotic and prothrombotic gene expression and nitric oxide (NO) as well as prostacyclin (PGI(2)) release. We also examined EPC migration and adhesion under flow conditions. We find that whereas all antiproliferative agents inhibited EPC proliferation and caused cell apoptosis, only paclitaxel and sirolimus reduced CFU formation. Paclitaxel treatment also resulted in the greatest down-regulation of antithrombotic gene expression and up-regulation of prothrombotic gene expression. NO release, migration, and adhesion of EPC under shear stress were inhibited by all antiproliferative drugs, most notably by paclitaxel and sirolimus. CONCLUSIONS: These results indicate that antiproliferative drugs on DES, particularly paclitaxel, impair the proliferative and antithrombotic functions of EPC, and thereby could contribute to incomplete vascular healing and increase the risk of stent thrombosis.

Enhanced endothelialization of a new stent polymer through surface enhancement and incorporation of growth factor-delivering microparticles.

In this study, we sought to develop strategies for improved endothelialization of a new polymer coating for vascular stents. Surface enhancement of the new poly-1,8-octanediol-co-citric acid (POC) polymer was achieved through conjugation of anti-CD34 antibody and incorporation of vascular endothelial growth factor and basic fibroblast growth factor-containing poly-lactic-co-glycolic acid microparticles to improve capture and proliferation of endothelial progenitor cells (EPC) and compared to untreated POC and poly-L-lactic acid (PLLA) polymer. Our results indicate that compared to PLLA, POC coating was more hemocompatible, with less platelet activation (p = 0.01), thrombogenicity (p < 0.05 for 20 and 30 min clot formation), and inflammatory response (IL-1ß release, p = 0.0009; TNF-α release, p = 0.004). EPC adhesion and proliferation on POC were significantly improved with surface enhancement and microparticle incorporation compared to untreated POC (p = 0.006) and PLLA (p = 0.003). These results suggest a new strategy for enhancing endothelialization of polymeric coatings of vascular prostheses.

Characteristics and outcome after hospitalization for acute right heart failure in patients with pulmonary arterial hypertension.

BACKGROUND: Although much is known about the risk factors for poor outcome in patients hospitalized with acute heart failure and left ventricular dysfunction, much less is known about the syndrome of acute heart failure primarily affecting the right ventricle (acute right heart failure). METHODS AND RESULTS: By using Stanford Hospital's pulmonary hypertension database, we identified consecutive acute right heart failure hospitalizations in patients with PAH. We used longitudinal regression analysis with the generalized estimating equations method to identify factors associated with an increased likelihood of 90-day mortality or urgent transplantation. From June 1999 to September 2009, 119 patients with PAH were hospitalized for acute right heart failure (207 episodes). Death or urgent transplantation occurred in 34 patients by 90 days of admission. Multivariable analysis identified a higher respiratory rate on admission (>20 breaths per minute; OR, 3.4; 95% CI, 1.5-7.8), renal dysfunction on admission (glomerular filtration rate <45 mL/min per 1.73 m2; OR, 2.7; 95% CI, 1.2-6.3), hyponatremia (serum sodium ≤136 mEq/L; OR, 3.6; 95% CI, 1.7-7.9), and tricuspid regurgitation severity (OR, 2.5 per grade; 95% CI, 1.2-5.5) as independent factors associated with an increased likelihood of death or urgent transplantation. CONCLUSIONS: These results highlight the high mortality after hospitalizations for acute right heart failure in patients with PAH. Factors identifiable within hours of hospitalization may help predict the likelihood of death or the need for urgent transplantation in patients with PAH.

Incidence, correlates, and consequences of acute kidney injury in patients with pulmonary arterial hypertension hospitalized with acute right-side heart failure.

BACKGROUND: Though much is known about the prognostic influence of acute kidney injury (AKI) in left-side heart failure, much less is known about AKI in patients with pulmonary arterial hypertension (PAH). METHODS AND RESULTS: We identified consecutive patients with PAH who were hospitalized at Stanford Hospital for acute right-side heart failure. AKI was diagnosed according to the criteria of the Acute Kidney Injury Network. From June 1999 to June 2009, 105 patients with PAH were hospitalized for acute right-side heart failure (184 hospitalizations). AKI occurred in 43 hospitalizations (23%) in 34 patients (32%). The odds of developing AKI were higher among patients with chronic kidney disease (odds ratio [OR] 3.9, 95% confidence interval [CI] 1.8-8.5), high central venous pressure (OR 1.8, 95% CI 1.1-2.4, per 5 mm Hg), and tachycardia on admission (OR 4.3, 95% CI 2.1-8.8). AKI was strongly associated with 30-day mortality after acute right-side heart failure hospitalization (OR 5.3, 95% CI 2.2-13.2). CONCLUSIONS: AKI is relatively common in patients with PAH and associated with a short-term risk of death.

Bone marrow stem cells for the treatment of ischemic heart disease: a clinical trial review.

Cardiovascular disease continues to represent a significant and growing source of morbidity and mortality despite advances in traditional treatments. As a result, increasing interest and research in regenerative therapies has emerged in recent years. Among them, cell therapy represents an area of significant potential. An expanding clinical literature now exists involving the use of bone marrow-derived stem cells in the treatment of ischemic heart disease. These early studies appear to provide promising results in patient populations that include those with refractory angina, ischemic cardiomyopathy with left ventricular dysfunction, and end-stage heart failure. This review serves to provide a comprehensive examination of these clinical trials focused on several components including cell preparation, cell delivery, safety, and efficacy of these trials.

The effect of frequency doubled double pulse Nd:YAG laser fiber proximity to the target stone on transient cavitation and acoustic emission.

PURPOSE: Scant information has been published describing the effect of laser fiber distance from the stone target on the mechanism of calculus fragmentation. Using high speed photography and acoustic emission measurements we characterized the impact of laser fiber proximity on stone comminution. We evaluated the effect of laser fiber distance from the stone target on resultant cavitation bubble formation and shock wave generation. MATERIALS AND METHODS: Stone fragmentation was assessed using a FREDDY (frequency doubled double pulse Nd:YAG) (World of Medicine, Orlando, Florida) laser and a holmium laser. The FREDDY laser was operated using a 420 microm fiber at an output energy of 120 and 160 mJ in single and double pulse settings, and a pulse repetition rate of 1 Hz. The holmium laser was operated using a 200 microm fiber at an output energy of 1 to 3 J and a pulse repetition rate of 1 Hz. The surface of a 1 cm square BegoStone (Bego, Bremen, Germany) attached to an X-Y-Z translational stage was aligned perpendicular to the laser fiber, which was immersed in a Lucite tank filled with water at room temperature. An Imacon 200 high speed camera was used to capture transient cavitation bubbles at a framing rate of up to 1,000,000 frames per second. Acoustic emission signals associated with shock waves generated during the rapid expansion and collapse of the cavitation bubble were measured using a 1 MHz focused ultrasound transducer. RESULTS: At laser fiber distances of 3.0 mm or less cavitation bubbles and shock waves were observed with the FREDDY laser. In contrast to the holmium laser, the bubble size and shock wave intensity of the FREDDY laser was inversely related to the fiber-to-stone distance over the range tested (0.5 to 3.0 mm). CONCLUSIONS: While bubble size was noted to increase with a larger stone-to-fiber distance using the holmium laser, to consistently generate cavitation bubbles and shock waves using the FREDDY laser the laser fiber should be operated within 3.0 mm of the target stone. These findings have significant implications during clinical laser stone fragmentation.

Review of animal models of surgically induced spinal neural tube defects: implications for fetal surgery.

Animal models have been used to help study the embryopathy and pathophysiology of neurological deterioration in open neural tube defects. Results from studies of lesion induction and defect repair in these animals have become the basis for intrauterine repair in humans. This review attempts to discern the advantages and flaws in animal models that may help us understand why spinal cord function is not preserved to the same degree in humans compared to the animal models.