Cell-specific discrimination of desmosterol and desmosterol mimetics confers selective regulation of LXR and SREBP in macrophages.

Activation of liver X receptors (LXRs) with synthetic agonists promotes reverse cholesterol transport and protects against atherosclerosis in mouse models. Most synthetic LXR agonists also cause marked hypertriglyceridemia by inducing the expression of sterol regulatory element-binding protein (SREBP)1c and downstream genes that drive fatty acid biosynthesis. Recent studies demonstrated that desmosterol, an intermediate in the cholesterol biosynthetic pathway that suppresses SREBP processing by binding to SCAP, also binds and activates LXRs and is the most abundant LXR ligand in macrophage foam cells. Here we explore the potential of increasing endogenous desmosterol production or mimicking its activity as a means of inducing LXR activity while simultaneously suppressing SREBP1c-induced hypertriglyceridemia. Unexpectedly, while desmosterol strongly activated LXR target genes and suppressed SREBP pathways in mouse and human macrophages, it had almost no activity in mouse or human hepatocytes in vitro. We further demonstrate that sterol-based selective modulators of LXRs have biochemical and transcriptional properties predicted of desmosterol mimetics and selectively regulate LXR function in macrophages in vitro and in vivo. These studies thereby reveal cell-specific discrimination of endogenous and synthetic regulators of LXRs and SREBPs, providing a molecular basis for dissociation of LXR functions in macrophages from those in the liver that lead to hypertriglyceridemia.

Prevalence, indications and management of balloon uncrossable chronic total occlusions: Insights from a contemporary multicenter US registry.

BACKGROUND: Balloon uncrossable lesions can be challenging to treat, requiring specialized techniques and equipment. METHODS: We examined the prevalence, clinical and angiographic characteristics, management and procedural outcomes of balloon uncrossable lesions in a multicenter chronic total occlusion (CTO) percutaneous coronary intervention (PCI) registry. RESULTS: Between 2012 and 2016, 718 CTO PCIs (in which the occlusion was successfully crossed with a guidewire) were performed in 701 patients at 11 US centers. Mean age was 65.6 ± 10 years and 84% of the patients were men. Balloon uncrossable lesions represented 9% of all CTOs. Balloon uncrossable CTOs had more moderate/severe calcification (82% vs. 52%, P < 0.0001), moderate/severe tortuosity (61% vs. 35% P < 0.0001) and higher J-CTO score (2.95 ± 1.32 vs. 2.43 ± 1.23, P = 0.005) as compared with the remaining lesions. Technical and procedural success was significantly lower for balloon uncrossable lesions (90.5% vs. 98.3%, P < 0.0001 and 88.9% vs. 96.6% P = 0.004), respectively, but the incidence of major adverse events was similar (1.6% vs. 2.2%, P = 0.751). Balloon uncrossable lesions required longer procedure (208 [interquartile range: 135, 258] vs. 135 [94, 194] min, P < 0.0001) and fluoroscopy (77 [52, 100] vs. 45 min [27, 75], P < 0.0001) time. Techniques used to treat balloon uncrossable lesions included balloon-assisted microdissection (23%), excimer laser atherectomy (18%), and rotational atherectomy (16%). Excimer laser atherectomy and balloon-assisted microdissection were associated with the highest technical and procedural success rates. CONCLUSIONS: Balloon uncrossable CTOs are common, are associated with high rates of technical failure, and require specialized techniques for successful treatment. © 2016 Wiley Periodicals, Inc.

Guidewire and microcatheter utilization patterns during antegrade wire escalation in chronic total occlusion percutaneous coronary intervention: Insights from a contemporary multicenter registry.

OBJECTIVES: We sought to describe contemporary guidewire and microcatheter utilization for antegrade wire escalation (AWE) during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). BACKGROUND: Equipment utilization for AWE has been variable and evolving over time. METHODS: We examined device utilization during 694 AWE attempts in 679 patients performed at 15 experienced US centers between May 2012 and April 2015. RESULTS: Mean age was 65.6 ± 9.7 years, and 85% of the patients were men. Successful wiring occurred in 436 AWE attempts (63%). Final technical and procedural success was 91% and 89%, respectively. The mean number of guidewire types used for AWE was 2.2 ± 1.4. The most frequently used guidewire types were the Pilot 200 (Abbott Vascular, 56% of AWE procedures), Fielder XT (Asahi Intecc, 45%), and the Confianza Pro 12 (Asahi Intecc, 28%). The same guidewires were the ones that most commonly crossed the occlusion: Pilot 200 (36% of successful AWE crossings), Fielder XT (20%), and Confianza Pro 12 (11%). A microcatheter or over-the-wire balloon was used for 81% of AWE attempts; the Corsair microcatheter (Asahi Intecc) was the most commonly used (44%). No significant association was found between guidewire type and incidence of major adverse cardiac events (MACE). CONCLUSIONS: Our contemporary, multicenter CTO PCI registry demonstrates that the most commonly used wires for AWE are polymer-jacketed guidewires. "Stiff" and polymer-jacketed guidewires appear to provide high crossing rates without an increase in MACE or perforation, and may thus be considered for upfront use. © 2016 Wiley Periodicals, Inc.

Coronary artery spatial distribution of chronic total occlusions: Insights from a large US registry.

OBJECTIVE: To assess the spatial distribution of chronic total occlusions (CTOs) within the coronary arteries and describe procedural strategies and outcomes during CTO percutaneous coronary intervention (PCI). BACKGROUND: Acute occlusions due to plaque rupture tend to cluster within the proximal third of the coronary artery. METHODS: We examined the clinical and procedural characteristics of 1,348 patients according to lesion location within the coronary tree. RESULTS: A total of 1,369 lesions in 1,348 patients (mean age 66 ± 10 years, 85% male) were included. CTO PCI of proximal segments (n = 633, 46%) was more common than of mid (n = 557, 41%) and distal segments (n = 179, 13%). Patients undergoing CTO PCI of proximal segments were more likely to be smokers (P < 0.01), have prior coronary artery bypass graft surgery (P = 0.03) and lower ejection fraction (P = 0.04). CTOs occurring in proximal segments had longer length (P <0.01), proximal cap ambiguity (P < 0.01), and moderate/severe calcification (P < 0.01) compared to mid or distally located CTOs. Interventional collaterals were more often present in CTO PCI of proximal segments (64%, 53%, 56%, P < 0.01) consistent with the higher use of retrograde approach (47%, 33%, 37%, P < 0.01) relative to antegrade wire escalation (67%, 82%, 82%, P < 0.01). Procedural complexity was higher in CTO PCI of proximal segments (vs. mid and distal): contrast volume= 275 ml (200-375), 260 ml (200-350), 250 ml (175-350), P = 0.01; fluoroscopy time 53 minutes (32-83), 39 minutes (24-65), 40 minutes (22-72), P < 0.01. However, procedural success (87%, 90%, 85%, P = 0.1), technical success (89%, 91%, 88%, P = 0.24), and complications rates (2.8%, 2.5%, 2.2%, P = 0.88) were not different. CONCLUSIONS: The most common target vessel location for CTO PCI is the proximal coronary segment. PCI of proximal occlusions is associated with adverse clinical and angiographic characteristics and often requires use of the retrograde approach, but can be accomplished with high procedural and technical success and low complication rates. © 2016 Wiley Periodicals, Inc.

Approaches to percutaneous coronary intervention of right coronary artery chronic total occlusions: insights from a multicentre US registry.

AIMS: The goal of this study was to describe the procedural characteristics, strategy selection and associated technical and efficiency outcomes for chronic total occlusion (CTO) percutaneous coronary intervention (PCI) of the right coronary artery (RCA). METHODS AND RESULTS: We examined the clinical and angiographic characteristics of patients who underwent RCA CTO PCI between 2012 and 2015 at 11 centres in the USA. The RCA was the CTO target vessel in 739 of 1,308 CTO PCIs (56%). Overall technical and procedural success rates were 90% and 88%, respectively. A major adverse cardiovascular event (MACE) occurred in 19 patients (2.6%). Technical success was most frequently achieved using antegrade wire escalation (38% of successful procedures) followed by retrograde (36%) and antegrade dissection/re-entry (26%). Technical success was similar between various locations of RCA CTOs (p=0.11). Compared with antegrade-only procedures, utilisation of any retrograde approach was associated with lower technical (85% vs. 95%, p<0.001) and procedural (82% vs. 94%, p<0.001) success and a higher MACE rate (3.8% vs. 1.4%, p=0.037). CONCLUSIONS: RCA CTOs represent the majority of CTO target lesions, can be treated with high success and acceptable complication rates, and require frequent use of the retrograde approach and antegrade dissection/re-entry.

Impact of Proximal Cap Ambiguity on Outcomes of Chronic Total Occlusion Percutaneous Coronary Intervention: Insights From a Multicenter US Registry.

OBJECTIVES: We sought to determine the impact of proximal cap ambiguity on procedural techniques and outcomes for coronary chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: We examined the clinical and angiographic characteristics and outcomes of 1021 CTO-PCIs performed between 2012 and 2015 at 11 United States centers. RESULTS: Proximal cap ambiguity was present in 31% of target lesions and was associated with increased clinical and angiographic complexity (prior coronary artery bypass graft surgery: 43% vs 33%; P=.01; moderate/severe calcification 66% vs 51%; P<.001) and lower technical success (85% vs 93%; P<.001) and procedural success (84% vs 91%; P=.01), but similar incidence of major adverse cardiac events (3.2% vs 2.9%; P=.77). A retrograde approach was more commonly utilized among cases with proximal cap ambiguity (68% vs 33%; P<.001), and was more likely to be the initial (39% vs 13%; P<.001) and successful approach (42% vs 20%; P<.001). Proximal cap ambiguity was associated with increased use of intravascular ultrasound (49% vs 36%; P=.01) and contrast (281 mL vs 250 mL; P<.001), higher air kerma radiation dose (4.0 Gy vs 3.0 Gy; P<.001), and longer procedure time (161 min vs 119 min; P<.001). CONCLUSIONS: Proximal cap ambiguity is present in one-third of CTO-PCI target lesions and is associated with lower success rates, higher utilization of the retrograde approach, and lower procedural efficiency, but no significant difference in the incidence of major adverse cardiac events.

Comparison of various scores for predicting success of chronic total occlusion percutaneous coronary intervention.

BACKGROUND: Various scoring systems have been developed to predict the technical outcome and procedural efficiency of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: We examined the predictive capacity of 3 CTO PCI scores (Clinical and Lesion-related [CL], Multicenter CTO registry in Japan [J-CTO] and Prospective Global Registry for the Study of Chronic Total Occlusion Intervention [PROGRESS CTO] scores) in 664 CTO PCIs performed between 2012 and 2016 at 13 US centers. RESULTS: Technical success was 88% and the retrograde approach was utilized in 41%. Mean CL, J-CTO and PROGRESS CTO scores were 3.9±1.9, 2.6±1.2 and 1.4±1.0, respectively. All scores were inversely associated with technical success (p<0.001 for all) and had moderate discriminatory capacity (area under the curve 0.691 for the CL score, 0.682 for the J-CTO score and 0.647 for the PROGRESS CTO score [p=non-significant for pairwise comparisons]). The difference in technical success between the minimum and maximum CL score strata was the highest (32%, vs. 15% for J-CTO and 18% for PROGRESS CTO scores). All scores tended to perform better in antegrade-only procedures and correlated significantly with procedure time and fluoroscopy dose; the CL score also correlated significantly with contrast utilization. CONCLUSIONS: CL, J-CTO and PROGRESS CTO scores perform moderately in predicting technical outcome of CTO PCI, with better performance for antegrade-only procedures. All scores correlate with procedure time and fluoroscopy dose, and the CL score also correlates with contrast utilization.

Use of Intravascular Imaging During Chronic Total Occlusion Percutaneous Coronary Intervention: Insights From a Contemporary Multicenter Registry.

BACKGROUND: Intravascular imaging can facilitate chronic total occlusion (CTO) percutaneous coronary intervention. METHODS AND RESULTS: We examined the frequency of use and outcomes of intravascular imaging among 619 CTO percutaneous coronary interventions performed between 2012 and 2015 at 7 US centers. Mean age was 65.4±10 years and 85% of the patients were men. Intravascular imaging was used in 38%: intravascular ultrasound in 36%, optical coherence tomography in 3%, and both in 1.45%. Intravascular imaging was used for stent sizing (26.3%), stent optimization (38.0%), and CTO crossing (35.7%, antegrade in 27.9%, and retrograde in 7.8%). Intravascular imaging to facilitate crossing was used more frequently in lesions with proximal cap ambiguity (49% versus 26%, P<0.0001) and with retrograde as compared with antegrade-only cases (67% versus 31%, P<0.0001). Despite higher complexity (Japanese CTO score: 2.86±1.19 versus 2.43±1.19, P=0.001), cases in which imaging was used for crossing had similar technical and procedural success (92.8% versus 89.6%, P=0.302 and 90.1% versus 88.3%, P=0.588, respectively) and similar incidence of major cardiac adverse events (2.7% versus 3.2%, P=0.772). Use of intravascular imaging was associated with longer procedure (192 minutes [interquartile range 130, 255] versus 131 minutes [90, 192], P<0.0001) and fluoroscopy (71 minutes [44, 93] versus 39 minutes [25, 69], P<0.0001) time. CONCLUSIONS: Intravascular imaging is frequently performed during CTO percutaneous coronary intervention both for crossing and for stent selection/optimization. Despite its use in more complex lesion subsets, intravascular imaging was associated with similar rates of technical and procedural success for CTO percutaneous coronary intervention. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02061436.

Effect of Lesion Age on Outcomes of Chronic Total Occlusion Percutaneous Coronary Intervention: Insights From a Contemporary US Multicenter Registry.

BACKGROUND: We sought to determine the effect of lesion age on procedural techniques and outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: We examined the characteristics and outcomes of 394 CTO PCIs with data on lesion age, performed between 2012 and 2016 at 11 experienced US centres. RESULTS: Mean patient age was 66 ± 10 years and 85.6% of the patients were men. Overall technical and procedural success rates were 90.1% and 87.5%, respectively. A major adverse cardiovascular event (MACE) occurred in 16 patients (4.1%). Mean and median lesion ages were 43 ± 62 months and 12 months (interquartile range, 3-64 months), respectively. Patients were stratified into tertiles according to lesion age (3-5, 5-36.3, and > 36.3 months). Older lesion age was associated with older patient age (68 ± 8 vs 65 ± 10 vs 64 ± 11 years; P = 0.009), previous coronary artery bypass grafting (62% vs 42% vs 30%; P < 0.001), and moderate/severe calcification (75% vs 53% vs 59%; P = 0.001). Older lesions more often required use of the retrograde approach and antegrade dissection/re-entry for successful lesion crossing. There was no difference in technical (87.8% vs 89.6% vs 93.0%; P = 0.37) or procedural (86.3% vs 87.4% vs 89.0%; P = 0.80) success, or the incidence of MACE (3.1% vs 3.0% vs 6.3%; P = 0.31) for older vs younger occlusions. CONCLUSIONS: Older CTO lesions exhibit angiographic complexity and more frequently necessitate the retrograde approach or antegrade dissection/re-entry. Older CTOs can be recanalized with high technical and procedural success and acceptable MACE rates. Lesion age appears unlikely to be a significant determinant of CTO PCI success.

New developments in the clinical use of drug-coated balloon catheters in peripheral arterial disease.

Peripheral arterial disease (PAD) involving the lower extremity is a major source of morbidity and mortality. Clinical manifestations of PAD span the spectrum from lifestyle limiting claudication to ulceration and gangrene leading to amputation. Advancements including balloon angioplasty, self-expanding stents, drug-eluting stents, and atherectomy have resulted in high technical success rates for endovascular therapy in patients with PAD. However, these advances have been limited by somewhat high rates of clinical restenosis and clinically driven target lesion revascularization. The recent introduction of drug-coated balloon technology shows promise in limiting neointimal hyperplasia induced by vascular injury after endovascular therapies. This review summarizes the contemporary clinical data in the emerging area of drug-coated balloons.

Outcomes With the Use of the Retrograde Approach for Coronary Chronic Total Occlusion Interventions in a Contemporary Multicenter US Registry.

BACKGROUND: We sought to examine the efficacy and safety of chronic total occlusion percutaneous coronary intervention using the retrograde approach. METHODS AND RESULTS: We compared the outcomes of the retrograde versus antegrade-only approach to chronic total occlusion percutaneous coronary intervention among 1301 procedures performed at 11 experienced US centers between 2012 and 2015. The mean age was 65.5±10 years, and 84% of the patients were men with a high prevalence of diabetes mellitus (45%) and previous coronary artery bypass graft surgery (34%). Overall technical and procedural success rates were 90% and 89%, respectively, and in-hospital major adverse cardiovascular events occurred in 31 patients (2.4%). The retrograde approach was used in 539 cases (41%), either as the initial strategy (46%) or after a failed antegrade attempt (54%). When compared with antegrade-only cases, retrograde cases were significantly more complex, both clinically (previous coronary artery bypass graft surgery prevalence, 48% versus 24%; P<0.001) and angiographically (mean Japan-chronic total occlusion score, 3.1±1.0 versus 2.1±1.2; P<0.001) and had lower technical success (85% versus 94%; P<0.001) and higher major adverse cardiovascular events (4.3% versus 1.1%; P<0.001) rates. On multivariable analysis, the presence of suitable collaterals, no smoking, no previous coronary artery bypass graft surgery, and left anterior descending artery target vessel were independently associated with technical success using the retrograde approach. CONCLUSIONS: The retrograde approach is commonly used in contemporary chronic total occlusion percutaneous coronary intervention, especially among more challenging lesions and patients. Although associated with lower success and higher major adverse cardiovascular event rates in comparison to antegrade-only crossing, retrograde percutaneous coronary intervention remains critical for achieving overall high success rates.

Contrast Utilization During Chronic Total Occlusion Percutaneous Coronary Intervention: Insights From a Contemporary Multicenter Registry.

BACKGROUND: Administration of a large amount of contrast volume during chronic total occlusion (CTO) percutaneous coronary intervention (PCI) may lead to contrast-induced nephropathy. METHODS: We examined the association of clinical, angiographic and procedural variables with contrast volume administered during 1330 CTO-PCI procedures performed at 12 experienced United States centers. RESULTS: Technical and procedural success was 90% and 88%, respectively, and mean contrast volume was 289 ± 138 mL. Approximately 33% of patients received >320 mL of contrast (high contrast utilization group). On univariable analysis, male gender (P=.01), smoking (P=.01), prior coronary artery bypass graft surgery (P=.04), moderate or severe calcification (P=.01), moderate or severe tortuosity (P=.04), proximal cap ambiguity (P=.01), distal cap at a bifurcation (P<.001), side branch at the proximal cap (P<.001), blunt/no stump (P=.01), occlusion length (P<.001), higher J-CTO score (P=.02), use of antegrade dissection and reentry or retrograde approach (P<.001), ad hoc CTO-PCI (P=.04), dual arterial access (P<.001), and 8 Fr guide catheters (P<.001) were associated with higher contrast volume; conversely, diabetes mellitus (P=.01) and in-stent restenosis (P=.01) were associated with lower contrast volume. On multivariable analysis, moderate/severe calcification (P=.04), distal cap at a bifurcation (P<.001), ad hoc CTO-PCI (P<.001), dual arterial access (P=.01), 8 Fr guide catheters (P=.02), and use of antegrade dissection/reentry or the retrograde approach (P<.001) were independently associated with higher contrast use, whereas diabetes (P=.02), larger target vessel diameter (P=.03), and presence of "interventional" collaterals (P<.001) were associated with lower contrast utilization. CONCLUSIONS: Several baseline clinical, angiographic, and procedural characteristics are associated with higher contrast volume administration during CTO-PCI.

First-in-human robotic percutaneous coronary intervention for unprotected left main stenosis.

The safety and feasibility of robotically-assisted percutaneous coronary intervention (PCI) for simple coronary lesions has been demonstrated. The CorPath robotic system (Corpath 200, Corindus, Waltham, MA) consists of a robotic arm mounted on the cardiac catheterization table that consists of a drive housing a single-use sterile cassette, which is connected to the guiding catheter. While sitting in the nonsterile, radiation-shielded cockpit, the operator remotely controls delivery and removal of coronary guidewires, angioplasty balloons, and stents. The database for the ongoing PRECISION registry was queried at a single center and results of unprotected left main robotic PCI procedures are reported. Of 102 robotic PCI procedures performed at this center, 6 were unprotected left main lesions (age 69 ± 14 years; 67% male). All 6 subjects underwent successful PCI (fluoroscopy time 26.8 ± 11.4 min;1.8 stents and 2.2 vessels treated/patient) with three requiring hemodynamic support (two with percutaneous left ventricular assistance using the Impella 2.5 (Abiomed, Danvers, MA) and one with intraaortic balloon pump counterpulsation). This report demonstrates the feasibility of performing robotically assisted unprotected left main PCI with or without hemodynamic support. © 2016 Wiley Periodicals, Inc.

Use of antegrade dissection re-entry in coronary chronic total occlusion percutaneous coronary intervention in a contemporary multicenter registry.

BACKGROUND: We assessed efficacy and safety of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) using antegrade dissection re-entry (ADR). METHODS: We examined outcomes of ADR among 1313 CTO PCIs performed at 11 US centers between 2012-2015. RESULTS: 84.1% of patients were men. Prevalence of prior coronary artery bypass graft surgery was 34.3%. Overall technical and procedural success were 90.1% and 88.7%, respectively. In-hospital major adverse cardiovascular events (MACE) occurred in 31 patients (2.4%). ADR was used in 458 cases (34.9%), and was the first strategy in 169 cases (12.9%). ADR cases were angiographically more complex than non-ADR cases (mean J-CTO score: 2.8±1.2 vs. 2.4±1.2, p<0.001). ADR was performed using the CrossBoss catheter in 246 of 458 (53.7%) and the Stingray system in 251 ADR cases (54.8%). Compared with non-ADR cases, ADR cases had lower technical (86.9% vs. 91.8%, p=0.005) and procedural success (85.0% vs. 90.7%, p=0.002), but similar risk for MACE (2.9% vs. 2.2%, p=0.42). ADR was associated with longer procedure and fluoroscopy time, and higher patient air kerma dose and contrast volume (all p<0.001). After excluding retrograde cases, ADR and antegrade wire escalation (AWE) had similar technical success (92.7% vs. 94.2%, p=0.43), procedural success (91.8% vs. 94.1%, p=0.23), and MACE (2.1% vs. 0.6%, p=0.12). CONCLUSIONS: ADR is used relatively frequently in contemporary CTO PCI, especially for challenging lesions and after failure of other strategies. ADR is associated with similar success rates and risk for complications as compared with AWE, and is important for achieving high procedural success.

Effect of Previous Failure on Subsequent Procedural Outcomes of Chronic Total Occlusion Percutaneous Coronary Intervention (from a Contemporary Multicenter Registry).

We sought to examine the impact of previous failure on the outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We examined the clinical and angiographic characteristics and procedural outcomes of 1,213 consecutive patients who underwent 1,232 CTO PCIs from 2012 to 2015 at 12 US centers. Mean age was 65 ± 10 years, and 84.8% of patients were men. A previously failed attempt had been performed in 215 patients (17.5%). As compared with patients without previous CTO PCI failure, patients with previous failure had higher Multicenter CTO Registry in Japan CTO score (2.40 ± 1.13 vs 3.28 ± 1.29, p <0.0001) and were more likely to have in-stent restenosis (10.5% vs 28.4%, p <0.0001) and to undergo recanalization attempts using the retrograde approach (41% vs 50%, p = 0.011). Technical (90% vs 88%, p = 0.390) and procedural (89% vs 86%, p = 0.184) success were similar in the 2 study groups; however, median procedure time (125 vs 142 minutes, p = 0.026) and fluoroscopy time (45 vs 55 minutes, p = 0.015) were longer in the previous failure group. In conclusion, a previously failed CTO PCI attempt is associated with higher angiographic complexity, longer procedural duration, and fluoroscopy time, but not with the success and complication rates of subsequent CTO PCI attempts.

Invasive Cardiologists Are Exposed to Greater Left Sided Cranial Radiation: The BRAIN Study (Brain Radiation Exposure and Attenuation During Invasive Cardiology Procedures).

OBJECTIVES: This study sought to determine radiation exposure across the cranium of cardiologists and the protective ability of a nonlead, XPF (barium sulfate/bismuth oxide) layered cap (BLOXR, Salt Lake City, Utah) during fluoroscopically guided, invasive cardiovascular (CV) procedures. BACKGROUND: Cranial radiation exposure and potential for protection during contemporary invasive CV procedures is unclear. METHODS: Invasive cardiologists wore an XPF cap with radiation attenuation ability. Six dosimeters were fixed across the outside and inside of the cap (left, center, and right), and 3 dosimeters were placed outside the catheterization lab to measure ambient exposure. RESULTS: Seven cardiology fellows and 4 attending physicians (38.4 ± 7.2 years of age; all male) performed diagnostic and interventional CV procedures (n = 66.2 ± 27 cases/operator; fluoroscopy time: 14.9 ± 5.0 min). There was significantly greater total radiation exposure at the outside left and outside center (106.1 ± 33.6 mrad and 83.1 ± 18.9 mrad) versus outside right (50.2 ± 16.2 mrad; p < 0.001 for both) locations of the cranium. The XPF cap attenuated radiation exposure (42.3 ± 3.5 mrad, 42.0 ± 3.0 mrad, and 41.8 ± 2.9 mrad at the inside left, inside center, and inside right locations, respectively) to a level slightly higher than that of the ambient control (38.3 ± 1.2 mrad, p = 0.046). After subtracting ambient radiation, exposure at the outside left was 16 times higher than the inside left (p < 0.001) and 4.7 times higher than the outside right (p < 0.001). Exposure at the outside center location was 11 times higher than the inside center (p < 0.001), whereas no difference was observed on the right side. CONCLUSIONS: Radiation exposure to invasive cardiologists is significantly higher on the left and center compared with the right side of the cranium. Exposure may be reduced similar to an ambient control level by wearing a nonlead XPF cap. (Brain Radiation Exposure and Attenuation During Invasive Cardiology Procedures [BRAIN]; NCT01910272).

Application and outcomes of a hybrid approach to chronic total occlusion percutaneous coronary intervention in a contemporary multicenter US registry.

BACKGROUND: A hybrid approach to chronic total occlusion (CTO) percutaneous coronary intervention (PCI) prioritizing and combining all available crossing techniques was developed to optimize procedural efficacy, efficiency, and safety, but there is limited published data on its outcomes. METHODS: We examined the procedural techniques and outcomes of 1036 consecutive CTO PCIs performed using a hybrid approach between 2012 and 2015 at 11 US centers. RESULTS: Mean age was 65 ± 10 years and 86% of the patients were men, with a high prevalence of diabetes mellitus (43%) and prior coronary artery bypass graft surgery (34%). Most target CTOs were located in the right coronary artery (59%), followed by the left anterior descending artery (23%) and the circumflex (19%). Dual injection was used in 71%. Technical success was achieved in 91% and a major procedural complication occurred in 1.7% of cases. The final successful crossing technique was antegrade wire escalation in 46%, antegrade dissection/re-entry in 26%, and retrograde in 28%. The initial crossing strategy was successful in 58% of the lesions, whereas 39% required an additional approach. Overall, antegrade wire escalation was used in 71%, antegrade dissection/re-entry in 36%, and the retrograde approach in 42% of procedures. Median contrast volume, fluoroscopy time, and air kerma radiation dose were 260 (200-360) ml, 44 (27-72) min, and 3.4 (2.0-5.4) Gray, respectively. CONCLUSION: Application of a hybrid approach to CTO crossing resulted in high success and low complication rates across a varied group of operators and hospital practice structures, supporting its expanding use in CTO PCI.

Endovascular therapy for critical limb ischemia.

Critical limb ischemia (CLI) represents an advanced disease state of peripheral arterial disease. It manifests as lower extremity ischemic rest pain or ischemic skin lesions leading to ulceration or gangrene. Patients with CLI often have multiple medical comorbidities and a 1-year mortality rate of 25% and a 1-year amputation rate of 25%. Historically, bypass surgery with autogenous veins for flow restoration has been the first-line therapy for CLI. However, advances in endovascular techniques and device technology have changed the treatment paradigm. Catheter-based technologies are rapidly evolving at a rate that is outpacing large-scale studies evaluating relevant clinical outcomes. Patients with CLI require a multidisciplinary management approach centered on aggressive medical therapies, wound care and prompt revascularization, with an emphasis on limb salvage. This review summarizes the contemporary endovascular therapies including balloon angioplasty, atherectomy and bare-metal stenting. In addition, we review emerging technologies, such as drug-eluting stents, drug-coated balloons and chronic total occlusion recanalization devices.

Percutaneous extraction of inadvertently placed left-sided pacemaker leads with complete cerebral embolic protection.

Lead wire malposition is a known, but rare complication of permanent pacemaker or defibrillator implantation. The actual incidence and prevalence is unknown and management options for inadvertent left ventricular lead malposition have not been uniform. Current recommendations include systemic anticoagulation with warfarin or surgical lead removal with circulatory arrest for compelling clinical scenarios. Percutaneous left-sided lead extraction is contraindicated due to the potentially increased risk of thromboembolic complications associated with this procedure. To our knowledge, this is the first report of percutaneous extraction of inadvertently placed left ventricular and left atrial endocardial pacemaker leads with flow-preserving complete cerebral embolic protection. We also review the current literature regarding the incidence, management, and percutaneous extraction of left-sided cardiac leads.

Comparison of bolus injection and constant infusion methods for measuring muscle protein fractional synthesis rate in humans.

BACKGROUND: The use of stable isotope tracer techniques to measure muscle protein fractional synthesis rate (FSR) has been well established and widely used. The most common method that has been utilized so far is a primed constant infusion (CI) method, which requires 3-4 h of tracer infusion. However, recently our group has developed a bolus injection (BI) method, which requires an injection of bolus of tracer and can be completed within 1 h. In this study, we compared calf (gastrocnemius) muscle protein FSR measured using these two different methods--CI and BI. METHOD: FSRs were measured in eight people (5 men and 3 women; age: 62.3±6.9 years (mean±SD); body weight: 75.4±21.5 kg) at basal, postabsorptive state using L-[ring-2H5]-phenylalanine. In the CI protocol, a primed continuous infusion was given for 4 h, and muscle biopsies were taken at 120 and 240 min; in the BI, a bolus injection of the tracer was given at 0 min and biopsies were taken at 5 and 60 min. Tracer enrichments in blood and muscle tissue were determined by gas chromatography-mass spectrometry. Data are expressed as mean±SE; t-test, linear regression and Levene Median equal variance test analyses were performed. RESULTS: CI FSR was 0.066±0.006%/h, whereas BI FSR was 0.058±0.008%/h, p=NS. The linear regression analysis showed a significant relationship between BI and CI, p=0.038. The intra-class correlation coefficient was 0.83. The standard deviation of the differences in the measurements was 0.015%/h. The Levene Median equal variance test demonstrated no difference in variance between the CI and BI measurements (p=0.722). CONCLUSION: No difference could be detected in calf muscle protein FSR measured by CI and BI methods; the BI method can be used for the measurement of muscle protein FSR in humans.