Angiographically silent atherosclerosis detected by intravascular ultrasound in patients with familial hypercholesterolemia and familial combined hyperlipidemia: Correlation with high density lipoproteins

AbstractObjectives. This study sought to evaluate the extent of atherosclerosis in coronary and iliac arteries in patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia, using intravascular ultraound imaging.Background. Intravascular ultrasound imaging provides cross-sectional tomographic views of the vessel wall and allows quantitative assessment of atherosclerosis.Methods. Forty-eight nonsmoking, asymptomatic patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia underwent intravascular ultrasound imaging of the left anterior descending coronary, left main coronary and common iliac arteries. Angiography showed only minimal or no narrowing in these vessels. Intravascular ultrasound images obtained during catheter pullback underwent morphometric analysis. Plaque burden was expressed as the mean and maximal intimal index (ratio of plaque area and area within the internal elastic lamina) and as the percent of vessel surface covered by plaque.Results. Intravascular ultrasound detected plaque more frequently than angiography in the left anterior descending (80% vs. 29%, respectively), left main (44% vs. 16%) and iliac arteries (33% vs. 27%). Plaque burden was higher in the left anterior descending (mean intimal index [±SD] 0.25 ± 0.16) than in the left main (0.11 ± 0.16, p < 0.001) and iliac arteries (0.02 ± 0.04, p < 0.001). Angiography detected lumen narrowing only in coronary arteries with a maximal intimal index ⪰0.42 (left anterior descending artery) and ⪰0.43 (left main artery). The area within the internal elastic lamina increased with plaque area in the left anterior descending (r = 0.82, p < 0.001) and left main arteries (r = 0.53, p < 0.001). By stepwise multiple regression analysis, the strongest predictor for plaque burden in the left anterior descending artery was the level of high density lipoprotein (HDL) cholesterol and total/HDL cholesterol ratio for the left main artery.Conclusions. In patients with heterozygous familial hypercholesterolemia and familial combined hyperlipidemia, extensive coronary plaque is present despite minimal or no angiographic changes. Compensatory vessel enlargement and diffuse involvement with eccentric plaque may account for the lack of angiographic changes. Levels of HDL cholesterol and total/HDL cholesterol ratio are far more powerful predictors of coronary plaque burden than are low density lipoprotein cholesterol levels in these patients with early, asymptomatic disease

Comparison of the retrograde and transseptal methods for ablation of left free wall accessory pathways

AbstractObjectives. The purpose of this study was to compare success rates, procedure and fluoroscopy times and complications for the transseptal and retrograde aortic approaches in a consecutive series of patients undergoing catheter ablation of left free wall accessory pathways.Background. Radiofrequency catheter ablation of left-sided accessory pathways can be performed either by a retrograde, transaortic approach or by means of a transseptal puncture,Methods. A total of 106 patients (mean age 33 years, range 4 to 79) underwent attempted catheter ablation of a single left-sided accessory pathway by either the retrograde or the transseptal approach, or both. In the first 65 patients, the retrograde aortic approach was the preferred initial method. In the most recent 51 patients, we first attempted the transseptal approach whenever a physician trained in the technique was available. Ultimately, 102 (96.2%) of 106 patients had successfull ablation.Results. Of 89 retrograde procedures, 85% resulted in elimination of accessory pathway conduction. Four retrograde procedures performed after failure of the transseptal approach were successful. Of the 13 patients with a failed retrograde procedure, 11 later underwent ablation using the transseptal approach. Twenty-six (85%) of 33 transseptal procedures were successful. All four patients with unsuccessful initial transseptal attempts were successfully treated with the retrograde method during the same session in the etectrophysiology laboratory. Ten of 11 transseptal procedures after unsuccessful retrograde procedures were successful. Crossover from the retrograde to the transseptal approach was performed during a separate session in 9 of these 11. There was no difference in total procedure time (220 ± 12.8 vs. 205 ± 12.5 min) (mean ± SEM) or fluoroscopy time (44.1 ± 4.4 vs. 44.7 ± 5.1 min) between the retrograde and transseptal methods. Ablation time was longer for the retrograde method (69.2 ± 10.5 vs. 43.4 ± 9.3 min) (p < 0.01). Of patients ≥ 65 or ≤ 16 years old, technical factors requiring crossover to the other technique or complications occurred in 7 (42%) of 17 patients undergoing the retrograde and 1 (11%) of 9 patients undergoing the transseptal approach (p < 0.01). The overall rate of complications was the same for both (6.7% for retrograde and 6.1% for transseptal). The most serious complication involved dissection of the left coronary artery with myocardial infarction during a retrograde procedure.Conclusions. The retrograde and transseptal approaches are complementary; if one method fails, the other should be attempted, yielding an overall success rate close to 100%. Because patients undergo heparinization immediately after the arterial system is entered during a retrograde procedure, failure of that approach requires crossover to the transseptal method during a separate session or reversal of heparin; if the transseptal method is tried first, crossover to the retrograde approach can be accomplished easily during the same session. To avoid complications related to access, the transseptal method should be the first used in children, the elderly and those with arterial disease or hypertrophic ventricles

Subgroup Analysis of Crisaborole for Mild-to-Moderate Atopic Dermatitis in Children Aged 2 to \u3c 18 Years

OBJECTIVES: This post hoc analysis of pooled data from two phase III studies (AD-301: NCT02118766; AD-302: NCT02118792) explored the efficacy and safety of crisaborole ointment, 2%, a nonsteroidal phosphodiesterase 4 inhibitor, for the treatment of mild-to-moderate atopic dermatitis (AD) in pediatric patients (aged 2 to \u3c 18 years) only, stratified by baseline characteristics. METHODS: Pediatric patients with mild or moderate AD per Investigator\u27s Static Global Assessment (ISGA) and percentage of treatable body surface area (%BSA) ≥ 5 at baseline were assessed. Crisaborole or vehicle (2:1 randomization ratio) was applied twice daily for 28 days. Of the 1313 pediatric patients included in this study, 874 received crisaborole and 439 received vehicle. ISGA success was defined as clear (0) or almost clear (1) with ≥ 2-grade improvement from baseline. Efficacy and safety were stratified by age group, sex, baseline ISGA, baseline %BSA per published severity strata, and prior AD therapy. RESULTS: Overall, the proportions of crisaborole-treated and vehicle-treated pediatric patients with ISGA success at week 4 were 32.5 and 21.5%, respectively. ISGA success rates at day 29 (week 4) were generally higher in crisaborole-treated (21.9-38.1%) than vehicle-treated (15.7-26.9%) patients across subgroups. Rates of treatment-related application site pain were 2.4-10.1% for crisaborole-treated patients and 0.6-2.2% for vehicle-treated patients across subgroups. No new safety concerns were noted in any patient subgroup. CONCLUSION: Crisaborole improved global disease severity and was reasonably well tolerated across all pediatric baseline characteristic subgroups. Application site discomfort was greater with crisaborole than with vehicle, but few patients discontinued treatment. CLINICALTRIALS: None GOV REGISTRATION NUMBERS: NCT02118766; NCT02118792 (registration date: April 21, 2014)

Increased Prevalence of Coronary Ectasia in Heterozygous Familial Hypercholesterolemia

Background Although coronary atherosclerosis most commonly produces clinical effects as a result of stenosis, aneurysmal disease also occurs. We have found an increased prevalence of ectasia and aneurysmal disease in familial hypercholesterolemia (FH) suggesting a link between plasma lipoproteins and coronary aneurysms. Methods and Results In 197 asymptomatic subjects with FH, we examined the prevalence of ectasia and its association with coronary risk factors. An ectatic segment was defined as one with a luminal diameter >1.5 times that of the adjacent normal segment, excluding poststenotic dilation. Among subjects with FH, 15% had ectasia compared with 2.5% of an age- and sex-matched control group of 198 subjects without FH pre- senting for coronary angiography ( P <.001). These control patients had significantly more severe coronary atherosclerosis than patients with FH. Ectasia was 3 times more common in men than women ( P <.025). Neither age nor hypertension was predictive. Although in part reflecting the striking sex differential, ectasia was strongly associated with a lower HDL cholesterol level ( P =.003), a higher LDL/HDL ratio ( P =.003), and to a lesser extent, a higher LDL cholesterol level ( P =.07). No association was found with plasma triglycerides or very low-density lipoprotein cholesterol levels. Among FH patients, ectasia was strongly associated with an overall index of occlusive atherosclerotic disease, based on quantitative angiography ( P =.004). Intracoronary ultrasound interrogation of aneurysmal segments revealed circumferential intimal thickening. Conclusions Coronary ectasia is more prevalent in patients with FH than in other patients with coronary atherosclerosis and shows a strong inverse association with HDL cholesterol levels. This suggests that disordered lipoprotein metabolism in FH may predispose patients to aneurysmal coronary artery disease

High femoral artery bifurcation predicts contralateral high bifurcation: implications for complex percutaneous cardiovascular procedures requiring large caliber and/or dual access

Recent advances in technology have led to an increase in the use of bilateral femoral artery access and the requirement for large-bore access. Optimal access is in the common femoral artery (CFA), rather than higher (in the external iliac artery) or lower (in one of the branches of the CFA). However, there is a paucity of data in the literature about the relationship between bifurcation level of one CFA and the contralateral CFA. To define the prevalence of high bifurcation of the CFA and the relationship between bifurcation level on both sides, we performed a retrospective analysis of all patients with bilateral femoral angiography. From 4880 femoral angiograms performed at UCSF cardiac catheterization laboratory between 2005-2013, a total of 273 patients had bilateral femoral angiograms. The prevalence of low/normal, high, and very-high femoral bifurcations was 70%, 26%, and 4%, respectively, with no difference between sides. A high or very-high bifurcation significantly increased the likelihood of a high bifurcation on the contralateral side (odds ratio >3.0). Multivariable logistic regression analysis revealed age, gender, self-reported race, height, weight, and body mass index were not predictive of high or very-high bifurcations on either side. In conclusion, high femoral artery bifurcations are common and increase the likelihood of a high bifurcation of the contralateral femoral artery