Ravish Sachar

Association Between Apolipoprotein E Alleles and Calcific Valvular Heart Disease

Background—Studies on apolipoprotein E (apoE) alleles have reported an increased risk of coronary heart disease in patients with the apoE4 allele. Given the risk factor and histological similarities between coronary and calcific valvular heart disease (aortic stenosis [AS] and mitral annular calcification [MAC]), we postulated that apoE alleles might be associated with the development of these valvular lesions. Methods and Results—We evaluated the association between apoE alleles and calcific valvular lesions in 802 patients undergoing transthoracic echocardiography using logistic regression analyses. No difference was noted in genotype distribution (P =0.59) or prevalence of apoE4 between those with or without MAC (30% versus 27%, respectively; P =0.57). Compared with patients without AS, the genotype distribution of patients with AS differed significantly (P =0.03), with increasing prevalences of the apoE 4 allele (27% in those without versus 40% in those with AS; P =0.01). In multivariate analyses adjusting for age, gender, low-density lipoprotein cholesterol levels, and coronary artery disease, increasing age and the apoE4 allele were significant independent predictors of AS (odds ratio, 1.94; 95% confidence interval, 1.01 to 3.71; P =0.046), whereas the apoE4 allele was not predictive of MAC. Conclusions—These findings support extension of the importance of the apoE4 allele beyond atherosclerosis and Alzheimer’s disease to calcific AS.

Transradial approach for carotid artery stenting: A feasibility study†

Background: Carotid artery stenting (CAS) has become accepted as an alternative to carotid endarterectomy for revascularization of the internal carotid artery (ICA) among high risk patients. CAS from the femoral approach can be problematic due to access site complications as well as technical difficulties related to peripheral vascular disease (PVD) and/or anatomical variations of the aortic arch. The purpose of the present study is to evaluate the feasibility of the radial artery as an alternative approach for CAS. Methods: Forty‐two patients (mean age 71 ± 1, 26 male) underwent CAS. All had a CA stenosis greater than 80% and comorbid conditions increasing the risk of carotid endarterectomy. The target common carotid artery (CCA) was initially cannulated via the radial artery using a 5F Simmons 1 diagnostic catheter which was then advanced to the external CA (ECA) over an extrasupport 0.014” coronary guidewire. After removing the coronary guidewire, a 0.035” guidewire was advanced into the ECA, and the Simmons 1 was exchanged for a 5F or 6F shuttle sheath and positioned in the distal CCA. In four patients with a bovine aortic arch, the left CCA was accessed with a 5F Amplatz R2 catheter which was then exchanged for a shuttle sheath over a 0.035” guidewire. CAS was performed using standard techniques with weight‐based bivalirudin for anticoagulation. Results: CAS was successful in 35/42 (83%) patients, including 28/29 (97%) right CA, 4/5 (80%) bovine left CA, 7/13 (54%) left CA. Mean interventional time was 30 ± 3 minutes. The sheath was removed immediately after the procedure. There were no radial access site complications. One patient sustained a stroke 24 hrs after the procedure with complete resolution of symptoms (Mean NIH stroke scale 2.0 ± 0.3 before, 1.9 ± 0.3 after). Median hospital stay was 2 ± 0.6 days. Inadequate catheter support at the origin of the CCA was the technical cause of failure in the seven unsuccessful cases. Conclusion: CAS using the transradial approach appears to be safe and technically feasible. The technique may be particularly useful in patients with right ICA lesions and severe PVD or unfavorable arch anatomy, and among patients with a bovine aortic arch.

The transradial approach for carotid artery stenting

Carotid artery stenting (CAS) is an alternative to carotid endarterectomy (CEA) for revascularization of the internal carotid artery (ICA). CAS from the femoral approach may be problematic due to peripheral vascular disease, anatomical variations of the aortic arch, and access site complications. The purpose of this study was to evaluate the right radial approach (RRA) for CAS.

Nine-month results of the REFORM study

To evaluate the 9‐month safety and effectiveness outcomes of the Formula™ balloon‐expandable renal stent (Cook Medical, Bloomington, IN) for the treatment of atherosclerotic renal artery stenosis (RAS) following suboptimal angioplasty.

Utility of IVUS-guided transaccess catheter in the treatment of long chronic total occlusion of the superficial femoral artery

Failure to reenter the true lumen distal to an occlusion is the most frequent cause of failure of the technique of subintimal angioplasty. We report the utility of an IVUS‐guided TransAccess catheter in overcoming this problem in the treatment of two patients with long chronic total occlusion of the superficial femoral artery. Catheter Cardiovasc Interv 2004;62:237–243.

Relation of albumin/creatinine ratio to C-reactive protein and to the metabolic syndrome.

We hypothesized that the association of high sensitivity C-reactive protein (CRP) with urinary albumin excretion (UAE) is predominately mediated through its correlation with the metabolic syndrome. Serum CRP and urine albumin:creatinine ratios (ACR) from 720 preventive cardiology patients were analyzed to estimate age- and gender-adjusted relative risk of high CRP and metabolic syndrome for high ACR. These data demonstrate that CRP independently predicts the presence of UAE, a marker of endothelial dysfunction.

Stellarex drug-coated balloon for treatment of femoropopliteal disease: Twelve-month outcomes from the randomized ILLUMENATE pivotal and pharmacokinetic studies

Background: Drug-coated balloons (DCBs) are a predominant revascularization therapy for symptomatic femoropopliteal artery disease. Because of the differences in excipients, paclitaxel dose, and coating morphologies, varying clinical outcomes have been observed with different DCBs. We report the results of 2 studies investigating the pharmacokinetic and clinical outcomes of a new DCB to treat femoropopliteal disease. Methods: In the ILLUMENATE Pivotal Study (Prospective, Randomized, Single-Blind, U.S. Multi-Center Study to Evaluate Treatment of Obstructive Superficial Femoral Artery or Popliteal Lesions With A Novel Paclitaxel-Coated Percutaneous Angioplasty Balloon), 300 symptomatic patients (Rutherford class 2–4) were randomly assigned to DCB (n=200) or standard angioplasty (percutaneous transluminal angioplasty [PTA]) (n=100). The primary safety end point was freedom from device- and procedure-related death through 30 days, and freedom from target limb major amputation and clinically driven target lesion revascularization through 12 months. The primary effectiveness end point was primary patency through 12 months. In the ILLUMENATE PK study (Pharmacokinetic Study of the Stellarex Drug-Coated Angioplasty Balloon), paclitaxel plasma concentrations were measured after last DCB deployment and at prespecified times (at 1, 4, 24 hours and at 7 and 14 days postprocedure) until no longer detectable. Results: In the ILLUMENATE Pivotal Study, baseline characteristics were similar between groups: 50% had diabetes mellitus, 41% were women, mean lesion length was 8.3 cm, and 44% were severely calcified. The primary safety end point was met (92.1% for DCB versus 83.2% for PTA, P=0.025 for superiority) and the primary patency rate was significantly higher with DCB (76.3% for DCB versus 57.6% for PTA, P=0.003). Primary patency per Kaplan-Meier estimates at day 365 was 82.3% for DCB versus 70.9% for PTA (P=0.002). The rate of clinically driven target lesion revascularization was significantly lower in the DCB cohort (7.9% versus 16.8%, P=0.023). Improvements in ankle-brachial index, Rutherford class, and quality of life were comparable, but the PTA cohort required twice as many revascularizations. Pharmacokinetic outcomes showed that all patients had detectable paclitaxel levels after DCB deployment that declined within the first hour (54.4±116.9 ng/mL to 1.4±1.0 ng/mL). Conclusions: The data demonstrate superior safety and effectiveness of the Stellarex DCB in comparison with PTA, and plasma levels of paclitaxel fall to low levels within 1 hour. Clinical Trial Registration: URL: http://clinicaltrials.gov. Unique identifiers: NCT01858428 and NCT01912937.

Treatment Effect of Drug-Coated Balloons Is Durable to 3 Years in the Femoropopliteal Arteries: Long-Term Results of the IN.PACT SFA Randomized Trial

Background— Randomized controlled trials have reported favorable 1-year outcomes with drug-coated balloons (DCBs) for the treatment of symptomatic peripheral arterial disease when compared with standard percutaneous transluminal angioplasty (PTA). Evidence remains limited on the durability of the treatment effect with DCBs in the longer term. Methods and Results— IN.PACT SFA is a single-blind, randomized trial (Randomized Trial of IN.PACT Admiral Paclitaxel-Coated Percutaneous Transluminal Angioplasty [PTA] Balloon Catheter vs Standard PTA for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery [SFA] and/or Proximal Popliteal Artery [PPA]) that enrolled 331 patients with symptomatic (Rutherford 2–4) femoropopliteal lesions up to 18 cm in length. Patients were randomized 2:1 to receive treatment with DCB or PTA. The 36-month assessments included primary patency, freedom from clinically driven target lesion revascularization, major adverse events, and functional outcomes. At 36 months, primary patency remained significantly higher among patients treated with DCB compared with PTA (69.5% versus 45.1%; log rank P<0.001). The rates of clinically driven target lesion revascularization were 15.2% and 31.1% (P=0.002) for the DCB and PTA groups, respectively. Functional outcomes were similarly improved between treatment groups even though subjects in the DCB group required significantly fewer reinterventions versus those in the PTA group (P<0.001 for target lesion revascularization, P=0.001 for target vessel revascularization). There were no device- or procedure-related deaths as adjudicated by an independent Clinical Events Committee. Conclusions— Three-year results demonstrate a durable and superior treatment effect among patients treated with DCB versus standard PTA, with significantly higher primary patency and lower clinically driven target lesion revascularization, resulting in similar functional improvements with reduced need for repeat interventions. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01175850 for IN.PACT SFA phase I in the European Union and NCT01566461 for IN.PACT SFA phase II in the United States.

Impact of diabetes mellitus on outcome of patients undergoing carotid artery stenting: Insights from a single center registry†

Objective: To evaluate the impact of diabetic status on outcome of patients undergoing carotid artery stenting (CAS). Background: Diabetes has been demonstrated to be a strong predictor of adverse outcome in patients undergoing coronary revascularization. Its significance in predicting outcome of patients undergoing carotid interventions has not been ascertained. Methods: We evaluated the short‐term outcomes of 833 patients who underwent CAS at our institution. The primary outcome of this analysis was 30 day incidence of stroke, myocardial infarction, and death. Results: Diabetes was present in 311 patients. Baseline characteristics were comparable between diabetics and nondiabetics except for the diabetics having a lower left ventricular ejection fraction, lower hemoglobin, and a higher body mass index at baseline. Further, they were more likely to have congestive heart failure and coronary artery disease. There was no difference in the incidence of stroke (1.9% versus 2.7%,), myocardial infarction (MI) (2.6% versus 1.9%), death (3.9% versus 2.5%), or the composite of death stroke or MI (6.8% versus 5.9%) at 30 days between diabetics and nondiabetics. Similar results were seen when the analysis was restricted to patients treated with an emboli protection device. Diabetes was not a risk factor for adverse outcome after CAS after multivariate adjustment. Conclusion: Diabetics undergoing CAS are more likely to have associated co‐morbidities. However despite this handicap, their short term outcome after CAS is similar to that of nondiabetics.

Treatment with ω-3 fatty acids reduces serum C-reactive protein concentration

Abstract Background: Studies have demonstrated that patients with diets high in w-3 fatty acids have a lower risk of adverse cardiovascular events. C-reactive protein (CRP), a marker of inflammation, is a strong predictor of future cardiovascular events. w-3 fatty acids have been shown to have anti-inflammatory properties. However, there is a paucity of data examining the effect of =-3 fatty acids on CRP levels. This randomized, double-blind, placebocontrolled trial tested the hypothesis that treatment with w-3 polyunsaturated fatty acids (n-3 PUFAs) would reduce serum high-sensitivity CRP levels. Materials & methods: Fifty three patients with elevated baseline CRP (?3 mg/l) were randomized to n-3 PUFA (27 patients) or placebo (26 patients). Patients with active infection, inflammatory disease, baseline CRP ?10 mg/l or those started on HMG-CoA reductase inhibitor therapy during the study period were excluded. The primary end point was CRP level following 8 weeks of treatment. Results: After 8 weeks of treatment with the study drug, the median CRP level in the n-3 PUFA group was 3.4 mg/l compared with 4.0 mg/l in the placebo group (p = 0.36). After controlling for baseline CRP, there was a significant percentage decrease in CRP from baseline in the n-3 PUFA group (-40.3%; p = 0.009) but not in the placebo group (-16.4%; p = 0.32) Conclusion: Treatment for 8 weeks with w-3 fatty acids resulted in a significant percentage reduction of CRP levels as compared with baseline, a finding not seen with placebo.