John H. Rundback

Stenting and Medical Therapy for Atherosclerotic Renal-Artery Stenosis

BACKGROUND Atherosclerotic renal-artery stenosis is a common problem in the elderly. Despite two randomized trials that did not show a benefit of renal-artery stenting with respect to kidney function, the usefulness of stenting for the prevention of major adverse renal and cardiovascular events is uncertain. METHODS We randomly assigned 947 participants who had atherosclerotic renal-artery stenosis and either systolic hypertension while taking two or more antihypertensive drugs or chronic kidney disease to medical therapy plus renal-artery stenting or medical therapy alone. Participants were followed for the occurrence of adverse cardiovascular and renal events (a composite end point of death from cardiovascular or renal causes, myocardial infarction, stroke, hospitalization for congestive heart failure, progressive renal insufficiency, or the need for renal-replacement therapy). RESULTS Over a median follow-up period of 43 months (interquartile range, 31 to 55), the rate of the primary composite end point did not differ significantly between participants who underwent stenting in addition to receiving medical therapy and those who received medical therapy alone (35.1% and 35.8%, respectively; hazard ratio with stenting, 0.94; 95% confidence interval [CI], 0.76 to 1.17; P=0.58). There were also no significant differences between the treatment groups in the rates of the individual components of the primary end point or in all-cause mortality. During follow-up, there was a consistent modest difference in systolic blood pressure favoring the stent group (-2.3 mm Hg; 95% CI, -4.4 to -0.2; P=0.03). CONCLUSIONS Renal-artery stenting did not confer a significant benefit with respect to the prevention of clinical events when added to comprehensive, multifactorial medical therapy in people with atherosclerotic renal-artery stenosis and hypertension or chronic kidney disease. (Funded by the National Heart, Lung and Blood Institute and others; ClinicalTrials.gov number, NCT00081731.).

A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism : The SEATTLE II Study

OBJECTIVES This study conducted a prospective, single-arm, multicenter trial to evaluate the safety and efficacy of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis, using the EkoSonic Endovascular System (EKOS, Bothell, Washington). BACKGROUND Systemic fibrinolysis for acute pulmonary embolism (PE) reduces cardiovascular collapse but causes hemorrhagic stroke at a rate exceeding 2%. METHODS Eligible patients had a proximal PE and a right ventricular (RV)-to-left ventricular (LV) diameter ratio ≥0.9 on chest computed tomography (CT). We included 150 patients with acute massive (n = 31) or submassive (n = 119) PE. We used 24 mg of tissue-plasminogen activator (t-PA) administered either as 1 mg/h for 24 h with a unilateral catheter or 1 mg/h/catheter for 12 h with bilateral catheters. The primary safety outcome was major bleeding within 72 h of procedure initiation. The primary efficacy outcome was the change in the chest CT-measured RV/LV diameter ratio within 48 h of procedure initiation. RESULTS Mean RV/LV diameter ratio decreased from baseline to 48 h post-procedure (1.55 vs. 1.13; mean difference, -0.42; p < 0.0001). Mean pulmonary artery systolic pressure (51.4 mm Hg vs. 36.9 mm Hg; p < 0.0001) and modified Miller Index score (22.5 vs. 15.8; p < 0.0001) also decreased post-procedure. One GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries)-defined severe bleed (groin hematoma with transient hypotension) and 16 GUSTO-defined moderate bleeding events occurred in 15 patients (10%). No patient experienced intracranial hemorrhage. CONCLUSIONS Ultrasound-facilitated, catheter-directed, low-dose fibrinolysis decreased RV dilation, reduced pulmonary hypertension, decreased anatomic thrombus burden, and minimized intracranial hemorrhage in patients with acute massive and submassive PE. (A Prospective, Single-arm, Multi-center Trial of EkoSonic® Endovascular System and Activase for Treatment of Acute Pulmonary Embolism (PE) [SEATTLE II]; NCT01513759).

Atherosclerotic Vascular Disease Conference Writing Group III: Pathophysiology

The existence of atherosclerosis has been recognized for >500 years; as a pathological condition, it has been recognized for >150 years. Understanding of atherosclerotic vascular disease (AVD) has evolved most dramatically over the past 25 years with the growth of the field of vascular biology.1 Numerous studies have described this disease as a diffuse and progressive process with a variable distribution and clinical presentation that is dependent on the regional circulation involved. Factors that may influence these differences include the size and structure of the affected artery, local and regional flow, changes in microcirculatory alterations, and end-organ damage. This report discusses the general concepts of atherosclerosis, pathophysiology, microcirculatory disturbances, regional responses to atherosclerosis and ischemia, and recommendations for future research, programs, and advocacy. Atherosclerosis involves several highly interrelated processes, including lipid disturbances, platelet activation, thrombosis, endothelial dysfunction, inflammation, oxidative stress, vascular smooth cell activation, altered matrix metabolism, remodeling, and genetic factors.2 This sequence is shown schematically in Figure 1 and described in detail below. Figure 1. The 7 stages of development of an atherosclerotic plaque. First LDL moves into the subendothelium and is oxidized by macrophage and SMCs (1 and 2). Release of growth factors and cytokines attracts additional monocytes (3 and 4). Foam cell accumulation and SMC proliferation result in growth of the plaque (6, 7, and 8). Risk factors play an important role in initiating and accelerating the complex process of atherosclerosis. Risk factors for atherosclerosis are also the primary method of risk assessment and the target for therapeutic intervention in the prevention of premature vascular disease. Interestingly, the impact of these risk factors on disease development and progression in the peripheral vasculature are not the same as those in the coronary vessels and may represent an avenue of investigation to explain variations in clinical presentation …

Quality Improvement Guidelines for Angiography, Angioplasty, and Stent Placement for the Diagnosis and Treatment of Renal Artery Stenosis in Adults

From the Department of Radiology (L.G.M.), Emory University Hospital, Atlanta, Georgia; Advanced Interventional Radiology Services (J.H.R.), Teaneck, New Jersey; Interventional Radiology, The University of Texas M.D. Anderson Cancer Center (M.J.W.), Houston, Texas; System Radiology (J.F.C.), Geisinger Health System, Danville, Pennsylvania; Department of Radiology (J.F.A.), University of Virginia Health System, Charlottesville, Virginia; Department of Medical Imaging (S.K.), Scarborough General Hospital, Toronto, Ontario, Canada; Department of Radiology and Radiologic Sciences (D.L.M.), Uniformed Services University of the Health Sciences; Department of Radiology (D.L.M.), National Naval Medical Center, Bethesda, Maryland; and Department of Radiology (J.C.W.), Our Lady of Lourdes Medical Center, Lafayette, Louisiana. Received November 1, 2009; final revision received December 6, 2009; accepted December 28, 2009. Address correspondence to L.G.M., c/o Debbie Katsarelis, 3975 Fair Ridge Dr., Suite 400 N., Fairfax, VA 22033; E-mail: lmart03@emory.edu

Drug eluting stents-potential applications for peripheral arterial occlusive disease

Many different approaches have been evaluated to prevent restenosis in stents after vascular implantation. Currently, drug-eluting stents are extremely promising in suppressing neointimal hyperplasia. Various animal studies and randomized trials in humans have shown excellent results in terms of safety and efficacy during intermediate-term follow-up. This article will give an overview of experimental and clinical data of the different agents in published and ongoing trials.

Guidelines for the Reporting of Renal Artery Revascularization in Clinical Trials

Although the treatment of atherosclerotic renal artery stenosis with use of percutaneous angioplasty, stent placement, and surgical revascularization has gained widespread use, there exist few prospective randomized controlled trials (RCTs) comparing these techniques to each other or against the standard of medical management alone. To facilitate this process as well as help answer many important questions regarding the appropriate application of renal revascularization, well-designed and rigorously conducted trials are needed. These trials must have clearly defined goals and must be sufficiently sized and performed so as to withstand intensive outcomes assessment. Toward this end, this document provides guidelines and definitions for the design, conduct, evaluation, and reporting of renal artery revascularization RCTs. In addition, areas of critically necessary renal artery revascularization investigation are identified. It is hoped that this information will be valuable to the investigator wishing to conduct research in this important area.

Indications for Renal Arteriography at the Time of Coronary Arteriography A Science Advisory From the American Heart Association Committee on Diagnostic and Interventional Cardiac Catheterization, Council on Clinical Cardiology, and the Councils on Cardiovascular Radiology and Intervention and on Kidney in Cardiovascular Disease

Atherosclerotic renal artery stenosis is commonly present in patients with clinically manifest atherosclerosis in other vascular beds and is independently associated with increased cardiovascular morbidity and mortality. Screening tests such as renal angiography should be selectively applied to patients at high risk for renal artery stenosis who are potential candidates for revascularization. This multispecialty consensus document describes the rationale for patient selection for screening renal angiography at the time of cardiac catheterization.

Renal Artery Stent Placement for the Management of Ischemic Nephropathy

PURPOSE To evaluate the angiographic and clinical results of percutaneously implanted renal artery endoprostheses (stents) for the treatment of patients with ischemic nephropathy. MATERIALS AND METHODS During a 52-month period, 45 patients with azotemia (serum creatinine > or = 1.5 mg/dL) and atheromatous renal artery stenosis untreatable by, or recurrent after, balloon angioplasty were treated by percutaneous placement of Palmaz stents. Stent implantation was unilateral in 32 cases and bilateral in 11 cases. Clinical results were determined by measurements of serum creatinine and follow-up angiography. Clinical benefit was defined as stabilization or improvement in serum creatinine level. Angiographic patency was defined as less than 50% diameter recurrent arterial stenosis. RESULTS Stent placement was technically successful in 51 of 54 (94%) renal arteries. Technical failures were stent misdeployment requiring percutaneous stent retrieval (n = 2) and inadvertent placement distal to the desired position (n = 1). Complications included acute stent thrombosis (n = 1) and early initiation of hemodialysis (within 30 days; n = 1). There were two periprocedural deaths. With use of life-table analysis, clinical benefit was seen in 78% of patients at 6 months (n = 36), 72% at 1 year (n = 24), 62% at 2 years (n = 12), and 54% at 3 years (n = 3). In patients with clinical benefit, average creatinine level was reduced from 2.21 mg/dL +/- 0.91 before treatment to 2.05 mg/dL +/- 1.05 after treatment (P = .018). Lower initial serum creatinine level was associated with a better chance of clinical benefit (P = .05). No other variables affected outcome, including patient age, sex, diabetes, implanted stent diameter, unilateral versus bilateral stent placement, or ostial versus nonostial stent positioning. Conventional catheter angiography or spiral computed tomographic (CT) angiography performed in 19 patients (28 stents) at a mean interval of 12.5 months demonstrated primary patency in 75%. Maintained stent patency appeared to correlate with renal functional benefit. CONCLUSIONS Percutaneous renal artery stent placement for angioplasty failures or restenoses provides clinical benefit in most patients with ischemic nephropathy.

Livedo reticularis, rhabdomyolysis, massive intestinal infarction, and death after carbon dioxide arteriography

In patients with renal insufficiency or hypersensitivity to iodinated contrast material, carbon dioxide gas (CO2) is generally considered a safe alternative contrast media for digital subtraction angiography. However, we herein report a previously undescribed fatal complication of CO2 angiography in a patient with acute renal dysfunction and congestive heart failure. The possible pathogenetic mechanisms of this complication are discussed.

Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis

Background The post‐thrombotic syndrome frequently develops in patients with proximal deep‐vein thrombosis despite treatment with anticoagulant therapy. Pharmacomechanical catheter‐directed thrombolysis (hereafter “pharmacomechanical thrombolysis”) rapidly removes thrombus and is hypothesized to reduce the risk of the post‐thrombotic syndrome. Methods We randomly assigned 692 patients with acute proximal deep‐vein thrombosis to receive either anticoagulation alone (control group) or anticoagulation plus pharmacomechanical thrombolysis (catheter‐mediated or device‐mediated intrathrombus delivery of recombinant tissue plasminogen activator and thrombus aspiration or maceration, with or without stenting). The primary outcome was development of the post‐thrombotic syndrome between 6 and 24 months of follow‐up. Results Between 6 and 24 months, there was no significant between‐group difference in the percentage of patients with the post‐thrombotic syndrome (47% in the pharmacomechanical‐thrombolysis group and 48% in the control group; risk ratio, 0.96; 95% confidence interval [CI], 0.82 to 1.11; P=0.56). Pharmacomechanical thrombolysis led to more major bleeding events within 10 days (1.7% vs. 0.3% of patients, P=0.049), but no significant difference in recurrent venous thromboembolism was seen over the 24‐month follow‐up period (12% in the pharmacomechanical‐thrombolysis group and 8% in the control group, P=0.09). Moderate‐to‐severe post‐thrombotic syndrome occurred in 18% of patients in the pharmacomechanical‐thrombolysis group versus 24% of those in the control group (risk ratio, 0.73; 95% CI, 0.54 to 0.98; P=0.04). Severity scores for the post‐thrombotic syndrome were lower in the pharmacomechanical‐thrombolysis group than in the control group at 6, 12, 18, and 24 months of follow‐up (P<0.01 for the comparison of the Villalta scores at each time point), but the improvement in quality of life from baseline to 24 months did not differ significantly between the treatment groups. Conclusions Among patients with acute proximal deep‐vein thrombosis, the addition of pharmacomechanical catheter‐directed thrombolysis to anticoagulation did not result in a lower risk of the post‐thrombotic syndrome but did result in a higher risk of major bleeding. (Funded by the National Heart, Lung, and Blood Institute and others; ATTRACT ClinicalTrials.gov number, NCT00790335.)