Peter Soukas

Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina : A phase I/IIa double-blind, randomized controlled trial

Background— A growing population of patients with coronary artery disease experiences angina that is not amenable to revascularization and is refractory to medical therapy. Preclinical studies have indicated that human CD34+ stem cells induce neovascularization in ischemic myocardium, which enhances perfusion and function. Methods and Results— Twenty-four patients (19 men and 5 women aged 48 to 84 years) with Canadian Cardiovascular Society class 3 or 4 angina who were undergoing optimal medical treatment and who were not candidates for mechanical revascularization were enrolled in a double-blind, randomized (3:1), placebo-controlled dose-escalating study. Patients received granulocyte colony-stimulating factor 5 &mgr;g · kg−1 · d−1 for 5 days with leukapheresis on the fifth day. Selection of CD34+ cells was performed with a Food and Drug Administration–approved device. Electromechanical mapping was performed to identify ischemic but viable regions of myocardium for injection of cells (versus saline). The total dose of cells was distributed in 10 intramyocardial, transendocardial injections. Patients were required to have an implantable cardioverter-defibrillator or to temporarily wear a LifeVest wearable defibrillator. No incidence was observed of myocardial infarction induced by mobilization or intramyocardial injection. The intramyocardial injection of cells or saline did not result in cardiac enzyme elevation, perforation, or pericardial effusion. No incidence of ventricular tachycardia or ventricular fibrillation occurred during the administration of granulocyte colony-stimulating factor or intramyocardial injections. One patient with a history of sudden cardiac death/ventricular tachycardia/ventricular fibrillation had catheter-induced ventricular tachycardia during mapping that required cardioversion. Serious adverse events were evenly distributed. Efficacy parameters including angina frequency, nitroglycerine usage, exercise time, and Canadian Cardiovascular Society class showed trends that favored CD34+ cell–treated patients versus control subjects given placebo. Conclusions— A randomized trial of intramyocardial injection of autologous CD34+ cells in patients with intractable angina was completed that provides evidence for feasibility, safety, and bioactivity. A larger phase IIb study is currently under way to further evaluate this therapy.

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).

Predicting blood pressure improvement in hypertensive patients after renal artery stent placement: Renal fractional flow reserve

Background: Renal stent placement improves or cures hypertension in only 60–70% of patients with renal artery stenosis (RAS) and uncontrolled hypertension. There is a need to better identify patients who are likely to respond to percutaneous renal revascularization. We investigated whether an abnormal renal fractional flow reserve (FFR) would predict blood pressure improvement in patients undergoing renal artery stent placement. Methods: We prospectively enrolled 17 patients with unilateral RAS and medically refractory hypertension (BP > 140/90 mm Hg). Renal FFR was measured at maximal hyperemia induced by papaverine followed by renal stent placement. Blood pressure improvement was defined as a blood pressure of ≤140/90 mm Hg or an absolute decrease in diastolic blood pressure by 15 mm Hg on the same or less number of medications. Patients not meeting the above criteria were nonresponders. Results: Renal stent placement was successful in all patients. The average follow‐up was 10 ± 2 months. In patients with an abnormal renal FFR (< 0.80) blood pressure improved at 90 days in 86% compared with 30% in the normal renal FFR group (P = 0.04). Translesional pressure gradients (resting, peak, or hyperemic) alone failed to differentiate blood pressure responders from nonresponders. Conclusions: Renal FFR is a promising tool to identify patients likely to benefit following renal stent placement. This finding was independent of translesional pressure gradients, which did not predict blood pressure improvement. The ability to segregate patients with RAS and coexisting hypertension from those with renovascular hypertension may help clinicians select patients most likely to benefit from revascularization.

Randomized Controlled Study of Excimer Laser Atherectomy for Treatment of Femoropopliteal In-Stent Restenosis: Initial Results From the EXCITE ISR Trial (EXCImer Laser Randomized Controlled Study for Treatment of FemoropopliTEal In-Stent Restenosis)

OBJECTIVES The purpose of this study was to evaluate the safety and efficacy of excimer laser atherectomy (ELA) with adjunctive percutaneous transluminal angioplasty (PTA) versus PTA alone for treating patients with chronic peripheral artery disease with femoropopliteal bare nitinol in-stent restenosis (ISR). BACKGROUND Femoropopliteal stenting has shown superiority to PTA for lifestyle-limiting claudication and critical limb ischemia, although treating post-stenting artery reobstruction, or ISR, remains challenging. METHODS The multicenter, prospective, randomized, controlled EXCITE ISR (EXCImer Laser Randomized Controlled Study for Treatment of FemoropopliTEal In-Stent Restenosis) trial was conducted across 40 U.S. centers. Patients with Rutherford Class 1 to 4 and lesions of target lesion length ≥4 cm, vessel diameter 5 to 7 mm were enrolled and randomly divided into ELA + PTA and PTA groups by a 2:1 ratio. The primary efficacy endpoint was target lesion revascularization (TLR) at 6-month follow up. The primary safety endpoint was major adverse event (death, amputation, or TLR) at 30 days post-procedure. RESULTS Study enrollment was stopped at 250 patients due to early efficacy demonstrated at a prospectively-specified interim analysis. A total of 169 ELA + PTA subjects (62.7% male; mean age 68.5 ± 9.8 years) and 81 PTA patients (61.7% male; mean age 67.8 ± 10.3 years) were enrolled. Mean lesion length was 19.6 ± 12.0 cm versus 19.3 ± 11.9 cm, and 30.5% versus 36.8% of patients exhibited total occlusion. ELA + PTA subjects demonstrated superior procedural success (93.5% vs. 82.7%; p = 0.01) with significantly fewer procedural complications. ELA + PTA and PTA subject 6-month freedom from TLR was 73.5% versus 51.8% (p < 0.005), and 30-day major adverse event rates were 5.8% versus 20.5% (p < 0.001), respectively. ELA + PTA was associated with a 52% reduction in TLR (hazard ratio: 0.48; 95% confidence interval: 0.31 to 0.74). CONCLUSIONS The EXCITE ISR trial is the first large, prospective, randomized study to demonstrate superiority of ELA + PTA versus PTA alone for treating femoropopliteal ISR. (Randomized Study of Laser and Balloon Angioplasty Versus Balloon Angioplasty to Treat Peripheral In-stent Restenosis [EXCITE ISR]; NCT01330628).

Correlations between coronary flow reserve measured with a Doppler guide wire and treadmill exercise testing

We compared exercise test results to a physiologic depiction of stenosis severity, coronary flow reserve (CFR), measured with a Doppler guide wire in 35 patients with single-vessel coronary disease. Group 1 (n = 21) had abnormal CFR, and group 2 (n = 14) had normal CFR. In group 1, 14 of 21 had ST-segment depression versus 3 of 14 in group 2 (p < 0.01). Exercise treadmill time (Bruce protocol) was normalized to the age- and sex-predicted time. Exercise time and normalized exercise time were less in group 1 (5.6 +/- 2.3 vs 9.9 +/- 1.8 min and 0.82 +/- 0.32 vs 1.25 +/- 0.23, p < 0.00001). Having either ST-segment depression or a normalized exercise time <1 during exercise had a 95% sensitivity, 71% specificity, and 86% predictive accuracy in identifying abnormal CFR. Coronary stenoses and minimal lumen diameter were similar in groups 1 and 2. By using stepwise logistical regression analysis, exercise time and ST-segment depression predicted CFR with a total r2 of 0.51. Minimal lumen diameter did not significantly add to the model. Exercise test variables, ST-segment depression, and exercise time are predictive of the physiologic significance of coronary lesions.

Rheolytic Pharmacomechanical Thrombectomy for the Management of Acute Limb Ischemia: Results From the PEARL Registry.

Purpose: To present the results of rheolytic pharmacomechanical thrombectomy (PMT) for the management of acute limb ischemia (ALI) as reported in the PEARL Registry (PEripheral Use of AngioJet Rheolytic Thrombectomy with a variety of catheter Lengths). Methods: A total of 283 patients (mean age 65±13 years; 170 men) presenting with ALI undergoing treatment with the AngioJet System at participating institutions were enrolled in the registry. Rutherford ALI categories included 26% with viable limbs, 38% with marginally threatened limbs, 35% with immediately threatened limbs, and <1% with irreversible damage. Procedure and follow-up data were collected for the calculation of outcomes. To control for patient selection bias, propensity score matching was used to compare outcomes for patients undergoing PMT with or without catheter-directed thrombolysis (CDT). Results: Procedure success was achieved in 235 (83%) of 283 patients. Half of the procedures (147, 52%) were completed without the need for adjunctive CDT. At 12-month follow-up, amputation-free survival and freedom from mortality were 81% and 91%, respectively; 12-month freedom from bleeding requiring transfusion was 91%, and freedom from renal failure was 95%. Subgroup analysis revealed significantly better outcomes in patients without infrapopliteal involvement and those who underwent PMT without CDT. In the matched cohorts, higher rates of procedure success, 12-month amputation-free survival, and 12-month freedom from amputation were observed in the PMT without CDT group (88% vs 74%, p=0.021; 87% vs 72%, p=0.028; 96% vs 81%, p=0.01, respectively). Conclusions: The results support the use of PMT as a first-line treatment for ALI, providing a rapid reperfusion to the extremity, reduced procedure time, and an acceptable risk profile without compromising limb salvage.

Use of a novel embolic filter in carotid artery stenting: 30-Day results from the EMBOLDEN Clinical Study

The EMBOLDEN study was conducted to test the safety and efficacy of a novel emboli protection filter design for use in carotid artery stenting (CAS) in patients with severe carotid stenosis who were at high risk of operative complications from carotid endarterectomy (CEA).

SEX DIFFERENCES IN DISEASE SPECIFIC HEALTH STATUS MEASURES IN PATIENTS WITH SYMPTOMATIC PERIPHERAL ARTERIAL DISEASE

Peripheral arterial disease (PAD) is associated with poor overall function and quality of life (QOL). Whether sex differences exist in PAD-specific health status is unknown. We examined sex differences in PAD-specific physical function, symptom frequency, social function, treatment satisfaction, and

Deep Vein Thrombosis: Final Report of the Prospective Multicenter Pearl Registry on Endovascular Treatment.

with lower extremity swelling, and 13 (37%) presented with pain in addition to swelling. Two patients presented with abdominal and back pain, and two were noted to have pelvic congestion. Of the patients with IVC thrombosis, 14 (40%) were identified as having a thrombophilic disorder, with Factor V Leiden being the most common. Eight patients (24%) had May-Thurner iliac vein compression. Fourteen patients (40%) had previously undergone IVC filter placement and, of these, 12 filters had thrombosed. Twenty-nine patients (83%) with IVC thrombosis were treated with pharmacomechanical thrombolysis, and 28 patients (80%) also received stents extending into the IVC, 14 (50%) of these bilateral. Of these bilateral stents, four were kissing, while 10 were fenestrated. In patients with IVC thrombosis, primary patency for any iliocaval stent at 1 year was 46% (13/35) and 36% (5/14) for bilateral stents. Of the bilateral stents, for kissing and 30% (3/10) for fenestrated, with secondary patencies of 75% (3/4) and 57% (4/6), respectively. Nine patients (26%) experienced rethrombosis within 60 days, while eight patients (23%) experienced recurrence of thrombosis after 60 days, five of whom were also noncompliant with their anticoagulation. The most common perioperative complication was an access site hematoma (14%). Conclusions: IVC thrombosis in patients presenting with symptomatic venous outflow obstruction is not uncommon. These patients likely represent a subset of patients more refractory to endovascular treatment, based on higher disease burden, indwelling IVC filters, thrombophilic disease, and noncompliance. Despite this, pharmacomechanical thrombolysis and stenting of the IVC appear to be feasible endovascular therapies for patients who otherwise may not have treatment options.