Daizo Kawasaki

Long-term results of direct and indirect endovascular revascularization based on the angiosome concept in patients with critical limb ischemia presenting with isolated below-the-knee lesions

OBJECTIVE We compared clinical outcomes between limbs with and without achievement of feeding artery flow by endovascular therapy (EVT) based on the angiosome concept in critical limb ischemia (CLI) patients with isolated below-the-knee (BTK) lesions and assessed factors influencing major amputation (MA). METHOD We analyzed 369 limbs from 329 consecutive patients (224 men; age, 70 ± 11 years) with ischemic ulceration or gangrene, or both, presenting with isolated BTK lesions (Rutherford class 5, 270 limbs; class 6, 99 limbs) with a pretreatment ankle-brachial index of 0.79 ± 0.26. Patients underwent successful EVT, without bypass surgery. Limbs were classified into direct (n = 200) and indirect (n = 169) groups by whether feeding artery flow to the site of ulceration or gangrene was successfully achieved, based on the angiosome concept. Unadjusted and adjusted (by propensity score matching) between-group rates of amputation-free survival (AFS) and freedom from major amputation (MA) and major adverse limb event (MALE) were compared by Kaplan-Meier analysis and the log-rank test. The independent determinants of MA in the direct and indirect groups were explored by multivariable analysis. RESULTS During follow-up (mean, 18 ± 16 months), the overall limb salvage rate was 81% (300 of 369), death occurred in 36% (119 of 329), and the reintervention rate was 31% (114 of 369). After propensity score adjustment, the estimated (± standard error) rates for AFS (49% ± 8% vs 29% ± 6%; P = .0002), freedom from MALE (51% ± 8% vs 28% ± 8%, P = .008), and major amputation (82% ± 5% vs 68% ± 5%, P = .01) were significantly higher in the direct group than in the indirect group for up to 4 years after the index procedure. After multivariable Cox proportional analysis, the independent factors associated with major amputation were hemoglobin A(1c) level (hazard ratio [HR], 1.4; 95% confidential interval [CI], 1.1-1.9; P = .006) and cilostazol administration (HR, 0.28; 95% CI, 0.11-0.70; P = .006) in the direct group, and C-reactive protein level (HR, 1.2; 95% CI, 1.1-1.4; P = .002) in the indirect group. CONCLUSION Achieving direct flow by angioplasty based on the angiosome concept in CLI patients with isolated BTK lesions is clinically important for AFS and freedom from MA and MALE. Limb salvage factors appear to differ between patients with and without direct flow from the feeding artery after EVT.

Endovascular Treatment for Infrainguinal Vessels in Patients With Critical Limb Ischemia OLIVE Registry, a Prospective, Multicenter Study in Japan With 12-Month Follow-up

Background—Recent technical advances have made endovascular treatment (EVT) an alternative first-line treatment for critical limb ischemia. Methods and Results—A prospective multicenter study was conducted to evaluate the clinical outcomes of 314 Japanese critical limb ischemia patients (mean age, 73±10 years) with infrainguinal arterial lesions who underwent EVT. Patients were enrolled from December 2009 to July 2011 and were followed-up for 12 months. The primary end point was amputation-free survival (AFS) at 12 months. Secondary end points were anatomic, clinical, and hemodynamic measures, including 12-month freedom from major adverse limb events. The 12-month AFS rate was 74%, with body mass index <18.5 (hazard ratio [HR], 2.22; P=0.008), heart failure (HR, 1.73; P=0.04), and wound infection (HR, 1.89; P=0.03) associated with a poor prognosis for AFS. The 12-month major adverse limb event-free rate was 88%, with hemodialysis (HR, 1.98; P=0.005), heart failure (HR, 1.69; P=0.02), and Rutherford classification 6 (HR, 2.25; P=0.002) associated with a poor prognosis for major adverse limb events. The median time for wound healing was 97 days, with body mass index <18.5 (HR, 0.54; P=0.03) and wound infection (HR, 0.60; P=0.04) being significant risk factors for unhealed wounds after EVT. At 12 months, 34% had undergone reintervention (bypass surgery, 2.6%; repeat EVT, 31.7%), and 73% were major adverse event–free. Conclusions—The high reintervention rate notwithstanding, EVT was an effective treatment for Japanese critical limb ischemia patients with infrainguinal disease, with satisfactory AFS and major adverse limb event-free rates. The results of this study will be helpful for the future evaluation of critical limb ischemia therapy. Clinical Trial Registration—URL: http://www.umin.ac.jp/ctr. Unique identifier: UMIN000002830.

OCT Assessment of Thin-Cap Fibroatheroma Distribution in Native Coronary Arteries

OBJECTIVES We evaluated the geographic distribution of thin-cap fibroatheromas (TCFAs) in the coronary arteries using optical coherence tomography (OCT), a high-resolution imaging modality. BACKGROUND Plaque rupture is the most frequent cause of acute myocardial infarction (AMI). It has been recognized that TCFA is the primary plaque type at the site of plaque rupture. METHODS We performed 3-vessel OCT examinations in 55 patients: 35 AMI and 20 stable angina pectoris patients. The criteria for TCFA in an OCT image was a lipid-rich plaque with fibrotic cap thickness <65 microm. The distance between each TCFA location and the respective coronary artery ostium was measured with motorized OCT imaging pullback. The total length of all 3 coronary arteries imaged by OCT pullbacks was 82 +/- 21 mm in the left anterior descending coronary artery (LAD), 67 +/- 26 mm in the left circumflex coronary artery (LCx), and 104 +/- 32 mm in the right coronary artery (RCA). RESULTS OCT detected 94 TCFAs in 165 coronary arteries. The minimum fibrous-cap thickness of TCFAs was 57.4 +/- 5.4 microm in AMI patients, and 55.9 +/- 7.3 microm in stable angina pectoris patients (p = 0.4). Of the total of 94 TCFAs, 28 were detected in the LAD, 18 in the LCx, and 48 in the RCA. Most LAD TCFAs were located between 0 and 30 mm from the LAD ostium (76%). Conversely, LCx and RCA TCFAs were evenly distributed throughout the entire coronary length. The clustering of the TCFAs was similar in culprit segments as compared with nonculprit segments. In AMI patients, most LAD TCFAs were distributed near side branches, mainly positioned opposite the side branch bifurcation. CONCLUSIONS Three-vessel OCT imaging showed that TCFAs tend to cluster in predictable spots within the proximal segment of the LAD, but develop relatively evenly in the LCx and RCA arteries.

Angiographic Restenosis and Its Clinical Impact after Infrapopliteal Angioplasty

OBJECTIVE To assess 3- and 12-month angiographic restenosis rates and their clinical impact after infrapopliteal angioplasty. DESIGN Prospective multicenter study. MATERIALS AND METHODS We analyzed 68 critical ischemic limbs (tissue loss: 58 limbs) from 63 consecutive patients due to isolated infrapopliteal lesions who underwent angioplasty alone. Primary endpoint was 3-month angiographic restenosis rate; secondary endpoints were 12-month angiographic restenosis rate, and 3- and 12-month rates of mortality, major amputation and reintervention. Three- and 12-month frequency of ambulatory status and of freedom from ischemic symptoms, and time to wound healing in the ischemic wound group, were compared between restenotic and non-restenotic groups. Angiographic restenosis predictors were assessed by multivariable analysis. RESULTS 95% of cases had 3-month angiography; restenosis rate was 73%: 40% restenosis and 33% re-occlusion. Twelve-month follow-up angiography was conducted for the patients without 3-month angiographic restenosis, and restenosis rate at 12 months was 82%. Non-administration of cilostazol and statin, and chronic total occlusion were 3-month angiographic restenosis predictors. Three- and 12-month mortality was 5% and 12%, respectively. Despite no patients having undergone amputation, 15% had persistent ischemic symptoms, and 48% of limbs underwent reintervention within 12 months. During the same study period, ambulatory status and limbs with complete healing were more frequently observed in the non-restenosis group than in the restenosis group. In the tissue loss group, time to wound healing in the restenosis group was longer than in the non-restenosis group (127 days vs. 66 days, p = 0.02). CONCLUSION The extremely high angiographic restenosis rate after infrapopliteal angioplasty may adversely impact clinical status improvement.

Cilostazol Reduces Angiographic Restenosis After Endovascular Therapy for Femoropopliteal Lesions in the Sufficient Treatment of Peripheral Intervention by Cilostazol Study

Background— It remains unclear whether cilostazol, which has been shown to improve the clinical outcomes of endovascular therapy for femoropopliteal lesions, also reduces angiographic restenosis. Methods and Results— The Sufficient Treatment of Peripheral Intervention by Cilostazol (STOP-IC) study investigated whether cilostazol reduces the 12-month angiographic restenosis rate after percutaneous transluminal angioplasty with provisional nitinol stenting for femoropopliteal lesions. Two hundred patients with femoropopliteal lesions treated from March 2009 to April 2011 at 13 cardiovascular centers were randomly assigned 1:1 to receive oral aspirin with or without cilostazol. The primary end point was 12-month angiographic restenosis rate. Secondary end points were the restenosis rate on duplex ultrasound, the rate of major adverse cardiac events, and target lesion event-free survival. Researchers evaluated all follow-up data and assessed the end points in a blinded fashion. The mean lesion length and reference vessel diameter at the treated segment were 128±86 mm and 5.4±1.4 mm, respectively. The frequency of stent used was similar between groups (88% versus 90% in the cilostazol and noncilostazol group, respectively, P=0.82). During the 12-month follow-up period, 11 patients died and 152 patients (80%) had evaluable angiographic data at 12 months. The angiographic restenosis rate at 12 months was 20% (15/75) in the cilostazol group versus 49% (38/77) in the noncilostazol group (P=0.0001) by intention-to-treat analysis. The cilostazol group also had a significantly higher event-free survival at 12 months (83% versus 71%, P=0.02), although cardiovascular event rates were similar in both groups. Conclusions— Cilostazol reduced angiographic restenosis after percutaneous transluminal angioplasty with provisional nitinol stenting for femoropopliteal lesions. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00912756; and URL: https://www.umin.ac.jp. Unique identifier: UMIN000002091.

Frequency and predictor of coronary thin-cap fibroatheroma in patients with acute myocardial infarction and stable angina pectoris a 3-vessel optical coherence tomography study.

To the Editor: Autopsy studies suggest that the main mechanisms of acute myocardial infarction (AMI) are plaque ruptures followed by thrombus formation ([1][1]). Post-mortem studies have shown that rupture-prone plaques, known as thin-cap fibroatheromas (TCFAs), have certain characteristics: a thin

1-Year Results of the ZEPHYR Registry (Zilver PTX for the Femoral Artery and Proximal Popliteal Artery): Predictors of Restenosis.

OBJECTIVES This study sought to assess the rate and predictors of 1-year restenosis after drug-eluting stent implantation for femoropopliteal (FP) lesions in patients with peripheral arterial disease. BACKGROUND Zilver PTX, a paclitaxel-eluting stent for FP lesions, provides superior outcomes to angioplasty and bare-metal stents in clinical trials. However, its real-world outcomes and the associated features remain unclear. METHODS This was a prospective multicenter study enrolling 831 FP lesions (797 limbs, 690 patients) treated by Zilver PTX implantation. The primary endpoint was 1-year restenosis. Secondary endpoints included major adverse limb event and stent thrombosis. RESULTS Mean lesion length was 17 ± 10 cm. One-year restenosis, major adverse limb event, and stent thrombosis rates were 37%, 22%, and 2%, respectively. The generalized linear mixed model showed that lesion length ≥16 cm assessed by angiography and distal external elastic membrane area ≤27 mm(2) and minimum stent area ≤12 mm(2) assessed by intravascular ultrasound were independent risk factors for restenosis. One-year restenosis rates were 15% in cases with none of these risk factors and 50% in those with ≥2 risk factors. CONCLUSIONS The current study demonstrated 1-year real-world outcomes after drug-eluting stent treatment for FP lesions, including challenging ones in clinical practice. Lesion length, external elastic membrane area, and minimum stent area were independent predictors for restenosis. (Zilver PTX for the Femoral Artery and Proximal Popliteal Artery-Prospective Multicenter Registry [ZEPHYR]; UMIN000008433).

Clinical efficacy of endovascular therapy for patients with critical limb ischemia attributable to pure isolated infrapopliteal lesions

BACKGROUND Prognosis of endovascular therapy (EVT) for isolated infrapopliteal lesions has not been adequately studied. We investigated and risk-stratified long-term prognosis after EVT for critical limb ischemia (CLI) attributable to isolated infrapopliteal lesions. METHODS Between March 2004 and October 2010, 884 patients (1057 limbs) with CLI attributable to isolated infrapopliteal lesions who underwent EVT with angioplasty alone were enrolled. Outcome measures were freedom from major adverse limb events with perioperative death (MALE+POD) and amputation-free survival. Cox proportional hazards models were used to assess independent predictors for these outcomes. RESULTS Freedom from MALE+POD was 82 ± 1% and 74 ± 2% at 1 and 5 years, respectively. Risk factors associated with MALE+POD were age ≥80 years (adjusted hazard ratio [HR], 0.4; P < .001), nonambulatory status (HR, 2.0; P < .001), albumin <3.0 g/dL (HR, 1.4; P < .0001), Rutherford 6 (HR, 2.2; P < .001), C-reactive protein ≥3.0 mg/dL (HR, 2.1; P < .001), and below-the-ankle disease (HR, 2.0; P < .001). One- and 5-year amputation-free survival was 71 ± 2% and 38 ± 3%, respectively. Risk factors associated with major amputation/mortality were nonambulatory status (adjusted HR, 2.1; P < .001), body mass index <18.5 kg/m(2) (HR, 1.4; P = .02), albumin <3.0 g/dL (HR, 1.8; P < .0001), end-stage renal disease (HR, 1.4; P = .004), ejection fraction <50% (HR, 1.6; P < .001), Rutherford 6 (HR, 1.9; P < .001), C-reactive protein ≥3.0 mg/dL (HR, 1.7; P < .0001), and below-the-ankle disease (HR, 1.8; P < .001). In patients with more than four risk factors, both end points at 1 year were below the 71% suggested efficacy objective performance goal. CONCLUSIONS Long-term clinical outcomes were acceptable after EVT for patients with CLI due to pure isolated infrapopliteal lesion. Risk stratification by baseline characteristics is useful in estimating long-term prognosis.

CorrespondenceResearch CorrespondenceFrequency and Predictor of Coronary Thin-Cap Fibroatheroma in Patients With Acute Myocardial Infarction and Stable Angina Pectoris: A 3-Vessel Optical Coherence Tomography Study

To the Editor: Autopsy studies suggest that the main mechanisms of acute myocardial infarction (AMI) are plaque ruptures followed by thrombus formation ([1][1]). Post-mortem studies have shown that rupture-prone plaques, known as thin-cap fibroatheromas (TCFAs), have certain characteristics: a thin

Prognosis of Critical Limb Ischemia in Hemodialysis Patients After Isolated Infrapopliteal Balloon Angioplasty: Results From the Japan Below-the-Knee Artery Treatment (J-BEAT) Registry

Purpose To evaluate the long-term clinical results after isolated infrapopliteal balloon angioplasty for critical limb ischemia (CLI) in end-stage renal disease patients on hemodialysis. Methods Between April 2004 and October 2010, 406 CLI consecutive patients (275 men; mean age 71±11 years) who underwent balloon angioplasty for primary treatment of isolated infrapopliteal artery lesions in 465 limbs were enrolled in a multicenter, nonrandomized registry. The patients were classified into 2 groups, those on hemodialysis (242 patients with 283 limbs) and those not (164 patients with 182 limbs), for a retrospective comparative study of clinical outcomes [target extremity revascularization (TER), major amputation (MA), and survival] at an average 3.4±1.9 years. Results Freedom from TER at 5 years was lower in the hemodialysis patients (48.3% vs. 65.4% in non-hemodialysis patients, p<0.001); 9.9% of hemodialysis patients had undergone bypass surgery in contrast to 3.8% of non-hemodialysis patients (p=0.011). Freedom from MA was 77.1% in hemodialysis patients and 85.1% in non-hemodialysis patients at 5 years (p=0.058). Hemodialysis patients had significantly poorer survival (24.3% vs. 48.0%, p<0.001) and MA-free survival (20.8% vs. 42.9%, p<0.001) than non-hemodialysis patients at 5 years. Multivariate predictors of MA or all-cause death were non-ambulatory status (p<0.001), gangrene (p=0.036), and higher C-reactive protein levels (p=0.048). Conclusion Although hemodialysis patients have a higher TER rate compared to the general population, the long-term limb salvage rate after balloon angioplasty for isolated infrapopliteal lesions is acceptable; nevertheless, the MA-free survival rate is very low.