Masashi Fukunaga

3-Year Outcomes of the OLIVE Registry, a Prospective Multicenter Study of Patients With Critical Limb Ischemia: A Prospective, Multi-Center, Three-Year Follow-Up Study on Endovascular Treatment for Infra-Inguinal Vessel in Patients With Critical Limb Ischemia.

OBJECTIVES This study sought to investigate the 3-year follow-up results of OLIVE registry patients. BACKGROUND Although favorable 12-month clinical outcomes after endovascular therapy (EVT) in OLIVE registry patients with critical limb ischemia (CLI) from infrainguinal disease have been reported, long-term results after EVT remain unknown. METHODS This was a prospective multicenter registry study that consecutively enrolled patients who received infrainguinal EVT for CLI. The primary outcome was 3-year amputation-free survival (AFS), whereas secondary outcome measures were 3-year freedom from major adverse limb events (MALE), wound-free survival, and wound recurrence rate. Prognostic predictors for each outcome were also elucidated by Cox proportional hazard regression analysis or the log-rank test. RESULTS The completion rate of 3-year follow-up was 95%. Three-year AFS, freedom from MALE, and wound-free survival rates were 55.2%, 84.0%, and 49.6%, respectively. Wound recurrence out to 3 years was 43.9%. After multivariable analysis, age (hazard ratio [HR]: 1.43, p = 0.001), body mass index ≤18.5 (HR: 2.17, p = 0.001), dialysis (HR: 2.91, p < 0.001), and Rutherford 6 (HR: 1.64, p = 0.047) were identified as predictors of 3-year major amputation or death. Statin use (HR: 0.28, p = 0.02), Rutherford 6 (HR: 2.40, p = 0.02), straight-line flow to the foot (HR: 0.27, p = 0.001), and heart failure (HR: 1.96, p = 0.04) were identified as 3-year MALE predictors. Finally, CLI due to isolated below-the-knee lesion was a wound recurrence predictor (HR: 4.28, p ≤ 0.001). Three-year survival, freedom from major amputation, and reintervention rates were 63.0%, 87.9%, and 43.2%. CONCLUSIONS In CLI patients with infrainguinal lesions, 3-year clinical results of EVT were reasonable despite high reintervention and moderate ulcer recurrence rate. (A Prospective, Multi-Center, Three-Year Follow-Up Study on Endovascular Treatment for Infra-Inguinal Vessel in Patients With Critical Limb Ischemia [OLIVE 3-Year Follow-Up Study]; UMIN000014759).

The Impact of Pravastatin Pre-Treatment on Periprocedural Microcirculatory Damage in Patients Undergoing Percutaneous Coronary Intervention

OBJECTIVES This study evaluated the effect of pravastatin pre-treatment on post-procedural index of microcirculatory resistance (IMR) values that are introduced for assessing the status of the microcirculation independently of the epicardial area. BACKGROUND Pre-treatment with statins decreased the incidence of cardiac enzyme increase after percutaneous coronary intervention (PCI). However, 2 different etiologies, distal embolization of atheroma or ischemia caused by side-branch occlusion, cannot be differentiated by measuring cardiac enzyme levels. METHODS Eighty patients with stable angina were randomly assigned to either pravastatin treatment (20 mg/day, n = 40) or no treatment (n = 40) 4 weeks before elective PCI. An intracoronary pressure/temperature sensor-tipped guidewire was used. Thermodilution curves were obtained during maximal hyperemia. The IMR was calculated from the ratio of the mean distal coronary pressure at maximal hyperemia to the inverse of mean hyperemic transit time. Creatine kinase-myocardial band and troponin I values were measured at baseline and at 8 and 24 h after PCI. RESULTS Post-PCI troponin I levels tended to be lower in patients with pravastatin treatment (median: 0.13 [interquartile range (IQR): 0.10 to 0.31] vs. 0.22 [IQR: 0.10 to 0.74] ng/ml, p = 0.1). However, patients with pravastatin treatment had significantly lower IMR than did patients without pravastatin treatment (median: 12.6 [IQR: 8.8 to 18.0] vs. 17.6 [IQR: 9.7 to 33.9], p = 0.007). Multivariate analysis revealed that the lack of pravastatin pre-treatment was the only independent predictor of post-PCI impaired IMR (p = 0.03). CONCLUSIONS Post-PCI measurement of the IMR confirmed that pre-treatment with pravastatin was associated with reduced microvascular dysfunction induced by PCI regardless of side branch occlusions. These data suggest that pre-treatment with statin is desired in patients undergoing elective PCI. (The Impact of Pravastatin Pretreatment on Periprocedural Microcirculatory Damage After Percutaneous Coronary Intervention; UMIN000002885).

Endothelium-dependent coronary vasomotor response and neointimal coverage of zotarolimus-eluting stents 3 months after implantation

Background Zotarolimus-eluting stents (ZES) have a higher rate of neointimal coverage than the first-generation drug-eluting stents on optical coherence tomography (OCT). Objective To determine whether neointimal coverage of stent struts detected by OCT can be used as a surrogate for endothelial function after ZES implantation. Design Cross-sectional observational study. Setting Three months after ZES implantation. Patients and methods OCT was performed in 20 patients with a ZES at 3 months after stent implantation to evaluate strut coverage. Endothelium-dependent coronary vasomotion was estimated by infusing incremental doses of acetylcholine into the coronary ostium. The vascular response was measured in the 10 mm segments proximal and distal to the stent. Results Of 20 ZES, 15 (75%) were covered completely with neointima, but the remaining 5 ZES had exposed struts. The high-dose acetylcholine infusion produced significant vasoconstriction in the proximal (−9.8±10.1%) and the distal stent segment (−29.7±22.7%). However, the degree of vasoconstriction to acetylcholine varied between individuals (from −0.6% to −77%). Although no relationship was observed between coronary vasomotor response (percentage change in diameter after acetylcholine administration) and average neointimal thickness, the number of cross-sections with uncovered struts showed an inverse correlation with coronary vasomotor response in proximal and distal stent segments (r=−0.57, p=0.007 and r=−0.83, p<0.001, respectively). Conclusions The existence of exposed struts was associated with abnormal vasoconstriction to acetylcholine at 3 months after ZES implantation. The findings suggest that complete neointimal coverage of stent struts assessed by OCT could be used as a surrogate for vasomotion impairment at 3 months after ZES implantation.

Endovascular therapy by CO2 angiography to prevent contrast‐induced nephropathy in patients with chronic kidney disease: A prospective multicenter trial of CO2 angiography registry

To assess the safety and efficacy of carbon dioxide (CO2) angiography‐guided endovascular therapy (EVT) for renal, iliofemoral artery disease.

Thermodilution-Derived Coronary Blood Flow Pattern Immediately After Coronary Intervention as a Predictor of Microcirculatory Damage and Midterm Clinical Outcomes in Patients With ST-Segment–Elevation Myocardial Infarction

Background—Despite a sufficient coronary blood flow after primary percutaneous coronary intervention for patients with ST-segment–elevation myocardial infarction; some patients have a poor outcome because of microcirculatory damage. This study evaluates whether the thermodilution-derived coronary blood flow parameters immediately after primary percutaneous coronary intervention predict early microvascular damage and midterm outcomes in patients with ST-segment–elevation myocardial infarction. Methods and Results—Using a pressure sensor/thermistor-tipped guidewire, we measured the index of microcirculatory resistance at maximum hyperemia, and coronary blood flow pattern was assessed from the thermodilution curves after successful primary percutaneous coronary intervention in 88 patients with ST-segment–elevation myocardial infarction. Coronary blood flow pattern was classified into 3 groups according to the shape of thermodilution curve: a narrow unimodal (n=41), a wide unimodal (n=32), or bimodal (n=15). All patients had contrast-enhanced cardiac magnetic resonance scans within 2 weeks. The index of microcirculatory resistance values were significantly higher both in a wide unimodal and in a bimodal groups than in a narrow unimodal group (65±41 and 76±38 versus 20±9U; P<0.001). Bimodal group had higher prevalence of microvascular obstruction on contrast-enhanced cardiac magnetic resonance when compared with the other groups (100%, 78%, and 30%; P<0.001). Patients in bimodal group had a higher risk of death and heart failure rehospitalization at 6 months (73%, 6.3%, 7.3%; P<0.001). Multivariate analysis revealed that bimodal shape of the thermodilution curve was the only independent predictor of cardiac death at 6 months after ST-segment–elevation myocardial infarction (P<0.01). Conclusions—A bimodal shape of the thermodilution curve, which may indicate myocardial edema and consequent extrinsic compression of the capillary network, is associated with microcirculatory damage and poor midterm clinical outcomes rather than index of microcirculatory resistance value itself.

Multiple complex coronary atherosclerosis in diabetic patients with acute myocardial infarction: a three-vessel optical coherence tomography study

AIMS The main cause of acute myocardial infarction (AMI) is the disruption of a thin-cap fibroatheroma (TCFA) and subsequent thrombosis. Mortality increases in diabetic patients due to cardiovascular events; there may be differences in the vulnerable plaques between diabetic and non-diabetic patients. We used optical coherence tomography (OCT) to assess the incidence of vulnerable plaques in diabetic patients with AMI. METHODS AND RESULTS OCT was performed in all three major coronary arteries of 70 AMI patients: 48 non-diabetic and 22 diabetic patients. The OCT criterion for TCFA was the presence of both a lipid-rich plaque composition and a fibrotic cap thickness of <65 µm. A ruptured plaque contains a cavity in contact with a lumen and a residual fibrous cap. OCT identified 68 plaque ruptures (1.0 per patient; range, 0-3) and 162 TCFAs (2.3 per patient; range, 0-5). The incidences of plaque rupture and TCFA at culprit lesions were similar. However, non-culprit-lesion TCFAs were observed more frequently in diabetic patients than in non-diabetic patients. CONCLUSIONS Although the prevalence of vulnerable plaque in culprit lesions was similar between diabetic and non-diabetic patients, vulnerable plaques were observed in non-culprit lesions more in diabetic patients than in non-diabetic patients.

Ex vivo assessment of neointimal characteristics after drug-eluting stent implantation: Optical coherence tomography and histopathology validation study.

BACKGROUND Optical coherence tomography (OCT) is one of the tools trying to distinguish neoatherosclerosis from other neointimal tissue but its role has to be still validated. This study evaluated the diagnostic accuracy of OCT for characterization of lipid-atherosclerotic neointima following drug-eluting stent (DES) implantation. METHODS Twelve stented coronary arteries from the 7 autopsy hearts were imaged by OCT. These OCT images were compared with histology. By OCT, the morphological appearances of neointima were classified into three patterns: homogeneous pattern, heterogeneous pattern with visible strut, or heterogeneous pattern with invisible strut. RESULTS Of 21 histological cross-sections, 6 were categorized as homogeneous patterns (29%), 11 as heterogeneous patterns with visible stent strut (52%), and 4 as heterogeneous patterns with invisible stent strut (19%). All homogeneous patterns were composed of smooth muscle cells with collagen fibers. The heterogeneous patterns with visible stent strut included proteoglycan-rich myxomatous matrix and calcium deposition. On the other hand, the heterogeneous patterns with invisible stent strut comprised atheromatous tissue, including a large amount of foam cell accumulation (25%) or large fibroatheroma/necrotic core (75%) inside the stent struts within neointima. The optical attenuation coefficient was highest in the heterogeneous pattern with invisible stent strut due to scattering of light by atheromatous tissue. CONCLUSION The heterogeneous patterns with invisible stent strut on OCT imaging identify the presence of lipid-atherosclerotic tissue within neointima after DES. This may suggest the potential capability of OCT based on visualization of stent struts for discriminating atheromatous formation within neointima from other neointimal tissue.

Intravascular Ultrasound-Derived Stent Dimensions as Predictors of Angiographic Restenosis Following Nitinol Stent Implantation in the Superficial Femoral Artery.

Purpose: To identify intravascular ultrasound (IVUS) measurements that can predict angiographic in-stent restenosis (ISR) following nitinol stent implantation in superficial femoral artery (SFA) lesions. Methods: A retrospective review was conducted of 97 patients (mean age 72.9±8.9 years; 63 men) who underwent IVUS examination during endovascular treatment of 112 de novo SFA lesions between July 2012 and December 2014. Self-expanding bare stents were implanted in 46 lesions and paclitaxel-eluting stents in 39 lesions. Six months after stenting, follow-up angiography was conducted to assess stent patency. The primary endpoint was angiographic ISR determined by quantitative vascular angiography analysis at the 6-month follow-up. Variables associated with restenosis were sought in multivariate analysis; the results are presented as the odds ratio (OR) and 95% confidence interval (CI). Results: At follow-up, 27 (31.8%) angiographic ISR lesions were recorded. The lesions treated with uncoated stents were more prevalent in the ISR group compared with the no restenosis group (74.1% vs 44.8%, p=0.02). Lesion length was longer (154.4±79.5 vs 109.0±89.3 mm, p=0.03) and postprocedure minimum stent area (MSA) measured by IVUS was smaller (13.9±2.8 vs 16.3±1.6 mm2, p<0.001) in the ISR group. Multivariate analysis revealed that bare stent use (OR 7.11, 95% CI 1.70 to 29.80, p<0.01) and longer lesion length (OR 1.08, 95% CI 1.01 to 1.16, p=0.04) were predictors of ISR, while increasing postprocedure MSA (OR 0.58, 95% CI 0.41 to 0.82, p<0.01) was associated with lower risk of ISR. Receiver operating characteristic analysis identified a MSA of 15.5 mm2 as the optimal cutpoint below which the incidence of restenosis increased (area under the curve 0.769). Conclusion: Postprocedure MSA can predict ISR in SFA lesions, which suggests that adequate stent enlargement during angioplasty might be required for superior patency.

Safety and Efficacy of Carbon Dioxide and Intravascular Ultrasound-Guided Stenting for Renal Artery Stenosis in Patients With Chronic Renal Insufficiency

We evaluated the feasibility, safety, and mid-term outcomes of renal artery stenting using carbon dioxide (CO2) digital subtraction angiography and intravascular ultrasound (IVUS) for patients with renal insufficiency and significant atherosclerotic renal artery stenosis (RAS). Eighteen consecutive patients with chronic renal insufficiency underwent renal artery stenting under the guidance of CO2 angiography and IVUS without contrast media. Renal function and blood pressure were assessed pre- and postintervention. A total of 27 de novo RAS in 18 patients (15 males; mean age: 72 ± 9 years) with renal insufficiency were treated by renal artery stenting with the combined use of the CO2 angiography and IVUS without any procedural complications. Although the mean serum creatinine concentration preprocedure and 6 months after treatment did not change (2.7 ± 1.0-2.4 ± 1.1 mg/dL), blood pressure significantly decreased 6 months after stenting (158 ± 10-147 ± 11 mm Hg, P < .01).

Histopathological validation of optical frequency domain imaging to quantify various types of coronary calcifications.

Aims This study evaluated whether optical frequency domain imaging (OFDI) could identify various coronary calcifications and accurately measure calcification thickness in comparison with histopathology. Methods and results A total of 902 pathological cross‐sections from 44 coronary artery specimens of human cadavers were examined to compare OFDI and histological images. Histological coronary calcification was classified into four different types: (i) superficial dense calcified plates, (ii) deep intimal calcification, (iii) scattered microcalcification, and (iv) calcified nodule. The thickness of calcification was measured when both the leading and trailing edges of calcification were visible on OFDI. Of the 902 histological cross‐sections, 158 (18%) had calcification: 105 (66%) were classified as superficial dense calcified plates, 20 (13%) as deep intimal calcifications, 30 (19%) as scattered microcalcifications, and 3 (2%) as calcified nodules. Superficial dense calcified plates appeared as well‐delineated heterogeneous signal‐poor regions with sharp borders on OFDI. Deep intimal calcifications could not be identified on OFDI. Scattered microcalcification appeared as homogeneous low intensity areas with indiscriminant borders. Calcified nodule, a high‐backscattering protruding mass with an irregular surface, also appeared as a low intensity area with a diffuse border. The ROC analysis identified calcium thicknesses <893 µm as cut points for the prediction of measurable calcification (72% sensitivity and 91% specificity, area under the curve = 0.893, P < 0.001). Conclusion Our study demonstrated the potential capability of OFDI to characterize various types of coronary calcifications, which may contribute to the understanding of the pathogenesis of coronary atherosclerosis.