The Effect of Clinical Frailty on Wound Healing in Patients With Chronic Limb-Threatening Ischemia.

PURPOSE: Clinical frailty increases the risk of adverse outcomes in older people. Patients with Chronic limb-threatening ischemia (CLTI) also had several clinical frailties. The aim of this study was to investigate the correlation between clinical frailty scales (CFS) at discharge and wound healing rate in patients with tissue loss. METHODS: A total of 510 limbs in 431 CLTI patients who were undergone endovascular treatment (EVT) from January 2013 to November 2018 were enrolled in this study. Patients were categorized into 4-groups based on the CFS stages: CFS 1 to 4 (well), CFS 5 (mild), CFS 6 (moderate) and CFS ≥7 (severe). And the change in patient's activities during hospitalize was classified into 3 groups based on CFS; improve, stable, worse. Primary endpoint was correlation between CFS at discharge and wound healing rate. Secondary endpoint was relationship between the changes in patient's activities and wound healing rate. RESULTS: A total of 365 limbs were obtained complete wound healing during this study period. Patient distribution into the 4 CFS groups was as follows: 13.3% (well), 21.8% (mild), 25.3% (moderate) and 39.6% (severe). Wound healing rate in severe CFS group was significantly lower than that in other CFS groups (p<0.0001). Wound healing rate in the patients who achieved improvement of activity was significantly higher than that in the other groups (p=0.008). CONCLUSIONS: CFS might be useful for risk stratification in patients with tissue loss. And improvement of activity during hospitalization might lead to increase the wound healing rate. CLINICAL IMPACT: Although the association between clinical frailty and prognosis outcome of Chronic limb-threatening ischemia (CLTI) has been reported, the effect of clinical frailty on wound healing remains unclear. Clinical frailty scale is independently associated with wound healing and might be useful for risk stratification in patients with tissue loss. Improvement of activity during hospitalization might lead to increase the wound healing rate.

Impact of Peak Systolic Velocity Ratio after Drug-Coated Balloon for Femoropopliteal Disease: Three-Month Serial Observation Vessel Echo Study.

AIM: No flow-limiting dissection after drug-coated balloon (DCB) treatment for femoropopliteal (FP) lesions is considered as one of the endpoints, but it has not investigated the difference between each vessel dissection. This study aimed to clarify whether there is a difference between no dissection and type C dissection without flow-limiting dissection for 3 months by peak systolic velocity ratio (PSVR) based on duplex ultrasonography. METHODS: Between February 2020 and April 2021, 44 consecutive de novo FP diseases that underwent endovascular therapy (EVT) with DCB were enrolled in this study. 65.9% of the patients had intermittent claudication, and mean lesion lengths were 194±107 mm. The chronic total occlusion was 38.6%. After DCB treatment, vessel dissection pattern was categorized by angiography. The minimum lumen area (MLA) identified by intravascular ultrasound was serially evaluated with PSVRs at 1 day, 1 month, and 3 months after EVT. RESULT: All lesions were treated with DCB without provisional stents. The vessel dissection pattern after DCB treatment showed that types D, E, and F were not observed, 9% were no dissection, 27% were type A, 32% were type B, and 32% were type C. In all cases, the PSVR values of MLA site were less than 2.6 at 3 months, and there were no significant differences between no dissection and type C dissection. CONCLUSION: Up to dissection pattern "C" is considered acceptable as one of the endpoints to determine the need for provisional stenting after DCB treatment.

Mechanisms of gradual pressure drop in angiographically normal left anterior descending and right coronary artery: Insights from wave intensity analysis.

BACKGROUND: This study evaluated the mechanism of decline in coronary pressure from the proximal to the distal part of the coronary arteries in the left anterior descending (LAD) versus the right coronary artery (RCA) from the insight of coronary hemodynamics using wave intensity analysis (WIA). METHODS: Twelve patients with angiographically normal LAD and RCA were prospectively enrolled. Distal coronary pressure, mean aortic pressure, and average peak velocity were measured at 4 different positions: 9, 6, 3, and 0 cm distal from each coronary ostium. RESULTS: The distal-to-proximal coronary pressure ratio during maximum hyperemia gradually decreased in proportion to the distance from the ostium (0.92±0.03 and 0.98±0.03 at 9 cm distal to the LAD and RCA ostium). WIA showed the dominant forward-traveling compression wave gradually decreased and the backward-traveling suction wave gradually decreased in proportion to the decrease in coronary pressure through the length of the non-diseased LAD but not the RCA. CONCLUSIONS: The pushing wave and suction wave intensities on WIA were diminished in proportion to the distance from the ostium of the LAD despite the wave intensity not changing across the length of the RCA, which may lead to gradual intracoronary pressure drop in the angiographically normal LAD.

Impact of IVUS-Derived Vessel Size on Midterm Outcomes After Stent Implantation in Femoropopliteal Lesions.

Purpose: To identify intravascular ultrasound (IVUS) findings that predict midterm stent patency in femoropopliteal (FP) lesions. Materials and Methods: A retrospective analysis was undertaken of 335 de novo FP lesions in 274 consecutive patients (mean age 72.4±8.2 years; 210 men) who had IVUS assessment before and after successful stent implantation. The mean lesion length was 13.2±9.8 cm. The primary outcome was primary patency at 24 months, defined as freedom from major adverse limb event (MALE) and in-stent restenosis (ISR). MALE was defined as major amputation or any target lesion revascularization (TLR). ISR was defined by a peak systolic velocity ratio >2.4 by duplex ultrasonography. Logistic regression analyses were performed to identify independent predictors of stent patency at 24 months; the results are presented as the odds ratio (OR) and 95% confidence interval (CI). Receiver operator characteristic (ROC) curve analysis was performed to determine the optimal threshold for prediction of stent patency at 24 months. Results: Over the 24-month follow-up, 18 (7%) patients died and 43 (15%) of 286 lesions were responsible for MALE (42 TLRs and 1 major amputation). Primary patency was estimated at 82.5% (95% CI 78.1% to 86.9%) at 12 months and 73.2% (95% CI 67.9% to 78.5%) at 24 months. Multivariable analysis revealed that longer lesion length (OR 0.89, 95% CI 0.82 to 0.97, p<0.01) was an independent predictor of declining patency, while cilostazol use (OR 3.45, 95% CI 1.10 to 10.78, p=0.03) and increasing distal reference external elastic membrane (EEM) area (OR 1.18, 95% CI 1.02 to 1.37, p=0.03) were associated with midterm stent patency. ROC curve analysis identified a distal reference EEM area of 29.0 mm2 as the optimal cut-point for prediction of 24-month stent patency (area under the ROC curve 0.764). Kaplan-Meier estimates of 24-month primary patency were 83.7% (95% CI 78.3% to 89.2%) in lesions with a distal EEM area >29.0 mm2 vs 53.1% (95% CI 42.9% to 63.3%) in those with a distal EEM area ≤29.0 mm2 (p<0.001). Conclusion: In FP lesions with a larger distal vessel area estimated with IVUS, stent implantation can be considered as a reasonable treatment option, with the likelihood of acceptable midterm results.

Clinical Effects of Planned Endovascular Therapy for Critical Limb Ischemia Patients with Tissue Loss.

AIM: The aim of this study was to investigate the clinical effect of planned endovascular therapy (EVT) for critical limb ischemia (CLI) patients with tissue loss. Although several rounds of EVT for CLI patients are required for complete wound healing, time required for complete wound healing depends on the wound severity. We hypothesized that planned EVT might reduce the time to wound healing. METHODS: A total of 89 limbs of 76 CLI patients with tissue loss, who had undergone more than at least two EVTs were included in this study. From January 2013 through December 2015 (Conventional-EVT-group, 52 limbs), indication of target lesion revascularization (TLR) was decided based on decreased skin perfusion pressure (SPP) values or delayed wound healing. From January 2016 through October 2016 (Planned-EVT-group, 37 limbs), TLR were done every two months regardless of the SPP values until complete wound healing was obtained. Time to wound healing and complete wound healing rates were compared between the two groups. RESULTS: No significant differences existed in baseline patients and lesion characteristics between the two groups. There was no significant difference in total EVT numbers between the two groups (2.0; interquartile range, 2.0-3.0 versus 2.0; interquartile range, 2.0-3.0; P=0.9). Although complete wound healing rate was similar in both groups (71.2% versus 73.0%, p=1.0), time to wound healing was significantly shorter (95 days versus 143 days, p=0.025) in the Planned-EVT-group than in the Conventional-EVT-group. CONCLUSIONS: Planned-EVT is a useful strategy to shorten the time to wound healing for CLI patients with tissue loss.

Impact of low tissue backscattering by optical coherence tomography on endothelial function after drug-eluting stent implantation.

This study evaluated the impact of optical coherence tomography (OCT)-derived low-backscattered tissue on mid-term coronary endothelial function after drug-eluting stent (DES) implantation. Although OCT enables detailed in vivo evaluation of neointimal tissue characterization after DES implantation, its association with physiological vascular healing response is unclear. Thirty-three stable angina pectoris patients underwent OCT examination and endothelial function testing with intracoronary infusion of incremental doses of acetylcholine 8-month after DES implantation in a single lesion of the left anterior descending artery. Neointimal tissue was classified into two patterns based on the predominant OCT light backscatter: high backscatter and low backscatter. Although the presence of uncovered or malapposed stent strut was not associated with the degree of vasoconstriction, the degree of vasoconstriction was significantly greater in the DES with low-backscattered neointima than in the DES without low-backscattered neointima (- 32.1 ± 25.7 vs. - 4.1 ± 20.1%, p = 0.003). Moreover, there was an inverse linear relationship between low backscatter tissue index and degree of vasoconstriction after acetylcholine infusion (r = 0.50 and p = 0.003). The endothelium-dependent vasomotor response after 8-month of DES was impaired in patients with low neointimal tissue backscatter on OCT imaging. OCT assessment of low-backscattered tissue may be used as surrogate markers for impairment of endothelial function after DES.

Atherosclerotic Component of the Yellow Segment After Drug-Eluting Stent Implantation on Coronary Angioscopy　- An Ex-Vivo Validation Study.

BACKGROUND: Coronary angioscopy (CAS) is used to comprehensively evaluate vascular responses after drug-eluting stent (DES) implantation. This study sought to evaluate the capability of CAS for evaluating DES strut coverage grade and color grade of the intima compared with histological images in coronary autopsy specimens. Methods and Results: A total of 23 DES extracted from 11 autopsy hearts were imaged by CAS. All stent segments were graded as white or yellow according to the luminal surface color, and thrombus was evaluated according to a previous report. Neointimal coverage over the DES was graded as 0 (stent struts fully visible) to grade 3 (stent struts fully embedded and invisible). Of 76 segments, neointimal coverage was graded as 0 in 35 (46%), 1 in 22 (29%), 2 in 8 (11%), and 3 in 11 (14%). The neointimal thickness increased significantly with increasing neointimal coverage grade on angioscopy. Neointimal color was graded as white in 40 (53%) and yellow in 36 segments (47%). Histological analysis revealed that yellow neointima contained fibroatheroma, foam cells accumulation or superficial calcium deposition. A thrombus was identified in 13 segments. Thrombi adherent around the stent strut were partly intimal erythrocyte accumulation around the strut. CONCLUSIONS: In-stent yellow segment had atherosclerotic components. CAS could evaluate vascular status comprehensively after DES implantation.

Portable negative-pressure wound therapy for pyoderma gangrenosum: Report of two cases.

Pyoderma gangrenosum is a chronic non-infectious neutrophilic dermatosis that causes undermining ulcers. Topical therapies for the deep ulcers of pyoderma gangrenosum have not been established. To investigate whether negative-pressure wound therapy is effective for a pyoderma gangrenosum ulcer, we used the PICO single use negative-pressure wound therapy system (Smith & Nephew, London, UK) for two pyoderma gangrenosum patients. In these cases, the ulcers decreased in size and necrolytic tissue was removed notably. Moreover, there were no secondary infections nor was there Koebner phenomena. Our cases suggest that portable negative-pressure wound therapy can be a treatment option for deep, intractable ulcers caused by pyoderma gangrenosum. Because portable negative-pressure wound therapy devices afford increased mobility to patients, they can give the patient a better quality of life than standard negative-pressure wound therapy systems do.

Loss of interaction between plectin and type XVII collagen results in epidermolysis bullosa simplex.

Plectin is a linker protein that interacts with intermediate filaments and ß4 integrin in hemidesmosomes of the epidermal basement membrane zone (BMZ). Type XVII collagen (COL17) has been suggested as another candidate plectin binding partner in hemidesmosomes. Here, we demonstrate that plectin-COL17 binding helps to maintain epidermal BMZ organization. We identified an epidermolysis bullosa (EB) simplex patient as having markedly diminished expression of plectin and COL17 in skin. The patient is compound heterozygous for sequence variants in the plectin gene (PLEC); one is a truncation and the other is a small in-frame deletion sequence variant. The in-frame deletion is located in the putative COL17-binding domain of plectin and abolishes the plectin-COL17 interaction in vitro. These results imply that disrupted interaction between plectin and COL17 is involved in the development of EB. Our study suggests that protein-protein binding defects may underlie EB in patients with unidentified disease-causing sequence variants.

The distribution of calcified nodule and plaque rupture in patients with peripheral artery disease: an intravascular ultrasound analysis.

In addition to plaque rupture (PR), calcified nodule (CN) may also have the potential to develop into arterial thrombus in the peripheral arteries. This study evaluated the distribution of plaque ruptures and calcified nodules in the peripheral arteries and their impact on the outcome of endovascular therapy (EVT). Consecutive 159 patients who underwent EVT with intravascular ultrasound guidance were enrolled. The position of CNs and PRs were assigned to any of common iliac artery, external iliac artery, common femoral artery, and superficial femoral artery. Forty-six (29%) patients had calcified nodule and twenty-eight (18%) patients had plaque rupture somewhere in the lower limb arteries. Although calcified nodules were evenly distributed throughout the length of the arteries plaque ruptures were predominantly located in the proximal segment of the iliofemoral arteries. Stent expansion ratio was significantly smaller in the target arteries with calcified nodules than in those with plaque rupture. Multivariate logistic regression analysis identified hemodialysis as an independent clinical predictor of calcified nodule (odds ratio 8.15, 95% confidence interval 1.73-38.3; P = 0.008). CN definitely affects incomplete stent deployment in the peripheral artery contributing to adverse events, on the other hand, PR has more acceptable outcomes after stent implantation. In the clinical setting, it is important that we realize the features of peripheral artery disease and its patient characteristics which having CNs and PRs to make a strategy for revascularization.

Impact of stent diameter on vascular response after self-expanding paclitaxel-eluting stent implantation in the superficial femoral artery.

BACKGROUND: The optimal sizing of self-expanding paclitaxel-eluting stents (PES) in the treatment for superficial femoral artery (SFA) lesions is unclear. This study sought to investigate the influence of PES diameter on stent patency in SFA lesions using optical frequency domain imaging (OFDI). METHODS: A total of 20 de novo SFA lesions were randomized 1:1 to receive either self-expanding PES with a nominal diameter of 6mm or 8mm. Follow-up angiography and OFDI was scheduled six months after stent implantation, and volumetric OFDI analysis was performed to evaluate vascular response to the stents. Volume index (VI) was defined as the volume divided by the stent length. The primary end point was lumen VI at the 6-month follow-up. Secondary end point was minimum lumen diameter (MLD) by quantitative vascular angiography (QVA) at the follow-up. RESULTS: Stent length was 78.0±23.9mm in the 6-mm group and 70.0±23.6mm in the 8-mm group (p=0.46). Baseline QVA data were also similar between the two groups. MLD immediately after stent implantation was similar between the two groups (4.2±0.5mm in the 6-mm group and 3.9±0.5mm in the 8-mm group, p=NS). At the 6-month follow-up, MLD was greater in the 8-mm group compared to the 6-mm group (4.0±1.0mm vs. 3.2±0.4mm, p<0.05). Stent VI was larger in the 8-mm group (28.4±6.7mm3/mm vs. 22.2±1.2mm3/mm, p=0.01). Neointimal VI was similar between the two groups (5.8±2.9mm3/mm vs. 5.2±2.6mm3/mm, p=0.68). Lumen VI was greater in the 8-mm group (23.2±7.6mm3/mm vs. 17.3±2.6mm3/mm, p=0.04). CONCLUSIONS: Chronic stent enlargement resulted in greater lumen area after implantation of self-expanding PES with a large diameter at the mid-term follow-up. Stent diameter might be important for stent patency in procedure with PES for SFA lesions.

Impact of thermodilution-derived coronary blood flow patterns after percutaneous coronary intervention on mid-term left ventricular remodeling in patients with ST elevation myocardial infarction.

We recently reported the coronary thermodilution curve can be evaluated by analyzing the thermodilution curve obtained from a pressure sensor/thermistor-tipped guidewire, and presence of a bimodal-shaped thermodilution curve following primary percutaneous coronary intervention (pPCI) in ST-segment elevation myocardial infarction (STEMI) patients was associated with worse outcomes. This study evaluated whether the bimodal-shaped thermodilution curve predicts left ventricular (LV) remodeling after STEMI. The coronary thermodilution curve patterns were evaluated for 75 patients treated by pPCI for their first STEMI using a pressure sensor/thermistor-tipped guidewire, and classified into the three groups according to the thermodilution curve shape: narrow unimodal (n = 39), wide unimodal (n = 26), and bimodal pattern (n = 10). Echocardiography was performed at baseline and 6 months after STEMI. LV remodeling was defined as a >20 % increase in LV end-diastolic volumes (LVEDV). LVEDV at 6-month follow-up was greater in the bimodal group than in the other groups (p < 0.001). The prevalence of LV remodeling was highest in the bimodal group than in the narrow and wide unimodal groups (60, 12, and 15 %, respectively; p = 0.003). Multivariate analysis revealed a bimodal-shaped thermodilution curve as an independent predictor of the prevalence of LV remodeling. A bimodal-shaped thermodilution curve is associated with LV remodeling after STEMI. This easily assessable coronary thermodilution curve pattern is useful to predict mid-term LV remodeling for STEMI patients at the catheterization laboratory.

Impact of analysis interval size on the quality of optical frequency domain imaging assessments of stent implantation for lesions of the superficial femoral artery.

OBJECTIVES: This study aimed to investigate the influence of analysis interval size on optical frequency domain imaging (OFDI) assessment of stent therapy for lesions of the superficial femoral artery (SFA). BACKGROUND: No consensus or validating data are available with respect to the methodology of intravascular imaging analysis for the peripheral arteries. METHODS: OFDI was performed for 30 SFA lesions, during endovascular therapy and at the 6-month follow-up. Initially, lumen and stent borders were traced at 1-mm axial intervals. Volumes were calculated using a PC-based software, and the volume index (VI) was defined as the volume divided by the stent length. Two additional OFDI analyses were performed using 2-mm and 5-mm intervals, thereby reducing the number of cross-sectional image frames analyzed. RESULTS: The mean stent length was 89.7 ± 35.2 mm. The mean difference in baseline minimum lumen area (MLA) was 0.4 mm2 between MLA values from the 1-mm and 2-mm interval analyses, and 2.2 mm2 between MLA values from the 1-mm and 5-mm interval analyses. In volumetric analysis, there were excellent correlations and good agreements for stent, lumen, and neointimal VI measurements obtained on the basis of different analysis intervals. CONCLUSIONS: Using large intervals in OFDI analyses of SFA lesions resulted in few differences in measurement variability of volumetric parameters. However, planar analysis for MLA assessment can be susceptible to high variability when large intervals are applied. © 2016 Wiley Periodicals, Inc.