Left atrial low voltage areas and heart failure in patients with atrial fibrillation: Implication of the atrial myopathy.

AIMS: Atrial fibrillation (AF) and heart failure (HF) affect each other and are often co-morbid. The fact that HF development is not uncommon even after ablation suggests that we need a deeper understanding of the pathology of these conditions. Atrial myocardial degeneration is an underlying factor in AF patients and may be associated with HF development after ablation. This study aimed to investigate the impact of low-voltage areas (LVAs) on HF prognosis after AF ablation. METHODS AND RESULTS: This observational study included 1481 consecutive patients undergoing initial ablation for AF. Left atrial LVAs were defined as regions with a bipolar peak-to-peak voltage of <0.50 mV. Patients were divided into three groups: no LVA (LVA size indexed to body surface area <3 cm2/m2, n = 1129), small LVA (3-10 cm2/m2, n = 217), and extensive LVA (≥10 cm2/m2, n = 135). A composite endpoint of HF hospitalization or death occurred more frequently in patients with larger LVAs (3.3% vs. 6.5% vs. 13.3%, P < 0.0001) during the 3-year follow up period. The extent of LVAs was independently related to the risk of the composite endpoint with an adjusted hazard ratio of 1.55 (95% confidence interval, 1.16-2.10) for each additional step of LVA classification (P = 0.003). CONCLUSIONS: LVA presence and its extent were associated with frequent HF hospitalization and death. Underlying atrial myopathy appears to define a poor HF prognosis after AF ablation.

Impact of wall thickness on the tissue cooling effect of cryoballoon ablation.

AIMS: Understanding of the tissue cooling properties of cryoballoon ablation during pulmonary vein (PV) isolation is lacking. The purpose of this study was to delineate the depth of the tissue cooling effect during cryoballoon freezing at the pulmonary venous ostium. METHODS AND RESULTS: A left atrial-PV model was constructed using a three-dimensional printer with data from a patient to which porcine thigh muscle of various thicknesses could be affixed. The model was placed in a 37°C water tank with a PV water flow at a rate that mimicked biological blood flow. Cryofreezing at the PV ostium was performed five times each for sliced porcine thigh muscle of 2, 4, and 6 mm thickness, and sliced muscle cooling on the side opposite the balloon was monitored. The cooling effect was assessed using the average temperature of 12 evenly distributed thermocouples covering the roof region of the left superior PV. Tissue cooling effects were in the order of the 2, 4, and 6 mm thicknesses, with an average temperature of -41.4 ± 4.2°C for 2 mm, -33.0 ± 4.0°C for 4 mm, and 8.0 ± 8.7°C for 6 mm at 180 s (P for trend <0.0001). In addition, tissue temperature drops were steeper in thin muscle (maximum temperature drop per 5 s: 5.2 ± 0.9°C, 3.9 ± 0.7°C, and 1.3 ± 0.7°C, P for trend <0.0001). CONCLUSION: The cooling effect of cryoballoon freezing is weaker in the deeper layers. Cryoballoon ablation should be performed with consideration to myocardial thickness.

Atrial Functional Substrates for the Prediction of Atrial Fibrillation Recurrence After Pulmonary Vein Isolation.

Low-voltage areas have been used as atrial structural substrates in estimating fibrotic degeneration in patients with atrial fibrillation (AF). The high-resolution maps obtained by recently developed mapping catheters allow the visualization of several functional abnormalities. We investigated the association between left atrial (LA) functional abnormal findings on a high-resolution substrate map and AF recurrence in patients who underwent pulmonary vein isolation without any additional LA substrate ablation. This observational study included 100 consecutive patients who underwent second ablation for AF (paroxysmal, 48%; persistent, 52%). Patients with extra-pulmonary-vein LA substrate ablation during the initial and second ablation were excluded. LA mapping was performed using a 64-pole mini-basket catheter on the RHYTHMIA mapping system (Boston Scientific, Marlborough [Cambridge] Massachusetts). Patients were followed for 2 years. AF recurrence developed in 39 (39%) patients. On the high-resolution substrate map, AF recurrence was associated with the presence of the following findings: low-voltage areas (<1.0 mV, >5 cm2; hazard ratio [HR] = 2.53; 95% confidence interval [CI] = 1.30 to 4.93; p <0.006), fractionated-electrogram areas (≥5 peaks, >5 cm2; HR = 2.15, 95% CI = 1.10 to 4.19; p = 0.025), LA conduction time of >130 ms (HR = 3.11, 95% CI = 1.65 to 5.88, p <0.0001), deceleration zone (≥5 isochrones/cm2; HR = 1.97, 95% CI = 1.04 to 3.37, p = 0.039), and multiple septal break-out points (HR = 3.27, 95% CI = 1.50 to 7.16, p = 0.003). Accumulation of these risk factors increased AF recurrence in a stepwise manner, with an HR = 1.90, 95% CI = 1.44 to 2.52, p <0.00001 for each additional risk factor. In conclusion, a high-resolution map revealed new LA functional substrates associated with AF recurrence. Implementation of functional substrates may improve the prediction of AF recurrence after ablation, and possibly aid the development of tailored AF ablation strategies.

Impact of diabetes mellitus and poor glycemic control on the prevalence of left atrial low-voltage areas and rhythm outcome in patients with atrial fibrillation ablation.

INTRODUCTION: Left atrial low-voltage areas (LVAs) are known to be correlated with atrial scarring and atrial fibrillation (AF) recurrence after ablation. However, the association between LVAs and glycemic status before ablation has not been fully clarified. The purpose of this study was to investigate associations among the prevalence of diabetes mellitus (DM), glycemic control, and the prevalence of LVAs in patients with AF ablation. METHODS: In total, 912 (age, 68 ± 10 years; female, 299 [33%]; persistent AF, 513 [56%]) consecutive patients who underwent initial AF ablation were included. A preprocedure glycated hemoglobin A1c (HbA1c) ≥7% was set as the cutoff for poor glycemic control in patients with DM. LVAs were defined as areas with a bipolar voltage of <0.5 mV covering ≥5 cm2 of left atrium. RESULTS: LVAs existed in 208 (23%) patients, and 168 (18%) patients had DM. LVAs were found more frequently in patients with DM and poor glycemic control. On multivariate analysis, DM with HbA1c ≥7% was an independent predictor of LVAs (odds ratio, 3.3; 95% confidence interval: 1.6-6.7; p = .001). In patients with LVAs, freedom from AF recurrence during the 24-month study period was significantly lower in patients who had DM with HbA1c ≥7% than in those without DM (37.9% vs. 54.7%, p = .02). CONCLUSION: In patients with AF ablation, LVAs were found more frequently in patients with DM and poor glycemic control. DM with HbA1c ≥7% was an independent predictor of LVAs.

Clinical impact of left atrial remodeling pattern in patients with atrial fibrillation: Comparison of volumetric, electrical, and combined remodeling.

INTRODUCTION: Atrial fibrillation (AF) is accompanied by various types of remodeling, including volumetric enlargement and histological degeneration. Electrical remodeling reportedly reflects histological degeneration. PURPOSE: To clarify the differences in determinants and clinical impacts among types of remodeling. METHODS: This observational study included 1118 consecutive patients undergoing initial ablation for AF. Patients were divided into four groups: minimal remodeling (left atrial volume index [LAVI] < mean value and no low-voltage area [LVA], n = 477); volumetric remodeling (LAVI ≥ mean value and no LVA, n = 361); electrical remodeling (LAVI < mean value and LVA presence, n = 96); and combined remodeling (LAVI ≥ mean value and LVA presence, n = 184). AF recurrence and other clinical outcomes were followed up for 2 and 5 years, respectively. RESULTS: Major determinants of each remodeling pattern were high age for electrical (odds ratio = 2.32, 95% confidence interval = 1.68-3.25) and combined remodeling (2.57, 1.88-3.49); female for electrical (3.85, 2.21-6.71) and combined remodeling (4.92, 2.90-8.25); persistent AF for combined remodeling (7.09, 3.75-13.4); and heart failure for volumetric (1.71, 1.51-2.53) and combined remodeling (2.21, 1.30-3.75). Recurrence rate after initial ablation increased in the order of minimal remodeling (20.1%), volumetric (27.4%) or electrical remodeling (36.5%), and combined remodeling (50.0%, p < .0001). A composite endpoint of heart failure, stroke, and death occurred in the order of minimal (3.4%), volumetric (7.5%) or electrical (8.3%), and combined remodeling (15.2%, p < .0001). CONCLUSION: Volumetric, electrical, and combined remodeling were each associated with a unique patient background, and defined rhythm and other clinical outcomes.

Comparison of voltage maps using OCTARAY catheter and PENTARAY catheter.

BACKGROUND: Recently, a new OCTARAY® mapping catheter was commercially launched. The catheter is designed to enable high-density mapping and precise signal recording via 48 small electrodes arranged on eight radiating splines. The purpose of this study was to compare bipolar voltage and low-voltage-area size, and mapping efficacy between the OCTARAY catheter and the PENTARAY® catheter METHODS: Twelve consecutive patients who underwent initial and second ablations for persistent atrial fibrillation within 2 years were considered for enrollment. Voltage mapping was performed twice, first during the initial ablation using the PENTARY catheter and second during the second ablation using the OCTARAY Long 3-3-3-3-3 (L3) catheter. RESULTS: Mean voltage with the OCTARAY-L3 catheter (1.64 ± 0.57 mV) was 32.3% greater than that with the PENTARAY catheter (1.24 ± 0.46 mV, p < .0001) in total left atrium. Low-voltage-area (<0.50 mV) size with the OCTARAY-L3 catheter was smaller than that with the PENTARAY catheter (6.9 ± 9.7 vs. 11.4 ± 13.0 cm2 , p < .0001). The OCTARAY-L3 catheter demonstrated greater efficacy than the PENTARAY catheter in terms of shorter mapping time (606 ± 99 vs. 782 ± 211 s, p = .008) and more mapping points (3,026 ± 838 vs. 781 ± 342 points, p < .0001). CONCLUSION: The OCTARAY catheter demonstrated higher voltage recordings, narrower low-voltage areas, and a more efficacious mapping procedure than the PENTARAY catheter.

Prognostic impact of atrial cardiomyopathy: Long-term follow-up of patients with and without low-voltage areas following atrial fibrillation ablation.

BACKGROUND: Atrial cardiomyopathy is known as an underlying pathophysiological factor in the majority of patients with atrial fibrillation (AF). Left atrial low-voltage areas (LVAs) are reported to coincide with fibrosis and likely represent atrial cardiomyopathy. OBJECTIVE: The purpose of this study was to delineate differences in the long-term prognosis of patients stratified by the size of LVAs. METHODS: This observational study included 1488 consecutive patients undergoing initial ablation for AF. LVAs were defined as regions with a bipolar peak-to-peak voltage <0.50 mV. The total study population was divided into 3 groups stratified by LVA size: patients with no LVAs (n = 1136); those with small (<20 cm2) LVAs (n = 250) LVAs; and those with extensive (≥20 cm2) LVAs (n = 102). Composite endpoints of death, heart failure, and stroke were followed for up to 5 years. RESULTS: Composite endpoints developed in 105 of 1488 patients (7.1%), and AF recurrence occurred in 410 (27.6%). Composite endpoints developed more frequently in the order of patients with extensive LVAs (19.1%), small LVAs (10.8%), and no LVAs (5.1%) (P for trend <.0001). Multivariable analysis revealed that LVA presence was independently associated with higher incidence of composite endpoints, irrespective of AF recurrence (modified hazard ratio 1.73; 95% confidence interval 1.13-2.64; P = .011) CONCLUSION: LVA presence and its extent both were associated with poor long-term composite endpoints of death, heart failure, and stroke, irrespective of AF recurrence or other confounders. Underlying atrial cardiomyopathy seems to define a poor prognosis after AF ablation.

Comparing Predictors Influencing Restenosis Following High-Dose Drug-Coated Balloon Angioplasty and Fluoropolymer-Based Drug-Eluting Stenting in Femoropopliteal Artery Lesions.

PURPOSE: Despite widespread use of anti-restenosis devices, drug-coated balloons (DCBs) and drug-eluting stents (DESs), their appropriate use for femoropopliteal (FP) lesions has not been well investigated and the risk factors for restenosis have not been compared. To investigate risk factors associated with restenosis after endovascular therapy using DCB and DES for contemporary FP lesions. MATERIALS AND METHODS: This single-center, retrospective, observational study evaluated 378 FP lesions in 273 patients treated with DCB (278 lesions in 193 patients) or DES (120 lesions in 106 patients). The DCB used was high-dose DCB (IN.PACT, Admiral. Medtronic, Inc.) and DES was fluoropolymer-based DES (ELUVIA, Boston Scientific). Vessel preparation failure was defined as a residual stenosis of ≥50% and a dissection grade of D or greater on pre-dilatation angiography. The outcome measure was restenosis, and factors associated with restenosis in the DCB and DES groups were assessed using a Cox proportional hazards model. RESULTS: The 2-year restenosis rate was not significantly different between the DCB and DES groups (29%±4% vs. 24%±5%, p=0.42). Interaction analysis demonstrated that popliteal lesions and plaque burden of ≥50% were restenosis-related factors for DES but not for DCB, whereas vessel preparation failure was a factor for DCB but not for DES (p<0.05). Vessel diameter of <6 mm and nodular calcification were risk factors in both groups (p<0.05). CONCLUSION: In contemporary FP lesions, smaller vessels and nodular calcification were shared restenosis-related factors for high-dose DCB and fluoropolymer-based DES. Popliteal lesions and plaque burden of ≥50% were restenosis-related factors for fluoropolymer-based DES and vessel preparation failure for high-dose DCB. CLINICAL IMPACT: Shared and differential restenosis-related factors after endovascular therapy using high-dose drug-coated balloons (DCBs) and fluoropolymer-based drug-eluting stents (DESs) in contemporary femoropopliteal (FP) lesions are unclear. This single-center retrospective study included 378 FP lesions in 273 patients with lower-extremity arterial disease (high-dose DCB, 278 lesions in 193 patients; fluoropolymer-based DES, 120 lesions in 106 patients). Smaller vessels and calcified nodules were shared restenosis-related factors for both high-dose DCB and fluoropolymer-based DES, whereas popliteal lesions and plaque burden of ≥50% were restenosis-related factors for fluoropolymer-based DES and vessel preparation failure for high-dose DCB.

Clinical Outcomes of Patients With Cholesterol Crystal Embolism Accompanied by Lower Extremity Wound.

Cholesterol crystal embolism (CCE) accompanied by a lower extremity wound is occasionally difficult to differentiate from chronic limb-threatening ischemia (CLTI) and treat. The present multi-center retrospective observational study investigated the clinical characteristics and prognosis of CCE with lower extremity wounds. Consecutive patients (n = 58) clinically diagnosed as CCE with lower extremity wounds between April 2010 and December 2019 were studied. CCE was diagnosed using histological findings, foot condition, renal impairment, and eosinophilia. The primary outcome was 1-year wound healing rate. Patients with CCE were compared with 1309 patients diagnosed with CLTI with tissue loss during the same study period. The CCE group had a significantly more severe Wound, Ischemia, and foot Infection (WIfI) classification compared with the CLTI group. After Kaplan-Meier analysis, the CCE group had a similar 1-year wound healing (55.1 vs 58.3%, P = .096) as the CLTI group. In multivariate stratified Cox regression analysis by WIfI stages, CCE was significantly associated with poor wound healing compared with CLTI [hazard ratio .36 (95% confidence interval .21-.62)]. In conclusion, among the similar WIfI clinical stages, wound healing was significantly worse in the CCE group than in the CLTI group.

Factors Associated With Early and Late Restenosis Following Drug-Coated Balloon Treatment for Patients With Femoropopliteal Lesions.

PURPOSE: Clinical trials have demonstrated the superiority of drug-coated balloon (DCB) to noncoated balloon angioplasty for the treatment of femoropopliteal (FP) lesions. In those trials, the difference of primary patency between DCB and noncoated angioplasty widens especially after 6 months, speculating that the antirestenosis effect of paclitaxel is manifested after 6 months. Factors associated with restenosis after 6 months differ from those associated with restenosis within 6 months. This study aimed to elucidate the prognostic factors associated with early (within 6 months) and late (after 6 months) restenosis following DCB treatment in real-world FP practice. MATERIALS AND METHODS: This multicenter, retrospective study analyzed 486 FP lesions (mean lesion length, 11.9±10.1 cm; chronic total occlusion, 21.0%) in 423 patients (diabetes mellitus, 59.3%; hemodialysis, 37.1%; chronic limb-threatening ischemia, 41.6%) who underwent successful DCB treatment between January 2018 and December 2019. The outcome measure was restenosis which is defined as a peak systolic velocity ratio >2.4 based on duplex ultrasound findings. Early and late restenosis were classified by the cutoff period of 6 months after the procedure. The associations of baseline and procedural characteristics with early and late restenosis were explored using Cox proportional hazards regression analysis. RESULTS: The mean follow-up period was 25.3±12.1 months. The 6, 12, 18, and 24 month cumulative incidences of restenosis were 7.4%±2.4%, 20.9%±3.9%, 29.9%±4.5%, and 38.4%±5.1%, respectively. During the follow-up period, early and late restenosis was evident in a total of 31 lesions and 138 lesions, respectively. Multivariate analysis revealed that chronic total occlusion (hazard ratio [HR], 2.29; 95% confidence interval [CI], 1.07-4.92; p=0.033) and superficial femoral artery ostial lesion (HR, 2.73; 95% CI, 1.28-5.80; p=0.009) were significantly associated with early restenosis. On the other hand, calcification circumference over 270° (HR, 1.67; 95% CI, 1.17-2.37; p=0.004), distal external elastic membrane diameter under 5 mm assessed by intravascular ultrasound (HR, 1.90; 95% CI, 1.29-2.79; p=0.001), and involving popliteal arterial lesion (HR, 1.54; 95% CI, 1.08-2.21; p=0.017) were significantly associated with late restenosis. CONCLUSION: The prognostic factors associated with late restenosis differed from those associated with early restenosis in the real-world FP-DCB practice. CLINICAL IMPACT: The current multicenter, retrospective study revealed that factors associated with early restenosis differed from those with late restenosis in the real-world FP-DCB practice. CTO and SFA ostial lesion were associated with early restenosis, while severe calcification, smaller vessel, and involving popliteal arterial lesions were associated with late restenosis.Early restenosis indicates "balloon failure" and would potentially result from recoil, which primary stent implantation might be required. On the other hand, late restenosis after 6 months would be attributed to "DCB failure", with inadequate drug uptake into the arterial wall, which might be minimized by the use of atherectomy devices.

Gender Differences in Atrial Fibrosis and Cardiomyopathy Assessed by Left Atrial Low-Voltage Areas During Catheter Ablation of Atrial Fibrillation.

Atrial myocardial degeneration predisposes to atrial fibrillation (AF), ischemic stroke, and heart failure. Studies suggest the presence of gender differences in atrial myocardial degeneration. This study aimed to delineate gender differences in the prevalence, predictors, and prognostic impact of left atrial low-voltage areas (LVAs). This observational study included 1,488 consecutive patients who underwent initial ablation for AF. Voltage mapping was performed after pulmonary vein isolation during sinus rhythm. LVAs were defined as regions where bipolar peak-to-peak voltage was <0.50 mV. LVA prevalence was higher in women (38.7%) than in men (16.0%). High age, persistent form of AF, diabetes mellitus, and a large left atrium were shown to be common predictors in both gender categories. Heart failure and history of stroke/thromboembolic events were men-specific predictors of LVA existence. Women experienced more AF recurrence than men (31.1% vs 25.7%, p = 0.027). LVA existence was significantly associated with increased AF recurrence in each gender category, with a respective hazard ratio, 95% confidence interval, and p value of 2.45, 1.87 to 3.22, and <0.0001 in men and 1.82, 1.33 to 2.49, and <0.0001 in women. In conclusion, LVA was more frequent in women than men, and predicted frequent AF recurrence irrespective of gender category.

Low atrial natriuretic peptide to brain natriuretic peptide ratio is associated with left atrial remodeling.

AIMS: Atrial natriuretic peptide (ANP) deficiency is thought to be one of the causes of heart failure induced by atrial fibrillation (AF). Although ANP deficiency is thought to occur as a result of atrial remodeling, data to explain this mechanism are limited. The purpose of this study was to investigate the association between ANP and left atrial remodeling or prognosis of heart failure in patients with AF ablation. METHODS: In total, 373 consecutive patients who underwent initial ablation for persistent AF [age, 67 ±â€Š10 years; female, 97 (26%)] were retrospectively enrolled. ANP and brain natriuretic peptide (BNP) were measured before the procedure and the ANP/BNP ratio was calculated. Left atrial volume index, left atrial appendage emptying velocity, and left atrial low-voltage areas (LVAs) were used as left atrial-remodeling parameters. The primary outcome of heart failure was defined as the composite of all-cause death or hospitalization due to worsening heart failure. RESULTS: The median ANP level was 116 (71-178) pg/ml and the median ANP/BNP ratio was 0.65 (0.46-1.00). The ANP/BNP ratio decreased with increasing left atrial volume index or LVAs and with decreasing left atrial appendage emptying velocity. During the 5-year follow-up, freedom from the primary outcome was significantly lower in patients with ANP/BNP ratio ≤0.65 than in those with ANP/BNP ratio >0.65 (84.6% versus 95.6%, P  < 0.01). CONCLUSION: Secretion of ANP relative to BNP decreased with progression of left atrial remodeling in patients with AF ablation. Furthermore, prognosis of heart failure was poor in patients with a low ANP/BNP ratio.

Angioscopic Evaluation of Vascular Response After Fluoropolymer-Based Drug-Eluting Stent Implantation for Femoropopliteal Artery Lesions.

BACKGROUND: Although favorable clinical outcomes have been demonstrated for fluoropolymer-based paclitaxel-eluting stents (FP-DES) in the treatment of femoropopliteal lesions, the vascular response after implantation has not been systematically studied through intravascular imaging.Methods and Results: We angioscopically compared FP-DES: 24 in the early phase (mean [±SD] 3±1 months), 26 in the middle phase (12±3 months), and 20 in the late phase (≥18 months) after implantation. The dominant neointimal coverage grade, heterogeneity of neointimal coverage grade, and thrombus adhesion in the stent segment were evaluated. Neointimal coverage was graded as follows: Grade 0, stent struts exposed; Grade 1, struts bulging into the lumen, although covered; Grade 2, struts embedded in the neointima, but visible; Grade 3, struts fully embedded and invisible. Dominant neointimal coverage and heterogeneity grades were significantly higher in the middle and late phases than in the early phase (all P<0.05), but did not differ significantly between the middle and late phases. The incidence of thrombus adhesion was recorded for all stents in each of the 3 different phases. CONCLUSIONS: The middle and late phases after FP-DES implantation were associated with significantly higher dominant neointimal coverage and heterogeneity grades than the early phase. However, thrombus adhesion was observed in all phases after FP-DES implantation. Arterial healing may not be completed even in the late phase after FP-DES implantation.

Impact of Cardiac Function on Loss of Patency in Patients With Peripheral Artery Disease Presenting the Femoropopliteal Lesions Endovascularly Treated With New-Generation Devices.

PURPOSE: The current study sought to investigate the impact of cardiac condition on loss of patency after endovascular therapy (EVT) using new-generation devices for femoropopliteal (FP) lesions. MATERIALS AND METHODS: We retrospectively studied 547 lesions (chronic limb-threatening ischemia: 44%, TASC II C/D lesion: 61%, chronic total occlusion: 37%, in-stent restenosis: 13%, involving popliteal arterial lesion: 45%) belonging to 416 patients (average age: 75±9 years, male: 69%, diabetes mellitus: 62%, hemodialysis: 33%) who underwent EVT with new-generation FP-specific devices (polymer-free paclitaxel-eluting stent, n=186; stent graft, n=119; fluoropolymer-based paclitaxel-eluting stent, n=29; interwoven stent, n=17; drug-coated balloon, n=196) from June 2012 to May 2019. Cardiac function was evaluated using echocardiography. The primary outcome measure was primary patency, which was defined as free from peak systolic velocity ratio (PSVR) >2.5 assessed by duplex ultrasound. Predictors for loss of patency were evaluated using Cox proportional hazards regression analysis. RESULTS: Overall 12 primary patency were 80.0±1.8%. After the multivariate analysis, reduced stroke volume evaluated by echocardiography (hazard ratio [HR]=0.99, 95% confidence interval [CI]=0.97-0.99, p=0.03), chronic heart failure (HR=1.76, 95% CI=1.05-2.97, p=0.03), and a smaller distal reference vessel diameter (HR=0.73, 95% CI=0.55-0.97, p=0.03) were significantly associated with loss of 12-month primary patency, whereas lesion length (HR=1.01, 95% CI=0.99-1.03, p=0.33) and presence of chronic total occlusion (CTO; HR=0.92, 95% CI=0.61-1.40, p=0.70) were not statistically significant. CONCLUSION: The current study revealed that cardiac function represented by reduced stroke volume and presence of chronic heart failure as well as a smaller distal reference vessel diameter were significantly associated with loss of 12-month primary patency in patients with peripheral artery disease (PAD) presenting FP lesions endovascularly treated with new-generation devices.

Clinical Impact of the Size of Drug-Coated Balloon Therapy on Restenosis Rate in Femoropopliteal Lesions.

PURPOSE: Although the size of drug-coated balloons (DCBs) is determined according to the vessel diameter during femoropopliteal (FP)-endovascular therapy (EVT), the measurements of the vessel diameter vary among modalities and its definitions. The aim of this study was to reveal whether the DCB size fitting (1) angiographically-measured lumen diameter (Angio-lumen size), (2) intravascular ultrasound (IVUS)-measured lumen diameter (IVUS-lumen size), or (3) IVUS-measured external elastic membrane (EEM) diameter (IVUS-EEM size) would be beneficial in restenosis occurrence. MATERIALS AND METHODS: This retrospective, single-center study included 231 de novo FP lesions in 165 patients with peripheral artery disease treated with IN.PACT Admiral DCB under IVUS evaluation. The reference vessel diameter was evaluated as the lumen or EEM diameter at the healthy site distal to the lesion. We retrospectively determined whether the DCB size was close to (ie, equal to or different by <0.5 mm from) Angio-lumen size, IVUS-lumen size, and IVUS-EEM size. The association of the size of DCB with restenosis risk was investigated. RESULTS: The mean lesion length was 13 ± 9 cm and the prevalence of chronic total occlusion was 18%. During a mean follow-up period of 17 ± 9 months, restenosis occurred in 26% of lesions. Lesions treated with a DCB of IVUS-EEM size had a lower 2 year restenosis rate than those treated with a DCB over/under IVUS-EEM size (19.7 ± 5.7% vs 34.5 ± 4.7%, p=0.02 by the log-rank test), while the restenosis rate was not significantly different between DCBs of Angio-lumen size or IVUS-lumen size and those over/under the size (both p>0.05). The multivariate Cox regression analysis revealed that DCBs of IVUS-EEM size were independently associated with a reduced risk of restenosis (adjusted hazard ratio 0.50; 95% confidence interval 0.27-0.95; p=0.03). CONCLUSION: The DCBs of IVUS-EEM size, but not of Angio-lumen size or IVUS-lumen size, were associated with a reduced risk of restenosis after FP-EVT. Determining the DCB size according to IVUS-evaluated EEM diameter would be potentially beneficial in restenosis occurrence.

Effects of Infra-malleolar Status According to Global Limb Anatomic Staging System on Clinical Outcomes in Patients With Chronic Limb-Threatening Ischemia.

The global vascular guideline proposed a novel anatomical classification of infra-malleolar (IM) arterial lesions. We aimed to investigate the association of IM classification with clinical outcomes in patients with chronic limb-threatening ischemia (CLTI) due to isolated infrapopliteal (IP) lesions. We retrospectively analyzed 509 limbs with tissue loss in 357 patients due to isolated IP lesions who underwent endovascular therapy (EVT) between April 2010 and December 2018. The primary outcome was 1-year wound healing rate. The association of patient and anatomic characteristics with non-healing was evaluated using Cox proportional hazards regression analysis. The 1-year cumulative wound healing rate was 59.7%. Multivariable analysis demonstrated that IM grade 2 (hazard ratio [HR], 1.41; P = .044), non-ambulatory status (HR, 1.49; P = .008), hemodialysis (HR, 1.37; P = .020), left ventricular ejection fraction < 50% (HR, 1.72; P = .030), and wound, ischemia, and foot infection (WIfI) classification 4 (HR, 1.33; P = .032) were significantly associated with non-healing, whereas no below-the-ankle (BTA), below-the-knee (BTK) runoff, and Global Limb Anatomic Staging System (GLASS) IP grade had no statistically significant association with non-healing. Global Limb Anatomic Staging System IM grade 2 was an independent risk factor for wound healing in patients who underwent EVT with CLTI due to isolated IP disease.

Factors in Sufficient Endovascular Vessel Preparation for Severely Calcified Femoropopliteal Lesions.

BACKGROUND: Vessel preparation for endovascular treatment (EVT) is important but because the contributory factors for favorable outcomes are not yet known, we conducted the present study to elucidate the factors associated with sufficient vessel preparation for severely calcified femoropopliteal (FP) lesions.Methods and Results: This was a single-center retrospective observational study of 97 patients (mean age, 75±8 years, 76% male) with 106 de novo severely calcified FP lesions who underwent EVT under intravascular ultrasound (IVUS) evaluation. The lesion definition was 360° of superficial calcification on IVUS. The primary outcome measure was sufficient vessel preparation, which was defined as successful cracking of severely calcified lesions evaluated by IVUS after predilation. The mean lesion length was 200±103 mm, and chronic total occlusion was present in 38% of patients. According to the greater difference between the preballoon size and the lumen diameter of the severely calcified lesion, the frequency of sufficient vessel preparation increased (odds ratio, 4.68; 95% confidence interval, 2.09-10.49; P<0.01). Balloon type (noncompliant, P=0.80; scoring: P=0.25) and pressure (P=0.27) were non-contributory. CONCLUSIONS: The difference between the lumen diameter at the severely calcified FP lesion site and the preballoon dilatation diameter was the sole factor contributing to sufficient vessel preparation.

Impact of intravascular ultrasound parameters and platelet reactivity on primary patency after drug-coated balloon angioplasty for femoropopliteal artery disease.

Although the superiority of DCBs to uncoated balloon angioplasty for the treatment of femoropopliteal (FP) lesions has been demonstrated, the association of clinical factors, including anatomical features evaluated by intravascular ultrasound (IVUS) and platelet reactivity, with the loss of patency has not been systematically studied. The current prospective, observational study enrolled 160 consecutive patients (male 67.5%, mean age 74.7 ± 9.7 years) with 213 FP lesions treated with DCBs under IVUS evaluation. The platelet reactivity was measured in P2Y12 reaction units for all of the patients at the DCB treatment. The primary end point was primary patency at 12 months, while the secondary end points were freedom from target lesion revascularization (TLR), all-cause death, major target limb amputation and bleeding events at 12 months. Mean lesion length was 11.9 ± 9.4 cm and 34 (16.0%) were chronic total occlusions (CTOs). Thirty-four (16.0%) were severely calcified lesions. Primary patency by Kaplan-Meier estimate was 79.2% at 12 months, while the 12-month freedom from TLR, all-cause death and bleeding events were observed in 89.1%, 93.4% and 97.4%, respectively. There were no major target limb amputations through 12 months. Multivariate analysis showed that subintimal angioplasty for CTO lesions was a sole risk factor for loss of 12-month primary patency, while other IVUS parameters and platelet reactivity were not.

Impact of Guideline-Directed Medical Therapy on 10-Year Mortality after Revascularization for Patients with Chronic Limb-Threatening Ischemia.

AIMS: This study aimed to investigate the long-term impact of guideline-directed medical therapy (GDMT) on 10-year mortality in patients with chronic limb-threatening ischaemia (CLTI) after revascularization. METHODS: We performed a retrospective multicentre study enrolle 459 patients with CLTI who underwent revascularization (396 endovascular therapy [EVT] and 63 bypass surgery [BSX] cases) between January 2007 and December 2011. The primary outcome measure was all-cause mortality. We additionally explored the predictors for all-cause mortality using Cox regression hazard models; the influence of GDMT, defined as prescription of antiplatelet agents, statins, and angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) in aggregate, on all-cause mortality, and the association between baseline characteristics using interaction effects. RESULTS: During the 10-year follow-up after revascularization, 234 patients died. In Kaplan-Meier analysis, 10-year mortality was significantly lower in patients who received statins (p＜.001) and ACE inhibitors or ARBs (p=.010) than those who did not. However, there were no differences in 10-year mortality between patients who received anti-platelet agents and those who did not (p=.62). Interaction analysis revealed that GDMT had a significantly different hazard ratio in patients who were and were not on hemodialysis and in those treated with EVT or BSX (p for interaction =.002 and .044, respectively). In the multivariate analysis, age ＞75 years, non-ambulatory status, hemodialysis, congestive heart failure, left ventricular ejection fraction ＜50%, and GDMT were significantly associated with all-cause mortality. CONCLUSIONS: Appropriate GDMT use was independently associated with 10-year mortality in patients with CLTI after revascularization.