Beyond Sarcomeric Hypertrophic Cardiomyopathy: How to Diagnose and Manage Phenocopies.

PURPOSE OF REVIEW: We describe the most common phenocopies of hypertrophic cardiomyopathy, their pathogenesis, and clinical presentation highlighting similarities and differences. We also suggest a step-by-step diagnostic work-up that can guide in differential diagnosis and management. RECENT FINDINGS: In the last years, a wider application of genetic testing and the advances in cardiac imaging have significantly changed the diagnostic approach to HCM phenocopies. Different prognosis and management, with an increasing availability of disease-specific therapies, make differential diagnosis mandatory. The HCM phenotype can be the cardiac manifestation of different inherited and acquired disorders presenting different etiology, prognosis, and treatment. Differential diagnosis requires a cardiomyopathic mindset allowing to recognize red flags throughout the diagnostic work-up starting from clinical and family history and ending with advanced imaging and genetic testing. Different prognosis and management, with an increasing availability of disease-specific therapies make differential diagnosis mandatory.

Drug-Coated Balloon Angioplasty Compared With Uncoated Balloons in the Treatment of Infrapopliteal Artery Lesions (AcoArt II-BTK).

PURPOSE: To compare the safety and efficacy of drug-coated balloon (DCB) vs uncoated balloon angioplasty in the treatment of de novo and restenotic infrapopliteal lesions in patients with chronic limb-threatening ischemia (CLTI). MATERIALS AND METHODS: The prospective, multicenter, randomized study AcoArt II-BTK study (ClinicalTrials.gov identifier NCT02137577) enrolled 120 patients who were randomly assigned to angioplasty with either a DCB (n=61; mean age 70.7±7.4 years; 36 men) or a conventional balloon catheter (n=59; mean age 70.8±9.0 years; 36 men). There were no significant differences observed in baseline clinical or target lesion characteristics between the groups. The target lesion length was 169.95±86.35 mm in the DCB group vs 179.93±80.16 mm in the control group, and approximately three-quarters of the lesions were chronic occlusions. Primary patency was assessed by angiography at 6 months, and mortality and clinically-driven target lesion revascularization (CD-TLR) were evaluated at 12 months. RESULTS: Primary patency at 6 months was 75.0% in the DCB group and 28.3% in the control group (p<0.001), while late lumen loss was 0.43±0.62 mm for DCBs vs 0.99±0.55 mm for controls (p<0.001). Freedom from CD-TLR at 12 months was 91.5% in the DCB group vs 76.8% in the controls (p=0.03); there was no significant difference in mortality (1.7% DCB vs 3.6% controls; p=0.53). CONCLUSION: This study demonstrated that the Litos/Tulip DCBs are safe and effective in treating infrapopliteal lesions, with improved angiographic and clinical outcomes vs plain balloon angioplasty. The DCBs demonstrated significantly higher primary patency with fewer CD-TLRs than conventional angioplasty. The safety of the DCBs was noninferior to that of the uncoated balloons after 1 year of follow-up.

Electroanatomic mapping-guided endomyocardial biopsy in patients with apparently idiopathic ventricular arrhythmias.

The management of ventricular arrhythmias (VA) in the presence of an apparently normal heart represents a major clinical challenge and a main field of clinical research. In the past years, new imaging techniques and the spreading of new generation genetic testing have improved our knowledge of the pathogenesis of apparently idiopathic VA. However, in the absence of specific recommendations, the type and the number of noninvasive and invasive studies necessary to rule out a possible underlying cause of VA or sudden cardiac death remain extremely variable. Therefore, in many patients the underlying cardiac disease is not recognized, and a possible specific therapeutic approach cannot be initiated. Endomyocardial biopsy (EMB) can provide a significant contribution to the identification of myocardial disorders causing VA but has never been definitively included in the routine diagnostic work-up of these patients due to the possible sampling error particularly in disorders with a focal or patchy distribution. Three-dimensional electroanatomic mapping (EAM) may guide EMB allowing to draw myocardial samples from abnormal voltage, areas of the ventricular wall, thus reducing sampling error and increasing the sensitivity of EMB. The systematic association of EAM with EMB represents a crucial approach to characterize the pathological substrate of electroanatomic abnormalities and VA and to further clarify the arrhythmogenic mechanisms of acquired and also inherited arrhythmic disorders.

Short and medium-term efficacy of sodium glucose co-transporter-2 (SGLT-2) inhibitors: A meta-analysis of randomized clinical trials.

AIMS: Sodium glucose co-transport-2 (SGLT-2) inhibitors reduce tubular glucose reabsorption, producing a reduction of blood glucose without stimulating insulin release. The aim of this meta-analysis was the systematic collection of available data from randomized trials, in order to establish the durability of the efficacy of SGLT-2 inhibitors on glycaemic control and body mass index. METHODS: A meta-analysis was performed, including all trials with a duration of at least 12 weeks, comparing SGLT-2 inhibitors with non-SGLT-2 inhibitor agents in type 2 diabetes. The principal outcome was the effect of SGLT-2 inhibitors on hemoglobin A1c (HbA1c) at 12, 24, 52 and 104 weeks. Data on body mass index at the same time points were also collected. RESULTS: Among 66 randomized trials, HbA1c reduction at 12, 24, 52 and 104 weeks was 0.63% (0.57; 0.68, 0.63% (0.57; 0.70), 0.66% (0.57; 0.74) and 0.60% (0.40; 0.81), respectively. SGLT-2 inhibitors showed a greater efficacy than dipeptidyl-peptidase-4 inhibitors (DPP-4i). Sulfonylureas appeared to be superior to SGLT-2 inhibitors at 12 weeks, but not at 24 and 52 weeks; SGLT-2 inhibitors produced a greater reduction in HbA1c than did sulfonylureas at 104 weeks. SGLT-2 inhibitor-induced weight loss in placebo-controlled trials appeared to increase progressively with the duration of treatment. CONCLUSIONS: SGLT-2 inhibitors showed a good persistence of efficacy, at least up to 2 years, with a small but significant superiority over DPP-4i. Sulfonylureas are more effective in the very short term, but less effective in the longer term.

Paclitaxel-Eluting Balloon vs Standard Angioplasty to Reduce Restenosis in Diabetic Patients With In-Stent Restenosis of the Superficial Femoral and Proximal Popliteal Arteries: Three-Year Results of the DEBATE-ISR Study.

PURPOSE: To report the 3-year safety and effectiveness outcomes from the prospective all-comers DEBATE-ISR study (ClinicalTrials.gov identifier NCT01558531) of symptomatic diabetic patients with femoropopliteal in-stent restenosis (ISR) undergoing treatment with paclitaxel-eluting balloons compared with historical diabetic controls. METHODS: From January 2010 to December 2011, 44 consecutive diabetic patients (mean age 74±11 years; 32 men) were treated with drug-eluting balloons (DEBs) and enrolled in the study. The control group comprised 42 consecutive diabetic patients (age 76±7 years; 23 men) treated with conventional balloon angioplasty (BA) from 2008 to 2009. RESULTS: No significant differences in terms of clinical, angiographic, or procedural characteristics were observed between the study groups. Critical limb ischemia was present in the majority of patients. Tosaka class III ISR was observed in more than half of the patients. Mean lesion length was 132±86 and 137±82 mm in the DEB and BA groups, respectively (p=0.7). At 3-year follow-up, the rate of target lesion revascularization (TLR) was 40% in the DEB group vs 43% in the BA group (p=0.8); Kaplan-Meier analysis showed no significant differences in terms of freedom from TLR. The presence of a Tosaka class III occlusion was associated with a worse outcome in both study groups (odds ratio 3.96, 95% confidence interval 1.55 to 10.1, p=0.004). CONCLUSION: Using DEBs for femoropopliteal ISR yielded similar results to BA in terms of TLR at 3-year follow-up. The treatment of more complex ISR lesions was associated with an increased rate of TLR, irrespective of the technology used.

Drug-eluting balloon in peripheral intervention for below the knee angioplasty evaluation (DEBATE-BTK): a randomized trial in diabetic patients with critical limb ischemia.

BACKGROUND: The 1-year restenosis rate after balloon angioplasty of long lesions in below-the-knee arteries may be as high as 70%. Our aim was to investigate the efficacy of a paclitaxel drug-eluting balloons versus conventional percutaneous transluminal angioplasty (PTA) for the reduction of restenosis in diabetic patients with critical limb ischemia undergoing endovascular intervention of below-the-knee arteries. METHODS AND RESULTS: The Drug-Eluting Balloon in Peripheral Intervention for below the knee angioplasty evaluation (DEBATE-BTK) is a randomized, open-label, single-center study comparing drug-eluting balloons and PTA. Inclusion criteria were diabetes mellitus, critical limb ischemia (Rutherford class 4 or higher), significant stenosis or occlusion >40 mm of at least 1 below-the-knee vessel with distal runoff, and life expectancy >1 year. Binary in-segment restenosis at a 1-year angiographic or ultrasonographic follow-up was the primary end point. Clinically driven target lesion revascularization, major amputation, and target vessel occlusion were the secondary end points. One hundred thirty-two patients with 158 infrapopliteal atherosclerotic lesions were enrolled. Mean length of the treated segments was 129±83 mm in the drug-eluting balloon group compared with 131±79 mm in the PTA group (P=0.7). Binary restenosis, assessed by angiography in >90% of patients, occurred in 20 of 74 lesions (27%) in the drug-eluting balloon group compared with 55 of 74 lesions (74%) in the PTA group (P<0.001); target lesion revascularization, in 12 (18%) versus 29 (43%; P=0.002); and target vessel occlusion, in 12 (17%) versus 41 (55%; P<0.001). Only 1 major amputation occurred, in the PTA group (P=0.9). CONCLUSIONS: Drug-eluting balloons compared with PTA strikingly reduce 1-year restenosis, target lesion revascularization, and target vessel occlusion in the treatment of below-the-knee lesions in diabetic patients with critical limb ischemia.

Paclitaxel-eluting balloon vs. standard angioplasty to reduce recurrent restenosis in diabetic patients with in-stent restenosis of the superficial femoral and proximal popliteal arteries: the DEBATE-ISR study.

PURPOSE: To test the ability of a drug-eluting balloon (DEB) to reduce recurrent in-stent restenosis (ISR) in diabetic patients with femoropopliteal stents. METHODS: A prospective all-comers study [Drug-Eluting Balloon in Peripheral Intervention for In-Stent Restenosis (DEBATE-ISR); ClinicalTrials.gov identifier NCT01558531] of symptomatic diabetic patients with femoropopliteal ISR undergoing treatment with paclitaxel-eluting balloons was designed to compare their 12-month recurrent restenosis rate with that of historical diabetic controls. From January 2010 to December 2011, 44 consecutive diabetic patients (32 men; mean age 74±11 years) were treated with DEBs and enrolled in the study. The control group comprised 42 diabetic patients (23 men; mean age 76±7 years) treated with a conventional balloon for femoropopliteal ISR from 2008 to 2009. RESULTS: No significant differences in terms of clinical, angiographic, or procedural characteristics were observed between the study groups. Lesion length was 132±86 mm in the DEB group vs. 137±82 mm in the BA group. Procedural success, defined as a residual stenosis <30% in the restenotic segment (stent +5 mm at proximal and distal edges), was obtained in all treated lesions. At 1-year follow-up, 6 patients died (3 in each group), and 1 patient in the BA group underwent major amputation. Recurrent restenosis, assessed by angiography (66%) or ultrasound (34%), occurred in 8/41 (19.5%) patients in the DEB group vs. 28/39 (71.8%) in the BA group (p<0.001). Target lesion revascularization for symptomatic recurrent restenosis was performed in 6/44 (13.6%) patients in the DEB vs.13/42 (31.0%) in the BA group (p=0.045). CONCLUSION: Using DEB for treating femoropopliteal ISR led to a significant reduction in recurrent restenosis and repeat angioplasty at 1-year follow-up as compared to historical controls.

Bypass surgery versus endovascular revascularization for occlusive infrainguinal peripheral artery disease: a meta-analysis of randomized controlled trials for the development of the Italian Guidelines for the treatment of diabetic foot syndrome.

To report a review and meta-analysis of all randomized controlled trials (RCTs) comparing bypass surgery (BS) and endovascular treatment (ET) in infrainguinal peripheral arterial disease (PAD) for several endpoints, such as major and minor amputation, major adverse limb events (MALEs), ulcer healing, time to healing, and all-cause mortality to support the development of the Italian Guidelines for the Treatment of Diabetic Foot Syndrome (DFS). A MEDLINE and EMBASE search was performed to identify RCTs, published since 1991 up to June 21, 2023, enrolling patients with lower limb ischemia due to atherosclerotic disease (Rutherford I-VI). Any surgical BS or ET was allowed, irrespective of the approach, route, or graft employed, from iliac to below-the-knee district. Primary endpoint was major amputation rate. Secondary endpoints were amputation-free survival major adverse limb events (MALEs), minor amputation rate, all-cause mortality, ulcer healing rate, time to healing, pain, transcutaneous oxygen pressure (TcPO2) or ankle-brachial index (ABI), quality of life, need for a new procedure, periprocedural serious adverse events (SAE; within 30 days from the procedure), hospital lenght of stay, and operative time. Twelve RCTs were included, one enrolled two separate cohorts of patients, and therefore, the studies included in the analyses were 13. Participants treated with ET had a similar rate of major amputations to participants treated with BS (MH-OR 0.85 [0.60, 1.20], p = 0.36); only one trial reported separately data on patients with diabetes (N = 1), showing no significant difference between ET and BS (MH-OR: 0.67 [0.09, 5.13], p = 0.70). For minor amputation, no between-group significant differences were reported: MH-OR for ET vs BS: 0.83 [0.21, 3.30], p = 0.80). No significant difference in amputation-free survival between the two treatment modalities was identified (MH-OR 0.94 [0.59, 1.49], p = 0.80); only one study reported subgroup analyses on diabetes, with a non-statistical trend toward reduction in favor of ET (MH-OR 0.62 [0.37, 1.04], p = 0.07). No significant difference between treatments was found for all-cause mortality (MH-OR for ET vs BS: 0.98 [0.80, 1.21], p = 0.88). A significantly higher rate of MALE was reported in participants treated with ET (MH-OR: 1.44 [1.05, 1.98], p = 0.03); in diabetes subgroup analysis showed no differences between-group for this outcome (MH-OR: 1.34 [0.76, 2.37], p = 0.30). Operative duration and length of hospital stay were significantly shorter for ET (WMD: - 101.53 [- 127.71, - 75.35] min, p < 0.001, and, - 4.15 [- 5.73, - 2.57] days, p < 0.001 =, respectively). ET was associated with a significantly lower risk of any SAE within 30 days in comparison with BS (MH-OR: 0.60 [0.42, 0.86], p = 0.006). ET was associated with a significantly higher risk of reintervention (MH-OR: 1.57 [1.10, 2.24], p = 0.01). No significant between-group differences were reported for ulcer healing (MH-OR: 1.19 [0.53, 2.69], p = 0.67), although time to healing was shorter (- 1.00 [0.18, 1.82] months, p = 0.02) with BS. No differences were found in terms of quality of life and pain. ABI at the end of the study was reported by 7 studies showing a significant superiority of BS in comparison with ET (WMD: 0.09[0.02; 0.15] points, p = 0.01). The results of this meta-analysis showed no clear superiority of either ET or BS for the treatment of infrainguinal PAD also in diabetic patients. Further high-quality studies are needed, focusing on clinical outcomes, including pre-planned subgroup analyses on specific categories of patients, such as those with diabetes and detailing multidisciplinary team approach and structured follow-up.

Elutax paclitaxel-eluting balloon followed by bare-metal stent compared with Xience V drug-eluting stent in the treatment of de novo coronary stenosis: a randomized trial.

BACKGROUND: Paclitaxel-eluting balloons (PEBs) are a promising alternative to drug-eluting stent (DES) in the treatment of coronary stenoses. The aim of our study was to compare the 9-month restenosis rates of a strategy of predilatation with PEB followed by bare-metal CoCr stent (PEB + BMS group) versus implantation of everolimus DES (DES group). METHODS: This randomized, single-center study planned to enroll 366 patients with stable angina (183 patients per arm) undergoing percutaneous coronary intervention of a de novo, native coronary artery stenosis ≤ 15 mm in length. Primary end point, in a noninferiority study design, was 9-month binary angiographic restenosis. A frequency-domain optical coherence tomography substudy investigated the percentage of uncovered stent struts per lesion, the percentage of malapposed/uncovered struts per lesion, and the percentage of net volume obstruction at 9-month follow-up among the first consecutive 30 patients enrolled in the PEB + BMS group. RESULTS: The study was prematurely halted after enrollment of 125 patients, 59 in the PEB + BMS group and 66 in the DES group, because of excess of ischemia-driven target lesion revascularization in the PEB + BMS group. When all the enrolled patients completed their follow-up, IDLTR rates were 14% in the PEB + BMS versus 2% in DES group (P = .001). Binary restenosis, either in-stent or in-segment, was significantly higher in the PEB + BMS compared with DES group (17% vs 3% [P = .01] and 25% vs 4% [P = .009] respectively). Frequency-domain optical coherence tomography demonstrated important neointimal regrowth in the PEB + BMS group, similar to historical BMS data. CONCLUSION: In the treatment of de novo coronary stenosis, a strategy of predilatation with PEB before BMS implantation was significantly inferior to implantation of an everolimus DES stent in terms of 9-month target lesion revascularization. Frequency-domain optical coherence tomography data confirm the lack of efficacy of this strategy.

Randomized comparison of Zotarolimus-Eluting Endeavor Sprint versus bare-metal stent implantation in uncertain drug-eluting stent candidates: rationale, design, and characterization of the patient population for the Zotarolimus-eluting Endeavor Sprint stent in uncertain DES candidates study.

BACKGROUND: The use of drug-eluting stent (DES) instead of bare-metal stent (BMS) in patients at high stent thrombosis or bleeding risk as well as in those at low restenosis risk (ie, uncertain DES candidates) remains a matter of debate. Zotarolimus-Eluting Endeavor Sprint stent (E-ZES) (Santa Rosa, CA) is a hydrophilic polymer-based second-generation device with unique drug fast-release profile, which may allow for a shorter dual antiplatelet therapy (DAPT) duration without safety concerns. HYPOTHESIS: The primary objective is to assess whether E-ZES implantation followed by a shorter than currently recommended course of DAPT will decrease the incidence of 12-month major adverse cardiovascular events as compared with BMS in undefined DES recipients. Actual duration of DAPT regimen will be dictated by patients' characteristics and not by stent type and, as such, can be as short as 30 days after intervention in both stent groups. STUDY DESIGN: The ZEUS study is an open-label randomized clinical trial conducted at 20 clinical sites in Italy, Switzerland, Portugal, and Hungary. With 1,600 individuals, this study will have 85% power to detect a 33% difference in the primary end point consisting of the composite of death, nonfatal myocardial infarction, or target vessel revascularization. SUMMARY: The ZEUS trial aims to assess whether the use of E-ZES, followed by a DAPT duration regimen based on patients' characteristics and not by stent type, is superior to conventional BMS implantation in undefined DES recipients who qualify for the presence of high thrombosis, bleeding, or low restenosis risk criteria.

Limb Salvage and Survival in Chronic Limb-Threatening Ischemia: The Need for a Fast-Track Team-Based Approach.

Chronic limb-threatening ischemia (CLTI) represents the end-stage form of peripheral arterial disease (PAD) and is associated with a very poor prognosis and high risk of limb loss and mortality. It can be considered very similar to a terminal cancer disease, reflecting a large impact on quality of life and healthcare costs. The aim of this study is to offer an overview of the relationship between CLTI, limb salvage, and mortality, with a focus on the need of a fast-track team-based management that is a driver to achieve better survival results. This review can be useful to improve management of this growing impact disease, and to promote the standardisation of care and communication between specialist and non-specialist healthcare professionals.

Drug-eluting balloon angioplasty for carotid in-stent restenosis.

PURPOSE: To report midterm results of 3 cases in which drug-eluting balloons (DEBs) were successfully used for the management of carotid in-stent restenosis (ISR). CASE REPORT: Two women aged 68 and 70 years and a 68-year-old man were referred to our institution for asymptomatic severe stenosis [>80% with peak systolic velocity (PSV) >300 cm/s by Doppler ultrasound assessment] of individual Carotid Wallstents implanted in the proximal left internal carotid artery (ICA). In the angiosuite, the left ICA was engaged in a telescopic fashion with a triple coaxial system formed by a 6-F long sheath and a preloaded 5-F, 125-cm diagnostic catheter over a 0.035-inch soft hydrophilic guidewire. Under distal filter protection, the lesions were predilated using a 3.5 × 20-mm coronary balloon and then treated with two 1-minute inflations of a 4 × 40-mm Amphirion In.Pact paclitaxel-eluting balloon, followed by 3 months of dual antiplatelet therapy. At 12, 22, and 36 months, respectively, the patients are still asymptomatic, with duplex-documented stent patency at 6, 12, and 24 months, respectively. CONCLUSION: DEBs are an emerging strategy for carotid ISR, with encouraging midterm results in these patients. Further experience in larger cohorts is needed to confirm these preliminary observations.

A tailored approach to overcoming challenges of a bovine aortic arch during left internal carotid artery stenting.

PURPOSE: To investigate the efficacy and safety of a tailored approach to fit access and engagement techniques to the individual arch anatomy in patients with bovine-type aortic arch (BTAA) to overcome the perceived increased risk of technical failure and cerebral embolization during left internal carotid artery (LICA) stenting. METHODS: Thirty-five high surgical risk patients (23 men; mean age 68.6 years, range 62-90) with BTAA and LICA stenosis underwent carotid artery stenting (CAS). Left common carotid artery (LCCA) engagement was achieved by means of different techniques according to the configuration of the BTAA, arch type (I, II, or III), and angle between the innominate artery and the LCCA. The clinical, anatomical, and procedural data were retrieved from a prospectively maintained database and analyzed retrospectively to identify technical modifications required during the procedure compared with planning. RESULTS: The technical success rate was 100%. Transfemoral access was used in 21 (60%) cases. In this group, the soft engagement technique with hockey stick (HS) guiding catheter and buddy wire in the external carotid artery (ECA) was used in 13 (62%) cases, a simple telescopic technique with 6-F armed introducer or 7-F 40° guiding catheter in 5 (24%) cases, and a sequential technique with a MOMA proximal protection system in the remaining 3 (14%) cases. Among the 14 (40%) right brachial access cases, the telescopic technique with 6-F armed introducer was used in 13 cases. The remaining case was the only one in which the planned technique was changed (from the telescopic to sequential technique with ECA wire exchange). There were no intraprocedural or 30-day neurological events. CONCLUSION: An appropriate tailored interventional strategy, planned by means of preprocedural recognition of bovine arch anatomy, is associated with satisfactory safety and good success.

Paclitaxel-coated balloons versus percutaneous transluminal angioplasty for infrapopliteal chronic total occlusions: the IN.PACT BTK randomised trial.

BACKGROUND: Data are mixed concerning the safety and effectiveness of drug-coated balloons (DCBs) for treating below-the-knee (BTK) lesions. AIMS: The aim of this study was to assess the safety and effectiveness of the IN.PACT 014 paclitaxel-coated balloon catheter versus conventional percutaneous transluminal angioplasty (PTA) for infrapopliteal chronic total occlusions (CTOs) in patients with chronic limb-threatening ischaemia (CLTI). METHODS: The IN.PACT BTK randomised study is a prospective, multicentre, randomised pilot study. Fifty CLTI participants (Rutherford clinical category 4-5) with BTK CTOs were randomised 1:1 to DCB (N=23) or PTA (N=27). The primary effectiveness endpoint was late lumen loss (LLL) at 9 months post procedure. Safety outcomes up to 9 months included all-cause mortality, major target limb amputation, and clinically driven target lesion revascularisation (CD-TLR). RESULTS: Mean lesion length was 215.41±83.81 mm in the DCB group and 218.19±80.43 mm for PTA (p=0.806). The 9-month angiographic LLL was 0.892±0.774 mm for the DCB group and 1.312±0.720 mm for the PTA group (p=0.070) in a classic analysis, and 0.592±0.944 mm for DCB and 1.260±0.810 mm for PTA (p=0.017) in a subsegmental analysis. The Kaplan-Meier estimated freedom from CD-TLR up to 9 months was 91.1% for DCB and 91.8% for PTA (log-rank p=0.942). At 9 months, 1 patient died in the DCB group and 2 in the PTA group (p=1.000); there were no major target limb amputations in either arm. CONCLUSIONS: The 9-month subsegmental LLL was lower after treatment with the IN.PACT 014 DCB compared with PTA with no differences in safety or revascularisation events in a small complex population of patients with BTK CTOs. CLINICALTRIALS: gov: NCT02963649.

Drug-Eluting Balloon for Below the Knee Angioplasty: Five-Year Outcome of the DEBATE-BTK Randomized Clinical Trial.

BACKGROUND: The aim of this study is to evaluate the 5-year clinical outcome of the DEBATE-BTK (Drug-eluting balloon for below-the-knee angioplasty evaluation) trial. METHODS: The DEBATE-BTK was a single-center, randomized trial that enrolled 132 diabetic patients with critical limb ischemia. Subjects were randomized 1:1 to DCB or plain old balloon angioplasty (POBA). Major clinical endpoints were, freedom from all-cause death, freedom from clinically driven target lesion revascularization (CDTLR) and the occurrence of major amputation. Additional analysis were conducted to assess overall survival in patients treated with DCB compared to those treated with only POBA in the entire 5-years period and to test the correlation between paclitaxel dose exposure (in terciles) and overall survival. RESULTS: Freedom from all-cause death at 5 years was 63.1% (41/65) in DCB vs. 53.7%(35/67) POBA patients (p = 0.4). Freedom from CDTLR was 82% in DCB and 63% in POBA patients (p = 0.002) at 1 year and 63 versus 54% at 5 years respectively P = 0.07. One patient in DCB and 2 patients in POBA underwent a major amputation of the target limb. During the 5-year follow-up, 24 patients originally randomized to POBA received DCB treatment for additional limb revascularization. According to DCB treatment in all the 5 years period, overall survival was 66.3.% (30/89) in DCB versus 40%(26/43) in POBA patients, p = 0.003. CONCLUSIONS: Overall survival at 5-year was similar in DCB treated patients compared to POBA. Moreover, survival was higher in patients that received DCB angioplasty at any time of the 5 years period. LEVEL OF EVIDENCE: Level 1b, Individual inception cohort study with > 80% follow-up.

Long-term mortality in patients undergoing lower-limb revascularization with Paclitaxel eluting devices.

BACKGROUND: Paclitaxel-eluting devices (PED) reduce restenosis and target lesion revascularization (TLR) in femoropopliteal intervention. Recent data suggest a two-fold increased long-term mortality in patients treated with PED. The aim of our study is to evaluate if endovascular therapy (EVT) with PED increases mortality risk in patients with symptomatic lower limb peripheral artery disease (PAD) compared to non-eluting devices (NED). METHODS: The study is a retrospective, single-center registry on patients undergoing EVT for PAD from January 2009 to June 2018. Propensity score analysis on logistic regression model for independent predictors of long-term mortality was used to match PED and NED patients. Mortality was assessed at 2, 5 and 7 years in the entired matched population and in a sub-group of patients ≤75 years. RESULTS: During the study period, 1294 patients, 718 NED and 576 PED, met the inclusion/exclusion criteria and entered in the study. Propensity score matching analysis identified 854 matched patients, 414 PED and 440 NED. The population was mainly characterized by diabetic patients with CLI (80%) and high prevalence of CAD (30%), heart failure (15%) and renal insufficiency (20%). Mean follow-up length was 58 ± 34 months, (median 52.5). Mortality was 18% in NED vs 12% in PED patients at two years (p = 0.01), 36% vs 30% at 5 years (p = 0.03) and 41% vs 39% at seven years (p = 0.2) respectively. In patients ≤75 years, mortality at 7-year was 28% in PED vs 36% in NED, p = 0.07. CONCLUSION: These results suggest a reduced mortality at 2 and 5 years with PED as compare to NED treatment in a real-world CLI scenario. At 7-year follow-up, the advantage was numerically evident only in patients ≤75 years.

Autologous Peripheral Blood Mononuclear Cells for Limb Salvage in Diabetic Foot Patients with No-Option Critical Limb Ischemia.

Peripheral blood mononuclear cells (PBMNCs) are reported to prevent major amputation and healing in no-option critical limb ischemia (NO-CLI). The aim of this study is to evaluate PBMNC treatment in comparison to standard treatment in NO-CLI patients with diabetic foot ulcers (DFUs). The study included 76 NO-CLI patients admitted to our centers because of CLI with DFUs. All patients were treated with the same standard care (control group), but 38 patients were also treated with autologous PBMNC implants. Major amputations, overall mortality, and number of healed patients were evaluated as the primary endpoint. Only 4 out 38 amputations (10.5%) were observed in the PBMNC group, while 15 out of 38 amputations (39.5%) were recorded in the control group (p = 0.0037). The Kaplan-Meier curves and the log-rank test results showed a significantly lower amputation rate in the PBMNCs group vs. the control group (p = 0.000). At two years follow-up, nearly 80% of the PBMNCs group was still alive vs. only 20% of the control group (p = 0.000). In the PBMNC group, 33 patients healed (86.6%) while only one patient healed in the control group (p = 0.000). PBMNCs showed a positive clinical outcome at two years follow-up in patients with DFUs and NO-CLI, significantly reducing the amputation rate and improving survival and wound healing. According to our study results, intramuscular and peri-lesional injection of autologous PBMNCs could prevent amputations in NO-CLI diabetic patients.

Randomized Controlled Trial of Acotec Drug-Eluting Balloon Versus Plain Balloon for Below-the-Knee Angioplasty.

OBJECTIVES: The aim of this study was to investigate the efficacy and safety of the Litos drug-coated balloon (DCB) versus plain old balloon angioplasty (POBA) for reduction of late lumen loss (LLL) in patients with critical limb ischemia undergoing below-the-knee (BTK) intervention. BACKGROUND: Restenosis after balloon angioplasty of BTK arteries approximates 70%. Previous studies of DCBs in BTK arteries produced conflicting results. METHODS: ACOART-BTK (Evaluation of the Use of ACOTEC Drug-Eluting Balloon Litos® in Below-the-Knee Arteries to Treat Critical Limb Ischemia) is a randomized controlled single-center study. Inclusion criteria were critical limb ischemia (Rutherford class ≥4) and significant stenosis or occlusion >40 mm of at least 1 BTK vessel with distal runoff successfully treated with angioplasty. Six-month angiographic LLL was the primary endpoint. Occlusive restenosis at 6 months and clinically driven target lesion revascularization at 12 months were secondary endpoints. RESULTS: From January 2016 through January 2019, 105 patients with 129 BTK lesions were enrolled in the study. Mean lesion length was 168 ± 109 mm in the DCB group and 187 ± 113 mm in the POBA group (p = 0.30). Almost 70% of lesions were occluded at baseline in both groups. On 6-month angiography, mean LLL was 0.51 ± 0.60 mm in the DCB group and 1.31 ± 0.72 mm in the POBA group (p < 0.001); rates of occlusive restenosis were 8.6% and 48.4%, respectively (p < 0.001). Twelve-month clinically driven target lesion revascularization occurred in 6 of 62 DCB-treated lesions (10%) versus 27 of 66 POBA-treated lesions (41%) (p < 0.001). Complete healing at 12 months was observed in 42 of 47 DCB-treated limbs (89.4) versus 35 of 47 POBA-treated limbs (74.5%) (p = 0.05); no major amputations occurred. CONCLUSIONS: Litos DCBs strikingly reduced LLL, vessel reocclusion, and clinically driven target lesion revascularization compared with POBA in BTK angioplasty.

Ticagrelor versus clopidogrel in patients undergoing implantation of paclitaxel-eluting stent in the femoropopliteal district: A randomized pilot study using frequency-domain optical coherence tomography.

OBJECTIVES: Aim of this study was to evaluate different response in platelet reactivity and vessel healing using high-resolution frequency-domain optical coherence tomography (FD-OCT) in patients with femoropopliteal artery disease treated with ZILVER PTX drug eluting stents (DES), and randomly assigned to clopidogrel or ticagrelor for 12 months. BACKGROUND: The optimal antithrombotic regimen for long-term management of patients with peripheral artery disease (PAD) after revascularization is poorly defined and often extrapolated from trials performed on patients undergoing percutaneous coronary intervention. METHODS: In this single center randomized trial 40 patients with femoropopliteal artery disease treated with ZILVER PTX DES stents, were randomized to Ticagrelor (T) + Aspirin for 3 months, subsequently continuing Ticagrelor alone for another 9 months or Clopidogrel (C) + Aspirin for 3 months, subsequently continuing Clopidogrel alone for 9 months. Platelet reactivity via the P2Y12 pathway was evaluated at baseline and at 3 months follow-up, angiographic and FD-OCT follow-up along the entire stented segment was performed at 12 months. RESULTS: No significant difference between T and C group was found concerning net percentage volume obstruction (29.7% ± 17.6% vs. 31.2% ± 10.7%; p = 0.78). FD-OCT at 12 months showed a high percentage of uncovered stent struts in both groups: 24.2% ± 32.8% in the T group vs 15.3% ± 15.8% in the C group (p = 0.4). Mean values of platelet reactivity units (PRU) at 3 month follow-up were 81 ± 72 in the T group and 200 ± 61 in the C group (p < 0.001). CONCLUSIONS: Significantly higher platelet reactivity remains in patients treated with clopidogrel as compared to ticagrelor 3 months after PTA and stent implantation. Ticagrelor does not reduce neointimal proliferation in patients treated with DES in the femoropopliteal district as compared with clopidogrel. A large amount of uncovered stent struts at 12-month follow-up was found in these patients regardless of the antiplatelet treatment assumed.