Simone Grotti

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. Clinical Trial Registration— URL: http://ClinicalTrials.gov. Unique identifier: NCT01558505.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. Clinical Trial Registration— URL: . Unique identifier: [NCT01558505][1]. # Clinical Perspective {#article-title-23} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01558505&atom=%2Fcirculationaha%2F128%2F6%2F615.atom

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.

Impact of Thrombus Aspiration on Myocardial Tissue Reperfusion and Left Ventricular Functional Recovery and Remodeling After Primary Angioplasty

Background—Failure to achieve myocardial reperfusion often occurs during percutaneous coronary intervention (PCI) in patients with myocardial infarction with ST-segment elevation. We hypothesized that manual thrombus aspiration during primary PCI would favorably influence tissue-level myocardial perfusion and left ventricular (LV) functional recovery and remodeling. Methods and Results—We prospectively randomized 111 patients with ST-segment elevation myocardial infarction to either standard or thrombus-aspiration PCI. Primary end point of the study was postprocedural incidence of ST-segment resolution ≥70%. Secondary end points included Thrombolysis in Myocardial Infarction (TIMI) myocardial perfusion grade ≥2, the combination of TIMI myocardial perfusion grade ≥2 and ST-segment resolution ≥70%, post-PCI TIMI grade 3 flow, corrected TIMI frame count, myocardial contrast echocardiography score index, the absence of persistent ST-segment deviation, and time course of wall-motion score index, LV ejection fraction, and LV volume in the 2 groups. The incidence of ST-segment resolution ≥70% was 71% and 39% in the thrombus-aspiration and standard PCI groups, respectively (odds ratio, 3.7; 95% CI, 1.7 to 8.3; P=0.001). TIMI myocardial perfusion grade ≥2 was attained in 93% in the thrombus-aspiration group compared with 71% in the standard PCI group (P=0.006). The percentage of patients with ST-segment resolution ≥70% and TIMI myocardial perfusion grade ≥2 was significantly greater in the thrombus-aspiration group compared with the standard PCI group (69% versus 36%, P=0.0006). Myocardial contrast echocardiography score index was significantly higher in the thrombus-aspiration group compared with the standard PCI group (0.86±0.20 versus 0.65±0.31; P<0.0001). A significantly greater improvement in LV ejection fraction and in wall-motion score index from baseline to 6-month follow-up was observed in the thrombus-aspiration group compared with the standard PCI group (LV ejection fraction from 48±6% to 55±6% versus 48.7±7% to 49±8%, P<0.0001; wall-motion score index from 1.59±0.13 to 1.31±0.19 versus 1.64±0.20 to 1.51±0.26, P=0.008). Twelve patients (11%) developed LV remodeling at 6 months, 2 (4%) in the thrombus-aspiration group and 10 (18%) in the standard PCI group (P=0.02). Conclusions—Manual thrombus aspiration in the setting of primary PCI improves myocardial tissue-level perfusion as well as LV functional recovery and remodeling.

Impact of Iso-Osmolar Versus Low-Osmolar Contrast Agents on Contrast-Induced Nephropathy and Tissue Reperfusion in Unselected Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention (From the Contrast Media and Nephrotoxicity Following Primary Angioplasty for Acute Myocardial Infarction [CONTRAST-AMI] Trial)

Conflicting data have been reported on the effects of low-osmolar and iso-osmolar contrast media on contrast-induced acute kidney injury (CI-AKI). In particular, no clinical trial has yet focused on the effect of contemporary contrast media on CI-AKI, epicardial flow, and microcirculatory function in patients with ST-segment elevation acute myocardial infarction who undergo primary percutaneous coronary intervention. The Contrast Media and Nephrotoxicity Following Coronary Revascularization by Angioplasty for Acute Myocardial Infarction (CONTRAST-AMI) trial is a prospective, randomized, single-blind, parallel-group, noninferiority study aiming to evaluate the effects of the low-osmolar contrast medium iopromide compared to the iso-osmolar agent iodixanol on CI-AKI and tissue-level perfusion in patients with ST-segment elevation acute myocardial infarction. Four hundred seventy-five consecutive, unselected patients who underwent primary percutaneous coronary intervention were randomized to iopromide (n = 239) or iodixanol (n = 236). All patients received high-dose N-acetylcysteine and hydration. The primary end point was the proportion of patients with serum creatinine (sCr) increases ≥25% from baseline to 72 hours. Secondary end points were Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade, increase in sCr ≥50%, increase in sCr ≥0.5 or ≥1 mg/dl, and 1-month major adverse cardiac events. The primary end point occurred in 10% of the iopromide group and in 13% of the iodixanol group (95% confidence interval -9% to 3%, p for noninferiority = 0.0002). A TIMI myocardial perfusion grade of 0 or 1 was present in 14% of patients in the 2 groups. No differences between the 2 groups were found in any of the secondary analyses of sCr increase. No significant difference in 1-month major adverse cardiac events was found (8% vs 6%, p = 0.37). In conclusion, in a population of unselected patients with ST-segment elevation acute myocardial infarction who underwent primary percutaneous coronary intervention, iopromide was not inferior to iodixanol in the occurrence of CI-AKI; no significant differences were found in terms of tissue-level reperfusion and major adverse cardiac events between the 2 contrast agents.

Comparison of pre-hospital 600 mg or 900 mg vs. peri-interventional 300 mg clopidogrel in patients with ST-elevation myocardial infarction undergoing primary coronary angioplasty. The Load&Go randomized trial

300 mg clopidogrel in patients with ST-elevation myocardial infarction undergoing primary coronary angioplasty. The Load&Go randomized trial☆ Kenneth Ducci , Simone Grotti , Giovanni Falsini , Paolo Angioli , Francesco Liistro , Massimo Mandò , Italo Porto , Leonardo Bolognese a,⁎ a Cardiovascular and Neurologic Department, San Donato Hospital, Arezzo, Italy b Emergency Department, San Donato Hospital, Arezzo, Italy

Congestive heart failure during imatinib mesylate treatment

Imatinib mesylate (IM) is a very important drug in the treatment of gastrointestinal stromal tumors (GISTs) and chronic myeloid leukaemia (CML). In large clinical trials conducted until now it demonstrated a good cardiac safety profile. However during the last years many reports indicated a possible IM-induced cardiotoxicity. Here we report a case of a patient with a GIST who developed a severe and irreversible cardiac failure during IM treatment. Interestingly, she suffered from chronic renal failure, a condition that does not contraindicate treatment. Our opinion is that IM-induced cardiotoxicity could be facilitated by the presence of relevant comorbidities such as pre-existing cardiovascular disease or renal failure, commonly present in daily practice but excluded from clinical trials. Phase IV studies are needed to address the question of the real incidence of IM-induced cardiotoxicity in the general population.

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.

Long-Term Effectiveness and Safety of Sirolimus Stent Implantation for Coronary In-Stent Restenosis: Results of the TRUE (Tuscany Registry of Sirolimus for Unselected In-Stent Restenosis) Registry at 4 Years

OBJECTIVES The aim of this study was to evaluate the long-term clinical outcome of the efficacy and safety of sirolimus-eluting stents (SES) for in-stent restenosis (ISR) in the TRUE (Tuscany Registry of Unselected In-Stent Restenosis) database. BACKGROUND The TRUE registry demonstrated that SES in the treatment of bare-metal stent ISR is efficacious (5% of target lesion revascularization [TLR]) and safe (stent thrombosis <1%) at 9 months. Clinical outcome at 4 years is reported. METHODS A total of 244 patients with ISR who were treated with SES implantation represent the study population. The incidence of major adverse cardiac events was collected at 4 years. RESULTS At 4-year follow-up, overall mortality was 9.8% (24 patients). Cardiac death occurred in 11 (4.5%), nonfatal myocardial infarction in 8 (3.2%), and TLR in 27 (11.1%) patients for a cumulative event-free survival rate of 80.3%. Definite stent thrombosis occurred in 5 (2%) patients and possible stent thrombosis in 2 (0.8%). Diabetes remained an independent negative predictor of freedom from TLR (odds ratio [OR]: 0.38; 95% confidence interval [CI]: 0.20 to 0.71, p = 0.002) and major adverse cardiac events (OR: 0.38; 95% CI: 0.20 to 0.71, p = 0.002). CONCLUSIONS The clinical benefit of SES implantation for bare-metal stent ISR is maintained at 4 years with a low TLR rate and an overall incidence of stent thrombosis of 0.7% per year.

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.

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.