Alessandro Lualdi

Drug-eluting balloon for treatment of in-stent restenosis after carotid artery stenting: Preliminary report

Purpose To evaluate the safety and efficacy of drug-eluting balloons (DEB) for the treatment of in-stent restenosis (ISR) after carotid artery stenting (CAS). Methods Among 830 consecutive patients undergoing CAS between November 2001 and June 2012, significant ISR (>80% stenosis) occurred in 10 (1.2%) asymptomatic patients. Angioplasty with DEB treatment was performed in 7 patients (6 internal and 1 common carotid arteries) at a mean of 20.9 ± 19.4 months (median 12.1) after CAS. Intravascular ultrasound (IVUS)–guided predilation with distal cerebral protection was carried out with a cutting balloon followed by inflation of a DEB with a 1:1 stent-to-balloon size ratio. Results Technical/procedural success was achieved in all cases. Angiographic stenosis decreased from 83% ± 5% to 18% ± 6%. At IVUS evaluation, minimal lumen area increased from 3.19 ± 1.73 to 12.78 ± 1.97 mm2 (p=0.0001), stent area was unchanged (from 17.36 ± 4.36 to 17.52 ± 4.34 mm2, p=0.70), and the restenosis area decreased from 13.58 ± 5.27 to 4.71 ± 3.06 mm2 (p=0.0005). At a mean follow-up of 13.7 ± 1.5 months (median 13.7), 1 patient had a minor stroke ipsilateral to the ISR vessel 2 months after DEB treatment; the stent was widely patent on duplex ultrasound and angiographic images. Overall, the average PSV decreased from 4.0 ± 1.0 to 0.9 ± 0.1 m/s (p=0.0001). At 6 and 12 months, PSVs after DEB treatment were significantly lower compared to those assessed at comparable intervals after CAS. Conclusion The use of DEBs to treat ISR after CAS shows promising acute and midterm results.

Rationale and design of the PERFECTION (comparison between stress cardiac computed tomography PERfusion versus Fractional flow rEserve measured by Computed Tomography angiography In the evaluation of suspected cOroNary artery disease) prospective study

BACKGROUND Non-invasive stress tests are commonly used as gatekeepers to invasive coronary angiography (ICA) in patients with suspected coronary artery disease (CAD). New computed tomography angiography (CTA) techniques such as fractional flow reserve calculated by CTA (FFRCT) and stress myocardial computed tomography perfusion (CTP) have emerged as potential strategies to combine anatomical and functional evaluation of CAD in one technique. The aim of this study is to compare per-vessel diagnostic accuracy of FFRCT versus stress myocardial CTP for the detection of functionally significant coronary artery disease (CAD), using invasive FFR as the reference standard. METHODS Subjects with suspected CAD due to chest pain who have no contra-indications to FFRCT or stress myocardial CTP and who are referred for non-emergent, clinically indicated invasive coronary angiography (ICA), will be enrolled. A total of 300 subjects will be enrolled within 24 months. RESULTS The primary study endpoint will be the comparison of per-vessel diagnostic accuracy of CTA versus FFRCT versus stress myocardial CTP for the diagnosis of hemodynamically significant stenosis as defined by invasive FFR ≤0.80. CONCLUSIONS In the PERFECTION study, the comparison between FFRCT and stress myocardial CTP will provide understanding about which technology is more accurate for the diagnosis of functionally significant CAD.

Nitric Oxide Synthetic Pathway in Red Blood Cells Is Impaired in Coronary Artery Disease

Background All the enzymatic factors/cofactors involved in nitric oxide (NO) metabolism have been recently found in red blood cells. Increased oxidative stress impairs NO bioavailability and has been described in plasma of coronary artery disease (CAD) patients. The aim of the study was to highlight a potential dysfunction of the metabolic profile of NO in red blood cells and in plasma from CAD patients compared with healthy controls. Methods We determined L-arginine/NO pathway by liquid-chromatography tandem mass spectrometry and high performance liquid chromatography methods. The ratio of oxidized and reduced forms of glutathione, as index of oxidative stress, was measured by liquid-chromatography tandem mass spectrometry method. NO synthase expression and activity were evaluated by immunofluorescence staining and ex-vivo experiments of L-[15N2]arginine conversion to L-[15N]citrulline respectively. Results Increased amounts of asymmetric and symmetric dimethylarginines were found both in red blood cells and in plasma of CAD patients in respect to controls. Interestingly NO synthase expression and activity were reduced in CAD red blood cells. In contrast, oxidized/reduced glutathione ratio was increased in CAD and was associated to arginase activity. Conclusion Our study analyzed for the first time the whole metabolic pathway of L-arginine/NO, both in red blood cells and in plasma, highlighting an impairment of NO pathway in erythrocytes from CAD patients, associated with decreased NO synthase expression/activity and increased oxidative stress.

Carotid stenting through the right brachial approach for left internal carotid artery stenosis and bovine aortic arch configuration.

Unfavorable complex anatomy or congenital anomalies of supra-aortic vessel take-off may increase carotid artery stenting (CAS) procedural difficulties and complications through the femoral route. We assessed the feasibility, safety, and efficacy of CAS through the right brachial approach in patients in whom left internal carotid artery stenosis and bovine aortic arch configuration were identified with computed tomography (CT) angiography. Bovine configuration of the aortic arch and left carotid artery stenosis were easily identified by CT angiography and successfully treated through the right brachial approach technique.

Carotid Artery Stenting With Proximal Embolic Protection via a Transradial or Transbrachial Approach: Pushing the Boundaries of the Technique While Maintaining Safety and Efficacy

Purpose: To compare the feasibility and safety of proximal cerebral protection to a distal filter during carotid artery stenting (CAS) via a transbrachial (TB) or transradial (TR) approach. Methods: Among 856 patients who underwent CAS between January 2007 and July 2015, 214 (25%) patients (mean age 72±8 years; 154 men) had the procedure via a TR (n=154) or TB (n=60) approach with either Mo.MA proximal protection (n=61) or distal filter protection (n=153). The Mo.MA group (mean age 73±7 years; 54 men) had significantly more men and more severe stenosis than the filter group (mean age 71±8 years; 100 men). Stent type and CAS technique were left to operator discretion. Heparin and a dedicated closure device or bivalirudin and manual compression were used in TR and TB accesses, respectively. Technical and procedure success, crossover to femoral artery, 30-day major adverse cardiovascular/cerebrovascular events (MACCE; death, all strokes, and myocardial infarction), vascular complications, and radiation exposure were compared between groups. Results: Crossover to a femoral approach was required in 1/61 (1.6%) Mo.MA patient vs 11/153 (7.1%) filter patients mainly due to technical difficulty in engaging the target vessel. Five Mo.MA patients developed acute intolerance to proximal occlusion; 4 were successfully shifted to filter protection. A TR patient was shifted to filter because the Mo.MA system was too short. CAS was technically successful in the remaining 55 (90%) Mo.MA patients and 142 (93%) filter patients. The MACCE rate was 0% in the Mo.MA patients and 2.8% in the filter group (p=0.18). Radiation exposure was similar between groups. Major vascular complications occurred in 1/61 (1.6%) and in 3/153 (1.96%) patients in the Mo.MA and filter groups (p=0.18), respectively, and were confined to the TB approach in the early part of the learning curve. Chronic radial artery occlusion was detected by Doppler ultrasound in 2/30 (6.6%) Mo.MA patients and in 4/124 (3.2%) filter patients by clinical assessment (p=0.25) at 8.1±7.5-month follow-up. Conclusion: CAS with proximal protection via a TR or TB approach is a feasible, safe, and effective technique with a low rate of vascular complications.

Use of multiple overlapping sirolimus-eluting stents for treatment of long coronary artery lesions: Results from a single-center registry in 318 consecutive patients

UNLABELLED Drug-eluting stents (DES) are superior to bare metal stents in the prevention of restenosis and target lesion revascularization (TLR). This has led to a more aggressive use of DES in everyday interventional cardiology practice. METHODS All consecutive patients who underwent coronary artery stenting with greater than 34 mm of overlapping, sirolimus-eluting stent (SES) were reviewed from a prospectively created database. A prespecified group of patients with greater than 60 mm of SES was also followed. RESULTS 318 patients were followed up at a minimum of 6 months and a mean of 9 months. The mean target lesion stented length was over 55 mm. Use of IVUS was 19.8%. Forty patients (12.6%) suffered a peri-procedural CK-MB rise. The MACE rate at 9 months was 17% with 12.6% being periprocedural myocardial infarction (MI). Clinically driven TLR was 4.4% and cardiac death was 1.3%. There were 4 cases defined as late stent thrombosis. The independent predictors of periprocedural MI were the presence of a major side branch and longer target lesion stented length, with stable angina being a negative predictor. The independent predictors of in-stent restenosis were unstable angina and target lesion number per patient. There was a trend to increased MACE in the subgroup with longer than 60 mm of SES length. CONCLUSION The use of multiple, overlapping SES is safe and effective with an acceptably low follow up MACE rate. A significant peri-procedural CK-MB rise appears to be a risk of long segment stenting. Whether this translates to long-term sequelae needs further investigation.

Carotid Artery Stenting in Patients With Left ICA Stenosis and Bovine Aortic Arch: A Single-Center Experience in 60 Consecutive Patients Treated Via the Right Radial or Brachial Approach

Purpose To assess the safety and efficacy of carotid artery stenting (CAS) of the left internal carotid artery (LICA) from a right radial/brachial approach in patients with bovine aortic arch. Methods: Among 505 consecutive CAS patients treated at our facility between June 2007 and December 2012, 60 (11.9%) patients (44 men; mean age 73±9 years) with LICA stenosis and bovine arch were treated from a right radial (n=32) or brachial (n=28) approach. Three quarters of the patients had characteristics qualifying them at high surgical risk; 52 were asymptomatic. The types of cerebral protection (a distal filter or proximal MO.MA system), stent, and technique were at the operations discretion. Results The radial/brachial approach was successful in 59 (98.3%) of 60 procedures; 1 case was converted to a femoral approach. Proximal protection was used in 15 cases (11 brachial, 4 radial) with severe, soft plaques, although the MO.MA system proved too short in a tall patient having a radial approach and a filter was used. Clinical success with no adverse events was 96.7% owing to 1 retinal embolism and 1 minor stroke. Vascular complications occurred in 2 (3.3%) brachial group patients. No major bleeding was encountered. Over a mean follow-up of 18.7±17.5 months, midterm event-free survival was 93%. No target vessel revascularization was necessary. Conclusion CAS via a right radial or brachial approach is safe and effective in patients with LICA stenosis and types 1 or 2 bovine arch.

Nitric Oxide Synthetic Pathway in Patients with Microvascular Angina and Its Relations with Oxidative Stress

A decreased nitric oxide (NO) bioavailability and an increased oxidative stress play a pivotal role in different cardiovascular pathologies. As red blood cells (RBCs) participate in NO formation in the bloodstream, the aim of this study was to outline the metabolic profile of L-arginine (Arg)/NO pathway and of oxidative stress status in RBCs and in plasma of patients with microvascular angina (MVA), investigating similarities and differences with respect to coronary artery disease (CAD) patients or healthy controls (Ctrl). Analytes involved in Arg/NO pathway and the ratio of oxidized and reduced forms of glutathione were measured by LC-MS/MS. The arginase and the NO synthase (NOS) expression were evaluated by immunofluorescence staining. RBCs from MVA patients show increased levels of NO synthesis inhibitors, parallel to that found in plasma, and a reduction of NO synthase expression. When summary scores were computed, both patient groups were associated with a positive oxidative score and a negative NO score, with the CAD group located in a more extreme position with respect to Ctrl. This finding points out to an impairment of the capacity of RBCs to produce NO in a pathological condition characterized mostly by alterations at the microvascular bed with no significant coronary stenosis.

Sex difference in long-term clinical outcome after sirolimus-eluting stent implantation

BackgroundCoronary stenting in women has been associated with worse results in terms of morbidity, mortality, and restenosis rate in the bare-metal stent era, possibly due to higher risk profile and smaller coronary vessels. Although drug-eluting stents have equalized clinical results, no data are available on long-term outcomes between sexes. ObjectivesTo evaluate the role of sex in acute, mid-term, and long-term clinical outcome after sirolimus-eluting stent (SES) implantation. MethodsWe retrospectively evaluated 1186 patients, 970 (81.8%) male and 216 (18.2%) female, treated with SES implantation between April 2002 and December 2005. ResultsWomen were older (P=0.049), more likely to have hypertension (43.5 vs. 33.7%, P=0.006), single-vessel disease (63.9 vs. 42.5%, P=0.03), and unstable angina (16.6% vs. 9.2%, P=0.001) and more frequently received small (⩽2.75 mm) vessel stenting (39.3 vs. 28.2%, P=0.001). The two groups were similar for lesion and procedural characteristics. Overall, the stent thrombosis rate was 0.4% (0.5% in women vs. 0.3% in men, P=not significant). At 6-month follow-up, no significant difference in major adverse cardiac event was observed. Long-term follow-up (median time 33.2 months), available in 180 (83.3%) women and 720 (75%) men, showed higher angina recurrence rate (17.7 vs. 11%, P=0.013), percutaneous coronary re-intervention (16.1 vs. 8.7%, P=0.001) and target vessel revascularization (3.9 vs. 0.9%, P=0.001) in women compared with men. Late stent thrombosis, need for coronary artery bypass grafting, and mortality were similar in both groups. ConclusionNo sex difference was observed in acute and 6-month outcome after SES implantation despite older age, more unstable clinical presentation, and more frequent small vessel stenting in women. However, long-term clinical follow-up (up to 5 years) in women showed higher symptom recurrence and target vessel revascularization rate but no difference in overall major adverse cardiac events.

Randomized trial of predilation versus direct stenting for treatment of carotid artery stenosis

BACKGROUND A controversial aspect of carotid artery stenting (CAS) is the placement of a stent with or without predilation. The study was designed to test the hypothesis that direct stenting (DS) was not inferior to CAS with predilation. METHODS Elective CAS with filter protection was performed in 205 consecutive, unselected patients with carotid artery stenosis (>50% if symptomatic and > or =75% if asymptomatic by Doppler assessment) who were randomly assigned to CAS with predilation (n=100) or direct stenting (DS, n=105). Filter and stent selection were left to the operators discretion. The study end-point was the angiographic success, defined as < or =30% angiographic residual stenosis after CAS without abnormal angiographic findings in cerebral circulation and without cross-over to predilation in the DS group. RESULTS At baseline, patient clinical characteristics and stenosis anatomic features did not differ between groups. Angiographic success was 99% and 97%, p=0.33, in predilation and DS, respectively. No cross-over to predilation occurred in the DS group. Procedural time was shorter in DS as compared to predilation (24.3+/-7% versus 19.9+/-6%, p=0.001) and visible debris were more frequently captured in predilation as compared to DS (50% versus 36%, p=0.003). No peri-procedural and 30-day death or major stroke occurred in both groups. Minor stroke and TIA rates were similar in either group (2% versus 0% and 8% versus 5.7%, p=ns, respectively). CONCLUSION In an unselected, consecutive series of patients submitted to CAS, DS is a feasible technique and is not inferior to CAS with predilation.