Davide Tavano

Circulating CD4+CD25hiCD127lo Regulatory T-Cell Levels Do Not Reflect the Extent or Severity of Carotid and Coronary Atherosclerosis

Objective—Regulatory T (Treg) cells play a protective role in experimental atherosclerosis. In the present study, we investigated whether the levels of circulating Treg cells relate to the degree of atherosclerosis in carotid and coronary arteries. Methods and Results—We studied 2 distinct populations: (1) 113 subjects, selected from a free-living population (carotid study), in which we measured the intima-media thickness of the common carotid artery, as a surrogate marker of initial atherosclerosis; and (2) 75 controls and 125 patients with coronary artery disease (coronary study): 36 with chronic stable angina, 50 with non-ST-elevation acute coronary syndrome, 39 with ST-elevation acute myocardial infarction. Treg-cell levels were evaluated by flow cytometry (Treg cells identified as CD3+CD4+CD25highCD127low) and by mRNA expression of forkhead box P3 or of Treg-associated cytokine interleukin 10. In the carotid study, no correlation was observed between Treg-cell levels and intima-media thickness. No differences in Treg-cell levels were observed comparing rapid versus slow intima-media thickness progressors from a subgroup of patients (n=65), in which prospective data on 6-year intima-media thickness progression were available. In the coronary group, Treg-cell levels were not altered in chronic stable angina patients. In contrast, nonunivocal variations were observed in patients suffering an acute coronary syndrome (with a Treg-cell increase in ST-elevation acute myocardial infarction and a Treg-cell decrease in non-ST-elevation acute coronary syndrome patients). Conclusion—The results suggest that determination of circulating Treg-cell levels based on flow cytometry or mRNA assessment is not a useful indicator of the extent or severity of atherosclerosis.

Comparison of bivalirudin monotherapy versus unfractionated heparin plus tirofiban in patients with diabetes mellitus undergoing elective percutaneous coronary intervention.

Bivalirudin demonstrated similar efficacy but resulted in a lower rate of bleeding compared to unfractionated heparin (UFH) plus platelet glycoprotein IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention. It has not been clearly evaluated whether this can also be applied to patients with diabetes mellitus. A total of 335 consecutive patients with diabetes mellitus referred for elective percutaneous coronary intervention were randomized in the Novel Approaches for Preventing or Limiting EventS (NAPLES) trial to receive bivalirudin monotherapy or UFH plus routine tirofiban. The primary composite end point (30-day composite incidence of death, urgent repeat revascularization, myocardial infarction, and all bleeding) was lower in the bivalirudin group than in the UFH plus tirofiban group (18.0% vs 31.5%, odds ratio 0.47, 95% confidence interval 0.28 to 0.79, p = 0.004). No death, urgent revascularization, or Q-wave myocardial infarction occurred. The rate of non-Q-wave myocardial infarction was similar in the 2 groups (10.2% in the bivalirudin group vs 12.5% in the UFH plus tirofiban group, p = 0.606). In contrast, fewer patients in the bivalirudin group experienced bleeding (8.4% vs 20.8%, odds ratio 0.34, 95% confidence interval 0.18 to 0.67, p = 0.002). This difference was mainly ascribed to the lower rate of minor bleeding (7.8% in the bivalirudin group vs 18.5% in the UFH plus tirofiban group, odds ratio 0.37, 95% confidence interval 0.19 to 0.74, p = 0.005), although the rate of major bleeding in the 2 groups was comparable (0.6% vs 2.4%, respectively; p = 0.371). In conclusion, in patients with diabetes mellitus undergoing elective percutaneous coronary intervention, the strategy of bivalirudin monotherapy compared to UFH plus routine tirofiban is safe and feasible and associated with a significant reduction of in-hospital bleeding.

Conservative Treatment of a Left Atrial Hematoma and a Localized Tamponade Occurring During Treatment of Coronary Total Occlusion

Cardiac tamponade during percutaneous coronary intervention is a rare but serious complication that can occur after coronary perforation. Even more infrequent is a tamponade subsequent to a localized left atrial hematoma. In the literature, we found just 5 similar cases, and all of them underwent surgical intervention.1–4 The surgical option, using a median sternotomy or left thoracotomy approach, was taken in the first hours after the procedure because of progressive hemodynamic deterioration. In 4 of them, it consisted of hematoma drainage and atrial decompression; in 1 patient, the surgical option was vessel wall repair. We report our experience of a patient who sustained this complication as a consequence of a large right coronary dissection. The patient was treated conservatively with a successful outcome. A 65-year-old man, previously treated with coronary artery bypass graft surgery and coronary percutaneous revascularization, was still symptomatic with effort angina refractory to maximal medical treatment. Myocardial scintigraphy showed evidence of inducible ischemia in the inferolateral left ventricular wall. He was hospitalized in our institution to attempt to recanalize the chronic occlusion of the right coronary artery (RCA). During the procedure, a subintimal dissection occurred in the middistal segment of the right coronary artery (Figure 1A and 1B), and in the more distal part of the posterolateral vessel, it resulted in a perforation of an atrial branch. Perivascular dye staining and contained extravasation were observed, although no pericardial opacification was noticed at fluoroscopy. After a few minutes, hemodynamic instability occurred, requiring dopamine support. The transthoracic echocardiogram showed a voluminous left atrial mass that almost obliterated the left atrial chamber. No pericardial effusion was present (Figure 2A and 2B). Protamine was administered to neutralize the heparin given during the procedure. Aspirin and clopidogrel were stopped. The patient was transferred to coronary care unit for monitoring and treatment. Hemodynamic instability (pulmonary congestion and hypotension) was treated with dopamine (10 ·k g 1 · min 1 ) and high-dose diuretic infusion. Cycles of facemask continuous positive airway pressure ventilation were used. A transesophageal echocardiogram showed a hypoechogenic, inhomogeneous, vacuolated large spheric mass (5560 mm in dimension) occupying a large portion of the left atrium. Flow obstruction was detected with color Doppler examination of mitral inflow (Figure 3A through 3C). A magnetic resonance examination clearly characterized the hemorrhagic nature of the mass (Movie I in the online Data Supplement and Figure 4). A new angiographic evaluation the day after the procedure excluded an ongoing blood supply to the hematoma, and the RCA was occluded proximally. Therapeutic options were discussed with the intensive care physicians and cardiac surgeons. We decided on conservative management. Dopamine was definitively withdrawn on the eighth day after the index procedure, and diuretic infusion was changed to oral. In the following days, the patient started mobilizing, and low-dose aspirin administration was restarted. The last transthoracic echocardiogram before discharge (15 days after the index complication) showed signs of initial hematoma reabsorption. Our patient had a follow-up 2 weeks after hospital discharge (25 days after the procedural complication); he was asymptomatic for dyspnea and had no angina on moderate effort. Transthoracic (Figure 5A and 5B) and transesophageal (Figure 5C and 5D) echocardiograms showed that the hematoma was almost completely reabsorbed.

Clinical and angiographic outcome of directional atherectomy followed by stent implantation in de novo lesions located at the ostium of the left anterior descending coronary artery

Background: Lesions located at the ostium of the left anterior descending coronary artery (LAD) are considered an ideal target for directional atherectomy (DCA), but few data are available about the value of using this strategy before stenting in comparison with stenting alone. Objectives: To investigate the immediate and mid term clinical and angiographic results of DCA followed by stent implantation for ostial LAD lesions. Design: Retrospective comparison of the immediate and mid term angiographic and clinical results of a series of 117 consecutive patients with de novo lesions located at the ostium of the LAD. Of these, 46 underwent DCA before stenting and 71 were treated with stenting alone. Results: Technical success in the two groups was similar at around 98%. DCA plus stenting provided a larger minimum lumen diameter at the end of the procedure than stenting alone (3.57 (0.59) mm v 3.33 (0.49) mm, p = 0.022). There were no differences for in-hospital major adverse events (MACE) (7.5% for atherectomy plus stenting, and 5.3% for stenting alone; p = 0.41). All patients had clinical follow up at a mean of 7.9 (2.7) months. Angiographic follow up was done in 89 patients (76%) at a mean of 5.9 (2.2) months. The atherectomy plus stenting group had a larger minimum lumen diameter than the stenting group (2.79 (0.64) mm v 2.26 (0.85) mm, p = 0.004) and a lower binary restenosis rate (13.8% v 33.3%, p = 0.031). Six month MACE were reduced in the atherectomy plus stenting group (8.7% v 23.9%, p = 0.048). Conclusions: Debulking before stenting in de novo lesions located at the ostium of the LAD is safe and is associated with a high rate of technical success. Follow up data show that DCA plus stenting results in a significantly larger minimum lumen diameter and a lower incidence of restenosis than stenting alone.

Limb revascularization feasibility in diabetic patients with critical limb ischemia: Results from a cohort of 344 consecutive unselected diabetic patients evaluated in 2009

AIMS To evaluate the feasibility of peripheral revascularization by angioplasty (PTA) or bypass grafting (BPG) in diabetic patients with critical limb ischemia (CLI). METHODS All diabetic patients referred to our Diabetic Foot Centre for foot lesion or rest pain were assessed for the presence of CLI as assessed by the TASC criteria. All patients underwent angiography that was evaluated jointly by an interventional radiologist, a vascular surgeon and a diabetologist of the diabetic foot care team. RESULTS During 2009, 344 diabetics were admitted because of CLI in a total of 360 limbs. PTA was performed in 308 (85.6%) limbs, and BPG was performed in 40 (11.1%) limbs in which PTA was not feasible. Revascularization could not be carried out in 12 (3.3%) limbs due to the lack of target vessel (9 limbs) or high surgical risk (3 limbs). According to the judgement of the vascular surgeon, BPG was anatomically feasible in 180 (58.4%) of the 308 limbs that underwent PTA. Therefore, considering also the 40 limbs that underwent BPG, surgical revascularization was judged anatomically possible in a total of 220 (61.1%) limbs. At 30 days, 19 (5.3%) above-the-ankle amputations were performed: 8 (66.7%) amputations were performed in the 12 non-revascularized limbs, 8 (2.6%) amputations were performed in the 308 limbs treated with PTA and 3 (7.5%) amputations were performed in the 40 limbs treated with BPG. CONCLUSIONS Revascularization by PTA is highly feasible in diabetics with CLI. The feasibility of revascularization by BPG is lower but nonetheless consistent. In centres where both revascularization procedures are available, it is possible to revascularize more than 96% of diabetics with CLI.

Revascularization by Angioplasty of Type D Femoropopliteal and Long Infrapopliteal Lesion in Diabetic Patients With Critical Limb Ischemia Are TASC II Recommendations Suitable? A Population-Based Cohort Study

Feasibility of revascularization of type D femoropopliteal and long infrapopliteal lesions by angioplasty (peripheral translumenal angioplasty [PTA]) in diabetic patients with critical limb ischemia (CLI) according to the TransAtlantic Inter-Society Consensus (TASC) II recommendations was studied. A total of 292 diabetic patients were admitted for CLI; 308 limbs underwent a PTA. Out of 211 femoropopliteal lesions treated with PTA, 44 were TASC II type A, 45 type B, 48 type C, and 76 type D lesions. In 44 of the 76 patients with type D lesions revascularized by PTA, no artery was patent down to the foot before the PTA. In 172 limbs with all infrapopliteal arteries occluded, revascularization was carried out down to the foot in 167 limbs. Follow-up was 3.1 ± 0.3 years. A first episode of restenosis occurred in 66/308 limbs with an incidence/year of 7.9. PTA procedures were successfully repeated in 57/66 restenosis episodes: secondary patency was 97.1%. The incidence/year of type D femoropopliteal lesions was 5.4, the incidence/year in others was 5.0, without statistically significant differences: P = .417. The only variable found significantly associated with restenosis occurrence on logistic analysis was the presence of lesions in both femoropopliteal and infrapopliteal axes. A total of 26/308 above-the-ankle amputations were performed, with an incidence/year of 2.5. Multivariate analysis showed the independent role of only crural artery occlusion after PTA. These data show that the choice to refer to angioplasty diabetic patients with type D and/or long infrapopliteal lesions without good run-off at the foot and/or high surgical risk allowed high revascularization feasibility, with an optimal amputation outcome.

The use of drug eluting stents in single and multivessel disease: results from a single centre experience

Objective: Drug eluting stents have been shown to reduce the rate of in-stent restenosis in cases where single lesions are treated. The performance of these stents, in patients with multivessel disease and complex lesions, however, remains unknown. Our experience with sirolimus eluting stents in such patients is presented. Design and patients: This study includes all consecutive patients treated at San Raffaele Hospital and EMO Centro Cuore Columbus, Milan, Italy treated with sirolimus eluting stents. Results: Between April 2002 and March 2003, 486 patients with 1027 lesions were treated (437 males, 49 females) with a mean (SD) age of 62.2 (10.5) years. Of all patients studied, 19.1% had single vessel disease, 33.8% had two vessel disease, and 47.1% had three vessel disease. Of the whole study group, 20.3% of patients had diabetes mellitus. A mean (SD) of 2.3 (0.4) stents per patient and 1.1 (0.2) stents per lesion were implanted. The baseline mean reference diameter was 2.7 (0.6) mm with a mean minimal luminal diameter of 0.9 (0.5) mm. Post-stenting, the acute gain was 1.8 (0.6) mm. During hospital stay one patient died (0.2%) and 13 (2.7%) patients had in-hospital myocardial infarction (MI). One patient required urgent repeat percutaneous coronary intervention. Six months clinical follow up was performed in all 347 eligible patients. Six months mortality was 2.0% (n  =  7) and acute MI occurred in 0.3% (n  =  1). Target lesion revascularisation occurred in 9.5% (n  =  33) of the patients and target vessel revascularisation (TVR) in 11.5% (n  =  40) of the patients. Major adverse cardiac event rate was 13.8% (n  =  48). TVR was 4.5% for single vessel disease and 13.2% for multivessel disease. Diabetes mellitus was the only significant predictor for TVR. Conclusion: The use of drug eluting stents in single and multivessel coronary disease produces good short and medium term results with a low rate of revascularisation. Longer term follow-up is required to confirm these observations.

Valvulopathies in sub-Saharan African children: Patterns, humanitarian interventions and cardiac surgical problems

Despite the high burden of rheumatic fever in sub-Saharan African, there is currently no sustained and comprehensive strategy to control the disease. Consequently in this area the number of patients affected by rheumatic valve disease (RVD), most with a surgical indication, is 10-20 fold higher than in industrialised countries and estimates indicate that more than 50% of African RVD patients will die before age 25. In this paper, we review clinical and management issues of RVD in children in sub-Saharan Africa. Severe heart failure and undergrowth are the prevalent presentation of the illness. Severe mitral regurgitation is the commonest rheumatic valvulopathy observed in the first and second decades. Valve repair, the approach of choice, may be associated with unfavourable outcomes in patients with extreme cardiomegaly. In young people, whenever correct anticoagulation may reasonably be achieved, mechanical mitral prostheses should be preferred, even in females. The early deterioration of biologic mitral prostheses strongly suggests limiting their use to those cases in which correct anticoagulation is not feasible. In most sub-Saharan countries, socioeconomic factors strongly limit access to health services and to cardiac surgery in particular. Efforts to overcome these barriers have resulted in humanitarian projects along two patterns: creation of high tech on site health care structures or transfer of children with complex diseases to receive highly specialised cardiac surgical care abroad. We summarise the experience of our programme that followed the latter approach.

CRosser As First choice for crossing Totally occluded coronary arteries (CRAFT Registry): focus on conventional angiography and computed tomography angiography predictors of success.

AIMS We investigated the use of the CROSSER catheter, a CTO crossing device based upon high frequency mechanical vibration, as a first resort to treat patients with chronic total occlusions (CTO) while describing angiographic and computed tomography coronary angiography (CTCA) serving as predictors for success. METHODS AND RESULTS Eighty consecutive patients were enrolled in this prospective multicentre registry of patients treated for a CTO. For 76.3% of the patients, this was the first attempt to open the CTO. Overall success rate was 75%. By conventional coronary angiography, the length of the occlusion was 26.7±14.1 mm and there was a difference in successful vs. unsuccessful cases (24.5±13.9 and 32.8±13.1, p=0.02). The presence of angulation, as defined qualitatively, was more prevalent in failed cases (60.0% vs. 32.2%, p=0.03). The mean ratio CROSSER distance within the occlusion site and length of the occlusion showed a trend towards statistical significance in successful procedures (0.56±0.90 vs. 0.30±0.34, p=0.08). During hospitalisation, two patients had a non-fatal myocardial infarction. One patient experienced delayed onset of tamponade six hours postprocedure. At 30 days, two patients had PCI in a non-treated vessel and one patient had a transient ischaemic attack. Relation to the CROSSER catheter was inconclusive. CONCLUSIONS The success rate of the use of a dedicated-CTO device--the CROSSER catheter--as a first choice to open a chronic total occlusion was 75%. By multivariate analysis, in a subset of patients that were imaged with computed tomography coronary angiography, the absence of angulation was related with higher success rate.

The CID Chrono™ cobalt–chromium alloy carbofilm-coated coronary stent system

BACKGROUND In an attempt to improve the stents safety, development of bare metal stents (BMS) continues, with new materials and geometry. Chrono (CID, Italy) is a thin strut cobalt-chromium (Co-Cr) stent combining the clinical benefits of the bio- and haemo-compatible Carbofilm coating. METHODS We assessed the safety and efficacy of percutaneous coronary interventions (PCI) using the new Co-Cr Chrono stent in patients undergoing elective PCI for de novo lesions in native coronary vessels. The patients were followed for 12 months for the occurrence of major cardiac events (MACE, defined as death, myocardial infarction, repeat PCI and bypass surgery). Patients with complex (B2/C) lesions were compared to those with non-complex lesions (A/B1). RESULTS A total of 340 consecutive patients were analysed: 155 patients with complex lesions (Complex group) and 185 patients with non-complex lesions (Non-complex group). Dual antiplatelet therapy was maintained >1 month in 21% of patients in both Complex and Non-complex group. Stent length was longer in the Complex group (25 ± 10 mm versus 17 ± 6 mm; p<0.001). Stent diameter <3.0 mm was most frequent in the Complex group (35.5% versus 27.5%; p<0.05). During the 12-month follow-up period MACE occurred in 10.6% of the global population (12.3% in the Complex group and 9.2% in the Non-complex group; p=0.43). Repeat PCI was most frequent in the Complex group (9.7% versus 3.8%; p=0.044). The incidence of definite and probable stent thrombosis (ARC criteria) was 1.29% in the Complex group and 1.08% in the Non-complex group (p=1.0). CONCLUSIONS Implantation of the Co-Cr Chrono stent results in a good safety and efficacy for both complex and non-complex de-novo coronary artery lesions.