The future of new aortic valve replacement approaches.

Aortic valve disease is a growing cause of mortality and morbidity, especially in developed countries. Whereas medical therapy is associated with an ominous prognosis, since the 1970s, surgical valve replacement has represented a standard therapy for fit patients. Indeed, this approach is safe and feasible in younger patients without comorbidities. However, in unfit patients, surgery may be associated with a very high risk. The advent of transcatheter valve replacement techniques, by means of percutaneous or transapical approaches, has been recently introduced into mainstream clinical practice and is likely to radically change the treatment of aortic valve disease. At present, further data are needed to thoroughly appraise the long-term risk-benefit balance of transcatheter valve replacement techniques. For this reason, it can only be considered for high surgical risk patients, but early results are so promising that in the future, transcatheter aortic valve implantation could became the first therapeutic choice, even for low-risk patients.

Altered nitric oxide/cGMP platelet signaling pathway in platelets from patients with acute coronary syndromes.

This study was aimed at evaluating whether the nitric oxide (NO)/cyclic GMP (cGMP) signaling pathway is altered in platelets from patients with an acute coronary syndrome (unstable angina and acute myocardial infarction). We investigated 10 patients with unstable angina (UA), 14 with acute myocardial infarction (AMI) and 14 age and sex-matched healthy subjects. The serum markers of platelet activation (sP-selectin), inflammation (TNF-alpha and erythrocyte sedimentation rate), thrombotic state (fibrinogen) and plaque disruption were significantly higher in both UA and AMI patients compared to the healthy controls. In their platelets we assessed the cGMP levels in basal conditions and after stimulation with sodium nitroprusside (SNP), and performed Western blot analysis of homogenates to measure the expression of soluble guanylate cyclase isoforms. Basal levels of cGMP (pmol/10(10) platelets) were significantly higher in platelets from UA patients (1,097 +/- 111; p < 0.0001) and AMI (1,122 +/- 77; p < 0.0001) compared to those collected from healthy controls (497 +/- 80). The platelets of AMI patients exhibited a lack of cGMP increase after SNP stimulation in comparison with UA patients. The phosphorylation of upstream (Akt1 protein kinase alpha and endothelial NO synthase) and downstream (vasodilator-stimulated phosphoprotein, VASP) signaling proteins of the NO/cGMP pathway was investigated: serine phosphorylation in Akt1, eNOS and VASP was enhanced in platelets from UA and AMI patients when compared to controls. Furthermore, in AMI patients the inhibitors of guanylate cyclase and cGMP-dependent protein kinase did not revert the VASP phosphorylation. These data suggest that platelets from AMI patients are more resistant to SNP stimulation, not only as cGMP production, but also in terms of VASP activation. From these ex vivo results we hypothesize that the increased inflammatory state which often accompanies patients with cardiovascular diseases might promote a platelet preactivation resulting in their reduced sensitivity to NO.

Results of percutaneous drug-eluting stent implantation for unprotected left main coronary disease according to left ventricular systolic function.

OBJECTIVES: We aimed to appraise the early and long-term outcome after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) in patients with unprotected left main disease (ULM) and left ventricular systolic dysfunction (LVD). BACKGROUND: PCI with DES has being performed with increasing frequency in subjects with ULM and LVD, but few specific data are available. SETTING AND PATIENTS: We identified patients undergoing PCI with DES for ULM at our Center and distinguished those with ejection fraction (EF) >50% from those with 40% 50%, 32.0% with 40% 50%, 41.6% in those with 40%

Impact of routine angiographic follow-up after percutaneous coronary drug-eluting stenting for unprotected left main disease: the Turin Registry.

BACKGROUND: Most cardiologists performing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) for unprotected left main disease (ULM) mandate mid-term angiographic follow-up, yet there are few data supporting this approach. We aimed to retrospectively compare the outcome of patients with ULM treated with DES according to their follow-up management strategy. METHODS: Patients with ULM stenosis undergoing PCI with DES and surviving up to 6 months were retrospectively identified from our ongoing database. We distinguished those undergoing clinical follow-up only, those with clinically driven angiographic follow-up, and those with routine angiographic follow-up. The primary end-point was the long-term rate of major adverse cardiac events (MACE, i.e., death, myocardial infarction, bypass surgery, or repeat ULM PCI). RESULTS: A total of 198 patients were included: 55 (28%) in the clinical follow-up group, 64 (32%) in the clinically driven angiographic follow-up group, and 79 (40%) in the routine angiographic follow-up group. After 37.0 +/- 15.7 months, mortality was similar in the 3 groups (respectively 7.3, 4.7, and 5.9%, p = 0.27). However, MACE were significantly more common in the clinically driven angiographic follow-up group (42.2 vs. 7.3 and 26.1%, p = 0.02), mainly due to the expected increase in repeat revascularization in those undergoing angiographic follow-up (23.4 vs. 1.8 and 13.14%). Notably, there were no differences in the rate of stent thrombosis across the three groups, with rates of 3.1 vs. 1.8 and 2.5% (p = 0.35). CONCLUSIONS: An expectant management can be safely adopted in most patients with ULM treated percutaneously, as long as a low threshold for control coronary angiography is maintained.

Very long-term results comparing a simple versus a complex stenting strategy in the treatment of coronary bifurcation lesions.

BACKGROUND: The optimal stenting strategy for coronary bifurcation lesions has not yet been defined, especially given the lack of very long-term data (>24 months). We compared our long-term results of a simple vs complex stenting strategy in patients with bifurcation lesions. METHODS: We retrospectively selected subjects undergoing percutaneous coronary intervention (PCI) with stenting in a bifurcation lesion between June 2002 and December 2005, comparing those treated with a simple technique vs those treated with a complex one. The primary end-point was the rate of major adverse cardiac events (MACE) at >24 months of follow-up. RESULTS: A total of 326 patients were included, 64.7% treated with a simple technique (Group A) and 35.3% with a complex strategy (Group B). Drug-eluting stents were used in 82.0% and 73.0%, respectively (P = 0.059), final kissing balloon in 47.9% and 53.0% (P = 0.37), and procedural success obtained in 99.5% and 99.1% (P = 0.66). After a median of 34 months, MACE occurred in 52 (26.5%) in Group A and in 32 (31.4%) in Group B (P = 0.37), cardiac death in six (3.1%) vs four (3.9%, P = 0.70), myocardial infarction in 13 (6.6%) vs 6 (5.9%, P = 0.80), target vessel revascularization in 36 (18.4%) vs 29 (28.4%, P = 0.04), and bypass in five (2.6%) vs two (2%, P = 0.74). Definite stent thrombosis was adjudicated in two (1%) vs one (0.9%, P = 0.98). CONCLUSIONS: This study, comparing simple and complex stenting strategies for the treatment of coronary bifurcation lesions, shows that both techniques are associated with favorable clinical results and low adverse events rates at long-term follow-up.

Bacteriology of infected extracted pacemaker and ICD leads.

INTRODUCTION: Pacemaker and implantable cardioverter defibrillator infections, when not treated, lead to serious consequences. The aim is to identify the prevalent strains of the responsible bacteria to guide an effective therapy. METHODS: Between May 2003 and April 2008, 118 leads were extracted from 61 patients, with chronic draining sinus, pocket infection, pacemaker endocarditis, or sepsis. Following extraction, samples of the leads underwent cultural and antibiogram examination. RESULTS: Staphylococcus epidermidis was the most frequently isolated bacterial strain (37.7%), followed by Gram-positive flora (16.1%), Staphylococcus aureus (14.3%), Candida parapsilosis (5.4%), Staphylococcus schleiferi (5.4%), Corynebacterium species, and Staphylococcus hominis (3.6%). Cultures were negative in 14.3% of the samples. Retained sensitivity to antibiotics were reported as follows: teicoplanin/vancomycin 100%, doxicyclin 96%, amikacin 94%, piperacillin-tazobactam 58%, cotrimoxazole 78%, gentamycin 65%, quinolones 47%, rifampicin 44%, cephalosporins 25%, and oxacillin 25%. Within staphylococci, involved in about 60% of the infections, S. hominis and S. epidermidis showed the highest antibiotic resistance. In case of sepsis, sensitivity was retained for glycopeptides and amikacin (about 100%), and to a lower degree for doxicyclin (80%). Arbitrarily stratifying into recent (<3 months) and chronic (>3 months) infections, an increase in time prior to referral for lead extraction was associated with a significant increase in antibiotic resistance. CONCLUSION: Bacteria associated with pacemaker and implantable cardioverter defibrillator-related infections, staphylococci in about 60% of the cases, show poor susceptibility to antibiotics, presenting three out of four methicillin-resistant features. Therefore, systemic antibiotics, mainly glycopeptides, must not be delayed awaiting the complete removal of the implanted system.

Update on dedicated bifurcation stents.

Coronary bifurcation lesions represent an area of ongoing challenge in interventional cardiology. Contemporary studies using drug-eluting stents report a reduction in main vessel (MV) restenosis; however, residual stenosis and restenosis at side-branch ostium remain an issue. Multiple two-stent bifurcation strategies exist, including T-stenting, V-stenting, simultaneous kissing stenting, culotte stenting, and crush stenting technique. Each strategy has its own advantages and disadvantages, but on the basis of results of numerous randomized trials, the provisional approach of implanting one stent on the main branch has became the default approach to most bifurcation lesions. Dedicated bifurcation stents have been designed to specifically address some of the shortcomings of the conventional percutaneous approach to bifurcation intervention. The majority of the devices are aimed at facilitating the provisional approach. Dedicated bifurcation stents should enable all operators to treat the side-branch ostium simultaneously with the main branch, preserving a safe, permanent access to side branch during the procedure. In the future, the use of these new devices will probably enhance the interaction between adequate mechanical scaffolding and accurate delivery of the appropriate dosage of any new antirestenosis drugs. There are currently 11 devices available that either have completed or are undergoing first-in-man trials. The development of further drug-eluting platforms and larger controlled studies should demonstrate their clinical applicability, efficacy, and safety before they are widely incorporated into daily practice.

Impact of multivessel stenting on top of percutaneous revascularization for unprotected left main disease in the drug-eluting stent era: insights from the Turin registry.

OBJECTIVE: Drug-eluting stents (DESs) are commonly used in patients with unprotected left main (ULM) disease. Although multivessel disease and stenting are frequent in this population, pertinent details on short-term and long-term outcomes are lacking. SETTING AND PATIENTS: We identified consecutive patients with DES treatment for ULM. We distinguished patients presenting isolated ULM stenting (group A) from those with additional treatment of at least another major vessel (group B). The primary end point was major adverse cardiovascular events (i.e. death, myocardial infarction or target vessel revascularization). We compared the impact of a DES-only versus a hybrid DES and bare metal stent strategy for non-ULM lesions. RESULTS: A total of 189 patients were included, 25% in group A and 75% in group B. In-hospital events were similarly favorable (cardiac death in 0 and 2%, respectively, P = 0.58). A total of 99% patients were followed for a median of 25 months, yielding major adverse cardiovascular events in 17 and 37.5% (P = 0.011). Specifically, death occurred in 4 and 8.5% (P = 0.52), cardiac death in 0 and 7% (P = 0.12), myocardial infarction in 6.5 and 9% (P = 0.76) and target vessel revascularization in 4.3 and 22% (P = 0.006). Adoption of a systematic DES-only strategy for non-ULM lesions conferred significant benefits on major adverse cardiovascular events and repeat non-ULM revascularizations in comparison to a hybrid strategy (22 versus 45%, P < 0.001, and 9 versus 19%, P = 0.004, respectively), at both bivariate and multivariable analyses. CONCLUSION: Multivessel stenting on top of DES implantation for ULM can be performed with favorable early results. Systematic DES implantation for both ULM and non-ULM lesions is pivotal to maximize clinical results and minimize long-term recurrences.

A long-term comparison of drug-eluting versus bare metal stents for the percutaneous treatment of coronary bifurcation lesions.

BACKGROUND: After the first exciting results on drug-eluting stents (DES), many concerns have been raised on their potential risk for late stent thrombosis. Whereas DES appear beneficial at early and mid-term for coronary bifurcation lesions, no data are available on their long-term safety in this setting in comparison to bare metal stents (BMS). We thus aimed to appraise the long-term (> 2 years) outcomes of patients with bifurcation lesions treated with DES vs. BMS. METHODS: We abstracted baseline, procedural and follow-up data on all patients with bifurcation coronary lesions (both branches with reference vessel diameter > 2.0 mm) treated with stent implantation at our centre. The primary end-point was the long-term (> 2 years) rate of major adverse cardiac events (MACE, i.e. cardiac death, myocardial infarction, coronary artery bypass grafting and target vessel revascularization). RESULTS: A total of 315 patients and 334 lesions were included, 84.4% treated with DES, and 15.6% treated with BMS. The side branch was stented in 108 cases, according to a provisional T in 76 (22.7%), crushing in 15 (4.5%),V in 14 (4.2%), and culottes in 1 (0.3%). In-hospital MACE occurred in 4 (1.5%) patients of the DES group and 2 (4.1%) of the BMS group (P = 0.22). After 35.8 +/- 12.9 months, MACE were 72 (27.1%) vs. 24 (49%), respectively (P = 0.002), with cardiac death in 7 (2.6%) patients vs. 3 (6.1%, P = 0.20), myocardial infarction in 12 (4.5%) vs. 6 (12.2%, P = 0.42), coronary artery bypass grafting in 5 (1.9%) vs. 1 (2%, P = 0.93), target lesion revascularization in 30 (11.3%) vs. 13 (26.5%, P = 0.0042), and target vessel revascularization in 48 (18%) vs. 13 (26.5%, P = 0.16). Definite stent thrombosis occurred in 2 (0.75%) patients in the DES group vs. 1 (2%, P = 0.93) in the BMS group, whereas probable stent thrombosis was adjudicated in 5 (1.9%) vs. 2 (4%, P = 0.93). CONCLUSION: This cohort study, reporting for the first time on the long-term outlook of patients treated with DES vs. BMS for coronary bifurcation lesions, supports the overall safety and efficacy of DES in comparison to BMS. Specifically, even after several years of follow-up, repeat revascularizations appeared significantly lower with DES, and stent thromboses occurred with equivalent frequency in both DES and BMS groups.

Early and long-term results of percutaneous coronary intervention for unprotected left main trifurcation disease.

OBJECTIVES: We aimed to conduct a retrospective cohort study focusing on our 5-year experience in the percutaneous treatment of unprotected left main (ULM) trifurcation disease. BACKGROUND: Percutaneous treatment of ULM trifurcation remains a challenging and rare procedure for most interventional cardiologists. Moreover, data on long-term outcomes are lacking. METHODS: We retrieved all patients with ULM trifurcation disease treated percutaneously at our Institution since 2002, and adjudicated baseline, procedural, and outcome data. The primary end point was the long-term rate of major adverse cardiovascular events (MACE, i.e., cardiac death, myocardial infarction, bypass surgery, or target vessel revascularization). RESULTS: A total of 27 patients underwent percutaneous coronary intervention with stent implantation for ULM trifurcation disease, with 14 (52%) cases of true trifurcations, i.e., with concomitant significant stenoses of the distal ULM/ostial left anterior descending plus ostial ramus intermedius and ostial circumflex. Bare-metal stents were implanted in 8 (29%) patients and drug-eluting stents (DES) in 26 (96%), with a main branch stent only strategy in 11 (40%), T stenting in 9 (33%), and V stenting in 6 (27%). Procedural and clinical success occurred in 26 (96%), with one postprocedural death. Angiographic follow-up was obtained in 22 patients (81%), and clinical follow-up was completed in all subjects after a median of 28 +/- 17 months, showing overall MACE in 9 (33%), with cardiac death in 4 (15%), myocardial infarction in 1 (4%), coronary artery bypass grafting (CABG) in 4 (15%), and percutaneous target vessel revascularization in 5 (19%). Definite stent thrombosis was adjudicated in 1 (3%) patient. Treatment of a true trifurcation lesion and recurrence of angina during follow-up were significantly associated with an increased risk of MACE (P = 0.029 and P = 0.050, respectively). CONCLUSIONS: Percutaneous treatment of ULM trifurcation disease is feasible, associated with favorable mid-term results, and may be considered given its low invasiveness in patients at high surgical risk or with multiple comorbidities.

Current management of unprotected left main coronary artery disease: run-in survey of the RITMO (Registro Italiano sul Trattamento del tronco coMune non protettO) study.

The optimal approach for a significant unprotected left main coronary stenosis (ULM) is debated, in light of the recent progresses of percutaneous coronary intervention (PCI). However, coronary artery bypass grafting (CABG) is still considered the first choice treatment. Randomized trials comparing PCI and CABG are ongoing, yet patient selection will considerably limit their clinical applicability. We thus designed a prospective multicenter registry which will include patients with ULM disease independently from the subsequent medical, interventional or surgical treatment: the RITMO Study (Registro Italiano sul Trattamento del tronco coMune non protettO). During the RITMO run-in phase, we conducted a systematic survey of Italian catheterization laboratories to define current management strategies for ULM. A total of 240 Italian catheterization laboratory were sent an email questionnaire on current practices for ULM, with 45 (19%) detailed replies, for a total of 61,370 annual coronary angiographies. Data provided from responders showed a 5% (95% interval: 2-16) prevalence of ULM, with 50% (9-99) of ULM treated surgically and 10% (0-81) treated percutaneously. In conclusion, treatment of ULM in Italy remains prevalently surgical, even if PCI is performed in a sizable portion of patients with ULM.

Impact of diabetes mellitus on early and long-term results of percutaneous drug-eluting stent implantation for unprotected left main coronary disease.

BACKGROUND: We aimed to appraise the outcomes of diabetic patients with unprotected left main (ULM) disease treated with drug-eluting stents. Percutaneous coronary intervention with drug-eluting stent implantation is increasingly used for ULM disease. However, there are no data on the clinical results of drug-eluting stents for ULM disease in patients with diabetes. METHODS: We collected baseline and outcome data from all patients undergoing percutaneous coronary intervention with drug-eluting stents for ULM disease at our institution since 2002. We identified three groups: insulin-requiring diabetes mellitus patients, noninsulin-requiring diabetes mellitus patients, and nondiabetes mellitus individuals. The primary end point was the rate of major adverse cardiac events, that is, cardiac death, myocardial infarction, or target vessel revascularization. We also appraised stent thrombosis according to the Academic Research Consortium. RESULTS: A total of 185 patients were enrolled, 25/185 (14%) insulin-requiring diabetes mellitus patients, 30/185 (16%) noninsulin-requiring diabetes mellitus patients, and 130/185 (70%) nondiabetes mellitus individuals. In-hospital adverse events were overall uncommon and not significantly different across groups. After a median follow-up period of 23.1 months, major adverse cardiac events had occurred in similar rates across groups: 6/25 (24%) insulin-requiring patients with diabetes mellitus, 8/30 (27%) noninsulin-requiring patients with diabetes mellitus, and 31/128 (24%) nondiabetes mellitus individuals (P = 0.96). No case of definite or probable stent thrombosis was adjudicated. Intriguingly, possible stent thrombosis was nonsignificantly more common among insulin-requiring diabetes mellitus patients than among noninsulin-requiring diabetes mellitus patients or nondiabetes mellitus individuals [1/25 (4%) vs. 0/30 (0%) and 1/128 (0.8%), respectively, P = 0.30]. CONCLUSION: Drug-eluting stents provide favorable early and long-term results in both selected patients with diabetes and nondiabetic individuals undergoing percutaneous coronary intervention for ULM disease. Nonetheless, further randomized data are eagerly awaited to definitely confirm or disprove these findings.

Appraising the pathophysiologic impact of coronary collaterals as measured by fractional flow reserve on symptoms and signs of myocardial ischemia.

BACKGROUND: The purpose of coronary revascularization in stable patients is anginal relief, yet there is no linear relationship between stenosis severity and clinical significance. A major factor in this complex lesion-myocardium interaction is collateral flow. We aimed to define which collateral flow cut-offs separate asymptomatic from symptomatic patients during coronary occlusion. METHODS: Patients undergoing percutaneous transluminal coronary angioplasty for a single stenotic lesion were selected, collaterals were appraised angiographically, and fractional flow reserve was used during prolonged balloon occlusion to measure collateral flow index (FFRcoll). Changes in anginal symptoms, ST-T segment, and left ventricular wall motion were appraised before and during/shortly after balloon dilation. Receiver-operating-characteristic curves and area under the curve were computed to identify the most appropriate FFRcoll cut-offs. RESULTS: Twenty consecutive patients were enrolled. At baseline, 10 patients had angiographic evidence of collaterals, whereas 10 had no angiographic evidence of collateral flow distal to the target lesion. FFRcoll had an excellent discriminatory performance for the presence of angiographic collaterals (area under the curve = 0.90, P = 0.003), a good discriminatory performance for the occurrence of angina (area under the curve = 0.80, P = 0.025), and a trend toward a good discriminatory performance for the occurrence of asynergy (area under the curve = 0.81, P = 0.06). On the basis of receiver-operating-characteristic curves, an FFRcoll cut-off greater than 0.26 could reliably distinguish patients with adequate collaterals (sensitivity = 0.90, specificity = 0.80), whereas a greater than 0.41 cut-off distinguished patients having angina or wall motion abnormalities from those remaining asymptomatic. CONCLUSION: This study shows that distal collateral pressure greater than 41% of proximal perfusion pressure protects from anginal symptoms or regional systolic dysfunction during coronary occlusion, whereas a greater than 26% cut-off is more appropriate to identify angiographically evident collaterals ensuring distal myocardial viability.

Effect of a novel drug-eluted balloon coated with genistein before stent implantation in porcine coronary arteries.

BACKGROUND: The major drawback of stent implantation in native human coronary vessels is the occurrence of restenosis. Drug-eluting stents significantly reduce restenosis after percutaneous coronary intervention (PCI), but may be associated with persistent local inflammation involved in the restenosis mechanisms. In this setting coating coronary devices with anti-inflammatory agents represents an intriguing alternative to stent-based local drug delivery. The aim of the present study was to test in a porcine model the safety and efficacy of a novel Genistein-eluting balloon preceding coronary stenting. DESIGN: Female piglets underwent PCI in a randomized fashion with either a Genistein-eluting or a standard balloon angioplasty, followed in all vessels by bare-metal stent implantation. Pigs were sacrificed at different time points to appraise safety (i.e. endothelialization) and efficacy (i.e. anti-inflammatory and anti-proliferative effects): 1, 4, and 6-8 weeks following PCI. RESULTS: Overall analysis was conducted on 14 piglets. Twenty-five bare-metal stents were implanted preceded by angioplasty with a conventional balloon in 13 vessels and by the Genistein-eluted balloon in 12. No untoward effects were reported in either group. Healing and endothelialization appeared universal within 4 weeks. The Genistein-eluted balloon group disclosed a significant reduction, at four weeks from implantation, of the peri-stent inflammatory cells count (mononucleocytes 39 +/- 32 Vs. 96 +/- 29 per square millimetre, P = 0.019). This effect did not clearly translate into a trend towards a reduced neointimal hyperplasia at 6-8 weeks (0.13 +/- 0.11 Vs. 0.14 +/- 0.09, P = 0.835). CONCLUSION: This study provides the first in vivo demonstration of the anti-inflammatory effects of a Genistein-eluting balloon in PCI, warranting further research including the combination of a Genistein-eluting balloon with standard drug-eluting stent.

Sirolimus-eluting stent implantation for bare-metal in-stent restenosis: is there any evidence for a late catch-up phenomenon?

OBJECTIVES: In-stent restenosis occurs not infrequently after intracoronary implantation of bare-metal stents. Many techniques have been proposed for the treatment of in-stent restenosis, but drug-eluting stents seem to provide the best early and mid-term results. We aimed to appraise whether the effectiveness of drug-eluting stents for in-stent restenosis is maintained even in the long term. METHODS: Participants in this prospective multicenter study were patients with in-stent restenosis treated with sirolimus-eluting stents. The primary endpoint was freedom from major adverse cardiovascular events (i.e. death, nonfatal myocardial infarction, target vessel revascularization, or stent thrombosis) in the long term (> or =24 months), with 6-month angiography planned for all patients. RESULTS: A total of 271 consecutive patients were enrolled (332 sirolimus-eluting stents). Procedural success was obtained in all patients, with no case of in-hospital death, acute/subacute stent thrombosis, stroke, or urgent coronary bypass. Survival free from major cardiovascular events decreased progressively from 98.8% at 1 month, to 95.7, 83.7, 75.4, and 65.8% at 6, 12, 24, and 30 months, respectively. A similar attrition in freedom from repeat target vessel was found from 97.6% at 6 months to 76.7% at 30 months. A total of four possible and one definite stent thromboses (2.6%) were noted, all occurring several months after clopidogrel discontinuation and in patients on life-long aspirin. CONCLUSION: The present study supports the mid-term safety and effectiveness of sirolimus-eluting stents for the treatment of in-stent restenosis in comparison with the other available treatments. Whether the late catch-up phenomenon observed in repeat target revascularization and stent thrombosis is an incidental finding deserves further rigorous scrutiny.

A prospective multicentre observational study on the management of unprotected left main coronary artery disease: rationale and design of the Registro Italiano sul Trattamento del tronco comune non protetto study.

BACKGROUND: The optimal approach for a significant unprotected left main coronary stenosis is debated in light of the recent progresses of percutaneous coronary intervention. However, bypass surgery is still considered the first choice treatment. Randomized trials comparing percutaneous intervention and bypass grafting are ongoing, yet patient selection will limit their applicability. We designed a prospective multicentre registry, which will include patients with unprotected left main disease independent of the subsequent medical, interventional or surgical treatment. OBJECTIVE: The aim of this study is to evaluate prospectively the prevalence, treatment, and prognosis of patients with unprotected left main stenosis. STUDY DESIGN: More than 30 Italian care centres will participate. Patients with unprotected left main stenosis will be enrolled, excluding those with only mild atherosclerotic irregularities or patent grafts. The primary endpoint will be the 12-month occurrence of major adverse cardiac and cerebral events (MACCE, i.e. the composite of death, non-fatal myocardial infarction, stroke, or coronary revascularization by percutaneous intervention or bypass surgery). Secondary endpoints will be the occurrence of individual components of the primary endpoint at 1, 6, 24, and 60 months, the rate of major adverse cardiac and cerebral events without stroke, functional class, and quality of life. Analyses will be stratified according to lesion severity, as well as other patient, lesion, and procedural characteristics. EXPECTED RESULTS AND IMPLICATIONS: This multicentre prospective registry of patients with unprotected left main coronary stenosis treated medically, percutaneously or surgically will provide important and updated data on the prevalence, therapeutic choices, and prognosis of this important patient population.

Systematic review and meta-analysis of randomized clinical trials appraising the impact of cilostazol after percutaneous coronary intervention.

BACKGROUND: Drug-eluting stents reduce the risk of restenosis after percutaneous coronary intervention (PCI) but may pose a risk of thrombosis. Cilostazol, an oral antiplatelet agent with pleiotropic effects including inhibition of neointimal hyperplasia, could hold the promise of preventing both restenosis and thrombosis. We systematically reviewed randomized clinical trials (RCTs) on the angiographic and clinical impact of cilostazol after PCI. METHODS: We searched RCT in BioMedCentral, CENTRAL, clinicaltrials.gov, EMBASE, and PubMed (November 2007). Coprimary end points were binary angiographic restenosis and repeat revascularization, abstracted and pooled by means of random-effect relative risks (RRs). Small study/publication bias was appraised with multiple methods. RESULTS: A total of 23 RCTs were included (5428 patients), with median follow-up of 6 months. Pooled analysis showed that cilostazol was associated with statistically significant reductions in binary angiographic restenosis (RR = 0.60 [0.49-0.73], P < .001) and repeat revascularization (RR = 0.69 [0.55-0.86], P = .001). Cilostazol appeared also safe, with no significant increase in the risk of stent thrombosis (RR = 1.35 [0.71-2.57], P = .36) or bleeding (RR = 0.71 [0.43-1.16], P = .17). However, small study bias was evident for both binary restenosis (P < .001) and repeat revascularization (P < .001), suggesting that at least part of the apparent benefits of cilostazol could be due to this type of confounding effect. CONCLUSIONS: Cilostazol appears effective and safe in reducing the risk of restenosis and repeat revascularization after PCI, but available evidence is limited by small study effects. Awaiting larger RCTs, this inexpensive treatment can be envisaged in selected patients in which drug-eluting stents are contraindicated or when there is a need for neointimal hyperplasia inhibition.

Long-term follow-up of patients eligible, deferred, or ineligible for heart transplantation.

BACKGROUND: When a patient is referred to a heart transplantation center, the patient and the physician should know the predicted long-term survival according to the first transplant committee decision. The aim of the study was to describe the follow-up of patients with heart failure referred to a heart transplantation center according to the initial decision to include (eligible), exclude (ineligible), or postpone (deferred) cardiac transplantation. METHODS: The study cohort consisted of 852 consecutive patients. Univariate and trend analyses were performed by classification of data into tertiles according to the date of the first visit. The Kaplan-Meier method was used to assess overall survival and probability of receiving a transplant. The Cox hazard model was used to identify predictors of survival. RESULTS: Transplantation incidence in the 3 groups (eligible, deferred, and ineligible) was 60%, 19%, and 5%, respectively. The 1-, 3-, 5-, and 10-year survival rates were 74%, 58%, 49%, and 37% among eligible patients; 87%, 72%, 62%, and 45% among deferred; and 69%, 50%, 39%, and 19% among ineligible patients (p < 0.001). The 10-year survival was 65% for eligible patients who received the transplant and 8.8% for eligible patients who did not receive the transplant. Transplantation was the most powerful predictor of survival. CONCLUSION: The initial decision identified 3 groups of patients with different survival rates. Heart transplantation increases the survival of eligible patients at a rate similar to that of less sick subjects for whom heart transplantation can be deferred.

A collaborative systematic review and meta-analysis on 1278 patients undergoing percutaneous drug-eluting stenting for unprotected left main coronary artery disease.

BACKGROUND: Cardiac surgery is the standard treatment for unprotected left main disease (ULM). Drug-eluting stent (DES) implantation has been recently reported in patients with ULM but with unclear results. We systematically reviewed outcomes of percutaneous DES implantation in ULM. METHODS: Several databases were searched for clinical studies reporting on > or = 20 patients and > or = 6-month follow-up. The primary end point was major adverse cardiovascular events (MACEs; ie, death, myocardial infarction, or target vessel revascularization [TVR]) at the longest follow-up. Incidence and adjusted risk estimates were pooled with generic inverse variance random-effect methods (95% CIs). RESULTS: From 823 initial citations, 16 studies were included (1278 patients, median follow-up 10 months). Eight were uncontrolled registries, 5 nonrandomized comparisons between DES and bare-metal stents and 3 nonrandomized comparisons between DES and CABG, with no properly randomized trial. Meta-analysis for DES-based PCI showed, at the longest follow-up, rates of 16.5% (11.7%-21.3%) MACE, 5.5% (3.4%-7.7%) death, and 6.5% (3.7%-9.2%) TVR. Comparison of DES versus bare-metal stent disclosed adjusted odds ratios for MACE of 0.34 (0.16-0.71), and DES versus CABG showed adjusted odds ratios for MACE plus stroke of 0.46 (0.24-0.90). Meta-regression showed that disease location predicted MACE (P = .001) and TVR (P = .020), whereas high-risk features predicted death (P = .027). CONCLUSIONS: Clinical studies report apparently favorable early and midterm results in selected patients with ULM. However, given their limitations in validity and the inherent risk for DES thrombosis, results from randomized trials are still needed to definitely establish the role of DES implantation instead of the reference treatment, surgery.