Mario Bollati

Incidence and predictors of coronary stent thrombosis: Evidence from an international collaborative meta-analysis including 30 studies, 221,066 patients, and 4276 thromboses

BACKGROUND Stent thrombosis remains among the most feared complications of percutaneous coronary intervention (PCI) with stenting. However, data on its incidence and predictors are sparse and conflicting. We thus aimed to perform a collaborative systematic review on incidence and predictors of stent thrombosis. METHODS PubMed was systematically searched for eligible studies from the drug-eluting stent (DES) era (1/2002-12/2010). Studies were selected if including ≥ 2000 patients undergoing stenting or reporting on ≥ 25 thromboses. Study features, patient characteristics, and incidence of stent thrombosis were abstracted and pooled, when appropriate, with random-effect methods (point estimate [95% confidence intervals]), and consistency of predictors was formally appraised. RESULTS A total of 30 studies were identified (221,066 patients, 4276 thromboses), with DES used in 87%. After a median of 22 months, definite, probable, or possible stent thrombosis had occurred in 2.4% (2.0%; 2.9%), with acute in 0.4% (0.2%; 0.6%), subacute in 1.1% (1.0%; 1.3%), late in 0.5% (0.4%; 0.6%), and very late in 0.6% (0.4%; 0.8%). Similar figures were computed for studies reporting only on DES. From a total of 47 candidate variables, definite/probable stent thrombosis was more commonly and consistently predicted by early antiplatelet therapy discontinuation, extent of coronary disease, and stent number/length, with acute coronary syndrome at admission, diabetes, smoking status, and bifurcation/ostial disease also proving frequent predictors, but less consistently. CONCLUSIONS Despite numerous possible risk factors, the most common and consistent predictors of stent thrombosis are early antiplatelet therapy discontinuation, extent of coronary disease, and stent number/length.

TIMI, GRACE and alternative risk scores in Acute Coronary Syndromes: A meta-analysis of 40 derivation studies on 216,552 patients and of 42 validation studies on 31,625 patients.

BACKGROUND Acute coronary syndromes (ACS) represent a difficult challenge for physicians. Risk scores have become the cornerstone in clinical and interventional decision making. METHODS AND RESULTS PubMed was systematically searched for ACS risk score studies. They were divided into ACS studies (evaluating Unstable Angina; UA, Non ST Segment Elevation Myocardial Infarction; NSTEMI, and ST Segment Elevation Myocardial Infarction; STEMI), UA/NSTEMI studies or STEMI studies. The c-statistics of validation studies were pooled when appropriate with random-effect methods. 7 derivation studies with 25,525 ACS patients and 15 validation studies including 257,654 people were formally appraised. Pooled analysis of GRACE scores, both at short (0.82; 0.80-0.89 I.C 95%) and long term follow up (0.84; 0.82-0.87; I.C 95%) showed the best performance, with similar results to Simple Risk Index (SRI) derivation cohorts at short term. For NSTEMI/UA, 18 derivation studies with 56,560 patients and 18 validation cohorts with 56,673 patients were included. Pooled analysis of validations studies showed c-statistics of 0.54 (95% CI = 0.52-0.57) and 0.67 (95% CI = 0.62-0.71) for short and long term TIMI validation studies, and 0.83 (95% CI = 0.79-9.87) and 0.80 (95% CI = 0.74-0.89) for short and long term GRACE studies. For STEMI, 15 studies with 134,557 patients with derivation scores, and 17 validation studies with 187,619 patients showed a pooled c-statistic of 0.77 (95% CI = 0.71-0.83) and 0.77 (95% CI = 0.72-0.85) for TIMI at short and long term, and a pooled c-statistic of 0.82 (95% CI = 0.81-0.83) and 0.81 (95% CI = 0.80-0.82) for GRACE at short and long terms respectively. CONCLUSIONS TIMI and GRACE are the risk scores that up until now have been most extensively investigated, with GRACE performing better. There are other potentially useful ACS risk scores available however these have not undergone rigorous validation. This study suggests that these other scores may be potentially useful and should be further researched.

Acute coronary syndromes in human immunodeficiency virus patients: a meta-analysis investigating adverse event rates and the role of antiretroviral therapy

AIMS Highly active antiretroviral therapy (HAART) dramatically reduces human immunodeficiency virus (HIV)-associated morbidity and mortality, but adverse effects of HAART are becoming an increasing challenge, especially in the setting of acute coronary syndromes (ACS). We thus performed a comprehensive review of studies focusing on ACS in HIV patients. METHODS AND RESULTS MEDLINE/PubMed was systematically screened for studies reporting on ACS in HIV patients. Baseline, treatment, and outcome data were appraised and pooled with random-effect methods computing summary estimates [95% confidence intervals (CIs)]. A total of 11 studies including 2442 patients were identified, with a notably low prevalence of diabetes [10.86 (4.11, 17.60); 95% CI]. Rates of in-hospital death were 8.00% (2.8, 12.5; 95% CI), ascribable to cardiovascular events for 7.90% (2.43, 13.37; 95% CI), with 2.31% (0.60, 4.01; 95% CI) developing cardiogenic shock. At a median follow-up of 25.50 months (11.25, 42; 95% CI), no deaths were recorded, with an incidence of 9.42% of acute myocardial infarction (2.68, 16.17; 95% CI) and of 20.18% (9.84, 30.51; 95% CI) of percutaneous coronary revascularization. Moreover, pooled analysis of the studies reporting incidence of acute myocardial infarction in patients exposed to protease inhibitors showed an overall significant risk of 2.68 (odds ratio 1.89, 3.89; 95% CI). CONCLUSION Human immunodeficiency virus patients admitted for ACS face a substantial short-term risk of death and a significant long-term risk of coronary revascularization and myocardial infarction, especially if receiving protease inhibitors.

Use and Misuse of Multivariable Approaches in Interventional Cardiology Studies on Drug-Eluting Stents: A Systematic Review

AIMS  Randomized clinical trials (RCTs) are the most reliable evidence, even if they require important resource and logistic efforts. Large, cost-free and real-world datasets may be easily accessed yielding to observational studies, but such analyses often lead to problematic results in the absence of careful methods, especially from a statistic point of view. We aimed to appraise the performance of current multivariable approaches in the estimation of causal treatment and effects in studies focusing on drug-eluting stents (DES). METHODS AND RESULTS Pertinent studies published in the literature were searched, selected, abstracted, and appraised for quality and validity features. Six studies with a logistic regression were included, all of them reporting more than 10 events for covariates and different length of follow-up, with an overall low risk of bias. Most of the 15 studies with a Cox proportional hazard analysis had a different follow-up, with less than 10 events for covariates, yielding an overall low or moderate risk of bias. Sixteen studies with propensity score were included: the most frequent method for variable selection was logistic regression, with underlying differences in follow-up and less than 10 events for covariate in most of them. Most frequently, calibration appraisal was not reported in the studies, on the contrary of discrimination appraisal, which was more frequently performed. In seventeen studies with propensity and matching, the latter was most commonly performed with a nearest neighbor-matching algorithm yet without appraisal in most of the studies of calibration or discrimination. Balance was evaluated in 46% of the studies, being obtained for all variables in 48% of them. CONCLUSIONS  Better exploitation and methodological appraisal of multivariable analysis is needed to improve the clinical and research impact and reliability of nonrandomized studies.

30 days and midterm outcomes of patients undergoing percutaneous replacement of aortic valve according to their renal function: A multicenter study

INTRODUCTION Chronic kidney disease (CKD) constitutes a predictor of adverse events for surgical aortic valve replacement. In patients undergoing TAVI no study was performed to evaluate outcomes according to renal clearance, which represents the most accurate instrument to assess kidney function. METHODS From January 2007 to December 2011 all TAVI patients of our institutions were prospectively divided into 3 cohorts. Preserved renal function those with clearance more or equal to 60 ml/min/1.73 m2, moderate CKD those between 30 and 60, and severe CKD those between 15 and 30. Patients with a clearance less than 15 or in dialysis were excluded. All outcomes were adjudicated according to VARC criterion. RESULTS 72 patients with preserved renal function, 219 with moderate and 73 with severe CKD were included; those in the latter group were older and with lower ejection fraction. At 30 days, severe CKD was associated with a trend toward a higher risk of major events than preserved and moderate CKD: cardiovascular death (2.8% vs 6.7% vs 9%; p=0.256) life threatening bleedings (10% vs 10% vs 16%; p=0.384), major stroke (1.4% vs 2.3% vs 4.1%; p=0.763). At a medium follow-up of 540 ± 250 days, cardiovascular death incidence was higher in patients with severe CKD (7% vs 8 vs 19%; p<0.0001), however this difference was not consistently significant after multivariable adjustment (p=0.300). Overall, 2% of patients developed kidney failure, whereas 47.1% of patients with severe CKD improved to moderate renal impairment. CONCLUSIONS Patients with severe chronic renal disease presented higher risk of adverse events, mainly driven by increased hazard of bleedings. TAVI procedures could offer kidney functional improvement in an important subset of patients.

Changing of SYNTAX score performing fractional flow reserve in multivessel coronary artery disease

Objectives To investigate the relationship between classic SYNTAX and functional SYNTAX score guided by fractional flow reserve (FFR). Background SYNTAX score predicts clinical outcome after percutaneous coronary intervention in patients with multivessel coronary artery disease (CAD), based on data from angiography alone. However, in the clinical setting, decision-making on myocardial revascularization should be guided by reliable demonstration of inducible ischemia, as detected by FFR. Methods FFR was collected in all 50–90% angiographic stenoses of 39 consecutive patients with stable multivessel CAD. SYNTAX score was calculated as usually described in SYNTAX groups reports. A functional SYNTAX (F-SYNTAX) score was determined by only considering ischemia-producing lesions (FFR ⩽ 0.80). The two scores were compared with correlation, Bland–Altman and agreement tests. Results FFR was measured in 97 lesions, with a median value of 0.82 ± 0.10. In the 50–70% and 70–90% category stenoses, FFR was greater than 0.80 in 68 and 16% of cases, respectively. F-SYNTAX was systematically inferior to SYNTAX score, with a median difference of 8.4 ± 7.4 (P < 0.05). The correlation between the two methods was globally weak (r = 0.621, rho = 0.563; P < 0.001). After determining F-SYNTAX score, more than 30% of the patients moved to a lower-risk tertile group (P = 0.003). No clinical and angiographic differences were found between patients whether or not reclassified in lower-risk tertiles with F-SYNTAX score. Conclusions In patients with multivessel CAD, implementation of SYNTAX score with FFR seems to be a more rational approach for revascularization. F-SYNTAX score reclassifies a significant proportion of patients to a lower-risk profile, thus leading to a possible change of therapeutic strategy.

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.

Takotsubo cardiomyopathy as a complication of pacemaker implantation.

To the editorTakotsubo cardiomyopathy (TCM), first described by Japanese physicians in the 1990s,1 normally occurs following stressful situations or events.2,3 Although the specific cause of TCM is still debated, several factors have been proposed, such as coronary artery spasm,4 microvascular invol

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

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.

Diffuse coronary disease: short- and long-term outcome after percutaneous coronary intervention

AIM The aim of this study was to evaluate short- and long-term results of PCI (percutaneous coronary intervention) in patients with small vessel coronary artery disease and the prognostic impact of the extension and the length of coronary lesions. METHODS AND RESULTS All consecutive patients treated with PCI in our centre between July 2002 and December 2004 were included and divided into two groups according to the diameter of the implanted stents: small vessel disease was defined as requiring implantation of stents < 2.75 mm in diameter. The primary end point was the long-term incidence of major adverse cardiac events (MACE), the composite of cardiac mortality, nonfatal myocardial reinfarction, and repeated percutaneous target vessel revascularization (re-PTCA TVR). 1599 patients were treated by PCI: 419 (26.2%) were implanted with 2.75 mm or smaller stents. At both 1 and 36 months as well as at 53 + 20 months of follow-up small vessel stenting was associated with a higher rate of MACE (4.2% vs 2.1%, P= 0.028; 20.3% vs 17.9%, P <0.001; 27.5% vs 22.4%, P= 0.04, respectively). Multivariate analysis showed higher rates of revascularization for patients with small vessel disease regardless of lesion length. Rates of death were higher in patients with small vessels and long lesions. CONCLUSION Atherosclerotic involvement of small vessels in patients with CAD confers a higher short- and long-term risk of adverse outcome after PCI.