Fabrizio D'Ascenzo

Catheter ablation of atrial fibrillation in patients with diabetes mellitus: a systematic review and meta-analysis.

AIMS Diabetes mellitus (DM) and atrial fibrillation (AF) share pathophysiological links, as supported by the high prevalence of AF within DM patients. Catheter ablation of AF (AFCA) is an established therapeutic option for rhythm control in drug resistant symptomatic patients. Its efficacy and safety among patients with DM is based on small populations, and long-term outcome is unknown. The present systematic review and meta-analysis aims to assess safety and long-term outcome of AFCA in DM patients, focusing on predictors of recurrence. METHODS AND RESULTS A systematic review was conducted in MEDLINE/PubMed and Cochrane Library. Randomized controlled trials, clinical trials, and observational studies including patients with DM undergoing AFCA were screened and included if matching inclusion and exclusion criteria. Fifteen studies were included, adding up to 1464 patients. Mean follow-up was 27 (20-33) months. Overall complication rate was 3.5 (1.5-5.0)%. Efficacy in maintaining sinus rhythm at follow-up end was 66 (58-73)%. Meta-regression analysis revealed that advanced age (P < 0.001), higher body mass index (P < 0.001), and higher basal glycated haemoglobin level (P < 0.001) related to higher incidence of arrhythmic recurrences. Performing AFCA lead to a reduction of patients requiring treatment with antiarrhythmic drugs (AADs) from 55 (46-74)% at baseline to 29 (17-41)% (P < 0.001) at follow-up end. CONCLUSIONS Catheter ablation of AF safety and efficacy in DM patients is similar to general population, especially when performed in younger patients with satisfactory glycemic control. Catheter ablation of AF reduces the amount of patients requiring AADs, an additional benefit in this population commonly exposed to adverse effects of AF pharmacological treatments.

Stent thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis

BACKGROUND The relative safety of drug-eluting stents and bare-metal stents, especially with respect to stent thrombosis, continues to be debated. In view of the overall low frequency of stent thrombosis, large sample sizes are needed to accurately estimate treatment differences between stents. We compared the risk of thrombosis between bare-metal and drug-eluting stents. METHODS For this network meta-analysis, randomised controlled trials comparing different drug-eluting stents or drug-eluting with bare-metal stents currently approved in the USA were identified through Medline, Embase, Cochrane databases, and proceedings of international meetings. Information about study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes was extracted. FINDINGS 49 trials including 50,844 patients randomly assigned to treatment groups were analysed. 1-year definite stent thrombosis was significantly lower with cobalt-chromium everolimus eluting stents (CoCr-EES) than with bare-metal stents (odds ratio [OR] 0·23, 95% CI 0·13-0·41). The significant difference in stent thrombosis between CoCr-EES and bare-metal stents was evident as early as 30 days (OR 0·21, 95% CI 0·11-0·42) and was also significant between 31 days and 1 year (OR 0·27, 95% CI 0·08-0·74). CoCr-EES were also associated with significantly lower rates of 1-year definite stent thrombosis compared with paclitaxel-eluting stents (OR 0·28, 95% CI 0·16-0·48), permanent polymer-based sirolimus-eluting stents (OR 0·41, 95% CI 0·24-0·70), phosphorylcholine-based zotarolimus-eluting stents (OR 0·21, 95% CI 0·10-0·44), and Resolute zotarolimus-eluting stents (OR 0·14, 95% CI 0·03-0·47). At 2-year follow-up, CoCr-EES were still associated with significantly lower rates of definite stent thrombosis than were bare-metal (OR 0·35, 95% CI 0·17-0·69) and paclitaxel-eluting stents (OR 0·34, 95% CI 0·19-0·62). No other drug-eluting stent had lower definite thrombosis rates compared with bare-metal stents at 2-year follow-up. INTERPRETATION In randomised studies completed to date, CoCr-EES has the lowest rate of stent thrombosis within 2 years of implantation. The finding that CoCr-EES also reduced stent thrombosis compared with bare-metal stents, if confirmed in future randomised trials, represents a paradigm shift. FUNDING The Cardiovascular Research Foundation.

Are propensity scores really superior to standard multivariable analysis

Clinicians often face difficult decisions despite the lack of evidence from randomized trials. Thus, clinical evidence is often shaped by non-randomized studies exploiting multivariable approaches to limit the extent of confounding. Since their introduction, propensity scores have been used more and more frequently to estimate relevant clinical effects adjusting for established confounders, especially in small datasets. However, debate persists on their real usefulness in comparison to standard multivariable approaches such as logistic regression and Cox proportional hazard analysis. This holds even truer in light of key quantitative developments such as bootstrap and Bayesian methods. This qualitative review aims to provide a concise and practical guide to choose between propensity scores and standard multivariable analysis, emphasizing strengths and weaknesses of both approaches.

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.

Which are the most reliable predictors of recurrence of atrial fibrillation after transcatheter ablation?: a meta-analysis.

CONTEXT Transcatheter ablation of atrial fibrillation (AF) has undergone important development, with acceptable midterm results in terms of the safety and recurrence. A meta-analysis was performed to identify the periprocedural complications, midterm success rates and predictors of recurrence after AF ablation. METHODS AND RESULTS 4357 patients with paroxysmal AF, 1083 with persistent AF and 1777 with long standing AF were included. The pooled analysis showed that there was an in-hospital complication rate of tamponade requiring drainage of 0.99% (0.44-1.54; CI 99%), stroke with neurological persistent impairment of 0.22% (0.04-0.47; CI 99%), and stroke without of 0.36% (0.03-0.70; CI 99%) After a follow up of 22 (13-28) months and 1.23 (1.19-1.5; CI 99%) procedures per patient, the AF recurrence rate was 31.20% (24.87-34.81; CI 99%). The persistent AF patients exhibited a greater risk of recurrence after the first ablation (OR 1.78 [1.14, 2.77] CI 99%), but a trend towards non significance was present in the patients with more than one procedure (OR 1.69 [0.95, 3.00] CI 99%). The most powerful predictors of an AF ablation failure in the overall population were a recurrence within 30-days (OR 4.30; 2.00-10.80), valvular AF (OR 5.20; 2.22-9.50) and a left atrium diameter of more than 50mm (OR 5.10 2.00-12.90; all CI 95%). CONCLUSIONS Persistent AF remains burdened from higher recurrence rates, however not so following redo-procedures. Three predictors, valvular AF, a left atrium diameter longer than 50mm and recurrence within 30 days, could be appraised to drive selection of patients and therapeutic strategy.

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.

Remote ischaemic preconditioning in coronary artery bypass surgery: a meta-analysis

Aim Randomised trials exploring remote ischaemic preconditioning (RIPC) in patients undergoing coronary artery bypass graft (CABG) surgery have yielded conflicting data regarding potential cardiovascular and renal protection, and are individually flawed by small sample size. Methods Three investigators independently searched the MEDLINE, EMBASE and Cochrane databases to identify randomised trials testing RIPC in patients undergoing CABG. Results Nine studies with 704 patients were included. Standardised mean difference of troponin I and T release showed a significant decrease (−0.36 (95% CI −0.62 to −0.09)). This difference held true after excluding the trials with cross-clamp fibrillation, the study with off-pump CABG and studies using a flurane as anaesthetic agent (−0.41 (95% CI −0.69 to −0.12), −0.38 (95% CI −0.70 to −0.07) and −0.37 (95% CI −0.63 to −0.12), respectively). A similar trend was also obtained for patients with multivessel disease (−0.41 (95% CI −0.73 to −0.08)). The trials evaluating postoperative creatinine reported a non-significant reduction (0.02 (95% CI −0.09 to 0.13)). Moreover, the length of in-hospital stay was not influenced by the kind of treatment (weighted mean difference 0.27 (95% CI −0.24 to 0.79)). Conclusion RIPC reduced the release of troponin in patients undergoing CABG. Larger randomised trials are needed to clarify the presence of a causal relationship between RIPC-induced troponin release and clinical adverse events.

Catheter Ablation of Atrial Fibrillation in Patients With Left Ventricular Systolic Dysfunction A Systematic Review and Meta-Analysis

Background—Catheter ablation of atrial fibrillation (AFCA) is an established therapeutic option for rhythm control in symptomatic patients. Its efficacy and safety among patients with left ventricular systolic dysfunction is based on small populations, and data concerning long-term outcome are limited. We performed this meta-analysis to assess safety and long-term outcome of AFCA in patients with left ventricular systolic dysfunction, to evaluate predictors of recurrence and impact on left ventricular function. Methods and Results—A systematic review was conducted in MEDLINE/PubMed and Cochrane Library. Randomized controlled trials, clinical trials, and observational studies including patients with left ventricular systolic dysfunction undergoing AFCA were included. Twenty-six studies were selected, including 1838 patients. Mean follow-up was 23 (95% confidence interval, 18–40) months. Overall complication rate was 4.2% (3.6%–4.8%). Efficacy in maintaining sinus rhythm at follow-up end was 60% (54%–67%). Meta-regression analysis revealed that time since first atrial fibrillation (P=0.030) and heart failure (P=0.045) diagnosis related to higher, whereas absence of known structural heart disease (P=0.003) to lower incidence of atrial fibrillation recurrences. Left ventricular ejection fraction improved significantly during follow-up by 13% (P<0.001), with a significant reduction of patients presenting an ejection fraction <35% (P<0.001). N-terminal pro-brain natriuretic peptide blood levels decreased by 620 pg/mL (P<0.001). Conclusions—AFCA efficacy in patients with impaired left ventricular systolic function improves when performed early in the natural history of atrial fibrillation and heart failure. AFCA provides long-term benefits on left ventricular function, significantly reducing the number of patients with severely impaired systolic function.

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.

Prevalence and predictors of culprit plaque rupture at OCT in patients with coronary artery disease: a meta-analysis

AIMS The prevalence of plaque rupture at the culprit lesion identified by optical coherence tomography (OCT) in different clinical subset of patients undergoing coronary angiography and its clinical predictors remain to be defined. METHODS All studies including patients with OCT evaluation of the culprit coronary plaque were included. The prevalence of culprit plaque rupture (CPR) and thin-cap fibro-atheroma (TCFA) were the primary endpoints. The factors associated with these findings were studied in a subset of patients with different clinical presentations [ST-elevation myocardial (STEMI) vs. nonST-elevation myocardial infarction (NSTEMI) vs. unstable angina (UA) vs. stable angina pectoris (SAP)]. RESULTS One hundred and fifty citations were initially appraised at the abstract level and 23 full-text studies were assessed. The mean prevalence of CPR and TCFA was 48.1% (40.5-55.8) and 48.7% (37.4-60.1), respectively. The prevalence of CPR and TCFA were higher in STEMI (70.4 and 76.6%) than in NSTEMI (55.6 and 56.3%) and UA (39.1 and 52.9%) or SAP (6.2 and 22.8%). In the overall population at meta-regression analysis, TCFA and current smoking were the only predictors of CPR (B 3.6:2.0-5.1, P < 0.001 and 0.06:0.02-0.1, P = 0.002, respectively). The factors associated with CPR were different depending on clinical presentation. Hypertension was the only clinical predictor for STEMI (B 3.3: 1.2.-5.3 P = 0.001), while advanced age (B 0.12: 0.02-0.22, P = 0.021), diabetes mellitus (B 0.04: 0.01-0.08, P = 0.012), and hyperlipidaemia (B 0.07:0.02-0.11, P = 0.005) were the predictors in NSTEMI and UA. No clinical predictor was found in SA. CONCLUSIONS Our analysis showed high rates of CPR and TCFA detected by OCT in CAD patients, especially in those with ACS, although their prevalence is not negligible in stable patients. TCFA seems to be a strong predictor of CPR in all the ACS scenarios.