branches with >50% stenosis, 19 (28.4%) had FFR≤0.80 and among 163 side branches with ≤50% stenosis, 22 (13.5%) had FFR≤0.80 after stent implantation in main vessels. Using receiver-operating characteristic curve, the optimal cutoff value of diameter stenosis of side branch was 54.9% and area under the curve was 0.64 (95% CI 0.580.71, p<0.001) with a 41.5% sensitivity, an 83.1% specificity, a 34.7% positive predictive value, an 86.3% negative predictive value and a 75.7% accuracy. Multivariate binary logistic regression analysis identified diameter stenosis (odds ratio [OR] 1.04, 95% CI 1.02-1.06, p=0.001) and reference vessel diameter (OR 0.28, 95% CI 0.10-0.77, p=0.014) of side branch before stent implantation as independent predictors of the side branches with FFR ≤0.80 after stent implantation. Conclusion: Most side branch lesions do not have functional significance after stent implantation in the main vessel and quantitative coronary angiography is unreliable in assessing the functional severity of these lesions.

A 29-year-old woman with two mechanical valve prostheses was referred to our institution for sudden and self-resolved diplopia 2 weeks after childbirth. From the beginning of pregnancy, nadroparin was started instead of warfarin. The echocardiogram performed at hospital admission revealed a severe aortic prosthesis regurgitation due to incomplete leaflet apposition with a prosthetic aortic transvalvular gradient increase. Three-dimensional transoesophageal echocardiography revealed a thrombus located between the two prostheses, causing intermittent aortic valve malfunction. Intravenous heparin was started. Three days later, a second transoesophageal echocardiogram revealed a decreased aortic transvalvular gradient, but an oval thrombus adhered to the mitral prosthesis and fluctuating through the prosthetic valve was detected. Tissue plasminogen activator infusion was started. To reduce cerebral embolization, carotid filters used during artery angioplasty were placed in common carotid arteries, left and right. No complication occurred during and after the procedure. With thrombus absence at 30-min transoesophageal echocardiography, filters were removed. The patient continued intravenous heparin until achievement of a therapeutic international normalized ratio range and she was asymptomatic on discharge.

Introduction Thirty-day readmission rates after percutaneous coronary intervention (PCI) have been related to adverse prognosis, and represent one of the most investigated indicators of quality of care. These data, however, derive from non-European centers evaluating all-cause readmissions, without stratification for diagnosis. Methods All consecutive patients undergoing PCI at our center from January 2009 to December 2011 were enrolled. Thirty-day readmissions related to postinfarction angina, myocardial infarction, unstable angina or heart failure were defined as acute coronary syndrome (ACS) or heart failure rehospitalizations. Major cardiac adverse event (MACE) was the primary outcome, and its single components (death, myocardial infarction and repeated revascularization) the secondary ones. Results A total of 1192 patients were included; among them, 53 (4.7%) were readmitted within 30 days, and 25 (2.1%) were classified as ACS/heart failure related. During hospitalization, patients with ACS/heart failure readmissions were more likely to suffer a periprocedural myocardial infarction (22 vs. 4%; P = 0.012), and to undergo PCI at 30 days (52 vs. 0.5%; P < 0.001). Logistic regression analysis indicated that periprocedural myocardial infarction represented the only independent predictor of an ACS/heart failure readmission [odds ratio (OR) 4.5; 1.1–16.8; P = 0.047]. After a median follow-up of 787 days (434–1027; first and third quartiles), patients with a 30-day ACS/heart failure readmission experienced higher rates of MACE, all-cause death and myocardial infarction (64 vs. 21%, P < 0.001; 28 vs. 6%, P = 0.017; and 20 vs. 2.7%, P < 0.001, respectively). Cox multivariate analysis indicated that ACS/heart failure 30-day readmissions were independently related to an increased risk of all-cause death (OR 3.3; 1.1–8.8; P = 0.02), differently from 30-day non-ACS/heart failure readmissions (OR 3.1; 0.7–12.9; P = 0.12). Conclusion Thirty-day readmissions after PCI in an Italian center are infrequent, and only those patients with ACS/heart failure show a detrimental impact on prognosis who have periprocedural myocardial infarction as the only independent predictor.

AIM:There is still controversy regarding the benefit of percutaneous closure of patent foramen ovale (PFO) among patients with cryptogenic stroke. Here we aimed to evaluate the factors associated with treatment choice and predictors of adverse events in patients with cryptogenic stroke or transient ischemic attack (TIA) and PFO. METHODS:Of 418 consecutive patients with PFO and cryptogenic stroke or TIA, 262 underwent percutaneous PFO closure, whereas 156 were medically treated. Multivariable logistic regression models were developed to evaluate factors influencing the treatment strategy and predictors of outcome, a composite of stroke, TIA or all-cause mortality. RESULTS:Patients with large interatrial right-to-left shunt were more likely treated with percutaneous closure [odds ratio (OR) = 4.79, 95% confidence interval (2.73-8.42); P < 0.0001], whereas those with multiple cerebrovascular accident (CVA) risk factors were more likely treated medically [OR = 0.15 (0.03-0.60); P = 0.023]. Age greater than 55 years [OR = 2.70 (1.05-6.88); P = 0.04], previous CVAs [OR = 2.49 (1.03-6.02); P = 0.02] and atrial septal aneurism [ASA, OR = 2.64 (1.09-6.39); P = 0.02], but not percutaneous closure of PFO [OR = 1.10 (0.44-2.74); P = 0.81], were independent predictors of outcome. CONCLUSION:Among patients with cryptogenic stroke and PFO, the presence of large interatrial right-to-left shunt and multiple CVA risk factors influenced the treatment choice. Older age, multiple previous CVAs and ASA, but not PFO closure, independently predicted the composite outcome of cryptogenic stroke, TIA or all-cause mortality.

AIMThe 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 RESULTSAll 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.CONCLUSIONAtherosclerotic involvement of small vessels in patients with CAD confers a higher short- and long-term risk of adverse outcome after PCI.

BackgroundDeveloped countries are facing a sustained increase in life expectancy. Along with all social and cultural implications of increase lifespan, very elderly patients are undergoing percutaneous coronary intervention (PCI) with increasing frequency. However, there is limited evidence to guide clinicians in evaluating pros and cons of PCI in this very frail patient population. We, thus, aimed to perform a systematic review and meta-analysis of clinical studies reporting on PCI with stenting in nonagenarians.MethodsStudies reporting on five or more nonagenarians undergoing PCI were systematically searched in PubMed (last updated on November 2011). Baseline and clinical characteristics, in-hospital and long-term outcomes were systematically appraised. End points of interest were in-hospital and long-term follow-up incidence of death and Major Adverse Cardiac Events (MACE; i.e. the composite of death from all causes, myocardial infarction or repeat revascularization). Events were pooled with a random-effect model, generating summary estimates of incidence rates [95% confidence intervals (CI)].ResultsA total of 10 studies were included, reporting on a total of 575 nonagenarians undergoing PCI with stenting who represented 1.99% (1.34-2.5) of those undergoing revascularization in the cath lab in a mean period of 5 (3-7) years. Twenty-three percent (13-45) of patients presented with STEMI (ST Segment Elevation Myocardial Infarction), 10% (7-12) with cardiogenic shock and in 78% (64-88) of cases a multivessel disease was diagnosed. Meta-analytic pooling of event rates showed an in-hospital death risk of 12.61% (9.71-15.50) with MACE in 16.41% (13.36-19.47). After a follow-up ranging from 6 to 29 months (median 12), the risk of long-term death was 31.00% (17.10-45.52), with MACE in 37.00% (19.56-55.95; all CI 95%).ConclusionOur meta-analysis, pooling the largest cohort ever of nonagenarians undergoing PCI with stents, confirms the feasibility of percutaneous coronary stenting even in this very frail patient subset, despite the expected severe event attrition during follow-up. Thus, nonagenarians with an acceptable risk profile, recent clinical instability and/or disabling symptoms should not be denied the possibility of percutaneous coronary revascularization.

AIMS:Human immunodeficiency virus infection (HIV) has been associated with cardiac dysfunction that, if present, can negatively affect morbidity and mortality of HIV-infected patients. Unfortunately, many of the studies on this topic were performed before the highly active antiretroviral therapy (HAART) was established. Thus, we performed a comprehensive meta-analysis to critically appraise the incidence of cardiac dysfunction in HIV-infected pauci symptomatic patients.METHODS AND RESULTS:Medline, Cochrane Library, and Biomed Central were systematically screened for studies reporting on systolic and/or diastolic dysfunctions in HIV pauci-symptomatic patients. Baseline treatment and cardiac imaging data were appraised and pooled with random effect methods computing summary. At pooled analysis, including a total of 2242 patients from 11 studies, an overall average incidence of traditional cardiovascular risk factors was observed, while a low rate of previous coronary artery disease was reported. Incidence of systolic and diastolic left ventricular dysfunction was 8.33% (95% CI: 2.20-14.25) and 43.38% (95% CI: 31.73-55.03), respectively. Diastolic dysfunction was graded as first [31.85% (95% CI: 24.85-43.73)], second [8.53% (95% CI: 2.12-14.93)], and third degree [3.02% (95% CI: 1.78-4.27)]. At multivariate analysis, a high sensitivity C-reactive protein level >5 mg/L, active tobacco smoking and previous history of myocardial infarction were predictors of left ventricular systolic dysfunction [odd ratio 1.70 (95% CI: 1.03-2.77); 1.57 (95% CI: 1.03-2.34); and 15.90 (95% CI: 1.94-329.00), respectively]. Hypertension (OR = 2.30; 95% CI: 1.20-4.50) and older age (OR = 2.50 per 10 years increase; 95% CI: 1.70-3.60) were predictors of left ventricular diastolic dysfunction (Figure  3).CONCLUSIONS:Systolic and diastolic dysfunction represent a common finding in pauci symptomatic HIV-infected patients, regardless to HAART.

Background Developed countries are facing a sustained increase in life expectancy. Along with all social and cultural implications of increase lifespan, very elderly patients are undergoing percutaneous coronary intervention (PCI) with increasing frequency. However, there is limited evidence to guide clinicians in evaluating pros and cons of PCI in this very frail patient population. We, thus, aimed to perform a systematic review and meta-analysis of clinical studies reporting on PCI with stenting in nonagenarians. Methods Studies reporting on five or more nonagenarians undergoing PCI were systematically searched in PubMed (last updated on November 2011). Baseline and clinical characteristics, in-hospital and long-term outcomes were systematically appraised. End points of interest were in-hospital and long-term follow-up incidence of death and Major Adverse Cardiac Events (MACE; i.e. the composite of death from all causes, myocardial infarction or repeat revascularization). Events were pooled with a random-effect model, generating summary estimates of incidence rates [95% confidence intervals (CI)]. Results A total of 10 studies were included, reporting on a total of 575 nonagenarians undergoing PCI with stenting who represented 1.99% (1.34–2.5) of those undergoing revascularization in the cath lab in a mean period of 5 (3–7) years. Twenty-three percent (13–45) of patients presented with STEMI (ST Segment Elevation Myocardial Infarction), 10% (7–12) with cardiogenic shock and in 78% (64–88) of cases a multivessel disease was diagnosed. Meta-analytic pooling of event rates showed an in-hospital death risk of 12.61% (9.71–15.50) with MACE in 16.41% (13.36–19.47). After a follow-up ranging from 6 to 29 months (median 12), the risk of long-term death was 31.00% (17.10–45.52), with MACE in 37.00% (19.56–55.95; all CI 95%). Conclusion Our meta-analysis, pooling the largest cohort ever of nonagenarians undergoing PCI with stents, confirms the feasibility of percutaneous coronary stenting even in this very frail patient subset, despite the expected severe event attrition during follow-up. Thus, nonagenarians with an acceptable risk profile, recent clinical instability and/or disabling symptoms should not be denied the possibility of percutaneous coronary revascularization.

High quality randomised clinical trials (RCTs) and meta-analysis represent the highest levels of evidence, but in everyday clinical practice, observational studies are often exploited as a quick and easy way to understand the performance of clinical and interventional strategies. In this setting, multivariate analyses are exploited to drive useful and independent information, but due to potentially confounding messages, should be critically appraised and used in everyday clinical practice.

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 group's 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.

Background Left main disease (LMD) and three-vessel disease (3VD) have important prognostic value in patients with coronary artery disease. However, uncertainties still exist about their prevalence and predictors in patients with acute coronary syndrome (ACS) and also in patients with stable coronary disease. Thus the aim of this study was to perform an international collaborative systematic review and meta-analysis to appraise the prevalence and predictors of LMD and 3VD.Methods Medline/PubMed were systematically searched for eligible studies published up to 2010, reporting multivariate predictors of LMD or 3VD. Study features, patient characteristics, and prevalence and predictors of LMD and 3VD were abstracted and pooled with random-effect methods (95% CIs).Results 17 studies (22 740 patients) were included, 11 focusing on ACS (17 896 patients) and six on stable coronary disease (4844 patients). In the ACS subgroup, LMD or 3VD occurred in 20% (95% CI 7.2% to 33.4%), LMD in 12% (95% CI 10.5% to 13.5%), and 3VD in 25% (95% CI 23.1% to 27.0%). Heart failure at admission and extent of ST-segment elevation in lead aVR on 12-lead ECG were the most powerful predictors of LMD or 3VD. In the stable disease subgroup, LMD or 3VD was found in 36% (95% CI 18.5% to 48.8%), with the most powerful predictors being transient ischaemic dilation during the imaging stress test, extent of ST-segment elevation in aVR and V1 during the stress test, and hyperlipidaemia.Conclusions This meta-analysis demonstrated that severe coronary disease-that is, LMD or 3VD-is more common in patients with ACS or stable coronary disease than generally perceived, and that simple and low-cost tools may help in the selection of the most appropriate therapeutic approach.

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.

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.

BACKGROUNDAssessment of chest pain patients remains a clinical challenge in the emergency department (ED). Several randomized controlled trials (RCTs) have shown the additive value of coronary computed tomographic angiography (CCTA) compared with standard care. Not all of them, however, had enough power to detect differences in clinical outcomes like revascularization. Therefore, we performed a meta-analysis to test the safety and efficacy of this non-invasive diagnostic approach in low- and intermediate-risk chest pain patients.METHODSMEDLINE/PubMed was systematically screened for RCTs comparing CCTA and non-CCTA approaches for ED patients presenting with chest pain. Baseline features, diagnostic strategies, and outcome data were appraised and pooled with random-effect methods computing summary estimates [95% confidence intervals (CIs)].RESULTSA total of four RCT studies including 2567 patients were identified, with similar inclusion and exclusion criteria. Patients in the CCTA group were more likely to undergo percutaneous or surgical revascularization during their index visit, with an odd ratio of 1.88 (1.21-2.92). Time to diagnosis was reduced with CCTA (-7.68 h;-12.70 to 2.66) along with costs of care in the ED (-$680; -1.060 to -270: all CI 95%).CONCLUSIONThe present meta-analysis shows that a strategy with CCTA used as first imaging test for low- and intermediate-risk patients presenting to the ED with chest pain appears safe and seems not to increase subsequent invasive coronary angiographies. The approach is cost-effective although limited data and incomplete cost analyses have been performed. CCTA increases coronary revascularizations, with still an unknown effect on prognosis, especially in the long term.

Objective Trans-radial and trans-ulnar access is increasingly used for percutaneous coronary procedures, but spasm or pain may limit comfort and compliance. Intra-arterial lidocaine administration could provide a local anaesthetic eff ect, but its risk-benefi t ratio is unclear. We aimed to compare intraarterial lidocaine versus saline to reduce peri-procedural discomfort during percutaneous trans-radial or trans-ulnar procedures. Methods and results Patients undergoing percutaneous trans-radial or trans-ulnar coronary procedures were single-blinded randomly assigned to intra-arterial treatment with 20 mg lidocaine or saline. The primary end-point of the study was local pain, measured on a 10-point scale. A total of 101 patients were enrolled (50 allocated to lidocaine and 51 to saline). Trans-radial access was employed in 48 (96%) and 47 (92%), respectively, trans-ulnar access in 2 (4%) and 4 (8%), and coronary intervention was performed in 18 (36%) and 11 (22%). Severity of local pain was equivalent in both groups (2.3 ± 2.3 vs. 3.0 ± 2.5, P = 0.167). Similar results for both groups were found also for local spasm, local access success, procedural success, and net clinical adverse events (all P > 0.05). No sustained cardiac arrhythmia or neurologic symptom developed in any patient. Conclusions Current approaches and techniques for percutaneous trans-radial or trans-ulnar coronary procedures are associated with few local or systemic complications. Local forearm/wrist pain is relatively frequent in this setting, and is not signifi cantly prevented by intra-arterial lidocaine.

Bollati, Mario; Giraudi, Elena; Moretti, Claudio; Millesimo, Giorgio; Sciuto, Filippo; Omedè, Pierluigi; Biondi Zoccai, Giuseppe; Sheiban, Imad Author Information