Giorgio Quadri

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.

Comparison of Mortality Rates in Women Versus Men Presenting With ST-Segment Elevation Myocardial Infarction

Women who present with coronary artery disease have different characteristics, undergo different treatment, and have a different prognosis than men. The increasing use of coronary stenting has improved the outcome of percutaneous coronary intervention (PCI). However, little is known about the outcomes for men versus women after PCI, especially for those presenting with a diagnosis of acute coronary syndrome. Thus, we compared the baseline features, management, and long-term outlook of men versus women undergoing PCI. All consecutive patients who had undergone PCI with stents at our center from July 1, 2002 to June 30, 2004 were identified retrospectively. The primary end point was the long-term rate of major adverse cardiac events (i.e., death, infarction, and repeat revascularization). The secondary end points were the individual components of the major adverse cardiac events and stent thrombosis. A total of 833 patients were included, 210 women (25.2%) and 623 men (75.8%). The women were significantly older (70.9 vs 63 years, p <0.001) and more often had diabetes mellitus (36.2% vs 21.0%, p <0.001) and hypertension (82.3% vs 73.7%, p = 0.006). The number of drug-eluting stents and the length were significantly lower in the female patients. The incidence of major adverse cardiac events after a median follow-up of 60 months was similar for both women and men (38.8% vs 46.4%, p = 0.075), with a trend toward greater mortality rate for women (21.2% vs 15.4%, p = 0.090). All other end points occurred with similar frequencies. Only in the subgroup of ST-segment elevation myocardial infarction were the rates of death significantly greater for the women than for the men (20.0% vs 8.1%; p = 0.029). In conclusion, very long-term follow-up of women undergoing PCI with coronary artery stenting resulted in similar rates of cardiac event compared to those of men, but greater care should be given to women presenting with ST-segment elevation myocardial infarction. Also, despite their greater baseline risk profile, women were significantly less likely to have received effective treatment, the use of including drug-eluting stents.

Accuracy of intravascular ultrasound and optical coherence tomography in identifying functionally significant coronary stenosis according to vessel diameter: A meta-analysis of 2,581 patients and 2,807 lesions

INTRODUCTION Accuracy of intracoronary imaging to discriminate functionally significant coronary stenosis according to vessel diameter remains to be defined. METHODS PubMed, Scopus, and Google Scholar were systematically searched for studies assessing diagnostic accuracy (area under the receiver operating characteristic curve [AUC], the primary end point) and sensitivity and specificity (the secondary end points) of minimal luminal area (MLA) or of minimal luminal diameter (MLD) derived from intravascular ultrasound (IVUS) or optical coherence tomography (OCT) to detect functionally significant stenosis as determined with fractional flow reserve (FFR). RESULTS Fifteen studies were included, 2 with 110 patients analyzing only left main (LM), 5 with 224 patients and 306 lesions using OCT, and 9 with 1532 patients and 1681 lesions with IVUS. Median MLA for the OCT studies was 1.96 mm(2) (1.85-1.98 mm(2)), 2.9 mm(2) (2.7-3.1 mm(2)) for MLA of all lesions assessed with IVUS, 2.8 mm(2) (2.7-2.9 mm(2)) for lesions with an angiographic diameter >3 mm, 2.4 mm(2) (2.4-2.5 mm(2)) for lesions <3 mm, and 5.4 mm(2) (5.1-5.6 mm(2)) for LM lesions. For OCT-MLA, AUC was 0.80 (0.74-0.86), with a sensitivity of 0.81 (0.74-0.87) and specificity of 0.77 (0.71-0.83), whereas OCT-MLD had an AUC of 0.85 (0.79-0.91), sensitivity of 0.74 (0.69-0.78), and specificity of 0.70 (0.68-0.73). For IVUS-MLA, AUC was 0.78 (0.75-0.81) for all lesions, 0.78 (0.73-0.84) for vessels with a diameter >3 mm, and 0.79 (0.70-0.89) for those with a diameter <3 mm. Left main AUC was 0.97 (0.93-1). CONCLUSION Intravascular ultrasound and OCT had modest diagnostic accuracy for identification hemodynamically significant lesions, also with specific cutoff for different diameters. Invasive imaging for assessment of LM severity demonstrated excellent correlation with FFR. What is already known about this subject? Fractional flow reserve represents the criterion standard to evaluate the prognostic value of coronary stenosis, whereas its relationship with IVUS and OCT remains to be assessed. What does this study add? Despite improvement, IVUS and OCT do not predict functional stenosis, even with dedicated cutoff, apart from LM disease. How might this impact on clinical practice? The recent guidelines of myocardial revascularization have stressed the crucial role of FFR before performing percutaneous coronary intervention on LM, whereas intravascular imaging is often exploited to drive revascularization. The present analysis stresses the point that LM percutaneous coronary intervention may be driven only by intravascular imaging, given the high accuracy for significant ischemic lesions, whereas for other vessels, these 2 techniques mirror 2 different aspects.

Meta-Analysis of Randomized Controlled Trials and Adjusted Observational Results of Use of Clopidogrel, Aspirin, and Oral Anticoagulants in Patients Undergoing Percutaneous Coronary Intervention

The optimal antiaggregant therapy after coronary stenting in patients receiving oral anticoagulants (OACs) is currently debated. MEDLINE and Cochrane Library were searched for studies reporting outcomes of patients who underwent PCI and who were on triple therapy (TT) or dual-antiplatelet therapy (DAPT) with aspirin and clopidogrel or dual therapy (DT) with OAC and clopidogrel. Major bleeding was the primary end point, whereas all-cause death, myocardial infarction (MI), stent thrombosis, and stroke were secondary ones. Results were reported for all studies and separately for those deriving from randomized controlled trials or multivariate analysis. In 9 studies, 1,317 patients were treated with DAPT and 1,547 with TT. DAPT offered a significant reduction of major bleeding at 1 year for overall studies and for the subset of observational works providing adjusted data (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.39 to 0.68, I2 60% and OR 0.36, 95% CI 0.28 to 0.46) compared to TT. No increased risk of major adverse cardiac events (MACE: death, MI, stroke, and stent thrombosis) was reported (OR 0.71, 95% CI 0.46 to 1.08), although not deriving from randomized controlled trials or multivariate analysis. Six studies tested OAC and clopidogrel (1,263 patients) versus OAC, aspirin, and clopidogrel (3,055 patients) with a significant reduction of bleeding (OR 0.79, 95% CI 0.64 to 0.98), without affecting rates of death, MI, stroke, and stent thrombosis (OR 0.90, 95% CI 0.69 to 1.23) also when including clinical data from randomized controlled trials or multivariate analysis. In conclusion, compared to TT, both aspirin and clopidogrel and clopidogrel and OAC reduce bleeding. No difference in major adverse cardiac events is present for clopidogrel and OAC, whereas only low-grade evidence is present for aspirin and clopidogrel.

Management of multivessel coronary disease in STEMI patients: A systematic review and meta-analysis

BACKGROUND Appropriate management for patients with multivessel coronary disease presenting with ST segment Elevation Myocardial Infarction (STEMI) remains to be defined. METHODS AND RESULTS Medline and Cochrane Library were searched for randomized controlled trials (RCTs) or observational studies adjusted with multivariate analysis, reporting about STEMI patients with multivessel coronary disease treated with either a culprit only or complete revascularization strategy, excluding patients in cardiogenic shock. Prespecified analysis was performed according to the strategy of complete revascularization, either during the same procedure of primary percutaneous coronary intervention (PCI) or during the index hospitalization. MACE (a composite and mutually exclusive end point of death or myocardial infarction or revascularization) at follow-up of at least one year was the primary end point. 9 studies with 4686 patients compared culprit only versus complete PCI performed during the primary PCI. Rates of MACE did not differ at 90 days (OR 0.70 [0.38, 1.27], I(2)=0%) or at 1 year (1-2.5) (OR 0.70 [0.47, 1.03], I(2)=0%). No significant difference was found for the components of the primary outcome, apart from a reduction in repeated revascularization for patients undergoing complete PCI during the STEMI procedure (OR 0.62 [0.39, 0.98], I(2)=0%). 6 studies (1 RCT) with 5855 patients compared culprit only lesions versus complete PCI performed during index hospitalization. 90 day risk of MACE did not differ nor 1 year (1-2.5) MACE (OR 0.86 [0.62, 1.08], I(2)=0%), with a similar reduction in repeated revascularization (0.60 [0.40, 0.90], I(2)=0%). CONCLUSIONS Complete revascularization performed during primary PCI or index hospitalizations for patients presenting with STEMI appears safe at short term follow-up and offers a reduction in repeated revascularization at one year.

Optical coherence tomography evaluation of intermediate-term healing of different stent types: systemic review and meta-analysis

Aims The intermediate-term incidence of strut malapposition (SM) and uncovered struts (US), and the degree of neointimal thickness (NIT) according to stent type have not been characterized. Methods and results All studies of >50 patients in which optical coherence tomography was performed between 6 and 12 months after stent implantation were included. The incidences of SM and US were the co-primary end points, while NIT was the secondary end point. A total of 458 citations were initially appraised at the abstract level, and 11 full-text studies (280 652 analysed struts, 921 patients) were assessed. The 6–12 months incidences of SM and US were 5.0 and 7.8%, respectively, and the mean NIT was 206 &mgr;m. Biolimus-eluting stents (BES) and bioresorbable vascular scaffolds (BVS) had the highest SM rates (2.7 and 3.8%, respectively), while everolimus-eluting stents (EES) and fast-release zotarolimus-eluting stents (ZES) had the lowest SM rates (0.9 and 0.1%, respectively). BES and sirolimus-eluting stents (SES) had the highest US rates (7.7 and 8.8%, respectively), while bare metal stents (BMS) and ZES had the lowest US rates (0.3 and 0.3%, respectively). BMS had the greatest NIT (340 &mgr;m), while SES, EES, and BES had the least NIT. Conclusion Second-generation drug-eluting stents (DES) have better intermediate-term strut apposition and coverage than first-generation DES, BVS, and BMS. EES demonstrate the overall best combination of healing with suppression of neointimal hyperplasia at 6–12 months. Further studies with clinical correlation are warranted to determine the implications of these findings.

RISK OF CARDIOVASCULAR DISEASE MORBIDITY AND MORTALITY IN FRAIL AND PRE-FRAIL OLDER ADULTS: RESULTS FROM A META-ANALYSIS AND EXPLORATORY META-REGRESSION ANALYSIS

Frailty is common and associated with poorer outcomes in the elderly, but its role as potential cardiovascular disease (CVD) risk factor requires clarification. We thus aimed to meta-analytically evaluate the evidence of frailty and pre-frailty as risk factors for CVD. Two reviewers selected all studies comparing data about CVD prevalence or incidence rates between frail/pre-frail vs. robust. The association between frailty status and CVD in cross-sectional studies was explored by calculating and pooling crude and adjusted odds ratios (ORs) ±95% confidence intervals (CIs); the data from longitudinal studies were pooled using the adjusted hazard ratios (HRs). Eighteen cohorts with a total of 31,343 participants were meta-analyzed. Using estimates from 10 cross-sectional cohorts, both frailty and pre-frailty were associated with higher odds of CVD than robust participants. Longitudinal data were obtained from 6 prospective cohort studies. After a median follow-up of 4.4 years, we identified an increased risk for faster onset of any-type CVD in the frail (HR=1.70 [95%CI, 1.18-2.45]; I2=66%) and pre-frail (HR=1.23 [95%CI, 1.07-1.36]; I2=67%) vs. robust groups. Similar results were apparent for time to CVD mortality in the frail and pre-frail groups. In conclusion, frailty and pre-frailty constitute addressable and independent risk factors for CVD in older adults.

THE STORM (acute coronary Syndrome in paTients end Of life and Risk assesMent) study

Introduction Elderly patients with coexisting frailty and multiple comorbidities frequently present to the emergency department (ED). Because non-cardiovascular comorbidities and declining health status may affect their life expectancy, management of these patients should start in the ED. This study evaluated the role of Gold Standards Framework (GSF) criteria for identifying patients with acute coronary syndromes (ACS) approaching end of life. Methods All consecutive patients admitted to the ED and hospitalised with a diagnosis of ACS between May 2012 and July 2012 were included. According to GSF criteria, patients were labelled as positive GSF status when they met at least one general criterion and two heart disease criteria; furthermore, traditional cardiovascular risk scores (the Global Registry for Acute Coronary Events (GRACE) score and the Age, Creatinine and Ejection Fraction (ACEF) score) were calculated and WHOQOL-BREF was assessed. Mortality and repeat hospitalisation due to cardiovascular and non-cardiovascular causes were evaluated at 3-month and 12-month follow-up. Results From a total of 156 patients with ACS enrolled, 22 (14%) had a positive GSF. A positive GSF was associated with higher rate of non-cardiovascular events (22.7% vs 6.7%; p=0.03) at 3 months and higher rates of both cardiovascular and non-cardiovascular events (36% vs 16.4%; p=0.04 and 27.3% vs 6.7%; p=0.009, respectively) at 12 months. In multivariate analysis, an in-hospital GRACE score was a predictor of cardiovascular events, while a positive GSF independently predicted non-cardiovascular events. Conclusions The GSF score independently predicts non-cardiovascular events in patients presenting with ACS and may be used along with traditional cardiovascular risk scores in choosing wisely the most appropriate treatment. The present results need to be externally validated on larger samples.

A meta-analysis investigating incidence and features of stroke in HIV-infected patients in the highly active antiretroviral therapy era.

Objective Recent studies have suggested a close biological and clinical association between HIV infection and risk of myocardial infarction, whereas contrasting data have been reported about incidence of stroke and its clinical predictors. Design and setting Studies including HIV-infected patients developing a cerebral ischemic event were systematically searched for in MEDLINE/PubMed. Patients and main outcome measures Baseline, treatment and outcome data were appraised and pooled with random-effects methods computing summary estimates (95% confidence intervals). Results Five studies comprising 89 713 participants were included: they were young [46 (46–50) years, mainly male (70% (68–79)] with a moderate prevalence of diabetes [19% (14–21)]. Atrial fibrillation and history of previous coronary artery disease were observed in 3% (2–5) and 18% (15–22), respectively. All patients were on highly active antiretroviral therapy (HAART) and had been treated for a mean of 5 (2–6) years. After a median of 4 (3–5) years of follow-up, 1245 ischemic strokes occurred [1.78% (0.75–2.81)]. Traditional risk factors such as age (five studies), hypertension (three studies), smoking (two studies), hyperlipidemia (one study), atrial fibrillation (one study) and diabetes (one study) were identified as independent predictors of stroke. In one study, RNA viral load [log of odds ratio = 1.10 (1.04–1.17)] and CD4+ cell count less than 200/&mgr;l were clinically related to stroke, whereas HAART therapy showed a neutral effect. Conclusion Stroke represents a relatively common complication in young, HAART-treated HIV patients. Apart from traditional cardiovascular risk factors, HIV-RNA viral load may help to target and manage patients at risk.

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.