Safety and efficacy of different P2Y12 inhibitors in patients with acute coronary syndromes stratified by the PRAISE risk score: a multicentre study.

AIMS: To establish the safety and efficacy of different dual antiplatelet therapy (DAPT) combinations in patients with acute coronary syndrome (ACS) according to their baseline ischaemic and bleeding risk estimated with a machine learning derived model [machine learning-based prediction of adverse events following an acute coronary syndrome (PRAISE) score]. METHODS AND RESULTS: Incidences of death, re-acute myocardial infarction (re-AMI), and Bleeding Academic Research Consortium 3-5 bleeding with aspirin plus different P2Y12 inhibitors (clopidogrel or potent P2Y12 inhibitors: ticagrelor or prasugrel) were appraised among patients of the PRAISE data set grouped in four subcohorts: low-to-moderate ischaemic and bleeding risk; low-to-moderate ischaemic risk and high bleeding risk; high ischaemic risk and low-to-moderate bleeding risk; and high ischaemic and bleeding risk. Hazard ratios (HRs) for the outcome measures were derived with inverse probability of treatment weighting adjustment. Among patients with low-to-moderate bleeding risk, clopidogrel was associated with higher rates of re-AMI in those at low-to-moderate ischaemic risk [HR 1.69, 95% confidence interval (CI) 1.16-2.51; P = 0.006] and increased risk of death (HR 3.2, 1.45-4.21; P = 0.003) and re-AMI (HR 2.23, 1.45-3.41; P < 0.001) in those at high ischaemic risk compared with prasugrel or ticagrelor, without a difference in the risk of major bleeding. Among patients with high bleeding risk, clopidogrel showed comparable risk of death, re-AMI, and major bleeding vs. potent P2Y12 inhibitors, regardless of the baseline ischaemic risk. CONCLUSION: Among ACS patients with non-high risk of bleeding, the use of potent P2Y12 inhibitors is associated with a lower risk of death and recurrent ischaemic events, without bleeding excess. Patients deemed at high bleeding risk may instead be safely addressed to a less intensive DAPT strategy with clopidogrel.

Predictors of fractional flow reserve/instantaneous wave-free ratio discordance: impact of tailored diagnostic cut-offs on clinical outcomes of deferred lesions.

BACKGROUND: Patient-related and lesion-related factors may influence instantaneous wave-free ratio (iFR)/fractional flow reserve (FFR) concordance, potentially affecting the safety of revascularization deferral. METHODS: Consecutive patients with at least an intermediate coronary stenosis evaluated by both iFR and FFR were retrospectively enrolled. The agreement between iFR and FFR at their diagnostic cut-offs (FFR 0.80, iFR 0.89) was assessed. Predictors of discordance were assessed using multivariate analyses. Tailored iFR cut-offs according to predictors of discordance best matching an FFR of 0.80 were identified. The impact of reclassification according to tailored iFR cut-offs on major cardiovascular events (MACE: cardiovascular death, myocardial infarction or target-lesion revascularization) among deferred lesions was investigated. RESULTS: Two hundred and ninety-nine intermediate coronary stenosis [FFR 0.84 (0.78-0.89), iFR 0.91 (0.87-0.95), 202 left main/left anterior descending (LM/LAD) vessels, 67.6%] of 260 patients were studied. Discordance rate was 23.4% (n = 70, 10.7% iFR-negative discordant, 12.7% iFR-positive discordant). Predictors of discordance were LM/LAD disease, multivessel disease, non-ST-elevation myocardial infarction, smoking, reduced eGFR and hypertension. Lesion reclassification with tailored iFR cut-offs based on patient-level predictors carried no prognostic value among deferred lesions. Reclassification according to lesion location, which was entirely driven by LM/LAD lesions (iFR cut-offs: 0.93 for LM/LAD, 0.89 for non-LM/LAD), identified increased MACE among lesions deferred based on a negative FFR, between patients with a positive as compared with a negative iFR (19.4 vs. 6.1%, P = 0.044), whereas the same association was not observed with the conventional 0.89 iFR cut-off (15 vs. 8.6%, P = 0.303). CONCLUSION: Tailored vessel-based iFR cut-offs carry prognostic value among FFR-negative lesions, suggesting that a one-size-fit-all iFR cut-off might be clinically unsatisfactory.

Fractional flow reserve guided versus angiographic guided surgical revascularization: A meta-analysis.

BACKGROUND: Clinical benefits of FFR (Fraction Flow Reserve) driven CABG (Coronary Artery Bypass Graft) remain to be established. METHODS: All randomized controlled trials (RCTs) and observational studies with multivariable adjustement were included. MACE (Major Adverse Cardiac Events) was the primary end point, while its single components (death, myocardial infarction, and total vessel revascularization [TVR]) along with number of anastomoses, on pump procedures and graft occlusion at angiographic follow-up were the secondary ones. Each analysis was stratified for RCTs versus observational studies. RESULTS: Four studies (two RCTs and two observational) were included, enrolling 983 patients, 542 angio-guided and 441 FFR-guided. Mean age was 68.45 years, 79% male, with a mean EuroSCORE I of 2.7. Coronary lesions were located in 37% of patients in the left anterior descending artery, 32% in the circumflex artery, and 26% in the right coronary artery. After a mean follow-up of 40 months, risk of MACE did not differ (OR 0.86 [0.63-1.18]) as that of all cause death (OR 0.86 [0.59-1.25]), MI (OR 0.57 [0.30-1.11]) and TVR (OR 1.10 [0.65-1.85]). FFR-driven CABG reduced on-pump procedures (OR 0.58 [0.35-0.93]) and number of anastomoses (-0.40 [-0.80: -0.01]) while incidence of graft occlusion at follow-up did not differ (OR 0.59 [0.30-1.15], all CI 95%). CONCLUSION: Fraction flow reserve driven CABG reduced the number of anastomoses and of on-pump procedures without increasing risk of MACE and without reducing graft occlusion at angiographic follow-up. ID CRD42020211945.

Percutaneous vs. surgical revascularization for patients with unprotected left main stenosis: a meta-analysis of 5-year follow-up randomized controlled trials.

AIMS: A 5-year survival of patients with unprotected left main (ULM) stenosis according to the choice of revascularization (percutaneous vs. surgical) remains to be defined. METHODS AND RESULTS: Randomized controlled trials (RCTs) comparing percutaneous coronary intervention (PCI) vs. coronary artery bypass graft (CABG) with a follow-up of at least 5 years were included. All-cause death was the primary endpoint. MACCE [a composite endpoint of all-cause mortality, myocardial infarction (MI), stroke, and repeat revascularization] along with its single components and cardiovascular (CV) death were the secondary ones. Analyses were stratified according to the use of first- vs. last-generation coronary stents. Subgroup comparisons were performed according to SYNTAX score (below or above 33) and to age (using cut-offs of each trial's subgroup analysis). Four RCTs with 4394 patients were identified: 2197 were treated with CABG, 657 with first generation, and 1540 with last-generation stents. At 5-year rates of all-cause death did not differ [odds ratio (OR) 0.93, 95% confidence interval (CI) 0.71-1.21], as those of CV death and stroke. Coronary artery bypass graft reduced rates of MACCE (OR 0.69, 95% CI 0.60-0.79), mainly driven by MI (OR 0.48, 95% CI 0.36-0.65) and revascularization (OR 0.53, 95% CI 0.45-0.64). Benefit of CABG for MACCE was consistent, although with different extent, across values of SYNTAX score (OR 0.76, 95% CI 0.59-0.97 for values < 32 and OR 0.63, 95% CI 0.47-0.84 for values ≥ 33) while was not evident for 'younger' patients (OR 0.83, 95% CI 0.65-1.07 vs. OR 0.65, 95% CI 0.51-0.84 for 'older' patients). CONCLUSION: For patients with ULM disease followed-up for 5 years, no significant difference was observed in all-cause and cardiovascular death between PCI and CABG. Coronary artery bypass graft reduced risk of MI, revascularization, and MACCE especially in older patients and in those with complex coronary disease and a high SYNTAX score.

In the midst of a dangerous intersection with unclear therapeutic strategies: a challenging case of severe aortic stenosis.

BACKGROUND: One out of seven patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) may be affected by transthyretin cardiac amyloidosis (ATTR-CA), mostly presenting with low-flow low-gradient AS with mildly reduced ejection fraction. The complex interaction of these two pathologies poses specific diagnostic and management challenges. The prognostic implications of this clinical intersection are not defined yet. Moreover, whether TAVR may have a prognostic benefit in ATTR-CA patients with symptomatic severe AS remains unclear, posing doubts on the best management strategy in this increasingly recognized subset of patients. CLINICAL CASE: We present a case of an 87-year old man with low-flow low-gradient severe AS, for whom a diagnosis of ATTR-CA was suspected based on clinical and echocardiographic criteria specific to coexisting AS and ATTR-CA. The diagnosis was eventually confirmed by positive bone tracer scintigraphy imaging. Following in-depth Heart team discussion, integrating frailty and prognostic information from combined cardiomyopathy states, a decision was made to manage the patient's severe AS conservatively. CONCLUSION: In the presented case, we deemed the natural history of ATTR-CA amyloidosis to negatively affect both the patient' prognosis and procedural risk, adversing TAVR indication despite symptomatic severe AS. No clear evidence is currently available to guide decision making in this setting, advocating for prospective studies to clarify if TAVR may have a prognostic benefit in ATTR-CA - and which ATTR-CA - patients.

P2Y12 inhibitors in acute coronary syndrome patients with renal dysfunction: an analysis from the RENAMI and BleeMACS projects.

AIMS: The aim of the present study was to establish the safety and efficacy profile of prasugrel and ticagrelor in real-life acute coronary syndrome (ACS) patients with renal dysfunction. METHODS AND RESULTS: All consecutive patients from RENAMI (REgistry of New Antiplatelets in patients with Myocardial Infarction) and BLEEMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registries were stratified according to estimated glomerular filtration rate (eGFR) lower or greater than 60 mL/min/1.73 m2. Death and myocardial infarction (MI) were the primary efficacy endpoints. Major bleedings (MBs), defined as Bleeding Academic Research Consortium bleeding types 3 to 5, constituted the safety endpoint. A total of 19 255 patients were enrolled. Mean age was 63 ± 12; 14 892 (77.3%) were males. A total of 2490 (12.9%) patients had chronic kidney disease (CKD), defined as eGFR <60 mL/min/1.73 m2. Mean follow-up was 13 ± 5 months. Mortality was significantly higher in CKD patients (9.4% vs. 2.6%, P < 0.0001), as well as the incidence of reinfarction (5.8% vs. 2.9%, P < 0.0001) and MB (5.7% vs. 3%, P < 0.0001). At Cox multivariable analysis, potent P2Y12 inhibitors significantly reduced the mortality rate [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.54-0.96; P = 0.006] and the risk of reinfarction (HR 0.53, 95% CI 0.30-0.95; P = 0.033) in CKD patients as compared to clopidogrel. The reduction of risk of reinfarction was confirmed in patients with preserved renal function. Potent P2Y12 inhibitors did not increase the risk of MB in CKD patients (HR 1.00, 95% CI 0.59-1.68; P = 0.985). CONCLUSION: In ACS patients with CKD, prasugrel and ticagrelor are associated with lower risk of death and recurrent MI without increasing the risk of MB.

Percutaneous coronary intervention or coronary artery bypass graft in left main coronary artery disease: a comprehensive meta-analysis of adjusted observational studies and randomized controlled trials.

BACKGROUND: Treatment of patients with ULMCA (unprotected left main coronary artery disease) with percutaneous coronary intervention (PCI) has been compared with coronary artery bypass graft (CABG), without conclusive results. METHODS: All randomized controlled trials (RCTs) and observational studies with multivariate analysis comparing PCI and CABG for ULMCA were included. Major cardiovascular events (MACEs, composite of all-cause death, MI, definite or probable ST, target vessel revascularization and stroke) were the primary end points, whereas its single components were the secondary ones, along with stent thrombosis, graft occlusion and in-hospital death and stroke. Subgroup analyses were performed according to Syntax score. RESULTS: Six RCTs (4717 patients) and 20 observational studies with multivariate adjustment (14 597 patients) were included. After 5 (3-5.5) years, MACE rate was higher for PCI [odds ratio (OR) 1.10, 95% confidence interval (CI) 1.07-1.14], without difference in death, whereas more relevant risk of MI was because of observational studies. Coronary stenting increased risk of revascularization (OR 1.52; 95% CI 1.34-1.72). At meta-regression, performance of PCI was improved by use of intra-coronary imaging and worsened by first generation stents, whereas two arterial grafts increased benefit of CABG. For patients with Syntax score less than 22, MACE rates did not differ, whereas for higher values, CABG reduced MACE because of lower risk of revascularization. Incidence of graft occlusion was 3.24% (2.25-4.23), whereas 2.13% (1.28-2.98: all CI 95%) of patients experienced stent thrombosis. CONCLUSION: Surgical revascularization reduces risk of revascularization for ULMCA patients, especially for those with Syntax score greater than 22, with a higher risk of in-hospital death. Intra-coronary imaging and use of arterial grafts improved performance of revascularization strategies.

Intracoronary versus intravenous adenosine to assess fractional flow reserve: a systematic review and meta-analysis.

AIMS: Intravenous infusion of adenosine is the reference method to measure fractional flow reserve (FFR). Intracoronary boluses are often used because of time and convenience, but their effectiveness has yet to be assessed. METHODS: We conducted a systematic review and meta-analysis of prospective studies directly comparing intravenous and intracoronary adenosine administration for FFR measurement. FFR values and prevalence of functionally critical lesions obtained with the different methods of adenosine administration were compared. RESULTS: Twelve studies evaluating 781 lesions from 731 patients were included (63.7 years, 25.5% women, median FFR 0.82). FFR values were significantly lower with intravenous adenosine than with intracoronary adenosine [mean difference 0.01, 95% confidence interval (CI) 0.00-0.02, P = 0.005], even if no significant differences were observed when only high doses of intracoronary adenosine (≥150 µg) were considered. The prevalence of functionally critical lesions did not significantly differ between intracoronary and intravenous adenosine. Concerning the use of different doses of intracoronary adenosine, low doses (≤60 µg) were associated with higher FFR values (mean difference 0.02, 95% CI 0.01-0.03, P < 0.001) and fewer functionally critical lesions (OR 0.57, 95% CI 0.40-0.81, P = 0.002) compared with high doses. Meta-regression analysis did not show any significant interaction between the way of adenosine administration and main clinical features. Intracoronary adenosine was associated with a higher incidence of atrioventricular blocks, whereas angina and/or systemic symptoms were more frequent with intravenous adenosine. CONCLUSION: Intracoronary adenosine might be as effective as intravenous adenosine to measure FFR, provided that adequate doses are used. Intracoronary adenosine represents a valuable alternative to intravenous adenosine whenever appropriately administered.

The EUROpean and Chinese cardiac and renal Remote Ischemic Preconditioning Study (EURO-CRIPS CardioGroup I): A randomized controlled trial.

BACKGROUND: The potential protective effects of remote ischemic preconditioning (RIPC) on contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI) remain to be defined. METHODS AND RESULTS: A double blind, randomized, placebo controlled multicenter study was performed. Patients younger than 85years old, with a renal clearance of 30-60ml/min/1.73m2, who were candidates for PCI for all clinical indications except for primary PCI, were allocated 1:1 to RIPC or to standard therapy. The primary endpoint was incidence of CIN. The secondary endpoint was incidence of peri-procedural myocardial infarction (PMI). From February 2013 to April 2014, 3108 patients who were scheduled for coronary angiography were screened for the study. 442 fulfilled the inclusion criteria and 223 received PCI. These patients were randomized to sham RIPC (n=107) or treatment group (n=116). The only pre-specified subgroup of diabetic patients included 85 (38%) cases. RIPC significantly reduced CIN incidence in the overall population (12.1% vs. 26.1%, p=0.01, with a NNT=9) and in non-diabetic patients (9.2% vs. 25.0%, p=0.02), but showed no benefit in diabetics (16.7% vs. 28.2%, p=0.21). A trend for lower PMI was seen in the intervention arm (creatine kinase - muscle brain >5 URL; 8.4% vs. 16.4%, p=0.07; troponin T >5 URL; 27% vs. 38%, p=0.21). CONCLUSIONS: Remote ischemic preconditioning significantly reduces the incidence of acute kidney injury in non-diabetic patients undergoing PCI. Larger sample size is presumably needed to assess the effect of RIPC for patients with diabetes mellitus. Clinical Trial number:NCT02195726https://www.clinicaltrial.gov/.

Angiography vs transesophageal echocardiography-guided patent foramen ovale closure: A propensity score matched analysis of a two-center registry.

OBJECTIVES: The purpose of this study is to compare the long-term outcomes of patent foramen ovale (PFO) closure using angiography or transesophageal echocardiography as procedural guidance. BACKGROUND: The interventional treatment is emerging as a safe and efficient option for patients with high likelihood of PFO-related cryptogenic stroke and high risk of recurrence. The "gold-standard" guidance technique remains an issue. METHODS: Two cohorts of patients undergoing PFO closure for cryptogenic stroke in two catheterization laboratories of the same institution, using similar inclusion criteria but different guidance, were compared with propensity score matching. RESULTS: A total of 374 patients were enrolled, 161 in Angio-group and 213 in Echo-group. No difference was detected in the procedural complication rate. In Angio-group, radiological exposure (P = .001) and 6-month residual shunt (16.8% vs 8.0%, P = .015) were higher. After a mean follow-up of 41 ± 30 months, 28 patients (7.5%) presented any adverse event (death, recurrent cerebral ischemia, device-related complications, reintervention), with a higher rate in Angio-group (13.0% vs 3.3%, P = .001), mainly due to repeated percutaneous intervention (10.6% vs 1.4%, P = .001). The results were confirmed after propensity score matching (118 patients/group). The rate of recurrent cerebral ischemia was 1.9% and was not significantly different in the two groups. Intra-procedural guidance and atrial septum aneurysm were independent predictors of the composite primary endpoint (OR 1.2, P = .016). CONCLUSIONS: The use of intra-procedural transesophageal echocardiography (TEE) guidance for PFO closure allows lower residual shunt rate, radiological exposure, and adverse events, mainly driven by a significant reduction in percutaneous reintervention.

What is the optimal treatment for symptomatic patients with isolated coronary myocardial bridge? A systematic review and pooled analysis.

BACKGROUND: Myocardial bridging is a common coronary anomaly, with few severe adverse events but a relevant symptom burden. Myocardial bridging treatment, however, remains uncertain because of the lack of randomized trials. MATERIAL: MEDLINE/PubMed was systematically screened for studies reporting on isolated myocardial bridging diagnosed at coronary angiography or with coronary computed tomography in patients admitted for suspected angina or with an acute coronary syndrome. Baseline, treatment and outcome data were appraised and pooled according to treatment (medical therapy, bypass surgery/myotomy or stenting). RESULTS: A total of 899 patients in 18 studies were included with a low prevalence of traditional risk factors, especially diabetes (15.6%, interquartile range 2.5-21.5). After a median of 31.0 months (interquartile range 12.4-37.1), major cardiovascular events (composite of death, myocardial infarction or target vessel revascularization) occurred in only 3.4% of the study patients and 78.7% [70.5-86.9; 95% confidence intervals (CI)] were managed conservatively and free of symptoms. When an invasive strategy was planned, freedom from angina was higher in patients treated with surgery [84.5% (78.4-90.7; 95% CI)] than in those treated with stenting [54.7% (38.9-70.6; 95% CI)]. Patients in the stenting group experienced a high incidence of major cardiovascular events related to target vessel revascularization [40.07% (19.83-60.32; 95% CI)]. Meta-regression showed that patients treated with beta-blockers or with a history of hypertension were more likely to remain free from angina (B -0.6, P = 0.013; B -0.66, P = 0.006). CONCLUSION: Patients with symptomatic isolated myocardial bridging generally have a good long-term prognosis. Pharmacological treatment alone, especially with beta-blockers, is able to improve angina in most cases. Surgical treatment appears to be more effective than stenting in nonresponders.

Handle With Care: A Ductus Arteriosus Aneurysm in an Elderly Patient.

A ductus arteriosus aneurysm (DAA) was corrected with an 18 mm Amplatzer patent foramen ovale occluder. DAA is a rare finding, with sporadic cases reported (the vast majority in children and infants). In the elderly, it poses serious therapeutic challenges, as the risk of rupture is counterbalanced by the high risk of its correction, which requires surgery or placement of an endovascular prosthesis in a critical region such as the aortic arch.

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.

Incidence, Management, and Immediate- and Long-Term Outcomes After Iatrogenic Aortic Dissection During Diagnostic or Interventional Coronary Procedures.

BACKGROUND: Aortic dissection type A is a disease with high mortality. Iatrogenic aortic dissection after interventional procedures is infrequent, and prognostic data are scarce. Our objective was to analyze its incidence, patient profile, and long-term prognosis. METHODS AND RESULTS: Between 2000 and 2014, we retrospectively analyzed 74 patients with dissection of the ascending aorta. Clinical and procedural data were reviewed, and later, we performed a prospective clinical follow-up by telephone or in the office. The incidence of aortic dissection was 0.06%. Our patients, predominantly male (67.6%), had a mean age of 66.9±10.8 years. With multiple cardiovascular risk factors, the main reason for cardiac catheterization was an acute coronary syndrome (n=54). The complication was detected acutely in all, trying to engage the right coronary artery in 47 and the left main artery in 30 and after other maneuvers in 2, mostly complex therapeutic procedures (78.4%). A coronary artery was involved in 45 patients (60.8%). Thirty-five patients underwent an angioplasty and stent implantation; 3 had cardiac surgery; and 36 were managed conservatively. Two patients died of cardiogenic shock after the dissection. After a median follow-up of 51.2 months (range, 16.4-104.8 months), none of the remaining patients developed complications as a result of the dissection, progression, ischemia, pain, or dissection recurrence. CONCLUSIONS: Iatrogenic catheter dissection of the aorta is a rare complication that carries an excellent short- and long-term prognosis with the adoption of a conservative approach. When a coronary artery is involved as an entry point, it usually can be safely sealed with a stent with good long-term outcomes.

Effect of gender after transcatheter aortic valve implantation: a meta-analysis.

BACKGROUND: The effect of gender on patients with aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) remains to be defined. METHODS: MEDLINE, Cochrane Library, and Scopus databases were searched for articles describing sex differences in baseline characteristics, procedures, and outcomes. All-cause death at follow-up of at least 1 year was the primary end point, and the independent effect of female gender was evaluated with pooled analysis using a random-effect model and with meta-regression. RESULTS: Six studies with 6,645 patients were included, half of them being women presenting with lower European System for Cardiac Operative Risk Evaluation (EuroSCORE) compared with men. At 30 days, more frequent major vascular complications and major and life-threatening bleeding occurred in women, with lower rates of moderate to severe aortic regurgitation, whereas 30-day mortality was similar. After a median follow-up of 365 days (range, 365 to 730 days) all-cause mortality was 24.0% in women and 34.0% in men. A pooled analysis of the multivariable approach found female gender was significantly related to a lower risk of death (odds ratio, 0.82; 95% CI, confidence interval, 0.73 to 0.93; I(2) = 0%). A meta-regression analysis showed age, ejection fraction, previous cardiovascular accident, renal insufficiency, and access site did not influence these data. CONCLUSIONS: Female patients undergoing TAVI present with a lower burden of comorbidities. The counterbalance between higher rates of vascular complications but lower of valve regurgitation may explain the reduced risk for women after TAVI, independently from baseline features and access site.

Heart failure in patients with human immunodeficiency virus: a review of the literature.

Coronary artery disease represents the leading cause of death for HIV patients treated with highly active antiretroviral treatment. Besides this, an extensive amount of data related to the risk of overt heart failure and consequently of atrial fibrillation and sudden cardiac death (SCD) in this population has been reported. It seems that persistent deregulation of immunity in HIV-infected patients is a common pathway related to both of these adverse clinical outcomes. Despite the fact that atrial fibrillation and heart failure are relatively common in HIV, few data are reported about screening, diagnosis, and potential treatment of these conditions.

The EUROpean and Chinese cardiac and renal Remote Ischemic Preconditioning Study (EURO-CRIPS): study design and methods.

AIMS: Contrast-induced nephropathy (CIN) and periprocedural myocardial infarction (PMI) represent frequent complications of percutaneous coronary intervention (PCI) and negatively impact subsequent length of hospitalization, costs of adjunctive diagnostic-therapeutic measures and mid-term cardiovascular events. The aim of the EURO-CRIPS trial is to test whether remote ischemic preconditioning (RIPC) may reduce the incidence of these complications and improve mid-term outcome. METHODS: This will be a double-blind, randomized, placebo-controlled multicentre study. Patients will be allocated 1 : 1 to RIPC or standard therapy if they were younger than 85 years old, with a renal clearance in the interval 30-60 ml/min/1.73 m and candidate to PCI for all clinical indications except for primary PCI in ST segment elevation myocardial infarction (STEMI), unstable haemodynamic presentations or ongoing severe arrhythmias. Incidence of CIN will be the primary end point and the amount of periprocedural cardiac enzyme leakage will be the secondary end point. In addition, we will evaluate whether the preconditioned patients will have a reduction of MACCE at 6 months (major adverse cardiac and cerebrovascular event). CONCLUSION: The EURO-CRIPS Study will be the first large-scale, multicentre clinical trial to test the role of RIPC in current clinical practice. The results of this randomized trial will provide important insights to optimize management strategy of patients undergoing PCI and to improve their outcome.

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/µl 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.

Prevalence of cardiovascular risk factors in long-term survivors of childhood cancer: 16 years follow up from a prospective registry.

BACKGROUND: Childhood cancer survivors (CCSs) have an increased risk of overweight and dyslipidaemia, but the distribution and the potential relationships between anticancer therapies and cardiovascular risk factors have been heterogeneously and not prospectively described. METHODS: All consecutive CCSs with primary cancer diagnosed between 1973-2007 and subsequently referred to our outpatient clinic were enrolled. Hypercholesterolaemia (total cholesterol >200 and/or low density lipoprotein (LDL)>160 mg/dl) was the primary end point, hypertriglyceridaemia (triglycerides >200 mg/dl) and body mass index >30 kg/m(2) the secondary end points. Cox multivariate adjustments were performed to account for differences in cancer and treatments. RESULTS: A total of 340 patients were included (197 male, 143 female; mean age at last follow-up 24.1 ± 3.2). The most common diagnosis were haematological malignancies (n = 227) and brain tumours (n = 51). After a median follow-up of 16.1 years, hypercholesterolaemia was diagnosed in 67 CCSs (20%), hypertriglyceridaemia in 20 CCSs (6%) and obesity in 28 CCSs (8%). Total body irradiation and growth hormone deficiency increased the risk of both hypercholesterolaemia (hazard ratio (HR) = 2.7; confidence interval (CI) 1.2-4.4 and HR = 2.3; CI 1.1-4.9; all p < 0.05) and hypertriglyceridaemia (HR = 6.5; CI 1.4-31 and HR = 7.2; CI 1.1-43; all p < 0.05). The risk of hypercholesterolaemia was also higher in CCSs who underwent autologous haematopoietic stem cell transplantation (HR = 3.2; CI 1.7-5.9; p < 0.001) or platinum-based chemotherapy (HR = 2.7; CI 1.5-4.9; p < 0.001), whereas a previous diagnosis of brain tumour (HR = 10; CI 1.2-45; p < 0.05) and anthracyclines exposure (HR = 1.3; CI 1.2-26; p < 0.05) significantly predicted obesity. CONCLUSION: CCSs show a high and variable risk for developing dyslipidaemia and obesity, depending on cancer diagnosis and treatments. Therefore, they need accurate and tailored control of their cardiovascular risk profile.

The prognostic impact of high on-treatment platelet reactivity with aspirin or ADP receptor antagonists: systematic review and meta-analysis.

OBJECTIVE: Negative results of recent randomized clinical trials testing the hypothesis of target therapy for patients with high on-treatment platelet reactivity (HOPR) have questioned its independent impact on clinical outcomes. 26 studies with 28.178 patients were included, with a median age of 66.8 (64-68) and 22.7% (22.4-27.8), of female gender. After a median follow-up of 1 year (0.1-1), cardiac adverse events occurred in 8.3% (3-11; all results are reported as median and interquartile range) of patients. Pooling all studies together, on-treatment platelet reactivity significantly increased the risk of adverse events (OR 1.33 [1.09, 1.64], I(2) = 0%). However, a sensitivity analysis showed that HOPR did not increase the risk of adverse events for patients with ACS, AMI, or stable angina as well as patients resistant to aspirin, ADP antagonists, or both. For all studies, publication bias was formally evident; after adjusting for this, HOPR did not significantly increase adverse cardiac events (OR 1.1 : 0.89-1.22, I(2) 0%). CONCLUSIONS: After adjusting for clinical confounders (like risk factors and clinical presentation) and for relevant publication bias, HOPR was not an independent prognostic indicator in unselected patients with both stable and unstable coronary disease for an adverse cardiac event. The clinical importance of HOPR for high-risk populations remains to be assessed.