Francesca Giordana

Mid-term prognostic value of coronary artery disease in patients undergoing transcatheter aortic valve implantation: a meta-analysis of adjusted observational results.

AIMS Coronary artery disease (CAD) negatively affects prognosis in patients undergoing surgical aortic valve replacement, being currently evaluated in the most common used risk score. Our meta-analysis aims to clarify the prognostic role of CAD on mid-term survival in patients undergoing TAVI. METHODS AND RESULTS Studies reporting multivariate predictors of adverse outcomes in patients undergoing TAVI were systematically searched for and pooled, when appropriate, using a random-effect method. 960 citations were first screened and finally 7 studies (2472 patients) were included. Diagnosis of CAD was reported in 52%(42-65) of patients and 1169 Edwards SAPIEN and 1303 CoreValve prostheses were implanted. After a median follow up of 452 days (357-585) 24% of patients (19-33) died, and 23 (14-32) for cardiovascular death. At pooled analysis of multivariate approach, diagnosis of coronary artery disease did not increase risk of death (OR 1.0, 95% CI, confidence interval, 0.67-1.50 I(2) 0%). CONCLUSION CAD does not affect mid-term TAVI outcome: this finding should be weighted to accurately evaluate risk and strategies for patients with severe aortic stenosis.

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.

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

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

A Gender Based Analysis of Predictors of All Cause Death After Transcatheter Aortic Valve Implantation

The impact of gender-related pathophysiologic features of severe aortic stenosis on transcatheter aortic valve implantation (TAVI) outcomes remains to be determined, as does the consistency of predictors of mortality between the genders. All consecutive patients who underwent TAVI at 6 institutions were enrolled in this study and stratified according to gender. Midterm all-cause mortality was the primary end point, with events at 30 days and at midterm as secondary end points. All events were adjudicated according to Valve Academic Research Consortium definitions. Eight hundred thirty-six patients were enrolled, 464 (55.5%) of whom were female. At midterm follow-up (median 365 days, interquartile range 100 to 516) women had similar rates of all-cause mortality compared with men (18.1% vs 22.6%, p = 0.11) and similar incidence of myocardial infarction and cerebrovascular accident. Gender did not affect mortality also on multivariate analysis. Among clinical and procedural features, glomerular filtration rate <30 ml/min/1.73 m(2) (hazard ratio [HR] 2.55, 95% confidence interval [CI] 1.36 to 4.79) and systolic pulmonary arterial pressure >50 mm Hg (HR 2.26, 95% CI 1.26 to 4.02) independently predicted mortality in women, while insulin-treated diabetes (HR 3.45, 95% CI 1.47 to 8.09), previous stroke (HR 3.42, 95% CI 1.43 to 8.18), and an ejection fraction <30% (HR 3.82, 95% CI 1.41 to 10.37) were related to mortality in men. Postprocedural aortic regurgitation was independently related to midterm mortality in the 2 groups (HR 11.19, 95% CI 3.3 to 37.9). In conclusion, women and men had the same life expectancy after TAVI, but different predictors of adverse events stratified by gender were demonstrated. These findings underline the importance of a gender-tailored clinical risk assessment in TAVI patients.

Gender differences in patients undergoing TAVI: a multicentre study.

AIMS In patients undergoing surgical valve replacement for severe aortic stenosis, female gender was associated with worse outcomes, not persisting after multivariable adjustment for baseline clinical differences, while contrasting data are reported about TAVI. METHODS AND RESULTS From January 2007 to December 2011 all patients with severe symptomatic aortic stenosis undergoing TAVI at our institutions were included in the present study, and were divided into two cohorts according to their gender. All endpoints were adjudicated according to VARC definition. Three hundred and seventy-seven patients were included: 161 male and 216 female. Male patients reported higher rates of previous coronary revascularisation, while both ejection fraction and mean aortic gradient were higher in female patients. At 30 days, rates of cardiovascular death were similar (6.0% vs. 8.1%; p=0.793), while overall bleedings (44% vs. 25%; p=0.024) and life-threatening bleedings (21.1% vs. 12.7%, p=0.016) were higher in female patients, also after multivariate analysis (OR 3.44; 1.23-9.22, and OR 2.1; 1.1-4.0, CI: 95%, respectively). Major vascular complications showed a tendency to be higher in female patients (12.9% vs. 9.8%, p=0.449). At a mean follow-up of 490 ± 250 days, no significant difference was reported between men and women for all endpoints, and after multivariate adjustment only life-threatening bleeding was reported as a predictor of death (OR 8.2:3.8-17, CI: 95%). CONCLUSIONS TAVI can be an effective and safe strategy in high surgical risk patients, regardless of the gender; life-threatening bleedings were reported more frequently in female patients, being the only independent predictor of death.

Provisional vs. two-stent technique for unprotected left main coronary artery disease after ten years follow up: A propensity matched analysis

AIMS There is uncertainty on which stenting approach confers the best long-term outlook for unprotected left main (ULM) bifurcation disease. METHODS AND RESULTS This is a non-randomized, retrospective study including all consecutive patients with 50% stenosis of the left main involving at least 1 of the arteries stemming from the left main treated with drug-eluting stents (DES) in 9 European centers between 2002 and 2004. Patients were divided into two groups: those treated with provisional stentings vs. those treated with two stent strategy. The outcomes of interest were 10-year rates of target lesion revascularization (TLR), major adverse cardiac events (MACE), and their components (cardiovascular death, myocardial infarction [MI], or repeat revascularization), along with stent thrombosis (ST). A total of 285 patients were included, 178 (62.5%) in the provisional stenting group and 87 (37.5%) in the two stent group. After 10 years, no differences in TLR were found at unadjusted analysis (19% vs 25%, p>0.05) nor after propensity score matching (25% vs 28%, p>0.05). Similar rates of MACE (60% vs 66%, p>0.05), death (34% vs 43%, p>0.05), MI (9% vs 14%, p>0.05) and ST were also disclosed at propensity-based analysis. CONCLUSION Even after 10 year follow-up, patients treated with provisional stenting on left main showed comparable rates of target lesion revascularization compared to two stent strategy.

Thirty-day readmission rates after PCI in a metropolitan center in Europe: incidence and impact on prognosis.

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.

BleeMACS: rationale and design of the study.

Background Bleeding events after an acute coronary syndrome have a negative impact on prognosis. Available risk scores are limited by suboptimal accuracy, prediction of only in-hospital events and absence of patients treated with new antiplatelet agents in the current era of widespread use of percutaneous coronary intervention. Design The BleeMACS (Bleeding complications in a Multicenter registry of patients discharged after an Acute Coronary Syndrome) project is a multicenter investigator-initiated international retrospective registry that enrolled more than 15 000 patients discharged with a definitive diagnosis of acute coronary syndrome and treated with percutaneous revascularization. The primary end point is the incidence of major bleeding events requiring hospitalization and/or red cell transfusion concentrates within 1 year. An integer risk score for bleeding within the first year after hospital discharge will be developed from a multivariate competing-risks regression. Conclusion The BleeMACS registry collaborative will allow development and validation of a risk score for prediction of major bleeding during follow-up for patients receiving contemporary therapies for acute coronary syndrome.

One-year follow-up of conduction disturbances following transcatheter aortic valve implantation.

Aims To describe the postprocedural and 1-year follow-up incidence of heart conduction disturbances in patients with severe symptomatic aortic stenosis undergoing transcatheter aortic valve implantation (TAVI). Methods Ninety-five patients were enrolled from 2008 to 2011 (mean age 81.8 ± 7.2 years, 63.1% women). Clinical and ECG data were recorded at admission, discharge, and 3, 6 and 12 months following TAVI. Results Fifty-seven Edwards SAPIEN (31 transapical, 26 transfemoral) and 38 transfemoral CoreValve implants were used. Two (2.1%) patients died during the procedure and 11 (11.6%) patients received a pacemaker prior to discharge (7 CoreValve, 3 transapical, 1 transfemoral SAPIEN; P = 0.18). Among the surviving patients not receiving a pacemaker, TAVI increased the PQ interval (176 ± 29 vs. 188 ± 36 ms; P = 0.001), QRS width (90 ± 15 vs. 108 ± 26 ms; P < 0.001), and first-grade atrioventricular block (17 vs. 29%; P < 0.001). Postprocedural complete left bundle branch block was reported most in transapical (from 10 to 36%; P = 0.01) and CoreValve (from 8 to 64%; P < 0.001) recipients compared to the transfemoral SAPIEN group. At the 12-month follow-up, 24 (25.3%) patients had died [two (2.1%) sudden deaths] and four (4.2%) required pacemaker implantation. Among the survivors not receiving a pacemaker at the 1-year follow-up, the PQ interval (178 ± 27 vs. 188 ± 36 ms; P = 0.39) remained unchanged in the ECG, whereas the QRS width (100 ± 22 vs. 108 ± 26 ms; P = 0.008) decreased compared to measurements taken at discharge. Conclusion Conduction disturbances following TAVI primarily develop during hospitalization and subsequently stabilize. However, the small percentage of patients suffering sudden death or pacemaker implantation requires attention.

Development and external validation of a post-discharge bleeding risk score in patients with acute coronary syndrome: The BleeMACS score

BACKGROUND Accurate 1-year bleeding risk estimation after hospital discharge for acute coronary syndrome (ACS) may help clinicians guide the type and duration of antithrombotic therapy. Currently there are no predictive models for this purpose. The aim of this study was to derive and validate a simple clinical tool for bedside risk estimation of 1-year post-discharge serious bleeding in ACS patients. METHODS The risk score was derived and internally validated in the BleeMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registry, an observational international registry involving 15,401 patients surviving admission for ACS and undergoing percutaneous coronary intervention (PCI) from 2003 to 2014, engaging 15 hospitals from 10 countries located in America, Europe and Asia. External validation was conducted in the SWEDEHEART population, with 96,239 ACS patients underwent PCI and 93,150 without PCI. RESULTS Seven independent predictors of bleeding were identified and included in the BleeMACS score: age, hypertension, vascular disease, history of bleeding, malignancy, creatinine and hemoglobin. The BleeMACS risk score exhibited a C-statistic value of 0.71 (95% CI 0.68-0.74) in the derivation cohort and 0.72 (95% CI 0.67-0.76) in the internal validation sample. In the SWEDEHEART external validation cohort, the C-statistic was 0.65 (95% CI 0.64-0.66) for PCI patients and 0.63 (95% CI 0.62-0.64) for non-PCI patients. The calibration was excellent in the derivation and validation cohorts. CONCLUSIONS The BleeMACS bleeding risk score is a simple tool useful for identifying those ACS patients at higher risk of serious 1-year post-discharge bleeding. ClinicalTrials.govIdentifier: NCT02466854.