Paola D'Errigo

Transcatheter aortic valve implantation versus surgical aortic valve replacement for severe aortic stenosis: Results from an intermediate risk propensity-matched population of the Italian OBSERVANT study

BACKGROUND Few studies have yielded information on comparative effectiveness of transcatheter aortic valve implantation (TAVI) versus surgical aortic valve replacement (SAVR) procedures in a real-world setting. The aim of this analysis is to describe procedural and post-procedural outcomes in a TAVI/SAVR intermediate risk propensity-matched population. METHODS OBSERVANT is an observational prospective multicenter cohort study, enrolling AS patients undergoing SAVR or TAVI. Propensity score method was applied to analyze procedural and post-procedural outcomes. Pairs of patients with the same probability score were matched (caliper matching). RESULTS The unadjusted enrolled population (N=2108) comprises 1383 SAVR patients, 602 transarterial-TAVI patients and 123 transapical-TAVI patients. Matched population comprised a total of 266 patients (133 patients for each group). A relatively low risk population was selected (mean logistic EuroSCORE 9.4 ± 10.4% vs 8.9 ± 9.5%, SAVR vs TAVI; p=0.650). Thirty-day mortality was 3.8% for both SAVR and TAVI (p=1.000). The incidence of stroke (1.5% SAVR and 0.0% TAVI; p=0.156) and myocardial infarction (0.8% SAVR and 0.8% TAVI; p=1.000) was not statistically different between groups, whereas a higher requirement for blood transfusion was reported across the surgical cohort (49.6% vs 36.1%; p=0.026). A higher incidence of major vascular damage (5.3% vs. 0.0%; p=0.007) and pacemaker implantation(0.8% vs 12.0%; p=0.001) were reported in the TAVI group. CONCLUSIONS Patients undergoing transcatheter and surgical treatment of severe aortic stenosis are still extremely distinct populations. In the relatively low-risk propensity-matched population analyzed, despite similar procedural and 30-day mortality, SAVR was associated with a higher risk for blood transfusion, whereas TAVI showed a significantly increased rate of vascular damage, permanent AV block and residual aortic valve regurgitation.

A Simple Risk Tool (the OBSERVANT Score) for Prediction of 30-Day Mortality After Transcatheter Aortic Valve Replacement

Risk stratification tools used in patients with severe aortic stenosis have been mostly derived from surgical series. Although specific predictors of early mortality with transcatheter aortic valve replacement (TAVR) have been identified, the prognostic impact of their combination is unexplored. We sought to develop a simple score, using preprocedural variables, for prediction of 30-day mortality after TAVR. A total of 1,878 patients from a national multicenter registry who underwent TAVR were randomly assigned in a 2:1 manner to development and validation data sets. Baseline characteristics of the 1,256 patients in the development data set were considered as candidate univariate predictors of 30-day mortality. A bootstrap multivariate logistic regression process was used to select correlates of 30-day mortality that were subsequently weighted and integrated into a scoring system. Seven variables were weighted proportionally to their respective odds ratios for 30-day mortality (glomerular filtration rate <45 ml/min [6 points], critical preoperative state [5 points], New York Heart Association class IV [4 points], pulmonary hypertension [4 points], diabetes mellitus [4 points], previous balloon aortic valvuloplasty [3 points], and left ventricular ejection fraction <40% [3 points]). The model showed good discrimination in both the development and validation data sets (C statistics 0.73 and 0.71, respectively). Compared with the logistic European System for Cardiac Operative Risk Evaluation in the validation data set, the model showed better discrimination (C statistic 0.71 vs 0.66), goodness of fit (Hosmer-Lemeshow p value 0.81 vs 0.00), and global accuracy (Brier score 0.054 vs 0.073). In conclusion, the risk of 30-day mortality after TAVR may be estimated by combining 7 baseline clinical variables into a simple risk scoring system.

Immediate and Intermediate Outcome After Transapical Versus Transfemoral Transcatheter Aortic Valve Replacement

A few studies recently reported controversial results with transfemoral transcatheter aortic valve replacement (TF-TAVR) versus transapical transcatheter aortic valve replacement (TA-TAVR), often without adequate adjusted analysis for baseline differences. Data on patients who underwent TF-TAVR and TA-TAVR from the Observational Study of Effectiveness of avR-tavI procedures for severe Aortic stenosis Treatment study were analyzed with propensity score 1-to-1 matching. From a cohort of 1,654 patients (1,419 patients underwent TF-TAVR and 235 patients underwent TA-TAVR), propensity score matching resulted in 199 pairs of patients with similar operative risk (EuroSCORE II: TF-TAVR 8.1 ± 7.1% vs TA-TAVR, 8.4 ± 7.3%, p = 0.713). Thirty-day mortality was 8.0% after TA-TAVR and 4.0% after TF-TAVR (p = 0.102). Postoperative rates of stroke (TA-TAVR, 2.0% vs TF-TAVR 1.0%, p = 0.414), cardiac tamponade (TA-TAVR, 4.1% vs TF-TAVR 1.5%, p = 0.131), permanent pacemaker implantation (TA-TAVR, 8.7% vs TF-TAVR 13.3%, p = 0.414), and infection (TA-TAVR, 6.7% vs TF-TAVR 3.6%, p = 0.180) were similar in the study groups but with an overall trend in favor of TF-TAVR. Higher rates of major vascular damage (7.2% vs 1.0%, p = 0.003) and moderate-to-severe paravalvular regurgitation (7.8% vs 5.2%, p = 0.008) were observed after TF-TAVR. On the contrary, TA-TAVR was associated with higher rates of red blood cell transfusion (50.0% vs 30.4%, p = 0.0002) and acute kidney injury (stages 1 to 3: 44.4% vs 21.9%, p <0.0001) compared with TF-TAVR. Three-year survival rate was 69.1% after TF-TAVR and 57.0% after TA-TAVR (p = 0.006), whereas freedom from major adverse cardiovascular and cerebrovascular events was 61.9% after TF-TAVR and 50.4% after TA-TAVR (p = 0.011). In conclusion, TF-TAVR seems to be associated with significantly higher early and intermediate survival compared with TA-TAVR. The transfemoral approach, whenever feasible, should be considered the route of choice for TAVR.

Years of life lost due to premature mortality in Italy

Background: The assessment of the burden of disease (BOD) is necessary for sensibly allocating limited health-related resources. No such assessment is available currently for Italy. Methods: Global burden of disease (GBD) methods were used to analyse in detail the years of life lost (YLLs) component of BOD for the most important diseases contributing to premature mortality in Italy in 1998. YLLs were computed with and without age-weighting and discounting. YLLs were also analysed by gender, for Italy vs. the Euro-A region (a group of 26 European countries) defined in the 2000 update of the GBD Study, and for northern, central and southern Italy, the three traditionally demarcated regions of the country. Results: The use of YLLs yields a ranking of diseases by their relative contribution to mortality burden which differs from a ranking based purely on death counts. Although males contributed 58.5% and females 41.5% of the total mortality burden in terms of YLLs, using death counts the percentages for males and females were similar (50.6% M, 49.4% F). The leading cause of mortality burden, both in terms of YLLs and death counts, was ischaemic heart disease, followed by stroke and lung cancer. Several other conditions, however, had rankings that varied depending on the measure used. While cardiovascular diseases accounted for 31.7% and ‘all cancers’ for 34.1% of YLLs, they were responsible, respectively, for 44.7 and 27.9% of death counts. The results for Italy generally corresponded with those obtained in GBD 2000 for EURO-A, but the proportion of the total mortality burden explained by the four leading causes is higher in Italy. For within Italy comparisons, there was a decreasing trend from north to south for ‘all cancers’ and for several specific cancers. Conversely, a consistent increase in YLL rates from north to south was observed for stroke and hypertensive disease. Conclusions: This analysis of Italys mortality burden represents the first phase in identifying Italys total BOD. Simply establishing death counts and rates is no longer sufficient for a full understanding of a countrys health status.

Early and Midterm Outcome of Propensity-Matched Intermediate-Risk Patients Aged ≥80 Years With Aortic Stenosis Undergoing Surgical or Transcatheter Aortic Valve Replacement (from the Italian Multicenter OBSERVANT Study)

The aim of this study was to analyze procedural and postprocedural outcomes of patients aged ≥80 years treated by transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR) as enrolled in the OBservational Study of Effectiveness of SAVR-TAVR procedures for severe Aortic steNosis Treatment (OBSERVANT) Study. TAVI is offered to patients with aortic stenosis judged inoperable or at high surgical risk. Nevertheless, it is common clinical practice to treat elderly (≥80 years) patients by TAVI regardless of surgical risk for traditional SAVR. OBSERVANT is a multicenter, observational, prospective cohort study that enrolled patients with symptomatic severe aortic stenosis who underwent SAVR or TAVI from December 2010 to June 2012 in 93 Italian participating hospitals. Information on demographic characteristics, health status before intervention, therapeutic approach, and intraprocedural and 30-day outcomes was collected. An administrative follow-up was set up to collect data on midterm to long-term outcomes. We reviewed baseline and procedural data of patients aged ≥80 years, looking for different early and late outcome after TAVI or SAVR. Patients treated by TAVI were sicker than SAVR because of higher rate of co-morbidities, advanced illness, frailty, and Logistic EuroSCORE. After propensity matching, early and midterm mortality were comparable between the 2 groups. However, patients treated by TAVI had higher rate of vascular complications (6.0% vs 0.5%; p <0.0001), permanent pacemaker implantation (13.4% vs 3.7%; p <0.0001), and paravalvular leak (8.9% vs 2.4%; p <0.0001). Patients who underwent SAVR had more frequent bleedings needing transfusion (63.2% vs 34.5%; p <0.0001) and acute kidney injury (9.6% vs 3.9%; p = 0.0010). In conclusion, patients aged ≥80 years treated by TAVI or SAVR had similar early and midterm mortality.

Prostate Cancer Gene 3 and Multiparametric Magnetic Resonance Can Reduce Unnecessary Biopsies: Decision Curve Analysis to Evaluate Predictive Models

OBJECTIVE To overcome the well-known prostate-specific antigen limits, several new biomarkers have been proposed. Since its introduction in clinical practice, the urinary prostate cancer gene 3 (PCA3) assay has shown promising results for prostate cancer (PC) detection. Furthermore, multiparametric magnetic resonance imaging (mMRI) has the ability to better describe several aspects of PC. METHODS A prospective study of 171 patients with negative prostate biopsy findings and a persistent high prostate-specific antigen level was conducted to assess the role of mMRI and PCA3 in identifying PC. All patients underwent the PCA3 test and mMRI before a second transrectal ultrasound-guided prostate biopsy. The accuracy and reliability of PCA3 (3 different cutoff points) and mMRI were evaluated. Four multivariate logistic regression models were analyzed, in terms of discrimination and the cost benefit, to assess the clinical role of PCA3 and mMRI in predicting the biopsy outcome. A decision curve analysis was also plotted. RESULTS Repeated transrectal ultrasound-guided biopsy identified 68 new cases (41.7%) of PC. The sensitivity and specificity of the PCA3 test and mMRI was 68% and 49% and 74% and 90%, respectively. Evaluating the regression models, the best discrimination (area under the curve 0.808) was obtained using the full model (base clinical model plus mMRI and PCA3). The decision curve analysis, to evaluate the cost/benefit ratio, showed good performance in predicting PC with the model that included mMRI and PCA3. CONCLUSION mMRI increased the accuracy and sensitivity of the PCA3 test, and the use of the full model significantly improved the cost/benefit ratio, avoiding unnecessary biopsies.

The impact of stroke in Italy: First step for a National Burden of Disease Study

Purpose: To calculate the impact of stroke in Italy in 1998, expressed in terms of disability adjusted life years (DALYs) according to the WHO Global Burden of Disease (GBD) Study. Method: The data on first-ever stroke incidence (FES), remission rate and case fatality derived from the health information system and a research on post-FES disability of the Friuli Venezia-Giulia (FVG) Region, were used to compute the years of life lived with disability (YLDs), which were added to the years of life lost due to premature mortality (YLLs), calculated from stroke mortality data, to obtain the DALYs. The results were extrapolated to the rest of Italy after examination of national stroke registries data. Results: Standardized estimated incidence of FES in FVG in 1998 was lower (135 cases of FES per 100 000 inhabitants) than that reported in other published national and international studies. Estimated case fatality rate and distribution of post-FES disability did not differ from other similar studies. About 100 000 YLLs and 273 000 YLDs due to FES were estimated in 1998 for Italy. Conclusions: The estimated proportion of the YLDs on total DALYs (27%) is comparable with that obtained in the EURO-A group (the European area including Italy) of the GBD 2000 Study (31%), and the Australian BoD Study (35%).

Prediction of severe bleeding after coronary surgery: the WILL-BLEED Risk Score.

Severe perioperative bleeding after coronary artery bypass grafting (CABG) is associated with poor outcome. An additive score for prediction of severe bleeding was derived (n=2494) and validated (n=1250) in patients from the E-CABG registry. Severe bleeding was defined as E-CABG bleeding grades 2-3 (transfusion of >4 units of red blood cells or reoperation for bleeding). The overall incidence of severe bleeding was 6.4 %. Preoperative anaemia (3 points), female gender (2 points), eGFR <45 ml/min/1.73 m2 (3 points), potent antiplatelet drugs discontinued less than five days (2 points), critical preoperative state (5 points), acute coronary syndrome (2 points), use of low-molecular-weight heparin/fondaparinux/unfractionated heparin (1 point) were independent predictors of severe bleeding. The WILL-BLEED score was associated with increasing rates of severe bleeding in both the derivation and validation cohorts (scores 0-3: 2.9 % vs 3.4 %; scores 4-6: 6.8 % vs 7.5 %; scores>6: 24.6 % vs 24.2 %, both p<0.0001). The WILL-BLEED score had a better discriminatory ability (AUC 0.725) for prediction of severe bleeding compared to the ACTION (AUC 0.671), CRUSADE (AUC 0.642), Papworth (AUC 0.605), TRUST (AUC 0.660) and TRACK (AUC 0.640) bleeding scores. The net reclassification index and integrated discrimination improvement using the WILL-BLEED score as opposed to the other bleeding scores were significant (p<0.0001). The decision curve analysis demonstrated a net benefit with the WILL-BLEED score compared to the other bleeding scores. In conclusion, the WILL-BLEED risk score is a simple risk stratification method which allows the identification of patients at high risk of severe bleeding after CABG.

Trends in mortality and heart failure after acute myocardial infarction in Italy from 2001 to 2011

BACKGROUND Uncertainties on long-term outcomes after acute myocardial infarction (AMI) still exist, despite the ongoing progresses in the management of patients with AMI. AIM OF THE STUDY Our aim was to appraise both the early prognosis and prognosis at 1-year after discharge of patients hospitalized due to AMI. METHODS This is a retrospective nationwide cohort study based on data from an administrative database on patients admitted with AMI from 2001 to 2011 in all Italian hospitals sites. Mortality and readmission rates within 30 days, 60 days and 1 year were calculated, as well as re-hospitalizations for all causes and for HF. RESULTS A total of 1,110,822 patients were included. Index admission mortality rate (I-MR) and total in-hospital mortality rate (T-MR) at up to 1 year both decreased respectively from 11.34% to 8.99% and from 16.46% to 14.68% in the years 2001 to 2011 (both p<0.0001), while fatal readmission rate (F-RR) at 1 year increased from 4.75% to 5.28% (p=0.0019). Patients that developed HF during the index admission had significantly higher I-MR and F-RR. I-MR, F-RR, and T-MR, however, remained low at any time point considered (30 days, 60 days and 1 year) in a subgroup of low-risk optimally-treated patients. CONCLUSIONS The risk of fatal readmission at 1 year increased slightly over time, in spite of the remarkable improvements currently achieved in overall prognosis after AMI. The identification of patients at high risk (mainly due to HF complicating AMI), and of patients at low risk is crucial to define and support management strategies.

Risultati dello studio OBSERVANT: Caratteristiche cliniche ed esiti a breve termine della popolazione arruolata sottoposta a sostituzione valvolare aortica (transcatetere versus chirurgica)

BACKGROUND OBSERVANT represents the first national observational study on the comparative effectiveness of transcatheter aortic valve implantation (TAVI) vs surgical aortic valve replacement (SAVR) at short, medium and long term, in a patient population with severe aortic stenosis (AS). The aim of this paper is to describe patient characteristics and short-term outcomes of the enrolled population. METHODS OBSERVANT is an observational prospective multicenter cohort study that enrolled AS patients undergoing SAVR or TAVI from December 2010 to June 2012 in the participating hospitals. Information on demographic characteristics, health status prior to intervention, therapeutic approach, intraprocedural and 30-day outcomes was collected. An administrative follow-up was set up to collect data on long-term outcomes. RESULTS The enrolled population included 7618 patients undergoing transfemoral/transubclavian TAVI (TF/TS-TAVI, n=1652), transapical TAVI (TA-TAVI, n=259) or SAVR (n=5707). SAVR patients were younger and with a lower risk profile than TAVI patients (logistic EuroSCORE: SAVR 6.4 ± 7.3%, TF/TS-TAVI 14.1 ± 12.1%, TA-TAVI 15.5 ± 11.0%; p<0.001). When 30-day mortality rates were stratified by logistic EuroSCORE, a statistically significant difference was found only in the patient subgroup with logistic EuroSCORE ≤5% (SAVR 1.0%, TF/TS-TAVI 4.7%, TA-TAVI 0.0%; p=0.005). CONCLUSIONS Findings from the OBSERVANT study confirm that patients undergoing TAVI are older and sicker than patients undergoing SAVR. Nevertheless, the logistic EuroSCORE shows that, in Italy, also patients at intermediate surgical risk are treated with TAVI. Stratifying by logistic EuroSCORE, SAVR seems to be superior to TAVI in the subgroup of patients at very low risk. More sophisticated analyses on patient subgroups with comparable risk profile and on long-term follow-up will allow to obtain valuable information on the effectiveness of TAVI and SAVR procedures.