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OBJECTIVES Sutureless aortic valve prostheses have been introduced to facilitate the implant process, speed up the operating time and improve haemodynamic performance. The goal of this study was to assess the potential advantages of using sutureless prostheses during minimally invasive aortic valve replacement in a large multicentre population. METHODS From 2011 to 2019, a total of 3402 patients in 11 hospitals underwent isolated aortic valve replacement with minimal access approaches using a bioprosthesis. A total of 475 patients received sutureless valves; 2927 received standard valves. The primary outcome was the incidence of 30-day deaths. Secondary outcomes were the occurrence of major complications following procedures performed with sutureless or standard bioprostheses. Propensity matched comparisons was performed based on a multivariable logistic regression model. RESULTS The annual number of sutureless valve implants increased over the years. The matching procedure paired 430 sutureless with 860 standard aortic valve replacements. A total of 0.7% and 2.1% patients with sutureless and standard prostheses, respectively, died within 30 days (P = 0.076). Cross-clamp times [48 (40–62) vs 63 min (48–74); P = 0.001] and need for blood transfusions (27.4% vs 33.5%; P = 0.022) were lower in patients with sutureless valves. No difference in permanent pacemaker insertions was observed in the overall population (3.3% vs 4.4% in the standard and sutureless groups; P = 0.221) and in the matched groups (3.6% vs 4.7% in the standard and sutureless groups; P = 0.364). CONCLUSIONS The use of sutureless prostheses is advantageous and facilitates the adoption of a minimally invasive approach, reducing cardiac arrest time and the number of blood transfusions. No increased risk of permanent pacemaker insertion was observed.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, occurring in 1–2% of the general population. Catheter ablation has become an important treatment modality for patients with symptomatic drug-refractory AF. We report data regarding the AF ablation approaches and modalities in the Italian “real world.” The survey was set-up to collect data on ablation procedure across Italy. All centers performing AF ablation were invited, regardless of the number of annual procedures, to complete a questionnaire regarding their ablation approaches. All centers reported data regarding procedures performed during the year 2017. A total of 3260 procedures were reported from 49 participating hospitals. Most of Italian regions were included in the study. The majority of the centers performed “Always” pulmonary vein isolation (PVI) in paroxysmal and persistent AF catheter ablation, while adjunctive lesions in persistent AF ablation were planned in most of them but not all, and 16% never performed lesions other than PVI. During ablation procedure, vitamin k inhibitors were uninterrupted in 55% of centers, while direct oral anticoagulant in 44% of centers was used uninterruptedly. No relationship was observed between patient data and the number of procedures performed at each center. This survey suggests that the adherence of Italian centers to the most recent European Society of Cardiology guidelines for AF ablation is reasonably high.

Mitral valve surgery (MVS) is evolving. Compared to standard sternotomy (S-MVS), minimally invasive method (Mini-MVS) has been increasingly adopted in the last years with encouraging results for both repairs and replacements. We evaluated trends of surgical approaches and operative outcomes in a multicenter study involving 10 cardiac surgical centers in Italy.Patients who received isolated mitral valve surgery, including only a concomitant tricuspid valve repair, from January 2011 up to December 2017. Minimally invasive approach (right anterior mini-thoracotomy) and standard sternotomy was performed in 2602 and 1947 patients, respectively. Stratifying by surgery, 1493 patients per group were paired using a propensity matching procedure.The minimally invasive approach has been progressively more frequent over the years (from 27.5% in 2011 to 71.7% in 2017). Compared to S-MVS, Mini-MVS patients were younger with less preoperative comorbidities and less frequently operated for valve replacement or in association with tricuspid repair. The 30-day mortality was lower in the Mini-MVS (overall 1.2% vs 2.7%; p 0.001) as well as the incidence of most postoperative complications. Subjects paired by propensity score had similar 30-day mortality (1.9% vs 1.8%, p = 0.786) but lower blood transfusion and permanent pace-maker insertion. Cardiopulmonary bypass and cross-clamp time, initially longer in the Mini-MVS patients, became shorter in recent years for the minimally invasive approach.In a large multi-institutional recent cohort, minimally invasive mitral valve surgery has drastically increased being the preferred technique and appears to be safe with procedural duration shorter than the beginning.

OBJECTIVES The need for concomitant tricuspid surgery in patients who need mitral valve surgery casts doubt on its feasibility via a minimally invasive approach. Our goal was to evaluate the short-term outcomes of patients undergoing concomitant mitral and tricuspid valve surgery either with a standard full sternotomy (full-MTS) or a minimally invasive approach (mini-MTS). METHODS The outcomes of patients who had combined mitral and tricuspid valve surgery in 11 centres were retrospectively evaluated. The primary outcome was the incidence of 30-day mortality. A propensity score matched cohort was selected to create 2 comparable groups stratified by surgery (valve replacement or repair). RESULTS During the study period, 1048 consecutive patients had combined mitral and tricuspid valve surgery (730 full-MTS, 318 mini-MTS). The matching procedure paired 192 full-MTS to 192 mini-MTS procedures. After matching, mini-MTS was associated with longer cardiopulmonary bypass [123 min, standard deviation (SD) 46, vs 102 min, SD 36, P = 0.001] and cross-clamping times (89 min, SD 34, vs 78 min, SD 29, P = 0.003). Although the hospital length of stay was shorter (8 days, interquartile range 7-12 vs 9 days, interquartile range 7–14, P = 0.034) with mini-MTS before matching, this difference disappeared after matching. No differences in other major complications or in 30-day mortality were observed: 48 deaths (4.6%), 36 of which (4.9%) occurred in patients who had a full-MTS and 12 (3.8%), in patients who had a mini-MTS (4.7% in both approaches paired by propensity). CONCLUSIONS The mini-MTS approach proved to be safe and effective in patients requiring concomitant mitral and tricuspid surgery. We could not demonstrate any difference in short-term outcomes between the 2 surgical approaches, indicating that there is not a preferred surgical approach.

Treatment approach for elderly patients with atrial fibrillation (AF) is difficult. The present prospective phase-II trial evaluated LINAC-based stereotactic arrhythmia radioablation safety in this population. The reported data of the first 5 patients worldwide, showed no side effects, absence of AF episodes and without antiarrhythmic drugs.Trial Registration:ClinicalTrials.gov, identifier: NCT04575662.

BackgroundAwareness of radiation exposure risks associated to interventional cardiology procedures is growing. The availability of new technologies in electrophysiology laboratories has reduced fluoroscopy usage during arrhythmias ablations. The aim of this study was to describe procedures with and without X-Rays and to assess feasibility, safety, and short-term efficacy of zero fluoroscopy intervention in a high-volume center oriented to keep exposure to ionizing radiation as low as reasonably achievable.MethodsCardiac catheter ablations performed in our hospital since January 2017 to June 2021.ResultsA total of 1,853 procedures were performed with 1,957 arrhythmias treated. Rate of fluoroless procedures was 15.4% (285 interventions) with an increasing trend from 8.5% in 2017 to 22.9% of first semester 2021. The most frequent arrhythmia treated was atrial fibrillation (646; 3.6% fluoroless) followed by atrioventricular nodal reentrant tachycardia (644; 16.9% fluoroless), atrial flutter (215; 8.8% fluoroless), ventricular tachycardia (178; 17.4% fluoroless), premature ventricular contraction (162; 48.1% fluoroless), and accessory pathways (112; 31.3% fluoroless). Although characteristics of patients and operative details were heterogeneous among treated arrhythmias, use of fluoroscopy did not influence procedure duration. Moreover, feasibility and efficacy were 100% in fluoroless ablations while the rate of major complications was very low and no different with or without fluoroscopy (0.45 vs. 0.35%).ConclusionLimiting the use of X-Rays is necessary, especially when the available technologies allow a zero-use approach. A lower radiation exposure may be reached, reducing fluoroscopy usage whenever possible during cardiac ablation procedures with high safety, full feasibility, and efficacy.

The prognostic value of change in six-minute walking distance (6MWD) after treatment to predict mortality in heart failure (HF) remains a controversial issue. We assessed the prognostic value of rehabilitation-induced improvement in 6MWD in predicting mortality in patients with HF.We studied 2257 patients admitted to six inpatient rehabilitation facilities after a hospitalization for HF (N. 912) or because of worsening functional capacity and/or deteriorating clinical status (N. 1345). A six-minute walking test was performed at admission and discharge. The primary outcome was 3-year all-cause mortality after discharge from cardiac rehabilitation. We used multivariable Cox proportional hazard modeling to assess the association of increase in 6MWD with 3-year mortality, adjusting for established predictors of mortality.6MWD significantly increased by 61 m (p .001) from admission to discharge and 969 patients (42.9%) achieved an increase in 6MWD50 m. After full adjustment, an increase in 6MWD50 m was associated with a 22% decreased risk for 3-year mortality (HR 0.78 [95% CI 0.68-0.91]; p = .002). When modeled as a continuous variable, improvement in 6MWD remained independently associated with decreased risk for 3-year mortality (HR per each 50 m increase: 0.92 [95% CI 0.88-0.96]).Rehabilitation-induced improvement in 6MWD was associated with a significantly reduced risk for 3-year mortality. Our data also suggest that an improvement in 6MWD of more than 50 m could represent a clinically meaningful endpoint of cardiac rehabilitation for patients with heart failure.

AIMS Atrial fibrillation (AF) has been highlighted as a growing epidemic. Evidence is lacking on the role of different risk factors within both genders especially in AF patients referred for catheter ablation (CA). The objective was the evaluation of differences between men and women in the associations with aging, obesity and hypertension as the most highly contributing factors to AF onset and progression. METHODS Cases selected among patients scheduled for CA as a rhythm-control strategy and controls from a recent Italian national survey on the population's health conditions were analysed to quantify the strength of association and to assess the existence of gender differences. To reduce the effect of possible confounding factors, both cases and controls were selected without preexisting comorbidities other than hypertension. RESULTS At multivariate logistic regression analysis, cases (534 patients, 166 women) were significantly associated with the male sex, higher age, presence of obesity and hypertension in comparison to controls (17,983 subjects, 9,409 women). At analyses gender-stratified, age and obesity had a significant greater association in women than men. On the contrary, hypertension was relatively more frequent in men than women. CONCLUSION Although mechanisms linking risk factors and AF are complex, this study suggests the existence of differences mediated by gender in AF drug-refractory patients who underwent CA. A tailored public health programme to reduce the growing burden of AF needs to be designed to prevent and counter the increasing epidemic of the most common cardiac arrhythmia as well as its progression in more resistant forms.

Background: Catheter ablation is a treatment option for sustained ventricular tachycardias (VTs) that are refractory to pharmacological treatment; however, patients with fast VT and electrical storm (ES) are at risk for cardiogenic shock. We report our experience using cardiopulmonary support with extracorporeal membrane oxygenation (ECMO) during catheter ablation of VT.Methods: Sixty-two patients (mean age 68 ± 9 years; 94% male) were referred to our center for catheter ablation of repeated episodes of hemodynamically unstable ventricular arrhythmias. ES was defined as the occurrence of three or more VT/ventricular fibrillation episodes requiring electrical cardioversion or defibrillation in a 24-h period. All patients had hemodynamically unstable VTs.Results: Thirty-one patients (group 1) performed catheter ablation without ECMO support and 31 patients (group 2) with ECMO support. At the end of the procedure, ventricular inducibility was not performed in 16 patients of group 1 (52%) due to significant hemodynamic instability. Ventricular inducibility was performed in the other 15 patients (48%); polymorphic VTs were inducible in eight patients. In group 2, VTs were not inducible in 29 patients (93%); polymorphic VTs were inducible in two patients. The median follow-up duration was 24 months. Four patients of group 1 (13%) and five patients of group 2 (16%) died due to refractory heart failure. An implantable cardioverter-defibrillator intervention (shock or antitachycardia pacing) was documented in 13 patients of group 1 (42%) and six patients of group 2 (19%).Conclusions: Extracorporeal membrane oxygenation support during catheter ablation for hemodynamically unstable VTs is a useful tool to prevent acute procedural heart failure and to reduce arrhythmic burden.

In a previous study, we found that miR-150-5p was specifically downregulated in patients with advanced heart failure (HF). Here, we investigated the long-term prognostic potential of miR-150-5p.We studied optimally-treated HF outpatients with reduced ejection fraction. The primary outcome comprised the composite of death, urgent heart transplantation (HT) and ventricular assist device (VAD) implantation within 30 months. We used recursive partitioning analysis to identify the optimal log miR-150-5p cut-off. The association of log miR-150-5p with the primary outcome was examined using Cox regression analysis. We used the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score for adjustment in multivariable analysis. Finally, we compared the global fit of three models (MAGGIC score + miR-150-5p, MAGGIC score + NT-proBNP, and NT-proBNP + miR-150-5p) using Akaike Information Criterion.Recursive partitioning analysis identified the value of -2.22 as the optimal cut-off for log miR-150-5p. Thirty-month survival free of urgent HT/VAD implantation was 31% among the patients with log miR-150-5p-2.22 and 86% among those with log miR-150-5p-2.22. Crude hazard ratio (HR) of the primary outcome for log miR-150-5p expression level-2.22 was 6.70 (95% CI: 2.31-19.38; P0.001). After adjusting for the MAGGIC score in multivariable analysis, the HR was 4.40 (95% CI: 1.52-12.77; P=0.006). Adding log miR-150-5p to the MAGGIC score led to an increase of 0.047 in C-index. The model combining miR-150-5p and MAGGIC score had a 73% likelihood of representing the best-fit model of those evaluated.Our data generate the hypothesis that miR-150-5p may represent a novel risk marker in HF with reduced ejection fraction.

Aims Uninterrupted anticoagulation is recommended during the ablation of atrial fibrillation. This meta-analysis compared the safety and efficacy of uninterrupted direct oral anticoagulants (DOACs) to uninterrupted vitamin K antagonists (VKAs) during atrial fibrillation ablation. Methods The meta-analysis included eligible randomized controlled trials from 2009 to 2019. Odds ratios (ORs) and 95% confidence intervals were pooled using a random effects model and a sensitivity analysis was performed by sequentially removing one study or DOAC at a time. Results Six studies were included; 1288 received DOAC and 1081 VKA. Pooled ORs indicated a lower nonsignificant incidence in DOACs vs. VKA of composite outcome of major bleeding, stroke, or transient ischemic attack, and mortality (0.69; 0.28-1.71; 31 vs. 45 events), major bleeding alone (0.66; 0.30-1.47; 27 vs. 41 events), and cardiac tamponade (0.56; 0.21-1.45; eight vs. 13 events) with a slightly higher occurrence of minor bleeding (1.17; 0.89-1.56; 139 vs. 106 events) and silent cerebral thromboembolic events (1.12; 0.75-1.66; 72 vs. 58 among 442 and 376 patients performing MRI study). Sensitivity analyses confirmed overall results: pooled ORs ranged from 0.56 to 1.00 for the composite outcome and from 0.54 to 0.92 for major bleedings. Conclusion Uninterrupted DOAC is a safe and effective alternative to uninterrupted VKA during atrial fibrillation ablation.

Background and Purpose— Prediction of outcome after stroke rehabilitation may help clinicians in decision-making and planning rehabilitation care. We developed and validated a predictive tool to estimate the probability of achieving improvement in physical functioning (model 1) and a level of independence requiring no more than supervision (model 2) after stroke rehabilitation. Methods— The models were derived from 717 patients admitted for stroke rehabilitation. We used multivariable logistic regression analysis to build each model. Then, each model was prospectively validated in 875 patients. Results— Model 1 included age, time from stroke occurrence to rehabilitation admission, admission motor and cognitive Functional Independence Measure scores, and neglect. Model 2 included age, male gender, time since stroke onset, and admission motor and cognitive Functional Independence Measure score. Both models demonstrated excellent discrimination. In the derivation cohort, the area under the curve was 0.883 (95% confidence intervals, 0.858–0.910) for model 1 and 0.913 (95% confidence intervals, 0.884–0.942) for model 2. The Hosmer–Lemeshow χ 2 was 4.12 ( P =0.249) and 1.20 ( P =0.754), respectively. In the validation cohort, the area under the curve was 0.866 (95% confidence intervals, 0.840–0.892) for model 1 and 0.850 (95% confidence intervals, 0.815–0.885) for model 2. The Hosmer–Lemeshow χ 2 was 8.86 ( P =0.115) and 34.50 ( P =0.001), respectively. Both improvement in physical functioning (hazard ratios, 0.43; 0.25–0.71; P =0.001) and a level of independence requiring no more than supervision (hazard ratios, 0.32; 0.14–0.68; P =0.004) were independently associated with improved 4-year survival. A calculator is freely available for download at https://goo.gl/fEAp81 . Conclusions— This study provides researchers and clinicians with an easy-to-use, accurate, and validated predictive tool for potential application in rehabilitation research and stroke management.

Cardiopulmonary bypass (CPB) surgery, despite heparin administration, elicits activation of coagulation system resulting in coagulopathy. Anti-inflammatory effects of steroid treatment have been demonstrated, but its effects on coagulation system are unknown. The primary objective of this study is to assess the effects of methylprednisolone on coagulation function by evaluating thrombin generation, fibrinolysis, and platelet activation in high-risk patients undergoing cardiac surgery with CPB. The Steroids In caRdiac Surgery study is a double-blind, randomized, controlled trial performed on 7507 patients worldwide who were randomized to receive either intravenous methylprednisolone, 250 mg at anesthetic induction and 250 mg at initiation of CPB (n = 3755), or placebo (n = 3752). A substudy was conducted in 2 sites to collect blood samples perioperatively to measure prothrombin fragment 1.2 (PF1+2, thrombin generation), plasmin-antiplasmin complex (PAP, fibrinolysis), platelet factor 4 (PF4 platelet activation), and fibrinogen. Eighty-one patients were enrolled in the substudy (37 placebo vs 44 in treatment group). No difference in clinical outcome was detected, including postoperative bleeding and need for blood products transfusion. All patients showed changes of all plasma biomarkers with greater values than baseline in both groups. This reaction was attenuated significantly in the treatment group for PF1.2 (P = 0.040) and PAP (P = 0.042) values at the first intraoperative measurement. No difference between groups was detected for PF4. Methylprednisolone treatment attenuates activation of coagulation system in high-risk patients undergoing CPB surgery. Reduction of thrombin generation and fibrinolysis activation may lead to reduced blood loss after surgery.

Objectives: Cardiac surgery induces a systemic inflammatory reaction that has been associated with postoperative mortality and morbidity. Many studies have characterized this reaction through laboratory biomarkers while clinical studies generally are lacking. This study aimed to assess the incidence of postoperative systemic inflammation after cardiac surgery, and the association of postoperative systemic inflammation with preoperative patients' characteristics and postoperative outcomes.Design: Retrospective analysis of prospectively collected data. Analysis of the overall population and of propensity-matched subgroups.Setting: Cardiac surgery intensive care unit.Patients: Adult patients who underwent cardiac surgery with cardiopulmonary bypass (CPB) between June 2016 and June 2017.Interventions: Mixed cardiac surgery operations on CPB.Measurements and Main Results: During the study period, 502 patients underwent cardiac surgery with CPB. One hundred forty-two patients (28.3%) fulfilled SIRS criteria at 24 hours. After performing a multivariate analysis to adjust for the procedure type and preoperative systemic inflammatory reaction syndrome (SIRS) parameters, the occurrence of SIRS was associated inversely with age and extracardiac arteriopathy, and it was associated positively with preoperative white blood cell count. Vasopressors were used more frequently in SIRS patients who further experienced longer mechanical ventilation time and length of stay in the intensive care unit (ICU). The incidence of a composite outcome including death, transient ischemic attack/stroke, renal replacement therapy, bleeding, postoperative intra-aortic balloon pump insertion, and a length of stay in ICU >96 hours was more frequent in SIRS-positive patients. There was no difference between overall and matched subgroups for in hospital mortality.Conclusion: In this retrospective study, the clinical signs of SIRS were detected in a substantial percentage of patients who underwent cardiac surgery. The postoperative SIRS criteria were associated with a more complicated postoperative course and higher postoperative morbidity. (C) 2019 Elsevier Inc. All rights reserved.

Objectives Treatment of aortic valve stenosis is evolving, indications for transcatheter approach (TAVI) have increased but also surgical valve replacement has changed with the use of minimally invasive approaches. Comparisons between TAVI and surgery have rarely been done with minimally invasive techniques (mini-SAVR) in the surgical arm. Aim of the present study is to compare mini-SAVR and TAVI in a multicenter recent cohort. Methods Evaluated were 2904 patients undergone mini-SAVR (2407) or TAVI (497) in 10 different centers in the period 2011–2016. The Heart Team approved treatment for complex cases. The primary outcome is the incidence of 30-day mortality following mini-SAVR and TAVI. Secondary outcomes are the occurrence of major complications following both procedures. Propensity matched comparisons was performed based on multivariable logistic regression model. Results In the overall population TAVI patients had increased surgical risk (median EuroSCORE II 3.3% vs. 1.7%, p ≤ 0.001) and 30-day mortality was higher (1.5% and 2.8% in mini-SAVR and TAVI respectively, p = 0.048). Propensity score identified 386 patients per group with similar baseline profile (median EuroSCORE II ~3.0%). There was no difference in 30-day mortality (3.4% in mini-SAVR and 2.3% in TAVI; p = 0.396) and stroke, surgical patients had more blood transfusion, kidney dysfunction and required longer ICU and hospital length of stay while TAVI patients had more permanent pace maker insertion. Conclusions Mini-SAVR and TAVI are both safe and effective to treat aortic stenosis in elderly patients with comorbidities. A joint evaluation by the heart-team is essential to direct patients to the proper approach., Highlights • A comparison between TAVI and minimally invasive techniques has rarely been done • In a propensity-matched comparison from 10 different hospitals, TAVI and mini-SAVR provided optimal short-term outcome. • 30-day mortality was 3.4% in mini-SAVR and 2.3% in TAVI (p = 0.396) • Mini-SAVR and TAVI are both safe and effective to treat aortic stenosis in elderly patients with comorbidities.

OBJECTIVE Long-term visit-to-visit SBP variability (VVV) has been shown to predict cerebro-cardiovascular events and end-stage renal disease in chronic kidney disease (CKD) patients. Whether SBP VVV is also a predictor of CKD development in diabetes is currently uncertain. We assessed the role of SBP VVV on the development of CKD in patients with type 2 diabetes (T2D) and hypertension in real life. METHODS Clinical records from 30 851 patients with T2D and hypertension, with normal estimated glomerular filtration rate (eGFR) and regular visits during a 4-year follow-up were analyzed. SBP variability was measured by three metrics: coefficient of variation; SD of the mean SBP and average absolute difference of successive values in each individual. CKD was defined as eGFR less than 60 and/or a reduction in eGFR at least 30% from baseline. RESULTS Over the 4-year follow-up, 9.7% developed eGFR less than 60 and 4.5% an eGFR reduction at least 30% from baseline. Several clinical characteristics (older age, male sex, SBP, DBP, albuminuria, glycated hemoglobin, insulin treatment) were related to intraindividual SBP variability. Patients with VVV in the upper quintile showed an increased risk of developing both components of CKD [adjusted odds ratio (OR) 1.21, P

Pulmonary vein isolation (PVI) is the cornerstone of catheter ablation in paroxysmal atrial fibrillation (PAF). Studies reported that the PVI single procedure was able to achieve durable sinus rhythm without the need of antiarrhythmic drugs in 60-80% of patients with PAF. In this study, we report data regarding bilateral left lateral ridge ablation for PAF.We retrospectively collected data of 120 consecutive patients (mean age 56 ± 10 years; 62% male) referred to our center to perform PVI. In 60 patients we performed PVI (group 1) and in 60 patients performed PVI and bilateral left lateral ridge ablation (group 2). All patients performed a clinical follow-up after 24 months from the ablation procedure.PVI was achieved in all patients. The mean radiofrequency time to perform ablation on the left atrial appendage ostium was 216 ± 49 s. In all patients of group 2 we obtained disappearance of local electrograms and the loss of local capture during pacing on posterior wall of left atrial appendage ridge. No significant differences were found between the two groups regarding mean contact force during ablation (14 ± 4 vs. 15 ± 4 g; groups 1 and 2, respectively, P = 0.34). At 24-month follow-up, single procedure success rate was significantly higher in group 2 compared with group 1 (88 vs. 74%, respectively; P = 0.03). No significant procedural complications were documented.Bilateral left lateral ridge ablation is a safe technique able to improve the success rate of PVI in patients with PAF.

BACKGROUND AND AIMS: Target and intensity of low-density lipoprotein cholesterol (LDL-C) lowering therapy should be tailored according to the individual global cardiovascular (CV) risk. We aimed at retrospectively evaluating real-life LDL-C goal attainment and predictive factors for predefined LDL-C therapeutic goals both in primary and secondary prevention. METHODS: We collected data from a large cohort of outpatients aged 40-65 years, followed by general practitioners, cardiologists and diabetologists in Italy. All data were centrally analysed for global CV risk assessment and rates of control of major CV risk factors, including LDL-C. Study population was stratified according to the presence or absence of previous CV events, including coronary artery disease (CAD), peripheral artery disease (PAD) or stroke/TIA. CV risk profile characterization was based on the European SCORE. Predefined therapeutic goals were set according to the European guidelines on dyslipidaemia: LDL-C levels

Objectives To assess the incremental prognostic utility of discharge serum creatinine (SCr), systolic blood pressure (SBP), and NT-proBNP and sodium concentrations in hospitalized patients with acutely decompensated chronic heart failure. Background Whether key prognostic variables at discharge provide incremental prognostic information beyond that provided by a model based on admission variables (referent) remains incompletely defined. Methods The primary outcome was a composite of death, urgent heart transplantation, or ventricular assist device implantation at 1 year. The gain in predictive performance was assessed using C index, Bayesian Information Criterion, and Net Reclassification Improvement. Results The best fit was obtained when discharge NT-proBNP was added to the referent model. No interaction between admission and discharge NT-proBNP was found. Discharge SCr, SBP, and sodium did not improve goodness-of-fit. Conclusions Admission and discharge NT-proBNP provide complementary and independent prognostic information; as such, they should be taken into account concurrently.

We thank Dijkland et al for their interest in our article1 on prediction of functional outcome after stroke rehabilitation. Dr Dijkland raises some issues about the outcome measures and the predictive model for the secondary outcome. In general, models predictive of dichotomous clinical outcomes are most relevant in medical applications. Consistently, dichotomized outcome measures, including the Barthel index and the modified Rankin Scale, have been used to assess the effects of stroke treatment in clinical trials. For patients undergoing rehabilitation after a moderate-to-severe stroke, regaining minimal levels of disability or physical independence are clinically highly relevant outcomes. According to the article of Altman cited by Dijkland, we did not convert continuous explanatory variables to 2 (dichotomization) or multiple (categorization) groups, but …

Background/Aims: Apparent treatment resistant hypertension (aTRH) is highly prevalent in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The impact of aTRH and achievement of recommended blood pressure (BP) values on the rate of glomerular filtration rate (eGFR) loss in CKD patients is poorly known. To assess the role of aTRH and time-updated BP control (BPC) on the progression of CKD in patients with T2D and hypertension (HT) in real life clinical practice. Methods: Clinical records from a total of 2,778 diabetic patients with HT and stage 3 CKD (i.e. baseline eGFR values between 30 and 60 ml/min) and regular visits during a four-year follow-up were analyzed. The association between BPC (i.e. 75% of visits with BP 30% reduction from baseline) or worsening of albuminuria status over time was assessed. Results: At baseline 33% of patients had aTRH. Over the 4-year follow-up, 20% had a >30% eGFR reduction. Patients with aTRH had an increased risk of eGFR loss >30% (OR 1.31; PConclusion: In patients with stage 3 CKD the presence of aTRH entails a faster loss of eGFR. More effective prevention of aTRH should be implemented as this condition is associated with a burden of risk not modifiable by tight BP reduction.

To assess the predictive role of changes in albuminuria on the loss of renal function under antihypertensive treatment in patients with type 2 diabetes (T2D).Clinical records from a total of 12 611 patients with hypertension and T2D, attending 100 antidiabetic centers in Italy, with normal estimated glomerular filtration rate (eGFR) at baseline and regular visits during a 4-year period were retrieved and analyzed. We assessed the association between changes in albuminuria status during a 1-year baseline period and time updated blood pressure (BP) and eGFR loss over the subsequent 4-year follow-up.Mean age at baseline was 65 ± 9 years, known duration of diabetes11 ± 8 years, eGFR 85 ± 13 ml/min and BP 142 ± 17/81 ± 9 mmHg. Patients with persistent albuminuria showed the highest 4-year risk of eGFR loss more than 30% from baseline or onset of stage 3 chronic kidney disease (eGFR 60 ml/min) as compared with those with persistent normal albuminuria (odds ratio 2.00, confidence interval 1.71-2.34; P 0.001). Female sex, age, disease duration, BMI, low baseline eGFR, lipid profile, the number of antihypertensive drugs and variations in albuminuria status were associated with renal risk in the whole study population. Furthermore, lower time updated BP values and the use of renin-angiotensin-aldosterone-system-inhibitors were related to the occurrence of renal endpoints only in the subgroup of patients without albuminuria.In patients with hypertension and T2D under real-life clinical conditions, changes in albuminuria parallel changes of renal risk. Albuminuria status could be a guide to optimize therapeutic strategy.

Background: Myocardial damage is an independent predictor of adverse outcome following cardiac surgery and myocardial protection is one of the key factors to achieve successful outcomes. Cardioplegia with Custodiol is currently the most used cardioplegia during minimally invasive cardiac surgery (MICS). Different randomized controlled trials compared blood and Custodiol cardioplegia in the context of traditional cardiac surgery. No data are available for MICS. Aim: The aim of this study was to compare the efficacy of cold blood versus Custodiol cardioplegia during MICS. Method: We retrospectively evaluated 90 patients undergoing MICS through a right mini-thoracotomy in a three-year period. Myocardial protection was performed using cold blood (44 patients, CBC group) or Custodiol (46 patients, Custodiol group) cardioplegia, based on surgeon preference and complexity of surgery. Results: The primary outcomes were post-operative cardiac troponin I (cTnI) and creatine kinase MB (CKMB) serum release and the incidence of Low Cardiac Output Syndrome (LCOS). Aortic cross-clamp and cardiopulmonary bypass times were higher in the Custodiol group. No difference was observed in myocardial injury enzyme release (peak cTnI value was 18±46 ng/ml in CBC and 21±37 ng/ml in Custodiol; p=0.245). No differences were observed for mortality, LCOS, atrial or ventricular arrhythmias onset, transfusions, mechanical ventilation time duration, intensive care unit and total hospital stay. Conclusions: Custodiol and cold blood cardioplegic solutions seem to assure similar myocardial protection in patients undergoing cardiac surgery through a right mini-thoracotomy approach.

It is not clear whether correlations exist within hospitals or operators among risk-adjusted mortality rates (RAMRs) for the most common cardiac interventions and how much of variations in outcomes are residually explained by providers and physicians. We examined these aspects by using recent national data on percutaneous coronary intervention (PCI) and cardiac surgery.Publically available data from New York State aggregated at hospital and operator level were downloaded by Department of Health website for in-hospital/30-day mortality after PCI, coronary artery bypass graft (CABG) and valve surgery. Correlations between RAMRs were evaluated by using Spearman's coefficient (rho). The proportion of mortality variation attributed to hospitals and operators was estimated.During the period 2008-2013, 390 cardiologists from 63 hospitals and 163 surgeons from 41 centres were evaluated. The RAMRs during 2008-2010 correlated with the RAMRs during 2011-2013 for valve surgery within providers (rho=0.55;p0.001) and within interventionists for PCI (rho=0.21;p0.001), isolated CABG (rho=0.25;p=0.009), and any valve surgery or CABG procedure (rho=0.49;p0.001). The most recent hospital's RAMRs (year 2012 and 2013) significantly correlated in PCI (rho=0.40;p=0.002) but not in CABG (rho=0.13;p=0.413).2% of mortality variations was attributed to providers and 2-3% to difference between operators.A correlation exists at provider and operator level in RAMRs for PCI and cardiac surgery procedures performed in New York State. Beyond patient's risk profile, that is the strongest predictor of early mortality after a cardiac procedure, hospitals and operators have a small but statistically significant contribution to variation in post-operative outcome.

Background Obesity has been suggested to confer a survival benefit in acute heart failure. The concentrations of NT-proBNP may be reduced in patients with high body mass index (BMI). Objectives To investigate the relationship among BMI, NT-proBNP, and mortality risk in decompensated chronic heart failure (DCHF). Methods This was a retrospective study. We studied 1001 patients with DCHF. Hazard ratios (HR) were calculated with Cox regression analysis. Results During the 1-year follow-up, 295 patients died. Compared with normal-weight patients, the unadjusted HR for death were 1.02 (95% CIs 0.79–1.33; p = 0.862) for patients with a BMI of 25.0–29.9 kg/m2 and 0.83 (95% CIs 0.61–1.12; p = 0.213) for patients with a BMI ≥ 30 kg/m2. NT-proBNP remained independently associated with mortality across the BMI categories. There was no statistically significant interaction between BMI and NT-proBNP levels for risk prediction. Conclusions Obesity was not associated with mortality risk. NT-proBNP remained an independent prognostic factor across the BMI categories.

Background Apparent treatment resistant hypertension ( aTRH ) is highly prevalent in patients with type 2 diabetes mellitus (T2D) and entails worse cardiovascular prognosis. The impact of aTRH and long‐term achievement of recommended blood pressure ( BP ) values on renal outcome remains largely unknown. We assessed the role of aTRH and BP on the development of chronic kidney disease in patients with T2D and hypertension in real‐life clinical practice. Methods and Results Clinical records from a total of 29 923 patients with T2D and hypertension, with normal baseline estimated glomerular filtration rate and regular visits during a 4‐year follow‐up, were retrieved and analyzed. The association between time‐updated BP control (ie, 75% of visits with BP aTRH . Over the 4‐year follow‐up, 19% developed low estimated glomerular filtration rate and 12% an estimated glomerular filtration rate reduction ≥30% from baseline. Patients with aTRH showed an increased risk of developing both renal outcomes (adjusted odds ratio, 1.31 and 1.43; P aTRH . No association was found between BP control and renal outcomes in non‐ aTRH , whereas in aTRH , BP control was associated with a 30% ( P =0.036) greater risk of developing the renal end points. Conclusions ATRH entails a worse renal prognosis in T2D with hypertension. BP control is not associated with a more‐favorable renal outcome in aTRH . The relationship between time‐updated BP and renal function seems to be J‐shaped, with optimal systolic BP values between 120 and 140 mm Hg.

Acute Kidney Injury (AKI) after cardiac surgery is a complication influencing postoperative outcome. Preoperative hemoglobin is a predictor of postoperative AKI. We aimed to identify preoperative predictors of Renal Replacement Therapy (RRT) and to develop a new risk-scoring system including hemoglobin to better stratify the risk of events.We evaluated 3288 consecutive patients of the Regional Cardiac Surgery Registry of Puglia operated in 2011-2012. Chronic dialysis and renal transplantation patients were excluded. Primary outcome was post-operative RRT incidence.The study sample was divided in two cohorts: 1642 patients (70 RRT) operated during the year 2011 as derivation cohort and 1646 patients (69 RRT) of the year 2012 as validation. In a multivariable logistic regression model using a stepwise method, six preoperative risk factors were associated with RRT in the derivation cohort: creatinine clearance, preoperative hemoglobin, neurological dysfunction, left ventricular ejection fraction, urgency and combined procedures (discrimination c-index 0.844 and 0.818 in the validation cohort). Scoring system included risk factors obtained from derivation cohort adjusting their relative weight with updated rounded coefficients in the validation cohort: creatinine clearance50ml/min (1 point), hemoglobin≤12.5g/dl (1 point), left ventricular ejection fraction≤30% (1 point), urgent operation (1 point), emergency-salvage surgery (2 points), and combined procedures (1 point). In both cohorts, outcomes were strongly correlated with score points.Our simple bedside prognostic score demonstrates good performance in predicting RRT. Hemoglobin plays an important role and future studies will clarify if preoperative anemia correction will lead to decreased RRT risk.

Background Antithrombin (AT) concentrations are reduced after cardiac surgery with cardiopulmonary bypass compared with the preoperative levels. Low postoperative AT is associated with worse short- and mid-term clinical outcomes. The aim of the study is to evaluate the effects of AT administration on activation of the coagulation and fibrinolytic systems, platelet function, and the inflammatory response in patients with low postoperative AT levels. Methods Sixty patients with postoperative AT levels of less than 65% were randomly assigned to receive purified AT (5000 IU in three administrations) or placebo in the postoperative intensive care unit. Thirty patients with postoperative AT levels greater than 65% were observed as controls. Interleukin 6 (a marker of inflammation), prothrombin fragment 1-2 (a marker of thrombin generation), plasmin–antiplasmin complex (a marker of fibrinolysis), and platelet factor 4 (a marker of platelet activation) were measured at six different times. Results Compared with the no AT group and control patients, patients receiving AT showed significantly higher AT values until 48 hours after the last administration. Analysis of variance for repeated measures showed a significant effect of study treatment in reducing prothrombin fragment 1-2 ( p = 0.009; interaction with time sample, p = 0.006) and plasmin–antiplasmin complex ( p p p = 0.877; interaction with time sample, p = 0.521) and platelet factor 4 ( p = 0.913; interaction with time sample, p = 0.543). No difference in chest tube drainage, reopening for bleeding, and blood transfusion was observed. Conclusions Antithrombin administration in patients with low AT activity after surgery with cardiopulmonary bypass reduces postoperative thrombin generation and fibrinolysis with no effects on platelet activation and inflammatory response.

OBJECTIVES: To evaluate performance of the European System for Cardiac Operation Risk Evaluation (EuroSCORE II), to assess the influence of model updating and to derive a hierarchical tree for modelling the relationship between EuroSCORE II risk factors and hospital mortality after cardiac surgery in a large prospective contemporary cohort of consecutive adult patients. METHODS: Data on consecutive patients, who underwent on-pump cardiac surgery or off-pump coronary artery bypass graft intervention, were retrieved from Puglia Adult Cardiac Surgery Registry. Discrimination, calibration, re-estimation of EuroSCORE II coefficients and hierarchical tree analysis of risk factors were assessed. RESULTS: Out 6293 procedures, 6191 (98.4%) had complete data for EuroSCORE II assessment with a hospital mortality rate of 4.85% and EuroSCORE II of 4.40 ± 7.04%. The area under the receiver operator characteristic curve (0.830) showed good discriminative ability of EuroSCORE II in distinguishing patients who died and those who survived. Calibration of EuroSCORE II was preserved with lower predicted than observed risk in the highest EuroSCORE II deciles. At logistic regression analysis, the complete revision of the model had most of reestimated regression coefficients not statistically different from those in the original EuroSCORE II model. When missing values were replaced with the mean EuroSCORE II value according to urgency and weight of intervention, the risk score confirmed discrimination and calibration obtained over the entire sample. A recursive tree-building algorithm of EuroSCORE II variables identified three large groups (55.1, 17.1 and 18.1% of procedures) with low-to-moderate risk (observed mortality of 1.5, 3.2 and 6.4%) and two groups (3.8 and 5.9% of procedures) at high risk (mortality of 14.6 and 32.2%). Patients with low-to-moderate risk had good agreement between observed events and predicted frequencies by EuroSCORE II, whereas those at greater risk showed an underestimation of expected mortality. CONCLUSIONS: This study demonstrates that EuroSCORE II is a good predictor of hospital mortality after cardiac surgery in an external validation cohort of contemporary patients from a multicentre prospective regional registry. The EuroSCORE II predicts hospital mortality with a slight underestimation in high-risk patients that should be further and better evaluated. The EuroSCORE II variables as a risk tree provides clinicians and surgeons a practical bedside tool for mortality risk stratification of patients at low, intermediate and high risk for hospital mortality after cardiac surgery.

Renal dysfunction may confound the clinical interpretation of N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration. This study investigated whether renal dysfunction influences the prognostic accuracy of NT-proBNP in acute decompensated heart failure (ADHF).We studied 908 ADHF patients. The primary outcome was 12-month mortality. Interaction between estimated glomerular filtration rate (eGFR) and NT-proBNP in predicting mortality was tested with the likelihood ratio test. The patients were classified into 3 eGFR strata: ≥60, 30-59, and30 ml·min(-1)·1.73 m(-2). Cox models were used to calculate the adjusted hazard ratios (HR) for NT-proBNP, modeled as a dichotomous or categorized variable, within each level of eGFR. NT-proBNP was categorized using optimal cut-offs defined in ROC analysis for each eGFR level. A total of 234 patients (25.8%) died. Testing for interaction was not significant (χ(2)=0.29; P=0.5928). The adjusted HR for NT-proBNP5,180 pg/ml was 2.09 (P0.001) in the highest, 1.7 (P0.001) in the intermediate, and 3.33 (P=0.010) in the lowest eGFR level. The adjusted HR for NT-proBNP above the optimal cut-offs defined on ROC analysis were 1.5 (P=0.239), 2.2 (P0.001), and 3.24 (P=0.002), respectively. The models incorporating NT-proBNP as a dichotomous or categorized variable had equivalent C-statistics.There was no evidence of interaction between eGFR and NT-proBNP in predicting mortality. The NT-proBNP cut-off of 5,180 ng/L provided independent prognostic information, irrespective of the level of residual renal function.

OBJECTIVES Minimally invasive valve surgery (MIVS) is associated with improved clinical outcome but longer cardiopulmonary bypass (CPB) time. The aim of the present study is to compare inflammatory and coagulation parameters in patients undergoing minimally invasive or standard valve surgery. METHODS A prospective non-randomized study was performed enrolling 79 patients undergoing mitral (20 right mini-thoracotomy and 18 standard sternotomy) and aortic valve (20 mini-sternotomy and 21 standard sternotomy) procedures. Blood samples were collected perioperatively to measure prothrombin fragment 1.2 (PF1.2, thrombin generation), plasmin antiplasmin complex (PAP, fibrinolysis), interleukin-6 (IL-6, inflammation). Plasma free haemoglobin (f-Hb) was assessed to evaluate haemolysis. RESULTS Patients in the minimally invasive group were younger and had less comorbidities CPB and cross-clamp times were comparable considering both aortic and mitral procedures, but longer in the mini-thoracotomy group. IL-6 and PAP were reduced in the minimally invasive group, particularly 2 h after CPB (respectively 102 ± 114 vs 34 ± 49 pg/ml, P

E.A.B. received consulting fees from Baldacci and Servier and travel/hotel/registration fee subsidies from Baldacci, Servier, Berlin Heart GmbH and Novartis. He is also a member of the steering committees of Servier, Novartis, Astra-Zeneca and Merck/Bayer; has performed “contracted research” from Servier and Amgen; and has received honoraria from Servier. The remaining authors have no conflicts of interest to disclose. This trial was supported by a grant from the Sao Paulo Research Foundation (2012/06163 to E. A.B.), Sao Paulo, Brazil (www.fapesp.br). No financial support was provided by any pharmaceutical company for the implementa tion, dissemination or publication of this study.

To evaluate the role of bioelectrical impedance vector analysis (BIVA) and brain natriuretic peptide (BNP) in detecting peripheral congestion in heart failure (HF).BIVA/BNP are biomarkers for congestion in acute (ADHF) and chronic HF.487 ADHF and 413 chronic HF patients underwent BIVA and BNP tests.BIVA was more accurate than BNP in detecting peripheral congestion both in ADHF (AUC 0.88 vs 0.57 respectively; p 0.001) and chronic HF patients (AUC 0.89 vs 0.68, respectively; p 0.001). In ADHF patients, the optimal BNP cut-off for discriminating presence or absence of edema was870 pg/mL (PPV = 48% and NPV = 58%) whereas in chronic HF it was216 pg/mL (PPV = 18% and NPV = 95%). The BIVA detected edema when the vector fell into the lower pole of 75th percentile tolerance ellipse (PPV = 84% and NPV = 78%) in ADHF, the lower pole of 50% (PPV = 68% and NPV = 95%) in chronic HF.In HF patients, BIVA is an easy, fast technique to assess peripheral congestion, and is even more accurate than BNP.

Objective Cardiopulmonary bypass (CPB) systems without a venous reservoir rarely are adopted clinically. The effects of a biocompatible CPB system with a venous reservoir were evaluated on the activation of the coagulation and inflammatory systems. Design A prospective, randomized controlled trial. Setting A university hospital (single center). Participants Eighty-three coronary artery bypass graft (CABG) surgery patients were assigned to the Physio group (closed venous reservoir, phosphorylcholine coating, and no cardiotomy suction) or the Standard group (open, noncoated, and cardiotomy suction used). Methods Blood samples were obtained at 6 different time points before, during, and after surgery. Nuclear factor-kB (NF-κB) was evaluated before surgery and 2 and 24 hours after surgery. Myocardial damage was evaluated measuring cardiac troponin I. Measurements and Main Results Interleukin (IL)-6 (a marker of inflammation), prothrombin fragment 1-2 (PF-1.2, a marker of thrombin generation), plasmin-antiplasmin complex (PAP, a marker of fibrinolysis), and platelet factor 4 (PF4, a marker of platelet activation) were measured. The DNA binding activity of proinflammatory transcription factor NF-κB was quantified in the isolated lymphomonocyte cells. Surgery caused changes of all plasma biomarkers. This reaction was attenuated strongly in the Physio group; PF-1.2, PAP, and PF4 all were decreased significantly. In the Physio group, a significantly lower cardiac troponin I release was observed postoperatively. After surgery, NF-κB activity was reduced in the Physio group although this difference was not statistically significant. Conclusions A multimodal strategy using a closed and phosphorylcholine-coated CPB circuit together with the avoidance of cardiotomy suction reduced activation of the coagulation and fibrinolytic systems intraoperatively, although these changes did not persist postoperatively. However, no difference in clinical outcome was appreciated on a larger scale.

Amino-terminal pro-B-type natriuretic peptide (NT-proBNP) has been associated with prognosis in heart failure. The aim of this study was to assess whether NT-proBNP enhances risk prediction in acute decompensated heart failure (ADHF). The authors enrolled 453 patients hospitalized for ADHF. The primary outcome was 12-month mortality. Two separate multivariable predictive models were built by using standard variables-only and NT-proBNP concentrations. The models were internally validated using the bootstrapping method. Twelve-month mortality was 28.3%. There was no statistical evidence of overfit. Compared with the standard variables-only model, the NT-proBNP model had a better predictive performance as judged by the Nagelkerke R(2) (0.410 vs 0.374) and the Brier score (0.136 vs 0.141), which are measures of overall performance; the Akaike Information Criterion (399.2 vs 415.0), which is a tool for model selection; and the C index (0.844 vs 0.831), which is a measure of the discriminative ability. Both models were well calibrated, as judged by the Hosmer-Lemeshow chi-square test. Both models predicted 12-month mortality significantly better than the Enhanced Feedback for Effective Cardiology Treatment risk score. In conclusion, the NT-proBNP model improved risk prediction compared with the standard variables-only model.

Background Surgery for acute aortic dissection (AAD) is frequently complicated by excessive postoperative bleeding and blood product transfusion. Blood flow through the nonendothelialized false lumen is a potential trigger for the activation of the hemostatic system; however, the physiopathology of the aortic dissection induced coagulopathy has never been precisely studied. The aim of the present study is the evaluation of the coagulation and fibrinolytic systems and platelet activation in patients undergoing surgery for AAD. Methods Eighteen patients undergoing emergent surgery for Stanford type A AAD were enrolled in the study. The activation of the coagulation and fibrinolytic systems and platelet activation were evaluated at 6 different time points before, during, and after the operation, measuring prothrombin fragment 1.2 (F1.2), plasmin-antiplasmin complex, and platelet factor 4, respectively. Results All measured biomarkers were increased before, during, and after the operations indicating a systemic activation of coagulation, fibrinolysis, and platelets. These changes were pronounced even preoperatively (T0), and soon after the beginning of cardiopulmonary bypass (T1) when the influence of hypothermia and prolonged cardiopulmonary bypass time were not yet involved. Time from symptom onset to intervention inversely correlated with preoperative F1.2 (r = −0.75; p = 0.002) and plasmin-antiplasmin levels (r = −0.57; p = 0.034). Conclusions Blood flow through the false lumen is a powerful activator of the hemostatic system even before the operation. This remarkable activation may influence postoperative outcome of AAD patients.

Cardiovascular diseases represent the leading cause of morbidity and mortality, worldwide. Early detection and appropriate management of cardiovascular risk factors and disease markers in daily clinical practice may improve preventive strategies and reduce the burden of cardiovascular disease. The EFFECTUS (Evaluation of Final Feasible Effect of Control Training and Ultra Sensitisation) programme was an educational programme aimed at evaluating prevalence of major cardiovascular risk factors among outpatients, and preferences and attitudes for cardiovascular disease management among Italian physicians in their routine clinical practice. This article provides an overview of the main findings of different analyses from the EFFECTUS database, which have demonstrated a high prevalence of cardiovascular risk factors, irrespective of the clinical settings and outpatient clinics in which patients were followed. Also, findings from this database suggest that more intensive clinical data recording was paralleled by better adherence to guidelines, and that use of electronic rather than conventional support for clinical data collection and registration improved accuracy in data recording, which translated into better management of patients at risk in daily clinical practice.

the test was potentiated by the administration of 300 μg of nitroglycerine after20 minutes. Occurrence of VVS and hemodynamic responses during passive and nitroglycerine phases ofHUT were evaluated; symptoms preceding HUT-induced syncope were recorded, together with heart rateand arterial blood pressure values.

Background The optimal timing for coronary artery bypass grafting (CABG) in patients with recent acute myocardial infarction (AMI) is unclear. Cardiac troponin I (cTnI) is a widely accepted biomarker of myocardial damage. The objective of this study was to determine whether preoperative cTnI values could be used to determine risk stratification for CABG operations in patients with recent AMI. Methods Evaluated were 184 patients who sustained an AMI within 21 days of undergoing nonurgent CABG operations. They were divided into two groups according to their preoperative cTnI values: 117 patients with cTnI of 0.15 ng/mL or less and 67 with cTnI exceeding 0.15 ng/mL. Associations between study variables and events were assessed with logistic regression modelling. Time from AMI to operation was evaluated to define preoperative cTnI variation. Results Values of cTnI tended to decrease when the interval between AMI and the operation increased. Preoperative cTnI values were significantly associated with a higher incidence of major postoperative complications (low cardiac output syndrome, intraaortic balloon pump necessity, mechanical ventilation >72 hours, acute renal failure, in-hospital mortality). Perioperative myocardial damage was more pronounced in patients with cTnI exceeding 0.15 ng/mL. Multivariate analyses revealed cTnI exceeding 0.15 ng/mL was an independent predictor for 6-month mortality (odds ratio, 3.7; p = 0.043). Conclusions Preoperative cTnI exceeding 0.15 ng/mL in patients with recent AMI undergoing CABG is associated with higher postoperative myocardial damage and is a strong determinant of postoperative morbidity and mortality within the 6-month period.

Aims To evaluate the prevalence, timing, and haemodynamic characteristics of prodromal symptoms in patients experiencing vasovagal syncope (VVS) during a head-up tilt test (HUT) potentiated with nitroglycerin, and their relationships with those reported before spontaneous episodes. Methods and results Symptoms preceding HUT-induced syncope were recorded, together with heart rate (HR) and arterial blood pressure (BP) values, in 149 otherwise healthy and drug-free subjects with recurrent unexplained syncope. Head-up tilt test significantly increase the number of patients capable of recognizing the premonitory symptoms of VVS than before spontaneous episodes (96 vs. 79%; P < 0.001). The nine most frequent symptoms were stratified into three groups on the basis of their characteristics: headache, hot flashes, and palpitations occurred more than 3 min before syncope, with a very slight reduction in BP; nausea, asthenia, diaphoresis, vertigo, and epigastric discomfort preceded syncope by 1–3 min and were associated with a slight reduction in BP; and blurred vision appeared the last minute before syncope and was characterized by the lowest BP and HR values. Conclusion In comparison with spontaneous syncopal episodes, HUT allows the more frequent recognition of prodromes also providing useful information in terms of timing and haemodynamic characteristics of symptoms that may allow more tailored patient counselling.

Aims The aim of this study was to evaluate arterial baroreflex control of heart rate immediately before head-up tilt test (HUT)-induced vasovagal syncope (VVS). Methods and results We enrolled 97 otherwise healthy subjects with recurrent unexplained syncope. After 10 min of rest in supine position, they underwent a passive HUT potentiated with nitroglycerin administration after 20 min. Beat-to-beat heart rate and systolic blood pressure were continuously recorded. Sequence method was used to measure two complementary parameters reflecting arterial baroreflex control of heart rate: the baroreflex sensitivity (BRS) and the baroreflex effectiveness index (BEI). Twenty-one patients fainted before nitrate administration (HUT+) and 37 after nitrate administration (NTG+). Immediately before syncope, the NTG+ patients showed significantly lower BRS values than those observed at the end of the test in the patients without syncope (5.5 ± 2.8 vs. 7.7 ± 3.4 ms/mmHg; P = 0.004) and a significantly lower BEI (30 ± 20% vs. 53 ± 24%; P < 0.001). The HUT+ patients did not show any significant differences in BRS and BEI before syncope from the values observed during the corresponding tilt period in the other groups. Conclusion A significant depression in BRS and BEI occurs immediately before syncope in patients who faint after nitrate administration, thus suggesting that arterial baroreflex dysfunction plays a role in mediating nitrate-induced VVS.

Background and aims The greatest decrease in mortality from cardiovascular disease (CAD) that can be achieved with 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) is seen in patients with the highest risk for CAD, such as diabetics. Yet, there is evidence for inadequate use of drug therapies to achieve lipid goals. Our aims were to: (1) assess the prevalence of statin use in patients attending diabetic clinics and (2) correlate the use of statins with their risk and clinical status. Methods and results Of 9921 patients included, only 20.4% of them were receiving statin therapy. Statins were more progressively prescribed in those with risk factors additional to that of diabetes. Patients under statin treatment were older, mostly type 2 diabetics, more hypertensive and hyperlipidemic, had a higher prevalence of both macro- and microvascular disease. Among those with a total cholesterol concentration above 252 mg/dl, statin treatment was given only to 60% of diabetic patients with prior myocardial infarction, 56% of those with angina, 66% of those having had prior revascularization procedure, 54% of those with cerebrovascular disease and 51% of those with peripheral artery disease. Conclusions At least in Italy, statins are not prescribed to the majority of diabetic patients, and a substantial proportion of patients not treated with statins present significant macro- and microvascular complications.

Background and Purpose— Prediction of functional outcome after stroke rehabilitation (SR) is a growing field of interest. The association between SR and survival still remains elusive. We sought to investigate the factors associated with functional outcome after SR and whether the magnitude of functional improvement achieved with rehabilitation is associated with long-term mortality risk. Methods— The study population consisted of 722 patients admitted for SR within 90 days of stroke onset, with an admission functional independence measure (FIM) score of Results— Age ( P P =0.003), time from stroke onset to rehabilitation admission ( P P P =0.021) were independently associated with FIM gain. The R 2 of the model was 0.275. During a median follow-up of 6.17 years, 36.9% of the patients died. At multivariable Cox analysis, age ( P P =0.018), atrial fibrillation ( P =0.042), total cholesterol ( P =0.015), and total FIM gain ( P Conclusions— Several factors are independently associated with functional gain after SR. Our findings strongly suggest that the magnitude of functional improvement is a powerful predictor of long-term mortality in patients admitted for SR.

Background The first few months after admission are the most vulnerable period in patients with acute decompensated heart failure (ADHF). Methods and results We assessed the association of the updated ADHF/N-terminal pro-B-type natriuretic peptide (NT-proBNP) risk score with 90-day and in-hospital mortality in 701 patients admitted with advanced ADHF, defined as severe symptoms of worsening HF, severely depressed left ventricular ejection fraction, and the need for i.v. diuretic and/or inotropic drugs. A total of 15.7% of the patients died within 90 days of admission and 5.2% underwent ventricular assist device (VAD) implantation or urgent heart transplantation (UHT). The C-statistic of the ADHF/NT-proBNP risk score for 90-day mortality was 0.810 (95% CI: 0.769-0.852). Predicted and observed mortality rates were in close agreement. When the composite outcome of death/VAD/UHT at 90 days was considered, the C-statistic decreased to 0.741. During hospitalization, 7.6% of the patients died. The C-statistic for in-hospital mortality was 0.815 (95% CI: 0.761-0.868) and Hosmer-Lemeshow χ(2)=3.71 (P=0.716). The updated ADHF/NT-proBNP risk score outperformed the Acute Decompensated Heart Failure National Registry, the Organized Program to Initiate Lifesaving Treatment in Patients Hospitalized for Heart Failure, and the American Heart Association Get with the Guidelines Program predictive models. Conclusions Updated ADHF/NT-proBNP risk score is a valuable tool for predicting short-term mortality in severe ADHF, outperforming existing inpatient predictive models.

Objective: To evaluate the role of brain natriuretic peptide (BNP) in predicting the progression of heart failure (HF) after cardiac resynchronization therapy (CRT). Background: It has been shown that BNP predicts the prognosis and can guide the treatment of HF. Methods: We studied 50 consecutive patients (61±10 years, 23 male) with HF (8 with ischaemic cardiomyopathy), NYHA class III, left bundle branch block, left ventricular ejection fraction (LVEF) ≤35% (mean 24±6%) who underwent CRT. All patients were taking conventional HF therapy and were clinically stable. Plasma BNP levels were evaluated by two-site dual-monoclonal immunochemiluminescent assay before, and 1 month after CRT. The predictive value of BNP was assessed using univariate and multivariate regression analyses. Results: During follow-up (mean 19±12 months), HF progression was observed in 14 patients (11 were hospitalised and 3 died after worsening of HF). Multivariate analysis showed that BNP levels before (HR: 2.07; CI: 1.19–3.62; p=0.01) and 1 month after CRT (HR: 2.23; CI: 1.26–3.94; p=0.006) were significantly related to events. At 1 month, a BNP level >91.5 pg/ml had 89% sensitivity, 59% specificity, and negative and positive predictive values of 96% and 33%, respectively, for HF progression after 12 months. Conclusions: HF patients with high BNP values after 1 month of CRT have worse prognosis during follow-up. Therefore, in these patients other therapeutic options should be considered.

BACKGROUND The offspring of hypertensive families are characterized by higher arterial blood pressure values and a depressed autonomic control of heart rate. The present study aimed to verify whether these differences are associated with a different genotype distribution of functionally relevant polymorphisms of the alpha- and beta-adrenergic receptor (AR) genes. METHODS We selected 109 age- and sex-matched young normotensive subjects with (FH+, n = 56) and without (FH-, n = 53) a family history of hypertension who underwent evaluation of arterial pressure; 24-h electrocardiogram monitoring to assess time-domain parameters of autonomic heart rate control [i.e. mean RR interval (NN), SD of RR intervals (SDNN) and mean square root of the differences of consecutive RR intervals (rMSSD)]; spectral baroreflex sensitivity measurement; and echo-Doppler to assess diastolic function and left ventricular mass. They were also characterized for the following polymorphisms by means of polymerase chain reaction-restriction fragment polymorphism analysis: Arg492Cys in the alpha1a-AR; Del301-303 in the alpha2b-AR; Ser49Gly and Arg389Gly in the beta1-AR; and the 5' leader cistron Arg19Cys, Arg16Gly and Gln27Glu in the beta2-AR. RESULTS FH+ individuals showed a higher systolic pressure, a lower SDNN and a greater isovolumic relaxation time compared to normotensive offspring. No differences were found between the two groups when genotype distribution of the studied polymorphisms was considered. Subjects carrying alpha1a-AR Cys492 allelic variant showed lower values of NN, SDNN and rMSSD, independent of age, gender and body mass index. CONCLUSIONS The functionally relevant polymorphisms of alpha2b-, beta1- and beta2-AR genes are not associated with a family history of essential hypertension. The Arg492Cys polymorphism of the alpha1a-AR gene, although not associated with a family history of hypertension, was strongly related to autonomic control of heart rate.