Claudia Loardi

EuroSCORE performance in valve surgery: a meta-analysis.

BACKGROUND The European System for Cardiac Operative Risk Evaluation (EuroSCORE) was developed to predict immediate outcomes after adult cardiac operations, but less than 30% of the cases used to develop this score were valve procedures. We studied EuroSCORE performance in valve procedures. METHODS We performed a meta-analysis of published studies reporting the assessment of discriminatory power of the EuroSCORE by receiver operating characteristics (ROC) curve analysis in adult valve operations. A comparison of observed and predicted mortality rates was also performed. RESULTS A literature search identified 37 potentially eligible studies, and 12 were selected for meta-analysis comprising 26,621 patients with 1250 events (mortality rate, 4.7%). Meta-analysis of these studies provided an average area under the curve (AUC) value of 0.730 (95% confidence interval [CI], 0.717 to 0.743). The same results were obtained when meta-analyses were performed separately in studies categorized on reliability of uncertainty estimation: in the seven studies reporting reliable uncertainty estimation (8175 patients with 358 events; mortality rate, 4.4%), the ROC curve provided an average AUC value of 0.724 (95% CI, 0.699 to 0.749). The five studies not reporting reliable uncertainty estimation (18,446 patients with 892 events; mortality rate, 4.8%) had an average AUC of 0.732 (95% CI, 0.717 to 0.747). We documented a constant trend to overpredict mortality by EuroSCORE, both in the additive and especially in the logistic form. CONCLUSIONS The EuroSCORE has low discrimination ability for valve surgery, and it sensibly overpredicts risk. Alternative risk scoring algorithms should be seriously considered.

Very Long-Term Outcomes of the Carpentier-Edwards Perimount Valve in Aortic Position

BACKGROUND The Carpentier-Edwards Perimount pericardial bioprosthesis (Edwards Lifesciences, Irvine, CA) has demonstrated good long-term outcomes, but its durability remains unclear depending on age at implantation. We report our 20-year experience with the Perimount valve implanted in the aortic position, with particular attention to the probability and time to reoperation required due to bioprosthesis deterioration. METHODS From 1984 to 2008 at our center, 2,659 patients (mean age, 70.7 ± 10.4 years) underwent aortic valve replacement using the Perimount pericardial bioprostheses. Patients were prospectively followed on an annual basis (mean 6.7 ± 4.8 years, range 0 to 24.6 years) with an echocardiogram at the time of follow-up. Cumulative follow-up was 18,404 valve-years. Bioprosthesis structural valve deterioration was determined by strict echocardiographic assessment. RESULTS Overall operative mortality was 2.8%. Actuarial survival rates including early deaths averaged 52.4% ± 1.2%, 31.1% ± 1.4%, and 14.4% ± 1.7% after 10, 15, and 20 years of follow-up, respectively. Age-stratified freedom from reoperation due to structural valve deterioration at 15 and 20 years was 70.8% ± 4.1% and 38.1% ± 5.6%, respectively, for the group aged 60 years or less, 82.7% ± 2.9% and 59.6% ± 7.6% for those 60 to 70 years, and 98.1% ± 0.8% at 15 years and above for the oldest group. Expected valve durability is 19.7 years for the entire cohort. CONCLUSIONS With a low rate of valve-related events at 20 years, and particularly a low rate of structural valve deterioration, the Carpentier-Edwards Perimount pericardial bioprosthesis remains a reliable choice for a tissue valve in the aortic position, especially in patients over 60 years of age.

Performance of EuroSCORE in CABG and off-pump coronary artery bypass grafting: Single institution experience and meta-analysis

AIMS To assess EuroSCORE performance in predicting in-hospital mortality in on-pump coronary artery bypass grafting (CABG) and off-pump coronary artery bypass grafting (OPCAB). METHODS AND RESULTS Additive and logistic EuroSCORE were computed for consecutive patients undergoing CABG (n = 3440, 75%) or OPCAB (n = 1140, 25%) at our hospital from 1999 to September 2007. The areas under the receiver operating characteristic (ROC) curves (AUCs) were used to describe performance and accuracy. No difference in performance between CABG and OPCAB and between additive and logistic EuroSCORE (additive EuroSCORE AUCs of 0.808 and 0.779 for CABG and OPCAB, respectively; logistic EuroSCORE AUCs of 0.813 and of 0.773 for CABG and OPCAB, respectively) was found, although a marked tendency to overpredict mortality by both models was evident. A meta-analysis of previously published data was done, and a total of eight studies representing 19 212 and 5461 patients undergoing CABG and OPCAB, respectively, met inclusion criteria. Meta-analysis confirmed similar performance of EuroSCORE in CABG and OPCAB: estimated AUCs were 0.767 and 0.766 for CABG and OPCAB, respectively, with an estimated difference of 0.001 (95% CI -0.061 to 0.063). CONCLUSION Additive and logistic EuroSCORE algorithms performed similarly, and cumulative evidence suggests comparable performance in CABG and OPCAB procedures; both risk models, however, significantly overestimated mortality.

Nonrheumatic calcific aortic stenosis: an overview from basic science to pharmacological prevention

Calcific aortic stenosis is a frequent degenerative disease, which represents the most common indication for adult heart valve surgery, and carries substantial morbidity and mortality. Due to ageing populations in western countries, its prevalence is expected to increase in the coming years. Basic science studies suggest that the progression of aortic valve stenosis involves an active biological process, and that the molecular mechanisms promoting this development resemble those of atherosclerosis, as stenotic aortic valves are characterized by complex histological lesions, consisting of activated inflammatory cells, lipid deposits, extracellular matrix remodeling, calcific nodules, and bone tissue. This has led to the hypothesis that drugs effective in delaying atherosclerosis progression (e.g. statins) might also be able to prevent the progression of calcific aortic valve stenosis. The potential benefit of statin therapy, however, is controversial and widely debated, as recent randomized studies done in patients with moderate to severe degrees of aortic stenosis failed to consistently show substantial benefits of this class of drugs. This review focuses on various aspects of molecular mechanisms underlying calcific aortic valve stenosis and discusses recent experimental and clinical studies that address the potential benefit of targeted drug therapies. Taken together, current evidence suggests that the progression of calcific aortic stenosis is a multi-factorial process; the multitude of the mechanisms potentially involved in aortic valve stenosis indicates that drug therapy aimed at reducing its progression is necessarily multi-factorial and should address the earliest stages of the disease, as it is now evident that pharmacological treatment administered in more advanced stages of the disease may be ineffective or, at best, much less effective.

Inflammatory Activation During Coronary Artery Surgery and Its Dose-Dependent Modulation by Statin/ACE-Inhibitor Combination

Background—On-pump coronary artery bypass graft (CABG) surgery triggers an inflammatory response (IR) which may impair revascularization. The study aimed at (1) characterizing the temporal profile of the IR by assaying appropriate markers in both systemic and coronary blood, and (2) determining whether (and which doses of) cardiovascular drugs known to have antiinflammatory properties, namely statins and ACE-inhibitors (ACEI), inhibit the response. Methods and Results—Patients scheduled for CABG (n=22) were randomized to statin/ACEI combination treatment at standard doses (STD, ramipril 2.5/simvastatin 20 mg, or atorvastatin 10 mg), or at high doses (HiDo, ramipril 10 mg, or enalapril 20 mg/simvastatin 80 mg, or atorvastatin 40 mg). Plasma levels of interleukin 6, tumor necrosis factor alpha, E-selectin, von Willebrand factor (vWF), and sVCAM-1 were serially assayed (ELISA) before, during, and after CABG. Blood was drawn from an artery, a systemic vein, and the coronary sinus. Myocardial perfusion scans were obtained before and 2 months after surgery in 19 out of 22 subjects. In the STD group both IL-6 and TNF displayed striking increases which were similar at all sites and peaked 10 to 60 minutes after aortic declamping. Such increases were drastically attenuated in the HiDo group. Instead, only modest increases in venous E-selectin, vWF, and sVCAM-1 were observed. Scintigraphic ischemia scores were entirely normalized after versus before CABG in the HiDo but not in the STD treatment group. Conclusions—On-pump CABG surgery is associated with an intense systemic inflammatory response, which can be almost completely prevented by early treatment with high (but not standard) doses of ACE-inhibitors and statins.

Do statins improve outcomes and delay the progression of non-rheumatic calcific aortic stenosis?

Context It is not known whether statin treatment improves clinical outcomes and reduces aortic stenosis progression in non-rheumatic calcific aortic stenosis. Objective A meta-analysis of studies was performed comparing statin therapy with placebo or no treatment on outcomes and on aortic stenosis progression echocardiographic parameters. Data sources The authors searched Medline and Pubmed up to January 2010. Data extraction Two independent reviewers independently abstracted information on study design (prospective vs retrospective or randomised vs non-randomised), study and participant characteristics. Fixed and random effects models were used. A-priori subanalyses assessed the effect of statins on low-quality (retrospective or non-randomised) and on high-quality (prospective or randomised) studies separately. Results Meta-analysis identified 10 studies with a total of 3822 participants (2214 non-statin-treated and 1608 statin-treated); five studies were classified as prospective and five as retrospective; concerning randomisation, three trials were randomised whereas seven were not. No significant differences were found in all-cause mortality, cardiovascular mortality or in the need for aortic valve surgery. Lower-quality (retrospective or non-randomised) studies showed that, in statin-treated patients, the annual increase in peak aortic jet velocity and the annual decrease in aortic valve area were lower, but this was not confirmed by the analysis in high-quality (prospective or randomised) studies. Statins did not significantly affect the progression over time of peak and mean aortic gradient. Conclusions Currently available data do not support the use of statins to improve outcomes and to reduce disease progression in non-rheumatic calcific aortic valve stenosis.

Very long-term outcomes of the Carpentier-Edwards Perimount aortic valve in patients aged 50–65 years

OBJECTIVES Aortic valve replacement (AVR) using a bioprosthesis remains controversial for patients aged 50-65 years. This cohort study reports the very long-term outcomes of AVR using Carpentier-Edwards Perimount pericardial bioprosthesis in this age group. METHODS From 1984 to 2008, 522 Carpentier-Edwards Perimount pericardial aortic bioprostheses were implanted in 516 patients aged 50-65 years (mean age, 60 ± 4 years; 19% female). Multiple valve replacements were excluded fro m our cohort. Baseline demographic, perioperative and follow-up data were recorded prospectively. Mean follow-up was 9 ± 6 years, for a total of 4428 valve-years. Follow-up was complete for 97% of patients included. RESULTS Operative mortality rate was 2%. One hundred and forty-six late deaths occurred for a linearized rate of 3%/valve-year. Actuarial survival rates averaged 73 ± 2, 59 ± 3 and 35 ± 5% after 10, 15 and 20 years of follow-up, respectively. Mortality rate associated with reoperation was 2%. Actuarial freedom from reoperation rates due to structural valve deterioration (SVD) at 10, 15 and 20 years was respectively of 91 ± 2, 76 ± 3 and 50 ± 6%. Competing risk analysis demonstrated an actual risk of explantation secondary to SVD at 20 years of 30 ± 3%. Expected valve durability was 19 years for this age group. Age was not a significant risk factor for SVD in this middle-aged population. CONCLUSIONS In patients aged 50-65 years undergoing AVR with the Carpentier-Edwards Perimount bioprosthesis, the expected valve durability was 19 years. Age was not a significant risk factor for SVD within this age group. Patient selection and attention to timing of reintervention may be determinants of long-term outcomes.

Do Women Currently Receive the Same Standard of Care in Coronary Artery Bypass Graft Procedures as Men? A Propensity Analysis

BACKGROUND The purpose of this study was to determine whether, in recent years, sex differences in the type of care during coronary artery bypass graft surgery procedures occurred. METHODS Between 1995 and 2004, 5,935 consecutive patients (4,867 men and 1,068 women) underwent isolated coronary artery bypass graft surgery; propensity score matching was used to investigate whether sex adversely impacts standard care and early outcomes of coronary revascularization. RESULTS Of the 1,068 women undergoing isolated coronary artery bypass graft surgery, only 280 (26.2%) were matched on propensity scores with men. Distribution of preoperative variables among matched pairs was, on average, equal. Propensity-matched women received similar number of distal anastomoses as men (2.70 +/- 0.89 versus 2.82 +/- 0.97; p = 0.13), had similar rates of complete revascularization (82.5% versus 81.6%; p = 0.78), and of off-pump procedures (24.3% versus 27.5%; p = 0.39); also, the rate of utilization of arterial grafts (left internal mammary artery 98.5% versus 98.2%; p = 0.73; right internal mammary artery 3.2% versus 3.2%; p > 0.99; radial artery 8.2% versus 9.6%; p = 0.55), as well as the number of distal anastomoses performed with arterial grafts (1.11 +/- 0.36 versus 1.13 +/- 0.39; p = 0.47), were similar in women and men. No differences were detected in major complications (in-hospital mortality, perioperative myocardial infarction, and stroke) in propensity-matched pairs, whereas women had lower reexploration for bleeding and blood transfusion rates. CONCLUSIONS The preoperative profiles of women and men were markedly different, as only one fourth of women could be matched. In the current era, after adjustment for preoperative variables, female patients received the same standard of care as men, with improved results in some minor early outcomes.

Proteomic analysis of plasma from patients undergoing coronary artery bypass grafting reveals a protease/antiprotease imbalance in favor of the serpin alpha1-antichymotrypsin.

We used proteomics to identify systematic changes in the plasma proteins of patients undergoing coronary artery bypass grafting (CABG) by means of cardiopulmonary bypass surgery. It is known that, after CABG, a complex systemic inflammatory responses ensues that favors the occurrence of adverse postoperative complications frequently recognizing inflammation itself and/or thrombosis as the underlying mechanism. We found a marked and persistent postoperative increase in the levels of the serpin-protease inhibitor alpha(1)-antichymotrypsin (alpha(1)-ACT) that fully maintains the inhibitory activity blunting its protease substrate cathepsin G. An intraoperative increase followed by a rapid decline in proteases activation was documented, accompanied by a substantial induction of leucine-rich-alpha-2-glycoprotein, a protein involved in neutrophilic granulocyte differentiation. Finally, a time-dependent alteration in the expression of haptoglobin, transthyretin, clusterin, and apoE was observed. In conclusion, we showed that after CABG, a protease/antiprotease imbalance occurs with early cathepsin G activation and a more delayed increase in alpha(1)-ACT. As cathepsin G is a serpin involved both in inflammation and coagulation activation, this confirms and expands the concept of a marked dysregulation of both inflammatory and hemostatic balances occurring after CABG. The pharmacologic modulation of this imbalance may be a new therapeutic target to reduce postoperative complications.

Postoperative Echocardiographic Reduction of Right Ventricular Function: Is Pericardial Opening Modality the Main Culprit?

Echocardiographic reduction of RV function, measured using TAPSE, is a well described phenomenon after cardiac surgery. The aim of the present study was to investigate the relation between the modality of pericardial opening (lateral versus anterior) and the postoperative right ventricular systolic function by comparing echocardiographic parameters in patients undergoing minimally invasive or traditional mitral valve repair. 34 patients with severe mitral regurgitation due to mitral valve prolapse underwent traditional (sternotomy) operation (Group A) or minimally invasive surgery with right anterolateral thoracotomy (Group B). A postoperative TAPSE fall was found in both groups. Group A experienced a significant postoperative TAPSE fall versus Group B with p < 0.0001.