Serenella Castelvecchio

Risk of assessing mortality risk in elective cardiac operations: age, creatinine, ejection fraction, and the law of parsimony.

Background— Several mortality risk scores exist in cardiac surgery. All include a considerable number of independent risk factors. In elective cardiac surgery patients, the operative mortality is low, the number of events recorded per year is limited, and the risk model may be overfitted. The present study aims to develop and validate an operative mortality risk score for elective patients based on a limited number of factors. Methods and Results— The development series included 4557 adult patients who had undergone an elective cardiac operation at our institution from 2001 to 2003; the validation series includes the 4091 patients who subsequently underwent an operation. Three independent factors were included in the mortality risk model: age, creatinine, and left ventricular ejection fraction (ACEF). The ACEF score was computed as follows: age (years)/ejection fraction (%)+1 (if serum creatinine value was >2 mg/dL). The ACEF score was compared with 5 other risk scores in the validation series. Discriminatory power (accuracy) was defined with a receiver-operating characteristics analysis. The best accuracy was achieved by the Cleveland Clinic score (0.812), with ACEF score just below it (0.808). In coronary operations, the 2 scores performed equally well (0.815 versus 0.813), and in isolated coronary operations, the best accuracy was achieved by ACEF (0.826), with the Cleveland Clinic score at 0.806. Conclusion— A risk model limited to 3 independent predictors has similar or better accuracy and calibration compared with more complex risk scores if applied to elective cardiac operations.

MicroRNA Dysregulation in Diabetic Ischemic Heart Failure Patients

Increased morbidity and mortality associated with ischemic heart failure (HF) in type 2 diabetic patients requires a deeper understanding of the underpinning pathogenetic mechanisms. Given the implication of microRNAs (miRNAs) in HF, we investigated their regulation and potential role. miRNA expression profiles were measured in left ventricle biopsies from 10 diabetic HF (D-HF) and 19 nondiabetic HF (ND-HF) patients affected by non–end stage dilated ischemic cardiomyopathy. The HF groups were compared with each other and with 16 matched nondiabetic, non-HF control subjects. A total of 17 miRNAs were modulated in D-HF and/or ND-HF patients when compared with control subjects. miR-216a, strongly increased in both D-HF and ND-HF patients, negatively correlated with left ventricular ejection fraction. Six miRNAs were differently expressed when comparing D-HF and ND-HF patients: miR-34b, miR-34c, miR-199b, miR-210, miR-650, and miR-223. Bioinformatic analysis of their modulated targets showed the enrichment of cardiac dysfunctions and HF categories. Moreover, the hypoxia-inducible factor pathway was activated in the noninfarcted, vital myocardium of D-HF compared with ND-HF patients, indicating a dysregulation of the hypoxia response mechanisms. Accordingly, miR-199a, miR-199b, and miR-210 were modulated by hypoxia and high glucose in cardiomyocytes and endothelial cells cultured in vitro. In conclusion, these findings show a dysregulation of miRNAs in HF, shedding light on the specific disease mechanisms differentiating diabetic patients.

Major bleeding, transfusions, and anemia: the deadly triad of cardiac surgery.

BACKGROUND Postoperative bleeding is common after cardiac surgery. Major bleeding (MB) is a determinant of red blood cell (RBC) transfusion, especially in patients with preoperative anemia. Preoperative anemia and RBC transfusions are recognized risk factors for operative mortality. The present study investigates the role of MB as an independent determinant of operative mortality in cardiac surgery. METHODS A single-center retrospective study based on the institutional database of cardiac surgery in the period 2000-2012 was conducted. Sixteen thousand one hundred fifty-four (16,154) consecutive adult patients undergoing cardiac surgery were analyzed. The impact of postoperative bleeding and MB on operative (30 days) mortality was analyzed univariately and after correction for preoperative anemia, RBC transfusions, and other confounders. RESULTS Postoperative bleeding was significantly (p < 0.001) associated with operative mortality, both in univariate and multivariable models. The main complications associated with MB were thromboembolic complications, infections, and surgical reexploration. In a multivariable model, MB remained an independent predictor of operative mortality (odds ratio, 3.45; 95% confidence interval, 2.78 to 4.28). Preoperative anemia and RBC transfusions coexist in the model, acting with a multiplying effect when associated with MB. CONCLUSIONS Major bleeding is per se a risk factor for operative mortality. However, its deleterious effects are strongly enhanced by RBC transfusions and, to a lesser extent, preoperative anemia. Major bleeding is a partially modifiable risk factor, and adequate preemptive and treatment strategies should be applied to limit this event.

Clinical efficacy of ivabradine in patients with inappropriate sinus tachycardia: a prospective, randomized, placebo-controlled, double-blind, crossover evaluation.

OBJECTIVES The purpose of this study was to investigate the role of ivabradine in the treatment of symptomatic inappropriate sinus tachycardia using a double-blind, placebo-controlled, crossover design. BACKGROUND Due to its I(f) blocking properties, ivabradine can selectively attenuate the high discharge rate from sinus node cells, causing inappropriate sinus tachycardia. METHODS Twenty-one patients were randomized to receive placebo (n=10) or ivabradine 5 mg twice daily (n=11) for 6 weeks. After a washout period, patients crossed over for an additional 6 weeks. Each patient underwent symptom evaluation and heart rate assessment at the start and finish of each phase. RESULTS After taking ivabradine, patients reported elimination of >70% of symptoms (relative risk: 0.25; 95% CI: 0.18 to 0.34; p<0.001), with 47% of them experiencing complete elimination. These effects were associated with a significant reduction of heart rate at rest (from 88±11 beats/min to 76±11 beats/min, p=0.011), on standing (from 108±12 beats/min to 92±11 beats/min, p<0.0001), during 24 h (from 88±5 beats/min to 77±9 beats/min, p=0.001), and during effort (from 176±17 beats/min to 158±16 beats/min, p=0.001). Ivabradine administration was also associated with a significant increase in exercise performance. No cardiovascular side effects were observed in any patients while taking ivabradine. CONCLUSIONS In this cohort, ivabradine significantly improved symptoms associated with inappropriate sinus tachycardia and completely eliminated them in approximately half of the patients. These findings suggest that ivabradine may be an important agent for improving symptoms in patients with inappropriate sinus tachycardia.

Hematocrit on Cardiopulmonary Bypass and Outcome After Coronary Surgery in Nontransfused Patients

BACKGROUND Preoperative anemia and the lowest registered hematocrit value on cardiopulmonary bypass are recognized risk factors for morbidity and mortality after coronary operations. A low hematocrit often results in blood transfusions with all of the associated possible complications. The relative contribution of these three factors to long-term outcome is still not well established. This study aimed to identify the role of preoperative anemia and hemodilution during cardiopulmonary bypass as determinants of morbidity and mortality after coronary operations. METHODS A consecutive series of 3,003 patients was analyzed. They had all undergone isolated coronary operations without receiving blood transfusions during their hospital stay. The preoperative hematocrit and the lowest hematocrit on cardiopulmonary bypass were analyzed in a multivariable model as predictors of major morbidity and operative mortality. RESULTS After adjustment for the other explanatory variables, both the preoperative hematocrit and the lowest hematocrit on cardiopulmonary bypass were found to be independent risk factors for major morbidity, but not for operative mortality. However, low values of preoperative hematocrit were not associated with an increased morbidity, provided that the lowest hematocrit on cardiopulmonary bypass was maintained above 28%. Median values of the lowest hematocrit on cardiopulmonary bypass below 25% were associated with an increased major morbidity rate. CONCLUSIONS Excessive hemodilution during cardiopulmonary bypass is a risk factor for major morbidity even in the absence of blood transfusions. Techniques that aim to reduce the fall in hematocrit during cardiopulmonary bypass, including blood cardioplegia, may be useful, especially in patients with a low preoperative hematocrit.

End-systolic volume following surgical ventricular reconstruction impacts survival in patients with ischaemic dilated cardiomyopathy

A left ventricular end‐systolic volume (LVESV) ≥60 mL/m2 has been shown to be associated with increased cardiac mortality after a reperfused myocardial infarction (MI). The reduction in LVESV following surgical ventricular reconstruction (SVR) is reported to be between 19% and 50% but its impact on prognosis is not well‐established. The aim of this study was therefore to assess the impact on survival of a residual LVESV index (LVESVI) of ≥ or <60 mL/m2 following SVR.

Impact of preoperative anemia on outcome in adult cardiac surgery: a propensity-matched analysis.

BACKGROUND Preoperative anemia is not considered an operative mortality risk factor by the majority of the risk stratification tools used in cardiac surgery. However, retrospective studies have found associations between preoperative anemia and morbidity and mortality in cardiac operations. The present study compares the postoperative outcome of a group of moderate-to-severe anemic patients with a propensity-matched group of nonanemic patients undergoing cardiac operations. METHODS This is a retrospective study based on 17,056 consecutive patients included in our Institutional Database. A total of 13,843 adult patients with preoperative hematocrit value available were selected for this study; 401 patients had a severe anemia (hematocrit<30%). From the remaining patients, a control group of 401 non-severely anemic patients was selected with a propensity-based matching. Postoperative morbidity and mortality were compared between the 2 groups. RESULTS The 2 groups were comparable for preoperative comorbidities and operative details. Anemic patients had a significantly (p=0.045) higher rate of stroke (1% vs 0%), major morbidity (27.4% vs 17.5%, p=0.001), and a significantly higher (0.014) operative mortality rate (12.7% vs 7.5%). An additional analysis, inclusive of patients with moderate preoperative anemia, confirmed these results. CONCLUSIONS Moderate-to-severe preoperative anemia is a risk factor for major morbidity and operative mortality in adult cardiac operations. This finding is confirmative of the role of preoperative anemia in determining adverse events in major noncardiac operations. The exclusion of preoperative anemia from the existing risk scores is probably a statistical consequence of the associated comorbid conditions that confound the specific role of anemia as a risk factor.

Accuracy, calibration and clinical performance of the new EuroSCORE II risk stratification system

OBJECTIVES The European System for Cardiac Operative Risk Evaluation (EuroSCORE) has been used for many years since its introduction in 1999. Recently, a new EuroSCORE (EuroSCORE II) has been developed to update the previous version. The EuroSCORE II includes some different predictors and/or introduces a new classification of the already existing predictors. This study presents a validation series for the EuroSCORE II compared with the previous additive and the logistic EuroSCORE and with the Age, Creatinine and Ejection Fraction (ACEF) score. METHODS A total of 1090 consecutive adult patients operated on at our institution from September 2010 to October 2011 were admitted to this retrospective study. All the patients received a risk stratification based on the EuroSCORE II and the other scores considered. Accuracy, calibration and clinical performance of the various risk models were assessed. RESULTS The accuracy of the EuroSCORE II was good (c-statistic 0.81) but not significantly higher than the other scores (range 0.78-0.8). Calibration at the Hosmer-Lemeshow statistic was good for all the scores; the difference between observed (3.75%) and predicted mortality in the overall population was not significant for the EuroSCORE II (3.1%) and the ACEF score (3.4%), whereas the additive EuroSCORE (5.8%) and the logistic EuroSCORE (7.3%) significantly overestimated the risk. In patients at low, mild moderate and high mortality risk, the EuroSCORE II provided a risk prediction not significantly different from the observed mortality rate, whereas in very high-risk patients (observed mortality rate 11%), it significantly underestimated (6.5%) the mortality risk. The accuracy of the EuroSCORE II was acceptable in isolated coronary surgery, and good or excellent in the other operations. CONCLUSIONS The EuroSCORE II represents a useful update of the previous EuroSCORE version, with a much better clinical performance and the same good level of accuracy. It is possible that for the risk stratification of very high-risk patients, other factors (rare but associated with a mortality rate >50%) should be included in the future models.

Functional ischemic mitral regurgitation in anterior ventricular remodeling : Results of surgical ventricular restoration with and without mitral repair

Ischemic functional mitral regurgitation following ischemic cardiomyopathy is a secondary phenomenon to ventricular dilation, and therapeutic approaches to this complication are not uniform. Solutions to improve mitral function include either mitral repair or observing the effects of coronary revascularization and/or ventricular rebuilding during surgical ventricular restoration (SVR).The present study of 108 patients (comprising 18% of our 588 SVR population) reports the effects of mitral repair following SVR and CABG by comparing geometric, functional, hemodynamic and outcome changes to SVR patients without mitral repair. The degree of mitral regurgitation went from 2.9 ± 1.2 before to 0.7 ± 0.7 after SVR and mitral repair. SVR improved EF from 29 ± 7% to 34 ± 10% p 0.001; reduced end diastolic volume from 243 ± 74 to 163 ± 53 ml and end systolic volume from 170 ± 63 to 107 ± 41 ml, p 0.000. Ventricular size and shape geometric measurements improved in all patients, either with and without mitral repair. SVR improved tenting and papillary muscle width between muscle heads in all patients, but alterations in mitral annular size improved only following mitral repair.Preoperative mitral regurgitation occurred in patients with larger ventricular volume and lower ejection fraction and was an independent predictor of operative mortality risk.

Surgical ventricular restoration: left ventricular shape influence on cardiac function, clinical status, and survival.

BACKGROUND Myocardial infarction can result in a spectrum of left ventricular (LV) shape abnormalities. Surgical ventricular restoration (SVR) can be applied to any, but there are no data that relate its effectiveness to LV shape. Moreover, there is no consensus on the benefit of SVR in patients with a markedly dilated ventricle, without clear demarcation between scarred and normal tissue. This study describes postmyocardial infarction shape abnormalities and cardiac function, clinical status, and survival in patients undergoing SVR. METHODS Echo studies of 178 patients were retrospectively reviewed. Three types of LV shape abnormalities were identified: type 1 (true aneurysm), type 2 (nonaneurysmal lesions defined as intermediate cardiomyopathy), and type 3 (ischemic dilated cardiomyopathy). RESULTS SVR induced significant improvement in cardiac and clinical status in all patients, regardless LV shape types. Although not significant, mortality was higher in types 2 and 3. CONCLUSIONS Ischemic dilated cardiomyopathy and not just the true aneurysm can be successfully treated with SVR. Shape classification may be useful to improve patient selection and compare results from different institutions that are otherwise impossible to compare.