Comparative application of multivariate models developed in Italy and Europe to predict early (28 days) and late (1 year) postoperative death after on- or off-pump coronary artery bypass grafting.

OBJECTIVES: The aim of this study was to compare the risk of death predictive performances of the OP-RISK, EuroSCORE, and Italian coronary artery bypass grafting (CABG) Outcome studies' functions when applied to a southern Italian cardiac surgery center (Sant'Anna hospital in Catanzaro [SAHCZ]), which contributed data to the Italian CABG Outcome study, and to see if this predictive index may be applied to on- and off-pump interventions. METHODS: The OP-RISK study data set was used to derive Weibull and logistic functions to predict early (28 days) and late (1 year) death rates following CABG based on ejection fraction, heart rate, age, and aortic cross-clamping time. Then the data of 385 CABG patients who underwent operations in 2003 in SAHCZ were collected with 1-year follow-up data, which also included data used to obtain EuroSCORE and Italian CABG Outcome study risk indices. RESULTS: Short- and long-term observed mortality rates after CABG were 2.59% and 5.88% in the SAHCZ series, largely dependent on whether CABG was alone (1.26% and 3.55%) or associated with ventriculoplasty (4.87% and 10.81%) or valve surgery (15.38% and 28.57%). There was a significant increasing trend (P = .002) of observed death rates in equinumeric tertiles of either OP-RISK (both Weibull and logistic) or EuroSCORE in the short term, whereas the trend was not significant for the Italian CABG Outcome study index. OP-RISK functions were significantly predictive for the long term (P < .005), as well as when only ejection fraction, heart rate, and age were considered (P < .011). CONCLUSIONS: It is essential to use clinical data following CABG when outcome prediction is concerned. OP-RISK and EuroSCORE indices are equally predictive in our experience, and a statistically significant (P = 0.02) difference was observed with the Italian CABG Outcome study index, whose trend in tertiles of calculated risk was not apparent, which is unexpected and unexplained. OP-RISK functions were adequate for long-term prediction. Since aortic cross-clamping time may be absent from tested predictive functions (for both short and long term), off-pump CABG mortality may also be predicted as similar to on-pump intervention mortality.

Dobutamine effects on spontaneous variability of ventricular arrhythmias in patients with severe chronic heart failure: the Italian Multicenter Study.

BACKGROUND: Dobutamina Studio Italiano Multicentrico (Do.S.I.M.) is a prospective, randomized, multicenter interuniversity Italian study aimed at assessing the effects of dobutamine on spontaneous variability of ventricular arrhythmias in sinus rhythm NYHA class III-IV patients with congestive heart failure (CHF). METHODS: Out of 74 pre-hoc estimated CHF patients, 68 (92%) were randomized electively to either being washed out of all active drugs except diuretics (group A) or to continue with the standard regimen including digitalis, diuretics and ACE-inhibitors (group B, standard therapy). In 63 patients, complete Holter data were obtained and are reported here. After 72 hours, in both groups, 48-hour Holter monitoring (Holter 1) was performed. The spontaneous variability of ventricular arrhythmias was assessed by calculating the natural logarithm of the sum of hourly incidences (during 48 consecutive hours) of index events such as the mean heart rate or the various forms of total and either sustained or non-sustained ventricular arrhythmias. The results were then grouped for the first and second 24-hour Holter periods. All patients were submitted to 10 microg/kg/min infusion of dobutamine for 72 hours and 48-hour Holter monitoring (Holter 2) was repeated 24 hours before the end of dobutamine infusion. The incidence of arrhythmia and the distribution of laboratory and echocardiographic variables was also studied in group A and B patients. The data of the two groups along with the intrapatient +/- 95% confidence intervals were pooled, both on and off dobutamine. RESULTS: There was no significant difference between Holter 1 and Holter 2 in the rates of index events in 63 patients with regard to pro-arrhythmic effects. Pro-arrhythmic effects were seen during dobutamine infusion in 21% of cases, an effect which subsided (to 5%) when dobutamine was discontinued. Interestingly, the positive inotropic effects of dobutamine (based on ejection fraction changes) were parallel (22%) to the pro-arrhythmic changes, although they persisted long after dobutamine discontinuation (18%). The pro-arrhythmic effects of dobutamine, both during (5%) as well as after (1%) drug infusion, were unrelated to heart rate changes. The prevalence and incidence of non-sustained ventricular tachycardia due to dobutamine were 47 and 29% respectively. CONCLUSIONS: In sinus rhythm patients with severe CHF, dobutamine had chronotropic effects and increased a depressed ejection fraction without significantly increasing arrhythmogenicity.

Exercise training counteracts the abnormal release of plasma endothelin-1 in normal subjects at risk for hypertension.

BACKGROUND: The hypothesis that in normotensive offspring of hypertensive parents exercise training could influence the systemic release of endothelin (ET)-1 during a provocative testing protocol was tested. METHODS: The provocative handgrip test was performed in four groups of healthy young age-matched males: offspring of hypertensive parents following a regular swimming exercise regimen (group A, n = 14); offspring of hypertensive parents and leading a sedentary lifestyle (group B, n = 11); normal volunteers with no family history of hypertension: sedentary (group C, n = 10), and following a regular swimming regimen (group D, n = 10). The plasma ET-1 was measured at baseline, after 4 min of handgrip exercise at 50% maximal capacity and following 2 (R2) and 10 (R10) min of recovery from handgrip. RESULTS: ET-1 plasma levels, within the normal range in all groups at baseline (group A 0.94 +/- 0.32 pg/ml, group B 0.84 +/- 0.26 pg/ml, group C 0.78 +/- 0.35 pg/ml, group D 0.85 +/- 0.26, p = NS) showed a progressive and significant increase in group B during and after handgrip exercise (peak handgrip 1.08 +/- 0.5 pg/ml, p = NS; R2 1.35 +/- 0.36 pg/ml, p < 0.05; R10 2.76 +/- 0.75 pg/ml, p < 0.01). Significant differences were found at R2 and R10 when the ET-1 levels measured in group B were compared to those observed in group A, group C and group D. Multivariate analysis demonstrated that the serum levels of ET-1 significantly contributed to predict handgrip-induced changes when the diastolic blood pressure was the dependent variable. CONCLUSIONS: Routine aerobic exercise appeared to counteract the handgrip-induced abnormal release of plasma ET-1 and may favorably affect the preclinical endothelial alterations seen in healthy offspring of hypertensive parents.

Prediction of early and delayed postoperative deaths after coronary artery bypass surgery alone in Italy. Multivariate predictions based on Cox and logistic models and a chart based on the accelerated failure time model.

BACKGROUND: The aim of the multicenter OP-RISK (OPerative RISK) study was to investigate the early (28 days) and delayed (365 days) death rates following coronary artery bypass grafting (CABG) among patients representing a nationwide distribution [Centers in Northern (2), Central (1) and Southern (1) Italy] and further to define the multivariate risk factors for the early and delayed mortality after CABG. METHODS: Data were collected from 1126 patients undergoing CABG alone. Data were analyzed using Cox and logistic regression models, to accurately assess the major factors influencing survival over time after CABG. Having defined the significant factors, we constructed a chart of the absolute early risk of mortality using the accelerated failure time model. RESULTS: Using the Cox proportional hazards model and logistic regression we have demonstrated that age, preoperative ejection fraction and heart rate, and the duration of aortic cross-clamping are multivariate risk factors in the short and long term. The role of one arterial conduit was also assessed. CONCLUSIONS: The OP-RISK study produced relevant information for risk assessment and control in CABG and the results may form the basis for the objective quality assurance and accreditation of cardiac surgical institutions in Italy. Incidentally, Cox model appeared more adequate than logistic model for the assessment of the major factors influencing survival over time after CABG. The risk factors so assessed were used to construct a chart for practical predictive purposes.

Comparision of the inotropic effects of levosimendan, rolipram, and dobutamine on human atrial trabeculae.

The aim of this study was to compare the positive inotropic effects of 3 different agents with 3 different mechanisms of actions-levosimendan, rolipram, and dobutamine-on human atrial trabecular muscles. Samples of right atrial appendage (1 cm, 500-1000 mg) were removed and immersed in preoxygenated and modified Tyrode solution. In oxygenated Tyrode solution, preparations were used to investigate the concentration-effect relationship of levosimendan, dobutamine, and rolipram on percentage developed tension (DT), from 10 to 10 M, each concentration for 15 minutes. All 3 agents produced concentration-dependent increments in DT. We found that levosimendan was the most efficacious positive inotropic agent on isolated human atrial trabeculae. Both the sensitivity (pD2) and maximum response (Emax) of human atrial trabeculae to levosimendan (6.711 +/- 0.26 and 23.2 +/- 2.2 mN, respectively) were significantly greater than those of dobutamine (6.663 +/- 0.19 and 17.6 +/- 2.8 mN) and rolipram (6.497 +/- 0.18 and 15.0 +/- 1.0 mN). pD2 and Emax values for dobutamine were significantly higher than those for rolipram. It was suggested that because of its potential to enhance cardiac performance without predisposition to calcium-induced arrhythmias, levosimendan might be more useful as a positive inotropic agent in clinical practice.