Circulating cardiovascular biomarkers in recurrent atrial fibrillation: data from the GISSI-atrial fibrillation trial.

OBJECTIVE: we evaluated the prognostic role of circulating cardiovascular biomarkers in patients with a history of recent atrial fibrillation (AF). BACKGROUND: predicting long-term maintenance of sinus rhythm in patients with AF is difficult. METHODS: plasma concentrations of three specific cardiac markers [high-sensitivity troponin T (hsTnT), N-terminal probrain natriuretic peptide (NT-proBNP) and mid-regional proatrial natriuretic peptide (MR-proANP)] and three stable fragments of vasoactive peptides [mid-regional proadrenomedullin (MR-proADM), copeptin (CT-proAVP) and CT-proendothelin-1 (CT-proET-1)] were measured at baseline and after 6 and 12 months in 382 patients enrolled in the GISSI-AF study, a prospective randomized trial to determine the effect of valsartan to reduce the recurrence of AF. The association between these markers, clinical characteristics and recurrence of AF was tested by univariate and multivariate Cox models. RESULTS: mean patient age was 68 ± 9 years (37.2% females). A total of 84.8% of patients had a history of hypertension. In total, 59.7% qualified for history of AF because of successful cardioversion, 11.8% because of two or more episodes of AF in the 6 months preceding randomization and 28.5% because of both. Patients in AF at 6 or 12 months (203 (53.1%) with first recurrence) had significantly higher concentrations of most biomarkers. Despite low baseline levels, higher concentrations of hsTnT {adjusted hazard ratio (HR) [95% confidence intervals (CIs) for 1 SD increment] (1.15 [1.04-1.28], P = 0.007), MR-proANP (1.15 [1.01-1.30], P = 0.04), NT-proBNP (1.24 [1.11-1.39], P = 0.0001) and CT-proET-1 (1.16 [1.01-1.33], P = 0.03) independently predicted higher risk of a first recurrence of AF. Changes over time of MR-proANP tended to predict subsequent recurrence (adjusted HR [95%CI]) (1.53 [0.98-2.37], P = 0.06). CONCLUSION: circulating markers of cardiomyocyte injury/strain and endothelin are related to recurrence of AF in patients in sinus rhythm with a history of recent AF.

Early detection of the graft failure after pediatric liver transplantation: a Bergamo experience.

BACKGROUND: Effective indicators of the early graft failure after pediatric liver transplantation are currently a crucial question. The aim of this study was to analyze retrospectively laboratory parameters that may help anticipate an early graft loss (GL). METHODS: The 131 pediatric liver transplantations, performed in our hospital from January 2002 to December 2005, were reviewed. Post-operative laboratory parameters, collected in the first 36 h of the Paediatric Intensive Care Unit (PICU) stay, were analyzed for children with both graft survival and GL. Receiver operating characteristics analysis was used to identify the optimal cut-off for the laboratory parameters. Multivariate logistic regression analysis was used to calculate the adjusted risk of GL for the prognostic parameters identified. RESULTS: The mean age at transplant was 1.1 years. The two groups were comparable for all recipient and donor variables considered. Children with GL showed significantly higher levels of ammonia and transaminase at the admission to the PICU and higher levels of prothrombin time, creatinine, lactate and a lower level of platelets at the 36 h of PICU. The laboratory parameters over the cut-off value by the multivariate logistic regression identified all early thromboses earlier than Doppler ultrasound. CONCLUSIONS: This study suggests that routine blood tests may help to anticipate an early loss of liver grafts in children after transplantation and may improve our diagnostic investigation in the case of thrombosis suspicion. Further validation by a prospective study is needed to carefully assess the sensitivity and specificity of the identified criteria.

Population structure of modern-day Italians reveals patterns of ancient and archaic ancestries in Southern Europe.

European populations display low genetic differentiation as the result of long-term blending of their ancient founding ancestries. However, it is unclear how the combination of ancient ancestries related to early foragers, Neolithic farmers, and Bronze Age nomadic pastoralists can explain the distribution of genetic variation across Europe. Populations in natural crossroads like the Italian peninsula are expected to recapitulate the continental diversity, but have been systematically understudied. Here, we characterize the ancestry profiles of Italian populations using a genome-wide dataset representative of modern and ancient samples from across Italy, Europe, and the rest of the world. Italian genomes capture several ancient signatures, including a non-steppe contribution derived ultimately from the Caucasus. Differences in ancestry composition, as the result of migration and admixture, have generated in Italy the largest degree of population structure detected so far in the continent, as well as shaping the amount of Neanderthal DNA in modern-day populations.

Long-term prognostic impact of repeated measurements over 1 year of pulse pressure and systolic blood pressure in the elderly.

Systolic blood pressure (SBP) and pulse pressure (PP) have been identified in western industrialized countries as major predictors of cardiovascular events in the elderly on the basis of measurements taken at a single visit. Considering the wide variability of blood pressure (BP) in older people, this study set out to assess the prognostic significance of measurements of SBP and PP taken over several months according to a monitoring scheme mimicking routine care. A total of 444 Italian general practitioners enrolled a cohort of 3858 unselected elderly outpatients and followed them up for 10 years. BP was recorded at recruitment, 1 week later and at quarterly visits during the first year. The average BP of these six visits was used to define the patient's BP status. During the 10-year follow-up, 1561 participants died, 709 from cardiovascular diseases. Proportional hazard regression analysis, adjusted for all main prognostic factors including antihypertensive treatment, showed that for each 10-mmHg increment in SBP and PP there were, respectively, 5 and 9% increases in risk for total mortality (TM) and 9 and 13% increases in risk for cardiovascular mortality (CVM) (all P < 0.01). However, including both SBP and PP in the model, only PP showed an independent, significant relationship with TM and CVM. In conclusion, prognostic information based on repeated measurements of PP is stronger than that given by SBP and consequently should be recommended in the definition of cardiovascular risk in the elderly.

Epidemiologic variables and outcome of 1972 young patients with acute myocardial infarction. Data from the GISSI-2 database. Investigators of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2).

BACKGROUND: Acute myocardial infarction in younger patients is uncommon, occurring mainly in men. The recent introduction of thrombolysis improved survival, left ventricular function, and infarct size. OBJECTIVE: To evaluate characteristics and clinical outcome of the patients younger than 50 years randomized in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico study. All patients received a thrombolytic treatment. METHODS: The 11483 patients were divided into 3 age subgroups: younger than 50 years (17.2%), between 50 and 70 years (60.2%), and older than 70 years (22.6%). All relations between variables were first determined by an unadjusted analysis. An adjusted analysis was performed by multiple logistic regression models for in-hospital and 6-month mortality. RESULTS: While older patients had a significantly higher rate of a history of hypercholesterolemia, diabetes, and hypertension, smoking and a positive family history were significantly more frequent in younger patients. Total in-hospital and 6-month mortality were significantly lower in patients younger than 50 years (2.7% and 1.2%, respectively) than in patients between 50 and 70 years old (6.9% and 2.7%) and those older than 70 years (21.1% and 8.4%). After multivariate analysis, the predictive value of age was confirmed. CONCLUSIONS: Our findings, based on a large group of patients who received thrombolytic treatment, suggest that younger age is a significant independent indicator of a favorable prognosis after acute myocardial infarction.

Autonomic cardiovascular modulation with three different anesthetic strategies during neurosurgical procedures.

BACKGROUND: Autonomic cardiovascular modulation during surgery might be affected by different anesthetic strategies. Aim of the present study was to assess autonomic control during three different anesthetic strategies in the course of neurosurgical procedures by the linear and non-linear analysis of two cardiovascular signals. METHODS: Heart rate (EKG-RR intervals) and systolic arterial pressure (SAP) signals were analyzed in 93 patients during elective neurosurgical procedures at fixed points: anesthetic induction, dura mater opening, first and second hour of surgery, dura mater and skin closure. Patients were randomly assigned to three anesthetic strategies: sevoflurane+fentanyl (S-F), sevoflurane+remifentanil (S-R) and propofol+remifentanil (P-R). RESULTS: All the three anesthetic strategies were characterized by a reduction of RR and SAP variability. A more active autonomic sympathetic modulation, as ratio of low to high frequency spectral components of RR variability (LF/HF), was present in the P-R group vs. S-R group. This is confirmed by non-linear symbolic analysis of RR series and SAP variability analysis. In addition, an increased parasympathetic modulation was suggested by symbolic analysis of RR series during the second hour of surgery in S-F group. CONCLUSION: Despite an important reduction of cardiovascular signal variability, the analysis of RR and SAP signals were capable to detect information about autonomic control during anesthesia. Symbolic analysis (non-linear) seems to be able to highlight the differences of both the sympathetic (slow) and vagal (fast) modulation among anesthetics, while spectral analysis (linear) underlines the same differences but only in terms of balance between the two neural control systems.

Electrocardiographic patterns in acute inferior myocardial infarction with and without right ventricle involvement: classification, diagnostic and prognostic value, masking effect.

BACKGROUND: In acute inferior myocardial infarction (AIMI), the ST depression from V1 to V4 has been the subject of many papers, while the ST changes in other leads, their association, and the right ventricular (RV) involvement have been studied less. HYPOTHESIS: This study was performed to contribute to the meaning of the ST changes and RV involvement in AIMI. METHODS: Seventy-one patients, admitted within 6 h from symptom onset, all thrombolysed, were enrolled. We classified them according to ST patterns and RV involvement. We divided the right coronary artery into three segments, considering the origin of RV branch and the crux as dividing points. We established a coronary score attributing 2 points to each terminal branch. Comparisons were performed between the electrocardiographic (ECG) findings at onset, the creatine phosphokinase (CPK) peaks, the radionuclide ejection fractions, and the coronary angiographies. RESULTS: We found that the ST changes give indications regarding the site, extension, and extent of AIMI; RV involvement can mask posterior extension, points to the right coronary as the culprit vessel (100%), and, with high probability, indicates the proximal segment as the site of the lesion; the ECG signs of isolated AIMI indicate a peripheral obstruction; and a collateral circulation may appear relatively early. CONCLUSIONS: Our findings prove the diagnostic and prognostic value of the ST changes and RV involvement at the onset of AIMI and suggest that the higher in-hospital mortality and complication rates found with RV involvement and reported in the literature are related more to posterior extension, masked by RV involvement than to this involvement per se. Furthermore, these findings prove the clinical value of our classification of the AIMIs and distinction in segments of the right coronary artery.

[Susceptibility gene to infarct: a review of the literature]. / I geni di suscettibilità all'infarto: una revisione della letteratura.

The investigation on the susceptibility genes of myocardial infarction has initiated substantially in the last 20 years. Most efforts have been mainly addressed to identify and evaluate genes involved in those systems already suspected to be implicated in the pathogenesis of coronary heart disease. Principal examples are lipid metabolism, coagulation and fibrinolytic systems, membrane receptors of platelets, levels of plasma homocysteine and vascular tone. Therefore up to now, the identification of the genetic factors of myocardial infarction has been carried out through case-control association studies employing a "candidate gene" approach. This method has often led to controversial results, usually difficult to compare. This is an attempt to provide a progress report on the principal susceptibility genes of coronary heart disease.

[PROCARDIS: A current approach to the study of the genetics of myocardial infarct]. / Il PROCARDIS: un approccio attuale allo studio della genetica dell'infarto miocardico.

Coronary artery disease is a complex and multifactorial pathology. Although the environmental component of coronary artery disease has been thoroughly investigated and is hence well known, knowledge about the genetic factors implicated in this disease is still scarce. Technological advances and the fact that the Human Genome Project has almost been completed allow the application of approaches that were not feasible few years ago to the genetic investigation of complex diseases. The aim of the PROCARDIS study is to identify new susceptibility genes of precocious coronary artery disease, through a genome-wide screen applying statistical methods of linkage analysis followed by a family-based association study. The originality of PROCARDIS lies in the fact that it is an international multicenter study. This allows recruitment of a very large number of individuals so that the population size, considered up to now unachievable, is adequate for the aims of the study.

Starc II, a multicenter randomized placebo-controlled double-blind clinical trial of trapidil for 1-year clinical events and angiographic restenosis reduction after coronary angioplasty and stenting.

The objective of this study was to investigate the effect of trapidil 200 mg t.i.d. in preventing the occurrence of death, of myocardial infarction and the need for repeat revascularization at 12 months after balloon PTCA with or without stenting. Coronary restenosis after stenting is still a major drawback of percutaneous coronary interventions (PCI) for 30-40% of patients. Trapidil has been shown to prevent restenosis after PTCA. Eligible patients were randomized to placebo or oral trapidil 200 mg t.i.d. at least 48 hr before PCI and continuing 6 months after a successful balloon angioplasty or stent implantation. Aspirin was given to all patients, and ticlopidine 250 mg b.i.d. to those who received a stent for 4 weeks. In a randomized subgroup of 216 patients, quantitative coronary angiography was performed also at 6-month follow-up. Out of the 933 patients enrolled, primary endpoint incidence was 20.3% in trapidil and 18.0% in placebo (P = 0.37). When recurrence or deterioration of angina was added to the combined endpoint, incidence was 27.4% in trapidil and 23.0% in placebo (P = 0.12). Restenosis rate in patients with 6-month angiography was 25.0% in trapidil arm vs. 30.1% in placebo (P = 0.43). Stent restenosis rate was similar in patients randomized to trapidil or placebo (30.2% vs. 23.8%, respectively; P = 0.44), while in patients treated with balloon angioplasty, it was lower in trapidil (17.1%) than in placebo (40.0%; P = 0.03). Oral trapidil 200 mg t.i.d. for 6 months in addition to aspirin did not influence the occurrence of major cardiac events after coronary angioplasty with or without stenting. In a prespecified subgroup of 191 patients treated with balloon angioplasty only, trapidil reduced angiographic restenosis.

[Successive ischemic events to a first acute myocardial infarct treated with fibrinolysis. An analysis of GISSI-2 patients considered reperfused by a clinical criterion. Participants in the GISSI-2 study. Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico]. / Eventi ischemici successivi a primo infarto miocardico acuto trattato con fibrinolisi. Analisi dei pazienti del GISSI-2 ritenuti ricanalizzati con criterio clinico. A nome dei partecipanti allo studio GISSI-2.

BACKGROUND: The fast normalisation of the ST, after thrombolysis, is early sign related to coronary artery reperfusion and to prognosis of acute myocardial infarction (AMI). The aim of this analysis is the evaluation, in the large patients cohort of the GISSI-2 trial, of the relationship between the ST segment evolution after fibrinolytic therapy of AMI and recurrent ischaemic events [angina-reinfarction-ischaemia to exercise testing (ET)] at 30 and 180 days from randomisation. METHODS: Patients with first confirmed IMA and ECG before randomisation and 4 hours later, are chosen from GISSI-2 trial. A decrease > or = 50% of the sigma ST elevation is adopted as cutoff for predicting coronary artery patency. Recanalisation is deemed to have occurred in group A patients versus not reperfused group B patients. The studied events are: angina, reinfarction, mortality, at 30 and 180 days from randomisation; ischemia to ET SL of 4-6 week. The results are presented in terms of Mantel-Haenszel odds ratios (OR) and 95% confidence intervals. RESULTS: Group A patients n. 5307 experienced versus group B patients n. 2718 a higher incidence of--in-hospital angina: 10.3% vs 7.9% OR 1.30 (1.11-1.52)-180 days reinfarction: 2.9% Vs 1.7% OR 1.66 (1.19-2.30)-Ischaemia to ET 25.4% vs 21.4% OR 1.24 (1.08-1.43), and a lower in-hospital mortality: 3.8% vs 8.5% OR 0.39 (0.32-0.48). CONCLUSIONS: Patients having indirect signs of early reperfusion post thrombolysis for IMA experience a higher in-hospital and 180 days recurrent ischaemia and a lower mortality; this fact can allow early identification of the patients who can receive a benefit from different therapeutical strategies.

Clinical and epidemiological characteristics of juvenile myocardial infarction in Italy: the GISSI experience.

BACKGROUND: No clinical and epidemiological data are available about acute myocardial infarction (AMI) at a young age in large populations, due to the low prevalence of AMI in younger people. The aim of the present study is to analyze epidemiological and clinical characteristics of AMI among younger people in Italy, using the data bases of the three GISSI studies. METHODS: Analysis of epidemiological and clinical characteristics of AMI according to different age groups in the three GISSI studies that collected data from 1985 to 1993. RESULTS: In the GISSI-2 and GISSI-3 data bases, the prevalence of AMI at a young age (2 and 1.8% respectively; difference -0.2% with 95% CI from -0.4 to 0.3%), hospital mortality (2.3 and 1.9% respectively; difference -0.4% with 95% CI from -1.9 to 1.0%), and the rate of young female patients (8 and 7% respectively; difference -1% with 95% CI from -3.6 to 1.6%) are similar. In the GISSI-2 study, we observed that in comparison to elderly patients (> 70 years) young patients (< 40 years) are more frequently smokers (83.9 vs 21.0%; difference 62.9% with 95% CI from 58.5 to 67.3%) and have a higher rate of family history for CAD (42.1 vs 21.1%; difference 21.0% with 95% CI from 15.3 to 26.7%) and of hypercholesterolemia (28.3 vs 15.0%; difference 13.3% with 95% CI from 18.5 to 80.8%), but show a lower prevalence of hypertension (12.2 vs 44.3%; difference from -32.1% with 95% CI from -28.0 to -36.2%) and diabetes (2.9 vs 18.8%; difference -15.9% with 95% CI from -13.5 to -18.3%). AMI at a young age is generally the first event in ischemic heart disease; in comparison with older patients with previous AMI (6.4 vs 17.4%; difference -11.0% with 95% CI from -7.8 to -14.0%) and history of angina (23.2 vs 40.0%, difference -16.8% with 95% CI from -11.8 to -21.9%) this is less frequent. The rate of complications is lower in younger as opposed to older patients for both early (7.7 vs 31.2%; difference -23.5% with 95% CI from -20.0 to -26.9%) and late heart failure (2.9 vs 18.5%; difference -15.6% with 95% CI from -13.2 to -18.0%), as well as for angina (6.4 vs 10.5%; difference -4.1% with 95% CI from -1.1 to -7.1%), reinfarction (1.0 vs 3.3%; difference -2.3% with 95% Ci from -1.1 to -3.6%) and complete AV block (1.6 vs 6.6%; difference -5.0% with 95% CI from -3.3 to -6.7%). In young patients, we observed lower in-hospital (1.6 vs 21.1%; difference -19.5% with 95% CI to -21.6%) and six-month mortality (1.3 vs 8.1%; difference -6.8% with 95% CI from -5.0 to -8.5%). CONCLUSIONS: The incidence and mortality of AMI at a young age was steady during the period between 1988 and 1993. AMI at a young age is a clinical entity with specific characteristics that differ from those found in old patients. In addition, it has peculiar risk profile with a better short- and medium-term outcome.

Incidence and short-term prognosis of late sustained ventricular tachycardia after myocardial infarction: results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-3) Data Base.

BACKGROUND: There is little epidemiologic information from large multicenter databases on sustained monomorphic ventricular tachycardia occurring after the initial 48 hours of myocardial infarction. METHODS: We reassessed its incidence and short-term prognosis in 16,842 patients with a definite myocardial infarction enrolled in the Gruppo Italiano per lo Studio della Soprovvivenza nell'Infarto Miocardico (GISSI-3) trial. RESULTS: The incidence rate of late sustained ventricular tachycardia by 6 weeks was around 1%. Older age, a history of hypertension, diabetes, and myocardial infarction, nonadministration of lytic therapy, Killip class > I, > or = 6 leads with ST-segment elevation, higher heart rate, and bundle branch block on admission were significantly more frequent among patients with than without late sustained ventricular tachycardia. Patients with ventricular tachycardia had a more complicated course in-hospital and posthospital to 6 weeks than the reference group did. The arrhythmia was associated with a significant excess of pump failure, atrial flutter-fibrillation, asystole, atrioventricular block, ventricular fibrillation within the first 48 hours of myocardial infarction, and recurrent ischemic events. Larger left ventricular end-systolic volumes and lower ejection fractions were more frequent among ventricular tachycardia patients than in the reference group by 6 weeks. Death rates by 6 weeks were 35% for patients with ventricular tachycardia and 5% for those without the arrhythmia. Irrespective of the stratification of patients by site and type of infarct and presence/absence of bundle branch block, the occurrence of the arrhythmia was associated with reduced 6-week survival. CONCLUSION: In a proportional hazard regression model late sustained ventricular tachycardia was retained as a strong, independent predictor of 6-week mortality after myocardial infarction (hazard ratio 6.13, 95% confidence interval 4.56-8.25).

Prognostic significance of double product and inadequate double product response to maximal symptom-limited exercise stress testing after myocardial infarction in 6296 patients treated with thrombolytic agents. GISSI-2 Investigators. Grupo Italiano per lo Studio della Sopravvivenza nell-Infarto Miocardico.

BACKGROUND: The aim of this study was to evaluate the prognostic significance of the pressure-rate product (PRP) obtained during exercise stress testing and of its change from rest to maximal exercise (dPRP) in a population of survivors of acute myocardial infarction treated with thrombolytic agents. METHODS AND RESULTS: Survivors of acute myocardial infarction (n = 6251) from the GISSI-2 database, who underwent a maximal symptom-limited exercise test with either bicycle ergometer or treadmill, were followed up for 6 months. PRP and dPRP values were dichotomized (21,700, 11,600, respectively) and analyzed in a multivariate Cox model individually and simultaneously with other ergometric variables. Six-month mortality rate was 0.8% in the high PRP group and 2.0% in the low PRP group. Low PRP was an independent predictor of 6-month mortality rate (relative risk [RR] 1.97, 95% confidence interval [CI] 1.24 to 3.13). Patients with low dPRP had mortality rates higher than patients with high dPRP (2.1% vs 0.8%). At the multivariate analysis, low dPRP showed negative predictive value (RR 1.97, 95% CI 1.23 to 3.16). A further multivariate analysis was performed with PRP and dPRP, also adjusting for low work capacity, abnormal systolic blood pressure response to exercise, and symptomatic-induced ischemia. The results showed that low work capacity, low PRP, and symptomatic exercise-induced ischemia were still significantly associated with higher 6-month mortality rate (P =.04,.02, and.05; RR = 1.68, 1.71, and 1.78 respectively). CONCLUSIONS: PRP is a predictive index to assess prognosis in survivors of acute myocardial infarction treated with thrombolytic agents able to perform an exercise test after acute myocardial infarction, but its usefulness appears to be limited, considering that these patients were at low risk.

Administration of thrombolytic therapy to 17,944 patients with acute myocardial infarction: the GISSI-3 database.

BACKGROUND: There is growing interest in assessing therapy for acute myocardial infarction. Because thrombolysis was not a study therapy in the GISSI-3 trial, the decision about thrombolysis was left to the responsible physicians. We evaluated the data on thrombolytic therapy among patients with acute myocardial infarction enrolled in the GISSI-3 trial to study the relation between rate of prescription and the characteristics of patients and participating coronary care units. METHODS: Complete clinical data were available for 17,944 patients randomized between June 1991 and July 1993 from 200 coronary care units in Italy. Demographic and clinical information were obtained for each patient, and each coronary care unit was classified according to patient volume, level of technology, and wide geographic area in which it was located. A multivariate logistic regression was performed with administration of thrombolytic therapy as the dependent variable and previously defined clinical and structural variables as independent variables. RESULTS: The most important factor in administration of thrombolytic therapy was that less than 6 hours elapse from symptom onset to hospital admission (odds ratio [OR] 14.05; 95% confidence interval [CI] 12.3 to 16.0). Next were location of coronary care unit in southern Italy (OR 1.81; 95% CI 1.62 to 2.01), presence of ST elevation at entrance electrocardiogram ECG (OR 1.47; 95% CI 1.35 to 1.61), absence of previous myocardial infarction (OR 1.35; 95% CI 1.22 to 1.49), and presence of catheterization laboratory or cardiac surgery program or both in the same hospital (OR 1.24; 95% CI 1.14 to 1.35). Coronary care units with high or low patient volume did not show different rates of administration of thrombolytic agents. CONCLUSIONS: The GISSI-3 experience confirmed a high rate of prescription of thrombolytic therapy to patients admitted within 6 hours of symptom onset and those with ST-segment elevation on entrance electrocardiogram. It demonstrated that patients admitted to coronary care units with catheterization laboratories or cardiac programs or both have higher chances of receiving thrombolytic treatment than those admitted to hospitals without these capabilities.

Relevance of heart rate as a prognostic factor in patients with acute myocardial infarction: insights from the GISSI-2 study.

AIMS: It is as yet undefined whether simple indexes of autonomic balance such as heart rate (HR) may play a role in risk stratification in patients with acute myocardial infarction (MI). The aim of this study was to quantify the prognostic significance of HR from the surface ECG obtained both at entry and at discharge, in a large population of patients all treated with fibrinolysis during the acute phase and having confirmed acute MI. METHODS AND RESULTS: Surface ECGs obtained at entry and at discharge in patients with confirmed MI enrolled in the GISSI-2 study, a large multicentre trial of different thrombolytic agents, were retrieved. Heart rhythm was evaluated and HR was measured; these data were then added to the main database of GISSI-2 allowing a complete evaluation of the prognostic significance of HR. Patients not in sinus rhythm or with grade 2-3 atrioventricular block were excluded. The prognostic significance of HR (cut-offs predefined at 60, 80, 100 beats.min-1) at entry for in-hospital mortality and at discharge for 6-month mortality was evaluated in the general population and in predefined subgroups. Multivariate analyses were used to assess the independent prognostic value of HR. A total of 8915 patients (more than 70% of the original population) were suitable for the analysis. There was a progressive increase in mortality with increasing HR in the general population (from 7.1% for HR < 60 beats.min-1) to 23.4% for HR > 100 beats.min-1) and in the predefined subgroups. Multivariate analysis showed that HR exerted an independent prognostic significance. Data for analysis of HR at discharge were available for 7831 patients. Consistent with the data observed at entry, a progressive increase of 6-month mortality with increasing HR was present in the general population (from 0.8% for HR < 60 beats.min-1) to 14.3% for HR > 100 beats.min-1) and for the different predefined subgroups. Multivariate analysis confirmed the independent prognostic significance of HR. There was no relation between HR and the incidence of fatal and non-fatal reinfarction. CONCLUSION: The present study indicates that HR values from a standard 12-lead ECG independently predict mortality in patients with acute MI during the in-hospital phase and after discharge. This simple index appears very useful for risk stratification in clinical practice.

Incidence and prognostic significance of atrial fibrillation in acute myocardial infarction: the GISSI-3 data.

BACKGROUND: Atrial fibrillation is the most common supraventricular arrhythmia in patients with acute myocardial infarction. Recent advances in pharmacological treatment of myocardial infarction may have changed the impact of this arrhythmia. OBJECTIVE: To assess the incidence and prognosis of atrial fibrillation complicating myocardial infarction in a large population of patients receiving optimal treatment, including angiotensin converting enzyme (ACE) inhibitors. METHODS: Data were derived from the GISSI-3 trial, which included 17 944 patients within the first 24 hours after acute myocardial infarction. Atrial fibrillation was recorded during the hospital stay, and follow up visits were planned at six weeks and six months. Survival of the patients at four years was assessed through census offices. RESULTS: The incidence of in-hospital atrial fibrillation or flutter was 7.8%. Atrial fibrillation was associated with indicators of a worse prognosis (age > 70 years, female sex, higher Killip class, previous myocardial infarction, treated hypertension, high systolic blood pressure at entry, insulin dependent diabetes, signs or symptoms of heart failure) and with some adverse clinical events (reinfarction, sustained ventricular tachycardia, ventricular fibrillation). After adjustment for other prognostic factors, atrial fibrillation remained an independent predictor of increased in-hospital mortality: 12.6% v 5%, adjusted relative risk (RR) 1.98, 95% confidence interval (CI) 1.67 to 2.34. Data on long term mortality (four years after acute myocardial infarction) confirmed the persistent negative influence of atrial fibrillation (RR 1.78, 95% CI 1.60 to 1.99). CONCLUSIONS: Atrial fibrillation is an indicator of worse prognosis after acute myocardial infarction, both in the short term and in the long term, even in an unselected population.

Prognostic value of residual ischaemia assessed by exercise electrocardiography and dobutamine stress echocardiography in low-risk patients following acute myocardial infarction.

BACKGROUND: Risk stratification after uncomplicated myocardial infarction is major clinical problem. In particular, the prognostic value of residual inducible ischaemia is still controversial. We compared the relative prognostic value of exercise ECG and dobutamine stress echocardiography performed in the early post-infarction period. METHODS: Four hundred and six patients (53 female) aged 57 +/- 9 years, undergoing maximal exercise ECG and dobutamine stress echocardiography within 10 days of an uncomplicated myocardial infarction off therapy, were prospectively followed-up for 8.8 months. Age, sex, diabetes, smoking habit, hypertension, dyslipidaemia, infarct location, thrombolysis and resting wall motion score index were taken into account among clinical variables. Prognostic correlations were made vs spontaneous events (cardiac death, non-fatal reinfarction and unstable angina requiring hospitalization) whilst patients undergoing revascularization (by means of percutaneous transluminal coronary angioplasty or coronary artery bypass surgery) at the time of the procedure were censored. RESULTS: One hundred and twenty-seven events occurred during the follow-up: 41 (10%) were spontaneous (five deaths, 12 reinfarctions and 24 unstable angina) and 86 procedural (27 angioplasty and 59 bypass surgery). Spontaneous events were not predicted by any clinical, exercise ECG or dobutamine stress echocardiography variable, but the negative predictive value of both tests was excellent (91% and 90% respectively). With a multivariate Cox analysis, male gender, positive low-workload (< 100 W) exercise ECG (P < 0.0001), positive low-dose dobutamine stress echocardiography (P < 0.0001) and rest-stress wall motion score index variation (P < 0.001) were found to predict cumulative cardiac events with an independent and additive value. Dobutamine stress echocardiography was significantly more sensitive (P < 0.05) and less specific (P < 0.01) in predicting the outcome of patients with anterior infarction, whilst exercise ECG was significantly more sensitive (P < 0.05) in patients with non-Q wave infarction. CONCLUSIONS: (1) Spontaneous events are poorly predicted by provocative tests in low-risk patients after uncomplicated myocardial infarction. (2) However, both exercise ECG and dobutamine stress echocardiography can predict a favourable outcome with a very high negative predictive value. (3) Dobutamine stress echocardiography should be considered a secondary option in cases where the exercise ECG is equivocal or when the location of ischaemia is a relevant issue. (4) The possibility that the two tests have a differential utility depending on the infarct location and type (Q wave vs non-Q wave) may be clinically relevant and deserves further evaluation.

The prognostic value of predischarge quantitative two-dimensional echocardiographic measurements and the effects of early lisinopril treatment on left ventricular structure and function after acute myocardial infarction in the GISSI-3 Trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico.

BACKGROUND: Left ventricular dilatation and a low ejection fraction after acute myocardial infarction are independent indicators of a poor prognosis. ACE inhibitors have been shown to decrease left ventricular dilatation after myocardial infarction. In the GISSI-3 trial, patients were randomly assigned, within 24 h of onset of myocardial infarction symptoms, to 6 weeks of treatment with lisinopril, nitroglycerin, both or neither, in an open, 2 x 2 factorial design. The study showed that early treatment in relatively unselected patients with lisinopril decreases mortality at 6 weeks and severe left ventricular dysfunction. We assessed (1) the prognostic value of pre-discharge 2-D echocardiographic variables, and (2) the effects of lisinopril on the progression of left ventricular dilatation. METHODS AND RESULTS: 2-D echocardiograms were available pre-discharge in 8619 GISSI-3 trial patients discharged alive. In 6405 of these patients, a 2-D echocardiographic study was also available at 6 weeks, and at 6 months. Pre-discharge end-diastolic and end-systolic volumes, and ejection fraction predicted 6-month mortality and non-fatal clinical congestive heart failure (P < 0.01). The increase in left ventricular volumes over time was significantly reduced by 6 weeks' lisinopril treatment in patients with wall motion asynergy pre-discharge of > or = 27%. Patients with wall motion asynergy < 27% showed no dilatation and lisinopril did not affect volumes at 6 months. Patients randomized to lisinopril also had smaller volumes after withdrawal of treatment at 6 weeks. Lisinopril did not affect left ventricular ejection fraction. CONCLUSIONS: 2-D echocardiography independently contributes to pre-discharge risk stratification in terms of 6-month mortality and clinical heart failure after myocardial infarction, and early, short-term treatment with lisinopril in unselected myocardial infarction patients attenuates left ventricular dilatation; an effect evident in patients with larger infarcts. These results probably only partly explain the effect of lisinopril on total mortality concentrated in the first week after infarction.

Aspirin does not interact with ACE inhibitors when both are given early after acute myocardial infarction: results of the GISSI-3 Trial.

Aspirin (ASA) and angiotensin-converting enzyme inhibitor (ACEi) therapy reduce mortality when administered early after the onset of myocardial infarction. ASA can antagonize some effects of ACEi therapy by inhibiting the synthesis of vasodilating prostaglandins; however, the evidence for this effect from large controlled trials is contradictory. The authors analyzed a database of 18,895 patients of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardio-3 (GISSI-3) Trial in which patients were allocated either to receive lisinopril or not to receive lisinopril within 24 hours of the onset of symptoms of myocardial infarction. The aim of the study was to verify the possible negative interaction between ASA and the ACEi lisinopril in the postacute phase of acute myocardial infarction. Of 18,895 analyzable patients, 15,841 received ASA at entry. Overall lisinopril reduced 42-day mortality from 7.1% to 6.3%. In patients receiving ASA, mortality was reduced by lisinopril from 6.0% to 5.4%, and from 13.0% to 10.8% in patients not receiving ASA. The difference in proportional reductions of mortality corresponds to the fact that a more marked lisinopril effect is seen in patients at higher baseline risk across all study subgroups, one of which coincides with the no-ASA group. The analysis of the inhospital incidence of major clinical events did not reveal a potentially negative interaction between ASA and lisinopril. The same findings were obtained from the analysis of reinfarction at 42 days. The interaction between ASA and lisinopril was also tested by multivariate analysis adjusted for confounding variables at entry, and the interaction tests were not statistically significant. Serum creatinine levels at 42 days were significantly higher in lisinopril group than in the control group. Systolic and diastolic blood pressures in lisinopril group were significantly lower than controls at 42 days. The effect of lisinopril on creatinine and blood pressure did not differ between the ASA and no-ASA groups. ASA does not decrease the mortality benefit of early lisinopril after myocardial infarction, nor does it increase the risk of major adverse events. Lisinopril is safe and effective when given early after the onset of myocardial infarction, regardless of a concomitant administration of ASA started early and continued over a 6-week period.