Donata Lucci

Prognostic Significance of the Long Pentraxin PTX3 in Acute Myocardial Infarction

Background—Inflammation has a pathogenetic role in acute myocardial infarction (MI). Pentraxin-3 (PTX3), a long pentraxin produced in response to inflammatory stimuli and highly expressed in the heart, was shown to peak in plasma ≈7 hours after MI. The aim of this study was to assess the prognostic value of PTX3 in MI compared with the best-known and clinically relevant biological markers. Methods and Results—In 724 patients with MI and ST elevation, PTX3, C-reactive protein (CRP), creatine kinase (CK), troponin T (TnT), and N-terminal pro-brain natriuretic peptide (NT-proBNP) were assayed at entry, a median of 3 hours, and the following morning, a median of 22 hours from symptom onset. With respect to outcome events occurring over 3 months after the index event, median PTX3 values were 7.08 ng/mL in event-free patients, 16.12 ng/mL in patients who died, 9.12 ng/mL in patients with nonfatal heart failure, and 6.88 ng/mL in patients with nonfatal residual ischemia (overall P<0.0001). Multivariate analysis including CRP, CK, TnT, and NT-proBNP showed that only age ≥70 years (OR, 2.11; 95% CI, 1.04 to 4.31), Killip class >1 at entry (OR, 2.20; 95% CI, 1.14 to 4.25), and PTX3 (>10.73 ng/mL) (OR, 3.55; 95% CI, 1.43 to 8.83) independently predicted 3-month mortality. Biomarkers predicting the combined end point of death and heart failure in survivors were the highest tertile of PTX3 and of NT-proBNP and a CK ratio >6. Conclusions—In a representative contemporary sample of patients with MI with ST elevation, the acute-phase protein PTX3 but not the liver-derived short pentraxin CRP or other cardiac biomarkers (NT-proBNP, TnT, CK) predicted 3-month mortality after adjustment for major risk factors and other acute-phase prognostic markers.

Usual versus tight control of systolic blood pressure in non-diabetic patients with hypertension (Cardio-Sis): an open-label randomised trial.

BACKGROUND The level to which systolic blood pressure should be controlled in hypertensive patients without diabetes remains unknown. We tested the hypothesis that tight control compared with usual control of systolic blood pressure would be beneficial in such patients. METHODS In this randomised open-label trial undertaken in 44 centres in Italy, 1111 non-diabetic patients with systolic blood pressure 150 mm Hg or greater were randomly assigned to a target systolic blood pressure of less than 140 mm Hg (usual control; n=553) or less than 130 mm Hg (tight control; n=558). After stratification by centre, we used a computerised random function to allocate patients to either group. Observers who were unaware of randomisation read electrocardiograms and adjudicated events. Open-label agents were used to reach the randomised targets. The primary endpoint was the rate of electrocardiographic left ventricular hypertrophy 2 years after randomisation. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00421863. RESULTS Over a median follow-up of 2.0 years (IQR 1.93-2.03), systolic and diastolic blood pressure were reduced by a mean of 23.5/8.9 mm Hg (SD 10.6/7.0) in the usual-control group and by 27.3/10.4 mm Hg (11.0/7.5) in the tight-control group (between-group difference 3.8 mm Hg systolic [95% CI 2.4-5.2], p<0.0001; and 1.5 mm Hg diastolic [0.6-2.4]; p=0.041). The primary endpoint occurred in 82 of 483 patients (17.0%) in the usual-control group and in 55 of 484 patients (11.4%) of the tight-control group (odds ratio 0.63; 95% CI 0.43-0.91; p=0.013). A composite cardiovascular endpoint occurred in 52 (9.4%) patients in the usual-control group and in 27 (4.8%) in the tight-control group (hazard ratio 0.50, 95% CI 0.31-0.79; p=0.003). Side-effects were rare and did not differ significantly between the two groups. INTERPRETATION Our findings lend support to a lower blood pressure goal than is recommended at present in non-diabetic patients with hypertension. FUNDING Boehringer-Ingelheim, Sanofi-Aventis, Pfizer.

Epidemiology of acute myocardial infarction in the Italian CCU network: the BLITZ study.

AIMS A large number of descriptive data on patients with acute myocardial infarction are based on clinical trials and registries on non consecutive patients: these data may give only a partial picture on treatment delay, patient characteristics, treatment and outcome of acute myocardial infarction in the real world. METHODS AND RESULTS The BLITZ survey prospectively enrolled all of the patients with acute myocardial infarction admitted in 296 (87%) Italian Coronary Care Units from 15-29 October 2001. Data on treatment delay, therapeutic strategies, duration of hospitalization and 30-day outcome were collected. One thousand nine hundred and fifty-nine consecutive patients (mean age 67+/-12 years, 70% males) were enrolled, 65% with ST-segment elevation (STEMI), 30% with no ST-segment elevation (NSTEMI) and 5% with undetermined ECG. The median delay between symptom onset and hospital arrival was 2h and 9 min with 76% of patients hospitalized within the sixth hour (26% within the first hour, 48% within the second). The median delay from hospital arrival to reperfusion therapy in STEMI was 45 min (IQR 26-85) for thrombolysis (50% of the patients) and 85 min (IQR 60-135) for primary angioplasty (15% of the patients). Coronary angiography was performed during hospital stay in 46% of the patients (STEMI 48%, NSTEMI 43%, undetermined AMI 35%), coronary angioplasty in 25% (STEMI 26%, NSTEMI 15%, undetermined AMI 13%) and coronary bypass in 1.4% (1%, 2.2% and 1% respectively). Twenty-two percent of the patients admitted to hospitals without cath-lab were transferred to a tertiary care hospital for invasive procedures. The overall median hospital stay was 10 days (IQR 7-12, STEMI 10, NSTEMI 9, undetermined AMI 11) and was not significantly different between hospitals with or without cath-lab (respectively, 9 and 10 days, P=0.38). After discharge and up to 30 days, coronary angiography was performed in 11% (STEMI 11%, NSTEMI 11%, undetermined MI 9%), angioplasty in 10% (STEMI 10%, NSTEMI 11%, undetermined MI 7%), bypass surgery in 7% (STEMI 5%, NSTEMI 11%, undetermined AMI 7%). The in-hospital and 30-day case fatality rates were 7.4% and 9.4%, respectively (7.5% and 9.5% for STEMI, 5.2% and 7.1% for NSTEMI, 18.2% and 21.2% for undetermined MI). CONCLUSIONS Patients with acute myocardial infarction admitted to the Italian CCUs, are older than those represented in clinical trials. A high proportion of these cases has the chance to receive early reperfusion therapy. Short-term mortality is lower than expected for patients with STEMI, but higher than reported for NSTEMI.

Current presentation and management of heart failure in cardiology and internal medicine hospital units: a tale of two worlds--the TEMISTOCLE study.

BACKGROUND The purpose pf the current article is to describe the clinical profile, use of resources, management and outcome in a population of real-world inpatients with heart failure. METHODS AND RESULTS With a prospective, cross-sectional survey on acute hospital admissions, we evaluated the overall and provider-related differences in patient characteristics, diagnostic work-up, treatment and inhospital outcome of 2127 patients with heart failure admitted to 167 cardiology departments and 250 internal medicine departments between February 14 and 25, 2000. Patients admitted to cardiology units were younger (56.3% >70 years vs 76.2%, P <.0001), had more severe symptoms (NYHA IV 35% vs 29%, P =.00014), and more often underwent evaluation of ventricular function (89.3% vs 54.8%, P <.0001) and coronary angiography (7.5% vs 0.9%, P <.0001) than those admitted to medical units. Moreover, they were more often prescribed beta-blockers (17.8% vs 8.7%, P <.0001). However, prescription of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers (78.7% vs 81.5%, P = not significant [NS]) and inhospital mortality (5.2% vs 5.9%, P = NS) were similar. A 6-month follow-up visit was performed in 56.4% of cases (68.2% of cardiology vs 49.4% of medicine patients, P <.0001); 6-month readmission (43.7% vs 45.4%, P = NS) and mortality (13.9% vs 16.7%, P = NS) rates were similar. CONCLUSIONS Patients with heart failure admitted to cardiology and internal medicine units represent 2 clearly different populations. In both groups, diagnostic procedures and evidence-based treatments, such as beta-blockers, appeared to be underused, and there was a lack of structured follow-up, as well as a poor 6-month prognosis.

Precipitating factors and decision-making processes of short-term worsening heart failure despite “optimal” treatment (from the IN-CHF Registry) ☆

This study sought to prospectively assess which factors were related to short-term worsening heart failure (HF) leading to or not to hospital admission, in long-term outpatients followed by cardiologists. The subsequent decision-making process was also analyzed. The study population consisted of 2,701 outpatients enrolled in the registry of the Italian Network on Congestive Heart Failure (IN-CHF) and followed by 133 cardiology centers (19% of all existing Italian cardiology centers). Clinical and follow-up data were collected by local trained clinicians; 215 patients (8%) had short-term decompensation (on average 2 months after the index outpatient visit). Multivariate analysis showed that previous hospitalization, long duration of symptoms, ischemic etiology, atrial fibrillation, higher functional class (New York Heart Association classification III to IV), higher heart rate, and low systolic blood pressure were independently associated with HF destabilization. Poor compliance (21%) and infection (12%) were the most frequent precipitating factors, but a precipitating factor was not identified in 40% of the patients. Poor compliance was more common in women, but no other clinical characteristics emerged as being related with a specific precipitating factor. Fifty-seven percent of the patients with a short-term recurrence of worsening HF required hospital admission; infusion treatment with inotropes and/or vasodilators was necessary in 19% of them. Long-term therapy was changed in 48% of the patients. Thus, in ambulatory HF patients, short-term worsening HF can be predicted according to the clinical characteristics on an outpatient basis. Nearly 1/3 of precipitating factors can be prevented. Patient education and avoidance of inappropriate treatment may reduce the number of relapses.

Anti-remodelling effect of canrenone in patients with mild chronic heart failure (AREA IN-CHF study): final results.

To test whether canrenone, an aldosterone receptor antagonist, improves left ventricular (LV) remodelling in NYHA class II heart failure (HF). Aldosterone receptor antagonists improve outcome in severe HF, but no information is available in NYHA class II.

Effects of rosuvastatin on atrial fibrillation occurrence: ancillary results of the GISSI-HF trial

AIMS This ancillary analysis of the GISSI-HF database aims at assessing the effect of rosuvastatin on the occurrence of atrial fibrillation (AF) in patients with chronic heart failure (HF) who were not in AF at study entry. METHODS AND RESULTS GISSI-HF was a double-blind, placebo-controlled trial testing n-3 PUFA and rosuvastatin vs. corresponding placebos in patients with chronic HF. Atrial fibrillation occurrence was defined as the presence of AF in the electrocardiogram (ECG) performed at each visit during the trial or AF as a cause of worsening HF or hospital admission or as an event during hospitalization. Among the 3690 patients (80.7%) without AF on their baseline ECG, 15.0% developed AF during a median follow-up period of 3.7 years, 258 randomized to rosuvastatin (13.9%) vs. 294 allocated to placebo (16.0%). Although the difference was not significant at unadjusted analysis (P = 0.097) and multivariable analysis adjusting for clinical variables (P = 0.067), it became significant after adjustment for clinical variables and laboratory examinations (P = 0.039), and for clinical variables, laboratory examinations, and background therapies (P = 0.038). CONCLUSION This study shows that there is some evidence of a beneficial effect of rosuvastatin in terms of reduction of AF occurrence in patients with HF. Larger populations are needed to provide a definite answer to the question. ClinicalTrials.gov Identifier: NCT00336336.

Comparison of one-year outcome in women versus men with chronic congestive heart failure

Using information from the Italian Network on Congestive Heart Failure, we examined whether clinical epidemiologic characteristics, drug prescription patterns, and outcome of patients with congestive heart failure differed according to sex and whether gender was an independent risk factor for mortality and hospital admissions.

Pentraxin-3 in chronic heart failure: the CORONA and GISSI-HF trials.

Pentraxin‐3 (PTX3) is a component of the humoral arm of innate immunity which can regulate inflammatory processes. Since the role of inflammation in the progression of chronic heart failure (HF) is debated, we investigated the prognostic value of PTX3 and the effect of a statin in two large populations of patients with HF.

Current presentation and management of 7148 patients with atrial fibrillation in cardiology and internal medicine hospital centers: the ATA AF study.

BACKGROUND Atrial fibrillation (AF) is associated with a high risk of stroke and mortality. AIMS To describe the difference in AF management of patients (pts) referred to Cardiology (CARD) or Internal Medicine (MED) units in Italy. METHODS AND RESULTS From May to July 2010, 360 centers enrolled 7148 pts (54% in CARD and 46% in MED). Median age was 77 years (IQR 70-83). Hypertension was the most prevalent associated condition, followed by hypercholesterolemia (28.9%), heart failure (27.7%) and diabetes (24.3%). MED pts were older, more frequently females and more often with comorbidities than CARD pts. In the 4845 pts with nonvalvular AF, a CHADS2 score ≥ 2 was present in 53.0% of CARD vs 75.3% of MED pts (p<.0001). Oral anticoagulants (OAC) were prescribed in 64.2% of CARD vs 46.3% of MED pts (p<.0001); OAC prescription rate was 49.6% in CHADS2 0 and 56.2% in CHADS2 score ≥ 2 pts. At the adjusted analysis patients managed in MED had a significantly lower probability to be treated with OAC. Rate control strategy was pursued in 51.4% of the pts (60.5% in MED and 43.6% in CARD) while rhythm control was the choice in 39.8% of CARD vs 12.9% of MED pts (p<.0001). CONCLUSIONS Cardiologists and internists seem to manage pts with large epidemiological differences. Both CARD and MED specialists currently fail to prescribe OAC in accordance with stroke risk. Patients managed by MED specialists have a lower probability to receive an OAC treatment, irrespective of the severity of clinical conditions.