Lucio Gonzini

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.

In-hospital and 1-year outcomes of acute heart failure patients according to presentation (de novo vs. worsening) and ejection fraction. Results from IN-HF Outcome Registry

BACKGROUND To investigate the outcomes of hospitalized patients with both de-novo and worsening heart failure (HF) with preserved left ventricular ejection fraction (LVEF) (HFpEF) (LVEF ≥ 50%), compared to those with reduced LVEF (HFrEF). METHODS AND RESULTS We studied 1669 patients (22.6% HFpEF) hospitalized for acute HF in the prospective multi-center nationwide Italian Network on Heart Failure (IN-HF) Outcome Registry. In all patients LVEF was assessed during hospitalization. De-novo HF presentations constituted 49.6% of HFpEF and 43.1% of HFrEF hospitalizations. All-cause mortality during hospitalization was lower in HFpEF than HFrEF (2.9% vs 6.5%, p=0.01), but this mortality difference was not significant at 1 year (19.6% vs 24.4%, p=0.06), even after adjusting for clinical covariates. Similarly, there were no differences in 1-year mortality between HFpEF and HFrEF when compared by cause of death (cardiovascular vs non-cardiovascular) or mode of presentation (worsening HF vs de novo). Rehospitalization rates (all-cause, non-cardiovascular, cardiovascular, HF-related) at 90 days and 1 year were also similar. Mode of presentation influenced rehospitalizations in HFpEF, where those presenting with worsening HFpEF had higher all-cause (36.8% vs 21.6%, p=0.001), cardiovascular (28.1% vs 14.9%, p=0.002), and HF-related (21.1% vs 7.7%, p=0.0003) rehospitalization rates at 1 year compared to those with de novo presentations. CONCLUSIONS Outcomes at 1 year following hospitalization for HFpEF are as poor as that of HFrEF. A prior history of HF decompensation or hospitalization identifies patients with HFpEF at particularly high risk of recurrent events. These findings may have implications for clinical practice, quality and process improvements and trial design.

The 'real' woman with heart failure. Impact of sex on current in-hospital management of heart failure by cardiologists and internists

To identify differences between sexes in the clinical profile, use of resources, management and outcome in a large population of ‘real world’ patients with heart failure (HF).

Temporal trends in the epidemiology, management, and outcome of patients with cardiogenic shock complicating acute coronary syndromes.

Despite advances in the management of patients with acute coronary syndrome (ACS), cardiogenic shock (CS) remains the leading cause of death in these patients. We describe the evolution of clinical characteristics, in‐hospital management, and outcome of patients with CS complicating ACS.

Clinical characteristics, management, and prognosis of octogenarians with acute heart failure admitted to cardiology wards: Results from the Italian Survey on Acute Heart Failure

BACKGROUND Heart failure is the leading cause of hospitalization among the elderly. This study compares clinical characteristics, management, and prognosis of octogenarians (OLD) with younger (YOUNG) patients in the Italian Survey on Acute Heart Failure (AHF). METHODS A nationwide, prospective, observational study on AHF was done. Two hundred six Italian departments with intensive cardiac care units enrolled 2,807 patients in 3 months. RESULTS Octogenarians (mean age 84 +/- 4 years) represented 28% of enrollees. Females were 50% in the OLD group versus 36% in the YOUNG group (P < .0001). Risk factors such as obesity, diabetes, and smoking were more frequent in the YOUNG group. Comorbidities such as anemia and renal dysfunction were more common in the OLD group (64% vs 53%, P < .0001, and 56% vs 43%, P < .0001). More octogenarians were admitted with cardiogenic shock and pulmonary edema, whereas younger patients presented more frequently in New York Heart Association class III to IV (P = .002). Left ventricular ejection fraction was measured in 90% of octogenarians versus 93% of the younger ones and was preserved in 41% of the OLD group versus 31% of the YOUNG group (P < .0001). Coronary angiography was performed in 20% of the YOUNG group and 10% of the OLD group. In-hospital mortality was twice as high in the OLD group (11.8% vs 5.6%, P < .001). In multivariable analysis, the strongest predictors of this event were use of inotropic agents, advanced age (> or =80 years), and elevated troponin at admission. CONCLUSIONS Octogenarians represent more than one fourth of the admissions for AHF and have a more severe clinical presentation. Their management is less aggressive, and treatments recommended by guidelines are underused. In-hospital mortality is high in the OLD group independently of left ventricular ejection fraction.

A decade of changes in clinical characteristics and management of elderly patients with non-ST elevation myocardial infarction admitted in Italian cardiac care units.

Objective To describe the evolution of clinical characteristics, in-hospital management and early outcome of elderly patients with non-ST elevation myocardial infarction (NSTEMI). Methods We analysed data from five consecutive Italian nationwide registries, conducted between 2001 and 2010, including patients with acute coronary syndromes admitted to cardiac care units (CCUs). Results Of 10 983 patients with NSTEMI enrolled in the 5 surveys, 4350 (39.6%) were ≥75 years old (mean age 81±5 years). Some clinical characteristics such as diabetes mellitus, hypertension, renal dysfunction and previous percutaneous coronary intervention increased significantly, whereas a history of stroke, myocardial infarction and heart failure decreased over time. An invasive approach increased from 26.6% in 2001 to 68.4% in 2010 (p<0.0001) and revascularisation rates increased from 9.9% to 51.7% (p<0.0001). Early use and prescription at discharge of β-blockers, statins and dual antiplatelet treatment increased significantly (p<0.0001). Thirty-day observed mortality decreased from 14.6% (95% CI 9.9 to 20.4) to 9.5% (95% CI 7.7 to 11.6). At the multivariate logistic regression analyses adjusted for baseline characteristics, compared with 2001, the risk of death was significantly lower in all the other studies performed at different times with reductions in adjusted mortality between 66% and 45%. Conclusions Over the past decade, substantial changes have occurred in the clinical characteristics and management of elderly patients admitted with NSTEMI in Italian CCUs, with a greater use of revascularisation therapy and recommended medications. These variations have been associated with a reduction in 30-day adjusted mortality rate.

Role of beta-blockers in patients admitted for worsening heart failure in a real world setting : data from the Italian Survey on Acute Heart Failure

Randomized trials have shown that beta‐blockers (BBs) reduce mortality in chronic heart failure (HF). Less data are available on the role of BBs in patients with acute HF, specifically if BBs should be continued or temporarily withdrawn. The aim of this study was to evaluate the role of BBs on in‐hospital outcomes of patients admitted for worsening HF in a Cardiology setting.

Baseline characteristics of patients recruited in the AREA IN-CHF study (Antiremodelling Effect of Aldosterone Receptors Blockade with Canrenone in Mild Chronic Heart Failure)

Objective Excess aldosterone activity contributes to the pathogenesis and progression of heart failure (HF). Aldosterone antagonists improve clinical outcome in patients with severe HF or left ventricular (LV) dysfunction after myocardial infarction, but knowledge of their impact in mild chronic HF is sparse. AREA IN-CHF was planned to investigate the effects of canrenone on progression of LV remodelling in mild HF. Methods AREA IN-CHF is a multicentre, randomised, double-blind, parallel group comparison of canrenone (up to 50 mg/day) versus placebo in mild stable HF. The primary endpoint is change in echocardiographic LV end-diastolic volume over 12 months. Patients had New York Heart Association class II HF, LV ejection fraction ≤45%, stable standard therapy, creatinine ≤2.5 mg/dl, potassium ≤5.0 mmol/l. Follow-up examinations were scheduled monthly for the first 3 months and every 3 months thereafter. Aldosterone was measured at baseline, brain natriuretic peptide and procollagen type III amino-terminal peptide (PIIINP) at baseline and at 6 months. Echocardiography was performed at baseline, at 6 and 12 months. Results Among 467 patients, median age 64 years (interquartile range (IQR) 56–70 years), 84% were men, 52% had ischaemic HF, 96% were receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, 79% β-blockers. Brain natriuretic peptide, aldosterone and PIIINP were 88 pg/ml (IQR 35–185 pg/ml), 118 pg/ml (IQR 75–177 pg/ml), and 5.38 μg/l (IQR 3.98–7.14 μg/l), respectively. LV end-diastolic volume was 79 ml/m2 (IQR 64–105 ml/m2) and LV ejection fraction was 40% (IQR 33–45%). Conclusions The role of aldosterone blockade in patients with mild HF remains to be established. AREA IN-CHF is addressing this issue in a large population on optimal medical therapy.

Evolution of renal function during and after an episode of cardiac decompensation: results from the Italian survey on acute heart failure.

Background Renal dysfunction is frequently associated with heart failure and strongly influences the outcome of heart failure patients. Although recommended pharmacological interventions for heart failure may contribute to the development of, or worsen renal dysfunction, their relations with renal function have not been fully explored in an unselected community population. Methods and aim We studied 1008 patients recruited in the Italian survey on acute heart failure to assess the prevalence, the prognostic role of renal function and the relations between the changes in renal function and the pharmacological interventions during hospitalization and at 6-month follow-up. Patients were categorized using the National Kidney Foundation cut-offs for degree of renal function measured by the glomerular filtration rate. Results Moderate-to-severe renal dysfunction was diagnosed in 59% of patients at hospital admission and 61% at discharge. These patients were older and had a higher prevalence of diabetes, anemia, history of hypertension, myocardial infarction and hospitalization for heart failure than those with normal or mildy impaired renal function. At admission the former were treated more frequently with diuretics, angiotensin converting enzyme-inhibitor (ACEi) or angiotensin receptor blockers (ARBs) than the latter. Diuretics were given at higher dose and for a longer time during the hospital stay while beta-blockers, digoxin, antialdosterone agents, ACEi and ARBs were given less frequently in patients who had moderate-to-severe renal dysfunction than those who did not. High-dose diuretic treatment, inability to start or maintain beta-blockers during hospital stay and the nonprescription of ACEi/ARBs at discharge emerged, by multivariate analysis, as predictors of death at 6-month follow-up (mortality rate = 14%), independent of the persistence of moderate-to-severe renal dysfunction over time, anemia, male sex and history of heart failure. Conclusions In acute heart failure, renal dysfunction is frequent and impacts prognosis. In this setting, the pharmacological interventions are significantly associated with changes in renal function and 6-month mortality.

Secondary prevention after acute myocardial infarction: Drug adherence, treatment goals, and predictors of health lifestyle habits. The BLITZ-4 Registry

Background To describe drug adherence and treatment goals, and to identify the independent predictors of smoking persistence and unsatisfactory lifestyle habits six months after an acute myocardial infarction (AMI). Methods and results 11,706 patients with AMI (30% female, mean age 68 years) were enrolled in 163 large-volume coronary care units (CCUs). At six months, drug adherence was ≥90%, while blood pressure (BP) <140/90 mmHg, low density lipoprotein (LDL) <100 mg/dl (in patients on statins), HbA1c <7% (in treated diabetics), and smoking persistence were observed in 74%, 76%, 45%, and 27% of patients, respectively. Inadequate fish intake decreased from 73% to 55%, inadequate intake of fruit and vegetables from 32% to 23%, and insufficient exercise in eligible patients from 74% to 59% (p < 0.0001). At multivariable analysis, a post-discharge cardiac visit and referral to cardiac rehabilitation at follow-up were independently associated with a lower risk of insufficient physical exercise (odds ratio (OR) 0.71 and 0.70, respectively) and persistent smoking (OR 0.68 and 0.60), whereas only referral to cardiac rehabilitation was associated with a lower risk of inadequate fish and fruit/vegetable intake (OR 0.70 and 0.65). Conclusions Six months after an AMI, despite a high adherence to drug treatments, BP, LDL, and diabetic goals are inadequately achieved. Subjects with healthy lifestyles improved after discharge, but the rate of those with regular exercise habits and adequate fish intake could be further improved. Access to post-discharge cardiac visit and referral to cardiac rehabilitation were associated with better adherence to healthy lifestyles. Knowledge of the variables associated with specific lifestyle changes may help in tailoring secondary prevention programmes.