Emanuele Carbonieri

The predictive value of stable precursor fragments of vasoactive peptides in patients with chronic heart failure: data from the GISSI‐heart failure (GISSI‐HF) trial

Though various neurohormonal systems are concurrently activated during heart failure (HF), their biological effectors are not always easy to measure due to their short life in vivo, instability in biological samples, or very low concentrations. We measured the plasma concentrations of four stable precursor fragments of neurohormonal systems in patients with chronic HF and evaluated their relationship with outcome.

Prevalence and Prognostic Value of Elevated Urinary Albumin Excretion in Patients With Chronic Heart Failure Data From the GISSI-Heart Failure Trial

Background—Increased urinary excretion of albumin is an early sign of kidney damage and a risk factor for progressive cardiovascular and renal diseases and heart failure. There is, however, only limited information on the prevalence and prognostic role of urinary albumin excretion in patients with established chronic heart failure. Methods and Results—A total of 2131 patients enrolled in 76 sites participating in the GISSI-Heart Failure trial provided a first morning spot sample of urine at any of the clinical visits scheduled in the trial to calculate the urinary albumin-to-creatinine ratio. The relation between log-transformed urinary albumin-to-creatinine ratio and all-cause mortality (428 deaths, time from urine collection to event or censoring) was evaluated with Cox multivariable models adjusted for all significant risk factors at the time of urine collection, in the study population, and in patients without diabetes or hypertension. Almost 75% of the patients had normal urinary albumin excretion, but 19.9% had microalbuminuria (30 to 299 mg/g creatinine) and 5.4% had overt albuminuria (≥300 mg/g). There was a progressive, significant increase in the adjusted rate of mortality in the study population (hazard ratio, 1.12; 95% CI, 1.05 to 1.18 per 1-U increase of log(urinary albumin-to-creatinine ratio), P=0.0002) and in the subgroup of patients without diabetes or hypertension. Randomized treatments (n-3 polyunsaturated fatty acids or rosuvastatin) had no major impact on albumin excretion. Conclusions—Independently of diabetes, hypertension, or renal function, elevated albumin excretion is a powerful prognostic marker in patients with chronic heart failure.

Prevalence and Prognostic Value of Elevated Urinary Albumin Excretion in Patients With Chronic Heart FailureCLINICAL PERSPECTIVE

Background—Increased urinary excretion of albumin is an early sign of kidney damage and a risk factor for progressive cardiovascular and renal diseases and heart failure. There is, however, only limited information on the prevalence and prognostic role of urinary albumin excretion in patients with established chronic heart failure. Methods and Results—A total of 2131 patients enrolled in 76 sites participating in the GISSI-Heart Failure trial provided a first morning spot sample of urine at any of the clinical visits scheduled in the trial to calculate the urinary albumin-to-creatinine ratio. The relation between log-transformed urinary albumin-to-creatinine ratio and all-cause mortality (428 deaths, time from urine collection to event or censoring) was evaluated with Cox multivariable models adjusted for all significant risk factors at the time of urine collection, in the study population, and in patients without diabetes or hypertension. Almost 75% of the patients had normal urinary albumin excretion, but 19.9% had microalbuminuria (30 to 299 mg/g creatinine) and 5.4% had overt albuminuria (≥300 mg/g). There was a progressive, significant increase in the adjusted rate of mortality in the study population (hazard ratio, 1.12; 95% CI, 1.05 to 1.18 per 1-U increase of log(urinary albumin-to-creatinine ratio), P=0.0002) and in the subgroup of patients without diabetes or hypertension. Randomized treatments (n-3 polyunsaturated fatty acids or rosuvastatin) had no major impact on albumin excretion. Conclusions—Independently of diabetes, hypertension, or renal function, elevated albumin excretion is a powerful prognostic marker in patients with chronic heart failure.

Effect of n-3 polyunsaturated fatty acids and rosuvastatin in patients with heart failure: results of the GISSI-HF trial

Epidemiological, experimental studies and post hoc analyses of randomized trials suggested that n-3 polyunsaturated fatty acids (PUFA) and statins could be beneficial in chronic heart failure. Two double-blind, placebo-controlled, randomized clinical trials investigated the efficacy and safety of n-3 PUFA 1 g daily (R1) and rosuvastatin 10 mg daily (R2) in patients with heart failure. In total, 6975 and 4574 patients were randomized in R1 and R2, respectively; the main reason for excluding patients from R2 being the open-label administration of statin treatment. Primary end points were death, and death or admission to hospital for cardiovascular reasons. n-3 PUFA, but not rosuvastatin, significantly decreased the two coprimary end points: 56 and 44 patients needed to be treated with n-3 PUFA for a median duration of 3.9 years to avoid one death or one cumulative event. Both drugs were safe and were tolerated. A simple and safe treatment with n-3 PUFA provides a beneficial advantage in patients with heart failure in a context of usual care.

Relation between serum sodium levels and prognosis in outpatients with chronic heart failure: neutral effect of treatment with beta-blockers and angiotensin-converting enzyme inhibitors

Introduction The predictive role of hyponatremia has been tested in acute and chronic heart failure. Sodium level is inversely related with renin–angiotensin–aldersterone system (RAAS) and sympathetic nervous activity but important issues remain unresolved. Our aim was to define the level of hyponatremia able to predict 1-year outcomes and investigate the relation between sodium levels and mortality and the effect of beta-blockers and angiotensin-converting enzyme (ACE) inhibitors on this relation. Methods We analyzed 4670 patients enrolled in the IN-CHF Italian Registry. We controlled the predictivity of hyponatremia, testing it either as a continuous variable and dividing the study sample into three severity groups: group 1 (≥136 mEq/l; n = 4207), group 2 (131–135 mEq/l; n = 389) and group 3 (⩽130 mEq/l; n = 74). The linearity of the relationship between sodium levels and mortality was also tested. Results Mild-to-moderate and severe hyponatremia (groups 2 and 3) independently predicted the 1-year mortality. The relation between sodium concentration and death was not linear and a decrease of 1 mEq/l of sodium increased death rate only for values of sodium 142.9 mEq/l or less. This relationship was not modified by beta-blocker and ACE inhibitor therapies. Conclusion Our data confirm the negative prognostic value of hyponatremia, even of moderate degree, independently of the use of recommended treatments for heart failure.

Treatment with inotropes and related prognosis in acute heart failure: Contemporary data from the Italian Network on Heart Failure (IN-HF) Outcome registry

BACKGROUND In the recent Italian Network on Heart Failure (IN-HF) Outcome registry, including 1,855 patients with acute heart failure (AHF), we reviewed the use of inotropes and their prognostic implication on in-hospital and 12-month mortality. METHODS IN-HF Outcome is a prospective, multicenter, observational, study involving 61 Italian cardiology centers. AHF patients have been enrolled over a 2-year period and followed-up for 1 year. Inotropes were used in 360 patients (19.4%). RESULTS Patients who received inotropes had a more severe clinical and hemodynamic profile than those who did not and exhibited a significantly higher rate of in-hospital (21.4% vs 2.7%, p < 0.01) and 1-year (50.6% vs 17.7%, p < 0.01) mortality. At entry, systolic blood pressure (SBP) was ≤ 110 mm Hg in 58%, 111 to 130 mm Hg in 24.5%, and > 130 mm Hg in 17.5%. Multivariable analyses showed use of inotropes was the strongest predictor of all-cause death. These data were confirmed by propensity score analyses. According to SBP at entry, the 2 groups with SBP > 110 mm Hg who took inotropes, despite a more favorable clinical profile, exhibited a similar worse prognosis, particularly at 1 year: 56.3% (≤ 110 mm Hg), 43.7% (111-130 mm Hg), and 40.3% (>130 mm Hg) vs 17.7%. CONCLUSIONS Inotropes were used in nearly 20% of the patient admitted for AHF, and this treatment was associated with a short-term to medium-term poor prognosis. An inappropriate use of inotropes in patients with normal to high SBP, and presumably preserved cardiac output, may have significantly contributed to affect the all-group outcome.

Levels of circulating pro-angiogenic cells predict cardiovascular outcomes in patients with chronic heart failure.

BACKGROUND Circulating pro-angiogenic cells (PACs) contribute to vascular and myocardial regeneration. A low level of PACs is associated with worse outcome in patients with coronary heart disease. However, little is known about PACs in heart failure (HF). METHODS AND RESULTS Blood was sampled at baseline in 111 patients with HF, 67 from 5 Italian Centers and 44 from Frankfurt, Germany. In cultured mononuclear cells from peripheral blood, PACs were counted as double-stained by tetramethylindocarbocyanine-labeled acetylated LDL and fluorescein-5-isothiocyanate-labeled lectin. Mean age of the patients was 62 years, 12 were females, 66 had ischemic etiology, 26 were in New York Heart Association Class >II. Cutoffs for PACs were assessed by receiver operating characteristic curves, to identify the optimal cutoffs for PAC level in predicting outcomes. Mean level of PACs was 35+/-29 (mean+/-SD) cells/mm(2), 2- to 3-fold lower than in age-matched healthy volunteers, but unrelated to severity of HF, age, or sex. Over 2.5 years, 12 cardiovascular deaths and 47 first hospitalizations for cardiovascular reasons were recorded. After adjustment for demographic and clinical variables, elevated creatinine and natriuretic peptides, and PACs <or=30.5/mm(2) were associated with a 2-fold higher risk of cardiovascular death and hospitalization, as shown by survival curves and by Cox multivariable. CONCLUSIONS The level of circulating PACs is an independent predictor of cardiovascular death and hospitalization in patients with chronic HF, it can be assessed in blood samples collected in a multicenter setting, and may offer an accessible tool to assess the role of vascular regeneration in patients with HF.

Prognostic role of B-type natriuretic peptide in patients with diabetes and acute decompensated heart failure.

Background  Several studies have reported the prognostic value of natriuretic peptides, but their predictive value in patients with diabetes mellitus is unknown. The aim of the study was to test the hypothesis that measurement of brain natriuretic peptide (BNP) levels in ambulatory patients with congestive heart failure (CHF) and diabetes can predict the occurrence of cardiovascular events at 6‐month follow‐up.

Prevalence and Prognostic Value of Elevated Urinary Albumin Excretion in Patients With Chronic Heart FailureCLINICAL PERSPECTIVE: Data From the GISSI-Heart Failure Trial

Background—Increased urinary excretion of albumin is an early sign of kidney damage and a risk factor for progressive cardiovascular and renal diseases and heart failure. There is, however, only limited information on the prevalence and prognostic role of urinary albumin excretion in patients with established chronic heart failure. Methods and Results—A total of 2131 patients enrolled in 76 sites participating in the GISSI-Heart Failure trial provided a first morning spot sample of urine at any of the clinical visits scheduled in the trial to calculate the urinary albumin-to-creatinine ratio. The relation between log-transformed urinary albumin-to-creatinine ratio and all-cause mortality (428 deaths, time from urine collection to event or censoring) was evaluated with Cox multivariable models adjusted for all significant risk factors at the time of urine collection, in the study population, and in patients without diabetes or hypertension. Almost 75% of the patients had normal urinary albumin excretion, but 19.9% had microalbuminuria (30 to 299 mg/g creatinine) and 5.4% had overt albuminuria (≥300 mg/g). There was a progressive, significant increase in the adjusted rate of mortality in the study population (hazard ratio, 1.12; 95% CI, 1.05 to 1.18 per 1-U increase of log(urinary albumin-to-creatinine ratio), P=0.0002) and in the subgroup of patients without diabetes or hypertension. Randomized treatments (n-3 polyunsaturated fatty acids or rosuvastatin) had no major impact on albumin excretion. Conclusions—Independently of diabetes, hypertension, or renal function, elevated albumin excretion is a powerful prognostic marker in patients with chronic heart failure.