Renato Urso

EURObservational Research Programme: regional differences and 1‐year follow‐up results of the Heart Failure Pilot Survey (ESC‐HF Pilot)

The ESC‐HF Pilot survey was aimed to describe clinical epidemiology and 1‐year outcomes of outpatients and inpatients with heart failure (HF). The pilot phase was also specifically aimed at validating structure, performance, and quality of the data set for continuing the survey into a permanent Registry.

Co-morbidities in patients with heart failure: an analysis of the European Heart Failure Pilot Survey

Co‐morbidities frequently accompany heart failure (HF), contributing to increased morbidity and mortality, and an impairment of quality of life. We assessed the prevalence, determinants, regional variation, and prognostic implications of co‐morbidities in patients with chronic HF in Europe.

Predictors of Mortality in 6975 Patients With Chronic Heart Failure in the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico-Heart Failure Trial Proposal for a Nomogram

Background —We developed a prognostic model to assess the risk of all-cause mortality in patients with chronic heart failure (HF). Methods and Results —We examined 6975 patients with chronic HF enrolled in the GISSI-HF trial (3.9 years follow-up). Multi-variable Cox regression models were developed to predict mortality (1969 deaths). By stepwise selection, the full final model included 25 predictors. A reduced model, considering the most significant variables ranked according to the Wald Chi-Square (p <0.0001) accounted for most of the prognostic information. Internal validation of the model was performed with bootstrap techniques. The discrimination ability of the reduced model constituted by 12 factors (CPE=0.693) was as good as the full final model (CPE= 0.70). Among the first 12 independent risk factors emerging in the reduced model, the three most powerful predictors were older age, higher NYHA class and lower estimated glomerular filtration rate (eGFR). Other independent predictors that increased risk included lower left ventricular ejection fraction, chronic obstructive pulmonary disease, lower systolic blood pressure, diabetes, male sex, higher uricemia, lower body mass index, lower hemoglobin and aortic stenosis. The reduced model was used to build a nomogram to estimate the risk of death in individual patients. In a subgroup of patients, the two well-known biomarkers (hs-cTnT and NT-proBNP) emerged as the most powerful predictors of outcome. Conclusions —In a large contemporary chronic HF population, this model offers good ability to assess the risk of death, confirming most of the risk factors that have emerged in recent trials. Clinical Trial Registration —URL: http://www.clinicaltrials.gov. Unique identifier: [NCT00336336][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00336336&atom=%2Fcirchf%2Fearly%2F2012%2F11%2F14%2FCIRCHEARTFAILURE.112.967828.atom

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.

Predictors of Mortality in 6975 Patients with Chronic Heart Failure in the GISSI-HF Trial: Proposal for a Nomogram

Background —We developed a prognostic model to assess the risk of all-cause mortality in patients with chronic heart failure (HF). Methods and Results —We examined 6975 patients with chronic HF enrolled in the GISSI-HF trial (3.9 years follow-up). Multi-variable Cox regression models were developed to predict mortality (1969 deaths). By stepwise selection, the full final model included 25 predictors. A reduced model, considering the most significant variables ranked according to the Wald Chi-Square (p <0.0001) accounted for most of the prognostic information. Internal validation of the model was performed with bootstrap techniques. The discrimination ability of the reduced model constituted by 12 factors (CPE=0.693) was as good as the full final model (CPE= 0.70). Among the first 12 independent risk factors emerging in the reduced model, the three most powerful predictors were older age, higher NYHA class and lower estimated glomerular filtration rate (eGFR). Other independent predictors that increased risk included lower left ventricular ejection fraction, chronic obstructive pulmonary disease, lower systolic blood pressure, diabetes, male sex, higher uricemia, lower body mass index, lower hemoglobin and aortic stenosis. The reduced model was used to build a nomogram to estimate the risk of death in individual patients. In a subgroup of patients, the two well-known biomarkers (hs-cTnT and NT-proBNP) emerged as the most powerful predictors of outcome. Conclusions —In a large contemporary chronic HF population, this model offers good ability to assess the risk of death, confirming most of the risk factors that have emerged in recent trials. Clinical Trial Registration —URL: http://www.clinicaltrials.gov. Unique identifier: [NCT00336336][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00336336&atom=%2Fcirchf%2Fearly%2F2012%2F11%2F14%2FCIRCHEARTFAILURE.112.967828.atom

Nimodipine: drug pharmacokinetics and plasma adenosine levels in patients affected by cerebral ischemia.

Nimodipine is a dihydropyridine calcium channel blocker used in the treatment of ischemic damage in subarachnoid hemorrhage. Recent investigations have shown that it is able to inhibit adenosine transport in human red blood cells and parietal cortex neurons. In this study we investigated the pharmacokinetics of nimodipine and the effect on plasma adenosine levels in patients affected by cerebral ischemia.

Activity of citalopram on adenosine and serotonin circulating levels in depressed patients.

Abstract: Citalopram is a selective serotonin reuptake inhibitor used in the treatment of depression. Recent investigations have shown that it reduces in rat brain the release of excitatory amino neurotransmitters acid glutamate and aspartate by the involvement of the inhibitory neuromodulator adenosine. In this study, we described citalopram and serotonin levels in plasma and platelets, as well as plasma adenosine levels, in depressive patients during acute and chronic administration of citalopram. Twelve patients affected by Major Depression (DSM-IV) received a single oral dose of citalopram in the morning, 5 mg in the first 5 days, 10 mg from the 6th to the 10th day, and 20 mg from the 11th to the 40th day. Blood samples for citalopram, serotonin, and adenosine were collected at Time 0 and 4, 12 and 24 hours after drug administration on the first day of citalopram 5 mg, and on the first and the last day of citalopram 20 mg. Citalopram, serotonin, and adenosine concentrations in plasma increased after citalopram administration, and the highest levels were observed on the last day of treatment. Citalopram was detectable in platelets with concentrations showing a time variation similar to plasma values. Serotonin levels in platelets decreased after drug administration, reaching the lowest values on the last day of treatment.

Pharmacokinetics of exogenous adenosine in man after infusion

SummaryThe plasma kinetics of adenosine was investigated in healthy volunteers after a 1 minute infusion of 2.5, 5 and 10 mg (38, 79 and 148 μg·kg−1 respectively) and after infusion of 200 μg·kg−1 in 10 min followed by 400 μg·kg−1 in 10 min.As the dose in the 1 min infusion study was increased the mean CL of adenosine decreased (10.7, 4.70 and 4.14 l·min−1, respectively), its mean half-life increased (0.91, 1.24 and 1.86 min, respectively), and the mean volume of distribution did not show any clear trend (8–13 l).After the 20 minute infusion the plasma level of adenosine reached a peak value comparable to that observed after infusion of 5 mg in 1 min (about 0.5 μg·ml−1), but the mean clearance and half-life were significantly different (12.1 l·min−1 and 0.63 min respectively).In all the subjects the plasma concentration of adenosine had returned to the baseline value in 5–15 min after the end of the infusion.

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.

Prognostic impact of in-hospital hyperglycemia in hospitalized patients with acute heart failure: Results of the IN-HF (Italian Network on Heart Failure) Outcome registry.

OBJECTIVES Although diabetes mellitus is frequently associated with heart failure (HF), the association between elevated admission glucose levels and adverse outcomes has not been well established in hospitalized patients with acute HF. METHODS We prospectively evaluated in-hospital mortality, post-discharge 1-year mortality and 1-year re-hospitalization rates in the Italian Network on Heart Failure (IN-HF) Outcome registry cohort of 1776 patients hospitalized with acute HF and stratified by their admission glucose levels (i.e., known diabetes, newly diagnosed hyperglycemia, no diabetes). RESULTS Compared with those without diabetes (n = 586), patients with either known diabetes (n = 749) (unadjusted-odds ratio [OR] 1.64, 95%CI 0.99–2.70) or newly diagnosed hyperglycemia (n = 441) (unadjusted-OR 2.34, 95%CI 1.39–3.94) had higher in-hospital mortality, but comparable post-discharge 1-year mortality rates. After adjustment for age, sex, systolic blood pressure, estimated glomerular filtration rate, left ventricular ejection fraction, HF etiology and HF worsening/de novo presentation, the results remained unchanged in patients with known diabetes (adjusted-OR 1.86, 95%CI 1.01–3.42), while achieved borderline significance in those with newly diagnosed hyperglycemia (adjusted-OR 1.81, 95%CI 0.95–3.45). One-year re-hospitalization rates were lower in patients with newly diagnosed hyperglycemia (adjusted-hazard ratio 0.74, 95%CI 0.56–0.96) than in other groups. CONCLUSIONS Elevated admission blood glucose levels are associated with poorer in-hospital survival outcomes in patients with acute HF, especially in those with previously known diabetes. This finding further highlights the importance of tight glycemic control during hospital stay and address the need of dedicated intervention studies to identify customized clinical protocols to improve in-hospital survival of these high-risk patients.