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Background: Clinical efficacy of sacubitril/valsartan administered for the recommended indication of patients with reduced (<40%) left ventricular ejection fraction (HFrEF) belonging to NYHA classes II-III appears to be higher than that one would expect based on the drug-induced variations of the left ventricular ejection fraction (LVEF). More thorough investigations with the use of indicators of longitudinal systolic function have been therefore recommended, to verify whether a part of the clinical improvement achieved with the use of sacubitril/valsartan might be supported by a reverse remodeling ensuing from changes other than a simple LVEF increase., Methods: In the present retrospective cohort study, which collected the pertinent data from two centers devoted to clinical management of outpatients with CHF and dating back to the years 2017 and 2018, we separated patients treated with sacubitril/valsartan from those treated with conventional medical therapy, including ACE inhibitors (ACEi) or angiotensin receptor blockers (ARBs). For the rest, the therapies practiced in the two cohorts - patients under sacubitril/valsartan and controls - were almost identical, including similar doses of beta-blockers and mineralocorticoid receptor antagonists (MRAs), plus loop diuretics, the latter administered at variable doses depending on the signs and symptoms of congestion. The endpoints were the variations of LVEF and global left ventricular longitudinal strain (GLS) over a study period not shorter than one year., Results: Patients collected within our retrospective cohort study were 132, of whom 44 treated with sacubitril/valsartan and 88 subjected to conventional therapy. All patients were marked by heart failure with reduced (LVEF<40%) left ventricular ejection fraction (HFREF). The mean duration of the retrospective observation period was 14±3 months. In the controls, LVEF was improved after one year of therapy - from 38.071±5.445% (mean±SD) to 41.595±5.282%; P=0.003. On the contrary, no significant improvement in the controls was identified for the GLS - from -12.059±4.016% to -12.250±4.287%; P=0.406. In analogy with controls, patients assigned to sacubitril/valsartan showed a significant increase in LVEF after one year of treatment - from 39.714±4.789% to 42.119±5.683%- (P<0.001). However, differently from the controls, sacubitril/valsartan group exhibited a significant improvement in GLS - from -10.142±3.080% to -18.238±7.284%; P<0.001)., Conclusions: The present retrospective cohort study demonstrates that the use of sacubitril/valsartan for HFREF patients, extended for a mean duration of 14 months, yields a significant improvement in the echocardiographic parameters of systolic function along the transverse (LVEF)and longitudinal (GLS) axes. For the GLS in particular a clear superiority emerges in comparison with conventional therapy including ACE-i or ARBs. From this data the hypothesis of a possible useful role of sacubitril/valsartan also for the therapy of HFpEF could be derived. In this regard, more exhaustive clarifications ensuing from the ongoing randomized controlled trials are eagerly awaited.

Introduction: In heart failure with reduced left ventricular ejection fraction (HFREF) patients, the dosage of sacubitril/valsartan is modulated according to a gradual increase regimen. Nevertheless, if patients exhibit tolerability problems, a provisional reduction of the dose of sacubitril/valsartan or even its interruption are recommended., Material and Methods: This study provides estimates of respective proportions of patients receiving minimum or intermediate doses of sacubitril/valsartan. In addition, a comparison was made to detect possible differences regarding all-cause mortality and heart failure hospitalization in patients treated with the recommended optimum dose compared to those receiving submaximum maintenance doses of sacubitril/valsartan., Results: Patients treated with sacubitril/valsartan in addition to beta-blocker and mineralocorticoid receptor blocker were 68. Among them, 20 patients (29.4%), were identified as having clinical features that were contraindications to the administration of sacubitril/valsartan at full dose. The subsequent decision was to maintain an intermediate dose in 11 patients and to reduce the dose to the minimum level allowed, i.e., 24 mg/26 mg twice daily in nine patients. After a median follow-up of 5.25 months, no differences were found concerning the risk of all-cause death by comparing patients treated with reduced versus those subjected to target doses of sacubitril/valsartan (odds ratio [OR] = 1.666; 95% confidence interval [CI] = 0.256-10.823; p = 0.6266). Patients taking reduced doses had a similar risk of heart failure hospitalizations when compared to patients treated with the target dose (OR = 0.789; 95% CI: 0.077-8.0808; p = 1.00)., Conclusion: During a median follow-up of 5.25 months, in the group of patients who had proven to be intolerant to the maximum dose of sacubitril/valsartan, use of reduced doses of the drug did not result in increased all-cause mortality or heart failure hospitalization compared to patients treated with sacubitril/valsartan at the target dose.

Background: Sacubitril, a neprilysin inhibitor in the combination molecule sacubitril/valsartan, slows down degradation of endogenous natriuretic peptides, thereby enhancing their beneficial cardiovascular effects. However, sacubitril might also promote neuronal dysfunction and cognitive impairment in patients with chronic heart failure (CHF) treated with sacubitril/valsartan, due to possible neprilysin inhibition at the level of Central Nervous System., Methods: A retrospective cohort study was undertaken to detect the effects exerted by sacubitril/valsartan on cognitive function in CHF patients. The patients' clinical data were examined for information provided in the Mini-Mental State Examination (MMSE), which was routinely administered during clinical visits at two centers from 15 March to 31 October 2017. Patients in the sacubitril/valsartan group had a clinical history of at least 3 months of continuous sacubitril/valsartan administration. The control group comprised CHF patients on conventional therapy not taking sacubitril/valsartan. In the between-group comparison, patients were matched for mean age, educational level, sex, NYHA class, and comorbidities. In the present retrospective study only patients in NYHA class II-III were enrolled., Results: The mean MMSE score was 22.72 ± 2.68 (mean ± standard deviation [SD]) in the sacubitril/valsartan group (n = 51 patients) vs. 21.96 ± 2.73 (mean ± SD) in the control group (n = 51; p = 0.1572, independent samples t-test). Thus, a similar mild-to-moderate impairment in cognitive performance was found in the comparison between the two groups., Conclusion: In our study, we did not find any evidence of the alleged harmful influence of sacubitril/valsartan on cognitive function. Patients taking sacubitril/valsartan for at least 3 months had similar mean MMSE scores to control subjects.

Background: The combination drug sacubitril/valsartan was reported to be superior to enalapril in reducing all-cause death, cardiovascular mortality, and heart failure (HF) hospitalizations in patients with cardiac insufficiency and reduced left ventricular ejection fraction (HFREF) with NYHA class II-IV., Methods: Our retrospective cohort study aimed to assess the effects of sacubitril/valsartan in addition to a beta-blocker and mineral receptor antagonist (MRA) in a group of HFREF patients with NYHA class II-III HF vs. conventional therapy (ACE inhibitor or angiotensin II receptor blocker added to a beta-blocker plus an MRA) administered to a control group of HFREF patients with comparable clinical features. In both groups, treatment was supplemented by a loop diuretic, usually furosemide, at variable doses. The primary outcomes were all-cause death and HF hospitalizations. Safety outcomes were symptomatic hypotension, angioedema, hyperkalemia, and worsening renal function., Results: Mortality at 6 months was 6.8% in patients taking sacubitril/valsartan vs. 34% in those on conventional therapy (odds ratio [OR] = 0.14; 95% CI: 0.04-0.49). Moreover, there was a 4.5% rate of HF hospitalizations in the sacubitril/valsartan group vs. 59% in the control group (OR = 0.03; 95% CI: 0.01-0.14). Safety outcomes were comparable in the two groups, although hypotension (systolic blood pressure < 100 mm Hg) was found in 15.9% of patients in the sacubitril/valsartan group vs. 5.7% in the control group (OR = 3.14; 95% CI: 0.94-10.55)., Conclusion: Sacubitril/valsartan offered strong protection against all-cause death and HF hospitalizations at 6 months without any significant side effects. To validate this efficacious molecule, further postmarketing observational studies, focusing mainly on hypotension and angioedema are warranted.

Despite recent advances in the management of heart failure with reduced ejection fraction (HFrEF), the burden of acute heart failure (AHF) remains significant with a high morbidity and mortality that has not been improved by any treatment modality. A meta-analysis summarized the study results on the effects of tolvaptan on AHF, which failed to demonstrate an improvement in short-term and long-term mortality, length of hospital stay and reduced frequency of worsening heart failure (WHF). Similar trial results were also reported in other AHF studies, such as the ASCEND-HF and the RELAX-AHF-2 trials. In view of these inconclusive studies it is evident that improving the prognosis of AHF patients remains an unmet medical need. Further efforts should focus on organ damage protection, individualized treatment, patient benefits and standardized management programs, including immediate identification and management of cardiogenic shock and establishment of HF networks for close monitoring of AHF patients.

Introduction: According to 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension (PH), no specific drug is currently indicated for PH related to left heart disease (PH-LDH), i.e., the one secondary to left chronic heart failure (CHF), which coincides with the group 2 of the PH classification endorsed by the above-mentioned guidelines. Indeed, adoption of therapies that specifically apply for so-called pulmonary arterial hypertension (group 1 of the PH classification) has been regarded as substantially contraindicated in patients with PH-LHD, according to current ESC/ERS guidelines. Nevertheless, based on some previous studies, phosphodiesterase 5 inhibitors (PDE5i) would seem to exert a beneficial effect in CHF patients, although the comparison between these studies shows quite inconsistent or heterogeneous findings. Thus, in order to better evaluate the effect of PDE5i therapy in CHF patients, we performed a meta-analysis of randomized controlled trials (RCTs)., Evidence Acquisition: PubMed and EMBASE databases were searched for RCTs that compared PDE5i with placebo in CHF with reduced (HFREF) or preserved (HFpEF) left ventricular ejection fraction. The endpoints of interest were: a composite of all-cause death or hospitalization, adverse events, peak VO2, Six-Minute Walk Test (6MWT), left ventricular ejection fraction (LVEF), E/e' ratio, mean pulmonary arterial pressure (mPAP), pulmonary arterial systolic pressure (PASP) and pulmonary vascular resistance (PVR)., Evidence Synthesis: Fourteen studies, enrolling a total of 928 patients, were comprised in the meta-analysis. Among these, 13 were RCTs and one was a subgroup analysis. Among patients with HFREF (N.=555), a significant benefit was conferred by PDE5i against the risk of the composite endpoint of death and hospitalization (OR=0.28; 95% CI: 0.10 to 0.74; P=0.03). Furthermore, among HFREF patients, therapy with PDE5i improved peak VO2 (difference in means [MD] 3.76 mL/min/kg; 95% CI: 3.27 to 4.25), as well as the 6MWT (MD=22.7 m; 95% CI: 8.19 to 37.21) and LVEF (MD=4.30%; 95% CI: 2.18% to 6.42%). For patients with HFREF, PDE5i therapy yielded a nonsignificant decrease in mPAP, while PASP was significantly reduced (MD=-11.52 mmHg; 95% CI: -15.56 to -7.49; P<0.001). By contrast, in the RCTs of patients with HFpEF (N.=373), no benefit ensued from PDE5i use regarding all of the investigated clinical, ergospirometric or hemodynamic endpoints., Conclusions: Therapy with PDE5i caused a statistically significant improvement of clinical outcomes, exercise capacity and pulmonary hemodynamics in patients with HFREF, but not in HFpEF. However, in view of the relatively small sample size of the HFpEF population recruited so far in the RCTs that investigated the effects of PDE5i treatment, further research in this field is required to clarify whether PDE5i are beneficial even in this subset.

In this brief review, the pathophysiology of hyponatremia and its clinical significance in the course of chronic heart failure (CHF) are illustrated. Moreover, issues concerning the optimal treatment for hyponatremia during CHF are addressed and discussed. In addition, advantages and limitations resulting from the use of vasopressin receptor antagonists, drugs that have recently emerged as the best available resource against hyponatremia, are highlighted.

Introduction: Aldosterone receptor antagonists (ARAs) were introduced in the treatment of chronic heart failure (CHF), as a result of the demonstration of their protective effect on the failing heart. However, important questions remain unanswered regarding the clinical efficacy of the ARAs on the clinical and echocardiographic phenotype of heart failure, called heart failure with preserved left ventricular ejection fraction (HFpEF)., Evidence Acquisition: The aim of the present meta-analysis was to verify the impact of the ARAs on some hard endpoints, such as all-cause death and hospitalizations from cardiovascular cause, making a comparative evaluation of these outcomes in CHF patients with reduced left ventricular ejection fraction (HFREF) and in those with HFpEF, respectively. Only randomized controlled trials (RCTs) were incorporated in our meta-analysis. The studies were included if they met the following criteria: experimental groups included patients with CHF treated with ARAs in addition to the conventional therapy; control groups included patients with CHF receiving conventional therapy without ARAs. Outcomes of interest were all-cause mortality, cardiovascular hospitalizations, hyperkalemia, or gynecomastia., Evidence Synthesis: Overall, 15 RCTs comprising a total of 15671 patients were eligible for inclusion in the meta-analysis. ARA use in patients with heart failure was associated with a significant reduction in adverse outcomes. Indeed, a significant reduced odds of all-cause death among CHF patients treated with ARAs compared to controls was found (OR=0.79; 95% CI: 0.73-0.87). Subgroup analysis based on the HF type revealed a statistically significant benefit as regards all-cause death for patients with HFREF (OR=0.77; 95% CI: 0.69-0.84), whereas a protective effect against the all-cause death was not attained by ARAs in the HFpEF subset (OR=0.91; 95% CI: 0.76-1.1). Furthermore reduced odds of CV hospitalizations was detected in the entire group of CHF patients under treatment with ARAs (OR=0.73; 95% CI: 0.61-0.89) as well as among HFREF patients treated with ARAs, compared to controls (OR=0.66; 95% CI: 0.51-0.85). Hyperkalemia was significantly more frequent with ARA use. In addition, subgroup analysis by ARA type documented that both nonselective and selective ARAs were similarly associated with increased odds of episodes of hyperkalemia compared to controls. Besides, ARA use was shown to be associated with the occurrence of gynecomastia. In particular, selective ARAs proved not to produce significant amounts of gynecomastia compared to controls (OR=0.74; 95% CI: 0.43-1.27), while nonselective ARAs did (OR 8.22; 95% CI: 4.9-13.81., Conclusions: Our meta-analysis provides further evidence that ARAs should be systematically used in patients with HFREF, in whom these drugs improve some hard clinical endpoints, such as all-cause mortality and hospitalizations from cardiac cause. Conversely, based on the present meta-analysis, ARA usage in HFpEF patients is questionable since in this CHF setting no significant improvement in clinical endpoints has been demonstrated so far, in the face of the well-known risks of hyperkalemia and/or gynecomastia that chronic ARA therapy entails. Furthermore, new selective ARAs are not burdened by significant risk of gynecomastia, while are similar to nonselective ARAs with regard to the efficacy profile as well as to the risk of eliciting hyperkalemia.

Background: Approximately one-third of patients with acute decompensated heart failure (ADHF) treated with an intravenous (iv) loop diuretic at a relatively high dose (>80 mg/day of furosemide, or an equivalent dose of another loop diuretic), exhibit worsening renal function (WRF) after a single course of iv infusions or iv bolus injections maintained for several days. WRF is currently defined as an increase in serum creatinine >0.3 mg/dL (WRF-Cr) or a decrease in the estimated glomerular filtration rate of ≥20% (WRF-GFR) compared to baseline measurements. Furthermore, small increases in serum creatinine in the high-normal range of its values are indicative of significant reductions in estimated glomerular filtration rate (eGFR) due to the exponential relationship between serum creatinine and eGFR. Therefore, underestimating this relationship could lead to an erroneous quantitative estimate of new-onset renal dysfunction, diuretic-related., Methods: The relationship between baseline serum creatinine (exposure variable) and the risk of diuretic-related WRF (dichotomous outcome variable), expressed either as WRF-Cr or as WRF-GFR, was assessed by logistic regression analysis. For this purpose, medical records with a diagnosis of previous ADHF were collated, and retrospectively analyzed. The eGFR was calculated using the equation "Modification of Diet in Renal Disease" (MDRD). The WRF was inferred from measurements of serum creatinine that had been made daily during the scheduled courses of intravenous diuretic therapy., Results: Thirty-eight patients with chronic heart failure (CHF) and history of a previous episode of ADHF were enrolled in the study. An increase higher than 0.3 mg/dL of serum creatinine (WRF-Cr) was detected in 14 of 38 patients (36.8%). In addition, a decrease of ≥20% in GFR (WRF-GFR) was detected in 14 of 38 patients (36.8%). However, a poor concordance between the two criteria was found (Cohen's Kappa =0.208, 95% CI: -0.110 to 0.526). WRF-Cr and WRF-GFR showed opposing relations with baseline serum creatinine. In fact, the risk of WRF-Cr appeared positively associated with baseline serum creatinine (odds ratio =33.56; 95% CI:2.93- 384.18 P=0.0047), while the risk of WRF-GFR was inversely associated with the same analyte (odds ratio =0.0393; 95% CI: 0.0039 to 0.3966 P=0.0061)., Conclusions: The criterion to discontinue the iv diuretic or to reduce its dosage in the presence of WRF-Cr for patients with ADHF or resistance to oral diuretic should be joined with the useful notion that this finding indicates a significant reduction of eGFR only for values of serum creatinine in the normal or near-normal ranges.

Background: The guidelines of the Scientific Societies of Cardiology recommend limiting fluid intake as a nonpharmacological measure for the management of chronic heart failure (HF). However, many patients with HF may suffer from severe thirst. A meta-analysis was performed to evaluate the effect of limiting fluid consumption based on various clinical and laboratory outcomes in patients with chronic HF., Methods: Only randomized controlled trials comparing liberal and restricted fluid oral intake in patients with HF were included. Primary outcomes were HF hospitalizations and all-cause mortality. Secondary outcomes were the sensation of thirst, the duration of therapy with intravenous diuretics, and the serum levels of creatinine, sodium, and B-type natriuretic peptide (BNP)., Results: Six studies met the inclusion criteria. Significant heterogeneity was detected for the majority of outcomes. In 5 studies, patients with restricted fluid intake compared to patients with free consumption of beverages had similar rehospitalization and mortality rates. There were no differences regarding patients' sense of thirst (4 studies), duration of intravenous diuretic treatment (2 studies), serum creatinine levels (5 studies), and serum sodium levels (5 studies). Serum BNP levels were significantly higher in the group with free fluid intake (4 studies)., Conclusion: In patients with HF, liberal fluid consumption does not seem to exert an unfavorable impact on HF rehospitalizations or all-cause mortality. Further randomized controlled trials are warranted to definitively confirm the present findings.

Background: In advanced congestive heart failure (CHF), intravenous (i.v.) inotropic agents, i.v. diuretics, ultrafiltration, and hemodialysis have been shown to not yield better clinical outcomes. In this scenario, the simultaneous administration of hypertonic saline solution (HSS) and furosemide may offer a more effective therapeutic option with a good safety profile., Methods: Therefore, a meta-analysis was performed to compare combined therapy, consisting of i.v. furosemide plus concomitant administration of HSS, with i.v. furosemide alone for acute decompensated heart failure (ADHF). The outcomes we chose were all-cause mortality, risk of re-hospitalization for ADHF, length of hospital stay, weight loss, and variation of serum creatinine., Results: Based on five randomized controlled trials (RCTs) involving 1,032 patients treated with i.v. HSS plus furosemide vs. 1,032 patients treated with i.v. furosemide alone, a decrease in all-cause mortality in patients treated with HSS plus furosemide was proven [RR = 0.57; 95 % confidence interval (CI) = 0.44-0.74, p = 0.0003]. Likewise, combined therapy with HSS plus furosemide was shown to be associated with a reduced risk of ADHF-related re-hospitalization (RR = 0.51; 95 % CI = 0.35-0.75, p = 0.001). Besides, combined therapy with HSS plus furosemide was found to be associated with a reduced length of hospital stay (p = 0.0002), greater weight loss (p < 0.00001), and better preservation of renal function (p < 0.00001)., Conclusion: HSS as an adjunct to i.v. furosemide for diuretic-resistant CHF patients led to a better renal safety profile and improved clinical endpoints such as mortality and heart failure-related hospitalizations.

Aim: Intravenous diuretics at relatively high doses are currently used for treating acute decompensated heart failure (ADHF). However, the existence of harmful side effects diuretic-related, such as electrolyte abnormalities, symptomatic hypotension and marked neuro-hormonal activation have led researchers to implement alternative therapeutic tools such as isolated ultrafiltration (IUF)., Methods: Our study aimed to compare intravenous diuretics vs. IUF as regards their respective efficacy and safety in ADHF patients through systematic review and meta-analysis of data derived from relevant randomized controlled trials., Results: 6 studies grouping a total of 477 patients were included in the systematic review. By contrast, data from only three studies were pooled for the meta-analysis, because of different adopted outcomes or marked dissimilarities in the data presentation . Weight loss at 48 h was greater in IUF group compared to the diuretics group [weighted mean difference (WMD)=1.77 kg; 95%CI: 1.18-2.36 kg; P<0.001)]. Similarly, greater fluid loss at 48 h was found in IUF group in comparison with diuretics group (WMD=1.2 liters; 95%CI: 0.73-1.67 liters; P< 0.001). In contrast, the probability of exhibiting worsening renal function (WRF), i.e., increase in serum creatinine > 0.3 mg/dl at 48 hours, was similar to the one found in the diuretics group (OR=1.33; 95% CI: 0.81-2.16 P=0.26)., Conclusion: On the basis of this meta-analysis, IUF induced greater weight loss and larger fluid removal compared to iv diuretics in ADHF patients, whereas the probability of developing WRF was not significantly different in the comparison between iv diuretics and IUF.

Purpose: It has been asserted that serial measurements of natriuretic peptides, specifically B-type natriuretic peptide (BNP) or the amino-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP), may serve as an objective practical guide to better tailor the drug treatment for patients with chronic heart failure (CHF), and especially to detect the cases of subclinical congestion that would require an increase in drug dosing. However, considerable uncertainty remains about the alleged useful role of natriuretic peptide-guided therapy in this context. Therefore, we decided to execute a meta-analysis of published randomized controlled trials (RCTs) to test the hypothesis that an improvement of clinical outcomes in outpatients with CHF may be achieved by adjustment of pharmacologic dosing performed according to natriuretic peptide determinations., Methods: The relevant studies were collected through a search across the PubMed database (January 1996 to September 2012). For our meta-analysis, parallel-group RCTs were eligible for inclusion if they met the following criteria: they enrolled patients with CHF, they randomized patients to a strategy of titrating drug therapy based on the level of a circulating natriuretic peptide (BNP or NT-proBNP) compared to a parallel control group treated according to the clinical conventional criteria, and they reported all-cause mortality. In addition, it was established that each RCT to be incorporated in the evaluation should have included more than 60 participants and its follow-up should have been longer than 90 days. The primary endpoint of the meta-analysis was all-cause mortality and hospitalization related to heart failure (combined endpoint)., Results: In the six pooled RCTs subjected to final meta-analysis (total of included patients = 1775), natriuretic peptide-guided therapy for outpatients with CHF was shown to be associated with a decreased risk of death and heart failure hospitalizations during follow-up (odds ratio - random effect model: 0.64; 95% confidence interval: 0.43-0.95; P = 0.026)., Conclusion: This meta-analysis supports the hypothesis that natriuretic peptide-guided therapy is superior to symptom-guided therapy for improving clinical outcomes in CHF outpatients. However, some large RCTs failed to document significant clinical improvement in terms of mortality and morbidity using a natriuretic peptide-guided strategy; thus, any attempt to clarify this still unresolved issue by means of further basic and clinical research is recommended in the future.

It has been asserted that serial measurements of natriuretic peptides (NPs), i.e., B-type natriuretic peptide (BNP) or the amino-terminal fragment of pro-B-type natriuretic peptide (NT-pro BNP), could help modulate more accurately the intensity of drug treatment in patients with chronic heart failure (CHF). Nevertheless, there are still several open questions about the presumed role of NP-guided pharmacologic adjustment as a valuable strategy in this setting. In this review, we outline the main randomized controlled trials (RCTs) carried out to date regarding NP-guided therapy in CHF patients and we focus on some of the still-unresolved issues. In particular, we discuss which NP plasma level should be assumed as the optimal target level to be attained, and we debate the possible influence exerted by different age classes on clinical end points during NP-guided therapy. The possible advantages and limitations for the cardiovascular system arising from the functional activation of NPs in CHF patients are also discussed. Although the pooling of data derived from the RCTs demonstrates an overall effect of slightly significant improvement in clinical outcomes with the NP-guided approach, we have noted that there are some relatively large studies that failed to document a significant clinical improvement in terms of mortality and morbidity using an NP-guided strategy. Thus, in our opinion, larger and better conducted trials addressing the unresolved issues of NP-guided therapy should be undertaken in the future.

Aim: It is not known whether therapy assisted by determinations of serum B-type natriuretic peptide (BNP) may improve the outcome for outpatients with chronic heart failure (CHF)., Methods: A retrospective case-control study was carried out, enrolling patients with acutely decompensated heart failure (ADHF) who were followed up for a mean period of four months. The patients who had died or had new episodes of ADHF were studied as the cases. For each case, one living patient who was free from ADHF-related re-hospitalisations was recruited as control. Cases and controls were also matched for some variables to minimise possible confounding. The possible role of BNP-guided therapy as a predictor of decreased risk of deaths or new hospitalisations related to heart failure was explored., Results: Twenty-eight cases and 44 controls were enrolled. A fall in BNP on the fifth day after admission was found to be a predictor of a decreased risk of the composite endpoint "death or new hospitalisation, heart failure-related" (hazard ratio=0.1508; 95% CI: 0.049 to 0.463; P=0.001). On the other hand, low glomerular filtration rate at admission (<60 mL/min/1.73 m2) was associated with increased risk of the abovementioned endpoint (hazard ratio=7.1785; 95% CI: 1.574 to 32.725; P=0.0113). On the contrary, BNP-guided therapy was associated with a similar risk of death and/or CHF-related hospitalisation, compared to the conventional clinical approach., Conclusion: A fall in BNP ≥60% from baseline on the fifth day after admission was found to be associated with a favorable clinical outcome in outpatients with CHF after four months of follow-up, irrespective whether this finding had been detected in patients treated according to the BNP-guided therapy or in patients treated with conventional clinical criteria. However, among the outpatients with previous ADHF, a substantial improvement in cardiovascular event rates could not be demonstrated in those treated with BNP-guided therapy compared with those undergoing usual, symptom-guided treatment.

Aim: Chronic hyponatremia is frequently found in some syndromes characterized by widespread edema coupled to impairment in arterial effective circulating volume, such as congestive chronic heart failure (CHF). In this setting, it is unclear whether the hyponatremia itself makes this condition worse or whether it represents a simply marker of decompensation. The factors responsible for development of hyponatremia in CHF have not exhaustively been elucidated yet. The aim of this paper was to ascertain whether some laboratory, clinical and therapeutical factors are able to predict occurrence of hyponatremia in CHF patients., Methods: A case-control study was carried out by recruiting 57 CHF patients, whose 19 characterized by hyponatremia (serum Na+<135 mEq/L) and 38 controls, matched for age, sex, etiology of CHF, time elapsed since beginning of both symptoms and diuretic therapy. Eligibility criteria included right or biventricular heart failure in NYHA class III, absence of hyponatremia at the first visit and therapy at enrollment with oral dose not less than 175 mg per week of furosemide or equivalent weekly dose of torsemide. Exclusion criteria were electrostimulation therapies (pace-maker or cardiac resynchronization therapy), documented episodes- one or more- of infective gastroenteritis or diarrhea and use of any drug influencing neuroendocrine mechanisms of arginin-vasopressin (AVP) secretion, such as opiates, tetracyclines, phenothiazines, lithium, serotonin selective reuptake inhibitors (SSRIs) etc., Results: At univariate analysis, intensive intravenous (iv) therapy with furosemide (one or more courses), ascites, mixed regimen with thiazide diuretic plus furosemide, high (>3 ng/mL/h) plasma renin activity, serum creatinine ≥2,2 mg/dl and oligoanuria were shown to be associated with hyponatremia. At multivariate analysis a role of predictor of hyponatremia was maintained by combined therapy with thiazide diuretic plus furosemide (OR=35.68 95%CI: 2.83-449.37 P=0.0057) as well as by intensive iv furosemide therapy (OR=12.44 95%CI: 1.207-128.27 P=0.0342)., Conclusion: Inhibition of free water clearance by thiazides may account for association found between their use and hyponatremia development in congestive CHF setting. Even though loop diuretics are known to promote free water excretion, in our experience hyponatremia might have been favored by iv furosemide high doses, because drop in effective circulating volume and further impairment in arterial underfilling due to overzealous iv loop diuretic administration are able to foster AVP non osmotic release, thereby leading to hemodilution hyponatremia.

Objective: In chronic heart failure (CHF), collapsibility index of the inferior vena cava (IVCCI) is used for noninvasive ultrasonographic appraisal of central venous pressure, but it also may be related both to estimated glomerular filtration rate (eGFR) and renal outcome., Methods: On the basis of retrospective observational cohort study, we analyzed 49 patients with right or biventricular CHF in III NYHA class, who had undergone intravenous intensive treatment with furosemide. Aggravated renal dysfunction (ARD) was defined by serum creatinine (Cr) increase of ≥0.3 mg/dL from baseline. IVCCI was categorized in three layers (IVCCI ≤15%, IVCCI 16-40% and IVCCI >40%). The predictors of ARD were searched for as well as any relation between basal IVCCI and both eGFR at admission and occurrence of ARD., Results: Overall, 15 cases and 34 controls were compared. Multivariate predictors of ARD were a lower basal eGFR (HR: 0.82 CI: 0.72-0.94 p=0.0045) and intravenous furosemide daily mean dose >80 mg (HR: 48.62 CI: 1.62-3841.5 p=0.0430). A very significant positive correlation was found between IVCCI at admission ≤ 15% and basal eGFR (r=0.96 p<0.0001), while a negative correlation with eGFR was detected in the IVCCI highest (>40%) range (r=-0.696 p=0.0013). Furthermore, the category with basal IVCCI >40% showed a higher rate of ARD compared to that with basal IVCCI 16-40% (p<0.05)., Conclusion: On the basis of the demonstrated u-shaped relationship between IVCCI and eGFR both the stratum with the highest (>40%) and the one with the lowest (≤15%) basal IVCCI may be associated with increased risk of ARD.

Background: In chronic heart failure patients (CHF), ultrasound measurement of inferior vena cava collapsibility index (IVCCI) has been proposed to yield careful assessment and grading of the hemodynamic congestion., Objective: The purpose of this study was to correlate the findings of physical examination with IVCCI in CHF patients., Methods: According to a retrospective cohort design, we analyzed 54 CHF patients with right or biventricular CHF, belonging to III NYHA class. We planned to determine whether any basal IVCCI range would be able to predict persistent or worsening clinical congestion found at the end of subsequent follow up (i.e. after 1-2 months of oral optimized therapy). For this purpose, the patients were subdivided by three groups according to the basal IVCCI value: ≤ 15% (13 pts), 16 - 40% (21 pts) and > 40% (20 pts).Several clinical criteria of congestion were compared across the three groups and subsequently entered in the Cox multivariate model., Results: Multivariate predictors of high congestion score were jugular venous distension (HR: 13,38 95% C.I.: 2,13 - 84 p = 0,0059) and rales (HR: 11 95% C.I : 1,45 - 83,8 p = 0,0213). IVCCI ≤ 15% was always associated with high congestion score at the second visit; but IVCCI ≤ 15% failed to predict high congestion score at the second visit., Conclusion: In CHF setting, low IVCCI did not reliably predict high congestion score. Nevertheless, the cluster with IVCCI ≤ 15% was always found associated with signs and symptoms from both right and left-sided decompensated CHF.

Background: Renoprotective effect of ACE-inhibitors has been questioned in case of decreased effective circulating volume, like in right or biventricular chronic heart failure., Objective: To detect clinical predictors of renal worsening in CHF patient population characterized by two types of ACE-inhibitor dosing regimens., Methods: According to a retrospective cohort design, we followed 2 groups of patients with CHF - whether right or biventricular -, all in III NYHA class treated with ACE-inhibitors (enalapril or lisinopril), and with left ventricular ejection fraction (LVEF) < 50%, by distinguishing them by ACE-inhibitor dosing: average-low (<10 mg per day) or "high" dose (>10 mg per day) of enalapril or lisinopril. Worsened renal failure (ARD) was defined by Cr increase >30% from baseline. Cox proportional hazards model was used to identify the predictors of ARD among the following variables: ACE-inhibitors "high" dose, age, basal LVEF, history of repeated intensive intravenous loop diuretic therapies (IV diur), diabetes, basal Cr, history of hypertension, systolic blood pressure < 100 mm Hg., Results: 57 patients were recruited, of whom 15 were treated with ACE-inhibitor "high" dose. During a mean follow-up of 718 days, ARD occurred in 17 (29.8%) patients. Only ACE-inhibitor "high" dose (HR: 12.4681 C.I.: 2.1614-71.9239 p=0.0050) and basal Cr (HR: 1.2344 C.I.: 1.0414-1.4632 p=0.0157) were shown to predict ARD. Moreover, ACE-inhibitor "high" doses were shown to fail to predict ARD in both CHF without IV diur and CHF with diabetes., Conclusion: In III NYHA class CHF, ACE-inhibitor "high" doses and a higher basal Cr predicted ARD. Nephrotoxicity related to ACE-inhibitor "high" doses was increased by IV diur, whereas it was not detected in CHF patients with diabetes.

Aim: In the presence of resistance to oral diuretics in chronic heart failure (CHF) patients with extreme hydrosaline retention, among the proposed therapeutic options the administration of high doses of loop diuretics - either intravenous (i.v.) boluses or i.v. continuous infusion - should first of all be considered. Nevertheless, the use of this therapy may lead to the risk of further aggravation of frequently coexisting renal dysfunction, especially when loop diuretics such as furosemide (FUR), torasemide etc. are administered at excessive doses leading to hypotension, hypoperfusion and/or relative dehydration in patients with decompensated CHF who could have benefit from intensive unloading therapy. The aim of this study was to identify the clinical and hematochemical markers which are able to predict a possible decline or rapid deterioration of renal function implying a rise in serum creatinine (Cr) >25% of its basal value, i.e. the so-called aggravated renal dysfunction (ARD), typically occurring during intensive unloading therapy with i.v. FUR or other loop diuretics, administered to CHF pts with extreme fluid retention., Methods: The protocol of our case-control observational study established to enroll every CHF patient who was demonstrated to develop a rise in Cr suggestive of ARD at the end of i.v. diuretic therapy (VI-VIII day). For each case enrolled, 3 patients at least were selected as controls, matched for age, sex and time elapsed from the beginning of the signs and symptoms of CHF. For the prediction of the dependent variable, represented by ARD diuretic infusion-related, the following independent variables were considered: creatinine clearance (Cr clear) <60 mL/min, Cr clear expressed as a continuous variable (Cr clear continuous), daily dose of i.v. furosemide ≥ 125 mg, left ventricular ejection fraction (LVEF), CHF with normal (≥ 50%) LVEF (HFNEF), urinary sodium concentration (U Na+) ≥ 40 mEq/L, U Na+expressed as a continuous variable (U Na+ continuous), sodium fractional excretion (FE Na+) >2%, urine/plasma concentration ratios for creatinine (U/P cr) <10, for urea (U/P urea) <5 and for osmolality (U/P osmolal) <1.1, mean duration of the symptoms of CHF, history of pre-existing parenchymal renal disease . The values of U Na+, FE Na+, U/P Cr, U/P urea and U/P osmolal were measured after discontinuance of diuretic oral therapy for four days, before the onset of intensive i.v. diuretic administration, so as to identify the patients with pathological values of tubular renal function indexes, known to be not interpretable in the presence of diuretics, suggestive of possible preexisting anatomic renal damage (acute tubular necrosis prior to onset of iv diuretic therapy)., Results: Nineteen 19 CHF patients with ARD and 60 controls were enrolled. At univariable analysis, Cr clear <60 mL/min, Cr clear continuous, daily dose of iv furosemide ≥ 125 mg, LVEF, HFNEF, FE Na+>2%, Na+≥ 40 mEq/L and U Na+ continuous were shown to be associated with ARD. At multivariate analysis, the role of prognostic indicator of ARD was maintained by daily dose only of iv FUR ≥125 mg (OR: 7.2088 95% CI: 1.3096-39.6802 P=0.0232). By using the 2x2 contingency tables, a qualitative interaction was identified by crossing ARD ‑ outcome variable - against dose of iv FUR ≥ 125 mg/day - exposure variable - and by subsequently stratifying by the HFNEF. Actually, a significant association with ARD was not present in any CHF patient with dilated left ventricle treated with high dosage of iv FUR, whereas a highly significant association with ARD was observed in HFNEF patients (OR: 72 95% CI: 6.601-785.2694 P=0.00001) who had experienced the same high iv fur dose., Conclusion: In CHF patients with widespread edema refractory to oral diuretic, ARD can be propitiated by high dosages of i.v. FUR, when not associated with other treatments to preserve the effective circulating volume and renal flow. The HFNEF patients appear to be more prone to ARD related to i.v. high dosages of FUR, perhaps because their hemodynamics is more seriously harmed by the drop, FUR-related, in venous return and cardiac preload, as compared to CHF patients with reduced (45-30%) LVEF.

During intensive therapy of chronic heart failure (CHF) patients with marked fluid retention using high doses of i.v. furosemide the additional effect of agents which might exert osmotic attraction of interstitial fluids has been proposed. They are thought to impede the impairment of renal blood supply and glomerular filtration rate, which may be caused by a combined action of cardiac preload acute reduction, hypotension and neurohormonal activation.We therefore assessed in CHF patients with NYHA class III and BNP values from 900 to 1500 pg/ml, who were treated with i.v. furosemide, the predictors of iatrogenic short term creatinine impairment by means of a case-control observational study from two centers. Patients with CHF had been treated for 6-8 days with intravenous loop diuretics alone or with an additional i.v. administration of other agents (plasma expanders, albumin, mannitol, inotropic support etc.). A rise in serum creatinine ≥ 25% of the basal value was considered as renal impairment.A total of 15 cases and 38 controls were enrolled. At univariate analysis, serum creatinine basal value ≥ 2.2 mg/dl, absence of hypertonic saline solution (HSS) in the therapeutic protocol, hyposodic diet and refractory oligoanuria were associated with an increased risk of worsening renal function precipitated by i.v. diuretic therapy. At multivariate analysis as a predictor of loop diuretic-related renal function impairment, we found a serum creatinine ≥ 2.2 mg/dl at baseline (OR: 63.33, 95% CI: 3.68-1088.73, p=0.0043) and the absence of HSS in the therapeutic regimen (OR: 25.0461, 95% CI: 2.07-302.53, p=0.0113). Moreover, in multivariate analysis ascites had some predictive value of renal deterioration (OR: 13.28, 95% CI: 1.0055-175.41, p=0,0495).

A well established part of therapeutic approaches applying to cases of chronic heart failure (CHF) with extreme fluid retention is represented by intensive intravenous (i.v.) therapy with loop diuretics. This kind of therapy, if appropriately modulated according to the individual clinical picture and biohumoral pattern, is able to decrease the abnormally high ventricular filling pressures, thereby relieving the breathlessness while being able to retrieve a suitable urine output, so as to propitiate regression or disappearance of edema without unfavorable influences on renal clearance of nitrogenous compounds. Nevertheless, the intensive i.v. diuretic therapy should be tailored on the basis of a close assessment of baseline hemodynamic data and hemodynamic response to the medications, in addition to the careful diuretic dose titration and cautious evaluation of risk/benefit ratio. Actually, by using this kind of therapy, there is a risk that a tubular or glomerular injury can be generated and that a frequently preexisting renal dysfunction can be aggravated, especially when excessive doses of loop diuretics are being erroneously administered, so as to cause hypotension, hypoperfusion and/or relative dehydration in patients with decompensated CHF who could have expressly benefitted from intensive unloading therapy. Recently, the genesis of CHF-related progressive renal deterioration has been highlighted by affirming that a major role may be played rather by neurovegetative disorders, that is, by increase in sympathetic tone and abnormalities in kidney's vasomotility than by cardiac inotropism deficiency. The measures, thought to be able to prevent renal arterial constriction and to impede deterioration of glomerular filtration rate (GFR) due to the ischemic-necrotic tubular injury, as occurring in the set of intensive unloading therapy with i.v. furosemide or other loop diuretic, are represented by application of inotropic and renal vasodilator support by dopamine i.v. infusion at low doses or by other inotropic agents provided with recognized renal vasodilator properties and/or by addition to i.v. furosemide of osmotic agents able to expand the hematic volume, so counteracting or minimizing the reflex renal vasoconstriction induced by furosemide-related reduction in intravascular circulating volume: i.v. infusion of small volumes of hypertonic saline solution, as well as administration of albumin, mannitol and/or plasma expanders. Because renal impairment, as developing in the setting of CHF, has proven to represent a very important indicator of adverse outcome, every effort should be addressed to prevent any significant (>25% of basal value) rise in serum creatinine consequent to diuretic unloading therapy or to other procedures (paracentesis of tense ascites, ultrafiltration) aimed at rapid fluid removal in edematous or ascitic CHF or cardiogenetic anasarca. Ultrafiltration, even though a promising technique highly valued for its acknowledged property to obtain a more rapid fluid and weight loss in CHF patients with marked fluid retention, has been demonstrated so far to produce neurohumoral activation, creatinine abnormalities and symptomatic hypotensions similar to those due to i.v. loop diuretics; thus, the hypothesized advantages of this technique remain to be further clarified and confirmed, with regard to its safety profile and cost-effectiveness.

Aim: The passage from II to III New York Heart Association (NYHA) class is indicative of cardiopulmonary impairment and unfavourable prognosis. Among chronic heart failure(CHF) II NYHA class patients, the topic has been debated what criteria have be assumed for identifying the patients prone to accelerated progression towards III NYHA class., Methods: A case cohort study, including a number of CHF II NYHA class patients, was carried out, to evaluate the role as predictor of CHF worsening of some ultrasonographic parameters, listed as follows: left ventricular ejection fraction, as continuous and as a dichotomous variable, i.e. subdivided as follows: 1) LVEF larger than 40% and 2) LVEF ranged from 30% to 40%; mitral regurgitation (MR), as continuous and as a dichotomic variable (i.e. moderate-to-severe MR, defined by transmitralic jet planimetric area estimated as larger than 20% of left atrium area), restrictive LV filling pattern and pulmonary systolic arterial pressure >40 mmHg. The pts were subdivided in 3 categories, as follows:1) diastolic CHF, i.e. heart failure with normal or only mildly impaired left ventricular ejection fraction - 20 patients; 2) systolic CHF, i.e. heart failure with reduced left ventricular ejection fraction - 19 patients; and 3) CHF due to "organic" mitral insufficiency-19 patients. All patients were treated with pharmacologic therapy, according to their respective clinical features and typology of basal heart disease. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) for the composite endpoint death and hospitalization due to worsening CHF were investigated, concerning each of the above-mentioned criteria. Moreover, the odds ratios (OR) were calculated, by not conditional logistic regression analysis, to achieve information about risk of death and/or worsening CHF, as well as the respective profiles of risk, assessed by relative risk (RR)., Results: From 173 followed-up patients, 58 patients,70+/-12 aged, whose 15 cases (transition to III NYHA class) and 43 controls, were included in retrospective analysis. Notewhorty, moderate-to-severe MR only seemed to play a role as reliable predictor of worsening CHF(sensitivity: 93.3%; specificity: 69.7%; PPV: 51.8%; NPV: 96.7%; RR:15.93; OR: 32.3), as its sensitivity and PPV, particularly, were shown to exceed far and away the values of sensitivity and PPV associated to each of other echographic and/or clinical variables. Nevertheless, at multivariate analysis,MR expressed as continuous variable only, but not as "categorical" variable-was demonstrated to independently predict the transition from II to III NYHA class, over two years clinical follow up., Conclusion: The present data seem to support the view that the larger regurgitant jet of mitral insufficiency, the higher the risk of worsening CHF during a two years follow up. Likewise, it is plausible the moderate-severe MR represents a predictor of increased risk of transition to III NYHA class among the CHF II NYHA class patients. In addition, this study seems to indicate that a surgical therapy (prosthetic replacement or mitral valvuloplasty)should always be planned in the case of II NYHA class CHF patient who has been recognized affected by moderate-to-severe MR, since the chances of successful pharmacological prevention of clinical impairment in this setting turned out to be very slight.

Objective: To identify the Doppler echocardiographic criteria able to predict clinical deterioration of mild-to- moderate chronic heart failure (CHF) as well as, whenever possible, to evaluate the features of chronological relation of cavitary remodelling in left chambers during follow-up (FU)., Methods: A retrospective, case-controlled study, including a number of CHF II NYHA class patients, was carried out, to evaluate, by means of univariate and multivariable logistic regression analyses, the role as predictor of CHF worsening of some Doppler echocardiographic parameters, listed as follows: left ventricular mass index, analyzed both as continuous and as dichotomous (>130 g/m2) variable; left ventricular end-systolic volume (LVESV) >57 ml; left ventricular ejection fraction (LVEF), divided into 2 classes: a) LVEF>45%, i.e. normal or mildly impaired LVEF, and 2) reduced (45%-30%) LVEF; restrictive left ventricular filling pattern (RFP); antero-posterior left atrial diameter (LADi) >50 mm; ratio of early mitral inflow to early myocardial velocity>8., Results: Of 173 patients enrolled, 60 patients (15 cases of transition to III NYHA class and 45 controls) were included in retrospective analysis. At univariate analysis, RFP and LADi>50 mm were shown to be associated with worsening of CHF. At multivariate analysis, the role of prognostic indicator of poor outcome was maintained by RFP (OR=17.0, 95%CI: 2.5-116.5) as well as by LADi>50 mm (OR=7.95, 95%CI: 1.27.0-49.6). On the other hand, in the subset of CHF with LVEF >45%, increased LADi was not associated with occurrence of increase in LVESV or left ventricular progressive dilation during the subsequent follow-up., Conclusions: In mild-to-moderate CHF, RFP and LADi>50 mm are predictors of adverse outcome, independently of the presence or severity of left ventricular systolic dysfunction.

Objectives: To verify and compare the effects respectively exercised in chronic heart failure patients by transdermal, slow release scopolamine patch and by the beta and alfa adrenoreceptor blocker carvedilol upon the main indexes derived from maximal cardiopulmonary stress test, as well as from analysis of heart rate variability., Methods: In each of 14 patients suffering from NYHA class II chronic heart failure, admitted to study, the maximal cardiopulmonary test and heart period power spectrum assessment were performed, firstly during usual therapy, then after 7 days of continuous adjunctive treatment with scopolamine patch, and, finally after 3 months of regular administration of oral carvedilol, added to the basal therapy. The need of time enough to the adaptation of the cardiovascular system against the carvedilol pharmacodynamics, together with the need of slow, progressive dose titration, caused that the onset of therapy with carvedilol was separated from assessment of its effects on ergometric and spectral parameters by an interval period of 3 months., Results: During administration of low doses of scopolamine, the values of VO2max, exercise time and double product were respectively 24 +/- 5.3 ml/kg/min, 12 +/- 3 min and 23630 +/- 3760, and resulted significantly higher than basal (p < 0.05 in all cases) and carvedilol-related readings (p < 0.01 by comparisons with VO2max and double product; p < 0.05 by comparison with exercise time). Again during scopolamine, the total variance, LF and HF powers exhibited the values reported as follows: 1255 msec2 and, respectively, 430 and 250 msec2, thus exceeding significantly the basal levels (p < 0.05 from comparison with total power, p < 0.01 from comparisons with LF and HF bands) as well as the levels reached during adrenergic blockade with carvedilol (LF scopolamine vs LF carvedilol: p < 0.01; total power and HF scopolamine vs corrispective carvedilol values p < 0.05). Compared to the basal findings, the carvedilol induced a significant reduction in VO2max (p < 0.05), double product (p < 0.01), peack of heart rate (p < 0.05) and LF power (p < 0.05), and elicited no significant decreases in exercise time; similarly a weak, not significant surge was product by carvedilol in total and HF powers., Conclusions: Therefore, in patients with left ventricle asymptomatic dysfunction, the low doses of scopolamine potentiate simultaneously the spontaneous heart rare variability and cardiopulmonary maximal testing; whereas, the carvedilol acts upon LF oscillatory component only, the effects upon total variance and HF band being negligible; moreover, this drug depress the myocardial functional capability; in fact, the carvedilol has been demonstrated to produce a remarkable fall in VO2max, this significant reduction in O2 maximal uptake involving the poor rise in cardiac output during the effort or less effective O2 removal from capillary beds or both.

Background: We evaluated the diuretic output in patients with decompensated chronic heart failure (CHF), previously treated by i.v. infusion with dobutamine and dopamine (dob-dop) or with amrinone (amr). Our target was to identify the possible discrepancies in urinary output perhaps linked to the different type of inotropic stimulation in the two subsets., Methods: Adjunctive therapy with dob-dop or amr was chosen because the administration of diuretics only, without cardiac support, as tested in previous hospitalizations, had been demonstrated to produce unfavourable results, mainly expressed by finding of a low output syndrome in 50% of cases or more. The administration of i.v. infusion was maintained during 17 hours (1000 min approximatively), and included infusion in separate pumps of the two amines, dobutamine at dose of 5 micrograms/kg/min and dopamine at dose of 2.8 micrograms/kg/min or, alternatively, i.v. infusion of amr, administered at dose of 7 micrograms/kg/min. Infusion volumes were similar in the two subsets. The two subsets were homogeneous relatively to renal impairment, i.e. to the parameters (urinary Na, U/P creatinine, U/P urea, urinary osmolality) we fixed as markers idoneous to demonstrate the occurrence of organic renal damage (acute tubular necrosis)., Results: The diuresis was recovered in all 24 patients, and the urine volume resulted more pronounced in the subset attributed to the dob-dop at both the 8th and the 17th hour readings. We found no harmful alterations in HR and AP, whereas renal function parameters have been shown to enhance in both the dob-dop and amr arms. The diuretic effectiveness of the SIEV obtained by catecholamine implementation exercised a synergistic, favourable effect on diuresis, renal flow, glomerular filtration rate, and sodium post-proximal delivery. Amr resulted less effective then dob-dop simultaneous administration relatively to the diuretic effect. No remarkable differences were found in the two subsets as regards the heart rate, whereas a decrease in arterial pressure was found after amr. A persistent shift towards a condition of chronic renal failure, was identified in 4/24 patients, the two groups despite of the prolonged treatment at optimized doses: no remarkable side effects were reported., Conclusions: Thus, the selective effect upon renal hemodynamics, as exercised by dob-dop infusion low doses of dop, together with the enhanced renal output due to dob, has been shown to be more effective than amr influence: thus, the catecholamine therapeutical approach has been demonstrated to possess the best effectiveness in excitation of diuresis, among the CHF oliguric patients.