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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. 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. 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). 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.

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. 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. 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. 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.

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. 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. 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

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.

Platypnea-orthodeoxia syndrome (POS) is a rare disorder characterized by the emergence of a right-to-left shunt at the intracardiac or intrapulmonary level. The clinical picture is distinguished by shortness of breath that worsens on standing due to an accentuation of oxygen desaturation, and instead improves, at least partly, in the recumbent position. In this article we present a brief review of the pathophysiology of POS, as well as its clinical picture, diagnostic assessment, and preferential therapeutic options. Pathophysiological issues that are still not completely understood or much debated are outlined. The currently accepted pathophysiological concepts are presented and a summary of the main diagnostic and therapeutic tools is provided.

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.

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. 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. 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

Therapy with ergot-derivative dopamine agonists (ergot-DAs) is suspected to cause or promote the development of insufficiency and regurgitation in previously normal cardiac valves. Thus, we conducted a systematic review and meta-analysis of the literature to determine whether administration of cabergoline, i.e., an ergot-DA used to treat Parkinson’s disease (PD) or hyperprolactinemia, is associated with an increased risk of valve regurgitation compared with pharmacological regimens not comprising ergot-DAs or with no therapy. Observational studies were selected from the Pubmed and Embase databases. Studies had to have assessed the prevalence, odds, or risk of cardiac valve regurgitation in patients who underwent chronic treatment with cabergoline for PD or hyperprolactinemia compared with patients with the same diseases whose therapy did not include cabergoline or another ergot-DA. Separate meta-analyses were performed for PD and hyperprolactinemia patients. On the basis of five studies, 634 PD patients were taking cabergoline, while 9,120 PD patients were treated with dopa/dopamine decarboxylase inhibitor, alone or associated with a non-ergot DA. Valvular regurgitation of any degree—at one cardiac valve or more —was more frequent in PD patients who were taking cabergoline compared to those treated with a non-ergot DA agent or not treated with any dopamine agonist [adjusted (inverse variance: iv) odds ratio: 7.25 95 % CI: 3.71–14.18; p

This article covers the main unsolved issues regarding the potential role that the patent foramen ovale (PFO) plays in the genesis of so-called cryptogenic stroke. Some brief notions of the anatomy and epidemiology of the PFO are outlined. Subsequently, the results of the three trials on secondary prevention (medical therapy vs. transcatheter closure) in patients with PFO and a history of cryptogenic stroke are presented. The conflicting results of numerous meta-analyses derived from the three randomized controlled trials are discussed. Official scientific guidelines dispute an alleged superior efficacy of transcatheter PFO occlusion in comparison with antithrombotic therapy alone (anticoagulants or antiplatelet agents), except for selected cases of patients with documented PFO and a concomitant clinical–instrumental picture of deep venous thrombosis. Nevertheless, considering recent doubts about the presumptive thrombogenic and arrhythmogenic potential of PFO occlusion, which concerns only one of the septal occluders previously used, further in-depth investigations are warranted, centered on the use of newer dedicated devices to be tested in comparison with antithrombotic regimens alone.

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.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).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).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.

The present meta-analysis attempted to assess whether an unfavourable cardiovascular risk profile could be identified in the case of two COX2 selective inhibitors (COXIBs), namely celecoxib and etoricoxib. Based on the data from the literature, our meta-analysis aimed to assess the probability of major cardiovascular events reported with the use of celecoxib or etoricoxib and compare this with the results seen in patients assigned to the placebo group. Furthermore, the risk of cardiovascular events found by using celecoxib or etoricoxib was also compared with that associated with the use of naproxen, a nonselective non-steroidal anti-inflammatory drug (NSAID) chosen as our reference drug.The studies had to be randomized controlled trials with at least 4-week duration. Studies were included if they compared celecoxib or etoricoxib against placebo or naproxen. Moreover, the selected studies had to have determined the risk, odds or incidence of myocardial infarction, stroke or cardiovascular death. For the comparisons versus placebo, the endpoints of interest were "serious vascular events", "non-fatal myocardial infarction", "non-fatal stroke" and "death from cardiovascular causes", whereas "myocardial infarction" and "stroke" were the endpoints of interest concerning the comparison versus naproxen.From the evaluation of 41 studies comparing celecoxib with placebo, we found a significantly higher incidence of serious vascular events in the celecoxib group compared to controls treated with placebo (rate ratio 1.598, 95% CI: 1.048 to 2.438; P=0.029). Furthermore, in patients allocated to treatment with celecoxib, we found an incidence rate of non-fatal acute myocardial infarction that was three times higher compared with the placebo group (rate ratio 3.074, 95% CI: 1.375-6.873, P=0.006). In contrast, we did not find any significant difference with regard to the incidence of nonfatal stroke and that of death from cardiovascular causes by comparing celecoxib and placebo. In addition, by examining cardiovascular outcomes that emerged from the 17 trials which compared etoricoxib with placebo, it was not possible to demonstrate statistically significant differences in incidence for each of the explored endpoints. With regard to the comparison of each coxib with the non-selective COX2 inhibitor naproxen, we did not find any significant difference for either the odds of myocardial infarction or that of stroke.On the basis of our meta-analysis, we can state that symptomatic benefits induced by the prolonged administration of celecoxib may be partially invalidated by a concomitant increase in vascular risk, particularly the increased risk of myocardial infarction found in celecoxib-treated patients, compared to controls taking placebo. In contrast, treatment with etoricoxib proved not to result in an increased risk of serious vascular events when compared with both the placebo and naproxen. Our meta-analysis also denotes that the alternative to COXIBs, represented by naproxen, does not show significant benefit in terms of reduced cardiovascular risk. Therefore, considering that the increase in incidence rate of cardiovascular events associated with treatment with celecoxib is small in absolute terms, it is reasonable to state that celecoxib is still a drug whose benefits outweigh the potential adverse effects on the cardiovascular system.

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).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.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; P0.001)]. 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; P0.001). In contrast, the probability of exhibiting worsening renal function (WRF), i.e., increase in serum creatinine0.3 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).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.

The authors summarize some current views regarding the pharmacologic therapies of hepatorenal and cardiorenal syndromes, respectively. A common pathogenetic background of the two edematous disorders is outlined, consisting in reduced effective blood arterial volume ‑ due to the splanchnic vasodilation in the hepatorenal syndrome (HRS) and to the fall in cardiac output and the rise in central venous pressure in cardiorenal syndrome (CRS). In both diseases, arterial underfilling elicits multiple water- and sodium- retentive mechanisms, by activating sympathetic nervous system and stimulating both rennin-angiotensin-aldosterone and vasopressin systems. These neurohormonal adjustments subsequently concur to a vasomotor nephropathy which originates - as a same kind of vasoconstrictor reflex renal response ‑ from the splanchnic vasodilation, in the case of liver cirrhosis, or from the fall in renal perfusion and filtration gradients in the case of cardiorenal syndrome. Despite these pathogenetic similarities, the renal insufficiency of HRS compared to that of CRS is treated using diametrically opposite approaches: actually withdrawal of diuretics and administration of vasoconstrictor agents is the first choice in the case of HRS, while CRS is tackled by forcing diuretic regimen and by continuing vasodilator treatment with ACE-inhibitors. The pros and cons of these strategies ‑ which are still matter of debate among the physicians and researchers ‑ are then succinctly presented and discussed.

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).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.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.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.

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.

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.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.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).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.

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.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).Nineteen 19 CHF patients with ARD and 60 controls were enrolled. At univariable analysis, Cr clear60 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.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.

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.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.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 (p0.05 in all cases) and carvedilol-related readings (p0.01 by comparisons with VO2max and double product; p0.05 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 (p0.05 from comparison with total power, p0.01 from comparisons with LF and HF bands) as well as the levels reached during adrenergic blockade with carvedilol (LF scopolamine vs LF carvedilol: p0.01; total power and HF scopolamine vs corrispective carvedilol values p0.05). Compared to the basal findings, the carvedilol induced a significant reduction in VO2max (p0.05), double product (p0.01), peack of heart rate (p0.05) and LF power (p0.05), and elicited no significant decreases in exercise time; similarly a weak, not significant surge was product by carvedilol in total and HF powers.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.

The influence on renal function caused by acute myocardial infarction complicated by hypotension has been studied. Particularly, a possible difference in renal functional pattern related to different localization and/or extension of necrotic myocardial area was investigated.The study has been performed in 12 cases of acute myocardial infarction, involving anteroseptal (7) or inferodorsal (5) myocardial wall. The score of parietal asynergy resulted 13.28 in anterior vs 7.6 in inferior localization (p0.001).The decrease in systolic pressure, conversely, resulted not significantly different in the two groups. The renal function was assessed by measuring the urinary output (V) and creatinine clearance (CrCl). During the first 24 hours, both parameters resulted more preserved in inferior than in anterior AMI (V-552 vs 214 ml; p0.005; CrCl 70.6 vs 33.42; p0.001). Thus 1) the pressure decrease resulted unrelated to the size of asynergy and 2) the markers of renal function, although the decrease in brachial pressure has been identical in the two groups, have been shown to decrease more profoundly in the anterior infarction.This may depends upon the reflex interruption of efferent nervous sympathetic drive toward the renal arteriolar bed, occurring in inferior infarction, despite of the systemic hypotension, and able to exercising a beneficial influence on the glomerular filtration rate (GFR). This reflex modulation has been demonstrated as effective in the inferior, but not in the anterior localization of infarction, this different haemodynamic pattern being able to explain the more pronounced decrease in GFR and diuresis in anterior than inferior AMI, as observed in our study.

In 17 patients suffering from recurrent episodes of vasovagal syncope as well as in 21 healthy subjects without clinical episodes of presyncope or syncope, we evaluated the reflex decrease in heart rate evoked by the phenilephrine test. In the syncopal patients, the measurements were taken 4-12 hours after the clinical appearance of syncope. We divided the syncopal patients as follows: 9 patients, undergoing pharmacological treatment, and 8 untreated patients (drug free arm). In the pharmacological arm of the study, an alternate, randomized administration of metoprolol (150 mg twice daily for 2 days) and verapamil (80 mg every 6 hours for 2 days) was provided. Therefore, in the pharmacological arm as well as in drug free patients, we tested again the baroreflex sensitivity, by means of iv phenilephrine bolus, 3 and 7 days after the clinical appearance of the syncopal event. The baroreflex sensitivity values were significantly higher in the syncopal group compared to the control group (21 +/- 5 vs 13 +/- 4.5 ms/mm Hg; p0.01). Of the two tested drugs, only the metoprolol produced a fast (day 3) decrease in baroreflex sensitivity. On the basis of measurements taken after 7 days, we noted a pattern of widespread reduction in baroreflex sensitivity values, found in both treated and untreated patients. In conclusion, patients with vasovagal syncope exhibited a more pronounced maximal parasympathetic activation compared to the control group. The high baroreflex sensitivity values were soon (day 3) reduced by metoprolol, but not by verapamil therapy; a spontaneous normalization in baroreflex sensitivity values was found 7 days after the clinical episode, regardless of therapy.

In 7 patients suffering from acute myocardial infarction (AMI) occurring in the previous 30 days, we investigated forearm vascular reactivity to lower body negative pressure (LBNP), by the strain gauge plethysmography with simultaneous administration of negative pressure around the lower limbs. This manoeuvre has then been repeated after 10 days of oral beta-blocker therapy (propanolol 160 mg/die). A significant flow reduction derived from LBNP associated to plethysmography with respect to plethysmography alone, but this significant difference was suppressed by propranolol treatment, that prevented the reflex decrease in forearm blood flow, (forearm blood flow from 5.97 to 3.85 ml/min/100 ml in wash-out vs 5.64 to 5.75 ml/min/100 ml during propranolol treatment). We hypothesize that this phenomenon is due to the desensitizing effect of propranolol on cardiopulmonary mechanoreceptors (CPB), with the consequent loss or reduction of their functional inhibition for the efferent sympathetic outflow towards resistance vessels in skeletal muscle. Therefore, LBNP does not elicit forearm reflex sympathetic vasoconstriction, because pressure unloading of CPB areas is no longer able to modify sympathetic discharge, since the influence on it of baroreceptor activity has already been weakened by prolonged beta-blockade. Thus, the LBNP low levels, by ruling out and/or by removing the CPB activity are theorically able to elicit sympathetic "disinhibition", and to exercise, consequently, a reflex, vasoconstrictor influence upon the forearm vascular bed, whereas the same reflex behaviour by forearm resistance vessels does not appear feasible if the CPB activity has been preventively minimized by prolonged, chronic beta-blockade.

We attempted to determine the relevance and relative prevalence of autonomic dysfunction in 7 patients with end-stage renal disease (ESRD) but no heart disease, 8 patients with left ventricular dysfunction (LVD) with no renal disease and 8 patients with ESRD + LVD. In each group, the assessment of autonomic function and location of the lesion was performed by using the baroreflex sensitivity tests, based upon heart rate (ie Valsalva, deep breathing, lying to standing) to study the parasympathetic system as well as based upon blood arterial pressure (ie standing and sustained handgrip) to evaluate the sympathetic system. The same tests were performed in 7 healthy volunteers enrolled as control group. Separate studies were performed on the efferent parasympathetic arc (atropine test) and the efferent sympathetic arc (cold pressor test). There was evidence of parasympathetic damage in 100% of ESRD patients, in 87.5% of ESRD + LVD patients, and in 62.5% of LVD. Only 1 of ESRD patients showed defective response to atropine whereas the remaining had a normal response, suggesting an afferent lesion alone. No abnormalities were found in the response to cold pressor test, thereby suggesting a lack of involvement of the efferent sympathetic arc. The response to handgrip was higher in LVD patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Transesophageal, electrophysiologic studies were conducted in 47 patients, with clinical and ECGgraphic diagnosis of paroxysmal reciprocating supraventricular tachycardia. After admission to hospital, the patients were enrolled in the study in accordance with the criterion concerning the exclusion of patients with signs and symptoms of severe heart pump failure (ie, NYHA III and IV class were excluded). The transesophageal study was performed during paroxysmal tachycardia in each patient to measure the V-A interval and to localize the site of reentry. Thereby, the patients could be grouped into 2 subsets, ie those with A-V nodal reentrant tachycardia (no. 30 patients) and those with accessory pathway reentrant tachycardia (no. 17 patients). Moreover, the prevalence in both subsets was evaluated in the following signs and symptoms: palpitations, dyspnoea, chest pain, pulsations in the neck, significant increase in urinary output, hypotension, dizziness, near-syncope, syncope, shock, focal brain injury. From the data analysis, significantly greater prevalence of palpitations in the neck resulted in the subset of patients with reentry confined to the A-V node (no. 20 cases) compared with those suffering from reentry via accessory pathway (no. 4 cases). Moreover the arterial pressure, in A-V nodal reentrant tachycardia, showed the lowest values and the best decreases, together with the finding of a more rapid trend to decline in comparison with the accessory pathway subset. On the other hand, no significant differences could be seen about the remaining symptoms. In an attempt to provide the reliable explanation for the differences found between the 2 subsets of study, concerning both the unpleasant pulsations in the neck and the pressure decrease, we postulated a remarkable role for the length of arrhythmic circle movement. The smaller dimensions of circuit limbs, in A-V nodal reentrant tachycardia, are likely to be the principle cause of the different clinical features of 2 types of reentry. We speculate actually that in susceptible patients the critical event is most likely to be A-V functional dissociation due to early and unphysiologic activation of atria by stimulus rapidly reentrant from the bottom portion of the AV node: the simultaneous occurrence, frequent in A-V node reentry, of both, atrial and ventricular mechanical activation, would result, however, in impairment of atrial haemodynamics due to development of cannon A waves, able either to activate a vasodepressor reflex from the atria or to stimulate instantaneous release of atrial natriuretic factor in the circulation. Further studies, however, are necessary to be performed on large cases-records, to confirm our hypothesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Left atrial enlargement may occur sometimes through only the increase of the supero-inferior (S-I) diameter, with normality of the antero-posterior (A-P) and latero-medial dimensions. In this study, both the largest dimensions of the left atrium and S-I and transversal dimensions of the left atrium and S-I and transversal dimensions of the right atrium were investigated, among the 98 pts suffering from recurrent paroxysms of atrial fibrillation (FAP). On the basis of the clinical, ECGraphic and echocardiographic data, a subgroup of 78 pts has been found, with FAP reliable to heart disease, which mostly appeared as accompanying a finding of atrial enlargement--left or right or both--. The remaining 20 pts distinguished, by means of the echocardiographic findings, as following: a) "idiopathic" FAP, neither dependent on heart disease nor on atrial enlargement (no. 11 pts); b) FAP dependent on "unexplained" atrial enlargement, i.e. unreliable to definite cardiac pathology (no. 9 pts). Among the b) pts, 7 showed the only, isolated S-I dimension increased. Therefore, the determination of the all largest dimensions of the atria, in pts with recurrent FAP, appeared able to more carefully distinguish the true cases of "idiopathic" FAP.

The Journal of Clinical Medicine retracts the article "Vasopressin Receptor Antagonists for the Correction of Hyponatremia in Chronic Heart Failure: An Underutilized Therapeutic Option in Current Clinical Practice [...].

The Journal of Clinical Medicine retracts the article "An Admission-to-Discharge BNP Increase Is a Predictor of Six-Month All-Cause Death in ADHF Patients: Inferences from Multivariate Analysis Including Admission BNP and Various Clinical Measures of Congestion" [...].

The journal retracts the article "Platypnea-Orthodeoxia Syndrome: Multiple Pathophysiological Interpretations of a Clinical Picture Primarily Consisting of Orthostatic Dyspnea" by De Vecchis, R [...].