Cognitive performance of patients with chronic heart failure on sacubitril/valsartan : A retrospective cohort study.

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.

In HFREF patients, sacubitril/valsartan, given at relatively low doses, does not lead to increased mortality or hospitalization : A retrospective cohort study.

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.

Sacubitril/valsartan for heart failure with reduced left ventricular ejection fraction : A retrospective cohort study.

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.

Acute heart failure : An unmet medical need.

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.

Vasopressin receptor antagonists in patients with chronic heart failure.

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.

Transcatheter closure of PFO as secondary prevention of cryptogenic stroke.

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.

Platypnea-orthodeoxia syndrome : Orthostatic dyspnea and possible pathophysiological substrates.

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.

Effects of limiting fluid intake on clinical and laboratory outcomes in patients with heart failure. Results of a meta-analysis of randomized controlled trials.

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.

Hypertonic saline plus i.v. furosemide improve renal safety profile and clinical outcomes in acute decompensated heart failure: A meta-analysis of the literature.

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.

Natriuretic peptide-guided therapy: further research required for still-unresolved issues.

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.

Cabergoline use and risk of fibrosis and insufficiency of cardiac valves. Meta-analysis of observational studies.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 < 0.0001]. On the other hand, pooled data from seven studies showed that patients with hyperprolactinemia who were taking cabergoline (n = 444) exhibited significantly higher odds of mild- to-moderate tricuspid regurgitation compared to untreated controls (n = 954) [adjusted (iv) odds ratio: 1.92 95 % CI:1.34-2.73; p = 0.0003]. No significant differences in mitral or aortic valve regurgitation were detected between hyperprolactinemic patients taking cabergoline and controls. CONCLUSION: In PD patients, the risk of valvular regurgitation of any grade involving one or more cardiac valves was proven to be strongly associated with cabergoline treatment. Furthermore, based on our results, hyperprolactinemic patients taking cabergoline have an increased risk of mild-to-moderate tricuspid valve regurgitation.

B-type natriuretic peptide. Guided vs. conventional care in outpatients with chronic heart failure: a retrospective study.

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.

In right or biventricular chronic heart failure addition of thiazides to loop diuretics to achieve a sequential blockade of the nephron is associated with increased risk of dilutional hyponatremia: results of a case-control study.

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.

[Renoprotective effect of small volumes of hypertonic saline solution in chronic heart failure patients with marked fluid retention: results of a case-control study]. / Renoprotektiver Effekt kleiner Volumina hypertoner Kochsalzlösung bei Patienten mit chronischer Herzinsuffizienz und Ödembildung: Ergebnisse einer Fall-Kontroll-Studie.

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).

In chronic heart failure with marked fluid retention, the i.v. high doses of loop diuretic are a predictor of aggravated renal dysfunction, especially in the set of heart failure with normal or only mildly impaired left ventricular systolic function.

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.

The risk of worsening CHF is positively related to unitary increase in mitral regurgitation size: a case-cohort study derived from a II NYHA class CHF patient population.

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.

Different impact of carvedilol and transdermal scopolamine on cardiovascular performance of mild-moderate chronic heart failure patients: evidence of useful effects of scopolamine on tolerance to work load.

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.

[Usefulness of a complete echographic evaluation of the atrial dimensions for the diagnosis of idiopathic atrial fibrillation]. / Utilità di una valutazione ecografica completa delle dimensioni atriali per la diagnosi di fibrillazione atriale "idiopatica".

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.

[Hypotension during acute myocardial infarct. Different pattern of parameters of renal function in relation to the localization of necrosis]. / Ipotensione durante IMA. Diverso contegno di alcuni parametri di funzione renale in rapporto alla sede di necrosi.

BACKGROUND: 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. METHODS: 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 (p < 0.001). RESULTS: 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; p < 0.005; CrCl 70.6 vs 33.42; p < 0.001). 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. DISCUSSION AND CONCLUSIONS: 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.

[The dobutamine-dopamine combination versus amrinone in congestive heart failure with a marked edematogenic sign complicated by functional kidney failure. A comparison between 2 different models of inotropic stimulation and diuresis potentiation]. / Associazione dobutamina-dopamina versus amrinone nello scompenso cardiaco congestizio a marcata impronta edemigena complicato da insufficienza renale funzionale. Confronto tra due diversi modelli di stimolazione inotropa e di potenziamento della diuresi.

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.