Water and sodium in heart failure: a spotlight on congestion.

Despite all available therapies, the rates of hospitalization and death from heart failure (HF) remain unacceptably high. The most common reasons for hospital admission are symptoms related to congestion. During hospitalization, most patients respond well to standard therapy and are discharged with significantly improved symptoms. Post-discharge, many patients receive diligent and frequent follow-up. However, rehospitalization rates remain high. One potential explanation is a persistent failure by clinicians to adequately manage congestion in the outpatient setting. The failure to successfully manage these patients post-discharge may represent an unmet need to improve the way congestion is both recognized and treated. A primary aim of future HF management may be to improve clinical surveillance to prevent and manage chronic fluid overload while simultaneously maximizing the use of evidence-based therapies with proven long-term benefit. Improvement in cardiac function is the ultimate goal and maintenance of a "dry" clinical profile is important to prevent hospital admission and improve prognosis. This paper focuses on methods for monitoring congestion, and strategies for water and sodium management in the context of the complex interplay between the cardiac and renal systems. A rationale for improving recognition and treatment of congestion is also proposed.

Collective Catering Activities and Official Controls: Dietary Promotion, Sustainability and Future Perspectives.

Ensuring safe meals with suitable hygienic-sanitary and nutritional features is an essential requirement to guarantee health in different settings. This study aims to evaluate the compliance of collective catering menus adopted in both school canteens and healthcare facilities in a regional area where specific guidelines have been issued, assessing many matters from food weight to single courses and from the use of wholegrain pasta and bread to the rotation of seasonal fruit and vegetables. Overall, 85 menus, edited by freelance professionals and endorsed by the Food Hygiene and Nutrition Service staff of the Local Health Authority, were assessed from 2018 to 2022, highlighting critical issues potentially attributable at a local level to the lack of complete knowledge of the existence of guidelines and official reference documents among nutrition professionals. Since the preliminary outcomes show non-compliance in both sectors investigated, it is essential to continue to strengthen the role of prevention departments entrusted with services dedicated to food and nutritional safety and promote joint official controls performed by healthcare workers and other professionals with different backgrounds in order to ensure safe food for the target population that use collective catering services. In school canteens and healthcare facilities, providing and administering food is an opportunity to promote health through a balanced diet and safe food and offers opportunities for the development of community well-being and the local economy in a sustainable manner, understood in economic, environmental and social terms.

Troponin I release after intravenous treatment with high furosemide doses plus hypertonic saline solution in decompensated heart failure trial (Tra-HSS-Fur).

BACKGROUND: High values of cardiac troponin in acute decompensated congestive heart failure (ADHF) identify patients at higher risk and worsened prognosis. A cardiac troponin increase during therapy indicates the need for more appropriate intervention, aimed at compensating cardiac disease and effectively minimizing myocardial wall stress and subsequent cytolysis. This study evaluated the effects of an intravenous high dose of furosemide with (group A) or without small volume hypertonic saline solution (HSS) (group B) on myocardial cytolysis in patients with ADHF. METHODS: A total of 248 consecutive patients with ADHF (148 men, mean age 74.9 ± 10.9 years) were randomly assigned to group A or B. Plasma levels of cardiac troponin-I, brain natriuretic peptide, glomerular filtration rate by Modification of Diet in Renal Disease formula, bioelectrical impedance analysis measurements, and delta pressure/delta time (dP/dt) rate were observed on admission and discharge for all patients. RESULTS: We observed a significant reduction of cardiac troponin in both groups and a significant improvement in renal function, hydration state, pulmonary capillary wedge pressure (P < .0001), end diastolic volume (P < .01), ejection fraction (P < .01), and dP/dt (P < .004) in group A. We also observed a significant reduction in body weight (64.4 vs 75.8 kg) (P < .001), cardiac troponin I (0.02 vs 0.31 ng/mL) (P < .0001) and brain natriuretic peptide (542 vs 1,284 pg/mL) (P < .0001), and hospitalization time (6.25 vs 10.2 days) (P < .0001) in the HSS group. CONCLUSIONS: These data demonstrate that intravenous high doses of furosemide do not increase myocardial injury and, in addition, when associated to HSS, significantly reduce cardiac troponin I release. This behavior is mirrored by the achievement of improved hemodynamic compensation at echocardiography and body hydration normalization.

Changes in estimating echocardiography pulmonary capillary wedge pressure after hypersaline plus furosemide versus furosemide alone in decompensated heart failure.

BACKGROUND: The aim of the study was to verify the effects of hypertonic saline solution (HSS) plus a high furosemide dose and light restriction of sodium intake compared with a high-dose infusion of furosemide alone on pulmonary capillary wedge pressure (PCWP), as determined by Doppler echocardiography and tissue Doppler imaging in patients suffering from decompensated heart failure. METHODS AND RESULTS: Consecutive patients in New York Heart Association functional class IV, unresponsive to oral high doses of furosemide up to 250-500 mg/d and/or combinations of diuretics, with ejection fraction <40%, serum creatinine <2 mg/dL, blood urea nitrogen ≤60 mg/dL, reduced urinary volume (<500 mL/24 h), and low natriuresis (<60 mEq/24 h) were randomized into 2 groups (double blind). The first group received a furosemide infusion (250 mg) plus HSS (150 mL 3.0% Na) bid and light Na restriction (120 mmol), and the second group received furosemide infusion (250 mg) twice daily, and low Na diet (80 mmol). The fluid intake of both groups was restricted (1 L/d). Body weight, whole-body bioelectrical impedance analysis (BIA), 24-hour urinary volume, and serum and urinary laboratory parameters were measured daily. Estimations of echocardiographic PCWP (Echo-PCWP) were detected on entry, 1 hour after concluding the initial treatment, and 6 days thereafter. A total of 133 patients (47 women and 86 men), aged 65-82 years, met the entry criteria.The HSS group revealed a significant increase in daily diuresis, natriuresis, and serum sodium compared with the furosemide group. Six days after treatment, renal function was significantly improved in the HSS group. Both groups showed a significant reduction in Echo-PCWP, but the HHS group revealed a faster reduction and significant lower values at 6 days compared with the group taking furosemide alone. We observed a positive correlation between values of Echo-PCWP and BNP and an inverse correlation between BIA parameters and Echo-PCWP. CONCLUSIONS: Our data show that the combination of high diuretic dose and HSS infusion plus light restriction in dietary sodium intake determine a more rapid and significant hemodynamic stabilization through the improvement of echo-PCWP, BNP levels, and BIA parameters than the group treated without HSS.

Case Report: Unusual Clinical Presentation of a Rare Cardiac Inflammatory Myofibroblastic Tumor in Children: The Differential Diagnosis With Pediatric Emergencies.

Introduction: There are still no guidelines about pediatric cardiac cancers. The purpose of this work is to provide new scientific data facilitating the differential diagnosis of a rare cardiac tumor with an unusual presentation, such as the cardiac inflammatory myofibroblastic tumor (IMT). Case Presentation: A 3-year-old male child presented with several symptoms including unconsciousness, vomiting, and drowsiness. A clinical and neurological examination revealed a unilateral (right) motor delay and positive unilateral Babinski sign. Electrocardiogram (ECG) was normal. Diagnostic Assessment: The total body computed tomography (CT) scans showed hypodensity in the left temporal-parietal lobe, a large hypodense area in the right frontal lobe, and a second area in the left frontal lobe were found with head CT. A magnetic resonance (MR) also noted cerebral areas of hypointensity. The echocardiographic images revealed an ovoid mass, adherent to the anterolateral papillary muscle. The histological exams, performed with hematoxylin-eosin, Masson's trichrome, Alcian blue PAS, Weigert and Van-Gieson stain, allowed observing the microscopic structure of the neoplastic mass. The immunohistochemical analysis was performed through subsequent antibodies: anti-vimentin, anti-actina, anti-ALK, anti-CD8, anti-CD3, anti-CD20, anti-kappa and lambda chains, and anti CD68 antibodies. The healthcare professionals diagnosed a cardiac IMT with brain embolism. Differential Diagnosis: The ventricular localization, observed through radiological exams, required a differential diagnosis with fibroma and rhabdomyoma, the presence of brain embolism with sarcoma, and its morphology with fibroma. Neurological symptoms might be attributed to encephalitis, primitive cerebral cancer, such as astrocytoma or neuroblastoma, cerebral metastases due to any malignancy, or embolic stroke. Conclusion: New studies are encouraged to better define IMT behavior and draw up guidelines confirming the crucial role of multidisciplinary approach and treatment protocol selected on the basis of the characteristics of the tumors, in the case of this rare type of cancer.

Cardiovascular Implantable Electronic Device Infection and New Insights About Correlation Between Pro-inflammatory Markers and Heart Failure: A Systematic Literature Review and Meta-Analysis.

Introduction: Surgical approaches to treat patients with abnormal pro-inflammatory parameters remain controversial, and the debate on the correlation between hematological parameter alteration in cardiac implantable electronic device (CIED) infection and the increase in mortality continues. Methods: We performed a systematic review using the PubMed, Scopus, and Cochrane Library databases. Twenty-two articles from May 2007 to April 2020 were selected and divided according to the following topics: prevalence of microbes in patients with CIED infection; characteristics of patients with CIED infection; comparison between patients who underwent and did not undergo replantation after device extraction; and correlation between alteration of hematological parameters and poor prognosis analysis. Results: Epidemiological analysis confirmed high prevalence of male sex, staphylococcal infection, and coagulase-negative staphylococci (CoNS). The most common comorbidity was heart failure. Complete removal of CIED and antimicrobial therapy combination are the gold standard. CIED replacement was associated with higher survival. High preoperative white blood cell count and C-reactive protein levels increased the risk of right ventricular failure (RVF) development. Increased red blood cell distribution width (RDW) value or decreased platelet count was correlated with poor prognosis. No correlation was noted between preoperative leukocytosis and CIED infection. Discussion: A relevant correlation between leukocytosis and RVF was observed. Heart failure may be related to high RDW values and decreased platelet count. Data on the correlation between hematological parameter alteration and poor prognosis are missing in many studies because of delayed implantation in patients showing signs of infection.

An Integrated Control Plan in Primary Schools: Results of a Field Investigation on Nutritional and Hygienic Features in the Apulia Region (Southern Italy).

Data concerning overweight and obesity in children and adolescent populations are alarming and represent one of the most serious public health problems of our time. Moreover, it is demonstrated that the school environment may play an important role in health promotion with regard to nutritional aspects. This article reports the results of a study conducted in the Apulia region (Southern Italy), aimed at providing an integrated surveillance of the behaviors related to nutrition habits in students and the hygienic and nutritional conditions of the school's canteens attended by enrolled students. To this purpose, a sample of 501 students attending primary school (third class-children approximately eight years old) replied to a validated questionnaire, and official controls (OC), of both food and nutritional safety, were performed in 22 primary schools. A team of healthcare professionals carried out the study, and the implementation of all the prescribed improvement actions were subsequently verified through follow-up OC. The results of our study show a critical situation in the student sample, with 41.3% of children having a weight excess (overweight or obesity). With regard to the children's behaviors, only 59.8% of children ate at least one fruit or had a fruit juice for breakfast, and 10.8% did not have breakfast at all. Overall, 40.1% of the total children played outdoors the afternoon before the survey and 45% reported going to school on foot or by bicycle. During the afternoon, 83.5% of the sample watched television or used video games/tablets/mobile phones, while 42.3% played sports. The schools had an internal canteen with on-site preparation of meals in 36.4%, the remaining 63.6% received meals from external food establishments. With regard to OC, for the hygienic-sanitary section, eleven prescriptions were issued, in the great part related to the structure and organization of the canteen. For the nutritional section, nine corrective actions were prescribed, mainly related to official documents and management. The follow-up OC showed that all prescriptions were subsequently addressed. Eating at school was less frequent among obese and overweight students compared with those with normal weight. Although this evidence needs to be further confirmed, it highlights the potential role that the school canteens may play in health promotion and prevention of nutritional disorders. On the other hand, in order to fulfill its health promotion task, the school canteens have to comply with official regulations and guidelines; therefore, OC during the management of the food service at school are needed.

International collaborative systematic review of controlled clinical trials on pharmacologic treatments for acute pericarditis and its recurrences.

BACKGROUND: Acute pericarditis is common, yet uncertainty persists on its treatment. We thus aimed to conduct a comprehensive systematic review on pharmacologic treatments for acute or recurrent pericarditis. METHODS: Controlled clinical studies were searched in several databases and were included provided they focused on pharmacologic agents for acute pericarditis or its recurrences. Random-effect odds ratios (ORs) were computed for long-term treatment failure, pericarditis recurrence, rehospitalization, and adverse drug effects. RESULTS: From 2,078 citations, 7 studies were finally included (451 patients); but only 3 were randomized trials. Treatment comparisons were as follows: colchicine versus standard therapy (3 studies, 265 patients), steroids versus standard therapy (2 studies, 31 patients), low-dose versus high-dose steroids (1 study, 100 patients), and statins versus standard therapy (1 study, 55 patients). Colchicine was associated with a reduced risk of treatment failure (OR = 0.23 [0.11-0.49]) and recurrent pericarditis (OR = 0.39 [0.20-0.77]), but with a trend toward more adverse effects (OR = 5.27 [0.86-32.16]). Overall, steroids were associated with a trend toward increased risk of recurrent pericarditis (OR = 7.50 [0.62-90.65]). Conversely, low-dose steroids proved superior to high-dose steroids for treatment failure or recurrent pericarditis (OR = 0.29 [0.13-0.66]), rehospitalizations (OR = 0.19 [0.06-0.63]), and adverse effects (OR = 0.07 [0.01-0.54]). Data on statins were inconclusive. CONCLUSIONS: Clinical evidence informing decision-making for the management of acute pericarditis and its recurrences is still limited to few, small, and/or low-quality clinical studies. Notwithstanding such major caveats, available studies routinely using nonsteroidal anti-inflammatory agents in both experimental and control groups suggest a beneficial risk-benefit profile for colchicine and a detrimental one for steroids, especially when used at high dosages.

Rhabdomyolysis induced by co-administration of fluvastatin and colchicine.

A case of fluvastatin-induced rhabdomyolysis after coadministration of colchicine is reported. A 77 year old man with ischemic heart disease, chronic pericardial effusion, diabetes mellitus, dyslipidemia, arterial hypertension, chronic renal failure (stage 2 of classification of chronic kidney disease of National Kidney Foundation) and chronic gout presented with a generalized muscle pain. The patient had been taking 80 mg/day of fluvastatin for 4 years, and, for four weeks before presentation, he had also been taking a dose of colchicine (1.0 mg daily) for an exacerbation of gout. Investigations confirmed the diagnosis of rhabdomyolysis. Discontinuation of fluvastatin and colchicine therapy and adequate fluid administration resulted in the resolution of clinical and biochemical features of rhabdomyolysis. Although neuromuscular adverse effects of fluvastatin and colchicine are well recognized, rhabdomyolysis is rare, making this is only the second case reported of fluvastatin and colchicine co-administration induced rhabdomyolysis in literature.

Long-term effects of dietary sodium intake on cytokines and neurohormonal activation in patients with recently compensated congestive heart failure.

BACKGROUND: A growing body of evidence suggests that the fluid accumulation plays a key role in the pathophysiology of heart failure (HF) and that the inflammatory and neurohormonal activation contribute strongly to the progression of this disorder. METHODS AND RESULTS: The study evaluated the long-term effects of 2 different sodium diets on cytokines neurohormones, body hydration and clinical outcome in compensated HF outpatients (New York Heart Association Class II). A total of 173 patients (105 males, mean age 72.5+/-7) recently hospitalized for worsening advanced HF and discharged in normal hydration and in clinical compensation were randomized in 2 groups (double blind). In Group 1, 86 patients received a moderate restriction in sodium (120mmol to 2.8g/day) plus oral furosemide (125 to 250mg bid); in Group 2, 87 patients: received a low-sodium diet (80mmol to 1.8g/day) plus oral furosemide (125 to 250mg bid). Both groups were followed for 12 months and the treatment was associated with a drink intake of 1000mL daily. Neurohormonal (brain natriuretic peptide, aldosterone, plasma rennin activity) and cytokines values (tumor necrosis factor-alpha, interleukin-6) were significantly reduced with a significant increase of the anti-inflammatory cytokine interleukin-10 at 12 months in normal, P < .0001) than low-sodium group. The low-sodium diet showed a significant activation of neurohormones and cytokines and worsening the body hydration, whereas moderate sodium restriction maintained dry weigh and improved outcome in the long term. CONCLUSIONS: Our results appear to suggest a surprising efficacy of a new strategy to improve the chronic diuretic response by increasing Na intake and limiting fluid intake. This counterintuitive approach underlines the need for a better understanding of factors that regulate sodium and water handling in chronic congestive HF. A larger sample of patients and further studies are required to evaluate whether this is due to the high dose of diuretic used or the low-sodium diet.

Comparison of ivabradine versus metoprolol in early phases of reperfused anterior myocardial infarction with impaired left ventricular function: preliminary findings.

BACKGROUND: beta-blockers in ST-segment elevation myocardial infarction (STEMI) are indicated for patients without a contraindication, particularly in patients with high heart rates (HR) or blood pressures. Epidemiological studies have shown that elevated HR represents a risk factor for cardiovascular morbidity. The study investigates the feasibility, tolerability, and the effects after 30 days of follow-up of ivabradine (IVA) versus metoprolol (METO) in early phases of anterior STEMI reperfused by percutaneous coronary intervention (PCI). METHODS AND RESULTS: Patients with a first anterior STEMI, Killip class I-II, an acceptable echocardiographic window, and admitted within 4hours of the onset of symptoms, with an ejection fraction <50%. METO or IVA, 12hours after PCI (double blind), were administered twice per day. Blood pressure (BP), heart rate (HR), electrocardiogram (ECG), and laboratory parameters were monitored during the study. At entry, day 10, day 30, and day 60, by echocardiography, the ESV, EDV, E/A ratio, E wave deceleration time, isovolumetric relaxation time were measured. A total of 155 (50 females, 105 males) patients were randomized in 2 groups: a group received METO (76 patients) 12hours after PCI and a group received IVA (79 patients) 12hours after PCI. The 2 groups were similar for clinical characteristics. No difference was evidenced in HR, systolic blood pressure, diastolic blood pressure, age (range, 39-73 years), sex, ejection fraction (EF), creatine kinase peak, between the 2 groups at entry. Both groups were similar for time to angiography and interventional procedures and number of vessels diseased. IVA group: the 79 patients showed 2 side effects and 5 readmissions: 4 for ischemic events and 1 for heart failure, and 1 sudden death; METO group: the 76 patients had 4 ischemic events, 2 side effects, and 1 patient died during re-acute MI (intrastent thrombosis) and 8 readmissions for heart failure signs. The systolic blood pressure and diastolic blood pressure showed a significant reduction in both groups, P < .0001, respectively), and significant lower values were observed in METO group, P=.0001). The HR was significantly reduced in both groups, P < .0001). IVA group showed a significant increase in EF, P=.0001, with concomitant reduction in ESV and EDV (P=.0001, and .048, respectively). The diastolic parameters were similar in both groups during study period. CONCLUSIONS: Our results suggest that ivabradine may be administered early (12hours after PCI) to patients with successful PCI for anterior STEMI with an impaired left ventricular function and high HR and sinus rhythm. A larger sample of patients and further studies are required to evaluate the effects of ivabradine on clinical end points.

An unusual presentation of massive pulmonary embolism mimicking septal acute myocardial infarction treated with tenecteplase.

A 31-year-old man (175 cm, 82 kg) was referred to the emergency department 2 h after the sudden onset of acute dyspnea. Immediate ECG showed sinus tachycardia with ST elevations from V1 through V2 and a diagnosis of septal acute myocardial infarction was made. ECG on admission to the cardiology department showed the same results plus the S1-Q3-T3 pattern. Echocardiogram revealed a normally contracting left ventricle, a distended right ventricle with free wall hypokinesia and displacement of the interventricular septum towards the left ventricle. Thrombolytic therapy with tenecteplase 8000 IU and heparin 5000 IU was administered 5-10 min after hospitalisation and the patient was haemodynamically stable 30 min later. Echocardiogram performed 12 h after thrombolysis showed a normal left ventricle and a less distended right ventricle. Lung spiral computed tomography (CT) and lower abdominal CT on the fourth day showed large emboli in the inferior pulmonary arteries of the right and left lung. Rarely, massive pulmonary embolism may mimic anteroseptal acute myocardial infarction on ECG and this case demonstrates the utility of echocardiography for a differential diagnosis, as well as the efficacy of tenecteplase for thrombolytic therapy.

One-year renal and cardiac effects of bisoprolol versus losartan in recently diagnosed hypertensive patients: a randomized, double-blind study.

BACKGROUND AND OBJECTIVES: Hypertension is a significant cause of chronic renal injury and its effective treatment is capable of reducing the rate of renal failure. beta-Adrenoceptor antagonists (beta-blockers) have been reported to induce a deterioration in renal function, while several data have indicated a renoprotective effect of treatment with the angiotensin II type 1 receptor antagonist losartan. Previous studies of the interaction between the selective beta(1)-blocker bisoprolol and kidney function were performed only for short- and medium-term periods. The aim of this study was to compare the antihypertensive efficacy and renal and cardiac haemodynamic effects of bisoprolol with those of losartan over a 1-year time period in patients with essential hypertension. METHODS: Seventy-two patients (40 males) with recently diagnosed uncomplicated (European Society of Hypertension [ESH] criteria stage 1-2) hypertension (mean +/- SD age 52 +/- 12 years) were enrolled in the study. After a run-in period of 14 days on placebo, the patients were randomized in a double-blind, prospective study to receive either bisoprolol 5 mg or losartan 50 mg, administered once daily for 1 year. At recruitment and 12 months after treatment, cardiac output and renal haemodynamics and function were evaluated by echocardiography and radionuclide studies, respectively. RESULTS: There were no significant differences in baseline clinical data, including glomerular filtration rate and blood pressure, between the two treatment groups. At 1 year, blood pressure had decreased significantly (p < 0.001) with both treatments, and heart rate was reduced only in the group taking bisoprolol. The long-term effects on renal haemodynamics and cardiac function were similar with both drugs, the only change being a significant reduction in the filtration fraction for each group. CONCLUSIONS: These data suggest that both bisoprolol and losartan are effective agents for the treatment of patients with recently diagnosed ESH stage 1-2 hypertension. Over a 1-year period, both agents maintained good renal and cardiac performance and haemodynamics.

The usefulness of bioelectrical impedance analysis in differentiating dyspnea due to decompensated heart failure.

BACKGROUND: Acute dyspnea poses a diagnostic challenge for physicians, and the current methods in differentiating cardiac from non-cardiac causes have been limited to date. Recently, the brain natriuretic peptide (BNP) rapid test has been validated in the emergency room. Nevertheless, the early accumulation of fluid in the interstitial space in the body and in the lungs, which characterizes patients with ADHF, is well estimated by BIA. We investigate whether bioelectrical impedance analysis (BIA) can serve as a noninvasive diagnostic tool in the differential diagnosis of acute decompensated heart failure (ADHF) in the emergency department (ED). METHODS AND RESULTS: A total of 292 patients presenting with acute dyspnea to the ED were evaluated by using a conventional diagnostic strategy and rapid BNP measures. Segmental (Seg) and whole-body (WB) BIA resistance (Rz) and reactance (Xc) on entry were immediately detected. After hospital discharge, an expert team classified enrolled patients into ADHF and non-ADHF. A total of 58.9% of patients had ADHF, whereas 41.1% were non-ADHF. ADHF patients showed significantly (P < .001) higher BNP values (591.8 +/- 501 versus 69.5 +/- 42 pg/mL), a significant (P < .001) reduction of Seg (35.5 + 8.2 versus 66.4 + 10.5) and WB (402.3 + 55.5 versus 513.2 + 41.8) Rz (Ohm), and a significant correlation (P < .0001) between BNP and Seg (r = -0,62) and WB (r = -0.63) bioelectrical Rz was also identified. Multiple regression analysis revealed that whole body and segmental BIA were strong predictors of ADHF alone or in combination with BNP. CONCLUSIONS: Our data suggest that Seg and WB BIA are a useful, simple, rapid, and noninvasive diagnostic adjunct in the early diagnosis of dyspnea from ADHF.

Normal-sodium diet compared with low-sodium diet in compensated congestive heart failure: is sodium an old enemy or a new friend?

The aim of the present study was to evaluate the effects of a normal-sodium (120 mmol sodium) diet compared with a low-sodium diet (80 mmol sodium) on readmissions for CHF (congestive heart failure) during 180 days of follow-up in compensated patients with CHF. A total of 232 compensated CHF patients (88 female and 144 male; New York Heart Association class II-IV; 55-83 years of age, ejection fraction <35% and serum creatinine <2 mg/dl) were randomized into two groups: group 1 contained 118 patients (45 females and 73 males) receiving a normal-sodium diet plus oral furosemide [250-500 mg, b.i.d. (twice a day)]; and group 2 contained 114 patients (43 females and 71 males) receiving a low-sodium diet plus oral furosemide (250-500 mg, b.i.d.). The treatment was given at 30 days after discharge and for 180 days, in association with a fluid intake of 1000 ml per day. Signs of CHF, body weight, blood pressure, heart rate, laboratory parameters, ECG, echocardiogram, levels of BNP (brain natriuretic peptide) and aldosterone levels, and PRA (plasma renin activity) were examined at baseline (30 days after discharge) and after 180 days. The normal-sodium group had a significant reduction (P<0.05) in readmissions. BNP values were lower in the normal-sodium group compared with the low sodium group (685+/-255 compared with 425+/-125 pg/ml respectively; P<0.0001). Significant (P<0.0001) increases in aldosterone and PRA were observed in the low-sodium group during follow-up, whereas the normal-sodium group had a small significant reduction (P=0.039) in aldosterone levels and no significant difference in PRA. After 180 days of follow-up, aldosterone levels and PRA were significantly (P<0.0001) higher in the low-sodium group. The normal-sodium group had a lower incidence of rehospitalization during follow-up and a significant decrease in plasma BNP and aldosterone levels, and PRA. The results of the present study show that a normal-sodium diet improves outcome, and sodium depletion has detrimental renal and neurohormonal effects with worse clinical outcome in compensated CHF patients. Further studies are required to determine if this is due to a high dose of diuretic or the low-sodium diet.

Fever of unclear origin and cytopenia because of acute splenic sequestration in a young immunocompetent carrier of beta-globin mutation for Hb Valletta.

Fever of unclear origin is a clinical challenge in medical practice. Infectious diseases, neoplasms, and collagen vascular illnesses are its main causes in adults and children. Acute splenic sequestration crises, a known potentially fatal complication of sickle cell disease and sickle beta-thalassemia, are uncommon in beta-heterozygosis. We describe a case of prolonged recurrent episodes of fever with spontaneous resolution, commencing at age 10 in a 15-year-old boy with a history of hypochromic microcytic anemia attributed to a thalassemic trait. He was admitted twice to our university hospital for continuous-remittent fever with a pruritic, macular evanescent Still's skin rash, severe splenomegaly, leucopenia, thrombocytopenia, and sudden aggravation of anemia. Infectious, rheumatologic, autoimmune, and hematologic illnesses were excluded. A genetic-based study revealed heterozygosis of the beta-globin gene for a A>C (Thr>Pro) substitution at position 87 called Hemoglobin Valletta (alpha 2 beta 2 87 PRO) with a C>G transition in homozygosis in beta-globin intronic polymorphism intervening sequence 2 at nucleotide 745. After a follow-up period of 1 year without treatment, the young patient remains apyretic and in good general clinical health with persistent microcythemia and hepatosplenomegaly. Acute splenic sequestration crisis and related cytopenia may be an unusual complication of fever of unclear origin in a beta-thalassemic carrier of a Hemoglobin Valletta mutation and polymorphism in homozygosis of intervening sequence 2 at nucleotide 745. This hemoglobinopathy may predispose to a clinical phenotype of minor or intermediate thalassemia and, during a febrile illness, to hemoglobin instability and splenic sequestration.

Combination of indomethacin and statin compared with indomethacin and placebo in patients with a first episode of acute pericarditis: preliminary findings.

The aim of the present study was to evaluate the safety and efficacy of the combination of indomethacin and statin compared with indomethacin plus placebo in patients with a first episode of pericarditis. A total of 55 consecutive patients with acute pericarditis were randomized in a double-blind manner into two groups: group 1 (statin group) was treated with 150 mg of indomethacin plus 10 mg of rosuvastatin, and group 2 (placebo group) was treated with 150 mg of indomethacin plus placebo. Both groups received treatment up to the normalization of inflammation markers and for the following week. Clinical and laboratory assessments [white cell count, ESR (erythrocyte sedimentation rate) and CRP (C-reactive protein), troponin I, creatine kinase and brain natriuretic peptide plasma levels], ECG and echocardiogram were performed at baseline and daily up to discharge. All of the patients were followed as outpatients for 3 months to evaluate any recurrence of pericarditis. The two groups were similar in age, sex and laboratory parameters [group 1 (the statin group), n=28 patients; gender, 18 male and ten female; and age, 29.5+/-5.7 years; group 2 (placebo group), n=27 patients; gender, 16 male/11 female; and age, 29.2+/-4.8 years]. The statin group, when compared with the placebo group, had a significantly faster reduction in CRP values (5.0+/-1.0 compared with 6.0+/-2.0 days respectively; P=0.022), ST segment normalization (3.5+/-1.0 compared with 4.5+/-1.0 days respectively; P=0.001), pericardial effusion (4.5+/-1.0 compared with 5.5+/-1.0 days respectively; P=0.001) and ESR (5.0+/-1 compared with 6.0+/-2 days respectively; P=0.022). Our results show that the combination of statin and indomethacin treatment in patients with acute pericarditis is feasible, with a significant reduction in inflammatory markers and a favourable trend in hospitalization time (5.5+/-2.0 compared with 6.5+/-2.0 days respectively; P=0.069). However, these preliminary findings require further studies in a larger sample of patients.

Novel strategies: challenge loop diuretics and sodium management in heart failure--part II.

The conflicting results of diuretic treatments in heart failure (HF) and the importance of Na management in the context of the cardiorenal syndrome and neurohormonal activation in HF have suggested novel and counterintuitive strategies, focused primarily on the use of vasopressin antagonists and hypertonic saline solution with high doses of loop diuretics and their neurohormonal interference. The emerging novel therapies involving direct inhibition of vasopressin receptors appear to show promising results. The use of hypertonic saline solution mixed with a high dose of loop diuretics produces, probably by indirect mechanisms, a reduction or inhibition of the activated neurohormonal systems in HF patients. This treatment opens a new window on the role of sodium management in these patients and on the relation between sodium and the kidney's role and function in heart failure. The authors review the current evidence for these therapies and suggest hypothetical bases for their efficacy.

Novel strategies: challenge loop diuretics and sodium management in heart failure--Part I.

This is the first of a 2-part series. This article reviews the relationships among diuretics, neurohormonal activation, renal function, fluid and Na management, the cardiorenal syndrome, and heart failure. Part II will describe novel therapies based on these relationships, focusing particularly on vasopressin antagonists and treatment using hypertonic saline solution with high-dose loop diuretics. Heart failure (HF) is a complex hemodynamic disorder characterized by chronic and progressive pump failure and fluid accumulation. Diuretics are a vital component of symptomatic management, and enhancing diuretic response in the setting of diuretic resistance is therefore pivotal. In HF patients treated with diuretics, compensatory pathophysiologic mechanisms to maintain vascular resistance, such as nonosmotic stimulation of vasopressin secretion and activation of the renin-angiotensin-aldosterone system and sympathetic nervous system, promote renal Na and water reabsorption. Thus, there remains a need to develop novel therapies for HF patients who are refractory to conventional medical treatment. The conflicting results of diuretic treatments in HF and the importance of Na management in the context of the cardiorenal syndrome and neurohormonal activation have suggested novel and counterintuitive strategies, focusing primarily on the use of vasopressin antagonists and hypertonic saline solution with high doses of loop diuretics and neurohormonal interference. The authors review the current evidence for these therapies and suggest hypothetical bases for their efficacy.