Molecular Pathogenesis of Central and Peripheral Nervous System Complications in Anderson-Fabry Disease.

Fabry disease (FD) is a recessive monogenic disease linked to chromosome X due to more than two hundred mutations in the alfa-galactosidase A (GLA) gene. Modifications of the GLA gene may cause the progressive accumulation of globotriaosylceramide (Gb3) and its deacylated form, globotriasylsphingosine (lyso-Gb3), in lysosomes of several types of cells of the heart, kidneys, skin, eyes, peripheral and central nervous system (not clearly and fully demonstrated), and gut with different and pleiotropic clinical symptoms. Among the main symptoms are acroparesthesias and pain crisis (involving the peripheral nervous system), hypohidrosis, abdominal pain, gut motility abnormalities (involving the autonomic system), and finally, cerebrovascular ischemic events due to macrovascular involvement (TIA and stroke) and lacunar strokes and white matter abnormalities due to a small vessel disease (SVS). Gb3 lysosomal accumulation causes cytoplasmatic disruption and subsequent cell death. Additional consequences of Gb3 deposits are inflammatory processes, abnormalities of leukocyte function, and impaired trafficking of some types of immune cells, including lymphocytes, monocytes, CD8+ cells, B cells, and dendritic cells. The involvement of inflammation in AFD pathogenesis conflicts with the reported poor correlation between CRP levels as an inflammation marker and clinical scores such as the Mainz Severity Score Index (MSSI). Also, some authors have suggested an autoimmune reaction is involved in the disease's pathogenetic mechanism after the α-galactosidase A deficiency. Some studies have reported a high degree of neuronal apoptosis inhibiting protein as a critical anti-apoptotic mediator in children with Fabry disease compared to healthy controls. Notably, this apoptotic upregulation did not change after treatment with enzymatic replacement therapy (ERT), with a further upregulation of the apoptosis-inducing factor after ERT started. Gb3-accumulation has been reported to increase the degree of oxidative stress indexes and the production of reactive oxygen species (ROS). Lipids and proteins have been reported as oxidized and not functioning. Thus, neurological complications are linked to different pathogenetic molecular mechanisms. Progressive accumulation of Gb3 represents a possible pathogenetic event of peripheral nerve involvement. In contrast, central nervous system participation in the clinical setting of cerebrovascular ischemic events seems to be due to the epitheliopathy of Anderson-Fabry disease with lacunar lesions and white matter hyperintensities (WMHs). In this review manuscript, we revised molecular mechanisms of peripheral and central neurological complications of Anderson-Fabry Disease. The management of Fabry disease may be improved by the identification of biomarkers that reflect the clinical course, severity, and progression of the disease. Intensive research on biomarkers has been conducted over the years to detect novel markers that may potentially be used in clinical practice as a screening tool, in the context of the diagnostic process and as an indicator of response to treatment. Recent proteomic or metabolomic studies are in progress, investigating plasma proteome profiles in Fabry patients: these assessments may be useful to characterize the molecular pathology of the disease, improve the diagnostic process, and monitor the response to treatment.

Nutritional predictors of mortality after discharge in elderly patients on a medical ward.

BACKGROUND: Malnutrition in elderly inpatients hospitalized on medical wards is a significant public health concern. The aim of this study was to investigate nutritional markers as mortality predictors following discharge in hospitalized medical elderly patients. MATERIALS AND METHODS: This is a prospective observational cohort study with follow-up of 48 months. Two hundred and twenty-five individuals aged 60 and older admitted from the hospital emergency room in the past 48 h were investigated at the medical ward in the University hospital in Palermo (Italy). Anthropometric and clinical measurements, Mini-nutritional Assessment (MNA) questionnaire, bioelectrical (BIA) phase angle (PA), grip strength were obtained all within 48 h of admission. Mortality data were verified by means of mortality registry and analysed using Cox-proportional hazard models. RESULTS: Ninety (40%) participants died at the end of follow-up. There were significant relationships between PA, MNA score, age and gender on mortality. Patients in the lowest tertile of PA (< 4·6°) had higher mortality estimates [I vs II tertile: hazard ratio (HR) = 3·40; 95% confidence interval (CI): 2·01-5·77; II vs III tertile: HR = 3·83; 95% CI: 2·21-6·64; log-rank test: χ(2) = 43·6; P < 0·001]. Similarly, the survival curves demonstrated low MNA scores (< 22) were associated with higher mortality estimates (HR = 1·85; 95% CI: 1·22-2·81 χ(2) = 8·2; P = 0·004). CONCLUSIONS: The MNA and BIA-derived phase angle are reasonable tools to identify malnourished patients at high mortality risk and may represent useful markers in intervention trials in this high-risk subgroup.

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.

Paraneoplastic Cerebellar Degeneration Associated with Breast Cancer: A Case Report and a Narrative Review.

Paraneoplastic neurological syndromes (PNSs) are an uncommon complication of cancer, affecting nearby 1/10,000 subjects with a tumour. PNSs can involve all the central and peripheral nervous systems, the muscular system, and the neuromuscular junction, causing extremely variable symptomatology. The diagnosis of the paraneoplastic disease usually precedes the clinical manifestations of cancer, making an immediate recognition of the pathology crucial to obtain a better prognosis. PNSs are autoimmune diseases caused by the expression of common antigens by the tumour and the nervous system. Specific antibodies can help clinicians diagnose them, but unfortunately, they are not always detectable. Immunosuppressive therapy and the treatment of cancer are the cornerstones of therapy for PNSs. This paper reports a case of PNSs associated with breast tumours and focuses on the most common paraneoplastic neurological syndromes. We report a case of a young female with a clinical syndrome of the occurrence of rigidity in the right lower limb with postural instability with walking supported and diplopia, with a final diagnosis of paraneoplastic cerebellar degeneration and seronegative rigid human syndrome associated with infiltrating ductal carcinoma of the breast.

Carotid atherosclerosis and chronic hepatitis C: a prospective study of risk associations.

UNLABELLED: There are contrasting results in studies of cardiovascular risk in patients with genotype 1 chronic hepatitis C (G1 CHC). We evaluated the prevalence of carotid atherosclerosis compared with a control population in order to assess the potential association between atherosclerosis, host and viral factors, and liver histological features. In all, 174 consecutive biopsy-proven G1 CHC patients were evaluated by anthropometric and metabolic measurements and 174 patients attending an outpatient cardiology unit were used as controls. Intima-media thickness (IMT) and carotid plaques, defined as focal thickening of >1.3 mm at the level of common carotid, were evaluated using ultrasonography. All G1 CHC biopsies were scored by one pathologist for staging and grading, and graded for steatosis. Carotid plaques were found in 73 (41.9%) G1 CHC patients compared with 40 (22.9%) control patients (P < 0.001). Similarly, G1 CHC patients had a greater IMT compared with control patients (1.04 ± 0.21 versus 0.90 ± 0.16; P < 0.001). Multivariate logistic regression analysis showed that older age (odds ratio [OR] 1.047, 95% confidence interval [CI]: 1.014-1.082, P = 0.005), and severe hepatic fibrosis (OR 2.177, 95% CI: 1.043-4.542, P = 0.03), were independently linked to the presence of carotid plaques. In patients ≤55 years, 15/67 cases with F0-F2 fibrosis (22.3%) had carotid plaques, compared with 11/21 (52.3%) with F3-F4 fibrosis (P = 0.008). By contrast, in patients >55 years the prevalence of carotid plaques was similar in those with or without severe fibrosis (25/43, 58.1% versus 22/43, 51.1%; P = 0.51). CONCLUSION: Severe hepatic fibrosis is associated with a high risk of early carotid atherosclerosis in G1 CHC patients.

Streptococcus mitis as a New Emerging Pathogen in Pediatric Age: Case Report and Systematic Review.

Streptococcus mitis, a normal inhabitant of the oral cavity, is a member of Viridans Group Streptococci (VGS). Generally recognized as a causative agent of invasive diseases in immunocompromised patients, S. mitis is considered to have low pathogenic potential in immunocompetent individuals. We present a rare case of sinusitis complicated by meningitis and cerebral sino-venous thrombosis (CSVT) caused by S. mitis in a previously healthy 12-year-old boy with poor oral health status. With the aim of understanding the real pathogenic role of this microorganism, an extensive review of the literature about invasive diseases due to S. mitis in pediatric patients was performed. Our data define the critical role of this microorganism in invasive infections, especially in immunocompetent children and in the presence of apparently harmful conditions such as sinusitis and caries. Attention should be paid to the choice of therapy because of VGS's emerging antimicrobial resistance patterns.

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.

The glucocorticoid in acute decompensated heart failure: Dr Jekyll or Mr Hyde?

Glucocorticoid administration is not recommended in patients with heart failure because of its related sodium and fluid retention. However, previous experimental and clinical studies have demonstrated that glucocorticoids can also induce a diuretic effect and improve renal function in patients with acute decompensated heart failure (ADHF) with refractory diuretic resistance. We report the case of a 65-year-old man with a known diagnosis of aortic stenosis, systolic ventricular dysfunction, and chronic obstructive pulmonary disease who was admitted for ADHF. After 3 days, during which resistance to conventional therapy was observed, intravenous methylprednisolone (60 mg/d) was added to ongoing medical treatment. Three days after the onset of glucocorticoid therapy, daily urine volume progressively increased (up to 5.8 L/d). Concurrently, signs and symptoms of congestion improved, the weight and brain natriuretic peptide plasma levels decreased (−7 kg and −46%, respectively) and glomerular filtration rate increased (+26%). Bioimpedance vector analysis showed a net reduction of fluid content (from 88.4% to 73.6% of hydration at discharge). In conclusion, this case report suggests that in a patient with ADHF and congestion resistant to diuretic therapy, glucocorticoid administration is safe and associated with improvement in congestion, neurohormonal status, and renal function. These data support the possible usefulness of glucocorticoids in this setting.

Large hiatal hernia at chest radiography in a woman with cardiorespiratory symptoms.

Hiatal hernia (HH) is a frequent entity. Rarely, it may exert a wide spectrum of clinical presentations mimicking acute cardiovascular events such as angina-like chest pain until manifestations of cardiac compression that can include postprandial syncope, exercise intolerance, respiratory function, recurrent acute heart failure, and hemodynamic collapse. A 69-year-old woman presented to the emergency department complaining of fatigue on exertion, cough, and episodes of restrosternal pain with less than 1 hour of duration. Her medical history only included some episodes of bronchitis and no history of hypertension. The 12-lead electrocardiogram demonstrated sinus rhythm with right bundle-branch block. Laboratory tests, including cardiac troponin I, were within normal reference values. Chest radiography showed no significant pulmonary alterations and revealed in mediastinum a huge abnormal shadow overlapping the right heart compatible with a gastric bubble.The gastroscopy confirmed a large HH. A 2-dimensional transthoracic echocardiogram, using all standard and modified apical and parasternal views, revealed an echolucent mass, compatible with HH, compressing the right atrium. Also, it showed an altered left ventricular relaxation and a mild increase of pulmonary artery pressure (35 mm Hg). Spirometry showed a mild obstruction of the small airways, whereas coronary angiography showed normal coronary arteries. We concluded that the patient's symptomatology was related to the compressive effects of the large hiatal ernia, a neglected cause of cardiorespiratory symptoms. The surgical repair of HH was indicated.

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.

Severe Brochostenosis by Oral Propafenone Immediately After Commencing Treatment.

Propafenone is a membrane-stabilizing agent belonging to a subgroup of the Vaughan Williams class I antidysrhythmic agents, structurally resembling propranolol and characterized by weaker beta-blocking activity. Despite respiratory complications having been reported as examples of side effects, very few reports have been published in the literature.We describe the case of an elderly woman with a history of hypertension and allergy to Parietaria, grass, olive, mites, and with periodic asthmatic manifestations, for whom the administration of oral propafenone for recurrent supraventricular dysrhythmia was associated with the sudden onset of severe bronchostenosis.A 78-year-old woman was frequently admitted to the Emergency Department for a recurrent supraventricular tachycardia, which was treated initially with veramapil and thereafter with ivabradin. During her last visit to the cardiologist, she was prescribed propafenone (150 mg, 3 times a day) in place of ivabradin. After the administration of the second dose on the first day of the therapy, the patient began to complain of the onset of progressively severe dyspnea at rest. In the Emergency Department, respiratory auscultation showed diffuse rhonchi, wheezing, and rales; and arterial pressure was 200/100 mm Hg. Hemogasanalysis revealed hypoxemia, respiratory acidosis with 83% of O2-saturation. Emergency treatment with O2 therapy, methylprednisolone intravenous, furosemide, and then salbutamol was also started; the electrocardiogram only showed sinusal tachycardia. Results of laboratory examinations, including a white cell count and cardiac enzymes, were within the normal range. The patient achieved good respiratory function, after a period of 3 days.This report describes that even a relatively small dose of oral propafenone after commencing treatment can have a severe effect in exacerbating the obstruction of the airways in a susceptible subject. The likely mechanisms are an allergic reaction or a direct bronchospastic effect. Considering the recognized asthmogenicity of propafenone due to beta-blocker activity, we suggest that the cardiologist always refer to the patient's medical history before prescribing this drug, which is capable of producing notable side effects in predisposed individuals, beginning the eventual administration in the hospital setting. The use of bronchial provocation test allows the selection of inclined patients, thus reducing the risk of bronchospasm.

Sudden severe abdominal pain after a single low dose of paracetamol/codein in a cholecystectomized patient: learning from a case report.

We report the case of an elderly patient with diastolic heart failure and renal insufficiency admitted to hospital as he complained of having a history of hypogastric pain and dysuria without fever due to renal lithiasis and urinary infection. Because the pain was persistence, and considering the presence of renal dysfunction, it was administered a single low dose of paracetamol/codein (500/30 mg). After about 1 hour of the administration, he suddenly complained of the onset of a lancinating epigastric pain radiating to the whole abdomen and retrosternum accompanied by nausea. The electrocardiogram (EKG) was negative for myocardial infarction and computed tomography excluded aortic dissection and other causes of acute abdomen. Laboratory tests showed instead liver and pancreatic damage. The symptomatology was relieved 3 hours later of the onset after antispastic treatment with anticholinergics (floroglucine). The likely underlying pathophysiological mechanism is the codein-induced spasm of the sphincter of Oddi combined with dysfunction of the same sphincter and reduced bile storage capacity related to a previous cholecystectomy. When a similar event does not regress, it may lead to more severe conditions such as acute pancreatitis. Since codein is a widely used drug, this report may suggest cholecystectomy as a contraindication during administration for the risk of occurrence of these complications.

Obesity related changes in cardiac structure and function: role of blood pressure and metabolic abnormalities.

Background: It has been reported that changes in cardiac structure and ventricular function associated with obesity have to be attributable to hemodynamic and non-hemodynamic alterations. Accordingly, the aim of this was to evaluate left ventricular hypertrophy (LVH) prevalence and its effect on left ventricular systolic and diastolic function in a cohort of obese patients.Materials and Methods: LV internal diameter (LVID), left ventricular mass (LVM) and LVM/height2.7(LVMI), relative wall thickness (RWT), LV ejection fraction (LVEF), E/A ratio, isovolumic relaxation time, deceleration time of E velocity by echocardiography and pulsed-wave Doppler and total circulating adiponectin (ADPN) by radioimmunoassay were measured in 319 obese subjects with and without LVH.Results: Increased values of BMI, WHR, SBP, DBP, MBP LVID, LVM, LVMI, IVST (p < .001), increased prevalence of subjects with LVEF< 50%,(p < .001), central fat distribution (p < .001), hypertension (p < .001), diabetes (p < .001), metabolic syndrome (p < .02), and reduced value of ADPN (p < .0001) and LVEF (p < .001) were detected in LVH obese subjects than controls without LVH. No significant differences in diastolic parameters were observed between the two groups. LVEF correlated directly with ADPN (p < .0001) and inversely with age (p < .01), BMI (p < .01), WHR (p < .001), MBP (p < .01) MetS (p < .02) and LVMI (p < .001). WHR, MBP, LVMI and ADPN were independently associated with LVEF.Conclusions: In conclusion, our data indicate that obese subjects with LVH might be considered a distinct phenotype of obesity, characterised by LVH, increased prevalence of cardiometabolic comorbidities, central fat distribution, hypoadiponectinemia and early left ventricular systolic dysfunction.

Metabolic and Cardiovascular Effects of Switching Thiazides to Amlodipine in Hypertensive Patients With and Without Type 2 Diabetes (the Diuretics and Diabetes Control Study).

Background: Different studies have indicated that thiazide diuretics can increase the risk of developing type 2 diabetes (T2D). Therefore, in this study, we investigated whether switching from hydrochlorothiazide (HCTZ) to amlodipine resulted in ameliorating different cardiovascular and metabolic measures in hypertensive patients with or without T2D. Methods: This study [Diuretics and Diabetes Control (DiaDiC)] was a 6-week, single-blind, single-center randomized controlled trial. The first 20 normal glucose-tolerant, 20 prediabetic, and 20 T2D consecutive patients were randomized to continue the previous antihypertensive treatment with HCTZ (12.5-25 mg/day) or to switch from HCTZ to amlodipine (2.5-10 mg/day). The primary endpoints were the absolute change in 7-day continuous subcutaneous glucose monitoring (CSGM) glycemia, serum uric acid concentrations, and endothelial function [measured as flow-mediated dilation (FMD)]. Other secondary endpoints were investigated, including changes in glycated hemoglobin (HbA1c), glycemic variability from 7-day CSGM, and the estimated glomerular filtration rate (eGFR). Results: Amlodipine treatment was associated with a significant reduction in HbA1c (P = 0.03) for both 7-day CSGM glycemia (P = 0.01) and glycemic variability (coefficient of variability %: HCTZ +3%, amlodipine -2.8%), and a reduction in uric acid concentrations (P < 0.001), especially in participants with T2D or prediabetes. Following amlodipine treatment, a significant increase in both eGFR (P = 0.01) and FMD (P = 0.02) was also observed. Conclusions: This study demonstrates that the replacement of HCTZ with amlodipine has several metabolic and cardiovascular beneficial effects. However, further intervention studies are necessary to confirm the clinical effects of thiazides, especially in diabetic people and in those at risk of diabetes.

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.

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.

Right ventricular diameter predicts all-cause mortality in heart failure with preserved ejection fraction.

Left ventricular ejection fraction (EF) is helpful to differentiate heart failure (HF) phenotype in clinical practice. The aim of the study was to identify simple echocardiographic predictors of post-discharge all-cause mortality in hospitalized HF patients. Patients with acute HF (75 ± 9.8 years), classified in preserved (≥ 50%) and reduced (< 50%) EF (HFpEF and HFrEF, respectively), were enrolled. The mean follow-up period was of 25.4 months. Patients definitively analyzed were 135. At multivariate Cox model, right ventricular diameter (RVd), inferior vena cava diameter (IVCd) and blood urea nitrogen (BUN) resulted to be significantly associated with all-cause mortality in HFpEF (HR 2.4, p = 0.04; HR 1.06, p = 0.02; HR 1.02, p = 0.01), whereas, left atrial volume (LAV) was significantly associated with mortality in HFrEF (HR 1.06, p = 0.006). Excluding LAV from the model, only COPD remained an independent predictor of all-cause mortality (HR 2.15, p = 0.04) in HFrEF. At Kaplan-Meier analysis, no differences of survival between HFrEF and HFpEF were found, however, significantly increased all-cause mortality for higher values of basal-RVd, BUN, and IVCd (log-rank p = 0.0065, 0.0063, 0.0005) in HFpEF, and for COPD and higher LAV (log-rank p = 0.0046, p = 0.033) in HFrEF. These data are indicative that in patients hospitalized with HF, EF is not a suitable predictor of long-term all-cause mortality, whereas, right ventricular volumetric remodeling and IVCd have a prognostic role in HFpEF as well as LAV in HFrEF. Our study suggests that besides EF, other echocardiographic parameters are helpful to optimize the phenotyping and prognostic stratification of HF.

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.