Glioblastoma multiforme with oculomotor nerve involvement: case report and literature review.

Gliomas involving the cranial nerves III-XIII are rare. Even rarer are glioblastomas multiforme (GBMs) with only 10 cases previously reported. Oculomotor nerve involvement was described in only 2 patients. The mechanisms proposed so far include an origin from the nerve itself or an extension within the nerve of a midbrain tumor. We report the case of a 69-year-old man who presented with an isolated left oculomotor nerve palsy. He was found to have a left temporal GBM extended to the frontal lobe. Diagnostics and intraoperative and pathological findings clearly demonstrated a massive infiltration of the cisternal portion of the left oculomotor nerve. We suppose this could be the first case of direct oculomotor nerve invasion by exophytic spread of a supratentorial GBM or by subarachnoid seeding from a temporal tumor. Less probably, it could be the first case of an oculomotor nerve GBM with a temporal lobe invasion.

Influenza burden, prevention, and treatment in asthma-A scoping review by the EAACI Influenza in asthma task force.

To address uncertainties in the prevention and management of influenza in people with asthma, we performed a scoping review of the published literature on influenza burden; current vaccine recommendations; vaccination coverage; immunogenicity, efficacy, effectiveness, and safety of influenza vaccines; and the benefits of antiviral drugs in people with asthma. We found significant variation in the reported rates of influenza detection in individuals with acute asthma exacerbations making it unclear to what degree influenza causes exacerbations of underlying asthma. The strongest evidence of an association was seen in studies of children. Countries in the European Union currently recommend influenza vaccination of adults with asthma; however, coverage varied between regions. Coverage was lower among children with asthma. Limited data suggest that good seroprotection and seroconversion can be achieved in both children and adults with asthma and that vaccination confers a degree of protection against influenza illness and asthma-related morbidity to children with asthma. There were insufficient data to determine efficacy in adults. Overall, influenza vaccines appeared to be safe for people with asthma. We identify knowledge gaps and make recommendations on future research needs in relation to influenza in patients with asthma.

Additional predictive value of nutritional status in the prognostic assessment of heart failure patients.

BACKGROUND AND AIMS: Nutritional status (NS) is not routinely assessed in HF. We sought to evaluate whether NS may be additive to a comprehensive pre-discharge evaluation based on a clinical score that includes BMI (MAGGIC) and on an index of functional capacity (six minute walking test, 6mWT) in HF patients. METHODS AND RESULTS: The CONUT (Controlling Nutritional Status) score (including serum albumin level, total cholesterol and lymphocyte count) was computed in 466 consecutive patients (mean age 61 ± 11 years, NYHA class 2.6 ± 0.6, LVEF 34 ± 11%, BMI 27.2 ± 4.5) who had pre-discharge MAGGIC and 6MWT. The endpoint was all-cause mortality. Mild or moderate undernourishment was present in 54% of patients with no differences across BMI strata. The 12-month event rate was 7.7%. Deceased patients had a more compromised NS (CONUT 2.8 ± 1.5 vs 1.7 ± 1.3, p < 0.0001), and a more advanced HF (MAGGIC 28.2 ± 6.0 vs 22.0 ± 6.6, p < 0.0001; 6MWT 311.1 ± 102.2 vs. 408.9 ± 95.9 m, p < 0.0001). The 12-month mortality rate varied from 4% for well-nourished to 11% for undernourished patients (p = 0.008). At univariate analysis, the CONUT was predictive for all-cause mortality with a Hazard Ratio of 1.701 [95% CI 1.363-2.122], p < 0.0001. Multivariable analysis showed that the CONUT significantly added to the combination of MAGGIC and 6MWT and improved predictive discrimination and risk classification (c-index 0.82 [95% CI 0.75-0.88], integrated discrimination improvement 0.028 [95% CI 0.015-0.081]). CONCLUSIONS: In HF patients assessment of NS, significantly improves prediction of 12-month mortality on top of the information provided by clinical evaluation and functional capacity and should be incorporated in the overall assessment of HF patients.

The novel cannabinoid antagonist SM-11 reduces hedonic aspect of food intake through a dopamine-dependent mechanism.

Cannabinoids, endogenous and exogenously administered, are known to positively regulate food intake and energy balance. Since CB1 receptor antagonists reduce food intake and antagonize overweight, we developed a new CB1 receptor antagonist in an attempt to identify a compound with potential application in overeating disorders. The newly developed SM-11 compound dose-dependently decreases food intake in rats by 15-20%. Moreover, SM-11 reduces self-administration of palatable food in both food restricted and ad libitum fed rats, suggesting an action on the hedonic component of food intake. Thus, we next tested the effect of SM-11 on the stimulating properties of the CB1 receptor agonist WIN55,212-2 (WIN) on the electrophysiological activity of Nucleus Accumbens-projecting dopaminergic neurons of the ventral tegmental area (VTA). SM-11 fully and readily antagonized the WIN-induced increments in single spiking and burst firing of antidromically-identified dopamine neurons. When administered to naïve (no WIN-pretreated) rats, SM-11 did not alter basal neuronal activity, thereby suggesting a pure antagonistic profile. SM-11 thus appears as a promising candidate in the search of potential anti-obesity medications.

Proto-oncogenic isoform A2 of eukaryotic translation elongation factor eEF1 is a target of miR-663 and miR-744.

BACKGROUND: Eukaryotic translation elongation factor 1A2 (eEF1A2) is a known proto-oncogene. We proposed that stimulation of the eEF1A2 expression in cancer tissues is caused by the loss of miRNA-mediated control. METHODS: Impact of miRNAs on eEF1A2 at the mRNA and protein levels was examined by qPCR and western blot, respectively. Dual-luciferase assay was applied to examine the influence of miRNAs on 3'-UTR of EEF1A2. To detect miRNA-binding sites, mutations into the 3'-UTR of EEF1A2 mRNA were introduced by the overlap extension PCR. RESULTS: miR-663 and miR-744 inhibited the expression of luciferase gene attached to the 3'-UTR of EEF1A2 up to 20% and 50%, respectively. In MCF7 cells, overexpression of miR-663 and miR-744 reduced the EEF1A2 mRNA level by 30% and 50%. Analogous effects were also observed at the eEF1A2 protein level. In resveratrol-treated MCF7 cells the upregulation of mir-663 and mir-744 was accompanied by downregulation of EEF1A2 mRNA. Both miRNAs were able to inhibit the proliferation of MCF7 cells. CONCLUSION: miR-663 and miR-744 mediate inhibition of the proto-oncogene eEF1A2 expression that results in retardation of the MCF7 cancer cells proliferation. Antitumour effect of resveratrol may include stimulation of the miR-663 and miR-744 expression.

Clinical value of baroreflex sensitivity.

The arterial baroreflex is an important determinant of the neural regulation of the cardiovascular system. It has been recognised that baroreflex-mediated sympathoexcitation contributes to the development and progression of many cardiovascular disorders. Accordingly, the quantitative estimation of the arterial baroreceptor-heart rate reflex (baroreflex sensitivity, BRS), has been regarded as a synthetic index of neural regulation at the sinus atrial node. The evaluation of BRS has been shown to provide clinical and prognostic information in a variety of cardiovascular diseases, including myocardial infarction and heart failure that are reviewed in the present article.

Degenerative cervical myelopathy: Neuroradiological, neurophysiological and clinical correlations in 27 consecutive cases.

•New insight into prognostic factors for recovery of clinical function following posterior decompression for degenerative cervical myelopathy.•An increase of IOM amplitude of at least 50% coupled with preoperative T2-only and diffuse T2 signal changes on MRI is a positive prognostic factors for clinical improvement 6 months after surgery.•Clinical improvement at 6 months follow-up can be expected in patients with T1 hypo intensity if a diffuse border of the lesion on T2 images is present.

Long-term time-course of nocturnal breathing disorders in heart failure patients.

Some important aspects of clinical manifestations of nocturnal breathing disorders in heart failure (HF) patients are still unknown. We questioned whether the severity of these disorders, first, is stable over time; secondly, shows any systematic trend; and, thirdly, can be predicted over time by a single baseline measurement. We studied 79 stable, optimally treated, moderate-to-severe HF patients who performed a monthly cardiorespiratory recording during 1-yr follow-up. According to their behaviour over time, nocturnal breathing disorders were classified as persistent, absent or occasional. During follow-up, clinically relevant breathing disorders were persistent in approximately 50% of the patients, absent in <20% and occasional in approximately 30%. Increasing/decreasing trends were rarely observed. The positive and negative predictive value of baseline measurement for persistent behaviour over time ranged, respectively, from 71% to 91% and from 91% to 95%, depending on different levels of severity of breathing disorders. A large portion of HF patients experience persistent clinically significant nocturnal breathing disorders over long periods of time. Breathing disorders occur irregularly in about one-third of the patients and are negligible in a minority of them. Rarely do they show a steady increase or decrease over time. A single baseline recording predicts a persistent behaviour with moderate-to-high accuracy.

PTSD in women is associated with a block in conversion of progesterone to the GABAergic neurosteroids allopregnanolone and pregnanolone measured in plasma.

There is a need to identify new and more effective treatments for posttraumatic stress disorder (PTSD). Allopregnanolone and its stereoisomer pregnanolone (together termed ALLO) are metabolites of progesterone that positively and allosterically modulate GABA effects at GABAA receptors, thereby reducing anxiety and depression. Previous research revealed that women with PTSD had low cerebrospinal fluid (CSF) ALLO levels and a low ratio of ALLO to the allopregnanolone precursor 5α-DHP, consistent with deficient activity of the ALLO synthetic enzyme 3α-hydroxysteroid dehydrogenase (3α-HSD). The current study examined ALLO and the ratio of ALLO to 5α-DHP in plasma at rest and in response to psychophysiological stressors in trauma-exposed, medication-free women with and without PTSD. Participants were examined twice in random order during the early follicular phase (eFP) and mid-luteal phase (mLP) of the menstrual cycle. Plasma neurosteroids were measured using gas chromatography-mass spectrometry. Results indicate that the ALLO to 5α-DHP ratio in plasma increases between the eFP and mLP. In addition, women with PTSD have a lower ratio of ALLO to 5α-DHP than trauma-exposed healthy women, as well as blunted increases in this ratio in response to a moderately stressful laboratory procedure, i.e., differential fear conditioning, across the menstrual cycle. Clinically feasible testing for 3α-HSD dysfunction is critical to translating this line of research into clinical care. Measurement of this ratio in plasma could facilitate patient stratification in clinical treatment trials, as well as precision medicine targeting of treatments that address ALLO synthesis deficits in women with PTSD.

Haemorrhagic stroke and vasculitic-like cerebral angiography in a patient with eosinophilic fasciitis. Case report.

Cerebral vasculitis is an uncommon cause of haemorrhagic stroke. A case of intracerebral haemorrhage in a patient with eosinophilic fasciitis, a rare scleroderma-like connective tissue disease, with a possible inflammatory involvement of cerebral vessels is reported. Pathogenetic mechanism of such association and diagnostic controversies are reviewed.

Thienocinnolinone alkanoic acid derivatives as aldose reductase inhibitors.

A new series of 8-halogen-4,4a,5,6-tetrahydrothieno[2,3-h]cinnolinone-N2-alkanoic acids was prepared and tested for aldose reductase (ALR2) inhibitory activities. These compounds showed significant inhibitory activity against bovine lens ALR2, with the best compound 2e showing an IC(50) value of 31.4 microM. The presence of the C8-substituents here studied (Cl, Br) on the thienocinnolinone scaffold caused a decrease of the inhibitory potency by a factor of about 4 with respect to the unsubstituted parent compound, while the presence of a C8-methyl group, considered in a previous paper decreased the activity by a factor of about 2. Moreover, the length of the N2 alkanoic chain influences strongly the enzyme inhibitory activity. While most of the carboxylic acids ALR2 inhibitors are acetic acid derivatives, in the case of thienocinnolinone compounds, homologues higher than acetic acids showed to be more active.

Morphology and anatomy of a leaf mine in Vismia guianensis (Aubl.) Choisy (Clusiaceae) in a fragment of Brazilian Atlantic forest.

Mines or hyponomes are channels caused by larva miners consuming internal plant tissues. These miners live on the leaf and feed from these tissues. Leaf mines are usually visible on the exterior of the leaf as serpentine paths, blotches, or other characteristic shapes of discolored tissues. Morphological and structural modifications undergone by mined leaves of Vismia guianensis (Aubl.) Choisy are presented here with the purpose of elucidating their structure and to contribute to studies about insect-plant interactions. Healthy and mined leaves were harvested from thirty plants and taken to the laboratory. For each branch, the total number of young and mature leaves, the number of leaves with mines and the number of mine per leaf were counted. Transverse sections of healthy and mined leaves were obtained to observe the morpho-anatomic aspects. From the 1,438 mature leaves and 379 young leaves analyzed, 214 (14.9%) and 70 (18.5%) were mined, where most of the leaves (67%) presented one mine per leaf. Transverse sections of the mine revealed that the larva consumed only mesophyll parenchyma tissue and the epidermis remains intact. There is not a pattern of leaf mining, but the larvae did not consume the druses observed on mesophyll and the vascular tissues of the mid-vein and lateral vein.

Chemoprevention of rat liver carcinogenesis by S-adenosyl-L-methionine: a long-term study.

Previous work has shown a consistent fall in S-adenosyl-L-methionine (SAM) in the liver of diethylnitrosamine-initiated rats, during the development of preneoplastic lesions, in persistent nodules (PNs), and hepatocellular carcinomas. The injection of SAM into rats causes the reconstitution of the SAM pool, coupled with growth restraint, remodeling, and apoptosis of preneoplastic cells, and inhibits the development of PNs and hepatocellular carcinomas. To evaluate if SAM treatment causes a long-term prevention of preneoplastic and neoplastic liver lesions or merely causes a delay in their development, we evaluated the effect of a relatively short SAM treatment on the development of preneoplastic and neoplastic lesions in a long-term study. Male Wistar rats were subjected to initiation with diethylnitrosamine, followed by selection and then by the administration of phenobarbital for 16 weeks. After selection, the rats were given i.m. injections of a purified SAM preparation (384 mumol/kg/day) for 24 weeks. In SAM-treated rats, a decrease in the incidence of PNs was found 6, 14, and 24-28 months after initiation. At the end of SAM treatment the number of PNs per rat liver, nodule diameter, and labeling and mitotic indices of nodular cells decreased considerably in control rats. Nodule diameter started to increase rapidly again only 8 months after arresting SAM treatment, when complete recovery of DNA synthesis in nodular cells occurred. The majority of nodules present in the liver 6-28 months after initiation belonged to the clear and acidophilic cell types, with lower percentages of mixed cell and basophilic cell types. A decrease in basophilic nodules occurred in SAM-treated rats. Fourteen and 24-28 months after initiation hepatocellular carcinoma incidence was 11 of 12 and 10 of 10 in control rats, respectively, and only 1 of 12 and 3 of 11 in SAM-treated rats. At the 24th-28th month all control rats had tumors identified as 2 poorly differentiated carcinomas, 6 trabecular carcinomas, or 3 adenocarcinomas, while only 2 relatively small trabecular carcinomas and 1 small glandular tumor developed in SAM-treated rats. In 3 of 11 SAM-treated rats, but in none of the control rats, leukemic infiltration of liver occurred 24-28 months after initiation. Leukemic infiltration of the spleen occurred in 5 and 3 control and SAM-treated rats, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

[Elastofibroma dorsi: case report and review of the literature]. / L'elastofibroma dorsi: descrizione di un caso clinico e analisi della letteratura.

Elastofibroma dorsi (ED) is a rare, benign, often bilateral lesion of the thoracic wall, occurring most commonly in the infra-scapular region beneath the muscular tissue, generally found in elderly women. Whether ED should be considered as a true neoplasm or merely as a reaction of connective tissue to repetitive minor trauma is still debated. ED has characteristic features but a low incidence and is therefore not always easily distinguished from other benign and malignant soft-tissue tumors. Inappropriate treatment may thus be administrated in the absence of a definitive diagnosis. We report a case of a 51-year-old woman who presented with a right infra-scapular swelling associated with pain and a clicking sensation during selective arm movements. Upon clinical and ultrasound examination, the lesion had the appearance of a deep dorsal lipoma, but intraoperative findings were suggestive of a sarcoma originating from the periosteum of ribs. Nonetheless, marginal surgical excision was performed and the tumor was histologically diagnosed as ED. In conclusion, ED should be always considered in the differential diagnosis of tumors deeply located in the infra-scapular area, especially in elderly women. As it is a benign lesion, surgical treatment is recommended only in symptomatic cases or if a large swelling is present.

Ependymoma with diffuse signet-ring features: report of a case and review of the literature.

Signet-ring cell ependymoma is a rare variant of ependymoma with only seven cases described in literature. Biological behavior and prognosis of this entity are not well-known until now. We present a case of a 49-year-old female with a history of headache and gait instability. Magnetic resonance imaging showed an upper cervical tumor with cystic component and mural nodule. The patient underwent surgery. Microscopically some cells displayed an eccentric nucleus compressed to the periphery by vacuolated cytoplasm. Perivascular pseudorosettes and ependymal rosettes were seen only focally. The cells were positive for glial fibrillary acidic protein and epithelial membrane antigen. The diagnosis was ependymoma with diffuse signet-ring features, grade II according to the World Health Organization. It may be difficult to diagnose this unusual variant of ependymoma especially on small biopsies or frozen sections. A complete examination of the specimen is recommended with immunohistochemical confirmation to rule out potential morphologic mimics, such as metastatic adenocarcinomas and gliomas in the differential diagnosis.

The transition from intra to extra-uterine life in late preterm infant: a single-center study.

BACKGROUND: Infants born at 34 to 36 weeks of gestation (late preterm) are at greater risk for adverse outcomes than those born at 37 weeks of gestation or later. Aim of this paper is to examine risk factors for late preterm births and to investigate the complications of the transition period in late preterm infants (LPIs). METHODS: All consecutive late preterm deliveries, excluded stillbirths, were included. Maternal and neonatal data, need for delivery room resuscitative procedures, temperature at birth (T1) and two hours after the admission (T2) were analyzed in all LPIs stratified by Gestational Age (GA) and divided into three groups (34, 35 and 36 weeks). RESULTS: Two hundred seventy-six LPIs were analyzed. Pregnancy complications were present in 72 mothers (26.1 %), more frequently at 34 weeks of gestation respect to 35 and 36 weeks (p = 0.008, p = 0.006 respectively). Forty seven LPIs (17.1 %) needed for any resuscitation and 37 (13.4 %) were ventilated at birth. LPIs at 34 weeks were significantly more likely to receive ventilation respect to those at 35 and 36. At T1 the mean temperature resulted lower at 34 weeks respect to 36 weeks (p = 0.03). At T2 respect to T1, the rate of normothermic neonates increased at 35 and 36 weeks (p = 0.003, p = 0.005, respectively). Hypoglicemia rate was similar among the groups; 66.7 % of hypoglicemic neonates were hypothermic at T1. The rate of respiratory diseases and NICU admission decreased with increasing GA. Higher number of neonates ventilated at birth developed respiratory disorders respect to those unventilated (40.5 % vs 8.4 %; p < 0.001). CONCLUSIONS: Transition period in LPIs may become critical, as resuscitation strategies can be required and heat loss can occur. LPIs, especially at 34 gestational weeks, are higher-risk group needing adequate and targeted management at birth.

Doppler echocardiography reliably predicts pulmonary artery wedge pressure in patients with chronic heart failure with and without mitral regurgitation.

OBJECTIVES: This study was performed to assess whether the combination of multiple echocardiographic and Doppler variables can provide a reliable estimation of pulmonary artery wedge pressure in patients with chronic heart failure. BACKGROUND: In patients with chronic heart failure a high pulmonary artery wedge pressure is associated with poor prognosis, more severe symptoms and low exercise tolerance. Several Doppler echocardiographic indexes have been shown to be related to pulmonary artery wedge pressure, but the dispersion of data has generally not allowed a quantitative assessment of this important variable. METHODS: Simultaneous Doppler echocardiographic examinations and right heart catheterizations were performed in 231 patients with chronic heart failure due to dilated cardiomyopathy. Mitral and pulmonary venous flow velocity variables, left atrial volumes, mitral regurgitation jet area and left ventricular ejection fraction were correlated with pulmonary artery wedge pressure by both single and multilinear regression analysis. The reliability of the obtained multilinear equations was then tested in a separate group of 60 patients. RESULTS: By univariate analysis, the deceleration rate of early diastolic mitral flow and the systolic fraction of pulmonary venous flow showed the strongest correlations (r=0.78 and =-0.76, respectively). Stepwise regression analysis led to two multilinear equations for predicting pulmonary artery wedge pressure in the whole population: the first included only two-dimensional echocardiographic and mitral flow velocity variables (r=0.84) and the second also included pulmonary venous flow variables (r=0.87). The highest correlation was obtained (r=0.89) by a third equation in the 73 patients without significant mitral regurgitation. Correlation coefficients between estimated and measured pulmonary artery wedge pressure were 0.91 (SEE=2.7 mm Hg) and 0.97 (SEE=1.8 mm Hg) when the first and the second equation, respectively, were applied to the testing group. CONCLUSIONS: These results indicate that, in patients with chronic heart failure due to dilated cardiomyopathy, pulmonary artery wedge pressure can be reliably estimated even when mitral regurgitation is present by combining Doppler echocardiographic variables of mitral and pulmonary venous flow.

Assessing baroreflex sensitivity in post-myocardial infarction patients: comparison of spectral and phenylephrine techniques.

OBJECTIVES: This study sought to compare, in post-myocardial infarction patients, baroreflex sensitivity (BRS) measured by the phenylephrine method (Phe-BRS) with that estimated by the Robbe (Robbe-BRS) and Pagani (alpha-low frequency [LF] and alpha-high frequency [HF]) spectral techniques. BACKGROUND: BRS assessed by Phe-BRS has been shown to be of prognostic value in patients with a previous myocardial infarction, but the need for drug injection limits the use of this technique. Several noninvasive methods based on spectral analysis of systolic arterial pressure and heart period have been proposed, but their agreement with Phe-BRS has never been investigated in post-myocardial infarction patients. METHODS: The linear association and the agreement between each spectral measurement and Phe-BRS were assessed by correlation analysis and by computing the relative bias and the limits of agreement in 51 post-myocardial infarction patients. RESULTS: The correlation with Phe-BRS was r = 0.63 for Robbe-BRS, r = 0.62 for alpha-LF and r = 0.59 for alpha-HF. The relative bias was significant for alpha-LF (2.6 ms/mm Hg, p < 0.001) and alpha-HF (2.5 ms/mm Hg, p = 0.01) and not significant (-0.6 ms/mm Hg, p = 0.3) for Robbe-BRS. The normalized limits of agreement ranged from -98% to 95% for Robbe-BRS, from -67% to 126% for alpha-LF and from -108% to 143% for alpha-HF. When patients were classified according to left ventricular ejection fraction (LVEF, cutoff value 40%), the relative bias was higher in patients with a depressed LVEF, although statistical significance was high only for Robbe-BRS and was borderline for alpha-LF. The limits of agreement were similar in both groups of patients (p > 0.3). CONCLUSIONS: Despite a substantial linear association, the agreement between spectral measurements and Phe-BRS in post-myocardial infarction patients is weak because the difference can be as large as the BRS value being estimated. Phe-BRS is the measurement most associated with hemodynamic impairment. Because several factors within each method contribute to the overall difference, neither method can be defined as being better than the other in estimating baroreflex gain, nor can one be used as an alternative to the other. Ad hoc studies are needed to assess which method provides the most useful physiologic or pathophysiologic information or the most accurate prediction of prognosis.

Predictors of primary atrial fibrillation and concomitant clinical and hemodynamic changes in patients with chronic heart failure: a prospective study in 344 patients with baseline sinus rhythm.

OBJECTIVES: This study investigated the incidence, predisposing factors and significance of the onset of atrial fibrillation (AF) in patients with chronic congestive heart failure (CHF). BACKGROUND: The association between CHF and AF is well documented, but the factors that predispose to the onset of the arrhythmia and its impact remain controversial. Methods. We prospectively followed up 344 patients with CHF and sinus rhythm (SR). Over a period of 19 +/- 12 months (mean +/- SD), 28 patients developed atrial fibrillation (AF), which became chronic in 18. RESULTS: At baseline, no differences were found in any clinical and hemodynamic variables between patients who developed chronic AF and those who did not. Reversible AF occurring during follow-up and lower mitral flow velocity at atrial contraction as detected at the last evaluation in SR were independent predictors of the subsequent development of chronic AF. When AF occurred, New York Heart Association functional class worsened (from 2.4 +/- 0.5 to 2.9 +/- 0.6, p = 0.0001), peak exercise oxygen consumption declined (from 16 +/- 5 to 11 +/- 5 ml/kg per min, p = 0.002), cardiac index decreased (from 2.2 +/- 0.4 to 1.8 +/- 0.4, p = 0.0008), and mitral and tricuspid regurgitation increased (from grade 1.8 +/- 1.1 to grade 2.4 +/- 1.4, p = 0.0001 and from grade 1.0 +/- 1.2 to grade 1.8 +/- 1.2, p = 0.001, respectively). Systemic thromboembolism occurred in 3 of the 18 patients with AF. Nine of 18 patients died after AF, and the occurrence of AF was a predictor of major cardiac events. CONCLUSIONS: In patients with CHF, reversible AF and reduction of left atrial contribution to left ventricular filling predict the subsequent development of chronic AF. The onset of AF is associated with clinical and hemodynamic deterioration and may predispose to systemic thromboembolism and poorer prognosis.

Nonselective beta-adrenergic blocking agent, carvedilol, improves arterial baroflex gain and heart rate variability in patients with stable chronic heart failure.

OBJECTIVES: The purpose of this study was to investigate in a case-controlled study whether carvedilol increased baroreflex sensitivity and heart rate variability (HRV). BACKGROUND: In chronic heart failure (CHF), beta-adrenergic blockade improves symptoms and ventricular function and may favorably affect prognosis. Although beta-blockade therapy is supposed to decrease myocardial adrenergic activity, data on restoration of autonomic balance to the heart and, particularly, on vagal reflexes are limited. METHODS: Nineteen consecutive patients with moderate, stable CHF (age 54 +/- 7 years, New York Heart Association [NYHA] class II to III, left ventricular ejection fraction [LVEF] 24 +/- 6%), treated with optimized conventional medical therapy, received carvedilol treatment. Controls with CHF were selected from our database on the basis of the following matching criteria: age +/- 3 years, same NYHA class, LVEF +/- 3%, pulmonary wedge pressure +/- 3 mm Hg, peak volume of oxygen +/- 3 ml/kg/min, same therapy. All patients underwent analysis of baroreflex sensitivity (phenylephrine method) and of HRV (24-h Holter recording) at baseline and after six months. RESULTS: Beta-blockade therapy was associated with a significant improvement in symptoms (NYHA class 2.1 +/- 0.4 vs. 1.8 +/- 0.5, p < 0.01), systolic and diastolic function (LVEF 23 +/- 7 vs. 28 +/- 9%, p < 0.01; pulmonary wedge pressure 17 +/- 8 vs. 14 +/- 7 mm Hg, p < 0.05) and mitral regurgitation area (7.0 +/- 5.1 vs. 3.6 +/- 3.0 cm2, p < 0.01). No significant differences were observed in either clinical or hemodynamic indexes in control patients. Phenylephrine method increased significantly after carvedilol (from 3.7 +/- 3.4 to 7.1 +/- 4.9 ms/mm Hg, p < 0.01) as well as RR interval (from 791 +/- 113 to 894 +/- 110 ms, p < 0.001), 24-h standard deviation of normal RR interval and root mean square of successive differences (from 56 +/- 17 to 80 +/- 28 ms and from 12 +/- 7 to 18 +/- 9 ms, all p < 0.05), while all parameters remained unmodified in controls. During a mean follow-up of 19 +/- 8 months a reduced number of cardiac events (death plus heart transplantation, 58% vs. 31%) occurred in those patients receiving beta-blockade. CONCLUSIONS: Besides the well-known effects on ventricular function, treatment with carvedilol in CHF restores both autonomic balance and the ability to increase reflex vagal activity. This protective mechanism may contribute to the beneficial effect of beta-blockade treatment on prognosis in CHF.