Beta-blocker treatment guided by head-up tilt test in neurally mediated syncope

This study was an open-label, uncontrolled, dose-escalation trial of beta-blockers in patients with a history of syncope without warning or syncope resulting in trauma (malignant vasovagal syncope) who had positive head-up tilt test (HUT) responses, with or without isoproterenol infusion. Thirty patients (mean age, 37 +/- 21 years) with recurrent syncopal and near-syncopal episodes of unexplained origin in the previous year (6 +/- 14 syncopal episodes and 17 +/- 3 near-syncopes) underwent HUT for diagnostic purposes and for guiding prophylactic treatment. After patients were given a 10-minute rest in a recumbent position, rye performed an WT at 70 degrees for 25 minutes; if indicated, isoproterenol testing was performed at incremental dosages (dye steps at 10-minute intervals at 80 degrees), AU patients experienced syncope during HUT, 15 (50%) at baseline HUT and 15 (50%) during isoproterenol infusion (1 to 3 mu g/min; mean, 1.6 mu g/min). Sixteen syncopes were of vasodepressor type, 10 were mixed, and 4 were of cardioinhibitory type. After baseline HUT, betablocking drugs were prescribed to all patients as follows: 1 patient was given propranolol (160 mg daily), and 29 patients were given metoprolol (246 +/- 49 mg daily), with a dose titration period of 14 days. HUT was repeated after 3 weeks, and 24 patients (80%) had negative results (no syncope or anomalous responses). After further dosage adjustment of beta-blockers in nonresponders, a negative HUT was obtained in 28 patients (93%). Overall mean metoprolol daily dose was 262 +/- 60 mg (29 patients), and propranolol was administered at 160 mg daily in 1 patient. Thirteen patients (43%) reported side effects, none of which required drug withdrawal. At an average follow-up of 16 +/- 4 months, none of the patients experienced syncope, a statistically significant reduction. Moreover, a statistically significant reduction in the number of near-syncopal episodes was observed in comparison to the previous year. None of the patients discontinued treatment because of long-term side effects. Beta-blockers were well tolerated and achieved a high rate of efficacy, even in cardioinhibitory syncopes. In conclusion, in selected patients with malignant vasovagal syncope, treatment with metoprolol or propranolol at relatively high doses is feasible and, if guided by HUT results, is associated with a favorable outcome in terms of freedom from syncopal recurrences. Appropriate titration to achieve the full beta-blocking effect appears to be advisable

Management of patients with atrial fibrillation: different therapeutic options and role of electrophysiology-guided approaches.

At present the approach to atrial fibrillation treatment is based on the electrophysiological patterns of atrial fibrillation (on the basis of multiple intra-atrial recordings or sophisticated new mapping techniques) only in a restricted minority of patients, those who are candidate to ablation of the substrate and/or of the triggers. Atrial fibrillation has a broad spectrum of clinical presentations and a heterogeneous electrophysiological pattern. The treatment of this arrhythmia, both with drugs and non pharmacological treatments, has been based, classically, on empirical basis and on a clinically-guided staged-approach. The limitations of pharmacological treatment led in recent years to the development of a wide spectrum of non pharmacological treatments. This implies a change in the approach to atrial fibrillation and the need to identify potentially ideal candidates to complex and expensive treatments. In this view it is currently under investigation the possibility to identify potential responders to a definitive treatment or a combination of treatments (both pharmacological and non-pharmacological) on the basis of the electrophysiological pattern

Outcomes in Mitral Regurgitation Due to Flail Leaflets. A Multicenter European Study

Objectives: The purpose of this study was to assess incidence and predictors of events associated with nonsurgical and surgical management of severe mitral regurgitation (MR) in European institutions. Background: The management of patients with MR remains disputed, warranting multicenter studies to define clinical outcome in routine clinical practice. Methods: The MIDA (Mitral Regurgitation International DAtabase) is a registry created for multicenter study of MR with echocardiographically diagnosed flail leaflet as a model of pure, organic MR. Our cases were collected from 4 European centers. We enrolled 394 patients (age 64 ± 11 years; 67% men; 64% in New York Heart Association functional class I to II; left ventricular ejection fraction 67 ± 10%). Results: During a median follow-up of 3.9 years, linearized event rates/year under nonsurgical management were 5.4% for atrial fibrillation (AF), 8.0% for heart failure (HF), and 2.6% for death. Mitral valve (MV) surgery was performed in 315 (80%) patients (repair in 250 of 315, 80%). Perioperative mortality, defined as death within 30 days from the operation, was 0.7% (n = 2). Surgery during follow-up was independently associated with reduced risk of death (adjusted hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.21 to 0.84; p = 0.014). Benefit was largely driven by MV repair (adjusted HR vs. replacement 0.37, 95% CI 0.18 to 0.76; p = 0.007). In 102 patients strictly asymptomatic and with normal ventricular function, 5-year combined incidence of AF, HF, or cardiovascular death (CVD) was 42 ± 8%. In these patients, surgery also reduced rates of CVD/HF (HR 0.26, 95% CI 0.08 to 0.89; p = 0.032). Conclusions: In this multicenter study, nonsurgical management of severe MR was associated with notable rates of adverse events. Surgery especially MV repair performed during follow-up was beneficial in reducing rates of cardiac events. These findings support surgical consideration in patients with MR due to flail leaflets for whom MV repair is feasible. © 2008 American College of Cardiology Foundation

Cardiogenic hypertension in maturing dogs

The purpose of this study was to evaluate whether the heart can induce high blood pressure by maintaining an inappropriately elevated cardiac output/body weight ratio during growth. Direct (femoral artery) mean arterial pressure (MAP), heart rate, cardiac output/body weight ratio (as defined by M-mode echocardiography), and total peripheral vascular resistance were measured and calculated every 2 months in nine conscious dogs during development from 2 to 10 months of age. In four dogs a J-shaped catheter for atrial pacing was chronically implanted at the age of 3 months, and their hearts were permanently paced at 130 beats/min until maturity. The aim of atrial pacing was to prevent the natural slowing of the heart rate and, consequently, to maintain a cardiac output/body weight ratio that was inappropriately high in relation to age during growth. Five dogs were studied as controls. No hemodynamic differences were observed until the age of 4 months. From the age of 5 to 10 months heart rate was kept at 130 beats/min by atrial pacing in the atrially paced group, and the mean cardiac output/body weight ratio did not decrease (196 +/- 24 vs 191 +/- 34 [SE] ml/min/kg). MAP rose from 62 +/- 4 to 116 +/- 8 mm Hg, and total peripheral resistance increased from 0.34 +/- 0.07 to to 0.61 +/- 0.09 mm Hg/ml/min/kg.(ABSTRACT TRUNCATED AT 250 WORDS

Effects of Beta-Blockade on Exercise Performance at High Altitude

Summary Aims Exposure to high altitude (HA) hypoxia decreases exercise performance in healthy subjects. Although β-blockers are known to affect exercise capacity in normoxia, no data are available comparing selective and nonselective β-adrenergic blockade on exercise performance in healthy subjects acutely exposed to HA hypoxia. We compared the impact of nebivolol and carvedilol on exercise capacity in healthy subjects acutely exposed to HA hypobaric hypoxia. Methods In this double-blind, placebo-controlled trial, 27 healthy untrained sea-level (SL) residents (15 males, age 38.3 ± 12.8 years) were randomized to placebo (n = 9), carvedilol 25 mg b.i.d. (n = 9), or nebivolol 5 mg o.d. (n = 9). Primary endpoints were measures of exercise performance evaluated by cardiopulmonary exercise testing at sea level without treatment, and after at least 3 weeks of treatment, both at SL and shortly after arrival at HA (4559 m). Results HA hypoxia significantly decreased resting and peak oxygen saturation, peak workload, VO2, and heart rate (HR) (P < 0.01). Changes from SL (no treatment) differed among treatments: (1) peak VO2 was better preserved with nebivolol (–22.5%) than with carvedilol (–37.6%) (P < 0.01); (2) peak HR decreased with carvedilol (–43.9 ± 11.9 beats/min) more than with nebivolol (–24.8 ± 13.6 beats/min) (P < 0.05); (3) peak minute ventilation (VE) decreased with carvedilol (–9.3%) and increased with nebivolol (+15.2%) (P= 0.053). Only peak VE changes independently predicted changes in peak VO2 at multivariate analysis (R= 0.62, P < 0.01). Conclusions Exercise performance is better preserved with nebivolol than with carvedilol under acute exposure to HA hypoxia in healthy subjects

A Cultural Quest: A Study of Organizational Use of New Cultural Resources in Strategy Formation.

Our study was motivated by the growing influence in cultural sociology and organizational research of the view of culture as a “toolkit”, from which individuals draw resources flexibly to develop strategies of action that address different circumstances. To investigate if and how organizations can also use new and diverse cultural resources, we undertook a historical case study of the incorporation of new cultural resources in an organization’s cultural repertoire. In-depth analysis of four rounds of incorporation of new cultural resources led to the development of a robust theoretical model that identifies cultural repertoire enrichment and organizational identity redefinition as two core mechanisms that facilitate the use of new cultural resources for the development of unconventional strategies and strategic versatility. Our model contributes to organizational research novel theoretical understanding regarding the use of cultural resources in strategy formation and change

Left atrial size is a potent predictor of mortality in mitral regurgitation due to flail leaflets results from a large international multicenter study

Background-Left atrium (LA) enlargement is common in organic mitral regurgitation (MR) and is an emerging prognostic indicator. However, outcome implications of LA enlargement have not been analyzed in the context of routine clinical practice and in a multicenter study. Methods and Results-The Mitral Regurgitation International DAtabase (MIDA) registry enrolls patients with organic MR due to flail leaflets, diagnosed in routine clinical practice, in 5 US and European centers. We investigated the relation between LA diameter and mortality under medical treatment and after mitral surgery in 788 patients in sinus rhythm (64±12 years; median LA, 48 [43 to 52] mm). LA diameter was independently associated with survival after diagnosis (hazard ratio, 1.08 [1.04 to 1.12] per 1 mm increment). Compared with patients with LA<55 mm, those with LA â¥55 mm had lower 8-year overall survival (P<0.001). LA â¥55 mm independently predicted overall mortality (hazard ratio, 3.67 [1.95 to 6.88]) and cardiac mortality (hazard ratio, 3.74 [1.72 to 8.13]) under medical treatment. The association of LA â¥55 mm and mortality was consistent in subgroups. Similar excess mortality associated with LA â¥55 mm was observed in asymptomatic and symptomatic patients (P for interaction, 0.77). In patients who underwent mitral surgery, LA â¥55 mm had no impact on postoperative outcome (P<0.20). Mitral surgery was associated with greater survival benefit in patients with LA â¥55 mm compared with LA <55 mm (P for interaction, 0.008). Conclusions-In MR caused by flail leaflets, LA diameter â¥55 mm is associated with increased mortality under medical treatment, independent of the presence of symptoms or left ventricular dysfunction. © 2011 American Heart Association, Inc

Combining Logics to Transform Organizational Agency: Blending Industry and Art at Alessi

To understand how organizations combine conflicting institutional logics strategically to create and pursue new market opportunities, we conducted an in-depth longitudinal study of the multiple efforts of the Italian manufacturer of household goods Alessi to combine the logics of industrial manufacturing and cultural production. Over three decades, Alessi developed three different strategies to combine normative elements of the two logics, using each strategy to envision and pursue different market opportunities. By combining the logics of industrial manufacturing and cultural production, Alessi was able to envision new possibilities for value creation and to enact them through innovation in product design. The three strategies triggered a common set of mechanisms through which the purposeful combining of logics enabled the pursuit of opportunity, while each strategy structured the process differently. We develop a theoretical model linking the development of recombinant strategies to the dynamic restructuring of organizational agency and the related capacity to create and pursue new market opportunities. Our findings and theoretical insights advance understanding of the processes through which organizations challenge taken-for-granted beliefs and practices to create new market opportunities, use logics as resources to enable embedded agency, and design hybrid organizational arrangements

MASked-unconTrolled hypERtension management based on office BP or on ambulatory blood pressure measurement (MASTER) Study: a randomised controlled trial protocol.

Masked uncontrolled hypertension (MUCH) carries an increased risk of cardiovascular (CV) complications and can be identified through combined use of office (O) and ambulatory (A) blood pressure (BP) monitoring (M) in treated patients. However, it is still debated whether the information carried by ABPM should be considered for MUCH management. Aim of the MASked-unconTrolled hypERtension management based on OBP or on ambulatory blood pressure measurement (MASTER) Study is to assess the impact on outcome of MUCH management based on OBPM or ABPM