Propranolol: A migraine prophylactic since the 1960s / Propranolol: um profilático para enxaqueca desde 1960

Introduction: Propranolol was the first non-selective beta-adrenergic blocker to be developed. Initially it was used in the treatment of cardiovascular diseases, but since the 60's it has been used in the prevention of migraine. Objective: The objective of this study was to know the history of propranolol and its use as a migraine prophylactic. Methods: This study was an integrative literature review using articles with historical data on propranolol, from its origin in cardiology to its indication in the preventive treatment of migraine. Results: Propranolol was described in 1962 for the treatment of cardiovascular diseases. In the same decade, it was prescribed for the preventive treatment of migraine and, recently, included in the consensus of the Brazilian Headache Society. Conclusion: Although propranolol was initially synthesized for the treatment of heart disease, it has proved to be an effective drug in preventing migraine attacks

Introdução: O propranolol foi o primeiro bloqueador beta-adrenérgico não seletivo a ser desenvolvido. Inicialmente era utilizado no tratamento de doenças cardiovasculares, mas desde a década de 60 tem sido utilizado na prevenção de enxaquecas. Objetivo: O objetivo deste estudo foi conhecer a história do propranolol e seu uso como profilático para enxaqueca. Métodos: Este estudo foi uma revisão integrativa da literatura utilizando artigos com dados históricos sobre o propranolol, desde sua origem na cardiologia até sua indicação no tratamento preventivo da enxaqueca. Resultados: O propranolol foi descrito em 1962 para o tratamento de doenças cardiovasculares. Na mesma década, foi prescrito para o tratamento preventivo da enxaqueca e, recentemente, incluído no consenso da Sociedade Brasileira de Cefaleia. Conclusão: Embora o propranolol tenha sido inicialmente sintetizado para o tratamento de doenças cardíacas, provou ser um medicamento eficaz na prevenção de crises de enxaqueca

Association between erectile dysfunction and the severity of obstruction to airflow in patients with chronic obstructive pulmonary disease / Asociación entre disfunción eréctil y la severidad de la obstrucción al flujo aéreo en pacientes con enfermedad pulmonar obstructiva crónica

Objectives: The objective of this study was to explore a possible association between ED and the severity of airflow obstruction in patients with COPD. Materials and methods: A cross-sectional study was conducted using the International Index Erectile Function (IIEF), a scale validated and translated to Spanish. Bivariate analyses between subgroups were made for quantitative variables using a t-test for means and Mann­Whitney U for medians; qualitative variables were compared using the χ2 test or Fisher's test, depending on distribution. Confusion bias in the association between ED and airflow obstruction was controlled using a logistic regression model. Results: The Spanish version of the IIEF-15 scale was valid and applicable to the Colombian population. The prevalence of ED in COPD patients living at high altitudes was similar to that found at sea level. Such prevalence is higher than in general population. Beta-blockers increased 7 times the risk of ED, but we found no association between the degree of airflow obstruction and ED. Conclusion: Although the severity of COPD is not associated with ED, the prevalence of ED in COPD is higher than in general population. Therefore, ED screening in COPD patients using the IIEF could be justified. The strong association between beta-blockers and ED had not been previously described in patients with COPD but must be considered in their clinical management.

Objetivos: Explorar una posible asociación entre DE y severidad de la obstrucción al flujo aéreo en pacientes con EPOC. Materiales y métodos: Estudio de corte transversal aplicando el Índice Internacional de Función Eréctil (IIFE), validado y traducido al español. Se realizó análisis bivariado para variables cuantitativas usando prueba-t para medias y U de Mann Whitney para medianas; las variables cualitativas fueron comparadas usando prueba de Chi2 o test de Fisher, según distribución. Los sesgos de confusión en la asociación entre DE y obstrucción al flujo aéreo fueron controlados usando un modelo de regresión logística. Resultados: La versión en español de la escala IIFE-15 fue aplicable en población colombiana. La prevalencia de DE en pacientes con EPOC viviendo a gran altura fue similar a lo encontrado a nivel del mar. Esta prevalencia es mayor que en población general. El uso de beta-bloqueadores aumentó hasta siete veces el riesgo de DE, pero no se encontró asociación entre el grado de obstrucción y la DE. Conclusiones: Aunque la severidad de la EPOC no está asociada con DE, la prevalencia de DE en EPOC es mayor que en población general. Está justificada la realización de tamizaje usando el IIFE. La asociación fuerte entre beta-bloqueadores y DE no se ha descrito previamente en pacientes con EPOC, pero debe considerarse en su manejo.

Short-Term Results of Ivabradine versus Metoprolol: The Effects on Atrial Fibrillation in Patients Undergoing Off-Pump Coronary Artery Bypass Grafting

ABSTRACT Introduction: Classic coronary artery bypass grafting (CABG) surgery involves diastolic cardiac arrest under cardiopulmonary bypass, while off-pump CABG (OPCABG) has become widespread in recent years. Methods: 174 patients who underwent OPCABG were included in the study. Patients were divided into two groups. Group I (n=90) received ivabradine and Group M (n=84) received metoprolol before surgery until postoperative day 10. Intraoperative arrhythmias and hypotension were recorded. Postoperative atrial fibrillation (AF) and arrhythmia, mortality and morbidity rates were assessed based on the 30-day postoperative follow-up. Results: There were no significant differences in the intraoperative amount of inotropic support and red blood cell transfusion between groups (P=0.87 and P=0.31). However, the rates of intraoperative arrhythmias and hypotension were not significantly higher in Group M (P=0.317 and P=0.47). Ventricular tachycardia/ventricular fibrillation (VT/VF) was observed in 2 patients in both groups. Postoperative AF occurred in 7 patients (7.7%) in Group I and in 10 patients (11.9%) in Group M. Although there was a trend towards a higher prevalence of AF in Group M patients, this did not reach statistical significance. In addition, mortality and morbidity rates were comparable between groups.

Nationwide surveillance for S-Metoprololtreatment effect on blood pressure control against sympathetic overdrive in Indian patients with hypertension (PROTECT)

Background:Patients with hypertension in India been reported with high heart rate owing to sympathetic overdrive (SO). Beta-blockers provides several positive effects to reduce SO in patients with hypertension. The aim of present survey studywasto understand current real-world prevalence of SO in Indian patients with hypertension and usage of beta-blocker therapy in them.Methods:A cross sectional, observational, questionnaire-based survey conducted across India between June 2020 to October 2020. A specially designed validated questionnaire was shared with 157 registered health care practitioners (HCP),their anonymous inputs were captured and analysed in qualitative manner. Categorical data was summarized by number (n) and percentage (%). Results:Total 157 HCP participated and completed the survey. Around 53% of HCP observed that patients with average heart rate above 75 beats/min were associated with negative prognosis. Around 43% of HCP reported that raised heart rate is associated with advancedage and increased body mass index (BMI). Two-third of HCP reported that tachycardia is associated with stage-2 hypertension and marked by restlessness and anxiety which is suggestive of SO. Over 70% HCP agreed that the HR below 75 beats/min is associated with good prognosis. Around 89% HCP reported beta-blockers as the drug of choice in patients with augmented SO. S-Metoprololwas reported to bethemost preferred beta-blocker agent and was recommended by 76% HCP in patients with hypertension and coexisting SO.Conclusions:SO been reported prevalent conditionin Indian patients with hypertension which likely worsensthe prognosis in these patients. Beta-blockers reported to be the preferred choice of anti-hypertensive and S-Metoprololseem to be themost preferred agent amongst the available beta-blockers against SO in patients with hypertension in India.

The Role of Beta-1 Receptor Gene Polymorphism in Beta-Blocker Therapy for Vasovagal Syncope

Background: Vasovagal syncope (VVS) is a common clinical condition involving genetic background. The role of beta-blockers in the treatment is controversial. Objective: The aim of this study was to investigate the effect of beta-1 gene polymorphism on beta-blocker therapy in patients with VVS. Methods: We included 123 patients who were diagnosed with VVS after the tilt-table test. We searched for the polymorphism Arg389Gly (rs1801253) in the beta-1 adrenoceptor gene. Results: Overall, 64 patients (52%) had Arg389Arg genotype and 59 patients (48%) had Arg389Gly genotype. The syncopal episodes of patients with Arg389Arg genotype were more frequent compared with patients having Arg389Gly genotype (total syncopal episodes [TSE], 7.9 ± 3.7 vs. 6.4 ± 3.0; p = 0.012). TSE in patients with Arg389Arg genotype decreased significantly after 18 months of beta-blocker treatment (7.9 ± 3.7 vs. 3.0 ± 1.4, p < 0.001). After 18 months of beta-blocker treatment, patients with Arg389Arg genotype had significantly fewer syncopal episodes than patients with Arg389Gly genotype (3.0 ± 1.4 vs. 6.8 ± 3.2, p < 0.001). Conclusions: Results of beta-blocker therapy in patients with Arg389Arg genotype suggest that VVS pathophysiology is a multifactorial condition, with genetic, psychological, and environmental components, and therefore, treatment selection can be based on gene polymorphism. (REV INVEST CLIN. 2020;72(5):300-7)

Metoprolol treatment of dual cocaine and bupropion cardiovascular and central nervous system toxicity

Cardiovascular and central nervous system (CNS) toxicity, including tachydysrhythmia, agitation, and seizures, may arise from cocaine or bupropion use. We report acute toxicity from the concomitant use of cocaine and bupropion in a 25-year-old female. She arrived agitated and uncooperative, with a history of possible antecedent cocaine use. Her electrocardiogram demonstrated tachycardia at 130 beats/min, with a corrected QT interval of 579 ms. Two doses of 5 mg intravenous metoprolol were administered, which resolved the agitation, tachydysrhythmia, and corrected QT interval prolongation. Her comprehensive toxicology screen returned positive for both cocaine and bupropion. We believe clinicians should be aware of the potential for synergistic cardiovascular and CNS toxicity from concomitant cocaine and bupropion use. Metoprolol may represent an effective initial treatment. Unlike benzodiazepines, metoprolol directly counters the pharmacologic effects of stimulants without respiratory depression, sedation, or paradoxical agitation. A lipophilic beta-blocker, metoprolol has good penetration of the CNS and can counter stimulant-induced agitation.

Propranolol inhibits myocardial infarction-induced brown adipose tissue D2 activation and maintains a low thyroid hormone state in rats

Considering the recognized role of thyroid hormones on the cardiovascular system during health and disease, we hypothesized that type 2 deiodinase (D2) activity, the main activation pathway of thyroxine (T4)-to-triiodothyronine (T3), could be an important site to modulate thyroid hormone status, which would then constitute a possible target for β-adrenergic blocking agents in a myocardial infarction (MI) model induced by left coronary occlusion in rats. Despite a sustained and dramatic fall in serum T4 concentrations (60-70%), the serum T3 concentration fell only transiently in the first week post-infarction (53%) and returned to control levels at 8 and 12 weeks after surgery compared to the Sham group (P<0.05). Brown adipose tissue (BAT) D2 activity (fmol T4·min-1·mg ptn-1) was significantly increased by approximately 77% in the 8th week and approximately 100% in the 12th week in the MI group compared to that of the Sham group (P<0.05). Beta-blocker treatment (0.5 g/L propranolol given in the drinking water) maintained a low T3 state in MI animals, dampening both BAT D2 activity (44% reduction) and serum T3 (66% reduction in serum T3) compared to that of the non-treated MI group 12 weeks after surgery (P<0.05). Propranolol improved cardiac function (assessed by echocardiogram) in the MI group compared to the non-treated MI group by 40 and 57%, 1 and 12 weeks after treatment, respectively (P<0.05). Our data suggested that the beta-adrenergic pathway may contribute to BAT D2 hyperactivity and T3 normalization after MI in rats. Propranolol treatment maintained low T3 state and improved cardiac function additionally.

Impact of the beta-1 adrenergic receptor polymorphism on tolerability and efficacy of bisoprolol therapy in Korean heart failure patients: association between beta adrenergic receptor polymorphism and bisoprolol therapy in heart failure (ABBA) study

BACKGROUND/AIMS: We evaluated the association between coding region variants of adrenergic receptor genes and therapeutic effect in patients with congestive heart failure (CHF). METHODS: One hundred patients with stable CHF (left ventricular ejection fraction [LVEF] < 45%) were enrolled. Enrolled patients started 1.25 mg bisoprolol treatment once daily, then up-titrated to the maximally tolerable dose, at which they were treated for 1 year. RESULTS: Genotypic analysis was carried out, but the results were blinded to the investigators throughout the study period. At position 389 of the beta-1 adrenergic receptor gene (ADRB1), the observed minor Gly allele frequency (Gly389Arg + Gly389Gly) was 0.21, and no deviation from Hardy-Weinberg equilibrium was observed in the genotypic distribution of Arg389Gly (p = 0.75). Heart rate was reduced from 80.8 +/- 14.3 to 70.0 +/- 15.0 beats per minute (p < 0.0001). There was no significant difference in final heart rate across genotypes. However, the Arg389Arg genotype group required significantly more bisoprolol compared to the Gly389X (Gly389Arg + Gly389Gly) group (5.26 +/- 2.62 mg vs. 3.96 +/- 2.05 mg, p = 0.022). There were no significant differences in LVEF changes or remodeling between two groups. Also, changes in exercise capacity and brain natriuretic peptide level were not significant. However, interestingly, there was a two-fold higher rate of readmission (21.2% vs. 10.0%, p = 0.162) and one CHF-related death in the Arg389Arg group. CONCLUSIONS: The ADRB1 Gly389X genotype showed greater response to bisoprolol than the Arg389Arg genotype, suggesting the potential of individually tailoring beta-blocker therapy according to genotype.

Management of Patients with Long QT Syndrome

Long QT syndrome (LQTS) is a rare cardiac channelopathy associated with syncope and sudden death due to torsades de pointes and ventricular fibrillation. Syncope and sudden death are frequently associated with physical and emotional stress. Management of patients with LQTS consists of life-style modification, β-blockers, left cardiac sympathetic denervation (LCSD), and implantable cardioverter-defibrillator (ICD) implantation. Prohibition of competitive exercise and avoidance of QT-prolonging drugs are important issues in life-style modification. Although β-blockers are the primary treatment modality for patients with LQTS, these drugs are not completely effective in some patients. Lifelong ICD implantation in young and active patients is associated with significant complications. LCSD is a relatively simple and highly effective surgical procedure. However, LCSD is rarely used.

Cost-effectiveness analysis of preventing esophageal variceal rebleeding in liver cirrhosis / 中华消化杂志

Objective To compare cost-effectiveness between endoscopical esophageal variceal ligation (EVL) combined non-selective beta-receptor blocker strategies and covered-stents transjugular intrahepatic portosystemic shunt (cTIPS) in preventing esophageal variceal rebleeding in liver cirrhosis with portal hypertension.And to explore the threshold of cost-effectiveness in stents in China.Methods According to clinical practice and associated guidelines,a six state Markov-based decision analytic model was established with TreeAge Pro Suite 2014 to compare the cost-effectiveness between two interfering strategies after followed up for seven years.The parameters such as costs,life years (LY),quality-adjusted life-years (QALY) and incremental costeffectiveness ratio (ICER) were directed.Results The results of baseline research in the seven-year follow-up period indicated that the cost of endoscopical EVL combined non-selective beta-receptor blocker B was 7 444.25 United States dollar (USD)/each,and yielded 1.98 QALY.The expected cost of cTIPS was 13 151.69 USD/ each and could have 2.34 QALY.In the 7th year,ICER was 16 001.74 USD.Based on willingness-to-pay (WTP) threshold of China (19 887.00 USD),cTIPS had better cost-effectiveness than endoscopical EVL combined non-selective beta-receptor blocker B.The price of covered stents less than 5 401.52 USD had cost-effectiveness.The results of single factor sensitivity analysis indicated that rebleeding probability of endoscopical EVL combined non-selective beta-receptor blocker B group was the most influential factor in the result of model.The second important factor was the cost of cTIPS.The probabilistic sensitivity analysis reported cTIPS to be the optimal strategy at WTP of 19 887.00 USD in 83％ of the iterations.Conclusions Seven-year follow-up indicates that cTIPS may be a more cost-effective strategy than endoscopical EVL combined non-selective beta-receptor blocker B in preventing esophageal variceal rebleeding.The price of covered stents less than 5 401.52 USD which have cost-effectiveness in China.

Propranolol en el tratamiento del hemangioma periocular: Presentación de un caso clínico / Propranolol in the treatment of periocular haemangioma: A clinical case

Los hemangiomas infantiles (HI) son los más comunes tumores vasculares benignos de la infancia. Más del 60% de HI ocurren en la cara, cabeza y cuello. Aunque son benignos, la localización en los párpados, punta nasal, labios y oídos pueden poner en peligro la respiración, la alimentación y la visión u ocasionar la desfiguración irreversible. El sangrado, la ulceración y la infección pueden ocurrir en hasta el 20% de los casos. Estudios anteriores han revelado que el propranolol, timolol y nadolol son eficaces en el tratamiento de los hemangiomas cutáneos, orbitales, hepáticos y subglóticos. La ambliopía es la preocupación principal por la deprivación del estímulo, produciendo anisometropía, estrabismo secundario o desplazamiento del globo ocular. Se presenta el caso de una paciente con diagnóstico de HI pericoular a quien se indicó tratamiento con Propranolol a 2mg/kg/día en los 6 primeros meses de vida.

Infantile haemangiomas (IH) are the most common benign vascular tumors of childhood. More than 60% of IH occur on the face, head and neck. Although they are benign, the location on the eyelids, tip of the nose, lips and ears can endanger breathing, feeding and vision or lead to irreversible disfigurement. Bleeding, ulceration and subsequent infection can occur in up to 20% of cases. Previous studies revealed that propranolol, nadolol and timolol are effective as treatment of cutaneous, orbital, subglottic and liver hemangiomas. Amblyopia is the primary concern due to the deprivation of the stimulus, producing anisometropia secondary strabismus or displacement of the eyeball. We present the case of a patient with the diagnosis of periocular IH, who was treated with propranolol, 2mg/kg/day during the 6 first months of life.

Short-term follow-up of exercise training program and beta-blocker treatment on quality of life in dogs with naturally acquired chronic mitral valve disease

This study aimed to evaluate the effects of carvedilol treatment and a regimen of supervised aerobic exercise training on quality of life and other clinical, echocardiographic, and biochemical variables in a group of client-owned dogs with chronic mitral valve disease (CMVD). Ten healthy dogs (control) and 36 CMVD dogs were studied, with the latter group divided into 3 subgroups. In addition to conventional treatment (benazepril, 0.3-0.5 mg/kg once a day, and digoxin, 0.0055 mg/kg twice daily), 13 dogs received exercise training (subgroup I; 10.3±2.1 years), 10 dogs received carvedilol (0.3 mg/kg twice daily) and exercise training (subgroup II; 10.8±1.7 years), and 13 dogs received only carvedilol (subgroup III; 10.9±2.1 years). All drugs were administered orally. Clinical, laboratory, and Doppler echocardiographic variables were evaluated at baseline and after 3 and 6 months. Exercise training was conducted from months 3-6. The mean speed rate during training increased for both subgroups I and II (ANOVA, P>0.001), indicating improvement in physical conditioning at the end of the exercise period. Quality of life and functional class was improved for all subgroups at the end of the study. The N-terminal pro-brain natriuretic peptide (NT-proBNP) level increased in subgroup I from baseline to 3 months, but remained stable after training introduction (from 3 to 6 months). For subgroups II and III, NT-proBNP levels remained stable during the entire study. No difference was observed for the other variables between the three evaluation periods. The combination of carvedilol or exercise training with conventional treatment in CMVD dogs led to improvements in quality of life and functional class. Therefore, light walking in CMVD dogs must be encouraged.

To study the comparative effects of nebivolol and metoprolol on lipid profile in patients of essential hypertension.

Background: Hypertension and certain alteration in serum lipoproteins are complementary coronary risk factors. The effect of antihypertensive agents on lipid metabolism exhibits a wide range. Numerous studies have established that vasodilating beta-blockers are associated with more favorable effects on glucose and lipid profiles than non-vasodilating beta-blockers. The study was conducted to study the comparative effects of nebivolol and metoprolol on lipid profile in patients of essential hypertension. Methods: A prospective, randomized open label single center study was conducted in the Department of Pharmacology in collaboration with Department of Medicine, MGM’s Medical College and Hospital, Aurangabad in newly diagnosed patients of essential hypertension. Sixty patients of either sex in the age group of 30-65 years with blood pressure (BP) of ≥140/90 mmHg with deranged lipid parameters according to National Cholesterol Education Program were randomized into two groups. Group I received metoprolol (50 mg) and Group II received nebivolol (5 mg), both given once daily for 12 weeks. BP and lipid parameters were evaluated at baseline as well as at the end of 12 weeks. Results: There was significant reduction in BP values (p<0.0001) as compared to baseline in both the groups, however no significant difference was observed between two drugs revealing that their efficacy in reducing systolic BP/diastolic BP is comparable. Furthermore, both the drugs had a favorable effect on lipid profile, but more significant results on lipid profile were observed in the nebivolol group as compared to metoprolol group (p<0.0001). Conclusions: In our comparison study, it is seen that the favorable effect of nebivolol on serum lipids and its good tolerability profile make it a good choice for control of hypertension as well as preventing the long-term cardiovascular morbidities and mortalities.

Espasmo coronariano durante a realização de ecocardiograma sob estresse com dobutamina / Coronaty spasm during the dobutamine stress echocardiography / Espasmo Coronario durante la Realización de Ecocardiograma bajo Estrés con Dobutamina

Stress echocardiography is an imaging method whose main objective is the diagnostic and prognostic evaluation of patients with known or suspected coronary artery disease. It is a safe method with few complications, even when used in large scale1... .

La ecocardiografía bajo estrés es un método de imagen cuyo principal objetivo es la evaluación diagnóstica y pronóstica de pacientes con enfermedad arterial coronaria conocida o sospechada. Es un método seguro, con pocas complicaciones, aun usado en gran escala1...

A ecocardiografia sob estresse é um método de imagem cujo principal objetivo é a avaliação diagnóstica e prognóstica de pacientes com doença arterial coronariana conhecida ou suspeitada. É um método seguro, com poucas complicações, mesmo quando usado em grande escala1... .

Clinical study on ACEI combined with beta-blocker in the treatment of chronic heart failure / 中国基层医药

Objective To investigate the effects of ACEI combined with beta-blocker on cardiac function in patients with chronic heart failure (CHF)and explore its action mechanisms.Methods 60 CHF patients were enrolled in this study.The patients were randomly divided into the two groups:conventional treatment group(group A,n =30),ACEI combined with beta-blocker treatment group (group B,n =30).The LVEF,LVEDD,MMP-9,and hsCRP were recorded after treatment.The expression of MMP-9 was measured by ELISA.The level of serum hs-CRP was measured by latex enhanced immunoturbidimetric assay.Results The improvement of LVEF and LVEDD in B group [(63.21 ± 6.09) ％,(58.42 ± 5.73)mm] were better than those in A group [(41.13 ± 3.67) ％,(66.24 ± 4.24) mm] (t =7.62,6.54,P ＜ 0.01).The expressions of MMP-9 and hs-CRP in group B [(1.31 ± 0.24) ng/ml,(6.34 ± 0.58) mg/L] were significantly lower than those in A group[(2.23 ±0.39) ng/mL,(8.31 ±0.74) mg/L] (t =6.82,7.03,P ＜0.01).The total effective rate in A group was 36.7％,which was significantly lower than 73.3％ in B group(x2 =6.90,P ＜ 0.05).Conclusion The cardiac function was improved by ACEI combined with beta-blocker treatment in CHF patients.The downregulation of MMP-9 and hs-CRP may play a key role in the effective ACEI combined with beta-blocker treatment.

The secondary prophylactic efficacy of beta-blocker after endoscopic gastric variceal obturation for first acute episode of gastric variceal bleeding

BACKGROUND/AIMS: The most appropriate treatment for acute gastric variceal bleeding (GVB) is currently endoscopic gastric variceal obturation (GVO) using Histoacryl(R). However, the secondary prophylactic efficacy of beta-blocker (BB) after GVO for the first acute episode of GVB has not yet been established. The secondary prophylactic efficacy of BB after GVO for the first acute episode of GVB was evaluated in this study. METHODS: Ninety-three patients at Soonchunhyang University Hospital with acute GVB who received GVO using Histoacryl(R) were enrolled between June 2001 and March 2010. Among these, 42 patients underwent GVO alone (GVO group) and 51 patients underwent GVO with adjuvant BB therapy (GVO+BB group). This study was intended for patients in whom a desired heart rate was reached. The rates of rebleeding-free survival and overall survival were calculated for the two study groups using Kaplan-Meyer analysis and Cox's proportional-hazards model. RESULTS: The follow-up period after the initial eradication of gastric varices was 18.14+/-25.22 months (mean+/-SD). During the follow-up period, rebleeding occurred in 10 (23.8%) and 21 (41.2%) GVO and GVO+BB patients, respectively, and 39 patients died [23 (54.8%) in the GVO group and 16 (31.4%) in the GVO+BB group]. The mean rebleeding-free survival time did not differ significantly between the GVO and GVO+BB groups (65.40 and 37.40 months, respectively; P=0.774), whereas the mean overall survival time did differ (52.54 and 72.65 months, respectively; P=0.036). CONCLUSIONS: Adjuvant BB therapy after GVO using Histoacryl(R) for the first acute episode of GVB could decrease the mortality rate relative to GVO alone. However, adjuvant BB therapy afforded no benefit for the secondary prevention of rebleeding in GV.

A Case of Long QT Syndrome Type 3 Aggravated by Beta-Blockers and Alleviated by Mexiletine: The Role of Epinephrine Provocation Test

Long QT syndrome (LQTs) is an uncommon genetic disease causing sudden cardiac death with Torsade de Pointes (TdP). The first line drug treatment has been known to be beta-blocker. We encountered a 15-year-old female student with LQTs who had prolonged QTc and multiple episodes of syncope or agonal respiration during sleep. Although her T wave morphology in surface electrocardiography resembled LQTs type 1, her clinical presentation was unusual. During the epinephrine test, TdP was aggravated during beta-blocker medication, but alleviated by sodium channel blocker (mexiletine). Therefore, she underwent implantable cardioverter defibrillator implantation.

The effect of beta-blockade on myocardial remodelling in Chagas' cardiomyopathy

OBJECTIVE: Chagas' disease has spread throughout Latin America because of the high rate of migration among these countries. Approximately 30% of Chagas' patients will develop cardiomyopathy, and 10% of these will develop severe cardiac damage leading to heart failure. Beta-blockade improves symptoms and survival in heart failure patients; however, its efficacy has not been well established in Chagas' disease. We evaluated the role of carvedilol in cardiac remodeling and mortality in a Chagas' cardiomyopathy animal model. METHODS: We studied Trypanosoma cruzi infection in 55 Syrian hamsters that were divided into three groups: control (15), infected (20), and infected + carvedilol (20). Animals underwent echocardiography, electrocardiography, and morphometry for collagen evaluation in ventricles stained with picrosirius red. RESULTS: The left ventricular diastolic diameter did not change between groups, although it was slightly larger in infected groups, as was left ventricular systolic diameter. Fractional shortening also did not change between groups, although it was slightly lower in infected groups. Collagen accumulation in the interstitial myocardial space was significantly higher in infected groups and was not attenuated by carvedilol. The same response was observed in the perivascular space. The survival curve showed significantly better survival in the control group compared with the infected groups; but no benefit of carvedilol was observed during the study. However, in the acute phase (up to 100 days of infection), carvedilol did reduce mortality. CONCLUSION: Carvedilol did not attenuate cardiac remodeling or mortality in this model of Chagas' cardiomyopathy. The treatment did improve survival in the acute phase of the disease.

Análisis de costo efectividad del uso de metoprolol succinato en el tratamiento de la hipertensión arterial y la falla cardiaca en Colombia / Analysis of cost effectiveness of the use of metoprolol succinate in the treatment of hypertension and heart failure in Colombia

Objetivo: realizar una evaluación de costo-efectividad del uso de metoprolol succinato frente a metoprolol tartrato y carvedilol en el tratamiento de pacientes con insuficiencia cardiaca congestiva e hipertensión arterial en Colombia, desde la perspectiva del tercero pagador. Métodos: el estudio se desarrolló mediante un modelo de Markov simulando la historia natural de la enfermedad para un horizonte temporal de cinco años, para lo cual se tomaron 100 pacientes con edad de 45 años. Se evaluaron como desenlaces tanto las hospitalizaciones como las muertes evitadas. Los datos de probabilidades se obtuvieron de estudios clínicos y los costos de bases de datos de instituciones y opinión de expertos, expresados en pesos colombianos de 2009. Se aplicó una tasa de descuento del 3%. Resultados: el costo del brazo tratado con metoprolol succinato fue el menor, con 299 millones de pesos frente a 364 millones y 346 millones de pesos para carvedilol y metoprolol tartrato, respectivamente. El menor número de hospitalizaciones se presentó con metoprolol succinato, y fue de 24 ingresos en el horizonte de tiempo. En el brazo con carvedilol fue donde ocurrieron menos muertes. Los índices mostraron que el metoprolol succinato fue dominante frente a los otros beta-bloqueadores en las hospitalizaciones evitadas y en las muertes en comparación con metoprolol tartrato. Conclusiones: se comprobó la escasa efectividad del metoprolol tartrato, que además generó los mayores costos de atención dentro del modelo. El carvedilol mostró ligeramente mejores resultados en mortalidad frente a metoprolol succinato aunque con costos mayores. El metoprolol succinato es la mejor opción puesto que es la menos costosa y más efectiva medida en relación con las hospitalizaciones. Para la atención de los pacientes con insuficiencia cardiaca congestiva e hipertensión arterial en Colombia, el tratamiento con metoprolol succinato es la opción más recomendable por su menor costo y mayor efectividad en las condiciones del caso base.

Objective: to conduct an assessment of cost-effectiveness of the use of metoprolol succinate versus metoprolol tartrate and carvedilol in the treatment of patients with congestive heart failure and hypertension in Colombia, from the third party payer's perspective. Methods: the study was conducted using a Markov model simulating the natural history of the disease for a time horizon of five years, taking 100 patients aged 45 years. Both hospitalizations and deaths avoided were evaluated as outcomes. The probability data were obtained from clinical studies and the costs of institutions databases and expert opinion, expressed in Colombian pesos of 2009. We applied a discount rate of 3%. Results: the cost of metoprolol succinate treated arm was the lowest, with 299 million pesos compared to 364 million and 346 million pesos for carvedilol and metoprolol tartrate, respectively. The lower number of hospitalizations occurred with metoprolol succinate, and corresponded with 24 admissions at the time horizon. In the carvedilol arm occurred fewer deaths. The indices showed that metoprolol succinate was dominant over the other beta-blockers in avoiding hospitalizations and deaths in comparison with metoprolol tartrate. Conclusions: we found the low effectiveness of metoprolol tartrate, which also generated the highest costs of care within the model. Carvedilol showed slightly better results in mortality compared to metoprolol succinate but with higher costs. Metoprolol succinate is the best choice since it is less costly and more effective in respect to hospitalizations. For the care of patients with congestive heart failure and hypertension in Colombia, treatment with metoprolol succinate is the most recommended option for its lower cost and greater effectiveness in the base case conditions.

Clínica de cães com cardiomiopatia dilatada idiopática, tratados ou não com carvedilol / Clinic of dogs with dilated cardiomyopathy (DCM) treated or not by carvedilol

O tratamento convencionalmente preconizado para cães acometidos pela CMD consiste na prescrição de vasodilatadores, agentes inotrópicos positivos (digitálico), diuréticos, dieta hipossódica e, quando necessário, antiarrítmicos. O carvedilol é um β-bloqueador de 3ª geração, não seletivo, que bloqueia igualmente e competitivamente os receptores (β1, β2 e α1). Produz uma evidente vasodilatação periférica, exerce efeitos anti-oxidantes, removendo radicais livres de oxigênio e prevenindo a peroxidação lipídica nas membranas cardíacas, prevenindo a perda de miócitos e a ocorrência de arritmias e reduzindo a taxa de mortalidade em pacientes humanos. O objetivo do presente estudo foi avaliar clínica, eletrocardiográfica, radiográfica e ecocardiograficamente a evolução de cães com cardiomiopatia dilatada (CMD) tratatos com terapia convencional associada ao carvedilol. Para tal foram avaliados 49 cães com CMD divididos em: grupo NT, tratado com terapia convencional, e grupo T, tratado com terapia convencional associada ao carvedilol. Os animais foram submetidos à avaliação clínica e a exames complementares durante o período de um ano. Os resultados demonstraram que a terapia com carvedilol apresentou boa tolerabilidade na dose de 0,3mg kg-1 12-12horas, aumentou a sobrevida dos cães em 30,9 por cento, não alterou as pressões sistólica e diastólica, reduziu a frequência cardíaca após três semanas de terapia, melhorou significantemente as frações de encurtamento e ejeção após seis meses de tratamento, não promoveu alterações radiográficas e da distância E-septo, diminuiu o índice de letalidade da doença, fato demonstrado pela melhora no escore clínico e na classe funcional dos animais, obtida após três semanas de terapia com carvedilol.

Commonly prescribed therapy for dogs presenting DCM consists of vasodilators, positive inotropic drugs (digitalics), diuretics, low-sodium diet and, when necessary, anti-arrhythmics. Carvedilol is a third generation non-selective β-blocker which blocks equally and competitively (β1, β2 and α1) receptors. Produces an evident peripheral vasodilation, exerts anti-oxidative effects, removing free radicals of oxygen and preventing lipidic peroxydation of cardiac membranes, and the loss of myocytes and arrhythmias, as well as reducing mortality rate in human patients. The aim of the present study was to evaluate by physical examination, electrocardiography, radiography, and echocardiography the evolution of dogs with dilated cardiomyopathy (DCM) treated by conventional therapy associated to carvedilol. Forty-nine dogs with DCM were divided in two groups: group NT: treated with conventional therapy, and group T: treated with conventional therapy associated to carvedilol. The animals were submitted to clinical and complementary examinations during one year. The results demonstrated that carvedilol therapy presented good tolerability on the dose of 0.3mg kg-1 each 12 hours, prolonged lifetime of the dogs in 30.9 percent, did not alter systolic or diastolic pressure, reduced heart frequency after three weeks of treatment, significantly enhanced shortening and ejection fractions after six months of treatment, did not promote radiographic or E-septum distance alterations, decreased patients letality, as demonstrated by improvement of clinical score and functional class (heart failure according to NYHA) of the animals, obtained three weeks after the beginning of cavedilol therapy.