Efficacy of Beta-Blockers and Angiotensin-Converting Enzyme Inhibitors in Non-Ischemic Dilated Cardiomyopathy: A Systematic Review and Meta-Analysis.

Background: Non-ischemic dilated cardiomyopathy (NIDCM) is a form of heart failure with a poor prognosis and unclear optimal management. The aim of the study was to systematically review the literature and assess the efficacy and safety of beta-blockers and angiotensin-converting enzyme (ACE) inhibitors in the management of chronic heart failure secondary to NIDCM and explore their putative mechanisms of action. Methods: Studies from 1990 to 2023 were reviewed using PubMed and EMBASE, focusing on their effects on left ventricular ejection fraction (LVEF) in NIDCM patients, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Beta-blockers showed a significant beneficial effect on LVEF improvement in NIDCM, with an overall effect size of Cohen's d = 1.30, 95% confidence interval (CI) (0.76, 1.84), high heterogeneity (Tau2 = 0.90; Chi2 = 162.05, df = 13, P < 0.00001; I2 = 92%), and a significant overall effect (Z = 4.72, P < 0.00001). ACE inhibitors also showed a beneficial role, but with less heterogeneity (Tau2 = 0.02; Chi2 = 1.09, df = 1, P = 0.30; I2 = 8%) and a nonsignificant overall effect (Z = 1.36, P = 0.17), 95% CI (-0.24, 1.31). Conclusions: The study highlights the efficacy of carvedilol in improving LVEF in NIDCM patients over ACE inhibitors, recommends beta-blockers as first-line therapy, and advocates further research on ACE inhibitors.

Effects of the Use of Beta-Blockers on Chronic Obstructive Pulmonary Disease Associated with Cardiovascular Comorbities: Systematic Review and Meta-analysis.

Cardiovascular comorbidity is common in individuals with chronic obstructive pulmonary disease (COPD). This factor interferes with pharmacological treatment. The use of ß-blockers has been proposed for their known cardioprotective effects. However, due to their adverse reactions, and the risk of causing bronchospasm, there is reluctance to use them. To summarize existing evidence on the effects of ß-blocker use in COPD associated with cardiovascular comorbidities in relation to disease severity, exacerbation, and mortality outcomes. EMBASE, Medline, Lilacs, Cochrane Library, and Science Direct databases were used. Observational studies that evaluated the effects of ß-blockers on individuals with COPD and cardiovascular comorbidities, and related disease severity, exacerbations, or mortality outcomes were included. Studies that did not present important information about the sample and pharmacological treatment were excluded. Twenty studies were included. Relevance to patient care and clinical practice: The use of ß-blockers in individuals with COPD and cardiovascular disease caused positive effects on mortality and exacerbations outcomes, compared with the results of individuals who did not use them. The severity of the disease caused a slight change in forced expiratory volume in 1 second. The odds ratio for mortality was 0.50 (95% confidence interval [CI], 0.39 to 0.63; p<0.00001), and for exacerbations, 0.76 (95% CI, 0.62 to 0.92; p=0.005), being favorable to the group that used ß-blockers. Further studies are needed to study the effect of using a specific ß-blocker in COPD associated with a specific cardiovascular comorbidity.

Impact of preoperative nonselective beta-blocker use on acute kidney injury after living donor liver transplantation: Propensity score analysis.

INTRODUCTION AND OBJECTIVES: Acute kidney injury (AKI) is prevalent and has deleterious effects on postoperative outcomes following liver transplantation (LT). The impact of nonselective beta-blockers (NSBBs) in patients with liver cirrhosis remains controversial. This study investigated the association between preoperative NSBB use and AKI after living donor LT (LDLT). PATIENTS AND METHODS: We evaluated 2,972 adult LDLT recipients between January 2012 and July 2022. The patients were divided into two groups based on the preoperative NSBB use. Propensity score matched (PSM) and inverse probability of treatment weighting (IPTW) analyses were performed to evaluate the association between preoperative NSBB use and postoperative AKI. Multiple logistic regression analyses were also used to identify the risk factors for AKI. RESULTS: The overall incidence of AKI was 1,721 (57.9%) cases. The NSBB group showed a higher incidence of AKI than the non-NSBB group (62.4% vs. 56.7%; P = 0.011). After PSM and IPTW analyses, no significant difference in the incidence of AKI was found between the two groups (Odds ratio, OR 1.13, 95% confidence interval, CI 0.93-1.37, P = 0.230, PSM analysis; OR 1.20, 95% CI 0.99-1.44, P = 0.059, IPTW analysis). In addition, preoperative NSBB use was not associated with AKI after multivariate logistic regression analysis (OR 1.16, 95% CI 0.96-1.40, P = 0.118). CONCLUSIONS: Preoperative NSBB use was not associated with AKI after LDLT. Further studies are needed to validate our results.

Evolving portal hypertension through Baveno VII recommendations.

The Baveno VII consensus workshop has provided several novel recommendations regarding the management of patients with clinically significant portal hypertension (CSPH). The expert panel summarized the existing data into simple clinical rules to aid clinicians in their clinical practice. The use of non-invasive tests (NITs), especially liver stiffness measurement (LSM), have gain an important role in daily practice. The use of LSM alone or in combination with platelet count can be used to rule-in and rule-out compensated advanced chronic liver disease (cACLD) and CSPH. Further decompensation events were defined as a prognostic stage associated with an even higher mortality than that associated with first decompensation. Moreover, the term hepatic recompensation was introduced in Baveno VII consensus implying a partial or complete regression of the functional and structural changes of cirrhosis after the removal of the underlying etiology. This review will summarize the reader main aspects of Baveno VII consensus regarding the use of NITs in cACLD, analyze further decompensation events, and evaluate recent recommendations for prophylaxis and management of liver decompensation events.

Beta-bloqueadores não seletivos em pacientes cirróticos com ascite refratária: onde estamos? / Non-selective beta-blockers in cirrhotic patients with refractory ascites: where are we?

ABSTRACT Background: The established use of non-selective beta-blockers (NSBB) in the primary and secondary prevention of esophageal varices has recently been questioned in the subgroup of patients with diuretic-refractory ascites. Objective: Critically analyze the body of evidence on the topic in order to assist clinical decisions. Methods: A literature review was carried out in the Pubmed® and Scielo® databases. In total, 20 articles between 2010 and 2023 were read by independent researchers. Conclusion: It remains doubtful whether the use of NSBB is deleterious in cirrhotic patients with refractory ascites, however our literature review allows us to conclude that these drugs should not be proscribed in these patients. On the contrary, a doctor-patient decision based on tolerability and hemodynamic parameters certainly seems to be a safe conduct.

RESUMO Contexto: O uso consagrado de betabloqueadores não seletivos (BBNS) na prevenção primária e secundária de varizes esofágicas foi recentemente questionado no subgrupo de pacientes com ascite refratária a diurético. Objetivo: Analisar criticamente o corpo de evidências sobre a temática a fim de auxiliar decisões clínicas. Métodos: Foi realizada uma revisão da literatura nos bancos de dados Pubmed® e Scielo®. No total, 20 artigos entre os anos 2010 e 2023 foram lidos por pesquisadores independentes. Conclusão: Ainda permanece duvidoso se o uso de BBNS é deletério nos cirróticos com ascite refratária, no entanto nossa revisão de literatura permite concluir que essas drogas não devem ser proscritas nesses pacientes. Ao contrário, uma decisão médico-paciente pautada na tolerabilidade e em parâmetros hemodinâmicos parece ser uma conduta decerto segura.

Ocular surface disease: a known yet overlooked side effect of topical glaucoma therapy.

Ocular surface disease (OSD), a disorder affecting the lacrimal and meibomian glands and the corneal and conjunctival epithelium, is a well-known complication of topical glaucoma therapy. OSD can present as a new or pre-existing condition that virtually any anti-glaucoma formulation can exacerbate. As such, both glaucoma and OSD frequently coexist. Typical OSD symptoms include ocular discomfort, redness, burning, and dryness, whereas signs include periorbital and eyelid skin pigmentation, conjunctival scarring, and superficial punctate keratitis. Pressure-lowering eyedrops can cause toxic, allergic, and inflammatory reactions on the ocular surface. The latter can result from either preservatives or direct toxicity from the active molecule. Although usually mild, OSD can cause significant symptoms that lead to poor quality of life, decreased compliance to therapy, glaucoma progression, and worse visual outcomes. Given the chronic nature of glaucoma, lack of curative therapy, and subsequent lifelong treatment, addressing OSD is necessary. This manuscript aims to provide an up-to-date overview of OSD's signs, symptoms, and pathogenic mechanisms from glaucoma therapy toxicity.

Beta-Blocker Therapy in Patients With Severe Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

INTRODUCTION: Traumatic brain injury (TBI), a leading cause of morbidity and mortality among trauma patients worldwide, poses the risk of secondary neurological insult due to significant catecholamine surge. We aim to investigate the effectiveness and outcomes of beta-blocker administration in patients with severe TBI. METHODS: A search through PubMed, EMBASE, JAMA network, and Google Scholar databases was conducted for relevant peer-reviewed original studies published before February 15, 2022. A standard random-effects model was used, as justified by a high Cohen's Q test. RESULTS: Twelve studies met inclusion criteria and were included in the meta-analysis. Severe TBI patients who were administered beta-blockers had a significantly reduced incidence of in-hospital mortality compared to the non-beta-blocker group (14.5% vs 19.2%). However, the beta-blocker group was reported to have a significantly greater number of ventilator days (5.58 vs 2.60 days). Similarly, intensive care unit (9.00 vs 6.84 days) and hospital (17.30 vs 11.02 days) lengths of stay (LOS) were increased in the beta-blocker group compared to those who were not administered beta-blocker therapy, but only the difference in hospital-LOS was significant. CONCLUSIONS: Beta-blockers have significantly decreased in-hospital mortality in patients with severe TBI despite being associated with an increase in ventilator days and hospital-LOS. The administration of beta-blocker therapy in the management of severe TBI may be warranted and should be discussed in future guidelines.

Propranolol inhibits cell viability and expression of the pro-tumorigenic proteins Akt, NF-ĸB, and VEGF in oral squamous cell carcinoma.

BACKGROUND: Propranolol (PPL) has been suggested as an option for the treatment of various types of cancer. However, data regarding its effectiveness against oral cancer are scarce. Thus, we aimed to evaluate the antitumor potential of PPL in oral squamous cell carcinoma (OSCC) in vitro. METHODS: OSCC cell lines, SCC-9, SCC-25, and Cal27, were treated with PPL at different times and concentrations. OSCC cells were treated with PPL alone or in combination with cisplatin (CDDP) or 5-fluorouracil (5-FU). Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of phosphorylated (p)-Akt, p-S6, p-PTEN, p-P65, and VEGF was verified by immunofluorescence. The migratory activity of OSCC cells was evaluated using a wound-healing assay. RESULTS: PPL reduced OSCC cell viability in a dose- and time-dependent manner. Concentrations above 300 µM, 110 µM, and 100 µM for SCC-9, Cal27, and SCC-25, respectively, significantly eliminated tumor cells. The combination of PPL with CDDP and 5-FU enhanced their antitumor effects. There was a modest difference between the use of the IC30 and IC50 of PPL in the combinatory options. PPL downregulated p-P65 NF-ĸB and VEGF expression in SCC-9 and Cal27 cells but not in SCC-25 cells. PPL inhibited the phosphorylation of Akt and s6 and increased the phosphorylation of PTEN in all OSCC cell lines studied. PPL inhibited OSCC cell migration after 24 h of treatment. CONCLUSION: PPL was effective against oral cancer cells and enhanced standard-of-care. PPL inhibited cell viability and the expression of pAkt, NF-ĸB, and VEGF.

Treatment of refractory ascites: Current strategies and new landscape of non-selective beta-blockers.

Ascites is the fluid accumulation in the peritoneal cavity, and it is the consequence of a wide variety of entities, being liver cirrhosis the most common one. In this kind of patients, the development of ascites results from splanchnic vasodilation; decreased effective circulating volume; the activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system; and a systemic inflammatory process. Its management is diverse and depends on the severity of the hemodynamic disturbance and other clinical manifestations. In recent years, therapeutic strategies have been developed, but they tend to result unconventional, so new evidence demonstrates the advantages of non-selective beta-blockers for the survival rate of patients with end-stage cirrhosis and ascites.

The Effect of Intravenous and Oral Beta-Blocker Use in Patients with Type B Thoracic Aortic Dissection.

BACKGROUND: Beta-blockers have become the cornerstone for medical management in patients with chronic type B aortic dissection (TBAD). However, the effect of being on and/or receiving intravenous beta-blockers during hospitalization on outcomes of surgical repair of TBAD is not fully described. We sought to investigate this association during open surgical repair (OSR) and endovascular (Endo) intervention for nontraumatic TBAD. METHODS: The Premier Healthcare Database was inquired (June/2009-March/2015). Patients with nontraumatic isolated TBAD were identified via ICD-9-CM diagnosis and procedural codes. Patients with codes that indicated TAAD were excluded. In-hospital mortality, cardiac complications (CHF, MI, arrythmia) and stroke were evaluated. Log binomial regression analyses with bootstrapping were performed to assess the relative risk of adverse outcomes. RESULTS: A total of 1,752 were admitted for OSR (54.3%) and Endo (45.7%) TBAD repair. Use of oral beta blocker (BB) was 16.0% in OSR and 56.4% in Endo groups. In each arm, patients on BB were more likely to be diabetic, on aspirin or statin and more likely to receive additional IV BB than nonBB patients. There was no significant difference in age, sex, race, or prior history of CHF between BB and nonBB groups. Mortality was proportionally lower in patients on BB in OSR group (7.9% vs. 16.7%; P = 0.006) and Endo (3.3% vs. 9.2%; P < 0.001). The adjusted relative risk for mortality and stroke were significantly lower in oral BB recipients compared with none [aRR (95% CI): 0.53 (0.32-0.90) and 0.46 (0.25-0.87); both P ≤ 0.02]. IV metoprolol was the only IV BB that reduced mortality [aRR (95% CI): 0.62 (0.46-0.85); P = 0.003]. A dose of ≤10 mg was associated with significant mortality reduction: 6.3% (3.0-9.5%) compared with 8.1% (4.6-11.6%) in no IV BB group. Cardiac complications were not affected by BB use. CONCLUSIONS: For patients with nontraumatic TBAD, use of oral BB was associated with significant protection against in-hospital mortality and stroke following repair. Metoprolol was the only Intravenous BB type associated with improved survival. Further research is warranted to elucidate the effect of beta-blockers on the long-term surgical outcomes of TBAD.

Anesthetic management of a patient with face hemangioma: case report.

Anesthetic agents and/or surgical positions, the total volume of hemangioma may increase under general anesthesia; thus, airway management of patients with a hemangioma may be very difficult. Our patient in this case report has a periorbital and oropharyngeal hemangioma that reaches down to the esophagus. We observed that the size and volume of the hemangioma increased significantly during elective nephrectomy surgery. After adequate therapy with steroids and beta-blockers, the size of the hemangioma decreased during the postoperative care unit monitoring period. We report this case to show the importance of airway management of hemangiomas with the potential for life-threatening complications.

Primary prophylaxis of variceal bleeding in patients with cirrhosis: A comparison of different strategies.

Patients with cirrhosis and esophageal varices bleed at a yearly rate of 5%-15%, and, when variceal hemorrhage develops, mortality reaches 20%. Patients are deemed at high risk of bleeding when they present with medium or large-sized varices, when they have red signs on varices of any size and when they are classified as Child-Pugh C and have varices of any size. In order to avoid variceal bleeding and death, individuals with cirrhosis at high risk of bleeding must undergo primary prophylaxis, for which currently recommended strategies are the use of traditional non-selective beta-blockers (NSBBs) (i.e., propranolol or nadolol), carvedilol (a NSBB with additional alpha-adrenergic blocking effect) or endoscopic variceal ligation (EVL). The superiority of one of these alternatives over the others is controversial. While EVL might be superior to pharmacological therapy regarding the prevention of the first bleeding episode, either traditional NSBBs or carvedilol seem to play a more prominent role in mortality reduction, probably due to their capacity of preventing other complications of cirrhosis through the decrease in portal hypertension. A sequential strategy, in which patients unresponsive to pharmacological therapy would be submitted to endoscopic treatment, or the combination of pharmacological and endoscopic strategies might be beneficial and deserve further investigation.

Colorimetric analysis of images in the follow-up of infantile hemangiomas.

BACKGROUND/OBJECTIVES: Infantile hemangiomas (IH) are common vascular tumors that appear early in life, have a rapid proliferative phase and slowly involute. There are no standardized ways to evaluate the regression of these lesions. We propose a colorimetric analysis of photographs to allow a more precise determination of IH treatment response and involution. METHODS: Patients 1-10 months of age with superficial or mixed IH were included. The lesions were managed with 0.5% topical timolol ophthalmic solution. Patients were followed for 16 weeks with 6 evaluations each. Photographic images were taken with a red and green circle placed beside each hemangioma. The photographs were treated as to equalize the size, color, and brightness among them based on the colors of the two circles. A grading scale was established based on the color of the patient skin (0) and the color of the hemangioma at the beginning of treatment (100) by pixel analysis using Adobe Photoshop® software. RESULTS: A total of 17 patients 1 to 10 months of age were included, of whom 16 were girls (94%). Fourteen lesions were superficial, and 3 were mixed IH. The median time prior to initiation of treatment was 105 days (44-232). All lesions showed some degree of clearing. The mean of lightening of color intensity observed was of 45% (17%-74%) over the period of follow-up. CONCLUSIONS: The colorimetric analysis of the digital images allowed an accurate and objective evaluation of IH clearing.

Retinopatía del prematuro: actualización en detección y tratamiento / Retinopathy of the premature: update in screening and treatment

Resumen: La Retinopatía del Prematuro (RDP) es una alteración proliferativa de los vasos sanguíneos de la retina inmadura, que afecta principalmente a los recién nacidos de muy bajo peso (RNMBP) y de menor edad gestacional. El objetivo de esta revisión es describir a qué niño se debe efectuar la detección de esta enfermedad y analizar los recientes avances en su tratamiento. La detección de RDP está dirigida principalmente a los RNMBP y a < de 32 semanas de edad gestacional, pero también se ha propuesto un criterio según edad postmenstrual. Además de la fotocoagulación con láser, tratamiento estándar en la actualidad, se han desarrollado nuevas terapias, como los agentes anti factor de crecimiento vas cular endotelial (VEGF), que se han utilizado exitosamente en la retinopatía umbral, especialmente localizada en zona I, con menos efectos adversos y mejores resultados oculares a futuro. que la fo tocoagulación con láser. En los últimos años, se han realizado ensayos clínicos con propranolol oral como tratamiento de la RDP, principalmente en la etapa pre-umbral (etapa 2 o 3 en zona II ó III). Este bloqueador beta-adrenérgico puede prevenir la progresión de la retinopatía en RNMBP de etapa pre- umbral a umbral y/o evitar la necesidad de terapias invasivas, como la fotocoagulación con láser o la administración intravítrea de agentes anti-VEGF. La fotocoagulación con láser continúa siendo el tra tamiento de elección en la RDP. Los agentes anti-VEGF y el propranolol oral, evitarían la progresión de esta patología de etapa pre-umbral a umbral, y podrían complementar el tratamiento de la RDP.

Abstract: Retinopathy of Prematurity (ROP) is a proliferative disorder of the blood vessels of the immature retina, which affects mainly very-low-birth-weight infants (VLBW). The objective of this review is to describe to which infant the screening examination of this disease should be performed and to analy ze the recent advances in the treatment of this disease, which have emerged in the last decade. The detection of this disease is mainly focused on VLBW infants and newborns < 32 weeks of gestational age. In addition to laser photocoagulation, standard treatment today, new therapies have appeared, such as the anti-VEGF agents, which have been successfully used in the threshold ROP, especially located in zone I. This therapy is less harmful than laser photocoagulation and with better ocular results in the future. In recent years, oral propranolol has been used as a treatment for ROP in clinical trials, mainly in the pre-threshold stage (stage 2 or 3 in zone II or III). This drug is a beta-adrenergic blocker that can prevent the progression of retinopathy in pre-threshold to threshold stage and/or avoid the need for invasive therapies, such as laser photocoagulation or intravitreal administration of anti-VEGF agents. Laser photocoagulation continues to be the standard treatment for ROP. New treatments have emerged for ROP, such as anti-VEGF agents and oral propranolol, which could pre vent the progression of this disease from the pre-threshold to the threshold stage.

Assessment of the ecotoxicity of the pharmaceuticals bisoprolol, sotalol, and ranitidine using standard and behavioral endpoints.

The pharmaceuticals bisoprolol (BIS), sotalol (SOT), and ranitidine (RAN) are among the most consumed pharmaceuticals worldwide and are frequently detected in different aquatic ecosystems. However, very few ecotoxicity data are available in the literature for them. To help fill these data gaps, toxicity tests with the algae Raphidocelis subcapitata, the macrophyte Lemna minor, the cnidarian Hydra attenuata, the crustacean Daphnia similis, and the fish Danio rerio were performed for assessing the ecotoxicity of these pharmaceuticals. Standard, as well as non-standard endpoint, was evaluated, including the locomotor behavior of D. rerio larvae. Results obtained for SOT and RAN showed that acute adverse effects are not expected to occur on aquatic organisms at the concentrations at which these pharmaceuticals are usually found in fresh surface waters. On the other hand, BIS was classified as hazardous to the environment in the acute III category. Locomotor behavior of D. rerio larvae was not affected by BIS and RAN. A disturbance on the total swimming distance at the dark cycle was observed only for larvae exposed to the highest test concentration of 500 mg L-1 of SOT. D. similis reproduction was affected by BIS with an EC10 of 3.6 (0.1-34.0) mg L-1. A risk quotient (RQ) of 0.04 was calculated for BIS in fresh surface water, considering a worst-case scenario. To the best of our knowledge, this study presents the first chronic toxicity data with BIS on non-target organisms.

Identification of two arylimides as cholinesterase inhibitors and testing of propranolol addition on impaired rat memory.

Alzheimer's disease (AD) is clearly linked to the decline of acetylcholine (ACh) effects in the brain. These effects are regulated by the hydrolytic action of acetylcholinesterase (AChE). Therefore, a central palliative treatment of AD is the administration of AChE inhibitors although additional mechanisms are currently described and tested for generating advantageous therapeutic strategies. In this work, we tested new arylamides and arylimides as potential inhibitors of AChE using in silico tools. Then, these compounds were tested in vitro, and two selected compounds, C7 and C8, as well as propranolol showed inhibition of AChE. In addition, they demonstrated an advantageous acute toxicity profile compared to that of galantamine as a reference AChE inhibitor. in vivo evaluation of memory performance enhancement was performed in an animal model of cognitive disturbance with each of these compounds and propranolol individually as well as each compound combined with propranolol. Memory improvement was observed in each case, but without a significant additive effect with the combinations.

BASIC AND CLINICAL INSIGHTS IN CATECHOLAMINERGIC (FAMILIAL) POLYMORPHIC VENTRICULAR TACHYCARDIA.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal disease, whose characteristic ventricular tachycardias are adrenergic-dependent. Although rare, CPVT should be considered in the differential diagnosis of young individuals with exercise-induced syncope. Mutations in five different genes (RYR2, CASQ2, CALM1, TRDN, and TECRL) are associated with the CPVT phenotype, although RYR2 missense mutations are implicated in up to 60 % of all CPVT cases. Genetic testing has an essential role in the diagnosis, management, pre-symptomatic diagnosis, counseling, and treatment of the proband; furthermore, genetic information can be useful for offspring and relatives. By expert consensus, CPVT gene testing is a Class I recommendation for patients with suspected CPVT. Beta-adrenergic and calcium-channel blockers are the cornerstones of treatment due to the catecholaminergic dependence of the arrhythmias. Unresponsive patients are treated with an implantable cardioverter-defibrillator to reduce the risk of sudden cardiac death. In the present article, a brief review of the genetic and molecular mechanisms of this intriguing disease is provided.

Basic and clinical insights in catecholaminergic (familial) polymorphic ventricular tachycardia

Abstract Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal disease, whose characteristic ventricular tachycardias are adrenergic-dependent. Although rare, CPVT should be considered in the differential diagnosis of young individuals with exercise-induced syncope. Mutations in five different genes (RYR2, CASQ2, CALM1, TRDN, and TECRL) are associated with the CPVT phenotype, although RYR2 missense mutations are implicated in up to 60 % of all CPVT cases. Genetic testing has an essential role in the diagnosis, management, pre-symptomatic diagnosis, counseling, and treatment of the proband; furthermore, genetic information can be useful for offspring and relatives. By expert consensus, CPVT gene testing is a Class I recommendation for patients with suspected CPVT. Beta-adrenergic and calcium-channel blockers are the cornerstones of treatment due to the catecholaminergic dependence of the arrhythmias. Unresponsive patients are treated with an implantable cardioverter-defibrillator to reduce the risk of sudden cardiac death. In the present article, a brief review of the genetic and molecular mechanisms of this intriguing disease is provided.

Diuretic window hypothesis in cirrhosis: Changing the point of view.

Since the 1970s, non-selective beta-blockers (NSBB) have been used to prevent variceal upper bleeding in advanced cirrhotic patients. However, several recent studies have raised the doubt about the benefit of NSBB in end-stage cirrhotic patients. In fact, they suggested a detrimental effect in these patients that even reduced survival. All of these studies have been assembled to compose the "window therapy hypothesis", in which NSBB would have traditional indication to be initiated to prevent variceal upper bleeding; however, treatment should be stopped (or not be initiated) in patients with end-stage cirrhosis. NSBB would reduce the cardiac reserve of these patients, worsening systemic perfusion and prognosis. However, it should be emphasized that these studies present important bias issues, and their results also suggested that diuretic treatment may also be behind the effects observed. In this opinion review, we changed the point of view from NSBB to diuretic treatment, based on a physiopathogenic approach of circulatory parameters of cirrhotic patients studied, and based on diuretic effect in blood pressure lowering and in other hypervolemic disease, as heart failure. We suggest a "diuretic window hypothesis", composed by an open window in hypervolemic phase, an attention window when patient present in a normal plasma volume phase, and a closed window during the plasma hypovolemic phase.