Primary Prevention of Sudden Cardiac Death in Heart Failure: Will the Solution Be Shocking?

Sudden cardiac death (SCD) may occur in as many as 40% of all patients who suffer from heart failure. This review describes the scope of the problem, risk factors for SCD, the effect of medications used in heart failure on SCD and the potential effect of the implantable cardioverter-defibrillator in primary prevention.     

癌瘤患者骨髓细胞c－erbB和c－erbA的基因异常

本文在大系列研究造血系统恶性肿瘤-白血病和白血病前期的基础上，对３１例恶性肿瘤患者骨髓进行血液学、细胞和分子遗传学研究。发现恶性肿瘤患者骨髓有与白血病前期骨髓相似的病态造血（Ｍｙｅｌｏｄｙｓｐｌａｓｉａ）和相关基因异常即ｃ－ｅｒｂＢ基因重排、扩增和ｃ－ｅｒｂＡ缺失。它们不仅同骨髓红系病态造血相关，也同巨核系病态造血相关。骨髓巨核系病态造血及其相关基因异常可能代表急性淋巴细胞白血病等多种恶性肿瘤的早期病变。而ｃ－ｅｒｂＢ重排及其相关的骨髓巨核系异常增生可能是肿瘤发病的遗传背景。     

Characterization and Management of Arrhythmic Events in Young Patients With Brugada Syndrome

Background

Information on young patients with Brugada syndrome (BrS) and arrhythmic events (AEs) is limited.

Aberrant lipid metabolism as a therapeutic target in liver cancer

Introduction: Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers. Progress has been made in treatment of HCC; however, improved outcomes are much needed. The increased metabolic needs of cancer cells underscore the importance of metabolic pathways in cancer cell survival. Lipid metabolism has a role in HCC development; aberrant overexpression of several key enzymes is seen in many solid human tumors.

Areas covered: We discuss aberrant lipid metabolism and the promise of multiple targets, in particular related to HCC treatment. We searched PubMed and clinicaltrials.gov for published and unpublished studies from 2000 to 2019. These terms were used: lipids, fatty acid metabolism, lipid metabolism, liver cancer, HCC, de novo fatty acid synthesis, ATP citrate lyase, stearoyl CoA denaturase, fatty acid synthase, acetyl coenzyme A carboxylase, CD147, KLF4, monoglyceride lipase, AMP activated protein kinase.

Expert opinion: The importance of dysregulation of fatty acid synthesis in cancer is a growing area of research. HCC demonstrates significant alteration in lipid metabolism, representing great potential as a target for novel therapeutics. Various agents have demonstrated promising anti-neoplastic activity. This strategy deserves further development for improved outcomes.     

Beliefs about hydroxyurea in youth with sickle cell disease

Background

Hydroxyurea reduces complications and improves health-related quality of life (HRQOL) in sickle cell disease (SCD) patients, however adherence remains suboptimal. Understanding patients’ views of hydroxyurea is critical to optimize adherence, particularly in adolescents and young adults (AYA). Study objectives were to assess beliefs about hydroxyurea using the Beliefs about Medicines Questionnaire (BMQ), and to examine the relationship of patients’ beliefs to their hydroxyurea adherence and HRQOL.

Long QT syndrome

The hereditary long QT syndrome (LQTS) is a genetic channelopathy with variable penetrance that is associated with increased propensity to syncope, polymorphous ventricular tachycardia (torsades de pointes), and sudden arrhythmic death. This inherited cardiac disorder constitutes an important cause of malignant ventricular arrhythmias and sudden cardiac death in young individuals with normal cardiac morphology. Risk assessment in affected LQTS patients relies upon a constellation of electrocardiographic, clinical, and genetic factors. Administration of beta-blockers is the mainstay therapy in affected patients, and primary prevention with an implantable cardioverter defibrillator or left cervicothoracic sympathetic denervation are therapeutic options in patients who remain symptomatic despite beta-blocker therapy. Accumulating data from the International LQTS Registry have recently facilitated a comprehensive analysis of risk factors for aborted cardiac arrest or sudden cardiac death in pre-specified age groups, including the childhood, adolescence, adulthood, and post-40 periods. These analyses have consistently indicated that the phenotypic expression of LQTS is time dependent and age specific, warranting continuous risk assessment in affected patients. Furthermore, the biophysical function, type, and location of the ion-channel mutation are currently emerging as important determinants of outcome in genotyped patients. These new data may be used to improve risk stratification and for the development of gene-specific therapies that may reduce the risk of life-threatening cardiac events in patients with this inherited cardiac disorder.     

Cardiovascular and Other Health Benefits of Sauna Bathing: A Review of the Evidence

Sauna bathing, an activity that has been a tradition in Finland for thousands of years and mainly used for the purposes of pleasure and relaxation, is becoming increasingly popular in many other populations. Emerging evidence suggests that beyond its use for pleasure, sauna bathing may be linked to several health benefits, which include reduction in the risk of vascular diseases such as high blood pressure, cardiovascular disease, and neurocognitive diseases; nonvascular conditions such as pulmonary diseases; mortality; as well as amelioration of conditions such as arthritis, headache, and flu. The beneficial effects of sauna bathing on these outcomes have been linked to its effect on circulatory, cardiovascular, and immune functions. It has been postulated that regular sauna bathing may improve cardiovascular function via improved endothelium-dependent dilatation, reduced arterial stiffness, modulation of the autonomic nervous system, beneficial changes in circulating lipid profiles, and lowering of systemic blood pressure. This review summarizes the available epidemiological, experimental, and interventional evidence linking Finnish sauna bathing and its effects on cardiovascular outcomes and other disease conditions on the basis of a comprehensive search for observational studies, randomized controlled trials, and non–randomized controlled trials from MEDLINE and EMBASE from their inception until February 24, 2018. An overview of the postulated biological mechanisms underlying the associations between sauna bathing and its health benefits, areas of outstanding uncertainty, and implications for clinical practice is also provided.     

Clinical Assessment of Spasticity in People With Spinal Cord Damage: Recommendations From the Ability Network,an International Initiative

A thorough assessment of the extent and severity of spasticity, and its effect on functioning, is central to the effective management of spasticity in persons with spinal cord damage (SCD). These individuals however do not always receive adequate assessment of their spasticity. Inadequate assessment compromises management when the effect of spasticity and/or need for intervention are not fully recognized. Assessment is also central to determining treatment efficacy. A barrier to spasticity assessment has been the lack of consensus on clinical and functional measures suitable for routine clinical practice. To extend on existing work, a working group of the Ability Network identified and consolidated information on possible measures, and then synthesized and formulated findings into practical recommendations for assessing spasticity and its effect on function in persons with SCD. Sixteen clinical and functional measures that have been used for this purpose were identified using a targeted literature review. These were mapped to the relevant domains of the International Classification of Functioning, Disability and Health to assess the breadth of their coverage; coverage of many domains was found to be lacking, suggesting a focus for future work. The advantages, disadvantages, and usefulness of the measures were assessed using a range of criteria, with a focus on usefulness and feasibility in routine clinical practice. Based on this evaluation, a selection of measures suitable for initial and follow-up assessments are recommended. The recommendations are intended to have broad applicability to a variety of health care settings where people with SCD are managed.     

The natural history of a genetic subtype of arrhythmogenic right ventricular cardiomyopathy caused by a p.S358L mutation in TMEM43

To determine the phenotype and natural history of a founder genetic subtype of autosomal dominant arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by a p.S358L mutation in TMEM43. The age of onset of cardiac symptoms, clinical events and test abnormalities were studied in 412 subjects (258 affected and 154 unaffected), all of which occurred in affected males significantly earlier and more often than unaffected males. Affected males were hospitalized four times more often than affected females (p ≤ 0.0001) and died younger (p ≤ 0.001). The temporal sequence from symptoms onset to death was prolonged in affected females by 1–2 decades. The most prevalent electrocardiogram (ECG) manifestation was poor R wave progression (PRWP), with affected males twice as likely to develop PRWP as affected females (p ≤ 0.05). Left ventricular enlargement (LVE) occurred in 43% of affected subjects, with 11% fulfilling criteria for dilated cardiomyopathy. Ventricular ectopy on Holter monitor was common and occurred early: the most diagnostically useful clinical test. No symptom or test could rule out diagnosis. This ARVC subtype is a sex‐influenced lethal arrhythmogenic cardiomyopathy, with a unique ECG finding, LV dilatation, heart failure and early death, where molecular pre‐symptomatic diagnosis has the greatest clinical utility.     

Implantable Cardioverter-Defibrillators in Children and Adolescents With Brugada Syndrome

Background

Young patients presenting with symptomatic Brugada syndrome have very high risks for ventricular arrhythmias and should be carefully considered for implantable cardioverter-defibrillator (ICD) placement. However, this therapy is associated with high rates of inappropriate shocks and device-related complications.