Markers of Cardiac Dysfunction in Cognitive Impairment and Dementia

Markers of cardiac dysfunction such as amino terminal pro-brain natriuretic peptide (NTpro-BNP) and high sensitivity cardiac troponin T (hs-cTnT) may be associated with dementia. However, limited data exist on their association with either pre-dementia stages, that is, cognitive impairment no dementia (CIND), or the burden of cerebrovascular diseases (CeVD).We therefore, examined the association of these biomarkers of cardiac dysfunction with CeVD in both CIND and dementia.A case–control study, with cases recruited from memory clinics and controls from memory clinics and community. All subjects underwent collection of blood samples, neuropsychological assessment, and neuroimaging. Subjects were classified as CIND and dementia based on clinical criteria whilst significant CeVD was defined as the presence of cortical infarcts and/or more than 2 lacunes and/or confluent white matter lesions in two regions of brain on Age-Related White Matter Changes Scale.We included a total of 35 controls (mean age: 65.9 years), 78 CIND (mean age: 70.2 years) and 80 cases with dementia (mean age: 75.6 years). Plasma concentrations of hs-cTnT were associated significantly with CeVD in both CIND (odds ratios [OR]: 9.05; 95% confidence interval [CI]: 1.64–49.79) and dementia (OR: 16.89; 95%CI: 2.02–142.67). In addition, NTpro-BNP was associated with dementia with CeVD (OR: 7.74; 95%CI: 1.23–48.58). These associations were independent of other vascular risk factors.In this study, we showed that plasma NTproBNP and hs-cTnT are associated with dementia and CIND, only when accompanied by presence of CeVD.     

进行性心脏传导疾病

进行性心脏传导疾病以心内传导系统的进行性退行性变导致房室或室内传导阻滞,病因不明,体表心电图上出现PR间期及QRS间期的延长和/或左或右束支传导阻滞,病情严重时可导致晕厥或猝死.早期发病者预后差.患者常有钠通道基因异常的遗传性基础,诊断主要依赖心电图学的随访,因为发病率不明,临床应予以注意.治疗主要依赖永久性起搏治疗,适应证较其他传导系统疾病宽,抗心律失常药物治疗应谨慎.     

Genetics of Cardiac Electrical Disease

Few tragedies compare to the sudden death of a family member. Sadly, this may represent the first sign of a familial vulnerability to such events. One common cause is an inherited cardiac arrhythmia syndrome. Sufferers are prone to premature sudden cardiac death due to altered ion channel function in the heart. Typical causes include Brugada syndrome, long QT syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia, and the newly recognized early repolarization syndrome. Our knowledge of the genetic underpinnings of each of these disorders has increased markedly in recent years. Genetic screening is now a routine part of clinical care and promises more accurate diagnosis and efficient family screening. This review summarizes the diagnosis and management of each of the listed syndromes in the context of currently available genetic testing.     

阿尔茨海默病与血管性痴呆的鉴别诊断

目的：观察阿尔茨海默病(AD)与血管性痴呆(VD)的临床特点，为痴呆提供诊断和鉴别诊断。方法：根据DSM—Ⅳ标准，对28例AD和42例VD病人的认知功能、情感反应、行为异常及疾病发展和头颅CT进行对比研究。结果：①AD认知功能减退常为全面广泛性，VD以记忆力减退和计算力减迟为主；②AD的非认知功能常受影响，VD的非认知功能较少受损；③AD发病隐，VD起病急骤；④AD病人无明显的局灶体征，VD病人多有局灶体征；⑤AD病人头颅CT、MRI示广泛皮质萎缩，VD多为局灶异常。结论：由于两种疾病的发病机制不同，其临床表现有相同之处，亦有区别，根据量表和影像学可以对这两种常见的老年期痴呆做出诊断和鉴别诊断。     

The Origin and Arrhythmogenic Potential of Fibroblasts in Cardiac Disease

Fibroblasts play a major role in normal cardiac physiology and in the response of the heart to injury and disease. Cardiac electrophysiological research has primarily focused on the mechanisms of remodeling that accompany cardiac disease with an emphasis on myocyte electrophysiology. Recently, there has been increasing interest in the potential role of fibroblasts in cardiac electrophysiology. This review focuses on the arrhythmia mechanisms involving interactions between myocytes and fibroblasts. We also discuss the available evidence supporting the contribution of intracardiac and extracardiac sources to the fibroblast and myofibroblast populations in diseased hearts.     

The Dynamic Role of Cardiac Fibroblasts in Development and Disease

Cardiac fibroblasts are the most abundant cell in the mammalian heart. While they have been historically overlooked in terms of functional contributions to development and physiology, cardiac fibroblasts are now front and center. They are currently recognized as key protagonists during both normal development and cardiomyopathy disease, and work together with cardiomyocytes through paracrine, structural, and potentially electrical interactions. However, the lack of specific biomarkers and fibroblast heterogeneous nature currently convolutes the study of this dynamic cell lineage; though, efforts to advance marker analysis and lineage mapping technologies are ongoing. These tools will help elucidate the functional significance of fibroblast?Ccardiomyocyte interactions in vivo and delineate the dynamic nature of normal and pathological cardiac fibroblasts. Since therapeutic promise lies in understanding the interface between developmental biology and the postnatal injury response, future studies to understand the divergent roles played by cardiac fibroblasts both in utero and following cardiac insult are essential.     

Cardiac Arrhythmias in Chagas'Heart Disease

Chagas’ Heart Disease. Chagas’ disease is a chronic parasitosis affecting most LatinAmerican countries, Its most important clinical manifestation is a late developing chronicmyocarditis and, much less frequently, an early acute myocarditis, Chagasic myocardial damage is microfocal and disseminated throughout the heart, In most cases, the coexistence ofareas of myocytic degeneration, inflammatory infiltration, and fibrosis suggests a permanentevolving process. Commonly, chronic chagasic myocarditis resemhies a dilated cardiomyopa–thy, with characteristic ECG abnormalities (atrial and ventricular extrasystoles, intraventricular and/or AV conduction disturbances, and primary ST-T wave changes), Since myocardialdamage is scattered throughout the heart, the ECG abnormalities (arrhythmias, conductiondisturbances, and repolarization changes) are also representative of the widespread cardiacinvolvement. Thus, sick sinus syndrome, atrial extrasystoles, intraatrial conduction disturbances, and atrial fibrillation or flutter are common findings in different stages of the disease, At the ventricular level, both conduction disturbances and arrhythmias are conspicuousexpressions of the myocardial damage. Right bundle branch block alone or in combinationwith left anterior hemiblock are the most common conduction defects, Further compromise ofthe conduction system can lead to different degrees of AV block, Chagas’ disease is the maincause of bundle branch block and AV block in endemic areas, In advanced cases of Chagas'heart disease, ventricular premature contractions are extremely frequent, multiforM. andrepetitive (couplets and runs of ventricular tachycardia), and show R on T phenomenon, Thesearrhythmias are usually aggravated by increased sympathetic tone, implying an enbanced riskof cardiac sudden death among chagasic patients, which is sometimes the first manifestation ofthe illness, Chronic chagasic myocarditis is the leading cause of cardiovascular death, mostly asa consequence of heart failure and sudden death, in areas where the disease is endemic.     

Cardiac Transplantation in Danon Disease

BackgroundDanon disease (DD) is a rare X-linked dominant cardioskeletal myopathy caused by mutations in the lysosome-associated membrane protein-2 (LAMP-2) gene that is usually lethal without cardiac transplantation. The purpose of this study was to characterize post-transplant outcomes in a large cohort of patients with DD who underwent cardiac transplantation.MethodsThe clinical phenotype and outcome data of patients with DD who underwent cardiac transplantation (n = 38; 19 males and 19 females) were obtained from 8 centers. Study outcomes included graft survival, defined as death or retransplantation, and episodes of acute cellular and antibody-mediated rejection and cardiac allograft vasculopathy at 1 year.ResultsMedian follow-up time after transplantation for the entire cohort was 4.4 years (IQR: 1.5–12.8 years). The median age at transplant for the cohort was 20.2 years (15.8–27.9 years), with no difference in age between sexes. Median pretransplant left-ventricular ejection fraction for the entire cohort was 30% (range 11%–84%). Males had higher pretransplant aspartate aminotransferase, alanine aminotransferase and creatine phosphokinase levels than females (P < 0.001). There were 2 deaths in the entire cohort and 2 retransplants. There was no difference in actuarial graft survival between males and females (P = 0.8965); the estimated graft survival was 87.1% (95%CI: 63.6%–95.9%) at 5 years. One episode (2.7%) of antibody-mediated rejection, grade 2, and 7 episodes (19%) of acute cellular rejection, grade 2 or 3, were reported in patients who survived to discharge (6 females and 1 male; P = 0.172).ConclusionsHeart transplantation outcomes are acceptable in DD with high probabilities of 5-year graft survival for males and females suggesting that cardiac transplantation is an effective treatment option for DD patients.     

Alcohol Abuse and Cardiac Disease

Background

Understanding the relationship between alcohol abuse, a common and theoretically modifiable condition, and the most common cause of death in the world, cardiovascular disease, may inform potential prevention strategies.

IgG4 Related Cardiac Disease

IgG4-related systemic disease is an inflammatory disorder that can affect many organs. This case report describes a patient who in 2004 was found to have an inflammatory pseudotumor with IgG4 pathology. Over the next 3 years, visual symptoms responded well to recurrent courses of prednisone. In 2009, the patient developed chest pain and bradycardia with subsequent third-degree heart block, necessitating placement of a pacemaker. A subsequent PET scan showed extensive involvement of multiple organs as described in IgG4 disease as well as involvement of the myocardium and SA node. Pseudotumors involving the heart have been reported but have not been shown to be related to IgG4 disease. Although there was no pathology confirmation of heart involvement, the nature and extent of the organ involvement led us to conclude that it was due to IgG4-related disease. The use of the PET scan may help identify involvement of the myocardium.     

Glycosylation of Transferrin in Alzheimer's Disease and Alcohol-Induced Dementia

Transferrin is a glycosylated metal-binding serum protein. Carbohydrate-deficient transferrin (CDT) is a marker of recent and heavy alcohol intake. A genetic variant of transferrin, TfC2, occurs with increased frequency in patients with Alzheimer's disease (AD). Hence the question arose whether, in addition to an altered amino acid sequence, there could also be a difference in the glycosylation state of transferrin in patients with dementia. Serum samples of 37 AD and 13 Alcohol-induced dementia patients as well as 10 healthy controls were analyzed for abnormal Tf variants, using isoelectric focusing followed by blotting with anti-Tf antibodies. This allowed the direct visualization of glycosylation variants of transferrin, and assessment of any increase in underglycosylated forms (di-, mono-and asialo transferrin).