An Update on MYBPC3 Gene Mutation in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most prevalent genetically inherited cardiomyopathy that follows an autosomal dominant inheritance pattern. The majority of HCM cases can be attributed to mutation of the MYBPC3 gene, which encodes cMyBP-C, a crucial structural protein of the cardiac muscle. The manifestation of HCM's morphological, histological, and clinical symptoms is subject to the complex interplay of various determinants, including genetic mutation and environmental factors. Approximately half of MYBPC3 mutations give rise to truncated protein products, while the remaining mutations cause insertion/deletion, frameshift, or missense mutations of single amino acids. In addition, the onset of HCM may be attributed to disturbances in the protein and transcript quality control systems, namely, the ubiquitin-proteasome system and nonsense-mediated RNA dysfunctions. The aforementioned genetic modifications, which appear to be associated with unfavorable lifelong outcomes and are largely influenced by the type of mutation, exhibit a unique array of clinical manifestations ranging from asymptomatic to arrhythmic syncope and even sudden cardiac death. Although the current understanding of the MYBPC3 mutation does not comprehensively explain the varied phenotypic manifestations witnessed in patients with HCM, patients with pathogenic MYBPC3 mutations can exhibit an array of clinical manifestations ranging from asymptomatic to advanced heart failure and sudden cardiac death, leading to a higher rate of adverse clinical outcomes. This review focuses on MYBPC3 mutation and its characteristics as a prognostic determinant for disease onset and related clinical consequences in HCM.

Pushing the Limits of Medical Management in HCM: A Review of Current Pharmacological Therapy Options.

Hypertrophic cardiomyopathy (HCM) is the most common monogenic cardiac disease with a highly variable phenotypic expression, ranging from asymptomatic to drug refractory heart failure (HF) presentation. Pharmacological therapy is the first line of treatment, but options are currently limited to nonspecific medication like betablockers or calcium channel inhibitors, with frequent suboptimal results. While being the gold standard practice for the management of drug refractory HCM patients, septal reduction therapy (SRT) remains an invasive procedure with associated surgical risks and it requires the expertise of the operating centre, thus limiting its accessibility. It is therefore with high interest that researchers look for pharmacological alternatives that could provide higher rates of success. With new data gathering these past years as well as the development of a new drug class showing promising results, this review provides an up-to-date focused synthesis of existing medical treatment options and future directions for HCM pharmacological treatment.

Uric Acid-An Emergent Risk Marker for Thrombosis?

Hyperuricemia is nowadays an established cardiovascular risk factor. Experimental studies linked elevated serum uric acid (SUA) levels with endothelial dysfunction (ED), inflammation, and prothrombotic state. The purpose of this review is to summarize the current evidence that emphasizes the possible role of uric acid as a biomarker for a prothrombotic state. A large number of clinical trials correlated SUA levels with both incident and recurrent cases of venous thromboembolism (VTE), independent of other confounding risk factors. Moreover, increased SUA levels may be an important tool for the risk stratification of patients with pulmonary embolism (PE). Left atrial thrombosis was correlated with high SUA levels in several studies and its addition to classical risk scores improved their predictive abilities. In patients with acute myocardial infarction (MI), hyperuricemia was associated with increased mortality, and the idea that hyperuricemia may be able to act as a surrogate to unstable coronary plaques was advanced. Finally, SUA was correlated with an increased risk of thromboembolic events in different systemic diseases. In conclusion, uric acid has been considered a marker of a thrombotic milieu in several clinical scenarios. However, this causality is still controversial, and more experimental and clinical data is needed.

What can hide behind an "idiopathic" dilated cardiomyopathy?

Myocarditis is an infectious-inflammatory disease with viral infections being one of the most common infectious cause. When it is superimposed to an individual genetic background, myocarditis may progress into a chronic heart muscle disorder, most often dilated cardiomyopathy (DCM), with a natural history similar to classic forms of genetic or idiopathic dilated cardiomyopathies. We present the case of a 30-year-old patient, with a persistent infectious episode in the last 8 weeks, pain and swelling in the large joints. At admission the patient had fever, tachycardia and a grade 2/6 systolic mitral murmur. Laboratory findings revealed inflammatory syndrome, hepatocytolysis syndrome and microalbuminuria. The electrocardiogram (ECG) showed possible right atrial tachycardia. The echocardiography revealed a globally enlarged heart with reduced ejection fraction and diffuse hypokinesia. When discussing the etiology of the DCM, the following were taken into consideration: a tachycardiomyopathy, ischemic etiology, genetic component, autoimmune etiology (elevated anti-Ro titer), and myocarditis. The diagnosis of myocarditis was confirmed by the cardiac magnetic resonance imaging which showed diffuse fibrosis of the interstitial space and an important increase of the extracellular volume. This case is distinguished by a particular immunological panel requiring dynamic monitoring in order to diagnose a possible associated autoimmune pathology.

Multi-modality cardiac imaging in advanced chronic kidney disease.

Cardiovascular disease (CVD) is the leading cause of death worldwide and is particularly frequent among those with severe renal impairment. Early diagnosis and therapeutic intervention may help alleviate the burden of cardiovascular complication within this population. In the last years, advances have been made toward developing noninvasive imaging techniques that could offer better insight into the cardiac involvement in end-stage renal disease (ESRD). Conventional transthoracic echocardiography remains the first-line investigation used to assess cardiac function, but encompassing in our daily practice, the newer approaches such as speckle-tracking imaging, cardiac computed tomography, or cardiac magnetic resonance can guide us to a more comprehensive understanding of CVD in ESRD. Given that patients with chronic kidney disease may not present with typical CVD symptoms, the amount of information brought by newer imaging techniques is crucial for an accurate diagnosis, risk stratification, and further management. The purpose of this review is to briefly summarize the specific applications of standard cardiac imaging techniques in patients with ESRD and to offer insight into the novel imaging modalities, highlighting the newest research in this field. By doing so, we aim to identify the most important imaging predictors of clinical outcomes in this population.

Cerebral vein thrombosis associated with MTHFR A1289C mutation gene in a young postpartum woman.

Cerebral venous thrombosis is a rare cerebrovascular disease that accounts for approximately 1% of strokes, with an incidence of 3-4 cases / million inhabitants per year, with a significant mortality rate of 10-13%. Pregnancy and puerperal period are physiological states that predispose to thrombosis through hypercoagulability due to hormonal change. These alterations occur in blood flow, vascular wall and clotting factors and while superimposed on a genetically predisposing field, create the optimal conditions for the occurrence of embolic phenomena. Here we present the case of a young, secondipara woman with recurrent thrombotic events, even under optimal anticoagulation therapy, where the extensive laboratory investigations identified the predisposing terrain: the heterozygous mutation of the MTHFR A1289C gene.