- [Interventional treatment in patients with myocarditis: Pro and Contra]. [Journal Article]
- KKardiologiia 2017 SMar; 57(S3):49-56
- CONCLUSIONS: In this selected group of patients with verified myocarditis and clinically significant VTs, catheter ablation seems at least partly effective. Patients with borderline myocarditis and symptomatic VTs may benefit from ablation. Therefore, morphological diagnostic of myocarditis can be a key point in choice of treatment.
- Left ventricular chamber geometry in cardiomyopathies: insights from a computerized anatomical study. [Journal Article]
- EHESC Heart Fail 2018 Feb 21
- CONCLUSIONS: Left ventricular chambers of anatomical specimens with dilated cardiomyopathies did not display a spherical shape and were not proportional to normal hearts.
- Genetic determinants of heart failure: facts and numbers. [Editorial]
- EHESC Heart Fail 2018 Feb 19
- The relevance of gene mutations leading to heart diseases and hence heart failure has become evident. The risk for and the course of heart failure depends on genomic variants and mutations underlying...
The relevance of gene mutations leading to heart diseases and hence heart failure has become evident. The risk for and the course of heart failure depends on genomic variants and mutations underlying the so-called genetic predisposition. Genetic contribution to heart failure is highly heterogenous and complex. For any patient with a likely inherited heart failure syndrome, genetic counselling is recommended and important. In the last few years, novel sequencing technologies (named next-generation sequencing - NGS) have dramatically improved the availability of molecular testing, the efficiency of genetic analyses, and moreover reduced the cost for genetic testing. Due to this development, genetic testing has become increasingly accessible and NGS-based sequencing is now applied in clinical routine diagnostics. One of the most common reasons of heart failure are cardiomyopathies such as the dilated or the hypertrophic cardiomyopathy. Nearly 100 disease-associated genes have been identified for cardiomyopathies. The knowledge of a pathogenic mutation can be used for genetic counselling, risk and prognosis determination, therapy guidance and hence for a more effective treatment. Besides, family cascade screening for a known familial, pathogenic mutation can lead to an early diagnosis in affected individuals. At that timepoint, a preventative intervention could be used to avoid or delay disease onset or delay disease progression. Understanding the cellular basis of genetic heart failure syndromes in more detail may provide new insights into the molecular biology of physiological and impaired cardiac (cell) function. As our understanding of the molecular and genetic pathophysiology of heart failure will increase, this might help to identify novel therapeutic targets and may lead to the development of new and specific treatment options in patients with heart failure.
- ZBTB17 loss-of-function mutation contributes to familial dilated cardiomyopathy. [Journal Article]
- HVHeart Vessels 2018 Feb 14
- Dilated cardiomyopathy (DCM) is a common primary myocardial disease leading to congestive heart failure, arrhythmia and sudden cardiac death. Increasing studies demonstrate substantial genetic determ...
Dilated cardiomyopathy (DCM) is a common primary myocardial disease leading to congestive heart failure, arrhythmia and sudden cardiac death. Increasing studies demonstrate substantial genetic determinants for DCM. Nevertheless, DCM is of substantial genetic heterogeneity, and the genetic basis for DCM in most patients remains unclear. The present study was sought to investigate the association of a genetic variant in the ZBTB17 gene with DCM. A cohort of 158 unrelated patients with idiopathic DCM and a total of 230 unrelated, ethnically matched healthy individuals used as controls were recruited. The coding exons and splicing boundaries of ZBTB17 were sequenced in all study participants. The functional effect of the mutant ZBTB17 was characterized by a dual-luciferase reporter assay system. A novel heterozygous ZBTB17 mutation, p.E243X, was discovered in an index patient. Genetic scan of the mutation carrier's available relatives showed that the mutation was present in all affected family members but absent in unaffected family members. Analysis of the proband's pedigree revealed that the mutation co-segregated with DCM, which was transmitted in an autosomal dominant pattern with complete penetrance. The nonsense mutation was absent in the 460 control chromosomes. Functional assays demonstrated that the truncated ZBTB17 protein had no transcriptional activity as compared with its wild-type counterpart. This study firstly associates ZBTB17 loss-of-function mutation with enhanced susceptibility to DCM in humans, which provides novel insight into the molecular mechanism underpinning DCM, implying potential implications for genetic counseling and personalized management of DCM.
- Characterization of TTN Novex Splicing Variants across Species and the Role of RBM20 in Novex-Specific Exon Splicing. [Journal Article]
- GGenes (Basel) 2018 Feb 13; 9(2)
- Titin(TTN) is a major disease-causing gene in cardiac muscle.Titin(TTN) contains 363 exons in human encoding various sizes of TTN protein due to alternative splicing regulated mai...
Titin(TTN) is a major disease-causing gene in cardiac muscle.Titin(TTN) contains 363 exons in human encoding various sizes of TTN protein due to alternative splicing regulated mainly by RNA binding motif 20 (RBM20). Three isoforms of TTN protein are produced by mutually exclusive exons 45 (Novex 1), 46 (Novex 2), and 48 (Novex 3). Alternatively splicing in Novex isoforms across species and whether Novex isoforms are associated with heart disease remains completely unknown. Cross-species exon comparison with the mVISTA online tool revealed that exon 45 is more highly conserved across all species than exons 46 and 48. Importantly, a conserved region between exons 47 and 48 across species was revealed for the first time. Reverse transcript polymerase chain reaction (RT-PCR) and DNA sequencing confirmed a new exon named as 48' in Novex 3. In addition, with primer pairs for Novex 1, a new truncated form preserving introns 44 and 45 was discovered. We discovered that Novex 2 is not expressed in the pig, mouse, and rat with Novex 2 primer pairs. Unexpectedly, three truncated forms were identified. OneTTNvariant with intron 46 retention is mainly expressed in the human and frog heart, another variant with co-expression of exons 45 and 46 exists predominantly in chicken and frog heart, and a third with retention of introns 45 and 46 is mainly expressed in pig, mouse, rat, and chicken. UsingRbm20knockout rat heart, we revealed that RBM20 is not a splicing regulator of Novex variants. Furthermore, the expression levels of Novex variants in human hearts with cardiomyopathies suggested that Novexes 2 and 3 could be associated with dilated cardiomyopathy (DCM) and/or arrhythmogenic right ventricular cardiomyopathy (ARVC). Taken together, our study reveals that splicing diversity of Novex exons across species and Novex variants might play a role in cardiomyopathy.
- Cardiomyopathy: An Overview. [Journal Article]
- AFAm Fam Physician 2017 Nov 15; 96(10):640-646
- The definition and classification of cardiomyopathy have evolved considerably in recent years. Cardiomyopathy can be separated into primary (genetic, mixed, or acquired) and secondary categories, whi...
The definition and classification of cardiomyopathy have evolved considerably in recent years. Cardiomyopathy can be separated into primary (genetic, mixed, or acquired) and secondary categories, which result in varied phenotypes including dilated, hypertrophic, and restrictive patterns. Hypertrophic cardiomyopathy is the most common primary cardiomyopathy and can cause exertional dyspnea, presyncope, atypical chest pain, heart failure, and sudden cardiac death. Dilated cardiomyopathy can be genetic or acquired and typically presents with classic symptoms of heart failure with reduced ejection fraction. Restrictive cardiomyopathy is much less common and often associated with systemic disease. Family physicians should be alert for acquired variants of cardiomyopathy, including peripartum and stress-induced cardiomyopathy, as well as rare variants, such as arrhythmogenic right ventricular dysplasia and left ventricular noncompaction. In addition to history and physical examination, diagnosis of cardiomyopathy includes electrocardiography and echocardiography testing. Treatment may include appropriately staged therapy for heart failure, appropriate activity restriction, evaluation for implantable cardioverter-defibrillator placement, and consideration of heart transplantation in refractory cases. Genetic testing of families is an emerging modality with some potential to augment traditional screening performed by family physicians.
- Right ventricular systolic echocardiographic parameters in dilated cardiomyopathy and prognosis. [Journal Article]
- TMTunis Med 2017; 95(2):87-91
- CONCLUSIONS: TAPSE, Sa, Tei index and strain of the lateral wall of the RV are independent predictors of major cardiovascular event in non ischemic dilated cardiomyopathy.
- [Multislice spiral computed tomography of the heart in dilated cardiomyopathy: possibilities in the verification of myocarditis (in comparison with myocardial biopsy) and in the evaluation of prognosis]. [Journal Article]
- TATer Arkh 2017; 89(12):15-27
- CONCLUSIONS: MSCT with the assessment of delayed contrast enhancement (and simultaneous CT coronary angiography) can be used for the non-invasive diagnosis of myocarditis in patients with DCM, including that in the presence of contraindications to MRI. DMCAA correlates with the presence of myocarditis, its activity, the degree of functional disorders, and prognosis.
- GDF-15 is a better complimentary marker for risk stratification of arrhythmic death in non-ischaemic, dilated cardiomyopathy than soluble ST2. [Journal Article]
- JCJ Cell Mol Med 2018 Feb 04
- Growth differentiation factor (GDF)-15 and soluble ST2 (sST2) are established prognostic markers in acute and chronic heart failure. Assessment of these biomarkers might improve arrhythmic risk strat...
Growth differentiation factor (GDF)-15 and soluble ST2 (sST2) are established prognostic markers in acute and chronic heart failure. Assessment of these biomarkers might improve arrhythmic risk stratification of patients with non-ischaemic, dilated cardiomyopathy (DCM) based on left ventricular ejection fraction (LVEF). We studied the prognostic value of GDF-15 and sST2 for prediction of arrhythmic death (AD) and all-cause mortality in patients with DCM. We prospectively enrolled 52 patients with DCM and LVEF ≤ 50%. Primary end-points were time to AD or resuscitated cardiac arrest (RCA), and secondary end-point was all-cause mortality. The median follow-up time was 7 years. A cardiac death was observed in 20 patients, where 10 patients had an AD and 2 patients had a RCA. One patient died a non-cardiac death. GDF-15, but not sST2, was associated with increased risk of the AD/RCA with a hazard ratio (HR) of 2.1 (95% CI = 1.1-4.3; P = .031). GDF-15 remained an independent predictor of AD/RCA after adjustment for LVEF with adjusted HR of 2.2 (95% CI = 1.1-4.5; P = .028). Both GDF-15 and sST2 were independent predictors of all-cause mortality (adjusted HR = 2.4; 95% CI = 1.4-4.2; P = .003 vs HR = 1.6; 95% CI = 1.05-2.7; P = .030). In a model including GDF-15, sST2, LVEF and NYHA functional class, only GDF-15 was significantly associated with the secondary end-point (adjusted HR = 2.2; 95% CI = 1.05-5.2; P = .038). GDF-15 is superior to sST2 in prediction of fatal arrhythmic events and all-cause mortality in DCM. Assessment of GDF-15 could provide additional information on top of LVEF and help identifying patients at risk of arrhythmic death.
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- Rare Case of Cocaine-Induced Aortic Aneurysm: A Near Dissection Event. [Journal Article]
- CRCase Rep Cardiol 2017; 2017:1785410
- Cocaine use has been associated with cardiovascular complications such as coronary atherosclerosis, coronary artery spasm, cardiac arrhythmias, acute myocardial infarction, myocarditis, and dilated c...
Cocaine use has been associated with cardiovascular complications such as coronary atherosclerosis, coronary artery spasm, cardiac arrhythmias, acute myocardial infarction, myocarditis, and dilated cardiomyopathies. Aortic dissection is a rare but life-threatening complication of cocaine use. Cocaine and stimulant use can cause aortic aneurysm by increasing the aortic wall stress, and the most feared complications are dissection, rupture, and death. There are no clear guidelines about screening cocaine abusers with CT scan of the chest. We do not know if the number of years of cocaine use or the amount of cocaine use can be associated with higher incidence of aortic aneurysm or dissection. Cocaine-induced aortic aneurysm does not have any specific clinical feature. Common presentation is chest discomfort or chest pain. This common presentation is bewildering enough for clinicians to think of more common causes of chest pain like myocardial infarction and myocarditis. The sudden onset of severe, sharp, stabbing chest or back pain is suggestive of aortic dissection. Here, we present a young otherwise healthy patient with chronic cocaine use presenting with chest pain and found to have significant size aortic aneurysm.