Systemic Embolization and Myocardial Infarction due to Clinically Unrecognized Left Atrial Myxoma

Myxomas are the most common primary tumors of the heart. We report an extraordinary severe case of left atrial myxoma, presenting with stroke, myocardial infarction, and multiple arterial embolism including aorta, splenic and renal arteries, and several peripheral arteries. The patient had previously been diagnosed with systemic vasculitis, a typical but less common finding caused by multiple emboli mimicking vasculitis. The myxoma was removed and atrial septum reconstruction was performed. In summary, early diagnostic differentiation of myxoma from vasculitis is critical, and immediate surgical removal of myxoma is required as the probability of thromboembolic complications increases over time

Functional improvement following direct interventional leaflet repair of severe tricuspid regurgitation

AIMS: Several new percutaneous tricuspid repair systems have recently been introduced as new treatment options for severe tricuspid regurgitation (TR). Clinical improvement following percutaneous tricuspid valve leaflet repair has been demonstrated by recent studies. A possible impact on exercise capacity has not yet been reported. METHODS AND RESULTS: Eleven patients with at least severe TR and successful tricuspid leaflet repair using the PASCAL Ace implant at our cardiology department were included in this analysis. All patients suffered from symptomatic right‐sided heart failure with compromised exercise capacity. Cardiopulmonary exercise testing (CPET), clinical, laboratory, and echocardiographic parameters were assessed at baseline and 3 months follow‐up. The primary endpoint was the change in maximal oxygen consumption [VO(2) max (mL/(min*kg))] at 3 months follow‐up. Secondary endpoints included improvement in TR, cardiac biomarkers, and other clinical outcomes. TR severity at 3 months follow‐up post‐PASCAL Ace implantation was significantly lower than at baseline (P = 0.004). Cardiac biomarkers including high‐sensitivity troponin T and N‐terminal pro‐brain natriuretic peptide as well as right ventricular diameter improved slightly without reaching statistical significance (P = 0.89, P = 0.32, and P = 0.06, respectively). PASCAL Ace implantation resulted in a significant improvement in cardiopulmonary exercise capacity at 3 months follow‐up compared with baseline. Mean VO(2) max improved from 9.5 ± 2.8 to 11.4 ± 3.4 mL/(min*kg) (P = 0.006), VO(2) max per cent predicted from 42 ± 12% to 50 ± 15% (P = 0.004), peak oxygen uptake from 703 ± 175 to 826 ± 198 mL/min (P = 0.004), and O(2) pulse per cent predicted from 67 ± 21% to 81 ± 25% (P = 0.011). Other CPET‐related outcomes did not show any significant change over time. CONCLUSIONS: In this single‐centre retrospective analysis, direct tricuspid valve leaflet repair using the transcatheter PASCAL Ace implant system was associated with a reduced TR severity and improved cardiopulmonary exercise capacity

Epigallocatechin-3-gallate (EGCG) for Clinical Trials: More Pitfalls than Promises?

Epigallocatechin-3-gallate (EGCG), the main and most significant polyphenol in green tea, has shown numerous health promoting effects acting through different pathways, as antioxidant, anti-inflammatory and anti-atherogenic agent, showing gene expression activity, functioning through growth factor-mediated pathways, the mitogen-activated protein kinase-dependent pathway, the ubiquitin/proteasome degradation pathway, as well as eliciting an amyloid protein remodeling activity. However, epidemiological inferences are sometimes conflicting and in vitro and in vivo studies may seem discrepant. Current knowledge on how to enhance bioavailability could be the answer to some of these issues. Furthermore, dose levels, administration frequency and potential side effects remain to be examined

Genomic structural variations lead to dysregulation of important coding and non-coding RNA species in dilated cardiomyopathy

The transcriptome needs to be tightly regulated by mechanisms that include transcription factors, enhancers, and repressors as well as non-coding RNAs. Besides this dynamic regulation, a large part of phenotypic variability of eukaryotes is expressed through changes in gene transcription caused by genetic variation. In this study, we evaluate genome-wide structural genomic variants (SVs) and their association with gene expression in the human heart. We detected 3,898 individual SVs affecting all classes of gene transcripts (e.g., mRNA, miRNA, lncRNA) and regulatory genomic regions (e.g., enhancer or TFBS). In a cohort of patients (n = 50) with dilated cardiomyopathy (DCM), 80,635 non-protein-coding elements of the genome are deleted or duplicated by SVs, containing 3,758 long non-coding RNAs and 1,756 protein-coding transcripts. 65.3% of the SV-eQTLs do not harbor a significant SNV-eQTL, and for the regions with both classes of association, we find similar effect sizes. In case of deleted protein-coding exons, we find downregulation of the associated transcripts, duplication events, however, do not show significant changes over all events. In summary, we are first to describe the genomic variability associated with SVs in heart failure due to DCM and dissect their impact on the transcriptome. Overall, SVs explain up to 7.5% of the variation of cardiac gene expression, underlining the importance to study human myocardial gene expression in the context of the individual genome. This has immediate implications for studies on basic mechanisms of cardiac maladaptation, biomarkers, and (gene) therapeutic studies alike

Atlas of the clinical genetics of human dilated cardiomyopathy

[Abstract] Aim. Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome these limitations and screened all DCM disease genes in a large cohort. Methods and results. In this multi-centre, multi-national study, we have enrolled 639 patients with sporadic or familial DCM. To all samples, we applied a standardized protocol for ultra-high coverage next-generation sequencing of 84 genes, leading to 99.1% coverage of the target region with at least 50-fold and a mean read depth of 2415. In this well characterized cohort, we find the highest number of known cardiomyopathy mutations in plakophilin-2, myosin-binding protein C-3, and desmoplakin. When we include yet unknown but predicted disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations is considerably high. Of note, we find that >38% of patients have compound or combined mutations and 12.8% have three or even more mutations. When comparing patients recruited in the eight participating European countries we find remarkably little differences in mutation frequencies and affected genes. Conclusion. This is to our knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes. Our results underline the high analytical quality and feasibility of Next-Generation Sequencing in clinical genetic diagnostics and provide a sound database of the genetic causes of DCM.Hôpitaux de Paris; PHRC AOM0414

Prevalencia de factores de riesgo cardiovascular en una población adulta ambulatoria urbana: estudio AsuRiesgo, Paraguay

OBJETIVO: Las enfermedades cardiovasculares son la principal causa de mortalidad en el mundo. Aunque la mayoría son prevenibles, su prevalencia sigue aumentando. El objetivo de este estudio fue estimar la prevalencia de factores de riesgo cardiovascular en una población hospitalaria ambulatoria urbana y adulta de Asunción, Paraguay. MÉTODOS: Se realizó un análisis transversal de todos los pacientes incluidos en el estudio prospectivo de prevención cardiovascular AsuRiesgo dirigido al cambio del estilo de vida a un estilo de vida saludable. Se invitó a participar a personas de 18 y más años de edad que se encontraban en las zonas de espera de consultorios de un hospital terciario. Se obtvuvo información anamnésica, antropométrica y de laboratorio. Resultados: Se incluyeron 18 287 pacientes de 51 ± 16 años de edad, de los cuales 67,5% fueron mujeres. La media de peso corporal fue 77,5 ± 16,2 kg y el índice de masa corporal, 29,7 ± 5,9 kg/m². Las prevalencias de antecedentes de infarto de miocardio, accidente vascular cerebral, diabetes mellitus e hipertensión fueron, respectivamente, 2,6, 3, 13,3 y 53%, y las del hábito de fumar, dieta no saludable, sedentarismo y estrés psicológico, 29,3, 41,2, 58,2 y 56,6%. Por último, la prevalencia global de obesidad y sobrepeso fue 79,6%, las de prehipertensión e hipertensión arterial sistémica, 39 y 25%, respectivamente, y la del síndrome metabólico, 34,7%. CONCLUSIONES: Si bien las prevalencias del hábito de fumar, hipertensión arterial sistémica y diabetes mellitus fueron bajas, las de obesidad, sedentarismo, estrés psicológico, dieta no saludable y síndrome metabólico fueron muy elevadas, lo cual justifica una acción global para prevenir discapacidades o fallecimientos por enfermedad isquémica cardiaca o cerebral. La implementación urgente de los programas con estos fines a escala nacional es imperativa