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- The circulating non-coding RNA landscape for biomarker research : lessons and prospects from cardiovascular diseasesPublication . Stępień, Ewa; Costa, Marina C.; Kurc, Szczepan; Drożdż, Anna; Cortez-Dias, Nuno; Enguita, Francisco J.Pervasive transcription of the human genome is responsible for the production of a myriad of non-coding RNA molecules (ncRNAs) some of them with regulatory functions. The pivotal role of ncRNAs in cardiovascular biology has been unveiled in the last decade, starting from the characterization of the involvement of micro-RNAs in cardiovascular development and function, and followed by the use of circulating ncRNAs as biomarkers of cardiovascular diseases. The human non-coding secretome is composed by several RNA species that circulate in body fluids and could be used as biomarkers for diagnosis and outcome prediction. In cardiovascular diseases, secreted ncRNAs have been described as biomarkers of several conditions including myocardial infarction, cardiac failure, and atrial fibrillation. Among circulating ncRNAs, micro-RNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) have been proposed as biomarkers in different cardiovascular diseases. In comparison with standard biomarkers, the biochemical nature of ncRNAs offers better stability and flexible storage conditions of the samples, and increased sensitivity and specificity. In this review we describe the current trends and future prospects of the use of the ncRNA secretome components as biomarkers of cardiovascular diseases, including the opening questions related with their secretion mechanisms and regulatory actions.
- Optimizing prognosis in atrial fibrillation: a call to action in PortugalPublication . Ferreira, Jorge; António, Natália; Cortez-Dias, Nuno; Gonçalves, Luciana Ricca; Sargento-Freitas, João; von Hafe, Pedro; Gil, VictorAtrial fibrillation (AF), the most common arrhythmia in the adult population worldwide, represents a significant burden in terms of cardiovascular mortality and morbidity and has repercussions on health economics. Oral anticoagulation (OAC) is key to stroke prevention in AF and, in recent years, results from landmark clinical trials of non-vitamin K oral anticoagulants (NOAC) have triggered a paradigm shift in thrombocardiology. Despite these advances, there is still a significant residual vascular risk associated with silent AF, bleeding, premature sudden death and heart failure. The authors review AF epidemiologic data, the importance of new tools for early AF detection, the current role of catheter ablation for rhythm control in AF, the state-of-the-art in periprocedural OAC, the optimal management of major bleeding, the causes of residual premature death and future strategies for improvements in AF prognosis.
- Triple-site pacing for cardiac resynchronization in permanent atrial fibrillation : acute phase results from a prospective observational studyPublication . Marques, Pedro; Menezes, Miguel Nobre; Lima da Silva, Gustavo; Bernardes, Ana; Magalhaes, Andreia; Cortez-Dias, Nuno; Carpinteiro, Luis A.; Sousa, João Carvalho de; Pinto, Fausto J.Introduction and Aim: Multi-site pacing is emerging as a new method for improving response to cardiac resynchronization therapy (CRT), but has been little studied, especially in patients with atrial fibrillation. We aimed to assess the effects of triple-site (Tri-V) vs. biventricular (Bi-V) pacing on hemodynamics and QRS duration. Methods: This was a prospective observational study of patients with permanent atrial fibrillation and ejection fraction <40% undergoing CRT implantation (n=40). One right ventricular (RV) lead was implanted in the apex and another in the right ventricular outflow tract (RVOT) septal wall. A left ventricular (LV) lead was implanted in a conventional venous epicardial position. Cardiac output (using the FloTracTM VigileoTM system), mean QRS and ejection fraction were calculated. Results: Mean cardiac output was 4.81±0.97 l/min with Tri-V, 4.68±0.94 l/min with RVOT septal and LV pacing, and 4.68±0.94 l/min with RV apical and LV pacing (p<0.001 for Tri-V vs. both BiV). Mean pre-implantation QRS was 170±25 ms, 123±18 ms with Tri-V, 141±25 ms with RVOT septal pacing and LV pacing and 145±19 with RV apical and LV pacing (p<0.001 for Tri-V vs. both BiV and pre-implantation). Mean ejection fraction was significantly higher with Tri-V (30±11%) vs. Bi-V pacing (28±12% with RVOT septal and LV pacing and 28±11 with RV apical and LV pacing) and pre-implantation (25±8%). Conclusion: Tri-V pacing produced higher cardiac output and shorter QRS duration than Bi-V pacing. This may have a significant impact on the future of CRT.
- circRNA-miRNA cross-talk in the transition from paroxysmal to permanent atrial fibrillationPublication . Costa, Marina C.; Cortez-Dias, Nuno; Gabriel, André F.; De Sousa, João; Fiuza, Manuela; Gallego, Javier; Nobre, Ângelo; Pinto, Fausto J.; Enguita, Francisco J.Background: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia in western countries. The factors governing the progression of AF to a permanent chronic condition are still not well characterized. Among epigenetic factors, non-coding RNAs (ncRNAs) such as miRNAs and lncRNAs have been recently described as important players involved in the AF progression. We hypothesize about the existence of additional regulatory layers in AF involving an intricate cross-talk between different ncRNA species, namely miRNAs and circRNAs for the establishment of a chronic AF condition. Methods and results: We have performed an unbiased study analyzing the expression profile for miRNAs and circRNAs in left-atrial biopsies from patients with paroxysmal and permanent AF by RNA-seq. The transition from paroxysmal to permanent AF is characterized by a pattern of down-regulated miRNAs, concomitant to the appearance of specific circRNA species. The analysis of the sponging activities of the circRNAs exclusively expressed in permanent AF samples, allowed us to determine that they could be responsible for the downregulation of specific miRNAs in establishment of a permanent AF condition. Conclusion: Sponging activity of circRNAs sequestering specific miRNAs is an important factor to be considered for the determination of the molecular mechanisms involved in AF progression.