SummaryTo understand the process of cardiac aging, it is of crucial importance to gain insight into the age-related changes in gene expression in the senescent failing heart. Age-related cardiac remodeling is known to be accompanied by changes in extracellular matrix (ECM) gene and protein levels. Small noncoding microRNAs regulate gene expression in cardiac development and disease and have been implicated in the aging process and in the regulation of ECM proteins. However, their role in age-related cardiac remodeling and heart failure is unknown. In this study, we investigated the aging-associated microRNA cluster 17-92, which targets the ECM proteins connective tissue growth factor (CTGF) and thrombospondin-1 (TSP-1). We employed aged mice with a failure-resistant (C57Bl6) and failure-prone (C57Bl6 · 129Sv) genetic background and extrapolated our findings to human age-associated heart failure. In aging-associated heart failure, we linked an aging-induced increase in the ECM proteins CTGF and TSP-1 to a decreased expression of their targeting microRNAs 18a, 19a, and 19b, all members of the miR-17-92 cluster. Failure-resistant mice showed an opposite expression pattern for both the ECM proteins and the microRNAs. We showed that these expression changes are specific for cardiomyocytes and are absent in cardiac fibroblasts. In cardiomyocytes, modulation of miR-18 ⁄ 19 changes the levels of ECM proteins CTGF and TSP-1 and collagens type 1 and 3. Together, our data support a role for cardiomyocyte-derived miR-18 ⁄ 19 during cardiac aging, in the fine-tuning of cardiac ECM protein levels. During aging, decreased miR-18 ⁄ 19 and increased CTGF and TSP-1 levels identify the failure-prone heart.

Heart failure (HF) is one of the most complex chronic disorders with high prevalence, mainly due to the ageing population and better treatment of underlying diseases. Prevalence will continue to rise and is estimated to reach 3% of the population in Western countries by 2025. It is the most important cause of hospitalisation in subjects aged 65 years or more, resulting in high costs and major social impact. The current “one-size-fits-all” approach in the treatment of HF does not result in best outcome for all patients. These facts are an imminent threat to good quality management of patients with HF. An unorthodox approach from a new vision on care is required. We propose a novel predictive, preventive and personalised medicine approach where patients are truly leading their management, supported by an easily accessible online application that takes advantage of artificial intelligence. This strategy paper describes the needs in HF care, the needed paradigm shift and the elements that are required to achieve this shift. Through the inspiring collaboration of clinical and high-tech partners from North-West Europe combining state of the art HF care, artificial intelligence, serious gaming and patient coaching, a virtual doctor is being created. The results are expected to advance and personalise self-care, where standard care tasks are performed by the patients themselves, in principle without involvement of healthcare professionals, the latter being able to focus on complex conditions. This new vision on care will significantly reduce costs per patient while improving outcomes to enable long-term sustainability of top-level HF care.

Telemedicine in chronic diseases like heart failure is rapidly evolving and has two important goals: improving and individualising care as well as reducing costs. In this paper, we provide a critical and an updated review of the current evidence by discussing the most important trials, meta-analyses and systematic reviews. So far, evidence for the CardioMEMS device is most convincing. Other trials regarding invasive and non-invasive telemonitoring and telephone support show divergent results, but several meta-analyses and systematic reviews uniformly reported a beneficial effect. Voice-over systems and ECG monitoring had neutral results. Lack of direct comparison between different modalities makes it impossible to determine the most effective method. Dutch studies showed predominantly non-significant results, mainly due to underpowered studies or because of a high standard of usual care. There are no conclusive results on cost-effectiveness of telemedicine because of the above shortcomings. The adherence of elderly patients was good in the trials, being essential for the compliance of telemedicine in the entire heart failure population. In the future perspective, telemedicine should be better standardised and evolve to be more than an addition to standard care to improve care and reduce costs.

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Previous uncontrolled studies suggested a possible benefit of intravenous immunoglobulin (IVIg) in parvovirus B19 (B19V)-related dilated cardiomyopathy (DCM). This randomized, double-blind, placebo-controlled, single-centre trial investigated the benefits of IVIg beyond conventional therapy in idiopathic chronic DCM patients with B19V persistence.