Emerging therapies for right ventricular dysfunction and failure
Autor: | Duncan J. Stewart, L. Christian Napp, Jason G.E. Zelt, Volker Rudolph, Torben Schubert, Ekaterina Legchenko, Georg Hansmann, Anna Klinke, Marion Müller, Tsukasa Shimauchi, Alexander M.K. Rothman, Sébastien Bonnet |
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Rok vydání: | 2020 |
Předmět: |
Denervation
medicine.medical_specialty Angiogenesis business.industry Context (language use) Inflammation 030204 cardiovascular system & hematology Review Article on Right Ventricular Dysfunction 03 medical and health sciences 0302 clinical medicine 030228 respiratory system Internal medicine medicine.artery microRNA Circulatory system Pulmonary artery medicine Cardiology Progenitor cell medicine.symptom Cardiology and Cardiovascular Medicine business |
Zdroj: | Cardiovasc Diagn Ther |
ISSN: | 2223-3660 2223-3652 |
Popis: | Therapeutic options for right ventricular (RV) dysfunction and failure are strongly limited. Right heart failure (RHF) has been mostly addressed in the context of pulmonary arterial hypertension (PAH), where it is not possible to discern pulmonary vascular- and RV-directed effects of therapeutic approaches. In part, opposing pathomechanisms in RV and pulmonary vasculature, i.e., regarding apoptosis, angiogenesis and proliferation, complicate addressing RHF in PAH. Therapy effective for left heart failure is not applicable to RHF, e.g., inhibition of adrenoceptor signaling and of the renin-angiotensin system had no or only limited success. A number of experimental studies employing animal models for PAH or RV dysfunction or failure have identified beneficial effects of novel pharmacological agents, with most promising results obtained with modulators of metabolism and reactive oxygen species or inflammation, respectively. In addition, established PAH agents, in particular phosphodiesterase-5 inhibitors and soluble guanylate cyclase stimulators, may directly address RV integrity. Promising results are furthermore derived with microRNA (miRNA) and long non-coding RNA (lncRNA) blocking or mimetic strategies, which can target microvascular rarefaction, inflammation, metabolism or fibrotic and hypertrophic remodeling in the dysfunctional RV. Likewise, pre-clinical data demonstrate that cell-based therapies using stem or progenitor cells have beneficial effects on the RV, mainly by improving the microvascular system, however clinical success will largely depend on delivery routes. A particular option for PAH is targeted denervation of the pulmonary vasculature, given the sympathetic overdrive in PAH patients. Finally, acute and durable mechanical circulatory support are available for the right heart, which however has been tested mostly in RHF with concomitant left heart disease. Here, we aim to review current pharmacological, RNA- and cell-based therapeutic options and their potential to directly target the RV and to review available data for pulmonary artery denervation and mechanical circulatory support. |
Databáze: | OpenAIRE |
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