In recent years, neuromodulation has been gaining popularity as a potential therapy method for various ailments, including acute heart failure (AHF). There are currently five clinical trials using neuromodulation techniques to improve hemodynamics among patients with AHF. However, these studies can be limited by their outcome measurement methods as they utilize variables such as C-Reactive protein levels (CRP), or blood pressure (BP), and adverse events that can be easily confounded. Thus, we propose that micro-RNAs (miRNAs) have great potential to be reliable biomarkers that would significantly enhance outcome measurements of these studies as changing levels of various miRNAs are correlated with many different aspects of AHF.
Neuromodulation; Micro-RNAs; Acute heart failure; Autonomic nervous system
Neuromodulation refers to manipulating the autonomic nervous system using electrical, electromagnetic, and chemical methodologies for therapeutic use . It strives for the long-term activation, inhibition, modification, and regulation of neural activity through alternating synaptic activity and potentiation . It has been used for over 20 years in neurological diseases such as movement disorders like Parkinson’s disease  and stroke .
More recently, there has been a growing interest in cardiovascular neuromodulation approaches due to the significant role that the autonomic nervous system plays in maintaining the integrity and proper functioning of the cardiovascular system (i.e., clinical studies using left ventricular assist devices (LVAD) and cardiac resynchronization therapy (CRT) for autonomic stimulation). Some of these approaches include vagus nerve stimulation , renal denervation , spinal cord stimulation , and baroreceptor activation therapy . Heart failure has also been an increasingly popular topic of research within the field of neuromodulation as it remains the most common diagnosis for hospital admission in patients greater than 65 years of age . Specifically, acute heart failure is associated with a 23% readmission rate at 30 days, a 6-fold increased mortality risk at 60 days, and a 2-fold increased mortality risk at two years .
Neuromodulation clinical studies focused on AHF have shown promise, although they conflict in the target site, duration of the study, and outcome measurement. Many of these studies are limited by their outcome measurement methods, ranging from easily confounded protein markers like CRP and BP to measuring adverse events and mortality rates. Thus, there is a need for a more specific, reliable biomarker that can be tracked to assess the outcomes of these neuromodulation studies. Of recent, miRNAs have been gaining substantial traction as potential biomarkers for various disease states due to their ease of measurement, high specificity for tissue or cell types, durability, and practicality . Given the growing interest and strength of data highlighting the benefit of using miRNAs as biomarkers in cardiovascular disease states, we are the first to suggest implementing miRNA measurements specifically into acute heart failure neuromodulation studies. This could be a promising strategy to obtain more efficient, robust, and specific outcome measurements in a rapidly growing cardiovascular device therapy research field.