Remote ischemic preconditioning for renal and cardiac protection in congestive heart failure (RICH) trial

NIH RePORTER · VA · I01 · · view on reporter.nih.gov ↗

Abstract

Contrast-associated acute kidney injury (CA-AKI) is a common complication of intravenous, iodinated contrast media, that is widely used for coronary angiography and percutaneous coronary intervention (PCI) in patients with coronary artery disease (CAD) and heart failure (HF). An estimated 38 million people worldwide suffer from HF most frequently as a consequence of CAD, the number one killer of all adults in the US. The expected growth of the elderly population including Veterans is estimated to be paralleled by a significant increase (50% in the US) in the number of patients diagnosed with HF every year. Although PCI restores blood flow to the heart and improves myocardial function in patients with HF, the contrast media used for the procedure can cause CA-AKI, possibly mediated by contrast–induced vasoconstriction of renal blood vessels and free radical–mediated direct renal tubular toxicity. The incidence of CA-AKI is estimated to range between 10 and 50% in patients undergoing coronary angiography and PCI with higher rates in patients with HF with reduced left ventricular ejection fraction (LVEF). In the U.S, approximately 1.4 million coronary angiogram procedures are performed each year. Among the U.S Veterans alone, approximately 30,000 coronary angiograms are performed annually, and over 1 million contrast-enhanced imaging studies are performed for other various purposes. This estimate is expected to increase exponentially in the next few decades. With increasing use of contrast media, the prevalence of CA-AKI is also expected to rise. CA-AKI predicts elevated risk of heart attack, longer hospital stay, more complicated hospitalization course, and higher in-hospital mortality. Although, periprocedural administration of isotonic saline intravenous fluid (IVF) has been the standard intervention to prevent CA- AKI, patients with HF with reduced LVEF may not tolerate IVF. Unfortunately, all the major clinical trials evaluating prophylactic IVF and other agents excluded patients with HF. Currently, there is no alternative preventive therapy for CA-AKI in patients with congestive HF with reduced LVEF who cannot tolerate IVF. This study proposes remote ischemic pre-conditioning (RIPC) elicited by application of one or more, brief episodes of ischemia and reperfusion of a limb, as a promising alternative therapy for preventing or attenuating CA-AKI. Given that renal ischemic injury and tubular toxicity are the most common pathophysiological concepts of CA-AKI, it stands to reason that RIPC may prevent CA-AKI via nitrite-induced vasodilation and damage associated molecular protein -mediated renal cell protection. In the preliminary analysis of data of patients with heart attack, an association of RIPC with lower rate of CA-AKI and in-hospital mortality was observed. In the subgroup with HF with reduced LVEF, RIPC was associated with lower incidence of CA-AKI, HF symptoms and lower level of plasma brain natriuretic peptide (BNP). Taken together, th...

Key facts

NIH application ID
10125428
Project number
1I01CX002045-01A2
Recipient
VETERANS HEALTH ADMINISTRATION
Principal Investigator
Oladipupo Olafiranye
Activity code
I01
Funding institute
VA
Fiscal year
2021
Award amount
Award type
1
Project period
2021-10-01 → 2026-09-30