In patients with cardiogenic shock (CS) who were treated with exogenous ketone ester (KE), investigators observed improved cardiac output, biventricular function, tissue oxygenation and glycemic control, a new study shows. These findings were reported by Kristoffer Berg-Hansen, MD, of Aarhus University Hospital, Denmark, and colleagues, in an article published Wednesday online in JACC: Heart Failure. Although there are some current treatment strategies for CS, such as improving hemodynamic status, the state of low cardiac output is consistently life-threatening. Patients with CS need new and more effective treatment options, the authors wrote. This double-blind, crossover, controlled study examined the effects of KE in 12 patients (mean age=73 years, 8% female) with CS. Patients received both the treatment, an enteral bolus of KE, and the placebo, an isocaloric, isovolumic solution containing maltodextrin. They were randomly assigned to one or the other treatment first, with a 3-hour washout period before receiving the other treatment. Pulmonary artery catheterization, arterial blood sampling, echocardiography and near-infrared spectroscopy were used to assess the patients hourly for three hours after each intervention. The primary endpoint of this study was the area under the 3-hour curve, an expression of cardiac output. Patients who received KE had increased levels of circulating 3-hydroxybutyrate (2.9 ± 0.3 mmol/L versus 0.2 ± 0.3 mmol/L, p < 0.001), increased cardiac power output (0.07 W [95% confidence interval (CI)}=0.01-0.14]; p=0.037), increased mixed venous saturation (3 percentage points [95% CI=1-5 percentage points]), increased forearm perfusion (3 percentage points [95% CI=0-6 percentage points]; p=0.026) and were associated with augmented cardiac output (area under the curve of relative change=61 ± 22 L versus 1 ± 18 L, p=0.044). Heart rate and mean arterial and pulmonary arterial pressures were comparable, while reduction was observed in right ventricular filling pressure (p=0.048) and left ventricular filling pressure(p=0.017). Improved left ventricular ejection fraction was observed (by 4 percentage points; 95% CI=2-6 percentage points; p=0.005). There was no observed change in insulin levels, but there was a decrease in glucose levels by 2.6 mmol/L (95% CI: -5.2 to 0.0; p=0.047). There were some limitations to this study. First, the design was a crossover investigation, which carries the risk of the carryover bias. In addition, patients with CS are at greater risk for developing gastroparesis, which can delay biological responses to KE. Overall, the patients receiving KE administration had increased levels of circulating 3-OHB, and the investigators observed clinically significant, favorable hemodynamic effects. In an accompanying editorial, Gary D. Lopaschuk, PhD, and Qutuba G. Karwi, BSc(Hons), MSc, PhD, of the University of Alberta, Edmonton, and the Memorial University of Newfoundland and Labrador, Saint John’s, discussed energy production fuels of the heart and their accompanying effects on cardiac contractile function, including ketones. The editorialists explained potential reasons why KE assisted patients in this present study. “The robust acute effects of KE in CS patients are likely mediated by acutely increasing ketone delivery to the heart and enhancing cardiac ketone oxidation and ATP [adenosine triphosphate] production. However, this has yet to be directly assessed,” they wrote. “Developing a clinically translational approach to enhance circulating ketone body levels is an active area of research.” Other approaches have been used to enhance cardiac efficiency, the editorialists noted. Strategies such as medium-chain triacylglycerol administration, sodium-glucose cotransporter-2 inhibitors and ketogenic diet feeding are examples. The editorialists concluded, “The study by Hansen et al. provides an important characterization of the hemodynamic effects and safety of orally administering KE as an adjunct therapy to inotropes to treat patients with CS.” They also wrote that this study is foundational for future large trials studying similar mechanisms. Sources: Berg-Hansen K, Christensen KH, Gopalasingam N, et al. Beneficial Effects of Ketone Ester in Patients With Cardiogenic Shock: . JACC Heart Fail. 2023 July 12 (Article in Press). Lopaschuk GD, Karwi QG. Jump Starting the Heart: Ketone Esters Improve Cardiac Function in Patients With Cardiogenic Shock. JACC Heart Fail. 2023 July 12 (Article in Press). Image Credit: Jonatan – stock.adobe.com