Hypocapnia is an independent predictor of in‐hospital mortality in acute heart failure

Abstract

Aims Acute heart failure (AHF) poses a major threat to hospitalized patients for its high mortality rate and serious complications. The aim of this study is to determine whether hypocapnia [defined as the partial pressure of arterial carbon dioxide (PaCO 2 ) below 35 mmHg] on admission could be associated with in‐hospital all‐cause mortality in AHF. Methods and results A total of 676 patients treated in the coronary care unit for AHF were retrospectively analysed, and the study endpoint was in‐hospital all‐cause mortality. The 1:1 propensity score matching (PSM) analysis, Kaplan–Meier curve, and Cox regression model were used to explore the association between hypocapnia and in‐hospital all‐cause mortality in AHF. Receiver operating characteristic (ROC) curve and Delong's test were used to assess the performance of hypocapnia in predicting in‐hospital all‐cause mortality in AHF. The study cohort included 464 (68.6%) males and 212 (31.4%) females, and the median age was 66 years (interquartile range 56–74 years). Ninety‐eight (14.5%) patients died during hospitalization and presented more hypocapnia than survivors (76.5% vs. 45.5%, P < 0.001). A 1:1 PSM was performed between hypocapnic and non‐hypocapnic patients, with 264 individuals in each of the two groups after matching. Compared with non‐hypocapnic patients, in‐hospital mortality was significantly higher in hypocapnic patients both before (22.2% vs. 6.8%, P < 0.001) and after (20.8% vs. 8.7%, P < 0.001) PSM. Kaplan–Meier curve showed a significantly higher probability of in‐hospital death in patients with hypocapnia before and after PSM (both P < 0.001 for the log‐rank test). Multivariate Cox regression analysis showed that hypocapnia was an independent predictor of AHF mortality both before [hazard ratio (HR) 2.22; 95% confidence interval (CI) 1.23–3.98; P = 0.008] and after (HR 2.19; 95% CI 1.18–4.07; P = 0.013) PSM. Delong's test showed that the area under the ROC curve was improved after adding hypocapnia into the model (0.872, 95% CI 0.839–0.901 vs. 0.855, 95% CI 0.820–0.886, P = 0.028). PaCO 2 was correlated with the estimated glomerular filtration rate ( r = 0.20, P = 0.001), left ventricular ejection fraction ( r = 0.13, P < 0.001), B‐type natriuretic peptide ( r = −0.28, P < 0.001), and lactate ( r = −0.15, P < 0.001). Kaplan–Meier curve of PaCO 2 tertiles and multivariate Cox regression analysis showed that the lowest PaCO 2 tertile was associated with increased risk of in‐hosp...

Sodium‐glucose transporter 2 inhibitors may improve the prognosis of acute heart failure by correcting hypocapnia

“… 2 We showed that CO 2 levels were significantly negatively correlated with B‐type natriuretic peptide ( r = −0.28, P < 0.001) and positively correlated with the estimated glomerular filtration rate ( r = 0.20, P = 0.001) and left ventricular ejection fraction ( r = 0.13, P < 0.001). 2 Indeed, as suggested by Guarnaccia et al, hypocapnia could also form a vicious circle with lower circulating oxygen in the progression of AHF. 3 This could cause a persistent lack of myocardial energy and deterioration of haemodynamics, ultimately leading to multi‐organ damage, including kidney damage.…”

“…Our previous work highlighted hypocapnia as a manifestation of cardiac and renal impairment during the progression of AHF 2 . We showed that CO 2 levels were significantly negatively correlated with B‐type natriuretic peptide ( r = −0.28, P < 0.001) and positively correlated with the estimated glomerular filtration rate ( r = 0.20, P = 0.001) and left ventricular ejection fraction ( r = 0.13, P < 0.001) 2 . Indeed, as suggested by Guarnaccia et al, hypocapnia could also form a vicious circle with lower circulating oxygen in the progression of AHF 3 .…”

“…As outlined by Guarnaccia et al, 1 SGLT2i could reduce glucose utilization and promote fatty acid utilization to achieve higher ATP production, a process that increases CO 2 production and an energy benefit. We agree with Guarnaccia et al and would like to further explore whether the administration of SGLT2i improves the in‐hospital prognosis of patients with hypocapnia.…”

“…SGLT2i have been reported to reprogram the energy metabolism of the myocardium, such as increasing fatty acid utilization to produce more ATP, 3 a process accompanied by more CO 2 production, 1 so the up‐regulation of CO 2 levels could be a reflection of the energy benefits of SGLT2i. Besides, SGLT2i have a diuretic effect and could inhibit sodium‐hydrogen exchangers of renal tubules, 4 reducing the patient's circulating volume burden and then improving the acid‐base profile to attenuate hypocapnia.…”

Prognostic effects of arterial partial pressure of carbon dioxide in critical patients with acute heart failure: a retrospective cohort study

“…In addition, Carrillo-Aleman et al [19] demonstrated that hypocapnia correlated with an increase of the in-hospital death rate in a population with cardiogenic acute pulmonary edema. Tang et al [20] showed that hypocapnia played an important role in the increased hospital death rate in AHF patients. The present study also suggested that lower PaCO 2 was related to a greater in-hospital death rate.…”