Holistic integrative interpretation for similarities and differences of cardiopulmonary exercise testing (CPET) pathophysiological characteristics in patients with left and right heart failure.

Background: This study is based on the theory of Holistic Integrative Physiology and Medicine (HIPM), which emphasizes a comprehensive understanding of the interplay of respiratory-circulatory-metabolic integration regulation. Within this theory, we recognize that left heart failure (LHF) and right heart failure (RHF) present distinct pathophysiological profiles, especially when assessed through cardiopulmonary exercise testing (CPET). We seek to elucidate the similarities and differences in CPET responses between LHF and RHF, thereby enhancing our understanding of their unique exercise pathophysiology.

Methods: In this retrospective study, we included 123 patients diagnosed with LHF and 101 patients with RHF, all of whom were treated at Fuwai Hospital between 2018 and 2023. Each patient underwent standard CPET, along with routine medical examinations. During the CPET, we calculated the key parameters, identified the presence of oscillatory breathing (OB), and assessed the occurrence of exercise-induced right-to-left shunting (R-LShunt) using standard methodologies. Additionally, a control group comprising 81 normal subjects (NS) also underwent CPET to provide a baseline for comparison. The data collected from all three groups-LHF patients, RHF patients, and NS-were then subjected to a comprehensive analysis. We used analysis of variance (ANOVA)-based statistical methods to analyze the differences in CPET parameters among these groups.

Results: Peak oxygen uptake ( ) in LHF [48.04±17.14 percentage of predicted (%pred)] and RHF (53.68±15.10 %pred) was significantly lower than in NS (85.37±14.01 %pred) (NS versus LHF and RHF, both P<0.001). Notably, the LHF demonstrated markedly lower exercise capacity in both peak (%pred) and anaerobic threshold (AT, %pred), but higher oxygen uptake efficiency plateau (OUEP, %pred) than the RHF group (P=0.008, 0.009, and <0.001, respectively). In the LHF group, OB manifestations were observed in 72 cases (59%), and in the RHF group, R-LShunt manifestations appeared in 64 cases (63%). Within the LHF subgroup, those with OB showed a significantly lower peak (39.95±12.84 %pred) compared to those without OB (59.46±15.99 %pred, P<0.001). In the RHF group, peak was also lower in the R-LShunt subgroup (50.1±12.52 %pred) compared to the no R-LShunt subgroup (59.87±17.24 %pred, P=0.001). Additionally, the R-LShunt group displayed an aberrant pattern of almost persistently decreased partial pressure of end-tidal carbon dioxide (PETCO) during CPET.

Conclusions: LHF patients exhibited lower exercise tolerance, in contrast to RHF patients, but showed a relatively small decrease in gas exchange capacity. Nevertheless, both LHF and RHF exhibited general functional limitations during CPET. Notably, patients exhibiting OB in the context of LHF, and those with R-LShunt in RHF, presented with even more pronounced functional limitations compared to their counterparts without these specific pathophysiological features.