Myocardial work analysis in patient with heart failure reveals subtype-specific alterations of cardiac performance during dynamic stress: the mystress pilot study

Background Myocardial Work (MyW) analysis is an echocardiography-based non-invasive tool that uses the pressure-strain relationship to quantify myocardial performance. Using MyW, we aimed to gain deeper insights into the pathophysiology of left ventricular (LV) performance during physical stress in patients with chronic heart failure (HF) compared to healthy controls. Methods & Results The MyStress Pilot Study enrolled 24 extensively phenotyped individuals from a convenience sample: 12 patients with chronic stable HF (n=6 with reduced ejection fraction [HFrEF], n=6 with preserved ejection fraction [HFpEF]) and 12 healthy controls. Study participants were aged 40-80 years, and subgroups (HFrEF vs HFpEF vs healthy) were stratified by sex (1:1 ratio). Exercise stress echocardiography (ESE) was performed using a 45° tilted ergometer and followed a pre-specified protocol: start at 15 W, followed by 15 W increments every 4 minutes at a constant pedaling rate of 60/min. For the current analysis, we used the measurements up to 75 W. Echocardiographic images were analyzed using EchoPAC Version 202, GE. To assess group differences and trends, we used generalized linear mixed models (GLMM) with random intercepts and slopes for global constructive work (GCW), global work index (GWI), and global work efficiency (GWE), while global wasted work (GWW) was log-transformed (after assessing for homoscedasticity and normality). As shown in the table, HF patients were older than the control group, but no differences were apparent regarding body mass index, heart rate, blood pressure, or peripheral vascular resistance (at rest). Patients with HFrEF reached a median stress level of 75 W (quartiles: 53–98), equal to patients with HFpEF (75 W [68–75], p=0.818). However, both groups reached lower workloads than healthy controls: 120 W (105–146), p<0.001; table. At rest, MyW indices in HF patients were different from healthy controls exhibiting lower constructive work in HFrEF and higher wasted work in both HF groups (table & figure). In HFrEF patients compared to healthy individuals, constructive work and work index remained unchanged during ESE (figure), whereas patients with HFpEF showed lower values of constructive work and higher values of wasted work – despite similar blood pressure levels as observed in healthy individuals. Conclusion This pilot study utilized MyW and found that the myocardial response to dynamic stress in chronic HF depends on the subtype (HFrEF vs HFpEF). While wasted work was increased in both HF subgroups, constructive work was reduced in in HFrEF, only. These differences were apparent at rest and were aggravated during dynamic stress. MyW analyses have the potential to facilitate a more nuanced evaluation of myocardial performance in patients with HF. Once validated across larger cohorts, these analyses could inform individualized treatment allocation and assess treatment response.