Functional, biochemical and hemodynamic assessment in stable heart failure patients with reduced ejection fraction: role of the six-minute walking test in a multiparametric outpatient management
N Bonini, M Vitolo, M Mantovani, E Tartaglia, P Trapanese, M Paolini, E Battigaglia, M Izzi, J Galloni, G Procaccia, E Caliano, F Baldisserri, D A Mei, J F Imberti, G BorianiAbstract
Background and aim of the study
This study aimed to evaluate the association between biochemical and hemodynamic assessment with functional capacity by the six-minute walking test (6MWT) distance and their prognostic values for short-term outcomes in stable heart failure patients with reduced ejection fraction (HFrEF) prescribed with full optimized guideline-directed medical therapy (GDMT) undergoing routine follow-up visits.
Methods
A prospective observational study was conducted in stable (defined as no previous HF hospitalization within 3 months) fully GDMT treated HFrEF outpatients. During follow-up visit, each patient underwent a standard and a multiparametric assessment with NT-proBNP point-of-care testing (LumiraDx®), non-invasive stroke volume index (SVi) evaluation by NICaS®, and the 6MWT. Correlation and linear regression analyses were performed to test the association with 6MWT distance, while logistic regression analyses were used to test associations with short-term HF outcome (urgent visit or hospitalization within 3 months). A sensitivity analysis was conducted stratifying patients in three groups according to 6MWT (cut off= 300 m) and stroke volume index (SVi cut off= 35 mL/m²).
Results
After one year of follow-up, seventy-four patients were included (median age 70 y.o., 18.9% female, median LVEF 38.5%). Median NT-proBNP was 820 ng/L, median SVi 35.5 mL/m², and median 6MWT distance 450 m (Figure 1). The 6MWT distance showed a strong inverse correlation with NT-proBNP (Pears.coeff.=-0.54; p=<0.001) and a moderate positive correlation with SVi (Pears.coeff.=0.44; p=<0.001). In multivariable linear regression analysis, NT-proBNP (β = –0.03, p < 0.001) and SVi (β = 3.99, p = 0.008) were independent predictors of walking distance. Overall, 16% of patients experienced the short-term HF outcome and only 6MWT distance was associated at univariate logistic regression analysis with a higher risk of adverse events (OR 0.99 per meter, p = 0.043, figure 1). Patients with both reduced SVi (<35 mL/m²) and impaired functional capacity (<300 m) showed the highest event rates (p=0.033) and markedly elevated NT-proBNP levels (Figure 2). Although not statistically significant, the sensitivity analysis revealed a consistent trend toward a worse outcome in patients with both lower SVi and shorter 6MWT distance (p = 0.054), but not in those with reduced SVi alone, highlighting the importance of the routine 6MWT assessment in HF outpatients (Figure 2).
Conclusions
In a contemporary cohort of full medically treated and stable HF patients, NT-proBNP and the bio-impedance SVi ealuation showed a strong correlation with 6MWT distance and both were independently predictors of the 6MWT distance. Only the 6MWT was significantly associated with short-term outcomes, supporting its prognostic value when routinely assessed during follow-up visit.Figure 1For image description, please refer to the figure legend and surrounding text.Figure 2For image description, please refer to the figure legend and surrounding text.