Left atrial function and maximal exercise capacity in heart failure with preserved and mid-range ejection fraction

Abstract

Aims: Exercise intolerance is the leading manifestation of heart failure with preserved or mid-range ejection fraction (HFpEF or HFmrEF), and left atrial (LA) function might contribute to modulating left ventricular filling and pulmonary venous pressures. We aim to assess the association between LA function and maximal exercise capacity in patients with HFpEF or HFmrEF.

Methods and results: Sixty-five patients, prospectively enrolled in the German HFpEF Registry, were analysed. Inclusion criteria were New York Heart Association functional class ≥ II, left ventricular ejection fraction > 40%, structural heart disease or diastolic dysfunction, and elevated levels of N terminal pro brain natriuretic peptide (NT-proBNP). LA function was evaluated through speckle-tracking echocardiography by central reading in the Charité Academic Echocardiography core lab. All patients underwent maximal cardiopulmonary exercise test and were classified according to a peak VO₂ cut-off of prognostic value (14 mL/kg/min). NT-pro-BNP was measured. Twenty-nine patients (45%) reached a peak VO₂ < 14 mL/kg/min (mean value 12.4 ± 1.5) and 36 patients (55%) peak VO₂ ≥ 14 mL/kg/min (mean value 19.4 ± 3.9). There was no significant difference in left ventricular ejection fraction (60 ± 9 vs. 59 ± 8%), left ventricular mass (109 ± 23 vs. 112 ± 32 g/m² ), LA volume index (45 ± 17 vs. 47 ± 22 mL/m² ), or E/e´ (13.1 ± 4.7 vs. 13.0 ± 6.0) between these groups. In contrast, all LA strain measures were impaired in patients with lower peak VO₂ (reservoir strain 14 ± 5 vs. 21 ± 9%, P = 0.002; conduit strain 9 ± 2 vs. 13 ± 4%, P = 0.001; contractile strain 7 ± 4 vs. 11 ± 6%, P = 0.02; reported lower limits of normality for LA reservoir, conduit and contractile strains: 26.1%, 12.0%, and 7.7%). In linear regression analysis, lower values of LA reservoir strain were associated with impaired peak VO₂ after adjustment for age, sex, body mass index, heart rhythm (sinus/AFib), and log-NTproBNP [β 0.29, 95% confidence interval (CI) 0.02-0.30, P = 0.02], with an odds ratio 1.22 (95% CI 1.05-1.42, P = 0.01) for peak VO₂ < 14 mL/kg/min for LA reservoir strain decrease after adjustment for these five covariates. Adding left ventricular ejection fraction, it did not influence the results. On the other hand, the addition of LA strain to the adjustment parameters alone described above provided a significant increase of the predictive value for lower peak VO₂ values (R² 0.50 vs. 0.45, P = 0.02). With receiver operating characteristic curve analysis, we identified LA reservoir strain < 22% to have 93% sensitivity and 49% specificity in predicting peak VO₂ < 14 mL/kg/min. Using this cut-off, LA reservoir strain < 22% was associated with peak VO₂ < 14 mL/kg/min in logistic regression analysis after comprehensive adjustment for age, sex, body mass index, heart rhythm, and log-NTproBNP [odds ratio 95% CI 10.4 (1.4-74), P = 0.02].

Conclusions: In this HFpEF and HFmrEF cohort, a reduction in LA reservoir strain was a sensible marker of decreased peak exercise capacity. Therefore, LA reservoir strain might be of clinical value in predicting exercise capacity in patients with HFpEF or HFmrEF.

Keywords: Cardiopulmonary exercise test; Heart failure; Left atrial strain; Mid-range ejection fraction; Preserved ejection fraction.

Figure 1

Left atrial function assessed by the speckle tracking echocardiography. Example of three‐beat strain curves in the three atrial segments in apical four‐chamber view. The mean value of the first positive peak of the three curves represent the reservoir strain, and that of the second lower positive peak represents the contractile strain.

Figure 2

Association of left atrial reservoir strain and contractile strain (A), left ventricular ejection fraction and left ventricular global longitudinal strain (B), and E/e´ and left atrial volume index (C) with peak VO₂ (mL/kg/min).

Figure 3

Association of LV and LA parameters with severely reduced exercise capacity (peak VO₂ < 14 mL/kg/min). Logistic regression analysis for predictability of peak VO₂ < 14 mL/kg/min: LVEF 1 unit (%) decrease odds ratio (OR) 95% confidence interval (CI) 0.99 (0.93–1.05), LV mass index 1 unit (g/m²) increase OR 95% CI 0.99 (0.98–1.01), LA volume index 1 unit (mL/m²) increase OR 95% CI 0.99 (0.97–1.02), LA reservoir strain 1 unit (%) decrease OR 95% CI 1.12 (1.03–1.20), E/e´ 1 unit increase OR 95% CI 1.01 (0.91–1.10). LA, left atrium; LVEF, left ventricular ejection fraction.