Diastolic dysfunction and mortality in 436 360 men and women: the National Echo Database Australia (NEDA)

Abstract

Aims: To examine the characteristics/prognostic impact of diastolic dysfunction (DD) according to 2016 American Society of Echocardiography (ASE) and European Society of Cardiovascular Imaging (ESCVI) guidelines, and individual parameters of DD.

Methods and results: Data were derived from a large multicentre mortality-linked echocardiographic registry comprising 436 360 adults with ≥1 diastolic function measurement linked to 100 597 deaths during 2.2 million person-years follow-up. ASE/European Association of Cardiovascular Imaging (EACVI) algorithms could be applied in 392 009 (89.8%) cases; comprising 11.4% of cases with 'reduced' left ventricular ejection fraction (LVEF < 50%) and 88.6% with 'preserved' LVEF (≥50%). Diastolic function was indeterminate in 21.5% and 62.2% of 'preserved' and 'reduced' LVEF cases, respectively. Among preserved LVEF cases, the risk of adjusted 5-year cardiovascular-related mortality was elevated in both DD [odds ratio (OR) 1.31, 95% confidence interval (CI) 1.22-1.42; P < 0.001] and indeterminate status cases (OR 1.11, 95% CI 1.04-1.18; P < 0.001) vs. no DD. Among impaired LVEF cases, the equivalent risk of cardiovascular-related mortality was 1.51 (95% CI 1.15-1.98, P < 0.001) for increased filling pressure vs. 1.25 (95% CI 0.96-1.64, P = 0.06) for indeterminate status. Mitral E velocity, septal e' velocity, E:e' ratio, and LAVi all correlated with mortality. On adjusted basis, pivot-points of increased risk for cardiovascular-related mortality occurred at 90 cm/s for E wave velocity, 9 cm/s for septal e' velocity, an E:e' ratio of 9, and an LAVi of 32 mL/m2.

Conclusion: ASE/EACVI-classified DD is correlated with increased mortality. However, many cases remain 'indeterminate'. Importantly, when analysed individually, mitral E velocity, septal e' velocity, E:e' ratio, and LAVi revealed clear pivot-points of increased risk of cardiovascular-related mortality.

Keywords: big; data; diastolic; echocardiography; function; guidelines; mortality.

Figure 1

Study flowchart. This graph shows the key inclusion and exclusion criteria, including the classification of patients according to the ASE/EACVI Diastolic Function algorithm, and the individual diastolic parameters. A total of 436 360 individuals had at least one diastolic function measurement for inclusion in the cohort, with 113 725 individuals (26.1%) with all diastolic function measures available. In ASE/EACVI groups, the percentage in each diastolic function category refers to the percent of the total included in that LVEF category. FU, follow-up.

Figure 2

Five-year adjusted cardiovascular mortality using ASE/EACVI algorithm. This graph shows the fully adjusted pattern of actual 5-year cardiovascular-related mortality in subjects with full 5-year follow-up according to ASE/EACVI diastolic function classification for the ‘preserved EF’ (A) and ‘impaired EF’ (B) algorithms. Both groups were analysed with separate logistic regression models with full adjustment for each of the co-variates with the following odds ratios (±95% CI). Preserved EF: age (per year) OR 1.026 (1.023–1.028)***; Male sex OR 0.992 (0.938–1.049); LVEF OR per unit 0.994 (0.991–0.997)*; Non-sinus rhythm OR 1.695 (1.585–1.812)***; VHD OR 1.655 (1.552–1.766)***; prior mitral or aortic valve replacement (MVR/AVR) OR 1.526 (1.366–1.704)***. Impaired EF: age (per year) OR 1.010 (1.006–1.015)*; Male sex OR 1.063 (0.949–1.191); LVEF OR per unit 0.981 (0.976–0.986)*; Non-sinus rhythm OR 1.026 (0.922–1.142); VHD OR 1.351 (1.215–1.503)**; MVR/AVR OR 1.139 (0.953–1.362). The smaller graph inset show long-term Cox-proportional mortality hazard adjusted for age and sex. The top graph refers to preserved LVEF, and the bottom graph to impaired LVEF. LVEF, left ventricular ejection fraction (%), non-sinus rhythm is compared with patients in sinus rhythm during echocardiography; VHD, valvular heart disease, defined as an aortic valve area <1.2 cm², mean AV or MV gradient >20 or 5 mmHg, respectively, or moderate or greater mitral or aortic regurgitation. The significance for each odds ratio is denoted by *P < 0.05, **P < 0.01, and ***P < 0.001.

Figure 3

Long-term all-cause mortality for each diastolic parameter. These graphs plot the Cox-proportional hazards for long-term all-cause mortality adjusted for age and sex, for each diastolic parameter in unit increments. Below each panel is the number of patients at risk at each time-point. (A) Mitral inflow E-wave velocity (cm/s), (B) LV septal e’ velocity (cm/s), (C) septal E:e’ ratio, and (D) indexed left atrial volume (mL/m²).

Figure 4

Five-year adjusted cardiovascular mortality for each diastolic parameter. This graph shows the fully adjusted pattern of actual 5-year cardiovascular-related mortality in subjects with full 5-year follow-up according to each of the following diastolic function parameters: (A) E-wave velocity (n = 436 360); (B) Medial mitral annular e’ velocity (n = 237 816); (C) E:e’ ratio (n = 217 181); (D) indexed left atrial volume (n = 170 614). Each of the four groups were analysed with separate logistic regression models and odds ratios (with 95% confidence intervals) for each adjustment shown in the text box. LVEF, left ventricular ejection fraction (%), non-sinus rhythm is compared with patients in sinus rhythm during echocardiography, VHD, valvular heart disease, defined as an aortic valve area <1.2 cm², mean AV or MV gradient >20 or 5 mmHg, respectively, an MV mean gradient >5 mmHg, or moderate or greater mitral or aortic regurgitation. The significance for each odds ratio is denoted by *P < 0.05, **P < 0.01, and ***P < 0.001. In a sensitivity analysis examining only patients with all diastolic function parameters present (n = 113 725), similar mortality pivot-points were identified.