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Trajectories of LVEF in Heart Failure
Study Questions:
What are the left ventricular ejection fraction (LVEF) trajectories in heart failure with reduced LVEF (<40%) and mid-range LVEF (40-49%), and the prognostic impact of LVEF dynamic changes over 15-year follow-up?
Methods:
The final study cohort was comprised of 1,160 ambulatory HF patients who had a minimum of two LVEF measurements. LVEF was scheduled to be assessed at baseline and at 1, 3, 5, 7, 9, 11, 13, and 15 years of follow-up by two-dimensional echocardiography. LVEF was calculated with the Simpson method. The study authors fitted random intercepts linear mixed-effects (LME) models in which the measured value of LVEF was assumed to have a set of parameters fixed across individuals including a specific random effect per each individual. Because the form of the Loess curves suggests at least a quadratic in time, all LME models included both the linear term time and the quadratic term timeˆ2 as fixed effects. By adding the quadratic term timeˆ2 to the models, the study authors could evaluate whether the effect of time changed significantly as the time progressed. Comparisons of LVEF between included and excluded patients and between alive and dead patients were performed with the Student’s t-test, Mann-Whitney U test, or chi-square test, as appropriate.
Results:
The main etiology in the 1,160 included patients was ischemic heart disease (56%), followed by dilated cardiomyopathy (14%). The mean number of LVEF measurements was 3.6 ± 1.7. As a whole, Loess curves of long-term LVEF trajectories showed an inverted U shape with a marked rise in LVEF during the first year, maintained up to a decade, and a slow LVEF decline thereafter (p for trajectory < 0.001). This pattern was more pronounced in HF of nonischemic origin and in women. Patients with new-onset HF (≤12 months) had a higher early increase in LVEF than in patients with longer HF duration at the baseline visit, followed by a plateau (p < 0.001 for both trajectories; p < 0.001 between groups). Nonischemic HF patients showed a more pronounced bump at 1 year and a more prolonged increase during follow-up than those with ischemic HF (approximately 7-10 LVEF points; p < 0.001 for both trajectories; p < 0.001 between groups), whereas patients with ischemic HF showed a lower LVEF increase at 1 year; both groups had a relative plateau thereafter. Patients with HF with mid-range LVEF had less of an increase (3 ± 9%) than those with HF with reduced LVEF (9 ± 12%) during the first year (p < 0.001), but the groups overlapped after 15 years. Hypertensive etiology (10.7% vs. 6.3%, p = 0.03) was significantly more frequent in HF with mid-range EF, whereas alcohol toxicity tended to be more frequent in HF with reduced EF (3.2% vs. 6.4%, p = 0.09). Patients who died had lower final LVEF and worse LVEF dynamics in the immediately preceding period than survivors.
Conclusions:
The study authors concluded that LVEF trajectories vary in HF depending on a number of disease modifiers, but an inverted U-shaped pattern with lower LVEF at both ends of the distribution emerged. A declining LVEF in the preceding period was associated with higher mortality.
Perspective:
The natural history of cardiomyopathy varies depending on the underlying etiology. This paper nicely delineates the trajectory of systolic function, and this study suggests that monitoring the trajectory may be important given that HF is a continuum. Multicenter studies are now needed to validate these important findings. It would be interesting to know how these trajectories are affected by associated right ventricular dysfunction.
Keywords: Cardiomyopathies, Cardiomyopathy, Dilated, Echocardiography, Geriatrics, Heart Failure, Hypertension, Myocardial Ischemia, Stroke Volume, Systole, Ventricular Function
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