Frequency, predictors, and prognosis of ejection fraction improvement in heart failure: an echocardiogram-based registry study

Abstract

Aims To identify variables predicting ejection fraction (EF) recovery and characterize prognosis of heart failure (HF) patients with EF recovery (HFrecEF). Methods and results Retrospective study of adults referred for ≥2 echocardiograms separated by ≥6 months between 2008 and 2016 at the two largest echocardiography centres in Alberta who also had physician-assigned diagnosis of HF. Of 10 641 patients, 3124 had heart failure reduced ejection fraction (HFrEF) (EF ≤ 40%) at baseline: while mean EF declined from 30.2% on initial echocardiogram to 28.6% on the second echocardiogram in those patients with persistent HFrEF (defined by <10% improvement in EF), it improved from 26.1% to 46.4% in the 1174 patients (37.6%) with HFrecEF (defined by EF absolute improvement ≥10%). On multivariate analysis, female sex [adjusted odds ratio (aOR) 1.66, 95% confidence interval (CI) 1.40–1.96], younger age (aOR per decade 1.16, 95% CI 1.09–1.23), atrial fibrillation (aOR 2.00, 95% CI 1.68–2.38), cancer (aOR 1.52, 95% CI 1.03–2.26), hypertension (aOR 1.38, 95% CI 1.18–1.62), lower baseline ejection fraction (aOR per 1% decrease 1.07 (1.06–1.08), and using hydralazine (aOR 1.69, 95% CI 1.19–2.40) were associated with EF improvements ≥10%. HFrecEF patients demonstrated lower rates per 1000 patient years of mortality (106 vs. 164, adjusted hazard ratio, aHR 0.70 [0.62–0.79]), all-cause hospitalizations (300 vs. 428, aHR 0.87 [0.79–0.95]), all-cause emergency room (ER) visits (569 vs. 799, aHR 0.88 [0.81–0.95]), and cardiac transplantation or left ventricular assist device implantation (2 vs. 10, aHR 0.21 [0.10–0.45]) compared to patients with persistent HFrEF. Females with HFrEF exhibited lower mortality risk (aHR 0.94 [0.88–0.99]) than males after adjusting for age, time between echocardiograms, clinical comorbidities, medications, and whether their EF improved or not during follow-up. Conclusion HFrecEF patients tended to be younger, female, and were more likely to have hypertension, atrial fibrillation, or cancer. HFrecEF patients have a substantially better prognosis compared to those with persistent HFrEF, even after multivariable adjustment, and female patients exhibit lower mortality risk than men within each subgroup (HFrecEF and persistent HFrEF) even after multivariable adjustment.

Circulating troponin and further left ventricular ejection fraction improvement in patients with previously recovered left ventricular ejection fraction

“…Our data confirm the association of baseline patient characteristics related to LVEF recovery 1,5,6,9–11 , and demonstrate two novel findings in patients with pre‐existing HFrecEF: (i) evidence of additional LVEF improvement at a median 2 years following initial diagnosis and (ii) lower baseline and stable serum hs‐TnT levels in contrast to increasing levels in those with persistent HFrEF. Taken together, these findings support the notion that significant improvement in LVEF may occur after 2 years and associate with lower and stable serum levels of cardiac damage.…”

“…5,10 We have previously reported a much higher rate of LV improvement (37%) using a EF cut point of 40% in very large cohort (10 641, of whom 3124 have baseline LVEF < 40%). 6 These results compare with previous reviews of reverse remodelling, which suggest a 35% rate of reverse remodelling as defined by >10% improvement in LVEF at 24 months from baseline and with an initial mean improvement of 8-10%. 1,7 Thus, the prevalence of LVRR depends greatly upon both definition and disease duration.…”

“…Several correlates for LVRR have been reported in most studies, including younger age, female sex, non-ischaemic aetiology, shorter duration of HF, higher baseline LV volume, and use of beta blockers. 1,6,7 Other factors reported to associate with LVRR, such as the presence of the minor allele of re777652, a hypocretin receptor-2. 17 Recently, hs-TnT has been reported to associate with outcomes in HF with a meta-analysis of studies suggesting a level < 18 ng/L to predict lower risk of death and hospitalization, but this level was not tested for prediction of reverse remodelling.…”

“…2,6,7 This phenomenon occurs in 20-45% of patients with HF with reduced EF (HFrEF), is associated with improved prognosis, and is more commonly seen in patients of female gender, non-ischaemic aetiology of HF, shorter duration of HF, and persistence of beta blocker use. 1,6,7 However, few reports detail serial clinical, biomarker, and imaging correlates of patients previously experiencing reverse remodelling. The Alberta Heart Failure and Etiology Analysis Team (HEART) study, patients with American Heart Association Stage B or C HF (irrespective of LVEF) were enrolled and followed with serial testing.…”

“…Previous reports suggest that patients may demonstrate significant improvement in LV ejection fraction (EF) with evidence‐based medical therapy (i.e. reverse remodelling), also referred to as heart failure with recovered EF (HFrecEF) 2,6,7 . This phenomenon occurs in 20–45% of patients with HF with reduced EF (HFrEF), is associated with improved prognosis, and is more commonly seen in patients of female gender, non‐ischaemic aetiology of HF, shorter duration of HF, and persistence of beta blocker use 1,6,7 .…”