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Received: 18 June 2020    Revised: 23 August 2020    Accepted: 24 August 2020

DOI: 10.1111/echo.14859

O R I G I N A L I N V E S T I G AT I O N

Echocardiographic parameters associated with recovery in

heart failure with reduced ejection fraction

Muhammad Azam Shah MBBS, FCPS Cardiology, NBE, SBE, CBCCT1  | Muhammad

Adil Soofi MBBS, FRCP, FCPS Medicine, FCPS Cardiology, SF-Card, NBE, CBCCT1 |
Zainab Jafary DSN1 | Ashwaq Alhomrani BSc, RDMS1 | Faisal Alsmadi MBBS, FRCPC,
FACP, FACC, FSCAI, MHRS1 | Tariq Ahmad Wani MSc2 | Iftikhar Ahmad Bajwa MRCP,
SF-Cardiology, SBE, NBE1

1
Adult Cardiology Department, King Salman
Heart Center, King Fahad Medical City,
Riyadh, Saudi Arabia
2
Clinical and Research Department, King
Fahad Medical City, Riyadh, Saudi Arabia
Correspondence
Muhammad Azam Shah, FCPS, Cardiology,
NBE, SBE, CBCCT, Adult Cardiology
Department, King Salman Heart Center,
King Fahad Medical City, P.O.BOX: 59046,
Riyadh 11525, Saudi Arabia.
Email: azamshah165@hotmail.com
Funding information
This work was supported by the research
department of King Fahad Medical City,
Riyadh, Saudi Arabia (Grant Number 18-
018).
Abstract
Objective: The study aims to determine the clinical and echocardiographic param-
eters of patients with recovered heart failure (HFrecEF).
Methodology: Sixty-seven patients (cases) were identified as heart failure with re-
covered ejection fraction (HFrecEF), defined as improvement in EF  ≥  10%. Sixty-
nine patients (controls) were randomly selected by convenience sampling with no or
<10% improvement in EF (HFrEF non-recovered).
Results: The mean interval between baseline and follow-up echocardiography was
10.5 months in cases and 11.2 months in the control group. HFrecEF showed a 22.7%
improvement in mean ejection fraction, and HFrEF non-recovered group also showed
a minor increment of 5.5%. HFrecEF patients were significantly younger (49.51 vs
57.54 years, P .001) with non-ischemic cardiomyopathy (86.6% vs 52.2%). Patients
with HFrecEF had significantly less left ventricular end-diastolic and end-systolic vol-
umes (LVEDV: 162.51 mL vs 208.54 mL, P < .001; LVESV: 119.81 mL vs 157.13 mL,
P < .001) and index left atrial volume (37.66 mL vs 47.09 mL, P < .001) than patients
with non-recovered EF. The right ventricle (RV) and inferior vena cava were signifi-
cantly dilated with higher mean tricuspid annular plane systolic excursion (TAPSE)
among patients with HFrecEF than HFrEF non-recovered.
Conclusion: Based on univariate analysis, younger age, non-ischemic etiology,
LVEDV, LVESV, deceleration time, better TAPSE, dilated right ventricle, dilated IVC,
and smaller left atrial volumes were found significant, but on multivariate logistic re-
gression model only left ventricle end-diastolic volume, left atrial volume, and TAPSE
were linked to the recovery of ejection fraction.

KEYWORDS

echocardiography, ejection fraction, heart failure, left ventricle, recovery

Echocardiography. 2020;00:1–9. wileyonlinelibrary.com/journal/echo© 2020 Wiley Periodicals LLC     1 |

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2       SHAH et al.
1 |  I NTRO D U C TI O N
Heart failure (HF) is a syndrome of left ventricular structural and
functional abnormalities causing a wide range of symptoms resulting
from decreased cardiac output and congestion. It is classically cate-
gorized into heart failure with reduced ejection fraction (HFrEF) and
heart failure with preserved ejection fraction (HFpEF) base on left
ventricular ejection fraction (LVEF).1 Various cutoffs of ejection frac-
tions were used to define both categories in different clinical trials
and guidelines. In 2016, the European Society of Cardiology (ESC)
defined HFrEF as LVEF < 40%, HFpEF ≥ 50%, and a third category
was introduced as HF with mid-range ejection fraction (HFmrEF)
with LVEF between ≥40 and <50%. 2 There is a significant percent-
age of patients who experience recovery of left ventricular func-
tions, either spontaneous or with therapeutic interventions.3 Thus, a
new class of HF is suggested as HF with recovered LVEF (HFrecEF).4
Echocardiography plays an essential role in the assessment of
5
patients with heart failure. The echocardiographic determinants
of recovery have not been established among heart failure with re-
duced ejection fraction whose LVEF has recovered. We conducted
a study to enhance our understanding of clinical and echocardio-
graphic features of heart failure with recovered ejection fraction.
2 |  M E TH O D O LO G Y
Records of patients with heart failure with reduced LVEF attending
the heart failure clinic over the last 5 years were screened. Patients
whose LVEF has improved on subsequent echocardiography (at least
6 months apart) were selected as cases, and an equal number of pa-
tients, whose LVEF did not improve, were selected as controls. Their
clinical and echocardiographic data were collected. Controls were
randomly selected by convenience sampling. All the study partici-
pants had left ventricular ejection fraction (LVEF) <40% at the base-
line. Heart failure with recovered ejection fraction (HFrecEF) was
defined as an improvement in ejection fraction of ≥10% at follow-up
echocardiogram. The control group was labeled as heart failure with
reduced ejection fraction (HFrEF non-recovered), which consists of
patients with either no or ≤10% improvement in ejection fraction.
All categorical data were presented in frequencies and percent-
ages. The normality of the metric data was assessed by the Shapiro-
Wilk test. The sociodemographic and clinical characteristics are
compared between the cases and control groups using Pearson's chi-
square test for categorical variables and t-test or Mann-Whitney's U
test for metric variables. The eleven independent factors “Age (yr),
Gender, Non-ischemic etiology, LVEDV, LVESV, right ventricular
systolic excursion velocity (RVS'), TAPSE, indexed left atrial volume
(LAVi), deceleration time DT, RV Basal diameter, and IVC Diameter”
were loaded for forward Wald binary logistic regression evalu-
ation. Hosmer and Lemeshow test predicted the applied model is
good (P = .950). Nagelkerke R 2 explained variation in the dependent
variable based on our model by 91.0%. Moreover, the data classifi-
cation ascertained with Recovered EF Sensitivity in 95.7% and No
Recovered EF Specificity in 93.1% with an accuracy of 94.7% in the
applied model. All data were analyzed through statistical package
SPSS 22 (SPSS Inc).
3 | R E S U LT S
A total of 136 patients with heart failure with reduced ejection frac-
tion were included in the study. All the study participants had left
ventricular ejection fraction <40% at the baseline. Sixty-seven pa-
tients were identified as heart failure with recovered ejection frac-
tion (HFrecEF) and were defined as improvement in ejection fraction
of ≥10% at follow-up echocardiogram. Sixty-nine patients were
randomly selected by convenience sampling with no or <10% im-
provement in left ventricular ejection fraction at follow-up echocar-
diogram and labeled as heart failure with HFrEF non-recovered
group; they served as a control for the study.
The mean interval between baseline and follow-up echocardi-
ography was 10.5 months in cases and 11.2 months in the control
group. HFrecEF showed a 22.7% improvement in mean ejection frac-
tion, and HFrEF non-recovered showed a minor increment of 5.5%.
The majority of the participants were males with equal distribution
among both groups (65.7% vs 75.4%) (Table  1). HFrecEF patients
were significantly younger (mean age 49.51  years vs 57.54  years,
p = 0.001) with non-ischemic cardiomyopathy as the most prevalent
etiology of heart failure (86.6% vs 52.2%), and the majority of them
had better renal functions (GFR > 60:83.6% vs 69.6%) than HFrEF
non-recovered (Tables 1 and 2).
There was no difference in mean body mass index, the preva-
lence of diabetes, hypertension, and laboratory findings among
both the groups at baseline and follow-up (Tables 1 and 2). Although
there was no statistical difference in mean levels of Pro-BNP/BNP
in both groups, it is important to note that 88.6% of patients in the
HFrEF non-recovered group had raised levels (>125 pg/mL) as com-
pared to 53.3% in HFrecEF group (P = .002). Both groups were on
comparable medications with higher use of diuretic therapy (81.2%
vs 65.7%, P = .04) in the patient who did not recover their ejection
fraction (cases). A total of nine controls and five cases had a cardiac
resynchronization therapy device (CRTD) implanted. There was no
difference of vitals (taken at the time of echocardiography) between
HFrEF non-recovered group compared to HFrecEF group at base-
line (pulse: 78.35  bpm vs 80.37  bpm, P-value  =  .472; blood pres-
sure: 117.51/66.65 mm/Hg vs 120.1/69.24 mm/Hg, P-value = .462)
and follow-up (pulse: 75.68  bpm vs 76.82  bpm, P-value  =  .422;
blood pressure: 118.12/67.84  mm/Hg vs 124.54/71.25  mm/Hg,
P-value = .521).
Echocardiographic parameters at baseline showed comparable
mean left ventricular ejection fraction and left ventricular systolic
diameter (LVIDS) but left diastolic dimension (LVIDD) was signifi-
cantly smaller in HFrecEF group (Table  3). Patients with HFrecEF
had significantly less left ventricular end-diastolic and end-systolic
volumes (LVEDV: mean 162.51 mL vs 208.54 mL, P < .001; LVESV:
mean 119.81 mL vs 157.13 mL, P < .001) and index left atrial volume
SHAH et al. |
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TA B L E 1   Demographic data
HFrEF non-recovered HFrecEF P
Characteristic (n = 69) (n = 67) value

Gender
Male 52 (75.4) 44 (65.7) .215
Female 17 (24.6) 23 (34.3)
Hypertension 42 (60.9) 43 (64.2) .69
Dyslipidemia 18 (26.1) 14 (20.9) .476
Smoking 12 (17.4) 6 (9.0) .147
Family history of ischemic heart 0 (0.0) 3 (4.5) .075
disease
Cerebrovascular accident (CVA) 1 (1.4) 1 (1.5) .983
Atrial fibrillation 6 (8.7) 6 (9.0) .957
Non-ischemic cardiomyopathy 36 (52.2) 58 (86.6) <.001
Idiopathic cardiomyopathy 25 (36.2) 24 (35.8) .96
Antiplatelets 50 (72.5) 39 (58.2) .081
Anticoagulation 10 (14.5) 2 (3.0) .018
ACEIs/ARBs 57 (82.6) 58 (86.6) .523
Valsartan/Sacubitril 3 (4.3) 2 (3.0) .673
Beta-blockers 62 (89.9) 61 (91.0) .814
Loop diuretics 56 (81.2) 44 (65.7) .041
Mineralocorticoid receptor 1 (1.4) 0 (0.0) .323
antagonists (MRAs)
Digoxin 8 (11.6) 5 (7.5) .413
Nitrates 3 (4.3) 0 (0.0) .084
Hydralazine 8 (11.6) 2 (3.0) .054
Statins 51 (73.9) 53 (79.1) .476
Permanent pacemakers 4 (5.8) 0 (0.0) .045
Implantable intracardiac defibrillator 30 (43.5) 21 (31.3) .144
(ICD)
Cardiac resynchronization therapy 9 (13.0) 5 (7.5) .284
device (CRTD)
Glomerular filtration rate (GFR)
>60 48 (69.6) 56 (83.6) .112
30-60 12 (17.4) 8 (11.9)
<30 9 (13.0) 3 (4.5)

(37.66  mL vs 47.09  mL, P  <  .001) than patients with non-recov-
ered left ventricular ejection fraction (Table 3). At baseline, relative
wall thickness (RWT) was similar in both groups and no significant
change was observed in HFrEF non-recovered group at follow-up
but the HFrecEF group showed a significant increase in RWT at fol-
low-up (0.31 vs 0.37, P = .001). A significant number of patients in
the HFrecEF group showed RWT of >0.40 at follow-up when com-
pared to baseline (16.4% vs 34.3%) suggesting remodeling of the left
ventricle.
The left ventricular diastolic parameters like E-wave velocity,
A-wave velocity, E/A ratio, and E/e′ are comparable in both groups
but deceleration time is significantly more in HFrecEF as compared to
HFrEF non-recovered group (200.8 ms vs 169.5 ms, P-value = .006)
(Table 3).
Although right ventricular basal diameter and inferior vena
caval diameters were within normal limits but both were signifi-
cantly larger in the HFrecEF group as compared to HFrEF non-re-
covered (RV base: 39.28  mm vs 32.38  mm, IVC: 16.77  mm vs
11.99  mm,). The right ventricular systolic functions assessed by
tricuspid annular plane systolic excursion (TAPSE) of the tricuspid
valve were better in the HFrecEF population (TAPSE: 15.71  mm
vs 11.56  mm, P  <  .001) (Table  3). Among patients with HFrecEF,
improvement in LV and RV contractile function was observed
with a mean increase in LVEF of 22.74% (49.14% vs 26.6%) and
tricuspid annular plane systolic excursion of 4.31  mm (19.68  mm
vs 15.37  mm, P  <  .001), respectively (Table  4). Improvement in
cardiac chambers geometry in patients with HFrecEF was evident
by reduction in LV systolic and diastolic volume (LVEDV 126.5 mL
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4       SHAH et al.

TA B L E 2   Demographic data and laboratory investigations

HFrEF non-recovered (n = 69) HFrecEF (n = 67)

P
Descriptive N Mean ± SD (Min, max) Mean ± SD (Min, max) value

Age (y) 69 57.54 ± 15.27 (19, 85) 67 49.51 ± 11.41 (17, 71) .001

Height (cm) 69 164.28 ± 10.13 (145, 196) 67 162.12 ± 15.7 (60, 185) .342
Weight (kgs) 69 84.32 ± 22.75 (47, 163) 67 86.28 ± 23.34 (41, 203) .621
Body mass index 69 31.12 ± 7.34 (18.4, 54) 67 31.76 ± 7.02 (17.4, 49.10) .602
Body surface area (m2) 69 1.95 ± 0.29 (1.4, 2.8) 67 1.95 ± 0.24 (1.3, 2.5) .926
Hematocrit 69 41.47 ± 4.52 (24.5, 51.3) 67 40.76 ± 6.1 (26.6, 53.3) .446
White cell count (109 per 69 8.18 ± 3.27 (3.43, 17.5) 67 8.31 ± 4.03 (0, 27.1) .836
liter)
Hemoglobin (g/dL) 69 13.52 ± 1.83 (6.89, 17.6) 67 13.24 ± 2.4 (6.89, 18.1) .448
9
Platelets (10 per liter) 69 278.19 ± 123.64 (115, 713) 67 282.04 ± 94.83 (38, 494) .839
Pro-BNP/BNP (pg/mL) 35 835.4 ± 1640.3 (27, 8395) 30 785.02 ± 2092.20 (24, 9293) .914
Sodium (mEq/L) 69 135.99 ± 4.1 (118, 143) 67 136.43 ± 4.84 (118, 143) .561
Potassium (mEq/L) 69 4.22 ± 0.81 (3.2, 8) 67 4.25 ± 0.72 (0, 5.6) .796
Creatinine (μmol/L) 69 99.57 ± 71.67 (0, 482) 67 95.24 ± 37.07 (41, 247) .660
Urea (mg/dL) 69 10.26 ± 14.41 (2.5, 111) 67 7 ± 3.31 (0, 17.7) .073
Troponin-T at 51 186.23 ± 656.58 (0, 3325) 34 215.49 ± 781.37 (0, 3292.9) .853
presentation (ng/L)
Cholesterol (mmol/L) 54 3.8 ± 1.32 (1, 6.6) 49 4.29 ± 1.31 (2.2, 6.6) .063
LDL Cholesterol 55 3.4 ± 7.57 (1, 58) 49 2.69 ± 1.07 (1, 4.8) .515
(mmol/L)
Alanine amino 63 34.84 ± 28.62 (6, 174) 58 90.36 ± 426.76 (6, 3277) .305
transferase (IU/L)
HbA1c (%) 54 8.26 ± 2.62 (4.6, 13.5) 45 8.47 ± 5.55 (4.9, 42) .814
Vitamin D (nmol/L) 22 41.48 ± 25.6 (10, 95.8) 17 32.78 ± 19.46 (10, 90.2) .252
Thyroxine (T4) (pmol/L) 30 13.7 ± 3.56 (0.5, 23.8) 28 14.48 ± 4.33 (0.5, 23.8) .454
Ferritin (ng/mL) 11 111.54 ± 110.28 (31.6, 427) 7 199.66 ± 123.33 (119.3, 427) .134

vs 162.84 mL, P < .001; LVESV 63.6 mL vs 120.25, P < .001), index
Left atrial volume (29.39 mL vs 38.08 mL, P < .001), and RV basal
diameter (35.05 mm vs 39.28 mm, P < .001) on follow-up as com-
pared to baseline (Table 4). The left ventricular diastolic parame-
ters like E/A and E/e′ ratio also showed significant improvement
on follow-up in the same population. Patients with HFrecEF had
improved volume status with a reduction in inferior vena cava
diameter from 16.77  mm to 13.55  mm (Table  4). It is important
to note that HFrEF non-recovered group also showed some im-
provement (5.5%) in ejection fraction on follow-up (30.5% vs 25%,
P  =  .002) along with significant reduction in left atrial volumes
(38.3 mL vs 47 mL, P < .001).
The eleven independent factors "Age (yr), Gender, Non-ischemic
etiology, LVEDV, LVESV, right ventricular systolic excursion velocity
(RVS'), TAPSE, indexed left atrial volume (LAVi), deceleration time
(DT), RV Basal diameter, and IVC Diameter" were loaded for for-
ward Wald binary logistic regression evaluation. Only three factors
(LVEDV, left atrial volume, and TAPSE) had their significant effect, in
its 5th step process, on the EF recovery (Figures 1 and 2). Moreover;
the LVEDD of more than 171  mL is associated with 3.7 times less
chances of recovery. The patients with indexed left atrial volume
more than 40 mm/m2 had 4 times the risk of inability to recover their
ejection fraction.
4 | D I S CU S S I O N
The primary goal of heart failure management is the recovery of left
ventricular functions in a patient with reduced ejection fraction. A
significant percentage of heart failure population with reduced ejec-
tion fraction observes recovery in left ventricular functions suggest-
ing the possibility of viable and salvageable myocardium. Although
recovery in ejection fraction is linked with improvement in the qual-
ity of life and event-free survival, this particular population remains
at the risk of adverse outcomes in the future.6
Baseline clinical characteristics remain controversial and unclear
as reliable predictors of LVEF recovery. Non-ischemic etiology, di-
abetes, hypertension, and female sex are associated with the re-
covery of left ventricular systolic functions.7 But on the contrary,
the IMPROVE-HF trial studied 3994 heart failure patients and con-
cluded that age, diabetes, and kidney disease are not related to im-
provement in ejection fraction.8 Our study concluded that younger
SHAH et al. |
      5

TA B L E 3   Baseline echocardiographic parameters of HFrEF non-recovered and HFrecEF

HFrEF non-recovered (n = 69) HFrecEF (n = 67)

P
Parameters N Mean ± SD (min, max) Mean ± SD (min, max) value

Interventricular septal end 69 8.82 ± 1.74 (5.8, 13) 67 8.54 ± 2.54 (0.7, 14) .452
diastole (IVSd)
Interventricular septal end 69 10.19 ± 2.37 (5.5, 15) 67 10.77 ± 1.74 (5.7, 16) .087
systole (IVSs)
Posterior wall diastole (PWd) 69 9.13 ± 1.94 (4.9, 14.0) 67 8.79 ± 2.54 (0.7, 13.2) .387
Posterior wall systole (PWs) 69 11.91 ± 3.01 (1.3, 18) 66 11.31 ± 2.82 (1.3, 16) .284
Left ventricular end-diastolic 69 63.84 ± 10.78 (32, 91) 67 57.83 ± 9.31 (36, 95) .001
internal dimension (LVIDd)
Left ventricular end-systolic 69 54.01 ± 11.5 (26, 80) 67 50.27 ± 18.9 (29, 181) .163
internal dimension (LVIDs)
Relative wall thickness (RWT) 69 0.30 ± 0.10 (0.11, 0.75) 67 0.31 ± 0.10 (0.03, 0.56) .391
Left ventricular end diastolic 68 213.02 ± 72.24 (40.6, 414.9) 67 162.84 ± 52.49 (52, 310) <.001
volume (LVEDV)
Left ventricular end systolic 68 160.65 ± 58.4 (29, 346.1) 67 120.25 ± 40.5 (33, 220) <.001
volume (LVESV)
LV ejection fraction (LVEF) 68 25.06 ± 7.06 (7.6, 42.6) 67 26.4 ± 5.75 (12.6, 36.5) .100
LV fractional shortening 66 14.92 ± 5.76 (1.3, 30.9) 61 14.18 ± 4.34 (6, 29) .284
(LVFS)
Left ventricular mass index 62 131 ± 87.68 (69, 193) 53 116.28 ± 37.87 (55.5, 250) .634
(LVMi)
RV systolic excursion velocity 45 9.19 ± 2.81 (4.5, 17.4) 61 10.2 ± 2.92 (2.6, 20.0) .038
(RV S')
Tricuspid annular plane 45 11.54 ± 0.5 (10.7, 12.6) 57 15.37 ± 4.14 (7.0, 30.0) <.001
systolic excursion (TAPSE)
Left atrial volume index (LAVi) 69 47.09 ± 11.76 (25, 76) 66 38.08 ± 12.55 (17, 76) <.001
Right atrial volume index 69 31.78 ± 12.96 (13, 64.7) 66 27.21 ± 12.44 (11.3, 64.7) .049
(RAVi)
Tricuspid regurgitation (TR) 48 266.62 ± 72.68 (112.9, 408) 47 262.58 ± 55.65 (120.5, 426) .878
Vmax
E-wave 68 89.41 ± 26.78 (32, 195) 65 86.75 ± 29.3 (13, 172) .161
A-wave 56 56.65 ± 31.13 (19.4, 124.5) 61 57.21 ± 24.9 (1.5, 142) .474
E/A ratio 63 2.04 ± 1.39 (0.4, 5.7) 61 1.83 ± 0.96 (0.3, 4.7) .076
Deceleration (DT) 68 169.48 ± 53.79 (80, 320) 60 202.27 ± 71.7 (100, 410) .006
E/e′ (septal) 59 21.73 ± 8.8 (8.1, 41.3) 62 22.35 ± 10.32 (9.15, 52) .556
E/e′ (lateral) 57 15.56 ± 9.49 (0.4, 41.7) 62 13.75 ± 6.93 (3.4, 32.3) .200
RV basal diameter 64 32.33 ± 4.68 (25, 40) 65 39.28 ± 8.13 (24, 56) <.001
IVC diameter 57 12 ± 0.7 (10.78, 14.5) 61 17 ± 4.75 (10.8, 27) <.001

age, non-ischemic etiology, and absence of chronic kidney disease
are significantly linked to chances of improvement in LVEF. Other
co-morbidities like diabetes, hypertension, and dyslipidemias are
equally distributed in both groups, and this finding is consistent with
previous studies with minor differences.9
Echocardiography plays an essential role in the assessment of
patients with heart failure.5 It provides clues to possible etiology,
the severity of ventricular systolic and diastolic dysfunction, val-
vular involvement, and pulmonary hypertension. In addition to the
above-mentioned information, echocardiography helps in predicting
the morbidity and mortality in the heart failure population.10 A large
variety of Doppler and echocardiographic parameters can be ob-
tained, many of which are related to each other physiologically and
mathematically. Assessment of left ventricular systolic function is in-
dicated in all patients suspected with heart failure, and it is the single
most powerful predictor of outcomes in this high-risk population. 2
In addition to LVEF assessment, multiple other parameters like frac-
tional shortening, peak Doppler E-wave velocity of mitral inflow, left
ventricular hypertrophy, higher indexed LV end-diastolic volume,
deceleration time (DT), and vena contracta of mitral regurgitation
are associated with a worse prognosis.10,11 In this single-centered,
retrospective study, we evaluated the echocardiographic factors
 |
6       SHAH et al.

TA B L E 4   Paired sample statistical analysis of HFrEF non-recovered EF with recovered EF (HFrecEF)

HFrEF non-recovered EF HFrecEF

P
Parameters Baseline Follow-up P value Baseline Follow-up value

Interventricular septal end 8.82 ± 1.74 8.98 ± 2.25 .553 8.54 ± 2.54 10.74 ± 12.22 .147

diastole (IVSd)
Interventricular septal end 10.19 ± 2.37 10.49 ± 2.76 .412 10.77 ± 1.74 12.55 ± 1.76 <.001
systole (IVSs)
Posterior wall diastole (PWd) 9.13 ± 1.94 9.59 ± 2.96 .251 8.79 ± 2.54 9.32 ± 2.18 .172
Posterior wall systole (PWs) 11.91 ± 3.01 12.11 ± 2.9 .671 11.31 ± 2.82 13.14 ± 2.17 <.001
Left ventricular end-diastolic 63.84 ± 10.78 65.63 ± 7.68 .053 57.83 ± 9.31 51.53 ± 7.20 <.001
internal dimension (LVIDd)
Left ventricular end-systolic 54.01 ± 11.5 56.14 ± 8.66 .058 50.27 ± 18.9 37.17 ± 12.04 <.001
internal dimension (LVIDs)
Relative wall thickness (RWT) 0.30 ± 0.10 0.31 ± 0.23 .421 0.31 ± 0.10 0.37 ± 0.09 .001
Left ventricular end diastolic 213.02 ± 72.24 215.05 ± 66.43 .775 162.84 ± 52.49 126.58 ± 41.12 <.001
volume (LVEDV)
Left ventricular end systolic 160.65 ± 58.4 151.51 ± 58.43 .161 120.25 ± 40.5 63.61 ± 21.03 <.001
volume (LVESV)
LV ejection fraction (LVEF) 25.06 ± 7.06 30.57 ± 11.88 .002 26.4 ± 5.75 49.14 ± 6.13 <.001
LV fractional shortening 14.92 ± 5.76 15.41 ± 5.99 .64 14.18 ± 4.34 28.63 ± 6.46 <.001
(LVFS)
Left ventricular mass index 131 ± 87.68 118 ± 72.12 .447 116.28 ± 37.87 100.59 ± 29.69 .003
(LVMi)
RV systolic excursion velocity 9.19 ± 2.81 9.12 ± 2.08 .892 10.2 ± 2.92 12.08 ± 2.94 <.001
(RV S′)
Tricuspid annular plane 11.54 ± 0.5 11.83 ± 1.89 .391 15.37 ± 4.14 19.68 ± 4.81 <.001
systolic excursion (TAPSE)
Left atrial volume index 47.09 ± 11.76 38.3 ± 10 <.001 38.08 ± 12.55 29.39 ± 8.55 <.001
(LAVi)
Right atrial volume index 31.78 ± 12.96 31.38 ± 9.96 .704 27.21 ± 12.44 21.88 ± 6.38 .001
(RAVi)
Tricuspid regurgitation (TR) 266.62 ± 72.68 283.39 ± 54.79 .238 262.58 ± 55.65 234.86 ± 49.67 .018
Vmax
E-wave 89.41 ± 26.78 96.9 ± 32.57 .134 86.75 ± 29.3 74.71 ± 27.34 .011
A-wave 56.65 ± 31.13 58.26 ± 30.45 .721 57.21 ± 24.9 73.35 ± 27.46 <.001
E/A ratio 2.04 ± 1.39 2.17 ± 1.63 .634 1.83 ± 0.96 1.09 ± 0.48 <.001
Deceleration (DT) 169.48 ± 53.79 175.03 ± 68.93 .635 202.27 ± 71.7 237.4 ± 66.09 .013
E/e′ (septal) 21.73 ± 8.8 21.69 ± 12.77 .981 22.35 ± 10.32 13.51 ± 6.74 <.001
E/e′ (lateral) 15.56 ± 9.49 14.04 ± 7.65 .412 13.75 ± 6.93 10.62 ± 5.76 .001
RV basal diameter 32.33 ± 4.68 31.67 ± 4.96 .426 39.28 ± 8.13 35.05 ± 6.28 <.001
IVC diameter 12 ± 0.7 12.07 ± 0.84 .519 17 ± 4.75 13.48 ± 3.09 <.001

associated with recovery in patients of heart failure with recovered
ejection fraction by comparing them to heart failure with non-im-
proved LV function.
Left ventricular ejection fraction assessment at baseline and se-
rial measurements is important in risk stratification and management
of heart failure patients. There was no significant difference in base-
line ejection fraction in both categories of patients, and mean LVEF
increased by about 22.7% in the recovered group as compared to a
minor increase of 5.5% in HFrEF non-recovered population. A minor
increase in left ventricular ejection fraction is reported in patients
with HFrEF in previous studies.8,12 Left ventricular 2D linear dimen-
sions (LVIDD and LVIDS) were smaller in heart failure recovered
EF group. Although previous studies proposed that less enlarged
LVEDD is associated with higher chances of recovery in ejection
fraction in a patient with dilated cardiomyopathy, it is a fact that 2D
linear measurements are not a true representation of the actual size
of the left ventricle due to multiple assumptions.13,14 Left ventricular
volume data have been extensively studied in various heart failure
SHAH et al. |
      7

F I G U R E 1   Results of univariate and

multivariate analyses

F I G U R E 2   Bar chart graph showing 250

the difference between the most
HFrEF Non-recovered HFRecEF
significant parameters of both groups

200

150 208.54

100
162.28

50
47.09

37.66

11.56

15.71
0
LVEDV (ml) LAVi (ml/m2) TAPSE (mm)
HFrEF Non-recovered 208.54 47.09 11.56
HFRecEF 162.28 37.66 15.71

trials, showing a favorable impact on outcome and association with
recovery in systolic functions.10,11,15 In our study, volume calcula-
tions were made by disks summation (Simpson's) method and anal-
ysis of baseline echocardiographic studies of both groups showed
that systolic and diastolic volumes were significantly less in patients
who later recovered their systolic functions. This study recommends
acquiring LV volumes in all heart failure patients. Left ventricular rel-
ative wall thickness (RWT) is a marker of remodeling. HFrecEF group
also showed a significant increase in RWT at follow-up suggesting
positive remodeling in this group leading to decrease LV size and
volumes.
Indexed left atrial volume (LAVi) is the most sensitive and de-
pendable in risk stratification and predicting cardiac outcomes.16
Moon j et al suggested that LAVi can predict recovery in LV func-
tions with high specificity.13 After multivariate analysis, our data
also suggest a strong correlation of smaller left atrial volumes with
higher chances of recovery in the heart failure population. Left atrial
volume also decreased significantly (but still abnormal) at follow-up
in the HFrEF-Non-recovery group (38.3  mL vs 47  mL, P  < .001).
This reduction in LAVi is likely because our heart failure population
was on adequate heart failure therapy with better volume status
on follow-up (Table  1). Left ventricular diastolic dysfunction is a
marker of poor prognosis in patients having heart failure with re-
duced and preserved ejection fraction.17 Hemodynamic patterns
and filling pressures may vary widely even within the heart failure
patients with reduced ejection fraction.18 An increased E/A ratio
suggests the rapid filling of the ventricle in the early phase com-
bined with the decreased atrial contribution in this process. Higher
E/A ratio at mitral inflow is associated with poor prognosis.19 Our
data revealed that although statistically not significant but E/A
ratio was less and deceleration time (DT) was prolonged among
patients with HFrecEF and suggest that less diastolic dysfunction
at baseline support the higher chances of LV recovery. All diastolic
parameters recovered after improvement in systolic functions sug-
gesting a simultaneous reversal of diastolic dysfunction along with
recovery of systolic functions.
 |
8       SHAH et al.
Right ventricular systolic dysfunction is an important predictor
20
of long-term outcomes in the heart failure population. La Vecchia,
L., et al21 proposed that biventricular involvement is more common
in non-ischemic cardiomyopathies as compared to ischemic etiolo-
gies, resulting in a higher rate of dilatation and dysfunction of the
right-sided chambers. RV size and IVC diameter were higher but still
within normal range among the HFrecEF group. Marker of RV func-
tion (TAPSE) can be used to risk-stratify heart failure patients with
reduced ejection fraction. 20 The presence of significant tricuspid
regurgitation influences the utility of TAPSE for RV function assess-
ment. 22 Only a minority of our population had significant tricuspid
regurgitation. Multivariate analysis identified that better TAPSE (a
marker of RV systolic function) is strongly associated with recovery
in LV functions. RV systolic function is an important marker, and
chances of recovery are good even if RV is dilated as long as its sys-
tolic function remains preserve.
The main limitation of our study is the retrospective nature and
inability to utilized and study modern echocardiographic techniques
to assess heart failure patients. The total duration of heart failure
was not known, and data were collected starting from the presen-
tation. The levels of BNP/Pro-BNP were not recorded at follow-up
in both groups. New echocardiographic techniques like tissue strain
analysis and 3D echocardiography might be useful in predicting the
chances of recovery in heart failure patients presenting with re-
duced ejection fraction.
In conclusion, smaller left ventricle end-diastolic volume (LVEDV),
smaller left atrial volume (LAVi), and higher tricuspid annular plane
systolic excursion (TAPSE) at baseline are strongly associated with
left ventricle recovery in patients of heart failure with reduced ejec-
tion fraction (HFrEF).
C O N FL I C T O F I N T E R E S T
Muhammad Azam Shah, Muhammad Adil Soofi, Zainab Jafary,
Ashwaq Alhomrani, Faisal alsmadi, Tariq wani, and Iftikhar Ahmad
Bajwa declare that they have no conflict of interest.
DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available from
the corresponding author upon reasonable request.
ORCID
Muhammad Azam Shah  https://orcid.
org/0000-0003-2451-413X
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