Beyond initial recovery: Heart failure with transient vs sustained improvement in left ventricular ejection fraction

Table 1 Baseline characteristics of the included patients

Variable	Transient improvement (n = 39)	Sustained improvement (n = 136)	P value
Age (years), mean ± SD	58.15 ± 11.69	54.51 ± 13.52	0.13
BMI (kg/m2), mean ± SD	28.36 ± 5.67	30.49 ± 7.20	0.09
Male	37 (94.9)	101 (74.3)	0.005
Female	2 (5.1)	35 (25.7)	-
HF etiology
Ischemic	32 (82.1)	68 (50.4)	0.002
Dilated	5 (12.8)	57 (42.2)
Others	2 (5.1)	10 (7.4)
Duration of HF diagnosis, mean ± SD	7.05 ± 3.81	5.79 ± 4.0	0.08
Comorbidities
Dyslipidemia	24 (61.5)	54 (39.7)	0.03
Hypertension	34 (87.2)	93 (68.4)	0.03
Diabetes	28 (71.8)	90 (66.2)	0.57
Atrial fibrillation	8 (20.5)	25 (18.4)	0.82
Ventricular arrhythmia	5 (12.8)	18 (13.2)	1.00
CVA/TIA	5 (12.8)	16 (11.8)	0.79
PAD	2 (5.1)	8 (5.9)	1.00
Renal impairment	17 (43.6)	35 (25.7)	0.05
Liver disease	2 (5.1)	5 (3.7)	0.65
Anemia	10 (25.6)	38 (27.9)	0.84
Sleep apnea	0 (0)	9 (6.6)	0.21
Chronic lung disease	6 (15.4)	21 (15.4)	1.00
Cancer	0 (0)	7 (5.1)	0.35
Dementia	2 (5.1)	3 (2.2)	0.31
Depression	0 (0)	6 (4.4)	0.34
Hypothyroidism	2 (5.1)	11 (8.1)	0.74
Hyperthyroidism	0 (0)	4 (2.9)	0.58

Data are presented as n (%). BMI: Body mass index; CVA: Cerebrovascular accident; HF: Heart failure; PAD: Peripheral artery disease; SD: Standard deviation; TIA: Transient ischemic attack.

Table 2 Vital signs and electrocardiographic measures of the included patients

Variable	Transient improvement (n = 39)	Sustained improvement (n = 136)	P value
Baseline (Echo-1), mean ± SD
Systolic BP (mmHg)	124.38 ± 22.41	125.30 ± 20.1 (n = 134)	0.81
Diastolic BP (mmHg)	72.64 ± 12.36	75.97 ± 12.99 (n = 134)	0.16
Heart rate (bpm)	86.43 ± 18.02 (n = 37)	89.69 ± 19.12 (n = 132)	0.36
Achieved target BP	26 (66.7)	87 (64.9)	1.00
Sinus rhythm	28 (90.3)	103 (86.6)	0.77
LBBB	7 (14.1)	19 (17.1)	0.42
QRS (ms), mean ± SD	109.45 ± 26.29 (n = 29)	109.43 ± 44.04 (n = 129)	1.0
QTc (ms), mean ± SD	468.86 ± 43.48 (n = 29)	462.84 ± 52.19 (n = 109)	0.57
Second follow-up (Echo-3), mean ± SD
Systolic BP (mmHg)	127.87 ± 21.43	133.47 ± 98.18 (n = 129)	0.73
Diastolic BP (mmHg)	73.85 ± 13.62	73.81 ± 11.49 (n = 129)	0.99
Heart rate (bpm)	79.41 ± 15.45	72.84 ± 12.90 (n = 128)	0.02
Achieved target BP	26 (66.7)	90 (69.8)	0.67
Sinus rhythm	33 (89.2)	111 (88.8)	1.00
LBBB	7 (19.4)	21 (17.4)	0.81
QRS (ms), mean ± SD	112.00 ± 26.87 (n = 37)	110.07 ± 26.34 (n = 120)	0.70
QTc (ms), mean ± SD	455.08 ± 31.57 (n = 37)	448.91 ± 42.92 (n = 120)	0.35

Data are presented as n (%). Echo-1: First (or baseline) echocardiogram; BP: Blood pressure; bpm: Beats per minute; LBBB: Left bundle branch block; QTc: Corrected QT interval; QRS: QRS complex duration; Echo-3: Third echocardiogram; SD: Standard deviation.

Table 3 Laboratory blood tests of the included patients

Variable	Transient improvement (n = 39)	Sustained improvement (n = 136)	P value
Baseline (Echo-1)
NT-pro-BNP (pg/mL)	5106.63 ± 6035.19 (n = 27)	4730.48 ± 6792.82 (n = 93)	0.80
Hemoglobin (g/dL)	13.16 ± 2.22 (n = 38)	14.20 ± 12.89 (n = 132)	0.62
Urea (mmol/L)	8.16 ± 4.53 (n = 38)	7.15 ± 4.17 (n = 133)	0.20
Creatinine (µmol/L)	120.03 ± 56.87 (n = 38)	113.55 ± 114.84 (n = 132)	0.74
eGFR (mL/min)	66.47 ± 27.79 (n = 38)	79.68 ± 33.27 (n = 132)	0.03
HbA1c (%)	8.38 ± 2.34 (n = 26)	7.54 ± 2.19 (n = 102)	0.09
LDL-C (mmol/L)	2.69 ± 0.92 (n = 35)	2.57 ± 1.18 (n = 120)	0.56
Iron (µmol/L)	8.87 ± 3.69 (n = 10)	10.43 ± 6.49 (n = 37)	0.47
TSAT (%)	16.77 ± 5.42 (n = 10)	20.37 ± 15.74 (n = 35)	0.48
Ferritin (ug/L)	325.75 ± 347.95 (n = 8)	208.50 ± 277.71 (n = 30)	0.32
TSH (pmol/L)	1.76 ± 1.51 (n = 22)	2.38 ± 2.18 (n = 92)	0.21
T4 (mIU/L)	13.51 ± 1.70 (n = 23)	14.87 ± 3.58 (n = 87)	0.08
Second follow-up (Echo-3)
NT-pro-BNP (pg/mL)	7672.15 ± 13459.32 (n = 27)	3184.52 ± 6564.79 (n = 81)	0.11
Hemoglobin (g/dL)	12.23 ± 2.25 (n = 37)	12.87 ± 2.08 (n = 120)	0.11
Urea (mmol/L)	10.28 ± 7.27 (n = 38)	8.50 ± 8.94 (n = 125)	0.26
Creatinine (µmol/L)	142.84 ± 88.49 (n = 38)	127.25 ± 126.01 (n = 128)	0.48
eGFR (mL/min)	59.89 ± 28.49 (n = 38)	70.35 ± 29.24 (n = 127)	0.05
HbA1c (%)	7.66 ± 2.04 (n = 33)	7.90 ± 4.88 (n = 103)	0.79
LDL-C (mmol/L)	1.81 ± 0.99 (n = 33)	2.03 ± 0.93 (n = 99)	0.25
Iron (µmol/L)	9.64 ± 4.33 (n = 18)	11.23 ± 6.24 (n = 41)	0.33
TSAT (%)	17.44 ± 8.69 (n = 18)	23.48 ± 16.53 (n = 41)	0.15
Ferritin (ug/L)	276.17 ± 489.76 (n = 14)	244.41 ± 429.58 (n = 30)	0.83
TSH (pmol/L)	2.43 ± 1.45 (n = 22)	3.22 ± 3.12 (n = 83)	0.26
T4 (mIU/L)	15.73 ± 2.23 (n = 19)	15.05 ± 3.86 (n = 73)	0.46

Data are presented as mean ± SD. Echo-1: First (or baseline) echocardiogram; eGFR: Estimated glomerular filtration rate; HbA1c: Glycated hemoglobin; Echo-3: Third echocardiogram; LDL-C: Low-density lipoprotein cholesterol; NT-proBNP: N-terminal pro-brain natriuretic peptide; T4: Thyroxine hormone; TSAT: Transferrin saturation; TSH: Thyroid-stimulating hormone.

Table 4 Echocardiographic parameters of the included patients

Variable	Transient improvement (n = 39)	Sustained improvement (n = 136)	P value
Baseline (Echo-1)
LVEF (%)	30.56 ± 6.95	26.77 ± 7.05	0.003
Average E/e’	15.01 ± 5.88 (n = 20)	14.52 ± 5.78 (n = 67)	0.74
LA volume index (mL/m2)	35.97 ± 12.51 (n = 25)	37.09 ± 11.35 (n = 82)	0.68
LVEDD (cm)	5.76 ± 0.79 (n = 37)	6.70 ± 4.17 (n = 130)	0.18
LVESD (cm)	4.76 ± 0.84 (n = 34)	5.08 ± 0.89 (n = 115)	0.80
RVSP (mmHg)	33.46 ± 11.06	37.35 ± 12.89 (n = 130)	0.13
Second follow-up (Echo-3)
LVEF (%)	28.46 ± 6.59	40.18 ± 0.12	0.001
Average E/e’	13.12 ± 5.46 (n = 19)	12.08 ± 5.86 (n = 77)	0.49
LA volume index (mL/m2)	41.41 ± 12.92 (n = 31)	34.30 ± 11.26 (n = 114)	0.003
LVEDD (cm)	6.06 ± 0.62 (n = 38)	5.81 ± 0.89 (n = 134)	0.05
LVESD (cm)	4.99 ± 0.75 (n = 37)	4.50 ± 0.95 (n = 131)	0.004
RVSP (mmHg)	38.78 ± 14.61 (n = 37)	33.10 ± 11.82 (n = 129)	0.04
LVEF (Echo-2)	38.59 ± 7.57	36.33 ± 7.69	0.11
∆ LVEF (Echo-2 - Echo-1) (%)	8.05 ± 6.53	9.54 ± 7.69	0.27
Duration between Echo-1 and Echo-2 (months)	19.82 ± 26.61	17.24 ± 21.15	0.53
∆ LVEF (Echo-3 - Echo-1) (%)	-2.10 ± 5.05	13.43 ± 9.09	0.001
Duration between Echo-2 and Echo-3 (months)	20.49 ± 13.40	21.79 ± 23.39	0.74

Data are presented as mean ± SD. Echo-1: First (or baseline) echocardiogram; Echo-2: Second echocardiographic examination at first follow-up; Echo-3: Third echocardiographic; LA: Left atrium/atrial; LVEDD: Left ventricular end-diastolic diameter; LVEF: Left ventricular ejection fraction; LVESD: Left ventricular ejection fraction; RVSP: Right ventricular systolic pressure.

Table 5 Medications at baseline and at second follow-up

Variable	Transient improvement (n = 39)	Sustained improvement (n = 136)	P value
Baseline (Echo-1)
Beta-blockers	19 (48.7)	78 (57.4)	0.37
ACEI/ARB	25 (64.1)	81 (59.6)	0.71
MRA	2 (5.1)	29 (21.3)	0.02
Diuretics	13 (33.3)	62 (45.6)	0.20
HDZ/ISDN	1 (2.6)	4 (2.9)	1.00
Ivabradine	0 (0)	6 (4.4)	0.34
Digoxin	0 (0)	9 (6.6)	0.21
Antiplatelet therapy	24 (61.5)	78 (57.4)	0.71
LLA	24 (61.5)	72 (52.9)	0.38
Iron (IV)	7 (17.9)	17 (12.5)	0.43
Inotropes (hospital)	4 (10.3)	23 (16.9)	0.45
Second follow-up (Echo-3)
Beta-blockers	36 (92.3)	126 (95.5)	0.43
ACEI/ARB	30 (76.9)	110 (80.9)	0.58
MRA	13 (33.3)	54 (40.9)	0.46
Diuretics	31 (79.5)	99 (75.0)	0.67
HDZ/ISDN	4 (10.3)	10 (7.6)	0.53
Ivabradine	3 (7.7)	11 (8.3)	1.00
Digoxin	2 (5.1)	7 (5.3)	1.00
Antiplatelet therapy	34 (87.2)	97 (73.5)	0.09
Lipid-lowering agents	36 (92.3)	106 (80.3)	0.08
Iron (IV)	4 (10.3)	5 (3.7)	0.12
Inotropes (hospital)	3 (7.7)	3 (2.2)	0.13

Echo-1: First (or baseline) echocardiogram; Echo-3: Third echocardiographic; ACEI: Angiotensin-converting enzyme inhibitors; ARB: Angiotensin receptor blockers; HDZ: Hydralazine; ISDN: Isosorbide dinitrate; IV: Intravenous; MRA: Mineralocorticoid receptor antagonists.

Table 6 Multivariate nominal logistic regression analysis

Variable	Adjusted OR (95%CI)	P value
Age in years	0.99 (0.95-1.0)	0.42
Female	6.8 (1.4-32.3)	0.02
HF etiology
Ischemic	1 (reference)	-
Dilated	3.1 (1.03-9.3)	0.04
Others	1.7 (0.30-9.3)	0.56
Hyperlipidemia	0.50 (0.21-1.11)	0.09
Hypertension	0.40 (0.13-1.16)	0.09
MRA use	7.0 (1.50-31.8)	0.01

CI: Confidence interval; OR: Odds ratio; HF: Heart failure; MRA: Mineralocorticoid receptor antagonists.