Prognostic value of plasma secretoneurin concentration in patients with heart failure with reduced ejection fraction in one-year follow-up

Figures & data

Figure 1. STARD diagram to report flow of participants through the study.

Table 1. Baseline data obtained in patients enclosed with and without HFrEF exacerbation.

Parameter	Exacerbation (n = 70)	Stable (n = 52)	p
Male gender (n, %)	48 (50.50)	47 (49. 47)	0.005
Age (years)	67.93 ± 14.38	51.58 ± 9.16	< 0.001
30-days all-cause mortality (n, %)	5 (7.14)	0	1.0
30-days all-cause readmission (n, %)	59 (15.7)	13 (25.00)	1.0
One year all-cause mortality (n, %)	19 (27.14)	0	<0.001
One year all-cause readmission (n, %)	34 (48.57)	5 (9.62)	<0.001
Composed end-point occurrence during one year (n, %)	42 (84.29)	5 (9.62)	< 0.001
TAPSE (mm)	16.99 ± 3.63	20.83 ± 3.93	<0.001
LVEF (%)	25.66 ± 9.07	28.65 ± 7.53	0.055
Etiology, DCM/ICM (n, %)	34 (48.57)	36 (69.26)	0.022
	36 (51.46)	16 (30.77)
BMI (kg/m^2)	29.78 ± 6.55	28.73 ± 4.99	0.335
Diabetes mellitus (n, %)	35 (50.00)	15 (28.85)	0.019
Hypertension (n, %)	47 (67.14)	18 (34.62)	<0.001
Atrial fibrillation (n, %)	40 (57.14)	20 (38.46)	0.071
cardiac implantable electronic devices (n, %)	36 (51.43)	27 (48.08)	<0.001
NT-proBNP (pg/ml)	6373.0 (3345.0 − 12364.0)	441.5 (179.5-1093.5)	<0.001
Secretoneurin (pmol/l)	71.20 (58.15-101.47)	9.11 (6.17-12.74)	<0.001
Troponin T (ng/ml)	0.04 (0.03-0.06)	0.02 (0.01-0.02)	<0.001
Creatinine (mg/dl)	1.34 ± 0.44	1.01 ± 0.27	<0.001
Glucose (mg/dl)	141.69 ± 50.29	110.89 ± 25.72	<0.001
hsCRP (mg/dl)	20.51 ± 34.60	3.98 ± 14.01	0.002
Hemoglobin (g/dl)	12.53 ± 2.23	14.64 ± 1.22	<0.001
White blood cells count (G/L)	8.68 ± 2.81	7.31 ± 1.89	0.003

Data presented as median ± standard deviation, or median (IQR), depending on variable.

distribution. TAPSE: tricuspid annular plane systolic excursion; LVEF: left ventricular ejection fraction; DCM/ICM: dilated cardiomyopathy/ischemic cardiomyopathy; BMI: body mass index; NT-proBNP: N-terminal fragment of B-type natriuretic propeptide; hsCRP: high-sensitivity C-reactive protein; RDW: red cell distribution; p: probability.

Table 2. Values of parameters studied in patients with respective NYHA class.

Parameter	NYHA II (n = 39)	NYHA III (n = 44)	NYHA IV (n = 39)	P23	P24	P34
Male gender (n, %)	37 (94.87)	30 (68.18)	28 (71.79)	0.002	0.006	0.724
Age (years)	50.59 ± 9.68	64.795 ± 15.05	67.00 ± 13.55	< 0.001	< 0.001	0.487
Death during 12 months (n, %)	0	6 (13.64)	13 (33.33)	0.016	< 0.001	0.033
One year readmission (n, %)	5 (12.82)	12 (27.27)	22 (56.41)	0.106	< 0.001	0.007
Composed end-point occurrence during one year (n, %)	5 (12.82)	15 (34.09)	27 (69.27)	0.02	< 0.001	< 0.001
TAPSE (mm)	20.41 ± 3.92	19.02 ± 4.30	16.385 ± 3.37	0.130	< 0.001	0.003
LVEF (%)	29.46 ± 6.83	27.07 ± 8.83	24.26 ± 9.15	0.175	0.006	0.159
Etiology, DCM/ICM (n, %)	25 (64.10)	27 (61.36)	18 (46.15)	0.800	0.114	0.169
	14 (35.90)	17 (38.64)	21 (53.85)
BMI (kg/m^2)	28.72 ± 5.48	30.47 ± 6.40	28.67 ± 5.81	0.187	0.973	0.187
Diabetes mellitus (n, %)	9 (23.08)	24 (54.55)	17 (43.59)	0.003	0.056	0.325
Hypertension (n, %)	14 (35.90)	25 (56.82)	26 (66.67)	0.058	0.006	0.364
Atrial fibrillation (n, %)	17 (43.59)	20 (45.45)	23 (58.97)	0.356	0.179	0.325
Cardiac implantable electronic devices (n, %)	19 (48.72)	26 (59.19)	23 (58.97)	0.310	0.330	0.938
NT-proBNP (pg/ml)	373.0 (168.0-1067.0)	5179.0 (1496.5-9429.5)	6173.0 (2986.0-13052.0)	< 0.001	< 0.001	0.366
Secretoneurin (pmol/l)	9.6 (6.5-12.82)	64.8 (14.5-84.2)	68.35 (57.5-103.3)	< 0.001	< 0.001	0.024
Troponin T (ng/ml)	0.01 (0.01-0.02)	0.03 (0.02-0.06)	0.03 (0.03-0.06)	0.009	0.002	0.651
Creatinine (mg/dl)	1.02 ± 0.23	1.21 ± 0.40	1.38 ± 0.48	0.009	< 0.001	0.090
Glucose (mg/dl)	110.54 ± 26.47	132.48 ± 43.04	142.15 ± 53.73	0.007	0.001	0.366
hsCRP (mg/dl)	4.46 ± 16.16	9.59 ± 14.22	26.84 ± 43.34	0.128	0.003	0.015
Hemoglobin (g/dl)	14.65 ± 1.25	13.10 ± 2.20	12.59 ± 2.25	< 0.001	< 0.001	0.302
White blood cells count (1000/mm3)	7.25 ± 1.79	7.77 ± 2.12	9.31 ± 3.16	0.238	0.001	0.010

Data presented as median ± standard deviation, or median (IQR), depending on variable distribution. TAPSE: tricuspid annular plane systolic excursion; LVEF: left ventricular ejection fraction; DCM/ICM: dilated cardiomyopathy/ischemic cardiomyopathy; BMI: body mass index; NT-proBNP: N-terminal fragment of B-type natriuretic propeptide; hsCRP: high-sensitivity C-reactive protein; RDW: red cell distribution.

Table 3. Clinical characteristics of patients studied who died during a 12 month follow-up in comparison to those who survived this period.

Parameter	Died (n = 19)	Survived (n = 103)	p
Male gender (n, %)	14 (73.68)	81 (78.64)	0.636
Age (years)	72.32 ± 11.98	58.86 ± 14.36	< 0.001
NYHA class (II, III vs IV)	0	39 (37.86)	0.115
	6 (31.58)	38 (36.89)
	13 (68.42)	26 (25.24)
All-cause read­mission (n, %)	11 (57.89)	28 (27.18)	< 0.01
TAPSE (mm)	16.89 ± 2.92	18.94 ± 4.33	0.051
LVEF (%)	25.26 ± 8.07	27.24 ± 8.63	0.356
Etiology, DCM/ICM (n, %)	9 (47.37)	61 (59.22)	0.341
	10 (52.63)	42 (40.78)
BMI (kg/m^2)	25.85 ± 8.07	29.98 ± 5.82	< 0.01
Diabetes mellitus (n, %)	8 (42.11)	42 (40.78)	0.915
Hypertension (n, %)	10 (52.63)	55 (53.40)	0.951
Atrial fibrillation (n, %)	12 (63.16)	48 (46.60)	0.620
Cardiac implantable electronic devices (n, %)	11 (57.89)	77 (74.76)	< 0.01
NT-proBNP (pg/ml)	6712.0 (3244.0-12767.5)	1143.0 (348.0-4756.0)	< 0.001
Secretoneurin (pmol/l)	68.28 (46.2-101.6)	13.23 (8.25-61.01)	< 0.001
Troponin T (ng/ml)	0.04 (0.03-0.06)	0.02 (0.01-0.03)	0.074
Creatinine (mg/dl)	1.43 ± 0.39	1.16 ± 0.40	< 0.01
Glucose (mg/dl)	146.26 ± 56.01	125.29 ± 41.18	0.057
hsCRP (mg/dl)	29.54 ± 37.73	10.50 ± 26.07	< 0.01
Hemoglobin (g/dl)	11.75 ± 2.43	13.74 ± 1.93	< 0.001
White blood cells count (1000/mm3)	8.87 ± 2.91	7.95 ± 2.46	0.151

TAPSE: tricuspid annular plane systolic excursion; LVEF: left ventricular ejection fraction; DCM/ICM:

dilated cardiomyopathy/ischemic cardiomyopathy; BMI: body mass index; NT-proBNP: N-terminal fragment of B-type natriuretic propeptide; hsCRP: high-sensitivity C-reactive protein; RDW: red cell distribution; p: probability.

Table 4. A comparison of the Spearman correlations obtained for SN and NT-proBNP.

Clinical feature	NT-proBNP (pmol/l)		Secretoneurin (pmol/l)
	R Spearman	p	R Spearman	p
Male gender	−0.259	0.004	−0.228	0.011
Age (years)	0.590	< 0.001	0.586	< 0.001
Exacerbated vs. stable course of CHF during follow-up	−0.772	< 0.001	−0.857	< 0.001
NYHA class	0.659	< 0.001	0.672	< 0.001
Need of hospitalization due to CHF exacerbation	0.349	< 0.001	0.288	0.001
Death during follow-up	0.470	< 0.001	0.426	< 0.001
Composite end-point occurrence	0.534	< 0.001	0.465	< 0.001
TAPSE (mm)	−0.487	< 0.001	−0.454	< 0.001
LVEF (%)	−0.272	0.002	−0.107	0.240
BMI (kg/m^2)	−0.143	0.116	0.089	0.331
History of DM	0.098	0.281	0.215	0.018
History of HT	0.101	0.267	0.291	0.001
History of AF	0.142	0.119	0.204	0.024
Creatinine (mg/dl)	0.419	0.000	0.425	0.000
hs-CRP (mg/dl)	0.569	0.000	0.581	0.000

NT-proBNP: N-terminal fragment of B-type natriuretic propeptide; HFrEF: heart failure with reduced ejection fraction; NYHA: New York Heart Association; TAPSE: tricuspid annular plane systolic excursion; LVEF: left ventricular ejection fraction; BMI: body mass index; DM: diabetes mellitus; HT: hypertension; AF: atrial fibrillation; hs-CRP: high-sensitivity C-reactive protein.

Table 5. Parameters of diagnostic usefulness obtained in ROC analysis for biomarkers discriminating HFrEF patients who died during one-year follow-up and those who survived observation period.

Biomarker	Cut-offs	AUC, 95%CI	P
Age (years)	63	0.769; 0.659-0.879	< 0.001
BMI (kg/m^2)	18.5	0.290; 0.154-0.427	0.003
Secretoneurin (pmol/l)	34.5	0.760; 0.669-0.852	<0.001
NT-proBNP (pg/ml)	2375	0.806; 0.712-0.901	<0.001
Creatinine (mg/dl)	1.11	0.715; 0.587-0.843	< 0.001
Hematocrit (%)	45.2	0.301; 0.157-0.445	0.007
Platelets count (1000/mm3)	319	0.337-0.178-0.496	0.044
Neutrophiles (%)	68.7	0.722; 0.600-0.844	< 0.001

AUC: area under curve; CI: confidence interval; ROC: receiver operating characteristic curve; BMI: body mass index; NT-proBNP: N-terminal fragment of B-type natriuretic propeptide; p: probability; AUC: area under the curve.

Table 6. T-test for secretoneurin and NT-proBNP grouping patients with diabetes mellitus.

variable	Test t; diabetes mellitus
	DM+	DM-	t	df	p	n1	n0	Sd1	Sd0
secreto­neurin (pmol/l)	75.662	41.799	3.043	120	0.003	50	72	80.589	41.150
NT-proBNP (pg/ml)	5608.520	5970.875	−0.253	120	0.800	50	72	5955.269	8801.171

NT-proBNP: N-terminal fragment of B-type natriuretic propeptide; DM: diabetes mellitus; n1: group with stable heart failure with reduced ejection fraction; n0: group with exacerbated heart failure with reduced ejection fraction, Sd: standard deviation; p: probability.

Table 7. T-test for secretoneurin grouping patients according to gender.

variable	Test-t; gender
	male	female	t	df	p	male	female	Sd1	Sd2
secretoneurin (pmol/l)	49.555	77.222	−2.057	120	0.042	95	27	60.322	66.264

df: degrees of freedom; Sd: standard deviation; p: probability.

Figure 2. Kaplan Meier’s plot for HFrEF patients survival in relation to plasma SN concentration.

Figure 3. Kaplan Meier’s plot for HFrEF patients survival in relation to plasma NT-proBNP concentration.

Figure 4. Kaplan Meier’s plot for HFrEF patients survival in relation to age.

Data availability statement

All data used to support the finding of this study are available from the corresponding author upon request.