Impact of Promising Biomarkers on Severity and Outcome of Acute Pulmonary Embolism

Figures & data

Table 1 Demographic and Clinical Characteristics of the Study Groups

	APE Patients with			p
	Low-Risk (n=14)	Moderate-Risk (n=16)	High-Risk (n=17)
Age (year)^†	49.71±16.59	58.44±15.66	60.88±12.87	0.084
Sex^‡
Female	7 (50.0)	4 (25.0)	11 (64.7)	0.071
Male	7 (50.0)	12 (75.0)	6 (35.3)
Smoking (pack/year)^†	15.71±21.74	8.13±12.5	17.94±23.46	0.314
BMI (kg/m2)^†	27.83±5.54	29.99±4.11	27.87±4.95	0.242
Comorbidities^‡
Hypertension	5 (35.7)	8 (50)	7 (41.2)	0.725
Diabetes mellitus	2 (14.3)	3 (18.8)	1 (5.9)	0.531
COPD	3 (21.4)	1 (6.3)	5 (29.4)	0.232
Major risk factors^‡
Immobilization	10 (71.4)	10 (62.5)	12 (70.6)	0.839
Long lasting travel	3 (21.4)	3 (18.8)	0 (0)	0.139
Previous major surgery	3 (21.4)	5 (31.3)	5 (29.4)	0.818
CVA	2 (14.3)	1 (6.3)	0 (0)	0.269
Previous APE	2 (14.3)	3 (18.8)	1 (5.9)	0.531
Trauma	0 (0.0)	2 (12.5)	0 (0.0)	0.132

Notes: ^†Mean ±standard deviation, ^‡n (%).

Abbreviations: APE, acute pulmonary embolism; BMI, body mass index; COPD, chronic obstructive pulmonary disease; CVA, cerebrovascular accident.

Table 2 The Distribution of the Clinical Parameters in the Study Groups

	APE Patients with			p
	Low-Risk (n=14)	Moderate-Risk (n=16)	High-Risk (n=17)
Heart rate per min^†	94.79±10.8	87.88±14.19	98.71±19.41	0.072
Respiratory rate per min†	22.21±5.12	23.75±4.91	25.18±5.26	0.191
SBP (mmHg)^†	119.29±11.91	120.31±14.66	92.65±13.71	<0.001
DBP (mmHg)^†	72.86±8.25	75.31±9.57	59.71±11.79	<0.001
PaO2 (mmHg)^†	68.1±11.04	67.31±9.23	59.94±11	0.060

Notes: ^†Mean ±standard deviation.

Abbreviations: APE, acute pulmonary embolism; SBP, systolic blood pressure; DBP, diastolic blood pressure; PaO₂, partial pressure of oxygen.

Table 3 Comparison of the Patients with Different Severity Grades According to the Laboratory, Computed Tomography and Echocardiography Findings

	APE Patients with			p
	Low-Risk (n=14)	Moderate-Risk (n=16)	High-Risk (n=17)
Laboratory parameters
Hemoglobin (g/dl)^†	12.44±1.5	10.89±3.3	11.81±2.76	0.353
White blood cell count (/mm³)^†	8945±3812.1	9281.88±3466	9730.59±4815.12	0.976
Platelet count. (/mm³)^†	273.79±93.67	288.5±164.3	199.29±91.27	0.020
Total protein (g/dl)^†	6.76±0.35	6.67±0.4	6.36±0.33	0.007
Albumin. (g/dl)^†	3.59±0.29	3.52±0.45	3.01±0.91	0.031
CRP (mg/dl)^†	44.64±39.16	54.62±43.93	55.04±44.73	0.749
ESR (mm/hr)^†	37.21±21.97	40.31±23.95	44.59±28.34	0.875
Cardiac biomarkers
cTnT (ng/mL)^†	0±0.01	0.03±0.09	0.04± 0.09	0.196
Myoglobin (ng/mL)^†	109.86±52.5	184.16±111.56	491.24±663.82	0.171
NT-proBNP (pg/mL)^†	75.21±67.2	274.32±490.56	809.76±705.12	0.009
H-FABP (ng/mL)^†	35.19±14.8	67. 53±77.39	161.84±341.72	0.183
D-dimer (ng/mL)^†	4486.64±3415.6	8251.5±5517.6	9624.65±1020.2	0.971
GDF-15 (ng/mL)^†	11.71±6.56	15.55±11.36	23.26±12.67	0.037
Involvement on Tomography
Peripheral ^‡	8 (61.5)	7 (43.8)	4 (23.5)	0.864
Central ^‡	2 (15.4)	7 (43.8)	5 (29.4)	0.132
Diffuse ^‡	2 (15.4)	2 (12.5)	8 (47.1)	0.097
Echocardiography
Interventricular septal deviation/paradoxical movements	0 (0)	1 (%6.3)	14 (%82.4)	<0.001
Admission PAP (mmHg)^†	31.36±7.91	42.88±10.26	59.53±13.69	<0.001
3rd month PAP (mmHg)^†	24.29±3.63	28.75±4.93	36.41±5.39	<0.001
TAPSE (cm)	24.2 ± 3.4	22.1 ± 3.4	19.6 ± 4.0	0.005 <0.001 0.031
RV/LV ratio ≥1 (n, %)	0 (0)	2 (12.5%)	13 (76.4%)
RV FAC values (%)	56.6 ± 7.9	49.9± 8.2	45.4 ± 8.9
LVEF (%)^†	65.64±6.05	61±4.16	59.94±5.73

Notes: ^†Mean ±standard deviation, ^‡n (%).

Abbreviations: APE, acute pulmonary embolism; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; cTnT, cardiac troponin T; NT-proBNP, N terminal pro-brain natriuretic peptide; H-FABP, heart-type fatty acid-binding protein; GDF-15, growth differentiation factor-15; PAP, pulmonary artery pressure; TAPSE, Tricuspid annular plane systolic excursion; RV/LV, right ventricular/left ventricular; FAC, Right ventricular fractional area change; LVEF, left ventricular ejection fraction.

Table 4 The Comparison of the Cardiac Biomarkers in Patients Who Survived and Non-Survived Patients

	Survived (n=38)	Non-Survived (n=9)	p
cTnT (ng/mL)^†	0.03±0.08	0.02±0.02	0.205
Myoglobin (ng/mL)^†	186.86±166.92	254.82±293.75	0.791
NT-proBNP (pg/mL)^†	313.03±502.39	910.41±812.35	0.058
H-FABP (ng/mL)^†	56.5±59.01	388.14±608.29	0.023
D-dimer (ng/mL)^†	6028.79±4458.79	18,299.2±15,223.82	0.008
GDF-15 (ng/mL)^†	14.83±9.85	25.72±13.7	0.047

Notes: ^†Mean ±standard deviation.

Abbreviations: cTnT, cardiac troponin T; NT-proBNP, N terminal pro-brain natriuretic peptide; H-FABP, heart-type fatty acid-binding protein; GDF-15, growth differentiation factor-15.

Table 5 The Receiver Operating Curve Analysis of the Cardiac Biomarkers in Predicting the Development of Morbidity

	AUC	CI 95%	Cut-Off	Sensitivity	Specificity	+LR	- LR	PPV	NPV
D-dimer	0.622±0.082	0.469–0.759	10,855	37	95	7.41	0.66	90.9	52.8
GDF-15	0.796±0.064	0.653–0.899	9.3	88.9	65	2.54	0.17	77.4	81.2
H-FABP	0.693±0.077	0.540–0.820	37.8	63	78.9	2.99	0.47	81	60
Myoglobin	0.589±0.084	0.436–0.730	100	77.8	45	1.41	0.49	65.6	60
NT-ProBNP	0.741±0.072	0.592–0.857	9.92	74.1	75	2.96	0.35	80	68.2

Abbreviations: AUC, area under curve; CI, confidence interval; +LR, positive likelihood ratio; -LR, negative likelihood ratio; PPV, positive predictive value; NPV, negative predictive value; cTnT, cardiac troponin T; NT-proBNP, N terminal pro-brain natriuretic peptide; H-FABP, heart-type fatty acid-binding protein; GDF-15, growth differentiation factor-15.

Table 6 The Receiver Operating Curve Analysis of the Cardiac Biomarkers in Predicting the Development of All-Cause Mortality

	AUC	CI 95%	Cut-Off	Sensitivity	Specificity	+LR	- LR	PPV	NPV
D-dimer	0.837±0.115	0.692–0.931	>6688	100	65.8	2.92	0	27.8	100
GDF-15	0.776±0.128	0.623–0.889	>19.7	80	76.3	3.38	0.26	30.8	96.7
HFABP	0.827±0.118	0.679–0.926	>85.8	80	83.8	4.93	0.24	40	96.9
Myoglobin	0.674±0.140	0.514–0.809	>245.8	60	86.8	4.56	0.46	37.5	94.3
NT-ProBNP	0.889±0.099	0.756–0.964	>229.2	100	71.1	3.45	0	31.3	100

Abbreviations: AUC, area under curve; CI, confidence interval; +LR, positive likelihood ratio; -LR, negative likelihood ratio; PPV, positive predictive value; NPV, negative predictive value; cTnT, cardiac troponin T; NT-proBNP, N terminal pro-brain natriuretic peptide; H-FABP, heart-type fatty acid-binding protein; GDF-15, growth differentiation factor-15.

Data Sharing Statement

The data supporting the revelations of this study can be retrieved from the corresponding author upon reasonable request.