Pentraxin-3 is Associated with Adverse Diastolic Remodeling in Patients with ST-Elevation Myocardial Infarction after Successful Reperfusion by Primary Percutaneous Intervention.

BACKGROUND: Determinants of adverse diastolic remodeling in ST-elevated myocardial infarction (STEMI) after successful revascularization are not well established. Besides, the relationship between Pentraxin-3 (PTX-3) and diastolic function deterioration is unknown. This study hypothesizes that PTX-3 level would be associated with diastolic remodeling.
MATERIALS AND METHODS: Ninety-eight STEMI patients were included in our study. Echocardiography was performed before and 12-18 weeks after discharge. Two groups were generated according to the PTX-3 value, and the follow-up/baseline echocardiographic parameters were compared. Diastolic adverse remodeling was accepted as a persistent restrictive filling pattern or an increase in at least one grade of diastolic dysfunction. The independent predictors of diastolic adverse remodeling were investigated.
RESULTS: Adverse diastolic remodeling was detected in 19.3% of patients. High left ventricular mass index (odds ratio [OR]: 1.096, confidence interval [CI] 95%: 1.023-1.174, P = 0.009), high PTX-3 (OR: 1.005, CI 95%: 1.001-1.009, P = 0.024), and failing to achieve thrombolysis in myocardial infarction flow 3 after percutaneous coronary intervention (OR: 6.196, CI 95%: 1.370-28.023, P = 0.005) were determined as independent predictors of adverse diastolic remodeling. The ratio of follow-up/baseline left atrial volume index was higher in the high PTX-3 group (1.15 vs. 1.05, P = 0.029). Moreover, being in the high PTX-3 group predicted adverse diastolic remodeling at 7.4 times.
CONCLUSION: Higher PTX-3 level is associated with adverse diastolic remodeling in STEMI patients. Copyright:

INTRODUCTION

Diastolic dysfunction (DD) after myocardial infarction (MI) is a common condition.[12] MI can cause DD, both by myocardial necrosis and subsequent myocardial edema, scar formation, and by recovery in the myocardium after MI and subsequent remodeling.[34] In addition, regional asynchrony between ischemic and normal myocardium after MI and impaired ventricular relaxation may contribute to this situation.[5] Different studies have shown that DD is an independent predictor of both adverse cardiovascular events and reduced functional capacity, regardless of the presence of systolic dysfunction after MI.[12]

Pentraxin-3 (PTX-3), a member of the pentraxin family, is thought to play a role in pro-inflammatory pathways as an acute phase protein. PTX-3 is released from many different cells such as dendritic cells, macrophages, neutrophils, fibroblasts, endothelial cells, and renal cells from the inflammation site.[67] While C-reactive protein is synthesized only from the liver and released into the bloodstream in conditions other than inflammation, PTX-3 is synthesized and released from the inflammation site and binds to the endothelium. Therefore, PTX-3 is thought to be a more specific indicator of inflammatory reaction.[8]

It has been found that PTX-3 is higher in patients with preserved ejection fraction heart failure (HFPEF) compared to those without heart failure (HF) and is an independent predictor of the disease.[9] Furthermore, it has been shown that PTX-3 can predict adverse events in patients with reduced ejection fraction HF (HFREF).[1011] However, there was no study examining the factors affecting the progression of DD after MI in the literature. Therefore, we aimed to determine the predictors of left ventricular (LV) diastolic adverse remodeling and the relationship between the change in diastolic functions and PTX-3 in patients with ST-elevated myocardial infarction (STEMI) who were successfully revascularized with percutaneous coronary intervention (PCI).

MATERIALS AND METHODS

Study population

The study population consisted of patients who were admitted to our center with STEMI and underwent revascularization with PCI. Patients who died during angiography or hospital follow-up; patients with an active infection, malignancy, active rheumatic disease, and systemic inflammatory disease; patients with severe mitral stenosis or mitral regurgitation, prosthetic valve, atrial fibrillation; and patients with planned coronary artery bypass graft after angiography were excluded from the study. In addition, patients who were hospitalized and underwent coronary procedures due to acute coronary syndrome before control echocardiography and patients with thrombolysis in myocardial infarction (TIMI) flow 0–1 after primary percutaneous coronary procedure, considered as failed revascularization, were excluded from the study. Consequently, a total of 98 patients were accepted as the study population after exclusion criteria [Figure 1].

Figure 1

Flowchart showing patient recruitment by inclusion and exclusion criteria. CABG = Coronary artery bypass graft, PCI = Percutaneous coronary intervention

All PCI procedures were performed by operators performing more than 100 PCIs per year in a single center. Beta-blockers and renin–angiotensin system inhibitors were started within 24 h if it was tolerable and tried to achieve maximum dose in a controlled manner. The vascular access site, PCI materials used, and the predilatation and postdilatation requirements were left to the operator's choice. Informed consent forms were obtained from all patients, and approval was obtained from the local ethics committee. The study was designed in accordance with the rules of the Helsinki Declaration.

Analysis of patient data

Patients' demographic information, medical charts, laboratory parameters, and angiographic characteristics were recorded. Five milliliters of peripheral venous blood was taken from all patients and placed in EDTA-lined vacuum tubes for PTX-3. Immediately, thereafter, it was separated by centrifugation and stored at −70°C. Following the manufacturer's protocol, PTX-3 levels were achieved by sandwich enzyme immunoassay using The Boster Picokine Human PTX-3 Pre-Coated ELISA kits. Within and between tests, the PTX-3 coefficients of variation were 8%–10%. The sensitivity of the PTX-3 test for plasma samples was 0.10 pg/mL.

Echocardiographic analysis

All patients underwent echocardiographic examination early (median 48 h, interquartile change 36–60 h) and follow-up (median: 102 days, interquartile: 84–129 days) after STEMI presentation. LV ejection fraction (LVEF) was calculated by the Simpson method using transthoracic echocardiography device (Vivid S5 probe 3 S-RS, GE Healthcare, Wisconsin, USA). LV diameters were measured using M mode as recommended by the American Society of Echocardiography.[12] Ventricular dilation was measured using the LV end-diastolic volume index (LVEDVI) and LV end-systolic volume index (LVESVI). LVEDVI and LVESVI were obtained by dividing the LV end-diastolic and LV end-systolic volumes measured by the Simpson method to the body surface area. All echocardiographic evaluations were made by an experienced cardiologist blinded to the study protocol.

DD was determined by measuring the mitral inflow and tissue Doppler imaging in the septal and lateral regions. Measurements were made during respiration over five subsequent cycles, and mean values were recorded. In order to determine the mitral inflow, a 1 mm pulsed sample box was measured using a sweep speed of 100 mm/s at the end of expiration to the mitral leaf tips from apical four-chamber view. 2-mm pulsed wave sample box was placed in the septal and lateral parts of the mitral annulus for Doppler tissue imaging. Average e' was calculated using the septal + lateral e'/2 formula. E/e' ratio was obtained by dividing mitral inflow E wave velocity to septal, lateral, and average e'. Disk summation algorithm was used while measuring left atrial volume index (LAVI). LAVI was measured from apical 4-chamber and apical 2-chamber views just before mitral valve opening after ventricular end-systole. LAVI was obtained by including the left atrial appendage and excluding the pulmonary vein inflow part.[12] Patients were divided into four groups in terms of diastolic functions (0 = normal, 1 = impaired relaxation, 2 = pseudonormal, and 3 = restrictive filling pattern). DD grading was performed using DD algorithm designed for the patient with underlying myocardial disease published in 2016.[13] Accordingly, Grade 3 DD criteria were E/A ratio >2, Grade 2 DD criteria were E/A ratio: 0.8–2 or E/A ratio <0.8 + E >0.5 cm/s, and one of the two factors (LAVI >34 ml/m2, E/average e'>14), Grade 1 DD criteria were E/A ratio <0.8 and E <0.5 cm/s, Grade 0 DD criteria were E/A ratio >0.8, E/e '<10 and LAVI <34 ml/m2. Grade 2 and 3 DD were considered severe DD. Adverse diastolic modeling was accepted as ≥1 grade increase in diastolic function phase in follow-up echoes or persistent continuation of Grade 3 DD in the light of other studies.[14] LV mass was measured using linear dimensions as suggested by Devereux et al. LV mass index over 109 g/m2 for women and over 132 g/m2 for men was evaluated as moderate/severe LV hypertrophy.[15]

Statistical analysis

SPSS software version 21.0 for Windows (SPSS Inc., Chicago, Illinois, USA) was used for statistical analysis. Whether the values were distributed normally was determined by visual and analytical methods. Patients were divided into two groups as high and low PTX-3 based on median value (2.9 ng/ml). The study groups were compared using independent sample t-test for continuous variables with normal distribution and using the Mann–Whitney U-test for continuous variables without normal distribution. Categorical data were compared with the Chi-square test. Logistic regression analysis was performed to determine the independent predictors of adverse diastolic remodeling. A P < 0.05 was considered statistically significant.

RESULTS

Ninety-eight patients (mean age: 59.9 ± 11.2) were included in the study. Study population was divided into two groups according to the median value as high PTX-3 group (n = 49, mean age: 58.6 ± 11.3) and low PTX-3 group (n = 49, mean age: 61.1 ± 11.2). Baseline clinical characteristics, laboratory values, angiographic characteristics, and information about discharge prescription were compared in Table 1, and there was no statistical difference between the groups in any parameter. When baseline echo parameters compared, there was no difference between the groups in terms of LV diameters, LVEF, and wall motion score index [Table 2]. There was only a statistical difference in mitral E velocity in terms of diastolic parameters and it was higher in the high PTX-3 group (0.65 ± 0.13 vs. 0.59 ± 0.13, P = 0.032).

Table 1

Baseline characteristics of study population according to pentraxin-3 group

	Total (n=98), n (%)	High PTX-3 group (n=49), n (%)	Low PTX-3 group (n=49), n (%)	P
Age (years)	59.9±11.2	58.6±11.3	61.1±11.2	0.311
Female	18 (18.4)	9 (18.4)	9 (18.4)	1.0
BMI (kg/m2)	27.4±4.1	27.6±4.7	27.2±3.4	0.806
Hypertension	35 (35.7)	16 (32.4)	19 (38.8)	0.527
Diabetes mellitus	22 (22.4)	14 (28.6)	8 (16.3)	0.146
Smoking	64 (65.3)	32 (65.3)	32 (65.3)	1.0
PCI	9 (9.2)	5 (10.2)	4 (8.2)	0.727
CABG	5 (5.1)	1 (2.0)	4 (8.2)	0.168
SBP (mmHg)	127.3±22.1	125.6±24.3	129.0±19.8	0.284
DBP (mmHg)	73.9±12.8	75.0±14.2	72.8±11.4	0.357
Heart rate (beats/min)	79.0±16.2	79.8±14.5	78.3±17.8	0.520
Previous angina	40 (40.8)	19 (38.8)	21 (42.9)	0.681
Killip class >1	20 (20.4)	11 (22.4)	9 (18.4)	0.616
Labaratory values
CK-MB (ng/ml)	127.6±99.0	138.4±11.5	116.8±96.4	0.284
Troponin (ng/ml)	4.3±3.1	4.8±3.2	3.8±3.0	0.137
GFR (ml/dk/1.73 m2)	81.7±26.2	79.7±27.4	83.8±25.1	0.365
WBC (×1000/mm3)	11.3±4.2	12.0±5.2	10.7±2.8	0.237
CRP (mg/dl)	21.3±22.6	23.3±21.2	19.3±24.0	0.115
Total cholesterol (mg/dl)	180.4±44.7	176.7±44.7	184.1±44.8	0.380
HDL (mg/dl)	39.4±11.1	39.7±12.1	39.1±10.0	0.862
LDL (mg/dl)	108.3±36.4	103.3±37.1	113.3±35.3	0.148
Intervention-related assesments
Predilatasyon	74 (75.5)	37 (75.5)	37 (75.5)	1.0
Postdlatasyon	39 (39.8)	19 (38.8)	20 (40.8)	0.836
Culprit artery
LAD	38 (38.8)	19 (38.8)	19 (38.8)	0.443
CX	12 (12.2)	5 (10.2)	7 (14.3)
RCA	46 (46.9)	25 (51.0)	21 (42.9)
Saphenous vein graft	2 (2.0)	0	2 (4.1)
Stent length (mm)	18.0±5.8	18.5±4.7	17.6±6.7	0.193
Stent diameter (mm)	3.03±0.40	3.08±0.44	2.98±0.36	0.418
Pre-TIMI flow
0	67 (68.4)	35 (71.4)	32 (65.3)	0.400
1	7 (7.1)	3 (6.1)	4 (8.2)
2	9 (9.2)	6 (12.2)	3 (6.1)
3	15 (15.3)	5 (10.2)	10 (20.4)
Drug eluting stent	65 (66.3)	32 (65.3)	33 (67.3)	0.831
Symptom-to-balloon time (min)	339.1±165.5	351.5±181.1	326.7±146.7	0.685
Final TIMI flow post PCI
2	13 (13.3)	8 (16.3)	5 (10.2)	0.372
3	85 (86.7)	41 (83.7)	44 (89.8)
Discharge medications
Dual antiplatelet	96 (98.0)	47 (95.9)	49 (100)	0.153
Beta blocker	84 (85.7)	41 (83.7)	43 (87.8)	0.564
ACE inh/ARB	70 (71.4)	35 (71.4)	35 (71.4)	1.0
Statin	85 (86.7)	44 (89.8)	41 (83.7)	0.372

GFR=Glomerular filtration rate, SBP=Systolic blood pressure, DBP=diastolic blood pressure, CABG=Coronary artery bypass graft, PCI=Percutaneous coronary intervention, CK-MB=Creatinin kinaz-MB, CRP=C-reactive protein, PTX-3=Pentraxin-3, BMI=Body mass index, LAD=Left anterior descending artery, CX=Circumflex artery, RCA=Right coronary artery, WBC=White blood cells, HDL=High density lipoprotein, LDL=Low density lipoprotein, ACE inh=Angiotensin-converting enzyme, ARB=Angiotensin receptor blockers, TIMI=Thrombolysis in myocardial infarction

Table 2

Echocardiographic parameters of study population according to pentraxin -3 group

	Total (n=98)	High PTX-3 group (n=49)	Low PTX-3 group (n=49)	P
LV size and LVEF
LVEF (%)	43.7±8.52	43.0±10.5	44.5±5.9	0.283
LVEDVI (ml/m2)	49.2±9.9	49.9±9.8	48.5±10.7	0.873
LVEDD (mm)	48.5±4.7	49.0±5.0	48.0±4.4	0.238
LVESVI (ml/m2)	27.9±8.6	28.2±8.6	27.6±8.3	0.502
LVESD (mm)	33.7±6.2	34.2±6.6	33.2±5.7	0.389
PWT (mm)	11.0±1.2	11.0±1.4	11.1±1.1	0.789
IVS thickness (mm)	11.7±1.7	11.5±1.7	12.0±1.8	0.313
WMSI	24.6±5.6	25.5±6.5	23.8±4.6	0.425
Diastolic parameters
E (cm/s)	0.62±0.13	0.65±0.13	0.59±0.13	0.032
A (cm/sn)	0.71±0.17	0.72±0.20	0.69±0.13	0.424
E/A ratio	0.94±0.36	0.99±0.41	0.88±0.29	0.116
DT (ms)	210±58	201±63.9	218±51	0.182
Septal e’ (cm/s)	6.15±1.89	5.93±1.97	6.36±1.85	0.265
Lateral e’ (cm/s)	7.87±2.64	7.65±2.64	8.10±2.66	0.400
Average e’ (cm/s)	7.01±2.12	6.79±2.09	7.23±2.14	0.312
E/e’ (septal) ratio	11.3±4.2	12.1±4.7	10.6±4.0	0.099
E/e’ (lateral) ratio	9.0±4.2	9.7±4.3	8.4±4.4	0.152
E/e’ (mean) ratio	10.0±4.1	10.6±4.3	9.4±3.7	0.155
LAVI (ml/m2)	29.7±5.6	30.3±4.6	29.1±5.9	0.248
LVMI (g/m2)	107.7±20.9	105.9±19.4	109.4±22.3	0.564

LV=Left ventricular, LVEF=LV ejection fraction, LVEDVI=LV end diastolic volume index, LVEDD=LV end diastolic diameter, LVESVI=LV end systolic volume index, LVESD=LV end systolic diameter, PWT=Posterior wall thickness, IVS=Interventricular thickness WMSI=Wall motion score index, LAVI=Left atrial volume index

The follow-up mitral inflows, tissue Doppler, and E/e' showing LV filling pressure values were compared. In addition, the follow-up/baseline differences of the same parameters for the two groups were also evaluated statistically [Table 3]. LAVI was found to be higher in the high PTX-3 group at follow-up values (34.5 ± 6.0 vs. 30.1 ± 5.5, P = 0.001). Furthermore, lower septal e' (5.4 ± 1.3 vs. 6.4 ± 1.8, P = 0.002) and lateral e' (7.0 ± 1.9 vs. 8.8 ± 2.8, P < 0.001) with higher E/e' septal (13.5 ± 6.6 vs. 10.5 ± 4.4, P = 0.011), E/e' lateral (10.4 ± 5.3 vs. 8.2 ± 4.9, P = 0.032), and E/e' mean (11.7 ± 5.7 vs. 9.0 ± 4.4, P = 0.014) values were determined in the high PTX-3 group at follow-up. When the follow-up/baseline comparison was made, the lateral e' difference (−0.58 ± 2.22 vs. 0.78 ± 2.37, P = 0.004) and the LAVI difference (4.1 ± 3.2 vs. 1.0 ± 1.4, P = 0.024) were statistically significant.

Table 3

Distribution of diastolic parameters of follow-up and follow-up/baseline change according to pentraxin-3 groups

	High PTX-3 group (n=49)	Low PTX-3 group (n=49)	P
E/A ratio
Follow-up	0.96±0.42	0.87±0.23	0.195
Change	−0.033±0.46	−0.008±0.33	0.954
E’ septal cm/s
Follow-up	5.40±1.34	6.45±1.85	0.002
Change	−0.53±1.62	0.09±1.87	0.071
E’ lateral cm/s
Follow-up	7.06±1.92	8.88±2.83	<0.001
Change	−0.58±2.22	0.78±2.37	0.004
E/E’ septal ratio
Follow-up	13.5±6.6	10.5±4.4	0.011
Change	1.4±4.5	−0.08±4.4	0.156
E/E’ lateral ratio
Follow-up	10.4±5.3	8.2±4.9	0.032
Change	0.73±0.45	−0.25±4.2	0.271
E/E’ mean ratio
Follow-up	11.7±5.7	9.0±4.4	0.014
Change	1.07±4.6	0.3±4.1	0.116
LAVI (ml/m2)
Follow-up	34.5±6.0	30.1±5.5	0.001
Change	4.1±3.2	1.0±1.4	0.024

LAVI=Left atrial volume index, PTX-3=Pentraxin-3

Figure 2 shows the baseline and follow-up DD grading of the patients. Accordingly, five patients advanced from Grade 0 to Grade 1, four patients from Grade 1 to Grade 2, one patient from Grade 1 to Grade 3, and one patient from Grade 2 to Grade 3 in the high PTX-3 group. In the same group, one patient regressed from Grade 1 to Grade 0, and one patient from Grade 2 to Grade 1. When low PTX-3 group was evaluated, 11 patients regressed from Grade 1 to Grade 0, one patient from Grade 2 to Grade 1, one patient from Grade 3 to Grade 2, while only two patients progressed from Grade 0 to Grade 1. There was no change in the grades of DD in 71.4% of the patients in total in both groups.

Figure 2

Bar graph showing classification of diastolic function at early and follow-up period according to PTX-3 groups. PTX-3 = Pentraxin-3

Persistence of DD as Grade 3 or an increase of at least 1 in diastolic grading was considered as adverse LV remodeling, and independent predictors of LV adverse remodeling were examined. Accordingly, the absence of post-PCI TIMI flow 3 (odds ratio [OR]: 6.196, confidence interval [CI] 95%: 1.370–28.023, P = 0.005), high LVMI (OR: 1.096, CI 95%: 1.023–1.174, P = 0.009), and PTX-3 level (OR: 1.005, CI 95%, 1.001–1.009, P = 0.024) were determined as independent predictors [Table 4]. Furthermore, moderate/ severe LVMI (OR: 6.01, CI 95%: 1.40–25.83, P = 0.004), and high PTX-3 group (OR: 7.44, CI 95%: 1.38–31.32, P = 0.003) predicted LV adverse remodeling [Figure 3].

Table 4

Independent predictors of adverse diastolic remodeling

Patients charactersitics	Univariate analysis		Multivariate analysis
	OR (95% CI)	P	OR (95% CI)	P
Age (per 1 year)	0.988 (0.933-1.046)	0.667
Diabetes mellitus	2.89 (0.819-10.26)	0.099	0.543 (0.037-7.908)	0.655
Hypertension	2.90 (0.845-9.95)	0.091	2.860 (0.333-23.629)	0.342
Baseline LVEF (per 1%)	1.009 (0.947-1.096)	0.616
Pre-PCI TIMI 0	0.688 (0.188-2.508)	0.570
Post-PCI TIMI <3	3.818 (1.865-9.931)	0.004	6.196 (1.370-28.023)	0.005
LAVI (per 1 ml/m2)	1.004 (0.906-1.134)	0.813
Peak troponin (per 1 ng/ml)	0.923 (0.752-1.133)	0.443
Peak CK-MB (per 1 ng/ml)	0.977 (0.990-1.004)	0.379
LVMI (per 1 g/m2)	1.110 (1.049-1.174)	<0.001	1.096 (1.023-1.174)	0.009
PTX-3 (per 1 ng/ml)	1.005 (1.002-1.008)	0.002	1.005 (1.001-1.009)	0.024
Previous angina	0.441 (0.112-1.745)	0.244

LVEF=Left vetricular ejection fraction, PCI=Percutaneous coronary intervention, LAVI=Left atrial volume index, LVMI=Left ventricular mass index, CK-MB=Creatine kinase-MB, TIMI=Thrombolysis in myocardial infarction, PTX-3=Pentraxin-3, OR=Odds ratio, CI=Confidence interval

Figure 3

Adjusted odds ratios for adverse diastolic remodeling according to LVMI severity, PTX-3 group and post-PCI TIMI flow <3. Cutoff values for PTX-3 were determined according to median value. LVMI = Left ventricular mass index, PTX-3 = Pentraxin-3, PCI = Percutaneous coronary intervention, TIMI = Thrombolysis in myocardial infarction

Finally, the rates obtained by dividing the follow-up LAVI by the baseline LAVI according to the PTX 3 group were compared [Figure 4]. Accordingly, this rate was higher in the high PTX-3 group (1.15 ± 0.26 vs. 1.05 ± 0.20, P = 0.034).

Figure 4

Bar graph showing LAVI ratios between PTX-3 groups. The ratio was determined by dividing the follow-up value into the baseline. LAVI = Left atrial volume index, PTX-3 = Pentraxin-3

DISCUSSION

We can list the important findings of our study as follows: (a) while 13.2% of the patients had progression in the LV diastolic function grade, 15.3% had regression. Nearly 71.3% of the patients had no change in the diastolic function grade, and 6.1% of these patients had persistent restrictive filling pattern; (b) moderate/severe LVMI predicted 6 times, post-PCI TIMI flow <3 predicted 6.1 times, high PTX-3 value predicted 7.4 times of LV diastolic adverse remodeling; (c) higher LAVI ratios were determined in the follow-up/baseline echo comparison in high PTX-3 group; (d) while there was no difference between the groups in terms of baseline septal, lateral, and mean E/e', septal, lateral, and mean E/e' ratios were higher in PTX-3 group in follow-up.

The rate of DD after MI shows differences in the literature. In a study conducted with more than 3000 MI patients, the rate of DD was found to be 20% in patients with an average LVEF of 46%, while it was found to be about 9% in patients with an LVEF >53.[1] The rate of DD after MI was as high as 61.1% in another study.[16] We found that the rate of Grade 2/3 DD, which we considered severe DD, was 16.3%. When Grade 1 DD was included, it was 69.3%. In addition, prognostic evaluation was made in patients with DD after MI in some studies. Detecting restrictive filling in MI patients was found to be prognostically significant in a meta-analysis of 12 prospective studies.[1] More LV dilatation and more congestive HF were detected in patients with impaired relaxation compared to patients with normal diastolic function.[17]

There are limited studies in the literature evaluating serial diastolic functions in post-MI patients. In these studies, worse prognosis and increased cardiac mortality and hospitalizations due to HF in patients with a persistent restrictive pattern or poorly increased diastolic grade were found.[1418] However, these studies did not focus on which factors cause adverse diastolic function. More major cardiovascular event (MACE) was observed in patients with increased grades of DD compared to patients with persistent restrictive filling pattern.[14] These findings also emphasize the importance of evaluating serial diastolic functions of these patients. DD during MI and months later are two different pathological conditions, and their clinical reflection may also be different. For this reason, it is important to determine how the remodeling is progressing. The lack of studies on the etiology of post-MI adverse diastolic remodeling in the literature and the lack of any research showing the relationship between PTX-3, an important inflammation and fibrosis biomarker, and diastolic remodeling make this study valuable.

Myocardial fibrosis is one of the important pathways in the development of adverse remodeling and DD after acute MI. Patients with minimal DD or normal diastolic function had no fibrosis except valvulopathy, congenital heart disease, and pericardial diseases, whereas patients with severe DD were found to have fibrosis regardless of the cause.[19] It has been stated that PTX-3 can be released from fibroblasts in cardiac interstitium and endothelial cells and trigger fibrosis in acute MI.[20] Moreover, it has been shown that endothelial dysfunction has an important role in the prognosis in DD.[21] In other words, PTX-3, released from myocardial fibroblasts and endothelial cells rather than subclinical atherosclerotic lesions, can cause the increase in severity of pathology by triggering fibrosis in individuals with LVDD. We planned this study with the hypothesis that PTX 3 is one of the important predictors of LVDD, and we detected 7.4 times more adverse diastolic remodeling in patients with high PTX-3 levels.

Myocardial remodeling is different in HFREF and HFPEF patients.[22] While cardiomyocytes play a role in this pathway in HFREF, systemic inflammatory state and oxidative stress in the coronary microvascular endothelium in HFPEF patients may play a role in myocardial dysfunction and remodeling.[22] Inflammatory cytokines have been shown to be high in HFPEF patients,[23] and IL 6 which is an important mediator of inflammation, triggers cardiac fibrosis and myocardial stiffening in HFPEF patients.[24] Moreover, PTX-3 can predict HFPEF independently from other factors and has severe correlation with MACE in HFPEF patients.[9] In conclusion, PTX-3 as an important indicator of local inflammatory status in tissues may be a useful biomarker for evaluation and management in patients with DD.

Increasing LV filling pressures will inevitably cause left atrial dilatation, which is one of the important predictors of survival after acute MI.[25] Long-term increase in atrial volumes will be one of the important parameters of DD in MI patients. In addition, concentric hypertrophy may impair active relaxation by decreasing diastolic capacitance by reducing cavity diameters.[26] We examined LAVI values and found a greater increase in LAVI rates in patients with high PTX-3 levels in our study. The detection of more adverse remodeling in patients with advanced LVMI in our study is parallel to the findings mentioned above. Besides, while there was no difference in baseline in the high PTX-3 group in terms of the septal, lateral, and average values of E/e showing LV filling pressures, the detection of increase in the follow-up suggests that PTX-3 is associated with the increase in filling pressure by increasing stiffening over inflammation.

Failure to achieve TIMI flow 3 after MI may cause the enlargement of the infarct area and consequently damage to both myocytes and the extracellular matrix. This acute injury is gradually followed by repair with fibrous tissue.[2728] In post-MI patients with persistent restrictive filling, more MACE was observed even if they were revascularized with PCI.[18] We found approximately six times more diastolic adverse remodeling in patients who could not achieve post-TIMI flow 3 in our study.

There are several limitations in our study. First, being a single-center study and excluded patients can lead to selection bias. However, although the number of patients was small, the study population was homogeneous and all participants consisted of MI patients who underwent successful reperfusion and were discharged with routine treatment based on guidelines. Second, our results should be interpreted with caution since echocardiographic strain is not performed, potentially due to the presence of regionally different fibrosis patterns. However, comparative studies have shown that strain measurement is not better than tissue Doppler.[29] Third, since echocardiographic evaluation of DD is a controversial issue, the definition for analysis may not be reproducible or easily applicable. Furthermore, since echocardiographic and biochemical evaluation is not performed at the same time, the correlation between these two may be suboptimal. Finally, repeating the PTX-3 would give us an idea of the dynamic changes in the infarct myocardium, but no measurement was repeated.

CONCLUSION

Our study showed that more adverse diastolic remodeling was detected in patients with high PTX-3 levels in STEMI patients underwent successfully PCI. Besides, LV hypertrophy and failed to achieve post-PCI TIMI flow 3 were independent predictors of adverse diastolic remodeling. Prospective controlled trials are needed for PTX-3 to guide patient management and treatment selection, in addition to other biomarkers and clinical predictors. New treatment goals may emerge with a better understanding of the pathways where PTX-3 is located.

Ethical clearance

This study was approved by the Ethics Committee of the Zonguldak Bulent Ecevit University under the protocol number 2020/3.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.