Interventional Left Atrial Appendage Closure Affects the Metabolism of Acylcarnitines
Abstract
:1. Introduction
2. Results
2.1. Baseline Characteristics and Procedures’ Indications
2.2. Numerical Non-Adjusted Changes of Acylcarnitine Levels
2.3. Subgroup Analyses
2.4. Adjusted Multivariable Regression Model
3. Discussion
Study Limitations
4. Materials and Methods
4.1. Sample Collection
4.2. Characterization of the Study Population and Changes over the Mid-Term Follow-Up
4.3. Metabolite Analyses
4.4. Outcome Measures
4.5. Statistics
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
AF | atrial fibrillation |
ANOVA | analysis of variance |
BMI | body mass index |
CAC | carnitine/acylcarnitine carrier protein |
CHA2DS2-VASc | congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or TIA or thromboembolism, vascular disease, age 65–74 years, sex category (i.e., female sex) |
CPT | carnitine palmitoytransferase |
CRP | C reactive protein |
CT | computed tomography |
EDTA | ethylenediaminetetra-acetic acid |
ESI–LC–MS/MS | electrospray ionization–liquid chromatography– mass spectrometry |
FDR | false discovery rate |
HAS-BLED | hypertension, abnormal renal or liver function, prior stroke, prior major bleeding or predisposition to bleeding, labile INR, elderly, i.e., age > 65 years, prior alcohol, drug, or medication usage predisposing to bleeding |
HCA | hierarchical cluster analysis |
INR | International Normalized Ratio |
LAA | left atrial appendage |
LAAC | left atrial appendage |
LABEL | Left Atrial Appendage Occlusion and Biomarker Evaluation |
LC | long chain |
LDH | lactate dehydrogenase |
LOD | limit of detection |
LV | left ventricular |
LVEF | left ventricular ejection fraction |
MC | medium chain |
MC | medium chain |
MDRD | Modification of Diet in Renal Disease |
NT-proBNP | amino-terminal pro-brain natriuretic peptide |
OAC | oral anticoagulation |
PCA | principal component analysis |
PLS-DA | partial least squares discrimination analysis |
SC | short chain |
TCA | tricarboxylic acid |
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Characteristic | Value |
---|---|
Demographics | |
sex, male n (%) | 30 (68.2) |
age, y (IQR) | 78 (75.8–83) |
BMI, kg/m2 (IQR) | 28.1 (24.7–32.7) |
Cardiovascular risk factors | |
arterial hypertension, n (%) | 42 (95.4) |
diabetes mellitus, n (%) | 16 (36.7) |
HbA1c, % (IQR) | 7.0 (6.2–7.0) |
hypercholesterinemia, n (%) | 22 (50) |
cholesterol, mg/dL (IQR) | 143 (124–186) |
low-density lipoprotein, mg/dL (IQR) | 89 (68–111) |
high-density lipoprotein, mg/dL (IQR) | 55 (41–62) |
triglycerides, mg/dL (IQR) | 117 (95–162) |
impaired left ventricular function, each n (%) | |
LVEF 45–54% | 4 (9.1) |
LVEF 30–44% | 4 (9.1) |
LVEF < 30% | 2 (4.5) |
diastolic dysfunction, n (%) | 11 (25.0%) |
combined with impaired left ventricular function, n (%) | 1 (2.3%) |
Medical history | |
atrial fibrillation, each n (%) | |
Paroxysmal | 24 (54.5) |
Persistent | 6 (13.6) |
Permanent | 14 (31.8) |
pulmonary vein isolation, n (%) | 4 (9.1) |
transitory ischemic attack, n (%) | 3 (6.8) |
stroke, n (%) | 7 (15.9) |
coronary artery disease, n (%) | 25 (56.8) |
myocardial infarction, n (%) | 10 (22.7) |
heart failure, n (%) | 10 (22.7) |
peripheral vascular disease, n (%) | 4 (9.1) |
chronic kidney disease, n (%) | 18 (40.9) |
chronic liver disease, n (%) | 3 (6.8) |
sleep apnea, n (%) | 4 (9.1) |
prior bleeding, n (%) | 34 (77.3) |
CHA2DS2-VASc score (IQR) | 4 (3–5) |
HAS-BLED score (IQR) | 4 (3–5) |
Postinterventional antithrombotic regimen | |
dual antiplatelet therapy for 6 months, n (%) | 44 (100.0) |
Reasons for rehospitalization/severe clinical events during mid-term follow-up | |
myocardial infarction, n (%) | 1 (2.3) |
heart failure, n (%) | 6 (13.6) |
arrhythmia, n (%) | 2 (4.5) |
vascular problem, n (%) | 2 (4.5) |
gastrointestinal bleeding, n (%) | 8 (18.2) |
renal failure, n (%) | 1 (2.3) |
infectious disease, n (%) | 2 (4.5) |
orthopedic, n (%) | 2 (4.5) |
Bleeding during mid-term follow-up, BARC-Score | |
1, n (%) | 1 (2.3) |
2, n (%) | 5 (11.4) |
3a, n (%) | 2 (4.5) |
≥3b, n (%) | 0 (0) |
Characteristics | T1 | T2 | p Value |
---|---|---|---|
Smoking status | |||
never, n (%) | 37 (84.1) | 37 (84.1) | 1.000 |
>1 year former, n (%) | 1 (2.3) | 1 (2.3) | 1.000 |
current, n (%) | 6 (13.6) | 6 (13.6) | 1.000 |
Pharmacotherapy | |||
beta blockers, n (%) | 17 (38.6) | 15 (34.1) | 0.825 |
calcium channel blockers, n (%) | 9 (20.5) | 7 (15.9) | 0.783 |
combined therapy, n (%) | 14 (31.8) | 15 (34.1) | 1.000 |
statines, n (%) | 27 (61.4) | 28 (63.6) | 1.000 |
statin and ezetimibe, n (%) | 1 (2.3) | 1 (2.3) | 1.000 |
other lipid-lowering drugs, n (%) | 1 (2.3) | 1 (2.3) | 1.000 |
Anticoagulation | |||
None | 15 (34.1) | 43 (97.7) | <0.001 |
Any | 29 (65.9) | 1 (2.3) | <0.001 |
phenprocoumon, n (%) | 10 (22.7) | 0 (0.0) | 0.001 |
dabigatran, n (%) | 3 (6.8) | 0 (0.0) | 0.241 |
rivaroxaban, n (%) | 3 (6.8) | 0 (0.0) | 0.241 |
apixaban, n (%) | 3 (6.8) | 1 (2.3) | 0.616 |
LMWH, n (%) | 10 (22.7) | 0 (0.0) | 0.001 |
Echocardiographic data | |||
LA diameter, mm (IQR) | 48.0 (43.7–55.0) | 49.0 (44.0–53.0) | 0.657 |
LA surface, cm2 (IQR) | 24.0 (19.7–28.0) | 22.0 (19.0–25.0) | 0.010 |
LA volume, cm3 (IQR) | 88.5 (70.2–105.3) | 83.0 (66.2–100.5) | 0.739 |
Laboratory values | |||
cholesterol, mg/dL (IQR) | 143 (124–186) | 155 (128–161) | 0.370 |
NT-proBNP, pg/mL (IQR) | 975 (455–1429) | 981 (488–1852) | 0.323 |
creatinine, mg/dL (IQR) | 1.10 (0.96–1.42) | 1.24 (1.01–1.71) | 0.430 |
MDRD-GFR, mL/min/1.73 m2 (IQR) | 65 (43–65) | 56 (37–65) | 0.140 |
Hb, g/dl (IQR) | 12.4 (10.7–14.5) | 10.8 (9.6–12.7) | 0.810 |
anemia < 10 g/dL, n (%) | 8 (18.2) | 8 (18.2) | 1.000 |
average blood glucose, g/dL (IQR) | 113 (94–133) | 108 (90–112) | 0.900 |
CRP, mg/L (IQR) | 5.1 (2.9–11.1) | 4.0 (2.9–14.3) | 0.560 |
LDH, U/L (IQR) | 198 (176–240) | 240 (199–253) | 0.930 |
T1 | T2 | ||||||
---|---|---|---|---|---|---|---|
Rank | Metabolite | Mean Conc. (µM) | SD | Mean Conc. (µM) | SD | Percentage Change | p Value |
1 | C18:1 | 0.171 | 0.051 | 0.149 | 0.054 | −12.9 | 0.005 |
2 | C2 | 10.12 | 5.02 | 8.41 | 3.77 | −16.9 | 0.005 |
3 | C5 | 0.206 | 0.252 | 0.312 | 0.481 | 51.5 | 0.013 |
4 | C14:1 | 0.119 | 0.042 | 0.107 | 0.043 | −10.1 | 0.035 |
5 | C16 | 0.125 | 0.034 | 0.116 | 0.035 | −7.2 | 0.050 |
6 | C3-DC/C4-OH | 0.076 | 0.043 | 0.070 | 0.073 | −7.9 | 0.071 |
7 | C3 | 0.385 | 0.161 | 0.424 | 0.232 | 10.1 | 0.155 |
8 | C4 | 0.336 | 0.221 | 0.360 | 0.212 | 7.1 | 0.337 |
9 | C14:2 | 0.033 | 0.021 | 0.031 | 0.025 | −6.1 | 0.380 |
10 | C18 | 0.054 | 0.024 | 0.052 | 0.012 | −3.7 | 0.422 |
11 | C0 | 36.93 | 11.42 | 35.15 | 10.15 | −4.8 | 0.430 |
12 | C18:2 | 0.042 | 0.014 | 0.041 | 0.023 | −2.4 | 0.430 |
13 | C10 | 0.231 | 0.114 | 0.220 | 0.091 | −4.8 | 0.493 |
Rank | Metabolite | FDR | Beta | Standard Error | t Value | p Value |
---|---|---|---|---|---|---|
1 | C18:1 | 0.0351 | −0.236 | 0.080 | −2.961 | 0.0050 |
2 | C2 | 0.0351 | −0.254 | 0.087 | 2.930 | 0.0054 |
3 | C5 | 0.0549 | 0.456 | 0.175 | 2.602 | 0.0127 |
4 | C14:1 | 0.1130 | −0.189 | 0.087 | −2.180 | 0.0348 |
5 | C16 | 0.1288 | −0.121 | 0.060 | −2.021 | 0.0495 |
6 | C3-DC/C4-OH | 0.1534 | −0.186 | 0.100 | −1.853 | 0.0708 |
7 | C3 | 0.2886 | 0.123 | 0.085 | 1.446 | 0.1554 |
8 | C4 | 0.4663 | 0.092 | 0.095 | 0.971 | 0.3368 |
9 | C14:2 | 0.4663 | −0.102 | 0.115 | −0.887 | 0.3801 |
10 | C18 | 0.4663 | −0.056 | 0.069 | −0.810 | 0.4222 |
11 | C0 | 0.4663 | −0.061 | 0.077 | −0.797 | 0.4297 |
12 | C18:2 | 0.4663 | −0.071 | 0.089 | −0.796 | 0.4304 |
13 | C10 | 0.4932 | −0.074 | 0.107 | −0.691 | 0.4932 |
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Fastner, C.; Behnes, M.; Sartorius, B.; Wenke, A.; Lang, S.; Yücel, G.; Sattler, K.; Rusnak, J.; Saleh, A.; Barth, C.; et al. Interventional Left Atrial Appendage Closure Affects the Metabolism of Acylcarnitines. Int. J. Mol. Sci. 2018, 19, 500. https://doi.org/10.3390/ijms19020500
Fastner C, Behnes M, Sartorius B, Wenke A, Lang S, Yücel G, Sattler K, Rusnak J, Saleh A, Barth C, et al. Interventional Left Atrial Appendage Closure Affects the Metabolism of Acylcarnitines. International Journal of Molecular Sciences. 2018; 19(2):500. https://doi.org/10.3390/ijms19020500
Chicago/Turabian StyleFastner, Christian, Michael Behnes, Benjamin Sartorius, Annika Wenke, Siegfried Lang, Gökhan Yücel, Katherine Sattler, Jonas Rusnak, Ahmad Saleh, Christian Barth, and et al. 2018. "Interventional Left Atrial Appendage Closure Affects the Metabolism of Acylcarnitines" International Journal of Molecular Sciences 19, no. 2: 500. https://doi.org/10.3390/ijms19020500