ADN libre y daño microvascular en el infarto agudo de miocardio con elevación del segmento ST tratado con intervención coronaria primaria / Cell-free DNA and microvascular damage in ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention

Introducción y objetivos: En el infarto agudo de miocardio con elevación del segmento ST, el ADN libre circulante podría originarse de los leucocitos activados en la lesión coronaria. El objetivo fue investigar la relación entre el ADN libre y la reperfusión coronaria. Métodos: Se incluyó a 116 pacientes, tratados con angioplastia primaria y tromboaspiración. Se cuantificó el ADN libre coronario (durante la aspiración) y periférico (al final del procedimiento), así como la troponina T ultrasensible y la mieloperoxidasa. El objetivo primario fue la no resolución del segmento ST (RST) (≥ 70%) y el secundario la ausencia de flujo Thrombolysis In Myocardial Infarction 3 (TIMI 3) final. Resultados: Se obtuvo RST en 51 (44%) pacientes y flujo TIMI 3 en 97 (84%). Los pacientes sin RST y flujo TIMI 3 tuvieron un menor gradiente ADN libre periférico-coronario (p = 0,02 y p = 0,04, respectivamente). Un gradiente pequeño de ADN libre (< 1,82 ng/ml) se asoció a una mayor frecuencia de no RST (65 frente al 30%; p = 0,001) y de falta de flujo TIMI 3 (21 frente al 3%; p = 0,05. Tras el ajuste multivariable, un gradiente de ADN libre pequeño fue predictivo de no RST (OR = 4,50; IC95%, 1,60-12,62; p = 0,004), en tanto que hubo una tendencia no significativa para el flujo TIMI 3 (p = 0,14). El ADN libre no se correlacionó con la troponina o la mieloperoxidasa. Conclusiones: Un gradiente pequeño de ADN libre periférico-coronario, como expresión de una alta carga de ADN libre coronario, se asocia con no RST en el infarto agudo de miocardio. El ADN libre coronario podría reflejar la activación de los neutrófilos. La potencial contribución de este fenómeno al fracaso de la tromboaspiración requiere nuevos estudios

Introduction and objectives: Cell-free DNA (cfDNA) in ST-segment elevation myocardial infarction might originate from hyperactivated leukocytes at the coronary lesion. Our aim was to investigate the relationship between cfDNA and coronary reperfusion. Methods: We studied 116 patients treated with primary angioplasty using thrombus aspiration. Coronary (during aspiration) and peripheral (at the end of the procedure) blood samples were drawn for cfDNA, as well as high-sensitivity troponin T and myeloperoxidase quantification. The primary endpoint was no ST-segment resolution (STR) (≥ 70%) and the secondary endpoint was lack of final Thrombolysis In Myocardial Infarction flow 3 (TIMI 3). Results: ST-segment resolution was achieved in 51 (44%) patients and TIMI 3 flow in 97 (84%). Patients without STR and TIMI 3 flow had a smaller peripheral-coronary cfDNA gradient (P = .02 and P = .04 respectively). A small cfDNA gradient (< 1.82 ng/mL) was associated with a higher rate of no STR (65% vs 30%; P = .001) and lack of TIMI 3 flow (21% vs 3%; P = .05). After multivariable adjustment, the small cfDNA gradient was predictive of no STR (OR, 4.50; 95%CI, 1.60-12.62; P = .004), while there was a nonsignificant trend for final TIMI 3 flow (P = .14). Cell-free DNA levels did not correlate with troponin T or myeloperoxidase. Conclusions: A small peripheral-coronary cfDNA gradient, as an expression of high coronary cfDNA burden, is associated with no STR in acute myocardial infarction. Intracoronary cfDNA might reflect neutrophil activation. Whether this phenomenon contributes to thrombus aspiration failure requires further study

Cell-free DNA and Microvascular Damage in ST-segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention.

INTRODUCTION AND OBJECTIVES: Cell-free DNA (cfDNA) in ST-segment elevation myocardial infarction might originate from hyperactivated leukocytes at the coronary lesion. Our aim was to investigate the relationship between cfDNA and coronary reperfusion. METHODS: We studied 116 patients treated with primary angioplasty using thrombus aspiration. Coronary (during aspiration) and peripheral (at the end of the procedure) blood samples were drawn for cfDNA, as well as high-sensitivity troponin T and myeloperoxidase quantification. The primary endpoint was no ST-segment resolution (STR) (≥ 70%) and the secondary endpoint was lack of final Thrombolysis In Myocardial Infarction flow 3 (TIMI 3). RESULTS: ST-segment resolution was achieved in 51 (44%) patients and TIMI 3 flow in 97 (84%). Patients without STR and TIMI 3 flow had a smaller peripheral-coronary cfDNA gradient (P = .02 and P = .04 respectively). A small cfDNA gradient (< 1.82 ng/mL) was associated with a higher rate of no STR (65% vs 30%; P = .001) and lack of TIMI 3 flow (21% vs 3%; P = .05). After multivariable adjustment, the small cfDNA gradient was predictive of no STR (OR, 4.50; 95%CI, 1.60-12.62; P = .004), while there was a nonsignificant trend for final TIMI 3 flow (P = .14). Cell-free DNA levels did not correlate with troponin T or myeloperoxidase. CONCLUSIONS: A small peripheral-coronary cfDNA gradient, as an expression of high coronary cfDNA burden, is associated with no STR in acute myocardial infarction. Intracoronary cfDNA might reflect neutrophil activation. Whether this phenomenon contributes to thrombus aspiration failure requires further study.

Usefulness of delta troponin for diagnosis and prognosis assessment of non-ST-segment elevation acute chest pain.

BACKGROUND: The additional diagnostic and prognostic information provided by delta high-sensitivity troponin T (hs-cTnT) in patients with acute chest pain and hs-cTnT elevation remains unclear. METHODS: The study group consisted of 601 patients presenting at the emergency department with non-ST-segment elevation acute chest pain and hs-cTnT elevation after two determinations (admission and within the first six hours). Maximum hs-cTnT and delta hs-cTnT (absolute or percentage change between the two measurements) were considered. Cutoff values were optimized using the quartile distribution for the endpoints. The endpoints were diagnostic (significant stenosis in the coronary angiogram) and prognostic (death or recurrent myocardial infarction at one year). RESULTS: Regarding the diagnostic endpoint, 114 patients showed a normal angiogram. Both maximum hs-cTnT ⩾80 ng/ml (OR 2.5, 95% CI 1.3-4.8, P=0.005) and delta hs-cTnT ⩾20 ng/l (OR 2.1, 95% CI 1.1-4.0, P=0.02) median value cutoffs were related to significant coronary stenosis. Furthermore, the combination of hs-cTn <80 ng/l and delta hs-cTn <20 ng/l showed the lowest probability of significant coronary stenosis (OR 0.3, 95% CI 0.1-0.4, P=0.001). During follow-up, 86 patients experienced the prognostic endpoint. After full adjustment for clinical data, maximum hs-cTnT ⩾30 ng/l, first quartile cutoff, was related to the outcome (HR 1.8, 95% CI 1.0-3.4, P=0.05), while delta hs-cTnT, either absolute or percentage change, lacked prognostic value. CONCLUSIONS: Maximum hs-cTnT captures all the prognostic information provided by hs-cTnT in non-ST-segment elevation acute chest pain. Low maximum and low delta hs-cTnT are associated with a normal coronary angiogram, which could make the final diagnosis challenging in some cases.

High-sensitivity versus conventional troponin for management and prognosis assessment of patients with acute chest pain.

OBJECTIVES: High-sensitivity troponin (hs-cTn) is substituting conventional cTn for evaluation of chest pain. Our aim was to assess the impact on patient management and outcome. METHODS: A total of 1372 consecutive patients presenting at the emergency department with non-ST-elevation acute chest pain were divided into two periods according to the cTn assay used, conventional (n=699, March 2008 to July 2010) or hs-cTn (n=673, November 2010 to March 2013). Management policies were similar and according to guidelines. The primary endpoint was major adverse cardiac events (MACE) at 6 months (death, myocardial infarction, readmission by unstable angina or postdischarge revascularisation). RESULTS: There were minor differences in baseline characteristics. In the hs-cTn period, more patients elevated cTn (73% vs 37%, p=0.0001) leading to more coronary angiograms (77% vs 55%, p=0.0001) and revascularisations (45% vs 31%, p=0.0001); conversely, fewer patients were initially assigned to exercise testing (14% vs 36%, p=0.0001) and, therefore, discharged early after a negative result (7% vs 22%, p=0.0001). At 6 months, 135 patients suffered MACE, including 54 deaths. After adjusting for a Propensity Score, hs-cTn use was not significantly associated with MACE (HR=0.99; 95% CI 0.70 to 1.41; p=0.98) or mortality (HR=1.02; 95% CI 0.59 to 1.77; p=0.95), though the risk of longer hospitalisation stay increased at the index episode (OR=1.35, 95% CI 1.07 to 1.71, p=0.02). CONCLUSIONS: hs-cTn simplified chest pain triage on avoiding a more complex evaluation with non-invasive tests in the chest pain unit, but prompted longer hospitalisations and more invasive procedures without impacting on the 6-month outcomes.