RESUMO
BACKGROUND: Beyond therapeutic implications, PCSK9 (proprotein convertase subtilisin/kexin 9) has emerged as a promising cardiovascular biomarker. The exact role of PCSK9 in the setting of acute ST-elevation myocardial infarction (STEMI) is incompletely understood. We aimed to investigate the association of PCSK9 with ischemia-reperfusion injury, visualized by cardiac magnetic resonance imaging, in patients with STEMI revascularized by primary percutaneous coronary intervention (PCI). METHODS: In this prespecified substudy from the prospective MARINA-STEMI (NCT04113356) registry, we included 205 patients with STEMI. PCSK9 concentrations were measured from venous blood samples by an immunoassay 24 and 48 hours after PCI. The primary end point was defined as presence of intramyocardial hemorrhage according to cardiac magnetic resonance T2* mapping. Secondary imaging end points were the presence of microvascular obstruction (MVO) and infarct size. The clinical end point was the occurrence of major adverse cardiac events. RESULTS: We observed a significant increase in PCSK9 levels from 24 to 48 hours (268-304 ng/mL; P<0.001) after PCI. PCSK9 24 hours after PCI did not show any relation to intramyocardial hemorrhage, MVO, and infarct size (all P>0.05). PCSK9 concentrations 48 hours post-STEMI were higher in patients with intramyocardial hemorrhage (333 versus 287 ng/mL; P=0.004), MVO (320 versus 292 ng/mL; P=0.020), and large infarct size (323 versus 296 ng/mL; P=0.013). Furthermore, patients with increased PCSK9 levels >361 ng/mL at 48 hours were more likely to experience major adverse cardiac events (15% versus 8%; P=0.002) during a median follow-up of 12 months. CONCLUSIONS: In patients with STEMI, a significant increase in PCSK9 was observed from 24 to 48 hours after PCI. While PCSK9 levels after 24 hours were not related to myocardial or microvascular injury, PCSK9 after 48 hours was significantly associated with intramyocardial hemorrhage, MVO, and infarct size as well as worse subsequent clinical outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier; NCT04113356.
Assuntos
Biomarcadores , Traumatismo por Reperfusão Miocárdica , Intervenção Coronária Percutânea , Pró-Proteína Convertase 9 , Sistema de Registros , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Masculino , Pró-Proteína Convertase 9/sangue , Feminino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/etiologia , Traumatismo por Reperfusão Miocárdica/diagnóstico por imagem , Biomarcadores/sangue , Estudos Prospectivos , Idoso , Imagem Cinética por Ressonância Magnética/métodos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The prognostic significance of various microvascular injury (MVI) patterns after ST-segment elevation myocardial infarction (STEMI) is not well known. OBJECTIVES: This study sought to investigate the prognostic implications of different MVI patterns in STEMI patients. METHODS: The authors analyzed 1,109 STEMI patients included in 3 prospective studies. Cardiac magnetic resonance (CMR) was performed 3 days (Q1-Q3: 2-5 days) after percutaneous coronary intervention (PCI) and included late gadolinium enhancement imaging for microvascular obstruction (MVO) and T2∗ mapping for intramyocardial hemorrhage (IMH). Patients were categorized into those without MVI (MVO-/IMH-), those with MVO but no IMH (MVO+/IMH-), and those with IMH (IMH+). RESULTS: MVI occurred in 633 (57%) patients, of whom 274 (25%) had an MVO+/IMH- pattern and 359 (32%) had an IMH+ pattern. Infarct size was larger and ejection fraction lower in IMH+ than in MVO+/IMH- and MVO-/IMH- (infarct size: 27% vs 19% vs 18% [P < 0.001]; ejection fraction: 45% vs 50% vs 54% [P < 0.001]). During a median follow-up of 12 months (Q1-Q3: 12-35 months), a clinical outcome event occurred more frequently in IMH+ than in MVO+/IMH- and MVO-/IMH- subgroups (19.5% vs 3.6% vs 4.4%; P < 0.001). IMH+ was the sole independent MVI parameter predicting major adverse cardiovascular events (HR: 3.88; 95% CI: 1.93-7.80; P < 0.001). CONCLUSIONS: MVI is associated with future adverse outcomes only in patients with a hemorrhagic phenotype (IMH+). Patients with only MVO (MVO+/IMH-) had a prognosis similar to patients without MVI (MVO-/IMH-). This highlights the independent prognostic importance of IMH in assessing and managing risk after STEMI.
Assuntos
Imagem Cinética por Ressonância Magnética , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Imagem Cinética por Ressonância Magnética/métodos , Estudos Prospectivos , Idoso , Prognóstico , Microcirculação , Microvasos/diagnóstico por imagem , Microvasos/lesões , Microvasos/patologiaRESUMO
BACKGROUND: Mitral annular disjunction (MAD), defined as defective attachment of the mitral annulus to the ventricular myocardium, has recently been linked to malignant arrhythmias. However, its role and prognostic significance in patients requiring cardiopulmonary resuscitation (CPR) remain unknown. This retrospective analysis aimed to describe the prevalence and significance of MAD by cardiac magnetic resonance (CMR) imaging in out-of-hospital cardiac arrest (OHCA) patients. METHODS: Eighty-six patients with OHCA and a CMR scan 5 days after CPR (interquartile range (IQR): 49 days before - 9 days after) were included. MAD was defined as disjunction-extent ≥ 1 mm in CMR long-axis cine-images. Medical records were screened for laboratory parameters, comorbidities, and a history of arrhythmia. RESULTS: In 34 patients (40%), no underlying cause for OHCA was found during hospitalization despite profound diagnostics. Unknown-cause OHCA patients showed a higher prevalence of MAD compared to definite-cause patients (56% vs. 10%, p < 0.001) and had a MAD-extent of 6.3 mm (IQR: 4.4-10.3); moreover, these patients were significantly younger (43 years vs. 61 years, p < 0.001), more often female (74% vs. 21%, p < 0.001) and had fewer comorbidities (hypertension, hypercholesterolemia, coronary artery disease, all p < 0.005). By logistic regression analysis, the presence of MAD remained significantly associated with OHCA of unknown cause (odds ratio: 8.49, 95% confidence interval: 2.37-30.41, p = 0.001) after adjustment for age, presence of hypertension, and hypercholesterolemia. CONCLUSIONS: MAD is rather common in OHCA patients without definitive aetiology undergoing CMR. The presence of MAD was independently associated to OHCA without an identifiable trigger. Further research is needed to understand the exact role of MAD in OHCA patients.
Assuntos
Hipercolesterolemia , Hipertensão , Parada Cardíaca Extra-Hospitalar , Humanos , Feminino , Estudos Retrospectivos , Parada Cardíaca Extra-Hospitalar/epidemiologia , Imageamento por Ressonância Magnética , Arritmias CardíacasRESUMO
BACKGROUND: Acute myocardial infarction is associated with the release of the co-transmitter neuropeptide-Y (NPY). NPY acts as a potent vasoconstrictor and is associated with microvascular dysfunction after ST-elevation myocardial infarction (STEMI). This study comprehensively evaluated the association of plasma NPY with myocardial function and infarct severity, visualized by cardiac magnetic resonance (CMR) imaging, in STEMI patients revascularized by primary percutaneous coronary intervention (PCI). METHODS: In this observational study, we included 260 STEMI patients enrolled in the prospective MARINA-STEMI (NCT04113356) study. Plasma NPY concentrations were measured by an immunoassay 24h after PCI from peripheral venous blood samples. Left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), infarct size (IS) and microvascular obstruction (MVO) were determined using CMR imaging. RESULTS: Median plasma concentrations of NPY were 70 [interquartile range (IQR):35-115] pg/ml. NPY levels above median were significantly associated with lower LVEF (48%vs.52%, p=0.004), decreased GLS (-8.8%vs.-12.6%, p<0.001) and larger IS (17%vs.13%, p=0.041) in the acute phase after infarction as well as after 4 months (LVEF:50%vs.52%, p=0.030, GLS:-10.5vs.-12.9,p<0.001,IS:13%vs.10%,p=0.011). In addition, NPY levels were significantly related to presence of MVO (58%vs.52%, p=0.041). Moreover, in multivariable linear regression analysis, NPY remained significantly associated with all investigated CMR parameters (LVEF:p<0.001,GLS:p<0.001,IS:p=0.003,MVO:p=0.042) independent of other established clinical variables including high-sensitivity cardiac troponin T, pre-interventional TIMI flow 0 and left anterior descending artery as culprit lesion location. CONCLUSION: High plasma levels of NPY, measured 24h after STEMI, were independently associated with lower LVEF, decreased GLS, larger IS as well as presence of MVO, indicating plasma NPY as a novel clinical risk marker post STEMI.
Assuntos
Neuropeptídeo Y , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Masculino , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Feminino , Pessoa de Meia-Idade , Neuropeptídeo Y/sangue , Idoso , Estudos Prospectivos , Função Ventricular Esquerda , Volume Sistólico , Índice de Gravidade de Doença , Imageamento por Ressonância Magnética , Modelos Lineares , Biomarcadores/sangue , Análise MultivariadaRESUMO
BACKGROUND: Microvascular obstruction (MVO) and intramyocardial hemorrhage (IMH) are well-established imaging biomarkers of failed myocardial tissue reperfusion in patients with ST-segment elevation-myocardial infarction treated with percutaneous coronary intervention. MVO and IMH are associated with an increased risk of adverse outcome independent of infarct size, but whether the size of the culprit lesion vessel plays a role in the occurrence and severity of reperfusion injury is currently unknown. This study aimed to evaluate the association between culprit lesion vessel size and the occurrence and severity of reperfusion injury as determined by cardiac magnetic resonance imaging. METHODS AND RESULTS: Patients (n=516) with first-time ST-segment-elevation myocardial infarction underwent evaluation with cardiac magnetic resonance at 4 (3-5) days after infarction. MVO was assessed with late gadolinium enhancement imaging and IMH with T2* mapping. Vessel dimensions were determined using catheter-based reference. Median culprit lesion vessel size was 3.1 (2.7-3.6) mm. MVO and IMH were found in 299 (58%) and 182 (35%) patients. Culprit lesion vessel size was associated with body surface area, diabetes, total ischemic time, postinterventional thrombolysis in myocardial infarction flow, and infarct size. There was no association between vessel size and MVO or IMH in univariable and multivariable analysis (P>0.05). These findings were consistent across patient subgroups with left anterior descending artery and non-left anterior descending artery infarctions and those with thrombolysis in myocardial infarction 3 flow post-percutaneous coronary intervention. CONCLUSIONS: Comprehensive characterization of myocardial tissue reperfusion injury by cardiac magnetic resonance revealed no association between culprit lesion vessel size and the occurrence of MVO and IMH in patients treated with primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction.
Assuntos
Infarto do Miocárdio , Traumatismo por Reperfusão Miocárdica , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Meios de Contraste , Gadolínio , Imageamento por Ressonância Magnética , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Infarto do Miocárdio/terapia , Traumatismo por Reperfusão Miocárdica/etiologia , Traumatismo por Reperfusão Miocárdica/complicações , Reperfusão Miocárdica/efeitos adversos , Hemorragia/epidemiologia , Intervenção Coronária Percutânea/efeitos adversos , MicrocirculaçãoRESUMO
BACKGROUND: Dysglycaemia increases the risk of myocardial infarction and subsequent recurrent cardiovascular events. However, the role of dysglycaemia in ischemia/reperfusion injury with development of irreversible myocardial tissue alterations remains poorly understood. In this study we aimed to investigate the association of ongoing dysglycaemia with persistence of infarct core iron and their longitudinal changes over time in patients undergoing primary percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction (STEMI). METHODS: We analyzed 348 STEMI patients treated with primary PCI between 2016 and 2021 that were included in the prospective MARINA-STEMI study (NCT04113356). Peripheral venous blood samples for glucose and glycated hemoglobin (HbA1c) measurements were drawn on admission and 4 months after STEMI. Cardiac magnetic resonance (CMR) imaging including T2 * mapping for infarct core iron assessment was performed at both time points. Associations of dysglycaemia with persistent infarct core iron and iron resolution at 4 months were calculated using multivariable regression analysis. RESULTS: Intramyocardial hemorrhage was observed in 147 (42%) patients at baseline. Of these, 89 (61%) had persistent infarct core iron 4 months after infarction with increasing rates across HbA1c levels (<5.7%: 33%, ≥5.7: 79%). Persistent infarct core iron was independently associated with ongoing dysglycaemia defined by HbA1c at 4 months (OR: 7.87 [95% CI: 2.60-23.78]; p < 0.001), after adjustment for patient characteristics and CMR parameters. The independent association was present even after exclusion of patients with diabetes (pre- and newly diagnosed, n = 16). CONCLUSIONS: In STEMI patients treated with primary PCI, ongoing dysglycaemia defined by HbA1c is independently associated with persistent infarct core iron and a lower likelihood of iron resolution. These findings suggest a potential association between ongoing dysglycaemia and persistent infarct core iron, which warrants further investigation for therapeutic implications.