Una puntuación de riesgo genético predice recurrencias en pacientes jóvenes con infarto agudo de miocardio / A genetic risk score predicts recurrent events after myocardial infarction in young adults

INTRODUCCIÓN Y OBJETIVOS: Evaluar si una puntuación de riesgo genético (GRS) mejora la predicción de eventos recurrentes en pacientes jóvenes con infarto agudo de miocardio (IAM) e identifica una forma de aterosclerosis más agresiva. MÉTODOS: Se diseñó un estudio prospectivo con pacientes <55 años, no diabéticos, ingresados por IAM. Se realizó un test genético, una tomografía computarizada cardiaca y determinación de varios biomarcadores. Se analizó la asociación de un GRS compuesto por 11 variantes genéticas con la aparición de un objetivo primario combinado (muerte cardiovascular, evento recurrente u hospitalización cardiovascular). RESULTADOS: Se siguió a 81 pacientes durante una mediana de 4,1 años, y se documentaron 24 eventos. La prevalencia de variantes de riesgo fue superior en 9 de los 11 alelos frente a población general. El GRS se asoció con recurrencias, particularmente cuando los niveles basales de colesterol-LDL estaban elevados. En el modelo multivariado, teniendo como referencia el tercil de bajo riesgo genético, el HR para el grupo de riesgo intermedio fue de 10,2 (IC95% 1,1-100,3; p = 0,04) y de alto riesgo 20,7 (2,4-181,0; p = 0,006) si el colesterol-LDL era≥2,8 mmol/l (≥ 110mg/dl). La incorporación del GRS al modelo multivariado mejoró el estadístico C (ΔC-statistic=0,086), el cNRI (30%) y el IDI (0,05). El TC cardiaco detectó ateromatosis calcificada frecuentemente, pero tuvo un valor pronóstico limitado. No se detectó una asociación entre metaloproteinasas, GRS y recurrencias. CONCLUSIONES: En una población de pacientes jóvenes no diabéticos con IAM, una puntuación de riesgo genético puede predecir recurrencias y mejorar los modelos clínicos de estratificación pronóstica, especialmente en aquellos pacientes con colesterol-LDL basal elevado

INTRODUCTION AND OBJECTIVES: To evaluate whether a genetic risk score (GRS) improves prediction of recurrent events in young nondiabetic patients presenting with an acute myocardial infarction (AMI) and identifies a more aggressive form of atherosclerosis. METHODS: We conducted a prospective study with consecutive nondiabetic patients aged <55 years presenting with AMI. We performed a genetic test, cardiac computed tomography, and analyzed several biomarkers. We studied the association of a GRS composed of 11 genetic variants and a primary composite endpoint (cardiovascular mortality, a recurrent event, and cardiac hospitalization). RESULTS: A total of 81 patients were studied and followed up for a median of 4.1 years. There were 24 recurrent cardiovascular events. Compared with the general population, study participants had a higher prevalence of 9 out of 11 risk alleles. The GRS was significantly associated with recurrent cardiovascular events, especially when baseline low-density lipoprotein cholesterol (LDL-C) levels were elevated. Compared with the low-risk GRS tertile, the multivariate-adjusted HR for recurrences was 10.2 (95%CI, 1.1-100.3; P=.04) for the intermediate-risk group and was 20.7 (2.4-181.0; P=.006) for the high-risk group when LDL-C was≥2.8 mmol/L (≥ 110mg/dL). Inclusion of the GRS improved the C-statistic (ΔC-statistic=0.086), cNRI (continuous net reclassification improvement) (30%), and the IDI (integrated discrimination improvement) index (0.05). Cardiac computed tomography frequently detected coronary calcified atherosclerosis but had limited value for prediction of recurrences. No association was observed between metalloproteinases, GRS and recurrences. CONCLUSIONS: A multilocus GRS may identify individuals at increased risk of long-term recurrences among young nondiabetic patients with AMI and improve clinical risk stratification models, particularly among patients with high baseline LDL-C levels

A genetic risk score predicts recurrent events after myocardial infarction in young adults.

INTRODUCTION AND OBJECTIVES: To evaluate whether a genetic risk score (GRS) improves prediction of recurrent events in young nondiabetic patients presenting with an acute myocardial infarction (AMI) and identifies a more aggressive form of atherosclerosis. METHODS: We conducted a prospective study with consecutive nondiabetic patients aged <55 years presenting with AMI. We performed a genetic test, cardiac computed tomography, and analyzed several biomarkers. We studied the association of a GRS composed of 11 genetic variants and a primary composite endpoint (cardiovascular mortality, a recurrent event, and cardiac hospitalization). RESULTS: A total of 81 patients were studied and followed up for a median of 4.1 years. There were 24 recurrent cardiovascular events. Compared with the general population, study participants had a higher prevalence of 9 out of 11 risk alleles. The GRS was significantly associated with recurrent cardiovascular events, especially when baseline low-density lipoprotein cholesterol (LDL-C) levels were elevated. Compared with the low-risk GRS tertile, the multivariate-adjusted HR for recurrences was 10.2 (95%CI, 1.1-100.3; P=.04) for the intermediate-risk group and was 20.7 (2.4-181.0; P=.006) for the high-risk group when LDL-C was≥2.8mmol/L (≥ 110mg/dL). Inclusion of the GRS improved the C-statistic (ΔC-statistic=0.086), cNRI (continuous net reclassification improvement) (30%), and the IDI (integrated discrimination improvement) index (0.05). Cardiac computed tomography frequently detected coronary calcified atherosclerosis but had limited value for prediction of recurrences. No association was observed between metalloproteinases, GRS and recurrences. CONCLUSIONS: A multilocus GRS may identify individuals at increased risk of long-term recurrences among young nondiabetic patients with AMI and improve clinical risk stratification models, particularly among patients with high baseline LDL-C levels.

Prognostic value of left atrial function by cardiovascular magnetic resonance feature tracking in hypertrophic cardiomyopathy.

Left atrium (LA) size has an important role in determining prognosis and risk stratification in hypertrophic cardiomyopathy (HCM). Cardiovascular magnetic resonance myocardial feature tracking (CMR-FT) is a novel technique for the quantification of LA function. Our aim was first to evaluate LA function by CMR-FT and volumetric analysis in patients with HCM; and secondly we sought to determine the association of LA-longitudinal strain (LA-LS) with major cardiovascular outcomes, particularly all cause mortality and heart failure. 75 patients with HCM and 75 control subjects underwent a conventional CMR study including assessment of LA function by CMR-FT (LA-LS) and volumetric analysis. A primary endpoint of all-cause mortality and secondary combined endpoint of hospital admission related to heart failure, lethal ventricular arrhythmias or cardiovascular death were defined. Compared to controls, LA-LS and all volumetric indices of LA function were significantly impaired in HCM even in patients with normal LA volume and normal LV filling pressures. LA-LS showed moderate-high correlation with LA-emptying fraction (total, active and passive LA-EF, r = 0.68, r = 0.67, r = 0.31, p < 0.001 for all) and with parameters of diastolic function (E/é, r = 0.4, p < 0.001). The age, minimum LA volume and % of LGE were independent predictors of LA-LS (p < 0.01 for all). During a mean follow-up of 3.3 ± 1.2 years LA-LS was associated with the primary (HR: 0.85 (0.73-0.98), p = 0.02) and the secondary end-point (HR: 0.88 (0.82-0.96), p = 0.003). LA-LS by CMR-FT provides accurate measurements of LA function in HCM patients. LA-LS may become a novel potential predictor of poor cardiac outcomes, particularly cardiovascular mortality and HF.

Three-dimensional full automated software in the evaluation of the left ventricle function: from theory to clinical practice.

Left ventricular systolic function evaluation is an essential part of all transthoracic echocardiographic (TTE) studies. 3D echocardiography (3DE) is superior to 2D and is recommended as the method of choice. However, since it is time consuming and requires training, it is rarely performed. Different automatic analysis software tries to overcome these limitations but they need to be accurate and reproducible before they can be used clinically. The aim of this study was to test the accuracy and reproducibility of new 3D automatic quantitative software in everyday clinical practice. 69 patients referred to our Echo Lab for a clinically indicated echocardiographic examination were included. All patients underwent a full TTE with 3D image acquisition. Left ventricular volumes and ejection fraction (LVEF) were obtained using Heart Model software, and compared with conventional 3D volumetric data. Automated analysis was performed using three different sliders setting, with or without regional editing if necessary. 20 patients underwent a cardiac magnetic resonance (CMR) study the same day of the echo and automated measurements were also compared with a CMR reference. Intra- and inter-technique comparisons including linear regression with Pearson correlation coefficients and Bland-Altman analyses were calculated. Mean age of the patients was 59 years, with 49.3% male. The automated 3DE model demonstrated excellent correlation with the conventional 3DE measurements of LVEF, using three different sliders settings (r = 0.906; r = 0.898 and r = 0.940). Correlations with CMR values were very good as well (r = 0.888; r = 0.869; r = 0.913). Similarly, no significant differences were noted between the values of EDV and ESV, measured with the automated model or CMR, with excellent correlation (EDV: r = 0.892, r = 0.842, 0.910; ESV: r = 0.925, r = 0.860, r = 0.907). Finally, volumes calculated with the automated software were significantly greater than those obtained manually, but they showed a very good correlation (EDV: r = 0.875, r = 0.856, r = 0.891; ESV: r = 0.929, r = 0.879, r = 949). 3D automatic software for LV quantification is feasible and shows excellent correlations with both CMR and 3D echocardiography, considered the gold standard. No clinically relevant differences were noted when applying different border settings. This technique holds promise to facilitate the integration of 3D TTE into clinical practice.